Simultaneous fluorescence and quantitative phase microscopy with single-pixel detectors

NASA Astrophysics Data System (ADS)

Liu, Yang; Suo, Jinli; Zhang, Yuanlong; Dai, Qionghai

2018-02-01

Multimodal microscopy offers high flexibilities for biomedical observation and diagnosis. Conventional multimodal approaches either use multiple cameras or a single camera spatially multiplexing different modes. The former needs expertise demanding alignment and the latter suffers from limited spatial resolution. Here, we report an alignment-free full-resolution simultaneous fluorescence and quantitative phase imaging approach using single-pixel detectors. By combining reference-free interferometry with single-pixel detection, we encode the phase and fluorescence of the sample in two detection arms at the same time. Then we employ structured illumination and the correlated measurements between the sample and the illuminations for reconstruction. The recovered fluorescence and phase images are inherently aligned thanks to single-pixel detection. To validate the proposed method, we built a proof-of-concept setup for first imaging the phase of etched glass with the depth of a few hundred nanometers and then imaging the fluorescence and phase of the quantum dot drop. This method holds great potential for multispectral fluorescence microscopy with additional single-pixel detectors or a spectrometer. Besides, this cost-efficient multimodal system might find broad applications in biomedical science and neuroscience.

Apparatus and method for performing two-frequency interferometry

DOEpatents

Johnston, Roger G.

1990-01-01

The present apparatus includes a two-frequency, Zeeman-effect laser and matched, doubly refracting crystals in the construction of an accurate interferometer. Unlike other interferometric devices, the subject invention exhibits excellent phase stability owing to the use of single piece means for producing parallel interferometer arms, making the interferometer relatively insensitive to thermal and mechanical instabilities. Interferometers respond to differences in optical path length between their two arms. Unlike many interferometric techniques, which require the measurement of the location of interference fringes in a brightly illuminated background, the present invention permits the determination of the optical path length difference by measuring the phase of an electronic sine wave. The present apparatus is demonstrated as a differential thermooptic spectrometer for measuring differential optical absorption simply and accurately which is but one of many applications therefor. The relative intensities of the heating beams along each arm of the interferometer can be easily adjusted by observing a zero phase difference with identical samples when this condition is obtained.

Apparatus and method for performing two-frequency interferometry

DOEpatents

Johnston, R.G.

1988-01-25

The present apparatus includes a two-frequency, Zeeman Effect laser and matched, doubly refracting crystals in the construction of an accurate interferometer. Unlike other interferometric devices, the subject invention exhibits excellent phase stability owing to the use of single piece means for producing parallel interferometer arms, making the interferometer relatively insensitive to thermal and mechanical instabilities. Interferometers respond to differences in optical path length between their two arms. Unlike many interferometric techniques, which require the measurement of the location of interference fringes in a brightly illuminated background, the present invention permits the determination of the optical path length difference by measuring the phase of an electronic sine wave. The present apparatus is demonstrated as a differential thermooptic spectrometer for measuring differential optical absorption simply and accurately which is but one of many applications therefor. The relative intensities of the heating beams along each arm of the interferometer can be easily adjusted by observing a zero phase difference with identical samples when this condition is obtained. 6 figs.

A RANDOMIZED TREATMENT TRIAL: SINGLE VERSUS 7 DAY DOSE OF METRONIDAZOLE FOR THE TREATMENT OF TRICHOMONAS VAGINALIS AMONG HIV-INFECTED WOMEN

PubMed Central

Kissinger, Patricia; Mena, Leandro; Levison, Judy; Clark, Rebecca A.; Gatski, Megan; Henderson, Harold; Schmidt, Norine; Rosenthal, Susan; Myers, Leann; Martin, David H.

2010-01-01

Objective To determine if the metronidazole (MTZ) 2 gm single dose (recommended) is as effective as the 7 day 500 mg BID dose (alternative) for treatment of Trichomonas vaginalis (TV) among HIV+ women. Methods Phase IV randomized clinical trial; HIV+ women with culture confirmed TV were randomized to treatment arm: MTZ 2 gm single dose or MTZ 500 mg BID 7 day dose. All women were given 2 gm MTZ doses to deliver to their sex partners. Women were re-cultured for TV at a test-of-cure (TOC) visit occurring 6-12 days after treatment completion. TV-negative women at TOC were again re-cultured at a 3 month visit. Repeat TV infection rates were compared between arms. Results 270 HIV+/TV+ women were enrolled (mean age = 40 years, ± 9.4; 92.2% African-American). Treatment arms were similar with respect to age, race, CD4 count, viral load, ART status, site, and loss-to-follow up. Women in the 7 day arm had: lower repeat TV infection rates at TOC [8.5% (11/130) versus 16.8% (21/125) (R.R. 0.50, 95% CI=0.25, 1.00; P<0.05)], and at 3 months [11.0% (8/73) versus 24.1% (19/79) (R.R. 0.46, 95% CI=0.21, 0.98; P=0.03)] compared to the single dose arm. Conclusions The 7 day MTZ dose was more effective than the single dose for the treatment of TV among HIV+ women. PMID:21423852

Isometric arm counter-pressure maneuvers to abort impending vasovagal syncope.

PubMed

Brignole, Michele; Croci, Francesco; Menozzi, Carlo; Solano, Alberto; Donateo, Paolo; Oddone, Daniele; Puggioni, Enrico; Lolli, Gino

2002-12-04

We hypothesized that isometric arm exercises were able to increase blood pressure (BP) during the phase of impending vasovagal syncope and allow the patient to avoid losing consciousness. Hypotension is always present during the prodromal phase of vasovagal syncope. We evaluated the effect of handgrip (HG) and arm-tensing in 19 patients affected by tilt-induced vasovagal syncope. The study consisted of an acute single-blind, placebo-controlled, randomized, cross-over tilt-table efficacy study and a clinical follow-up feasibility study. In the acute tilt study, HG was administered for 2 min, starting at the time of onset of symptoms of impending syncope. In the active arm, HG caused an increase in systolic blood pressure (SBP) from 92 +/- 10 mm Hg to 105 +/- 38 mm Hg, whereas in the placebo arm SBP decreased from 91 +/- 11 mm Hg to 73 +/- 21 mm Hg (p = 0.008). Heart rate behavior was similar in the two arms. In the active arm, 63% of patients became asymptomatic, versus 11% in the control arm (p = 0.02); conversely, only 5% of patients developed syncope, versus 47% in the control arm (p = 0.01). The patients were trained to self-administer arm-tensing treatment as soon as symptoms of impending syncope occurred. During 9 +/- 3 months of follow-up, the treatment was actually performed in 95/97 episodes of impending syncope (98%) and was successful in 94/95 (99%). No patients suffered injury or other adverse morbidity related to the relapses. Isometric arm contraction is able to abort impending vasovagal syncope by increasing systemic BP. Arm counter-pressure maneuvers can be proposed as a new, feasible, safe, and well accepted first-line treatment for vasovagal syncope.

A phase II study of lapatinib in recurrent/metastatic squamous cell carcinoma of the head and neck.

PubMed

de Souza, Jonas A; Davis, Darren W; Zhang, Yujian; Khattri, Arun; Seiwert, Tanguy Y; Aktolga, Serdal; Wong, Stuart J; Kozloff, Mark F; Nattam, Sreenivasa; Lingen, Mark W; Kunnavakkam, Rangesh; Stenson, Kerstin M; Blair, Elizabeth A; Bozeman, Jeffrey; Dancey, Janet E; Vokes, Everett E; Cohen, Ezra E W

2012-04-15

This study sought to determine the efficacy and safety profile of lapatinib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). This phase II multiinstitutional study enrolled patients with recurrent/metastatic SCCHN into two cohorts: those without (arm A) and those with (arm B) before exposure to an epidermal growth factor receptor (EGFR) inhibitor. All subjects were treated with lapatinib 1,500 mg daily. Primary endpoints were response rate (arm A) and progression-free survival (PFS; arm B). The biologic effects of lapatinib on tumor growth and survival pathways were assessed in paired tumor biopsies obtained before and after therapy. Forty-five patients were enrolled, 27 in arm A and 18 in arm B. Diarrhea was the most frequent toxicity occurring in 49% of patients. Seven patients experienced related grade 3 toxicity (3 fatigue, 2 hyponatremia, 1 vomiting, and 1 diarrhea). In an intent-to-treat analysis, no complete or partial responses were observed, and stable disease was the best response observed in 41% of arm A (median duration, 50 days, range, 34-159) and 17% of arm B subjects (median, 163 days, range, 135-195). Median PFS was 52 days in both arms. Median OS was 288 (95% CI, 62-374) and 155 (95% CI, 75-242) days for arms A and B, respectively. Correlative analyses revealed an absence of EGFR inhibition in tumor tissue. Lapatinib as a single agent in recurrent/metastatic SCCHN, although well tolerated, appears to be inactive in either EGFR inhibitor naive or refractory subjects. ©2012 AACR.

Accounting for uncertainty in the historical response rate of the standard treatment in single-arm two-stage designs based on Bayesian power functions.

PubMed

Matano, Francesca; Sambucini, Valeria

2016-11-01

In phase II single-arm studies, the response rate of the experimental treatment is typically compared with a fixed target value that should ideally represent the true response rate for the standard of care therapy. Generally, this target value is estimated through previous data, but the inherent variability in the historical response rate is not taken into account. In this paper, we present a Bayesian procedure to construct single-arm two-stage designs that allows to incorporate uncertainty in the response rate of the standard treatment. In both stages, the sample size determination criterion is based on the concepts of conditional and predictive Bayesian power functions. Different kinds of prior distributions, which play different roles in the designs, are introduced, and some guidelines for their elicitation are described. Finally, some numerical results about the performance of the designs are provided and a real data example is illustrated. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A Bayesian-frequentist two-stage single-arm phase II clinical trial design.

PubMed

Dong, Gaohong; Shih, Weichung Joe; Moore, Dirk; Quan, Hui; Marcella, Stephen

2012-08-30

It is well-known that both frequentist and Bayesian clinical trial designs have their own advantages and disadvantages. To have better properties inherited from these two types of designs, we developed a Bayesian-frequentist two-stage single-arm phase II clinical trial design. This design allows both early acceptance and rejection of the null hypothesis ( H(0) ). The measures (for example probability of trial early termination, expected sample size, etc.) of the design properties under both frequentist and Bayesian settings are derived. Moreover, under the Bayesian setting, the upper and lower boundaries are determined with predictive probability of trial success outcome. Given a beta prior and a sample size for stage I, based on the marginal distribution of the responses at stage I, we derived Bayesian Type I and Type II error rates. By controlling both frequentist and Bayesian error rates, the Bayesian-frequentist two-stage design has special features compared with other two-stage designs. Copyright © 2012 John Wiley & Sons, Ltd.

Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study

PubMed Central

Kanda, S.; Goto, K.; Shiraishi, H.; Kubo, E.; Tanaka, A.; Utsumi, H.; Sunami, K.; Kitazono, S.; Mizugaki, H.; Horinouchi, H.; Fujiwara, Y.; Nokihara, H.; Yamamoto, N.; Hozumi, H.; Tamura, T.

2016-01-01

Background The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods Patients who had stage IIIB without indication for definitive radiotherapy, stage IV, or recurrent NSCLC were eligible. Regimens were nivolumab 10 mg/kg + gemcitabine/cisplatin (arm A), pemetrexed/cisplatin (arm B), paclitaxel/carboplatin/bevacizumab (arm C), or docetaxel (arm D). Regimens A, B, and D were repeated every 3 weeks for up to four cycles and regimen C was repeated for up to six cycles; nivolumab alone (arm A), with pemetrexed (arm B), bevacizumab (arm C), or docetaxel (arm D) was continued every 3 weeks as maintenance therapy until disease progression or unacceptable toxicity. Dose-limiting toxicity (DLT) was evaluated during the first treatment cycle. Results As of March 2014, six patients were enrolled in each arm. The combination of nivolumab 10 mg/kg and chemotherapy was well tolerated. DLT was observed in only one patient in arm A (alanine aminotransferase increased). Select adverse events (those with a potential immunologic cause) of any grade were observed in six, four, six, and five patients in arms A, B, C, and D, respectively. Three, three, six, and one patient achieved partial response while median progression-free survival was 6.28, 9.63 months, not reached, and 3.15 months in arms A, B, C, and D, respectively. Conclusions Combination of nivolumab 10 mg/kg and chemotherapy showed an acceptable toxicity profile and encouraging antitumor activity in patients with advanced NSCLC. Clinical trials number Japanese Pharmaceutical Information Center Clinical Trials Information (JapicCTI)-132071. PMID:27765756

Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study.

PubMed

Kanda, S; Goto, K; Shiraishi, H; Kubo, E; Tanaka, A; Utsumi, H; Sunami, K; Kitazono, S; Mizugaki, H; Horinouchi, H; Fujiwara, Y; Nokihara, H; Yamamoto, N; Hozumi, H; Tamura, T

2016-12-01

The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Patients who had stage IIIB without indication for definitive radiotherapy, stage IV, or recurrent NSCLC were eligible. Regimens were nivolumab 10 mg/kg + gemcitabine/cisplatin (arm A), pemetrexed/cisplatin (arm B), paclitaxel/carboplatin/bevacizumab (arm C), or docetaxel (arm D). Regimens A, B, and D were repeated every 3 weeks for up to four cycles and regimen C was repeated for up to six cycles; nivolumab alone (arm A), with pemetrexed (arm B), bevacizumab (arm C), or docetaxel (arm D) was continued every 3 weeks as maintenance therapy until disease progression or unacceptable toxicity. Dose-limiting toxicity (DLT) was evaluated during the first treatment cycle. As of March 2014, six patients were enrolled in each arm. The combination of nivolumab 10 mg/kg and chemotherapy was well tolerated. DLT was observed in only one patient in arm A (alanine aminotransferase increased). Select adverse events (those with a potential immunologic cause) of any grade were observed in six, four, six, and five patients in arms A, B, C, and D, respectively. Three, three, six, and one patient achieved partial response while median progression-free survival was 6.28, 9.63 months, not reached, and 3.15 months in arms A, B, C, and D, respectively. Combination of nivolumab 10 mg/kg and chemotherapy showed an acceptable toxicity profile and encouraging antitumor activity in patients with advanced NSCLC. Japanese Pharmaceutical Information Center Clinical Trials Information (JapicCTI)-132071. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Integral equation theory study on the phase separation in star polymer nanocomposite melts.

PubMed

Zhao, Lei; Li, Yi-Gui; Zhong, Chongli

2007-10-21

The polymer reference interaction site model theory is used to investigate phase separation in star polymer nanocomposite melts. Two kinds of spinodal curves were obtained: classic fluid phase boundary for relatively low nanoparticle-monomer attraction strength and network phase boundary for relatively high nanoparticle-monomer attraction strength. The network phase boundaries are much more sensitive with nanoparticle-monomer attraction strength than the fluid phase boundaries. The interference among the arm number, arm length, and nanoparticle-monomer attraction strength was systematically investigated. When the arm lengths are short, the network phase boundary shows a marked shift toward less miscibility with increasing arm number. When the arm lengths are long enough, the network phase boundaries show opposite trends. There exists a crossover arm number value for star polymer nanocomposite melts, below which the network phase separation is consistent with that of chain polymer nanocomposite melts. However, the network phase separation shows qualitatively different behaviors when the arm number is larger than this value.

Development of a single-phase 30 m HTS power cable

NASA Astrophysics Data System (ADS)

Cho, Jeonwook; Bae, Joon-Han; Kim, Hae-Jong; Sim, Ki-Deok; Kim, Seokho; Jang, Hyun-Man; Lee, Chang-Young; Kim, Dong-Wook

2006-05-01

HTS power transmission cables appear to be the replacement and retrofitting of underground cables in urban areas and HTS power transmission cable offers a number of technical and economic merits compared to the normal conductor cable system. A 30 m long, single-phase 22.9 kV class HTS power transmission cable system has been developed by Korea Electrotechnology Research Institute (KERI), LS Cable Ltd., and Korea Institute of Machinery and Materials (KIMM), which is one of the 21st century frontier project in Korea since 2001. The HTS power cable has been developed, cooled down and tested to obtain realistic thermal and electrical data on HTS power cable system. The evaluation results clarified such good performance of HTS cable that DC critical current of the HTS cable was 3.6 kA and AC loss was 0.98 W/m at 1260 Arms and shield current was 1000 Arms. These results proved the basic properties for 22.9 kV HTS power cable. As a next step, we have been developing a 30 m, three-phase 22.9 kV, 50 MV A HTS power cable system and long term evaluation is in progress now.

Dynamic balance control in elders: gait initiation assessment as a screening tool

NASA Technical Reports Server (NTRS)

Chang, H.; Krebs, D. E.; Wall, C. C. (Principal Investigator)

1999-01-01

OBJECTIVE: To determine whether measurements of center of gravity-center of pressure separation (CG-CP moment arm) during gait initiation can differentiate healthy from disabled subjects with sufficient specificity and sensitivity to be useful as a screening test for dynamic balance in elderly patients. SUBJECTS: Three groups of elderly subjects (age, 74.97+/-6.56 yrs): healthy elders (HE, n = 21), disabled elders (DE, n = 20), and elders with vestibular hypofunction (VH, n = 18). DESIGN: Cross-sectional, intact-groups research design. Peak CG-CP moment arm measures how far the subject will tolerate the whole-body CG to deviate from the ground reaction force's CP; it represents dynamic balance control. Screening test cutoff points at 16 to 18 cm peak CG-CP moment arm predicted group membership. RESULTS: The magnitude of peak CG-CP moment arm was significantly greater in HE than in DE and VH subjects (p<.01) and was not different between the DE and VH groups. The peak CG-CP moment arm occurred at the end of single stance phase in all groups. As a screening test, the peak moment arm has greater than 50% sensitivity and specificity to discriminate the HE group from the DE and VH groups with peak CG-CP moment arm cutoff points between 16 and 18 cm. CONCLUSIONS: Examining dynamic balance through the use of the CG-CP moment arm during single stance in gait initiation discriminates between nondisabled and disabled older persons and warrants further investigation as a potential tool to identify people with balance dysfunction.

Unbiased estimation in seamless phase II/III trials with unequal treatment effect variances and hypothesis-driven selection rules.

PubMed

Robertson, David S; Prevost, A Toby; Bowden, Jack

2016-09-30

Seamless phase II/III clinical trials offer an efficient way to select an experimental treatment and perform confirmatory analysis within a single trial. However, combining the data from both stages in the final analysis can induce bias into the estimates of treatment effects. Methods for bias adjustment developed thus far have made restrictive assumptions about the design and selection rules followed. In order to address these shortcomings, we apply recent methodological advances to derive the uniformly minimum variance conditionally unbiased estimator for two-stage seamless phase II/III trials. Our framework allows for the precision of the treatment arm estimates to take arbitrary values, can be utilised for all treatments that are taken forward to phase III and is applicable when the decision to select or drop treatment arms is driven by a multiplicity-adjusted hypothesis testing procedure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

The Design of Phase II Clinical Trials Testing Cancer Therapeutics: Consensus Recommendations from the Clinical Trial Design Task Force of the National Cancer Institute Investigational Drug Steering Committee

PubMed Central

Seymour, Lesley; Ivy, S. Percy; Sargent, Daniel; Spriggs, David; Baker, Laurence; Rubinstein, Larry; Ratain, Mark J; Le Blanc, Michael; Stewart, David; Crowley, John; Groshen, Susan; Humphrey, Jeffrey S; West, Pamela; Berry, Donald

2010-01-01

The optimal design of phase II studies continues to be the subject of vigorous debate, especially with regards to studies of newer molecularly targeted agents. The observations that many new therapeutics ‘fail’ in definitive phase III studies, coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical trials further emphasizes the critical importance of robust and efficient phase II design. The Clinical Trial Design Task Force(CTD-TF)of the NCI Investigational Drug Steering Committee (IDSC) has published a series of discussion papers on Phase II trial design in Clinical Cancer Research. The IDSC has developed formal recommendations regarding aspects of phase II trial design which are the subject of frequent debate such as endpoints(response vs. progression free survival), randomization(single arm designs vs. randomization), inclusion of biomarkers, biomarker based patient enrichment strategies, and statistical design(e.g. two stage designs vs. multiple-group adaptive designs). While these recommendations in general encourage the use of progression-free survival as the primary endpoint, the use of randomization, the inclusion of biomarkers and the incorporation of newer designs, we acknowledge that objective response as an endpoint, and single arm designs, remain relevant in certain situations. The design of any clinical trial should always be carefully evaluated and justified based on the characteristic specific to the situation. PMID:20215557

Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial.

PubMed

Guo, J; Carvajal, R D; Dummer, R; Hauschild, A; Daud, A; Bastian, B C; Markovic, S N; Queirolo, P; Arance, A; Berking, C; Camargo, V; Herchenhorn, D; Petrella, T M; Schadendorf, D; Sharfman, W; Testori, A; Novick, S; Hertle, S; Nourry, C; Chen, Q; Hodi, F S

2017-06-01

The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT-mutated advanced melanoma without prior KIT inhibitor treatment. Forty-two patients with KIT-mutated advanced melanoma were enrolled and treated with nilotinib 400 mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients; the design was amended to a single-arm trial due to an observed low number of KIT-mutated melanomas. Thirteen patients were randomized to DTIC before the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors. ORR was 26.2% (n = 11/42; 95% CI, 13.9%-42.0%), sufficient to reject the null hypothesis (ORR ≤10%). All observed responses were partial responses (PRs; median response duration, 7.1 months). Twenty patients (47.6%) had stable disease and 10 (23.8%) had progressive disease; 1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, four with an L576P mutation. The median progression-free survival and overall survival were 4.2 and 18.0 months, respectively. Three of the 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib. Nilotinib activity in patients with advanced KIT-mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations. ClinicalTrials.gov, NCT01028222. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Network meta-analysis combining individual patient and aggregate data from a mixture of study designs with an application to pulmonary arterial hypertension.

PubMed

Thom, Howard H Z; Capkun, Gorana; Cerulli, Annamaria; Nixon, Richard M; Howard, Luke S

2015-04-12

Network meta-analysis (NMA) is a methodology for indirectly comparing, and strengthening direct comparisons of two or more treatments for the management of disease by combining evidence from multiple studies. It is sometimes not possible to perform treatment comparisons as evidence networks restricted to randomized controlled trials (RCTs) may be disconnected. We propose a Bayesian NMA model that allows to include single-arm, before-and-after, observational studies to complete these disconnected networks. We illustrate the method with an indirect comparison of treatments for pulmonary arterial hypertension (PAH). Our method uses a random effects model for placebo improvements to include single-arm observational studies into a general NMA. Building on recent research for binary outcomes, we develop a covariate-adjusted continuous-outcome NMA model that combines individual patient data (IPD) and aggregate data from two-arm RCTs with the single-arm observational studies. We apply this model to a complex comparison of therapies for PAH combining IPD from a phase-III RCT of imatinib as add-on therapy for PAH and aggregate data from RCTs and single-arm observational studies, both identified by a systematic review. Through the inclusion of observational studies, our method allowed the comparison of imatinib as add-on therapy for PAH with other treatments. This comparison had not been previously possible due to the limited RCT evidence available. However, the credible intervals of our posterior estimates were wide so the overall results were inconclusive. The comparison should be treated as exploratory and should not be used to guide clinical practice. Our method for the inclusion of single-arm observational studies allows the performance of indirect comparisons that had previously not been possible due to incomplete networks composed solely of available RCTs. We also built on many recent innovations to enable researchers to use both aggregate data and IPD. This method could be used in similar situations where treatment comparisons have not been possible due to restrictions to RCT evidence and where a mixture of aggregate data and IPD are available.

How does a planet excite multiple spiral arms?

NASA Astrophysics Data System (ADS)

Bae, Jaehan; Zhu, Zhaohuan

2018-01-01

Protoplanetary disk simulations show that a single planet excites multiple spiral arms in the background disk, potentially supported by the multi-armed spirals revealed with recent high-resolution observations in some disks. The existence of multiple spiral arms is of importance in many aspects. It is empirically found that the arm-to-arm separation increases as a function of the planetary mass, so one can use the morphology of observed spiral arms to infer the mass of unseen planets. In addition, a spiral arm opens a radial gap as it steepens into a shock, so when a planet excites multiple spiral arms it can open multiple gaps in the disk. Despite the important implications, however, the formation mechanism of multiple spiral arms has not been fully understood by far.In this talk, we explain how a planet excites multiple spiral arms. The gravitational potential of a planet can be decomposed into a Fourier series, a sum of individual azimuthal modes having different azimuthal wavenumbers. Using a linear wave theory, we first demonstrate that appropriate sets of Fourier decomposed waves can be in phase, raising a possibility that constructive interference among the waves can produce coherent structures - spiral arms. More than one spiral arm can form since such constructive interference can occur at different positions in the disk for different sets of waves. We then verify this hypothesis using a suite of two-dimensional hydrodynamic simulations. Finally, we present non-linear behavior in the formation of multiple spiral arms.

Randomized phase 3 trial comparing 2 cisplatin dose schedules in 326 patients with locally advanced squamous cell cervical carcinoma: long-term follow-up.

PubMed

Nagy, Viorica Magdalena; Ordeanu, Claudia; Coza, Ovidiu; Alin, Cristian Rancea; Traila, Alexandru; Todor, Nicolae

2012-11-01

The evaluation of 5-year results obtained through 2 radiochemotherapy (RCT) regimens: cisplatin (CDDP), 20 mg/m × 5 days every 21 days; and CDDP, 40 mg/m per week in locally advanced cervical carcinoma. In this single-institution prospective randomized phase 3 study, 326 patients with stage IIB to IIIB squamous cell cervical carcinoma treated from March 2003 to March 2005 were included. One hundred sixty patients (49%) had stage IIB cervical carcinoma, 103 patients (31.5%) had stage IIIA cervical carcinoma, and 63 patients (19.5%) had stage IIIB cervical carcinoma. The patients were randomly assigned to 2 therapeutic arms: 164 patients in arm A (5 days) concurrent RCT with CDDP, 20 mg/m per day, days 1 to 5 every 21 days; and 162 patients in arm B (weekly), concurrent RCT with CDDP, 40 mg/m per day weekly. All patients were treated with external beam radiotherapy on the abdominopelvic region using 15-MV x-rays and a cervical boost using the x-rays arch technique or medium-dose-rate intracavitary brachytherapy. The 5-year survival rate obtained through the 2 RCT regimens are not statistically different, even if a tendency of superiority can be observed in the 5-day arm as far as overall survival (78% in arm A vs 72% in arm B; p = 0.14) and disease-free survival (73% in arm A and 69% in arm B; p = 0.09) are concerned. Five-year local relapse-free survival was significantly superior in the 5-day CDDP arm (87%) in comparison with the weekly CDDP arm (77%); p < 0.01. In the 5-day arm, local relapse rate was twice lower, 21/164 (13%), compared with the weekly arm, 40/162 (25%); p < 0.01). Distance failures were identical in the 2 therapeutic groups: 22/164 (13%) and 21/162 (13%), respectively, which shows the superiority of arm A regarding local control. The results of our study demonstrate that RCT with cisplatin, 20 mg/m × 5 days every 21 days, is superior regarding local efficacy and is less toxic compared with the weekly chemotherapy regimen.

Anchoring in a novel bimanual coordination pattern.

PubMed

Maslovat, Dana; Lam, Melanie Y; Brunke, Kirstin M; Chua, Romeo; Franks, Ian M

2009-02-01

Anchoring in cyclical movements has been defined as regions of reduced spatial or temporal variability [Beek, P. J. (1989). Juggling dynamics. PhD thesis. Amsterdam: Free University Press] that are typically found at movement reversal points. For in-phase and anti-phase movements, synchronizing reversal points with a metronome pulse has resulted in decreased anchor point variability and increased pattern stability [Byblow, W. D., Carson, R. G., & Goodman, D. (1994). Expressions of asymmetries and anchoring in bimanual coordination. Human Movement Science, 13, 3-28; Fink, P. W., Foo, P., Jirsa, V. K., & Kelso, J. A. S. (2000). Local and global stabilization of coordination by sensory information. Experimental Brain Research, 134, 9-20]. The present experiment examined anchoring during acquisition, retention, and transfer of a 90 degrees phase-offset continuous bimanual coordination pattern (whereby the right limb lags the left limb by one quarter cycle), involving horizontal flexion about the elbow. Three metronome synchronization strategies were imposed: participants either synchronized maximal flexion of the right arm (i.e., single metronome), both flexion and extension of the right arm (i.e., double metronome within-limb), or flexion of each arm (i.e., double metronome between-limb) to an auditory metronome. In contrast to simpler in-phase and anti-phase movements, synchronization of additional reversal points to the metronome did not reduce reversal point variability or increase pattern stability. Furthermore, practicing under different metronome synchronization strategies did not appear to have a significant effect on the rate of acquisition of the pattern.

Coherently coupled high-power fiber arrays

NASA Astrophysics Data System (ADS)

Anderegg, Jesse; Brosnan, Stephen; Cheung, Eric; Epp, Paul; Hammons, Dennis; Komine, Hiroshi; Weber, Mark; Wickham, Michael

2006-02-01

A four-element fiber array has demonstrated 470 watts of coherently phased, linearly polarized light energy in a single far-field spot. Each element consists of a single-mode fiber-amplifier chain. Phase control of each element is achieved with a Lithium-Niobate phase modulator. A master laser provides a linearly polarized, narrow linewidth signal that is split into five channels. Four channels are individually amplified using polarization maintaining fiber power amplifiers. The fifth channel is used as a reference arm. It is frequency shifted and then combined interferometrically with a portion of each channel's signal. Detectors sense the heterodyne modulation signal, and an electronics circuit measures the relative phase for each channel. Compensating adjustments are then made to each channel's phase modulator. This effort represents the results of a multi-year effort to achieve high power from a single element fiber amplifier and to understand the important issues involved in coherently combining many individual elements to obtain sufficient optical power for directed energy weapons. Northrop Grumman Corporation and the High Energy Laser Joint Technology Office jointly sponsored this work.

Planet-driven Spiral Arms in Protoplanetary Disks. I. Formation Mechanism

NASA Astrophysics Data System (ADS)

Bae, Jaehan; Zhu, Zhaohuan

2018-06-01

Protoplanetary disk simulations show that a single planet can excite more than one spiral arm, possibly explaining the recent observations of multiple spiral arms in some systems. In this paper, we explain the mechanism by which a planet excites multiple spiral arms in a protoplanetary disk. Contrary to previous speculations, the formation of both primary and additional arms can be understood as a linear process when the planet mass is sufficiently small. A planet resonantly interacts with epicyclic oscillations in the disk, launching spiral wave modes around the Lindblad resonances. When a set of wave modes is in phase, they can constructively interfere with each other and create a spiral arm. More than one spiral arm can form because such constructive interference can occur for different sets of wave modes, with the exact number and launching position of the spiral arms being dependent on the planet mass as well as the disk temperature profile. Nonlinear effects become increasingly important as the planet mass increases, resulting in spiral arms with stronger shocks and thus larger pitch angles. This is found to be common for both primary and additional arms. When a planet has a sufficiently large mass (≳3 thermal masses for (h/r) p = 0.1), only two spiral arms form interior to its orbit. The wave modes that would form a tertiary arm for smaller mass planets merge with the primary arm. Improvements in our understanding of the formation of spiral arms can provide crucial insights into the origin of observed spiral arms in protoplanetary disks.

Boron neutron capture therapy for newly diagnosed glioblastoma multiforme: an assessment of clinical potential

PubMed Central

Sköld, K; Gorlia, T; Pellettieri, L; Giusti, V; H-Stenstam, B; Hopewell, J W

2010-01-01

The purpose of this study was to assess the potential of boron neutron capture therapy (BNCT), with a 6-h infusion of the boron carrier l-boronophenylalanine as a fructose preparation (BPA-f), as first-line radiotherapy for newly diagnosed glioblastoma multiforme (GBM). Patient survival data from a Phase II study using BNCT were compared with retrospective data from the two arms of a Phase III study using conventional radiotherapy (RT) in the reference arm and using RT plus concomitant and adjuvant medication with temozolomide (TMZ) in the experimental arm, and were also compared with small subgroups of these patients for whom the methylation status of the MGMT (O6-methylguanine–DNA methyltransferase) DNA repair gene was known. Differences in the baseline characteristics, salvage therapy after recurrence and levels of severe adverse events were also considered. The results indicate that BNCT offers a treatment that is at least as effective as conventional RT alone. For patients with an unmethylated MGMT DNA repair gene, a possible clinical advantage of BNCT over RT/TMZ was suggested. BNCT is a single-day treatment, which is of convenience to patients, with mild side effects, which would offer an initial 6 weeks of good-quality life during the time when patients would otherwise be undergoing daily treatments with RT and TMZ. It is suggested that the use of BNCT with a 6-h infusion of BPA-f should be explored in a stratified randomised Phase II trial in which patients with the unmethylated MGMT DNA repair gene are offered BNCT in the experimental arm and RT plus TMZ in the reference arm. PMID:20603410

Release from proactive interference in rat spatial working memory.

PubMed

Roberts, William A; MacDonald, Hayden; Brown, Lyn; Macpherson, Krista

2017-09-01

A three-phase procedure was used to produce proactive interference (PI) in one trial on an eight-arm radial maze. Rats were forced to enter four arms for reward on an initial interference phase, to then enter the four remaining arms on a target phase, and to then choose among all eight arms on a retention test, with only the arms not visited in the target phase containing reward. Control trials involved only the target phase and the retention test. Lower accuracy was found on PI trials than on control trials, but performance on PI trials significantly exceeded chance, showing some retention of target memories. Changes in temporal and reward variables between the interference, target, and retention test phases showed release from PI, but changes in context and pattern of arm entry did not. It is suggested that the release from PI paradigm can be used to understand spatial memory encoding in rats and other species.

Phase II Trial of Cetuximab With or Without Paclitaxel in Patients With Advanced Urothelial Tract Carcinoma

PubMed Central

Wong, Yu-Ning; Litwin, Samuel; Vaughn, David; Cohen, Seth; Plimack, Elizabeth R.; Lee, James; Song, Wei; Dabrow, Michael; Brody, Marion; Tuttle, Holly; Hudes, Gary

2012-01-01

Purpose The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer. Patients and Methods Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m2 with or without paclitaxel 80 mg/m2 per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks. Results We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases). Conclusion Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers. PMID:22927525

Computer game-based upper extremity training in the home environment in stroke persons: a single subject design.

PubMed

Slijper, Angelique; Svensson, Karin E; Backlund, Per; Engström, Henrik; Sunnerhagen, Katharina Stibrant

2014-03-13

The objective of the present study was to assess whether computer game-based training in the home setting in the late phase after stroke could improve upper extremity motor function. Twelve subjects with prior stroke were recruited; 11 completed the study. The study had a single subject design; there was a baseline test (A1), a during intervention test (B) once a week, a post-test (A2) measured directly after the treatment phase, plus a follow-up (C) 16-18 weeks after the treatment phase. Information on motor function (Fugl-Meyer), grip force (GrippitR) and arm function in activity (ARAT, ABILHAND) was gathered at A1, A2 and C. During B, only Fugl-Meyer and ARAT were measured. The intervention comprised five weeks of game-based computer training in the home environment. All games were designed to be controlled by either the affected arm alone or by both arms. Conventional formulae were used to calculate the mean, median and standard deviations. Wilcoxon's signed rank test was used for tests of dependent samples. Continuous data were analyzed by methods for repeated measures and ordinal data were analyzed by methods for ordered multinomial data using cumulative logistic models. A p-value of < 0.05 was considered statistically significant. Six females and five males, participated in the study with an average age of 58 years (range 26-66). FMA-UE A-D (motor function), ARAT, the maximal grip force and the mean grip force on the affected side show significant improvements at post-test and follow-up compared to baseline. No significant correlation was found between the amount of game time and changes in the outcomes investigated in this study. The results indicate that computer game-based training could be a promising approach to improve upper extremity function in the late phase after stroke, since in this study, changes were achieved in motor function and activity capacity.

Efficacy and tolerability of the single-pill combination of aliskiren 300 mg/amlodipine 10 mg in hypertensive patients not controlled by olmesartan 40 mg/amlodipine 10 mg.

PubMed

Axthelm, Christoph; Sieder, Christian; Meister, Franziska; Kaiser, Edelgard

2012-01-01

We aimed to investigate whether the single pill combination (SPC) of aliskiren 300 mg and amlodipine 10 mg (ALIS 300/AMLO 10) improves blood pressure (BP) reduction in hypertensive patients not adequately controlled by the SPC olmesartan 40 mg and amlodipine 10 mg (OLM 40/AMLO 10). Open-label, non-randomized single-arm study. Patients with stage 2 hypertension were titrated to the SPC OLM 40/AMLO 10 (4-week Phase 1). If hypertension was not controlled they were switched to the SPC ALIS 300/AMLO 10 (4-week Phase 2). In the optional 4-week study extension hydrochlorothiazide (HCT) 12.5 mg was added. EudraCT 2009-016693-33. In the 342 patients treated, OLM 40/AMLO 10 reduced systolic BP (SBP)/diastolic BP (DBP) by 24.5/14.5 mmHg by end of Phase 1. Those 187 patients with uncontrolled hypertension at the end of Phase 1 switched to ALIS 300/AMLO 10 experienced a further SBP reduction of 5.1 mmHg (95% confidence interval [CI] 3.7 to 6.5, p < 0.0001) and a DBP reduction of 4.8 mmHg (95% CI 3.8 to 5.8; p < 0.0001) in Phase 2. DBP or SBP responder rates were achieved by 51.3% or 44.4%, respectively, SBP and DBP normalization by 36.4%. In 65 patients whose BP was not controlled in Phase 2, SPC ALIS 300/AMLO 10/HCT 12.5 mg decreased SBP/DBP by further 8.1/6.7 mmHg (p < 0.0001 each). No deaths or serious adverse events were noted. Significant adverse events leading to study discontinuation were reported in 2.6% (Phase 1), 2.7% (Phase 2), and 0% (extension). Limitations included the open-label, single-arm non-randomized design, and the relatively short duration. In this switch study reflecting clinical practice, patients with moderate hypertension not controlled by the SPC OLM 40/AMLO 10 achieved a clinically and statistically significant reduction of blood pressure from the SPC ALIS 300/AMLO 10 and the optional addition of HCT. All drug combinations were well tolerated.

Dynamic optical arbitrary waveform shaping based on cascaded optical modulators of single FBG.

PubMed

Chen, Jingyuan; Li, Peili

2015-08-10

A dynamic optical arbitrary waveform generation (O-AWG) with amplitude and phase independently controlled in optical modulators of single fiber Bragg Grating (FBG) has been proposed. This novel scheme consists of several optical modulators. In the optical modulator (O-MOD), a uniform FBG is used to filter spectral component of the input signal. The amplitude is controlled by fiber stretcher (FS) in Mach-Zehnder interference (MZI) structure through interference of two MZI arms. The phase is manipulated via the second FS in the optical modulator. This scheme is investigated by simulation. Consequently, optical pulse trains with different waveforms as well as pulse trains with nonuniform pulse intensity, pulse spacing and pulse width within each period are obtained through FSs adjustment to alter the phase shifts of signal in each O-MOD.

Force-induced desorption of 3-star polymers: a self-avoiding walk model

NASA Astrophysics Data System (ADS)

Janse van Rensburg, E. J.; Whittington, S. G.

2018-05-01

We consider a simple cubic lattice self-avoiding walk model of 3-star polymers adsorbed at a surface and then desorbed by pulling with an externally applied force. We determine rigorously the free energy of the model in terms of properties of a self-avoiding walk, and show that the phase diagram includes four phases, namely a ballistic phase where the extension normal to the surface is linear in the length, an adsorbed phase and a mixed phase, in addition to the free phase where the model is neither adsorbed nor ballistic. In the adsorbed phase all three branches or arms of the star are adsorbed at the surface. In the ballistic phase two arms of the star are pulled into a ballistic phase, while the remaining arm is in a free phase. In the mixed phase two arms in the star are adsorbed while the third arm is ballistic. The phase boundaries separating the ballistic and mixed phases, and the adsorbed and mixed phases, are both first order phase transitions. The presence of the mixed phase is interesting because it does not occur for pulled, adsorbed self-avoiding walks. In an atomic force microscopy experiment it would appear as an additional phase transition as a function of force.

A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian patients with MET diagnostic positive, advanced gastric cancer.

PubMed

Sakai, Daisuke; Chung, Hyun Cheol; Oh, Do-Youn; Park, Se Hoon; Kadowaki, Shigenori; Kim, Yeul Hong; Tsuji, Akihito; Komatsu, Yoshito; Kang, Yoon-Koo; Uenaka, Kazunori; Wijayawardana, Sameera R; Wacheck, Volker; Wang, Xuejing; Yamamura, Ayuko; Doi, Toshihiko

2017-12-01

Mesenchymal-epithelial transition factor (MET) is expressed in gastric cancer and associated with poor clinical outcomes. We assessed activity, safety, and pharmacokinetics of emibetuzumab, a bivalent monoclonal anti-MET antibody that blocks ligand-dependent and ligand-independent MET signaling. This non-randomized, single-arm, Phase 2 study enrolled Asian patients with MET diagnostic positive advanced gastric adenocarcinoma. Emibetuzumab (2000 mg, intravenous) was given on days 1 and 15 (28-day cycle). The primary endpoint was 8-week progression-free survival rate. Secondary objectives included safety, pharmacokinetics, overall survival, and change in tumor size. Tumors from 65 patients were immunohistochemically screened to enroll 15 MET diagnostic positive patients (23% positivity; 8 Japanese, 7 Korean; 10 male). Eight-week progression-free survival rate was 0.47 (70% CI, 0.33-0.59). Disease control rate was 40% (target lesion decreases, three patients; no complete/partial responses according to RECIST). Median overall survival was 17.1 weeks (95% CI, 6.3-not achievable). No serious emibetuzumab-related adverse events or new safety signals emerged. Grade ≥ 3 possibly drug-related adverse events were hyperkalemia, hyponatremia, and hyperuricemia (one each). Emibetuzumab's pharmacokinetics profile was similar to that observed previously. MET expression and clinical outcomes were not obviously associated. Emibetuzumab was well tolerated with limited single-agent activity in advanced gastric adenocarcinoma.

Comparing oncology clinical programs by use of innovative designs and expected net present value optimization: Which adaptive approach leads to the best result?

PubMed

Parke, Tom; Marchenko, Olga; Anisimov, Vladimir; Ivanova, Anastasia; Jennison, Christopher; Perevozskaya, Inna; Song, Guochen

2017-01-01

Designing an oncology clinical program is more challenging than designing a single study. The standard approaches have been proven to be not very successful during the last decade; the failure rate of Phase 2 and Phase 3 trials in oncology remains high. Improving a development strategy by applying innovative statistical methods is one of the major objectives of a drug development process. The oncology sub-team on Adaptive Program under the Drug Information Association Adaptive Design Scientific Working Group (DIA ADSWG) evaluated hypothetical oncology programs with two competing treatments and published the work in the Therapeutic Innovation and Regulatory Science journal in January 2014. Five oncology development programs based on different Phase 2 designs, including adaptive designs and a standard two parallel arm Phase 3 design were simulated and compared in terms of the probability of clinical program success and expected net present value (eNPV). In this article, we consider eight Phase2/Phase3 development programs based on selected combinations of five Phase 2 study designs and three Phase 3 study designs. We again used the probability of program success and eNPV to compare simulated programs. For the development strategies, we considered that the eNPV showed robust improvement for each successive strategy, with the highest being for a three-arm response adaptive randomization design in Phase 2 and a group sequential design with 5 analyses in Phase 3.

Auxotonic to isometric contraction transitioning in a beating heart causes myosin step-size to down shift

PubMed Central

Sun, Xiaojing; Wang, Yihua; Ajtai, Katalin

2017-01-01

Myosin motors in cardiac ventriculum convert ATP free energy to the work of moving blood volume under pressure. The actin bound motor cyclically rotates its lever-arm/light-chain complex linking motor generated torque to the myosin filament backbone and translating actin against resisting force. Previous research showed that the unloaded in vitro motor is described with high precision by single molecule mechanical characteristics including unitary step-sizes of approximately 3, 5, and 8 nm and their relative step-frequencies of approximately 13, 50, and 37%. The 3 and 8 nm unitary step-sizes are dependent on myosin essential light chain (ELC) N-terminus actin binding. Step-size and step-frequency quantitation specifies in vitro motor function including duty-ratio, power, and strain sensitivity metrics. In vivo, motors integrated into the muscle sarcomere form the more complex and hierarchically functioning muscle machine. The goal of the research reported here is to measure single myosin step-size and step-frequency in vivo to assess how tissue integration impacts motor function. A photoactivatable GFP tags the ventriculum myosin lever-arm/light-chain complex in the beating heart of a live zebrafish embryo. Detected single GFP emission reports time-resolved myosin lever-arm orientation interpreted as step-size and step-frequency providing single myosin mechanical characteristics over the active cycle. Following step-frequency of cardiac ventriculum myosin transitioning from low to high force in relaxed to auxotonic to isometric contraction phases indicates that the imposition of resisting force during contraction causes the motor to down-shift to the 3 nm step-size accounting for >80% of all the steps in the near-isometric phase. At peak force, the ATP initiated actomyosin dissociation is the predominant strain inhibited transition in the native myosin contraction cycle. The proposed model for motor down-shifting and strain sensing involves ELC N-terminus actin binding. Overall, the approach is a unique bottom-up single molecule mechanical characterization of a hierarchically functional native muscle myosin. PMID:28423017

Evaluation of arm-leg coordination in flat breaststroke.

PubMed

Chollet, D; Seifert, L; Leblanc, H; Boulesteix, L; Carter, M

2004-10-01

This study proposes a new method to evaluate arm-leg coordination in flat breaststroke. Five arm and leg stroke phases were defined with a velocity-video system. Five time gaps quantified the time between arm and leg actions during three paces of a race (200 m, 100 m and 50 m) in 16 top level swimmers. Based on these time gaps, effective glide, effective propulsion, effective leg insweep and effective recovery were used to identify the different stroke phases of the body. A faster pace corresponded to increased stroke rate, decreased stroke length, increased propulsive phases, shorter glide phases, and a shorter T1 time gap, which measured the effective body glide. The top level swimmers showed short time gaps (T2, T3, T4, measuring the timing of arm-leg recoveries), which reflected the continuity in arm and leg actions. The measurement of these time gaps thus provides a pertinent evaluation of swimmers' skill in adapting their arm-leg coordination to biomechanical constraints.

A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain.

PubMed

Whitehead, John; Valdés-Márquez, Elsa; Lissmats, Agneta

2009-01-01

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to be stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase II and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail. Copyright 2008 John Wiley & Sons, Ltd.

Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction

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

Baker, Anna W.; Satyshur, Kenneth A.; Moreno Morales, Neydis

2016-02-01

ABSTRACT Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacteriumRamlibacter tataouinensis. RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, theR. tataouinensisbacteriophytochrome response regulatormore » (RtBRR), and a homolog, AtBRR fromAgrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRR mon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems. IMPORTANCEBphP histidine kinases and their cognate response regulators comprise widespread red light-sensing two-component systems. Much work on BphPs has focused on structural understanding of light sensing and on enhancing the natural infrared fluorescence of these proteins, rather than on signal transduction or the resultant phenotypes. To begin to address this knowledge gap, we solved the crystal structures of two single-domain response regulators encoded by a region immediately downstream of that encoding BphPs. We observed a previously unknown arm-in-arm dimer linkage. Monomerization via deletion of the C-terminal dimerization motif had an inhibitory effect on net response regulator phosphorylation, underlining the importance of these unusual dimers for signal transduction.« less

Spatiotemporal Distribution of Location and Object Effects in Primary Motor Cortex Neurons during Reach-to-Grasp

PubMed Central

Rouse, Adam G.

2016-01-01

Reaching and grasping typically are considered to be spatially separate processes that proceed concurrently in the arm and the hand, respectively. The proximal representation in the primary motor cortex (M1) controls the arm for reaching, while the distal representation controls the hand for grasping. Many studies of M1 activity therefore have focused either on reaching to various locations without grasping different objects, or else on grasping different objects all at the same location. Here, we recorded M1 neurons in the anterior bank and lip of the central sulcus as monkeys performed more naturalistic movements, reaching toward, grasping, and manipulating four different objects in up to eight different locations. We quantified the extent to which variation in firing rates depended on location, on object, and on their interaction—all as a function of time. Activity proceeded largely in two sequential phases: the first related predominantly to the location to which the upper extremity reached, and the second related to the object about to be grasped. Both phases involved activity distributed widely throughout the sampled territory, spanning both the proximal and the distal upper extremity representation in caudal M1. Our findings indicate that naturalistic reaching and grasping, rather than being spatially segregated processes that proceed concurrently, each are spatially distributed processes controlled by caudal M1 in large part sequentially. Rather than neuromuscular processes separated in space but not time, reaching and grasping are separated more in time than in space. SIGNIFICANCE STATEMENT Reaching and grasping typically are viewed as processes that proceed concurrently in the arm and hand, respectively. The arm region in the primary motor cortex (M1) is assumed to control reaching, while the hand region controls grasping. During naturalistic reach–grasp–manipulate movements, we found, however, that neuron activity proceeds largely in two sequential phases, each spanning both arm and hand representations in M1. The first phase is related predominantly to the reach location, and the second is related to the object about to be grasped. Our findings indicate that reaching and grasping are successive aspects of a single movement. Initially the arm and the hand both are projected toward the object's location, and later both are shaped to grasp and manipulate. PMID:27733614

A strategy for computer-assisted mental practice in stroke rehabilitation.

PubMed

Gaggioli, Andrea; Meneghini, Andrea; Morganti, Francesca; Alcaniz, Mariano; Riva, Giuseppe

2006-12-01

To investigate the technical and clinical viability of using computer-facilitated mental practice in the rehabilitation of upper-limb hemiparesis following stroke. A single-case study. Academic-affiliated rehabilitation center. A 46-year-old man with stable motor deficit of the upper right limb following subcortical ischemic stroke. Three computer-enhanced mental practice sessions per week at the rehabilitation center, in addition to usual physical therapy. A custom-made virtual reality system equipped with arm-tracking sensors was used to guide mental practice. The system was designed to superimpose over the (unseen) paretic arm a virtual reconstruction of the movement registered from the nonparetic arm. The laboratory intervention was followed by a 1-month home-rehabilitation program, making use of a portable display device. Pretreatment and posttreatment clinical assessment measures were the upper-extremity scale of the Fugl-Meyer Assessment of Sensorimotor Impairment and the Action Research Arm Test. Performance of the affected arm was evaluated using the healthy arm as the control condition. The patient's paretic limb improved after the first phase of intervention, with modest increases after home rehabilitation, as indicated by functional assessment scores and sensors data. Results suggest that technology-supported mental training is a feasible and potentially effective approach for improving motor skills after stroke.

Electro-optic routing of photons from a single quantum dot in photonic integrated circuits

NASA Astrophysics Data System (ADS)

Midolo, Leonardo; Hansen, Sofie L.; Zhang, Weili; Papon, Camille; Schott, Rüdiger; Ludwig, Arne; Wieck, Andreas D.; Lodahl, Peter; Stobbe, Søren

2017-12-01

Recent breakthroughs in solid-state photonic quantum technologies enable generating and detecting single photons with near-unity efficiency as required for a range of photonic quantum technologies. The lack of methods to simultaneously generate and control photons within the same chip, however, has formed a main obstacle to achieving efficient multi-qubit gates and to harness the advantages of chip-scale quantum photonics. Here we propose and demonstrate an integrated voltage-controlled phase shifter based on the electro-optic effect in suspended photonic waveguides with embedded quantum emitters. The phase control allows building a compact Mach-Zehnder interferometer with two orthogonal arms, taking advantage of the anisotropic electro-optic response in gallium arsenide. Photons emitted by single self-assembled quantum dots can be actively routed into the two outputs of the interferometer. These results, together with the observed sub-microsecond response time, constitute a significant step towards chip-scale single-photon-source de-multiplexing, fiber-loop boson sampling, and linear optical quantum computing.

A randomized phase II trial evaluating different schedules of zoledronic acid on bone mineral density in patients with prostate cancer beginning androgen deprivation therapy.

PubMed

Lang, Joshua M; Wallace, Marianne; Becker, Jordan T; Eickhoff, Jens C; Buehring, Bjoern; Binkley, Neil; Staab, Mary Jane; Wilding, George; Liu, Glenn; Malkovsky, Miroslav; McNeel, Douglas G

2013-12-01

To assess the effects of timing and schedule of zoledronic acid (ZA) administration on bone mineral density (BMD) in patients beginning androgen deprivation therapy (ADT) for the treatment of recurrent prostate cancer. In this randomized, 3-arm trial, we evaluated changes in BMD after 3 different ZA administration schedules in men with recurrent prostate cancer who were beginning ADT. Forty-four patients were enrolled and randomized to receive a single dose of ZA given 1 week before beginning ADT (arm 1), a single dose of ZA given 6 months after beginning ADT (arm 2), or monthly administration of ZA starting 6 months after beginning ADT, for a total of 6 doses (arm 3). Patients who received ZA before ADT had a significant improvement in BMD at the total proximal femur and trochanter after 6 months compared with the other groups. In addition, only patients in the arm that received multiple doses improved lumbar spine BMD while on ADT, with these findings persisting to 24 months. However, this group also experienced more grade 1 adverse events. Analysis of these data suggests that ZA administration before initiation of ADT was superior to treatment 6 months after starting ADT in maintaining BMD. In addition, monthly ZA administration can increase BMD above baseline but is associated with more adverse events. Further study is needed to examine whether the timing and frequency of ZA therapy in patients on ADT can reduce fracture risk. Copyright © 2013 Elsevier Inc. All rights reserved.

Multicenter, Double-Blind, Placebo-Controlled, Randomized Phase II Trial of Gemcitabine/Cisplatin Plus Bevacizumab or Placebo in Patients With Malignant Mesothelioma

PubMed Central

Kindler, Hedy L.; Karrison, Theodore G.; Gandara, David R.; Lu, Charles; Krug, Lee M.; Stevenson, James P.; Jänne, Pasi A.; Quinn, David I.; Koczywas, Marianna N.; Brahmer, Julie R.; Albain, Kathy S.; Taber, David A.; Armato, Samuel G.; Vogelzang, Nicholas J.; Chen, Helen X.; Stadler, Walter M.; Vokes, Everett E.

2012-01-01

Purpose Gemcitabine plus cisplatin is active in malignant mesothelioma (MM), although single-arm phase II trials have reported variable outcomes. Vascular endothelial growth factor (VEGF) inhibitors have activity against MM in preclinical models. We added the anti-VEGF antibody bevacizumab to gemcitabine/cisplatin in a multicenter, double-blind, placebo-controlled randomized phase II trial in patients with previously untreated, unresectable MM. Patients and Methods Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 and no thrombosis, bleeding, or major blood vessel invasion. The primary end point was progression-free survival (PFS). Patients were stratified by ECOG performance status (0 v 1) and histologic subtype (epithelial v other). Patients received gemcitabine 1,250 mg/m2 on days 1 and 8 every 21 days, cisplatin 75 mg/m2 every 21 days, and bevacizumab 15 mg/kg or placebo every 21 days for six cycles, and then bevacizumab or placebo every 21 days until progression. Results One hundred fifteen patients were enrolled at 11 sites; 108 patients were evaluable. Median PFS time was 6.9 months for the bevacizumab arm and 6.0 months for the placebo arm (P = .88). Median overall survival (OS) times were 15.6 and 14.7 months in the bevacizumab and placebo arms, respectively (P = .91). Partial response rates were similar (24.5% for bevacizumab v 21.8% for placebo; P = .74). A higher pretreatment plasma VEGF concentration (n = 56) was associated with shorter PFS (P = .02) and OS (P = .0066), independent of treatment arm. There were no statistically significant differences in toxicity of grade 3 or greater. Conclusion The addition of bevacizumab to gemcitabine/cisplatin in this trial did not significantly improve PFS or OS in patients with advanced MM. PMID:22665541

Shoulder motor performance assessment in the sagittal plane in children with hemiplegia during single joint pointing tasks.

PubMed

Formica, Domenico; Petrarca, Maurizio; Rossi, Stefano; Zollo, Loredana; Guglielmelli, Eugenio; Cappa, Paolo

2014-07-29

Pointing is a motor task extensively used during daily life activities and it requires complex visuo-motor transformation to select the appropriate movement strategy. The study of invariant characteristics of human movements has led to several theories on how the brain solves the redundancy problem, but the application of these theories on children affected by hemiplegia is limited. This study aims at giving a quantitative assessment of the shoulder motor behaviour in children with hemiplegia during pointing tasks. Eight children with hemiplegia were involved in the study and were asked to perform movements on the sagittal plane with both arms, at low and high speed. Subject movements were recorded using an optoelectronic system; a 4-DOF model of children arm has been developed to calculate kinematic and dynamic variables. A set of evaluation indexes has been extracted in order to quantitatively assess whether and how children modify their motor control strategies when perform movements with the more affected or less affected arm. In low speed movements, no differences can be seen in terms of movement duration and peak velocity between the More Affected arm (MA) and the Less Affected arm (LA), as well as in the main characteristics of movement kinematics and dynamics. As regards fast movements, remarkable differences in terms of strategies of motor control can be observed: while movements with LA did not show any significant difference in Dimensionless Jerk Index (JI) and Dimensionless Torque-change Cost index (TC) between the elevation and lowering phases, suggesting that motor control optimization is similar for movements performed with or against gravity, movements with MA showed a statistically significant increase of both JI and TC during lowering phase. Results suggest the presence of a different control strategy for fast movements in particular during lowering phase. Results suggest that motor control is not able to optimize Jerk and Torque-change cost functions in the same way when controls the two arms, suggesting that children with hemiplegia do not actively control MA lowering fast movements, in order to take advantage of the passive inertial body properties, rather than to attempt its optimal control.

Safety and Efficacy of HIV Hyperimmune Globulin (HIVIGLOB) for Prevention of Mother-to-Child HIV Transmission in HIV-1 infected Pregnant Women and their Infants in Kampala, Uganda (HIVIGLOB/NVP STUDY)

PubMed Central

Onyango-Makumbi, Carolyne; Omer, Saad B.; Mubiru, Michael; Moulton, Lawrence H.; Nakabiito, Clemensia; Musoke, Philippa; Mmiro, Francis; Zwerski, Sheryl; Wigzell, Hans; Falksveden, Lars; Wahren, Britta; Antelman, Gretchen; Fowler, Mary Glenn; Guay, Laura; Jackson, J. Brooks

2011-01-01

Background This phase III randomized clinical trial compared single dose nevirapine (sdNVP) plus HIV immunoglobulin (HIVIGLOB) to sdNVP alone for preventing maternal-to-child transmission (PMTCT) of HIV. Primary objectives were to determine rates of HIV infection among infants, and to assess the safety of HIVIGLOB in combination with sdNVP in HIV-infected Ugandan pregnant women and their infants. Methods Mother-infant pairs were randomized to receive 200mg of NVP to women in labor and 2mg/kg NVP to newborns within 72 hours after birth (sdNVP arm) or to receive sdNVP plus a single intravenous 240ml dose of HIVIGLOB given to women at 36-38 weeks gestation and a single intravenous 24ml dose to newborns within 18 hours of birth (HIVIGLOB/sdNVP arm). Risk of HIV infection was determined using Kaplan-Meier and risk ratio estimates at birth, 2, 6, 14 weeks, 6 and 12 months of age. Results Intent-to-treat analysis included 198 HIVIGLOB/sdNVP and 294 sdNVP mother-infant pairs. At 6 months of age, the primary endpoint, there was no statistically significant difference in HIV transmission in the HIVIGLOB/sdNVP arm versus the sdNVP arm (18.7% vs.15.0%; RR =1.240 [95% CI: 0.833-1.846]; p= 0.290). Similarly, the proportion of serious adverse events in the HIVIGLOB/sdNVP and sdNVP arms, respectively for mothers (18.9% vs. 19.3%; p= 0.91) and infants (62.6% vs. 59.5%; p=0.51), were not significantly different. Conclusion Giving mother-infant pairs an infusion of peripartum HIV hyperimmunoglobulin in addition to sdNVP for PMTCT was as safe as sdNVP alone, but was no more effective than sdNVP alone in preventing HIV transmission. PMID:21826009

Bimonthly 24 h infusion of high-dose 5-fluorouracil vs EAP regimen in patients with advanced gastric cancer. A randomized phase II study.

PubMed

Popov, I P; Jelić, S B; Krivokapić, Z V; Jezdić, S D; Pesko, P M; Micev, M T; Babić, D R

2008-01-01

To investigate the activity and toxicity of high dose (HD) infusional 5-FU in comparison to EAP regimen as first-line chemotherapy in patients with advanced gastric cancer. Histologically confirmed measurable advanced gastric cancer, age < 72 yr, ECOG performance status 0-2, no prior chemo- and radiotherapy, adequate organ functions. EAP arm: doxorubicin (40 mg/m(2)), etoposide (360 mg/m(2)), and cisplatin (80 mg/m(2)) every 28 d; HD 5-FU arm: 5-FU 2.6 g/m(2) 24 h infusion, biweekly. Sixty patients were randomized. Patient characteristics (arms EAP/HD 5-FU): Median age 57/55 yr, median PS 1/1, LAD (patients) 3/8, M1 (patients) 27/22. Median number of cycles (range): EAP arm 4 (2-8), HD 5-FU arm 2 (1-8). Worst toxicity per cycle (grade 3 and 4 in%): Neutropenia 20/3, thrombocytopenia 9/0, anemia 9/13, diarrhea 3/10, nausea 17/7, vomiting 10/0 for EAP and HD 5-FU arms, respectively. All patients were eligible for response in both arms. Confirmed response rate (95%CI): EAP arm 34% [16-50%]/HD 5-FU arm 10% (0-21%), no change: 46/40%, progression of disease: 20/50, respectively. Overall survival (range): EAP arm A 7 mo [3-27], HD 5-FU arm 6 mo (4-25). Infusional HD 5-FU showed a low incidence of severe toxicity. But given the low efficacy of 5-FU in the dosage we applied in the study, it cannot be recommended as a single treatment for further studies. Assessment of higher dose intensity and/or dose density of 5-FU, with introduction of other active drugs in combination, could be an option for further studies.

An open-label, single arm, phase III clinical study to evaluate the efficacy and safety of CJ smallpox vaccine in previously vaccinated healthy adults.

PubMed

Kim, Nak-Hyun; Kang, Yu Min; Kim, Gayeon; Choe, Pyoeng Gyun; Song, Jin Su; Lee, Kwang-Hee; Seong, Baik-Lin; Park, Wan Beom; Kim, Nam Joong; Oh, Myoung-don

2013-10-25

The increased possibility of bioterrorism has led to reinitiation of smallpox vaccination. In Korea, more than 30 years have passed since the last smallpox vaccinations, and even people who were previously vaccinated are not regarded as adequately protected against smallpox. We evaluated the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, in healthy adults previously vaccinated against smallpox. We conducted an open label, single arm, phase III clinical trial to evaluate the efficacy and safety of CJ-50300. Healthy volunteers, previously vaccinated against smallpox, born between 1950 and 1978 were enrolled. CJ-50300 was administered with a bifurcated needle over the deltoid muscle according to the recommended method. The rate of the cutaneous take reaction, humoral immunogenicity, and safety of the vaccine was assessed. Of 145 individuals enrolled for vaccination, 139 completed the study. The overall rates of cutaneous take reactions and humoral immunogenicity were 95.0% (132/139) and 88.5% (123/139), respectively. Although 95.9% (139/145) reported adverse events related to vaccination, no serious adverse reactions were observed. CJ-50300 can be used safely and effectively in healthy adults previously vaccinated against smallpox. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Characteristic investigation and control of a modular multilevel converter-based HVDC system under single-line-to-ground fault conditions

DOE PAGES

Shi, Xiaojie; Wang, Zhiqiang; Liu, Bo; ...

2014-05-16

This paper presents the analysis and control of a multilevel modular converter (MMC)-based HVDC transmission system under three possible single-line-to-ground fault conditions, with special focus on the investigation of their different fault characteristics. Considering positive-, negative-, and zero-sequence components in both arm voltages and currents, the generalized instantaneous power of a phase unit is derived theoretically according to the equivalent circuit model of the MMC under unbalanced conditions. Based on this model, a novel double-line frequency dc-voltage ripple suppression control is proposed. This controller, together with the negative-and zero-sequence current control, could enhance the overall fault-tolerant capability of the HVDCmore » system without additional cost. To further improve the fault-tolerant capability, the operation performance of the HVDC system with and without single-phase switching is discussed and compared in detail. Lastly, simulation results from a three-phase MMC-HVDC system generated with MATLAB/Simulink are provided to support the theoretical analysis and proposed control schemes.« less

Phase II Trials for Heterogeneous Patient Populations with a Time-to-Event Endpoint.

PubMed

Jung, Sin-Ho

2017-07-01

In this paper, we consider a single-arm phase II trial with a time-to-event end-point. We assume that the study population has multiple subpopulations with different prognosis, but the study treatment is expected to be similarly efficacious across the subpopulations. We review a stratified one-sample log-rank test and present its sample size calculation method under some practical design settings. Our sample size method requires specification of the prevalence of subpopulations. We observe that the power of the resulting sample size is not very sensitive to misspecification of the prevalence.

Carrier-to-noise power estimation for the Block 5 Receiver

NASA Technical Reports Server (NTRS)

Monk, A. M.

1991-01-01

Two possible algorithms for the carrier to noise power (P sub c/N sub 0) estimation in the Block V Receiver are analyzed and their performances compared. The expected value and the variance of each estimator algorithm are derived. The two algorithms examined are known as the I arm estimator, which relies on samples from only the in-phase arm of the digital phase lock loop, and the IQ arm estimator, which uses both in-phase and quadrature-phase arm signals. The IQ arm algorithm is currently implemented in the Advanced Receiver II (ARX II). Both estimators are biased. The performance degradation due to phase jitter in the carrier tracking loop is taken into account. Curves of the expected value and the signal to noise ratio of the P sub c/N sub 0 estimators vs. actual P sub c/N sub 0 are shown. From this, it is clear that the I arm estimator performs better than the IQ arm estimator when the data to noise power ratio (P sub d/N sub 0) is high, i.e., at high P sub c/N sub 0 values and a significant modulation index. When P sub d/N sub 0 is low, the two estimators have essentially the same performance.

Skill transfer from symmetric and asymmetric bimanual training using a robotic system to single limb performance

PubMed Central

2012-01-01

Background Humans are capable of fast adaptation to new unknown dynamics that affect their movements. Such motor learning is also believed to be an important part of motor rehabilitation. Bimanual training can improve post-stroke rehabilitation outcome and is associated with interlimb coordination between both limbs. Some studies indicate partial transfer of skills among limbs of healthy individuals. Another aspect of bimanual training is the (a)symmetry of bimanual movements and how these affect motor learning and possibly post-stroke rehabilitation. Methods A novel bimanual 2-DOF robotic system was used for both bimanual and unimanual reaching movements. 35 young healthy adults participated in the study. They were divided into 5 test groups that performed movements under different conditions (bimanual or unimanual movements and symmetric or asymmetric bimanual arm loads). The subjects performed a simple tracking exercise with the bimanual system. The exercise was developed to stimulate motor learning by applying a velocity-dependent disturbance torque to the handlebar. Each subject performed 255 trials divided into three phases: baseline without disturbance torque, training phase with disturbance torque and evaluation phase with disturbance torque. Results Performance was assessed with the maximal values of rotation errors of the handlebar. After exposure to disturbance torque, the errors decreased for both unimanual and bimanual training. Errors in unimanual evaluation following the bimanual training phase were not significantly different from errors in unimanual evaluation following unimanual training. There was no difference in performance following symmetric or asymmetric training. Changing the arm force symmetry during bimanual movements from asymmetric to symmetric had little influence on performance. Conclusions Subjects could adapt to an unknown disturbance torque that was changing the dynamics of the movements. The learning effect was present during both unimanual and bimanual training. Transfer of learned skills from bimanual training to unimanual movements was also observed, as bimanual training also improved single limb performance with the dominant arm. Changes of force symmetry did not have an effect on motor learning. As motor learning is believed to be an important mechanism of rehabilitation, our findings could be tested for future post-stroke rehabilitation systems. PMID:22805223

Mesomorphic properties of multi-arm chenodeoxycholic acid-derived liquid crystals

NASA Astrophysics Data System (ADS)

Dong, Liang; Yao, Miao; Wu, Shuang-jie; Yao, Dan-Shu; Hu, Jian-She; He, Xiao-zhi; Tian, Mei

2017-12-01

Four multi-arm liquid crystals (LCs) based on chenodeoxycholic acid, termed as 2G-PD, 2G-IB, 2G-BD and 5G-GC, respectively, have been synthesised by convergent method, which nematic LC, 6-(4-((4-ethoxybenzoyl)oxy)phenoxy)-6-oxohexanoic acid, was used as side arm, and chenodeoxycholic acid (CDCA) was used as the first core, 1,2-propanediol (PD), isosorbide (IB), 4,4‧-biphenyldiol (BD) and glucose (GC) were used as the second core, respectively. The first generation product, CDCA2EA, displayed cholesteric phase. The second generation products 2G-BD and 5G-GC displayed cholesteric phase, while 2G-PD and 2G-IB exhibited nematic phase. The multi-arm LC, 2G-IB, did not display cholesteric phase although the two cores were all chiral ones. The result indicated that chirality of the second core sometimes made the multi-arm LCs display nematic phase when cholesteric CDCA-derivative were introduced into the second core. Some attention should be paid on molecular conformation besides the introduction of chiral cores for multi-chiral-core LCs to obtain cholesteric phase.

Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia

PubMed Central

2013-01-01

Background As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. Methods We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon’s two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Results Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. Conclusions SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics. PMID:23819695

Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia.

PubMed

Yap, Christina; Pettitt, Andrew; Billingham, Lucinda

2013-07-03

As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon's two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics.

Investigation of phase transitions of saturated phosphocholine lipid bilayers via molecular dynamics simulations.

PubMed

Khakbaz, Pouyan; Klauda, Jeffery B

2018-08-01

Lipid bilayers play an important role in biological systems as they protect cells against unwanted chemicals and provide a barrier for material inside a cell from leaking out. In this paper, nearly 30 μs of molecular dynamics (MD) simulations were performed to investigate phase transitions of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-phosphocholine (DPPC) lipid bilayers from the liquid crystalline (L α ) to the ripple (P β ) and to the gel phase (L β ). Our MD simulations accurately predict the main transition temperature for the single-component bilayers. A key focus of this work is to quantify the structure of the P β phase for DMPC and compare with measures from x-ray experiments. The P β major arm has similar structure to that of the L β , while the thinner minor arm has interdigitated chains and the transition region between these two regions has large chain splay and disorder. At lower temperatures, our MD simulations predict the formation of the L β phase with tilted fatty acid chains. The P β and L β phases are studied for mixtures of DMPC and DPPC and compare favorably with experiment. Overall, our MD simulations provide evidence for the relevancy of the CHARMM36 lipid force field for structures and add to our understanding of the less-defined P β phase. Copyright © 2018 Elsevier B.V. All rights reserved.

An integrated optical sensor for measuring glucose concentration

NASA Astrophysics Data System (ADS)

Liu, Y.; Hering, P.; Scully, M. O.

1992-01-01

We used an optical sensor combined with a Mach-Zehnder interferometric waveguide and optical fibers to measure slight changes of aqueous sugar concentrations. The merits of this sensor are simplicity, reliability, high sensitivity and continuous monitoring. The technique is based on the fact that the refractive index of sugar solution changes with the concentration of sugar. In the experiment, one arm of the interferometer is clad with glue and is thus isolated from the sugar solution. The other one is exposed to the sugar solution. A single mode fiber is directly glued onto the interferometric waveguide, to guide the light into the interferometer. If the concentration of sugar covering the waveguide changes, the phase of propagating light in the exposed arm will be changed, while the phase in the other arm is fixed. Hence the output intensity from the interferometer is directly related to the concentration of the sugar solution. The result of this experiment yields the relation between the sugar concentration and output signal. From 0% to 1% concentration of sugar solution, there is only a 1.4×10-3 refractive index difference. Two sets of experimental data have been obtained, showing a linear relation between the sugar concentration and the output signal from our sensor. This sensor could be used for continuous monitoring of blood sugar in the human body.

Changes in kinematics and arm-leg coordination during a 100-m breaststroke swim.

PubMed

Oxford, Samuel W; James, Rob S; Price, Michael J; Payton, Carl J; Duncan, Michael J

2017-08-01

The purpose of this study was to compare arm-leg coordination and kinematics during 100 m breaststroke in 26 (8 female; 18 male) specialist breaststroke swimmers. Laps were recorded using three 50-Hz underwater cameras. Heart rate and blood lactate were measured pre- and post-swim. Arm-leg coordination was defined using coordination phases describing continuity between recovery and propulsive phases of upper and lower limbs: coordination phase 1 (time between end of leg kick and start of the arm pull phases); and coordination phase 2 (time between end of arm pull and start of leg kick phases). Duration of stroke phases, coordination phases, swim velocity, stroke length (SL), stroke rate (SR) and stroke index (SI) were analysed during the last three strokes of each lap that were unaffected by turning or finishing. Significant changes in velocity, SI and SL (P < 0.05) were found between laps. Both sexes showed significant increase (P < 0.05) in heart rate and blood lactate pre- to post-swim. Males had significantly (P < 0.01) faster swim velocities resulting from longer SLs (P = 0.016) with no difference in SR (P = 0.064). Sex differences in kinematic parameters can be explained by anthropometric differences providing males with increased propelling efficiency.

Generation of “Virtual” Control Groups for Single Arm Prostate Cancer Adjuvant Trials

PubMed Central

Koziol, James A.; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M.; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-guo; McLaren, Christine E.; Gurley, Michael J.; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W.; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies. PMID:24465467

Generation of "virtual" control groups for single arm prostate cancer adjuvant trials.

PubMed

Jia, Zhenyu; Lilly, Michael B; Koziol, James A; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-Guo; McLaren, Christine E; Gurley, Michael J; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies.

Michelson interferometer with diffractively-coupled arm resonators in second-order Littrow configuration.

PubMed

Britzger, Michael; Wimmer, Maximilian H; Khalaidovski, Alexander; Friedrich, Daniel; Kroker, Stefanie; Brückner, Frank; Kley, Ernst-Bernhard; Tünnermann, Andreas; Danzmann, Karsten; Schnabel, Roman

2012-11-05

Michelson-type laser-interferometric gravitational-wave (GW) observatories employ very high light powers as well as transmissively-coupled Fabry-Perot arm resonators in order to realize high measurement sensitivities. Due to the absorption in the transmissive optics, high powers lead to thermal lensing and hence to thermal distortions of the laser beam profile, which sets a limit on the maximal light power employable in GW observatories. Here, we propose and realize a Michelson-type laser interferometer with arm resonators whose coupling components are all-reflective second-order Littrow gratings. In principle such gratings allow high finesse values of the resonators but avoid bulk transmission of the laser light and thus the corresponding thermal beam distortion. The gratings used have three diffraction orders, which leads to the creation of a second signal port. We theoretically analyze the signal response of the proposed topology and show that it is equivalent to a conventional Michelson-type interferometer. In our proof-of-principle experiment we generated phase-modulation signals inside the arm resonators and detected them simultaneously at the two signal ports. The sum signal was shown to be equivalent to a single-output-port Michelson interferometer with transmissively-coupled arm cavities, taking into account optical loss. The proposed and demonstrated topology is a possible approach for future all-reflective GW observatory designs.

Total robotic radical rectal resection with da Vinci Xi system: single docking, single phase technique.

PubMed

Tamhankar, Anup Sunil; Jatal, Sudhir; Saklani, Avanish

2016-12-01

This study aims to assess the advantages of Da Vinci Xi system in rectal cancer surgery. It also assesses the initial oncological outcomes after rectal resection with this system from a tertiary cancer center in India. Robotic rectal surgery has distinct advantages over laparoscopy. Total robotic resection is increasing following the evolution of hybrid technology. The latest Da Vinci Xi system (Intuitive Surgical, Sunnyvale, USA) is enabled with newer features to make total robotic resection possible with single docking and single phase. Thirty-six patients underwent total robotic resection in a single phase and single docking. We used newer port positions in a straight line. Median distance from the anal verge was 4.5 cm. Median robotic docking time and robotic procedure time were 9 and 280 min, respectively. Median blood loss was 100 mL. One patient needed conversion to an open approach due to advanced disease. Circumferential resection margin and longitudinal resection margins were uninvolved in all other patients. Median lymph node yield was 10. Median post-operative stay was 7 days. There were no intra-operative adverse events. The latest Da Vinci Xi system has made total robotic rectal surgery feasible in single docking and single phase. With the new system, four arm total robotic rectal surgery may replace the hybrid technique of laparoscopic and robotic surgery for rectal malignancies. The learning curve for the new system appears to be shorter than anticipated. Early perioperative and oncological outcomes of total robotic rectal surgery with the new system are promising. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Safety results from a phase III study (TURANDOT trial by CECOG) of first-line bevacizumab in combination with capecitabine or paclitaxel for HER-2-negative locally recurrent or metastatic breast cancer.

PubMed

Lang, I; Inbar, M J; Kahán, Z; Greil, R; Beslija, S; Stemmer, S M; Kaufman, B; Zvirbule, Z; Steger, G G; Messinger, D; Brodowicz, T; Zielinski, C

2012-11-01

We report safety data from a randomised, phase III study (CECOG/BC.1.3.005) evaluating first-line bevacizumab plus paclitaxel or capecitabine for locally recurrent or metastatic breast cancer. Patients aged ≥18 years with human epidermal growth factor receptor-2-negative breast adenocarcinoma were randomised to Arm A: bevacizumab 10 mg/kg days 1 and 15; paclitaxel 90 mg/m(2) days 1, 8, and 15, every 4 weeks; or Arm B: bevacizumab 15 mg/kg day 1; capecitabine 1000 mg/m(2) b.i.d., days 1-14, every 3 weeks, until disease progression, unacceptable toxicity or consent withdrawal. A post hoc interim safety analysis included 561 patients (Arm A: 284, Arm B: 277). The regimens demonstrated similar frequencies of all-grade and serious adverse events (SAEs), but different safety profiles. Treatment-related events occurred in 85.2% (Arm A) and 78.0% (Arm B) of patients. Fatigue was most common in Arm A (30.6% versus 23.5% Arm B), and hand-foot syndrome (HFS) most common in Arm B (49.5% versus 2.5% Arm A). Diarrhoea (Arm A: 0.4%, Arm B: 1.4%) and pulmonary embolism (Arm A: 0.7%, Arm B: 1.1%) were the most frequently reported SAEs. These findings are in-line with safety data for bevacizumab plus paclitaxel or capecitabine, reported in previous phase III trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

Validation of post-operative residual contrast enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma.

PubMed

Ellingson, Benjamin M; Abrey, Lauren E; Nelson, Sarah J; Kaufmann, Timothy J; Garcia, Josep; Chinot, Olivier; Saran, Frank; Nishikawa, Ryo; Henriksson, Roger; Mason, Warren P; Wick, Wolfgang; Butowski, Nicholas; Ligon, Keith L; Gerstner, Elizabeth R; Colman, Howard; de Groot, John; Chang, Susan; Mellinghoff, Ingo; Young, Robert J; Alexander, Brian M; Colen, Rivka; Taylor, Jennie W; Arrillaga-Romany, Isabel; Mehta, Arnav; Huang, Raymond Y; Pope, Whitney B; Reardon, David; Batchelor, Tracy; Prados, Michael; Galanis, Evanthia; Wen, Patrick Y; Cloughesy, Timothy F

2018-04-05

In the current study, we pooled imaging data in newly diagnosed GBM patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between post-operative residual enhancing tumor volume and overall survival (OS). Data from 1,511 newly diagnosed GBM patients from 5 data sources were included in the current study: 1) a single institution database from UCLA (N=398; Discovery); 2) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N=262 from 8 centers; Confirmation); 3) the chemoradiation placebo arm from an international phase III trial (AVAglio; N=394 from 120 locations in 23 countries; Validation); 4) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N=404 from 120 locations in 23 countries; Exploratory Set 1); and 5) an Alliance (N0874) Phase I/II trial of vorinostat plus chemoradiation (N=53; Exploratory Set 2). Post-surgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, MGMT status, and residual tumor volume on OS. A log-linear relationship was observed between post-operative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Post-operative tumor volume is a prognostic factor for OS (P<0.01), regardless of therapy, age, and MGMT promoter methylation status. Post-surgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed glioblastoma treated with chemoradiation with or without concomitant experimental therapy.

Rationale and Study Design for a Single-Arm Phase IIa Study Investigating Feasibility of Preventing Ischemic Cerebrovascular Events in High-Risk Patients with Acute Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning

PubMed Central

Liu, Shi-Meng; Zhao, Wen-Le; Song, Hai-Qing; Meng, Ran; Li, Si-Jie; Ren, Chang-Hong; Ovbiagele, Bruce; Ji, Xun-Ming; Feng, Wu-Wei

2018-01-01

Background: Acute minor ischemic stroke (AMIS) or transient ischemic attack (TIA) is a common cerebrovascular event with a considerable high recurrence. Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning (RIC) in secondary stroke prevention in patients with intracranial stenosis. We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA. This study aimed to investigate the feasibility, safety, and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA. Methods: This is a single-arm, open-label, multicenter Phase IIa futility study with a sample size of 165. Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen. RIC consists of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days. The antiplatelet strategy is based on individual physician's best practice: aspirin alone, clopidogrel alone, or combination of aspirin and clopidogrel. We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes. Conclusions: The data gathered from the study will be used to determine whether a further large-scale, multicenter randomized controlled Phase II trial is warranted in patients with AMIS/TIA. Trial Registration: ClinicalTrials.gov, NCT03004820; https://www.clinicaltrials.gov/ct2/show/NCT03004820. PMID:29363651

Mechanically Reconfigurable Single-Arm Spiral Antenna Array for Generation of Broadband Circularly Polarized Orbital Angular Momentum Vortex Waves.

PubMed

Li, Long; Zhou, Xiaoxiao

2018-03-23

In this paper, a mechanically reconfigurable circular array with single-arm spiral antennas (SASAs) is designed, fabricated, and experimentally demonstrated to generate broadband circularly polarized orbital angular momentum (OAM) vortex waves in radio frequency domain. With the symmetrical and broadband properties of single-arm spiral antennas, the vortex waves with different OAM modes can be mechanically reconfigurable generated in a wide band from 3.4 GHz to 4.7 GHz. The prototype of the circular array is proposed, conducted, and fabricated to validate the theoretical analysis. The simulated and experimental results verify that different OAM modes can be effectively generated by rotating the spiral arms of single-arm spiral antennas with corresponding degrees, which greatly simplify the feeding network. The proposed method paves a reconfigurable way to generate multiple OAM vortex waves with spin angular momentum (SAM) in radio and microwave satellite communication applications.

Cloud Macro- and Microphysical Properties Derived from GOES over the ARM SGP Domain

NASA Technical Reports Server (NTRS)

Minnis, P.; Smith, W. L., Jr.; Young, D. F.

2001-01-01

Cloud macrophysical properties like fractional coverage and height Z(sub c) and microphysical parameters such as cloud liquid water path (LWP), effective droplet radius r(sub e), and cloud phase, are key factors affecting both the radiation budget and the hydrological cycle. Satellite data have been used to complement surface observations from Atmospheric Radiation Measurements (ARM) by providing additional spatial coverage and top-of-atmosphere boundary conditions of these key parameters. Since 1994, the Geostationary Operational Environmental Satellite (GOES) has been used for deriving at each half-hour over the ARM Southern Great Plains (SGP) domain: cloud amounts, altitudes, temperatures, and optical depths as well as broadband shortwave (SW) albedo and outgoing longwave radiation at the top of the atmosphere. A new operational algorithm has been implemented to increase the number of value-added products to include cloud particle phase and effective size (r(sub e) or effective ice diameter D(sub e)) as well as LWP and ice water path. Similar analyses have been performed on the data from the Visible Infrared Scanner (VIRS) on the Tropical Rainfall Measuring Mission satellite as part of the Clouds and Earth's Radiant Energy System project. This larger suite of cloud properties will enhance our knowledge of cloud processes and further constrain the mesoscale and single column models using ARM data as a validation/initialization resource. This paper presents the results of applying this new algorithm to GOES-8 data taken during 1998 and 2000. The global VIRS results are compared to the GOES SGP results to provide appropriate context and to test consistency.

Learning robotic eye-arm-hand coordination from human demonstration: a coupled dynamical systems approach.

PubMed

Lukic, Luka; Santos-Victor, José; Billard, Aude

2014-04-01

We investigate the role of obstacle avoidance in visually guided reaching and grasping movements. We report on a human study in which subjects performed prehensile motion with obstacle avoidance where the position of the obstacle was systematically varied across trials. These experiments suggest that reaching with obstacle avoidance is organized in a sequential manner, where the obstacle acts as an intermediary target. Furthermore, we demonstrate that the notion of workspace travelled by the hand is embedded explicitly in a forward planning scheme, which is actively involved in detecting obstacles on the way when performing reaching. We find that the gaze proactively coordinates the pattern of eye-arm motion during obstacle avoidance. This study provides also a quantitative assessment of the coupling between the eye-arm-hand motion. We show that the coupling follows regular phase dependencies and is unaltered during obstacle avoidance. These observations provide a basis for the design of a computational model. Our controller extends the coupled dynamical systems framework and provides fast and synchronous control of the eyes, the arm and the hand within a single and compact framework, mimicking similar control system found in humans. We validate our model for visuomotor control of a humanoid robot.

Contribution of inter-muscular synchronization in the modulation of tremor intensity in Parkinson's disease.

PubMed

He, Xin; Hao, Man-Zhao; Wei, Ming; Xiao, Qin; Lan, Ning

2015-12-01

Involuntary central oscillations at single and double tremor frequencies drive the peripheral neuromechanical system of muscles and joints to cause tremor in Parkinson's disease (PD). The central signal of double tremor frequency was found to correlate more directly to individual muscle EMGs (Timmermann et al. 2003). This study is aimed at investigating what central components of oscillation contribute to inter-muscular synchronization in a group of upper extremity muscles during tremor in PD patients. 11 idiopathic, tremor dominant PD subjects participated in this study. Joint kinematics during tremor in the upper extremity was recorded along with EMGs of six upper arm muscles using a novel experimental apparatus. The apparatus provided support for the upper extremity on a horizontal surface with reduced friction, so that resting tremor in the arm can be recorded with a MotionMonitor II system. In each subject, the frequencies of rhythmic firings in upper arm muscles were determined using spectral analysis. Paired and pool-averaged coherence analyses of EMGs for the group of muscles were performed to correlate the level of inter-muscular synchronization to tremor amplitudes at shoulder and elbow. The phase shift between synchronized antagonistic muscle pairs was calculated to aid coherence analysis in the muscle pool. Recorded EMG revealed that rhythmic firings were present in most recorded muscles, which were either synchronized to form phase-locked bursting cycles at a subject specific frequency, or unsynchronized with a random phase distribution. Paired coherence showed a stronger synchronization among a subset of recorded arm muscles at tremor frequency than that at double tremor frequency. Furthermore, the number of synchronized muscles in the arm was positively correlated to tremor amplitudes at elbow and shoulder. Pool-averaged coherence at tremor frequency also showed a better correlation with the amplitude of resting tremor than that of double tremor frequency, indicating that the neuromechanical coupling in peripheral neuromuscular system was stronger at tremor frequency. Both paired and pool-averaged coherences are more consistent indexes to correlate to tremor intensity in a group of upper extremity muscles of PD patients. The central drive at tremor frequency contributes mainly to synchronize peripheral muscles in the modulation of tremor intensity.

Activity of upper limb muscles during human walking.

PubMed

Kuhtz-Buschbeck, Johann P; Jing, Bo

2012-04-01

The EMG activity of upper limb muscles during human gait has rarely been studied previously. It was examined in 20 normal volunteers in four conditions: walking on a treadmill (1) with unrestrained natural arm swing (Normal), (2) while volitionally holding the arms still (Held), (3) with the arms immobilized (Bound), and (4) with the arms swinging in phase with the ipsilateral legs, i.e. opposite-to-normal phasing (Anti-Normal). Normal arm swing involved weak rhythmical lengthening and shortening contractions of arm and shoulder muscles. Phasic muscle activity was needed to keep the unrestricted arms still during walking (Held), indicating a passive component of arm swing. An active component, possibly programmed centrally, existed as well, because some EMG signals persisted when the arms were immobilized during walking (Bound). Anti-Normal gait involved stronger EMG activity than Normal walking and was uneconomical. The present results indicate that normal arm swing has both passive and active components. Copyright © 2011 Elsevier Ltd. All rights reserved.

Intelligence and arms control - a marriage of convenience

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

Hirschfeld, T.J.

1987-01-01

This book offers the first comprehensive look at how the vast US intelligence network enables negotiators to forge viable arms control agreements. The intelligence role in all three phases of the arms control process is discussed - from the design phase when reliable information is needed, to the execution phase when proposals are modified, to the maintenance phase when agreed-upon obligations begin to constrain adversary behavior and compliance becomes the key political issue. Contributors include: former CIA Director William E. Colby; Douglas George, Chief of the CIA's Control Intelligence Staff, Admiral Bobby R. Inman, former NSA Director; Hans Mark, formermore » Air Force Secretary and NSA administrator; Walt W. Rostow, National Security Adviser to President Johnson; and Paul Warnke, former Director of the Arms Control and Disarmament Agency and Chief Negotiator for SALT II.« less

Oxygen vacancies controlled multiple magnetic phases in epitaxial single crystal Co0.5(Mg0.55Zn0.45)0.5O1-v thin films

PubMed Central

Zhu, Dapeng; Cao, Qiang; Qiao, Ruimin; Zhu, Shimeng; Yang, Wanli; Xia, Weixing; Tian, Yufeng; Liu, Guolei; Yan, Shishen

2016-01-01

High quality single-crystal fcc-Cox(MgyZn1-y)1-xO1-v epitaxial thin films with high Co concentration up to x = 0.5 have been fabricated by molecular beam epitaxy. Systematic magnetic property characterization and soft X-ray absorption spectroscopy analysis indicate that the coexistence of ferromagnetic regions, superparamagnetic clusters, and non-magnetic boundaries in the as-prepared Cox(MgyZn1-y)1-xO1-v films is a consequence of the intrinsic inhomogeneous distribution of oxygen vacancies. Furthermore, the relative strength of multiple phases could be modulated by controlling the oxygen partial pressure during sample preparation. Armed with both controllable magnetic properties and tunable band-gap, Cox(MgyZn1-y)1-xO1-v films may have promising applications in future spintronics. PMID:27062992

Aprepitant as an add-on therapy in children receiving highly emetogenic chemotherapy: a randomized, double-blind, placebo-controlled trial.

PubMed

Bakhshi, Sameer; Batra, Atul; Biswas, Bivas; Dhawan, Deepa; Paul, Reeja; Sreenivas, Vishnubhatla

2015-11-01

Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years. A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5-18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15-40 kg = days 1-3, 80 mg; 41-65 kg = day 1, 125 mg and days 2-3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase. Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p < 0.001). No major adverse effects were reported by patients/guardians. This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children receiving highly emetogenic chemotherapy.

Evaluation of the immunogenicity and safety of different doses and formulations of a broad spectrum influenza vaccine (FLU-v) developed by SEEK: study protocol for a single-center, randomized, double-blind and placebo-controlled clinical phase IIb trial.

PubMed

van Doorn, Eva; Pleguezuelos, Olga; Liu, Heng; Fernandez, Ana; Bannister, Robin; Stoloff, Gregory; Oftung, Fredrik; Norley, Stephen; Huckriede, Anke; Frijlink, Henderik W; Hak, Eelko

2017-04-04

Current influenza vaccines, based on antibodies against surface antigens, are unable to provide protection against newly emerging virus strains which differ from the vaccine strains. Therefore the population has to be re-vaccinated annually. It is thus important to develop vaccines which induce protective immunity to a broad spectrum of influenza viruses. This trial is designed to evaluate the immunogenicity and safety of FLU-v, a vaccine composed of four synthetic peptides with conserved epitopes from influenza A and B strains expected to elicit both cell mediated immunity (CMI) and humoral immunity providing protection against a broad spectrum of influenza viruses. In a single-center, randomized, double-blind and placebo-controlled phase IIb trial, 222 healthy volunteers aged 18-60 years will be randomized (2:2:1:1) to receive two injections of a suspension of 500 μg FLU-v in saline (arm 1), one dose of emulsified 500 μg FLU-v in Montanide ISA-51 and water for injection (WFI) followed by one saline dose (arm 2), two saline doses (arm 3), or one dose of Montanide ISA-51 and WFI emulsion followed by one saline dose (arm 4). All injections will be given subcutaneously. Primary endpoints are safety and FLU-v induced CMI, evaluated by cytokine production by antigen specific T cell populations (flow-cytometry and ELISA). Secondary outcomes are measurements of antibody responses (ELISA and multiplex), whereas exploratory outcomes include clinical efficacy and additional CMI assays (ELISpot) to show cross-reactivity. Broadly protective influenza vaccines able to provide protection against multiple strains of influenza are urgently needed. FLU-v is a promising vaccine which has shown to trigger the cell-mediated immune response. The dosages and formulations tested in this current trial are also estimated to induce antibody response. Therefore, both cellular and humoral immune responses will be evaluated. EudraCT number 2015-001932-38 ; retrospectively registered clinicaltrials.gov NCT02962908 (November 7th 2016).

Discrimination of What, When, and Where: Implications for Episodic-Like Memory in Rats

ERIC Educational Resources Information Center

Babb, S.J.; Crystal, J.D.

2005-01-01

We investigated the discrimination of what, when, and where in rats (n=5) using an eight-arm radial maze. Rats received daily training consisting of forced-choice visits to four baited arms, one of which was randomly chosen each day to contain chocolate (Phase 1). In Phase 2, all eight arms were available. After a short (30min) retention interval…

Evaluation of nutritional indicators and body composition in patients with advanced liver disease enrolled for liver transplantation.

PubMed

Vulcano, Daniela Salate Biagioni; Carvalhaes, Maria Antonieta de Barros Leite; Bakonyi Neto, Alexandre

2013-10-01

Malnutrition is prevalent in patients with advanced liver disease (LD) related to multifactorial causes. Fluid retention can underestimate the nutritional status based on anthropometric measures. We evaluated nutritional indicators and body composition (BC) in patients with liver cirrhosis and correlated them with LD severity. Forty three patients with LD enrolled for liver transplantation were evaluated by Anthropometric measures, subjective evaluation (Global Assessment of Nutritional Status - SGA) and biochemical indicators. Single-frequency electrical bioimpedance (SFE-BIA) was used to evaluate body composition (BC). It measured resistance (R), reactance (Xc) and the phase angle (PA). LD severity was estimated by Child-Pugh and Meld criteria (Model for End-Stage Liver Disease). Child-Pugh index between patients was 7.11 ± 1.70 and Meld was 12.23 ± 4.22. Arm Circumference, Arm Muscle Circumference and Arm Muscle Area, SGA, hemoglobin, hematocrit and albumin showed better correlation with disease severity. Xc and PA showed correlation both with Meld and Child-Pugh score when BC were evaluated. PA was depleted in 55.8% of the patients. Diagnosis of malnutrition varied according to the method. Global assessment of nutritional status showed better correlation with disease severity than with objective methods. Single-frequency electrical bioimpedance for body composition analysis in cirrhotic patients must be cautiously used; however, primary vectors seems to be valid and promising in clinical practice.

Star-Shaped Conjugated Systems

PubMed Central

Detert, Heiner; Lehmann, Matthias; Meier, Herbert

2010-01-01

The present review deals with the preparation and the properties of star-shaped conjugated compounds. Three, four or six conjugated arms are attached to cross-conjugated cores, which consist of single atoms (B, C+, N), benzene or azine rings or polycyclic ring systems, as for example triphenylene or tristriazolotriazine. Many of these shape-persistent [n]star compounds tend to π-stacking and self-organization, and exhibit interesting properties in materials science: Linear and non-linear optics, electrical conductivity, electroluminescence, formation of liquid crystalline phases, etc.

Gas Sensors Based on Single-Arm Waveguide Interferometers

NASA Technical Reports Server (NTRS)

Sarkisov, Sergey; Curley, Michael; Diggs, Darnell; Adamovsky, Grigory

1998-01-01

Various optical technologies can be implemented in chemical sensing. Sensitive, rugged, and compact systems will be more likely built using interferometric waveguide sensors. Currently existing sensors comprise dual-arm systems with external reference arm, dual-arm devices with internal reference arm such as integrated Mach-Zehnder interferometer, and single-arm systems which employ the interference between different waveguide modes. These latter ones are the most compact and rugged but still sensitive enough to monitor volatile pollutants such as NH3 coming out of industrial refrigerators and fertilizer plants and stocks, NO, NO2, SO2, emitted by industrial burning processes. Single-arm devices in planar waveguide configuration most frequently use two orthogonally polarized modes TE (sub i) and TM (sub i) of the same order i. Sensing effect is based on the difference in propagation conditions for the modes caused by the environment. However, dual-mode single-order interferometers still have relatively low sensitivity with respect to the environment related changes in the waveguide core because of small difference between propagation constants of TE (sub i) and TM (sub i) modes of the same order. Substantial sensitivity improvement without significant complication can be achieved for planar waveguide interferometers using modes of different orders with much greater difference between propagation constants.

Laboratory Performance of the Single-Sided E-A-R (registered trademark) Combat Arms Hearing Protective Earplug

DTIC Science & Technology

2010-01-01

mdividu a eté evalue sans protection auditive ctaye.c port. binaural du protecteur dans chacun des deux modes. Les seuils auditifs en champ hbre...which the ears were: unocciuded (Unocelud), fitted binaurally with the single- sided version of the Combat Arms earplug in the steady state noise mode...CAE SS), and fitted binaurally with the single-sided version of the Combat Arms earplug in the weapons fire mode (CAE WF). The unoccluded condition was

Randomized Phase II Study of Carboplatin and Paclitaxel With Either Linifanib or Placebo for Advanced Nonsquamous Non–Small-Cell Lung Cancer

PubMed Central

Ramalingam, Suresh S.; Shtivelband, Mikhail; Soo, Ross A.; Barrios, Carlos H.; Makhson, Anatoly; Segalla, José G.M.; Pittman, Kenneth B.; Kolman, Petr; Pereira, Jose R.; Srkalovic, Gordan; Belani, Chandra P.; Axelrod, Rita; Owonikoko, Taofeek K.; Qin, Qin; Qian, Jiang; McKeegan, Evelyn M.; Devanarayan, Viswanath; McKee, Mark D.; Ricker, Justin L.; Carlson, Dawn M.; Gorbunova, Vera A.

2015-01-01

Purpose Linifanib, a potent, selective inhibitor of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors, has single-agent activity in non–small-cell lung cancer (NSCLC). We evaluated linifanib with carboplatin and paclitaxel as first-line therapy of advanced nonsquamous NSCLC. Patients and Methods Patients with stage IIIB/IV nonsquamous NSCLC were randomly assigned to 3-week cycles of carboplatin (area under the curve 6) and paclitaxel (200 mg/m2) with daily placebo (arm A), linifanib 7.5 mg (arm B), or linifanib 12.5 mg (arm C). The primary end point was progression-free survival (PFS); secondary efficacy end points included overall survival (OS) and objective response rate. Results One hundred thirty-eight patients were randomly assigned (median age, 61 years; 57% men; 84% smokers). Median PFS times were 5.4 months (95% CI, 4.2 to 5.7 months) in arm A (n = 47), 8.3 months (95% CI, 4.2 to 10.8 months) in arm B (n = 44), and 7.3 months (95% CI, 4.6 to 10.8 months) in arm C (n = 47). Hazard ratios (HRs) for PFS were 0.51 for arm B versus A (P = .022) and 0.64 for arm C versus A (P = .118). Median OS times were 11.3, 11.4, and 13.0 months in arms A, B, and C, respectively. HRs for OS were 1.08 for arm B versus A (P = .779) and 0.88 for arm C versus A (P = .650). Both linifanib doses were associated with increased toxicity, including a higher incidence of adverse events known to be associated with VEGF/PDGF inhibition. Baseline plasma carcinoembryonic antigen/cytokeratin 19 fragments biomarker signature was associated with PFS improvement and a trend toward OS improvement with linifanib 12.5 mg. Conclusion Addition of linifanib to chemotherapy significantly improved PFS (arm B), with a modest trend for survival benefit (arm C) and increased toxicity reflective of known VEGF/PDGF inhibitory effects. PMID:25559798

Randomised phase III trial of vinflunine plus capecitabine versus capecitabine alone in patients with advanced breast cancer previously treated with an anthracycline and resistant to taxane.

PubMed

Martin, M; Campone, M; Bondarenko, I; Sakaeva, D; Krishnamurthy, S; Roman, L; Lebedeva, L; Vedovato, J-C; Aapro, M

2018-05-01

Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II studies in this setting and activity and tolerability when combined with capecitabine. We compared the combination of vinflunine plus capecitabine (VC) with single-agent capecitabine. Patients with locally recurrent/metastatic BC previously treated or resistant to an anthracycline and resistant to taxane therapy were randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine [825 mg/m2 twice daily (b.i.d.), days 1-14] every 3 weeks (q3w) or single-agent oral capecitabine (1250 mg/m2 b.i.d., days 1-14) q3w. The primary end point was progression-free survival (PFS) assessed by an independent review committee. The study had 90% power to detect a 30% improvement in PFS. Overall, 770 patients were randomised. PFS was significantly longer with VC than with capecitabine alone [hazard ratio, 0.84, 95% confidence interval (CI), 0.71-0.99; log-rank P = 0.043; median 5.6 versus 4.3 months, respectively]. Median overall survival was 13.9 versus 11.7 months with VC versus capecitabine alone, respectively (hazard ratio, 0.98; 95% CI, 0.83-1.15; log-rank P = 0.77). No difference in quality of life was observed between the two treatment arms. The most common adverse events (NCI CTCAE version 3.0) in the combination arm were haematological and gastrointestinal. Grade 4 neutropenia was more frequent with VC (12% versus 1% with capecitabine alone); febrile neutropenia occurred in 2% versus 0.5%, respectively. Hand-foot syndrome was less frequent with VC (grade 3: 4% versus 19% for capecitabine alone). Peripheral neuropathy was uncommon in both arms (grade 3: 1% versus 0.3%). Vinflunine combined with capecitabine demonstrated a modest improvement in PFS and an acceptable safety profile compared with capecitabine alone in patients with anthracycline- and taxane-pretreated locally recurrent/metastatic BC. NCT01095003.

Phase-dependent organization of postural adjustments associated with arm movements while walking.

PubMed

Nashner, L M; Forssberg, H

1986-06-01

This study examines the interactions between anteroposterior postural responses and the control of walking in human subjects. In the experimental paradigm, subjects walked upon a treadmill, gripping a rigid handle with one hand. Postural responses at different phases of stepping were elicited by rapid arm pulls or pushes against the handle. During arm movements, EMG's recorded the activity of representative arm, ankle, and thigh segment muscles. Strain gauges in the handle measured the force of the arm movement. A Selspot II system measured kinematics of the stepping movements. The duration of support and swing phases were marked by heel and toe switches in the soles of the subjects' shoes. In the first experiment, subjects were instructed to pull on the handle at their own pace. In these trials all subjects preferred to initiate pulls near heel strikes. Next, when instructed to pull as rapidly as possible in response to tone stimuli, reaction times were similar for all phases of the step cycle. Leg muscle responses associated with arm pulls and pushes, referred to as "postural activations," were directionally specific and preceded arm muscle activity. The temporal order and spatial distribution of postural activations in the muscles of the support leg were similar when arm pull movements occurred while the subject was standing in place and after heel strike while walking. Activations began in the ankle and radiated proximally to the thigh and then the arm. Activations of swing leg muscles were also directionally specific and involved flexion and forward or backward thrust of the limb. When arm movements were initiated during transitions from support by one leg to the other, patterns of postural activations were altered. Alterations usually occurred 10-20 ms before hell strikes and involved changes in the timing and sometimes the spatial structure of postural activations. Postural activation patterns are similar during in-place standing and during the support phase of locomotion. Walking and posture control appear to be separately organized but interrelated activities. Our results also suggest that the stepping generators, not peripheral feedback time locked to heel strikes, modulate postural activation patterns.

Naturally stable Sagnac–Michelson nonlinear interferometer

DOE PAGES

Lukens, Joseph M.; Peters, Nicholas A.; Pooser, Raphael C.

2016-11-16

Interferometers measure a wide variety of dynamic processes by converting a phase change into an intensity change. Nonlinear interferometers, making use of nonlinear media in lieu of beamsplitters, promise substantial improvement in the quest to reach the ultimate sensitivity limits. Here we demonstrate a new nonlinear interferometer utilizing a single parametric amplifier for mode mixing conceptually, a nonlinear version of the conventional Michelson interferometer with its arms collapsed together. We observe up to 99.9% interference visibility and find evidence for noise reduction based on phase-sensitive gain. As a result, our configuration utilizes fewer components than previous demonstrations and requires nomore » active stabilization, offering new capabilities for practical nonlinear interferometric-based sensors.« less

Quantum-enhanced multiparameter estimation in multiarm interferometers

PubMed Central

Ciampini, Mario A.; Spagnolo, Nicolò; Vitelli, Chiara; Pezzè, Luca; Smerzi, Augusto; Sciarrino, Fabio

2016-01-01

Quantum metrology is the state-of-the-art measurement technology. It uses quantum resources to enhance the sensitivity of phase estimation over that achievable by classical physics. While single parameter estimation theory has been widely investigated, much less is known about the simultaneous estimation of multiple phases, which finds key applications in imaging and sensing. In this manuscript we provide conditions of useful particle (qudit) entanglement for multiphase estimation and adapt them to multiarm Mach-Zehnder interferometry. We theoretically discuss benchmark multimode Fock states containing useful qudit entanglement and overcoming the sensitivity of separable qudit states in three and four arm Mach-Zehnder-like interferometers - currently within the reach of integrated photonics technology. PMID:27381743

Randomized ablation strategies for the treatment of persistent atrial fibrillation: RASTA study.

PubMed

Dixit, Sanjay; Marchlinski, Francis E; Lin, David; Callans, David J; Bala, Rupa; Riley, Michael P; Garcia, Fermin C; Hutchinson, Mathew D; Ratcliffe, Sarah J; Cooper, Joshua M; Verdino, Ralph J; Patel, Vickas V; Zado, Erica S; Cash, Nancy R; Killian, Tony; Tomson, Todd T; Gerstenfeld, Edward P

2012-04-01

The single-procedure efficacy of pulmonary vein isolation (PVI) is less than optimal in patients with persistent atrial fibrillation (AF). Adjunctive techniques have been developed to enhance single-procedure efficacy in these patients. We conducted a study to compare 3 ablation strategies in patients with persistent AF. Subjects were randomized as follows: arm 1, PVI + ablation of non-PV triggers identified using a stimulation protocol (standard approach); arm 2, standard approach + empirical ablation at common non-PV AF trigger sites (mitral annulus, fossa ovalis, eustachian ridge, crista terminalis, and superior vena cava); or arm 3, standard approach + ablation of left atrial complex fractionated electrogram sites. Patients were seen at 6 weeks, 6 months, and 1 year; transtelephonic monitoring was performed at each visit. Antiarrhythmic drugs were discontinued at 3 to 6 months. The primary study end point was freedom from atrial arrhythmias off antiarrhythmic drugs at 1 year after a single-ablation procedure. A total of 156 patients (aged 59±9 years; 136 males; AF duration, 47±50 months) participated (arm 1, 55 patients; arm 2, 50 patients; arm 3, 51 patients). Procedural outcomes (procedure, fluoroscopy, and PVI times) were comparable between the 3 arms. More lesions were required to target non-PV trigger sites than a complex fractionated electrogram (33±9 versus 22±9; P<0.001). The primary end point was achieved in 71 patients and was worse in arm 3 (29%) compared with arm 1 (49%; P=0.04) and arm 2 (58%; P=0.004). These data suggest that additional substrate modification beyond PVI does not improve single-procedure efficacy in patients with persistent AF. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00379301.

Functional and evolutionary trade-offs co-occur between two consolidated memory phases in Drosophila melanogaster

PubMed Central

Lagasse, Fabrice; Moreno, Celine; Preat, Thomas; Mery, Frederic

2012-01-01

Memory is a complex and dynamic process that is composed of different phases. Its evolution under natural selection probably depends on a balance between fitness benefits and costs. In Drosophila, two separate forms of consolidated memory phases can be generated experimentally: anaesthesia-resistant memory (ARM) and long-term memory (LTM). In recent years, several studies have focused on the differences between these long-lasting memory types and have found that, at the functional level, ARM and LTM are antagonistic. How this functional relationship will affect their evolutionary dynamics remains unknown. We selected for flies with either improved ARM or improved LTM over several generations, and found that flies selected specifically for improvement of one consolidated memory phase show reduced performance in the other memory phase. We also found that improved LTM was linked to decreased longevity in male flies but not in females. Conversely, males with improved ARM had increased longevity. We found no correlation between either improved ARM or LTM and other phenotypic traits. This is, to our knowledge, the first evidence of a symmetrical evolutionary trade-off between two memory phases for the same learning task. Such trade-offs may have an important impact on the evolution of cognitive capacities. On a neural level, these results support the hypothesis that mechanisms underlying these forms of consolidated memory are, to some degree, antagonistic. PMID:22859595

Experimental verification of arm-locking for LISA using electronic phase delay [rapid communication

NASA Astrophysics Data System (ADS)

Thorpe, J. I.; Mueller, G.

2005-07-01

We present results of an electronic model of arm-locking, a proposed technique for reducing the laser phase noise in the laser interferometer space antenna (LISA). The model is based on a delay of 500 ms, achieved using the electronic phase delay (EPD) method. The observed behavior is consistent with predictions.

Dual-reference digital holographic interferometry for analyzing high-density gradients in fluid mechanics.

PubMed

Desse, Jean-Michel; Olchewsky, François

2018-04-15

This Letter proposes a dual-reference digital holographic interferometer for analyzing the high refractive index encountered in transonic and supersonic flows. For that, a Wollaston prism is inserted in the reference arm in order to simultaneously generate two orthogonally polarized reference waves. As a consequence, recorded interferograms contain two crossed and perpendicular interference patterns that give two orders fully separated in the Fourier spectrum. It is then possible to analyze a transparent object regardless of the orientation of the refractive index gradient using the two phase maps reconstructed with each of the two first interference orders. Fusion of the phase maps yields a single phase map in which the phase singularities are removed. Experimental results demonstrate the suitability of the proposed approach for analyzing shock waves in the unsteady wake flow around a circular cylinder at Mach 0.75.

Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial

PubMed Central

Wasunna, Monique; Njenga, Simon; Balasegaram, Manica; Alexander, Neal; Omollo, Raymond; Edwards, Tansy; Dorlo, Thomas P. C.; Musa, Brima; Ali, Mohammed Hassan Sharaf; Elamin, Mohammed Yasein; Kirigi, George; Kip, Anke E.; Schoone, Gerard J.; Hailu, Asrat; Olobo, Joseph; Ellis, Sally; Kimutai, Robert; Wells, Susan; Khalil, Eltahir Awad Gasim; Strub Wourgaft, Nathalie; Alves, Fabiana; Musa, Ahmed

2016-01-01

Background SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. Methods A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments. Results In sequential analyses with 49–51 patients per arm, initial cure was 85% (95% CI: 73–92) in all arms. At D210, definitive cure was 87% (95% CI: 77–97) for AmBisome + SSG, 77% (95% CI 64–90) for AmBisome + miltefosine and 72% (95% CI 60–85) for miltefosine alone, with lower efficacy in younger patients, who weigh less. Miltefosine pharmacokinetic data indicated under-exposure in children compared to adults. Conclusion No major safety concerns were identified, but point estimates of definitive cure were less than 90% for each regimen so none will be evaluated in Phase III trials in their current form. Allometric dosing of miltefosine in children needs to be evaluated. Trial Registration The study was registered with ClinicalTrials.gov, number NCT01067443 PMID:27627654

Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study.

PubMed

Morris, Van K; Salem, Mohamed E; Nimeiri, Halla; Iqbal, Syma; Singh, Preet; Ciombor, Kristen; Polite, Blase; Deming, Dustin; Chan, Emily; Wade, James L; Xiao, Lianchun; Bekaii-Saab, Tanios; Vence, Luis; Blando, Jorge; Mahvash, Armeen; Foo, Wai Chin; Ohaji, Chimela; Pasia, Manolo; Bland, Gail; Ohinata, Aki; Rogers, Jane; Mehdizadeh, Amir; Banks, Kimberly; Lanman, Richard; Wolff, Robert A; Streicher, Howard; Allison, James; Sharma, Padmanee; Eng, Cathy

2017-04-01

Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169. We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15-33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported. To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease. National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study

PubMed Central

Morris, Van K; Salem, Mohamed E; Nimeiri, Halla; Iqbal, Syma; Singh, Preet; Ciombor, Kristen; Polite, Blase; Deming, Dustin; Chan, Emily; Wade, James L; Xiao, Lianchun; Bekaii-Saab, Prof Tanios; Vence, Luis; Blando, Jorge; Mahvash, Armeen; Foo, Wai Chin; Ohaji, Chimela; Pasia, Manolo; Bland, Gail; Ohinata, Aki; Rogers, Jane; Mehdizadeh, Amir; Banks, Kimberly; Lanman, Richard; Wolff, Robert A; Streicher, Howard; Allison, Prof James; Sharma, Prof Padmanee; Eng, Prof Cathy

2018-01-01

Summary Background Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. Methods We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169. Findings We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15–33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported. Interpretation To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease. Funding National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor. PMID:28223062

The effects of additional arm weights on arm-swing magnitude and gait patterns in Parkinson's disease.

PubMed

Yoon, Jiyeon; Park, Jinse; Park, Kunbo; Jo, Geunyeol; Kim, Haeyu; Jang, Wooyoung; Kim, Ji Sun; Youn, Jinyoung; Oh, Eung Seok; Kim, Hee-Tae; Youm, Chang Hong

2016-01-01

Recently, arm facilitation has been interested in gait rehabilitation. However, there have been few studies concerning arm facilitation in patients with Parkinson's disease (PD). The aim of our study was to investigate the effect of increasing arm weights on gait pattern in patients with PD. Twenty-seven patients with PD were enrolled, and they underwent gait analysis using a three-dimensional motion capture system. Sandbags were applied to the distal forearms in all participants. We compared gait parameters including arm swing, pelvic motion, spatiotemporal data, and relative rotational angle between the weighted and unweighted gaits. The total arm-swing amplitude and pelvic rotation were significantly higher when walking with additional arm weights than without arm weights. Cadence, walking speed, stride length, and swing phase were significantly higher, whereas stride time, double-support time, and stance phase were significantly lower, when walking with additional arm weights than without arm weights. We conclude that adding weights to the arm during walking may facilitate arm and pelvic movements, which results in changes to gait patterns. The therapeutic use of additional arm weights could be considered for gait rehabilitation in PD to improve gait impairment. Arm-swing facilitation using weight load improved gait in Parkinson's disease. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Standardisation of information submitted to an endpoint committee for cause of death assignment in a cancer screening trial – lessons learnt from CAP (Cluster randomised triAl of PSA testing for Prostate cancer).

PubMed

Williams, Naomi J; Hill, Elizabeth M; Ng, Siaw Yein; Martin, Richard M; Metcalfe, Chris; Donovan, Jenny L; Evans, Simon; Hughes, Laura J; Davies, Charlotte F; Hamdy, Freddie C; Neal, David E; Turner, Emma L

2015-01-23

In cancer screening trials where the primary outcome is target cancer-specific mortality, the unbiased determination of underlying cause of death (UCD) is crucial. To minimise bias, the UCD should be independently verified by expert reviewers, blinded to death certificate data and trial arm. We investigated whether standardising the information submitted for UCD assignment in a population-based randomised controlled trial of prostate-specific antigen (PSA) testing for prostate cancer reduced the reviewers' ability to correctly guess the trial arm. Over 550 General Practitioner (GP) practices (>415,000 men aged 50-69 years) were cluster-randomised to PSA testing (intervention arm) or the National Health Service (NHS) prostate cancer risk management programme (control arm) between 2001 and 2007. Assignment of UCD was by independent reviews of researcher-written clinical vignettes that masked trial arm and death certificate information. A period of time after the process began (the initial phase), we analysed whether the reviewers could correctly identify trial arm from the vignettes, and the reasons for their choice. This feedback led to further standardisation of information (second phase), after which we re-assessed the extent of correct identification of trial arm. 1099 assessments of 509 vignettes were completed by January 2014. In the initial phase (n = 510 assessments), reviewers were unsure of trial arm in 33% of intervention and 30% of control arm assessments and were influenced by symptoms at diagnosis, PSA test result and study-specific criteria. In the second phase (n = 589), the respective proportions of uncertainty were 45% and 48%. The percentage of cases whereby reviewers were unable to determine the trial arm was greater following the standardisation of information provided in the vignettes. The chances of a correct guess and an incorrect guess were equalised in each arm, following further standardisation. It is possible to mask trial arm from cause of death reviewers, by using their feedback to standardise the information submitted to them. ISRCTN92187251.

Parametric analysis of a shape memory alloy actuated arm

NASA Astrophysics Data System (ADS)

Wright, Cody; Bilgen, Onur

2016-04-01

Using a pair of antagonistic Shape Memory Allow (SMA) wires, it may be possible to produce a mechanism that replicates human musculoskeletal movement. The movement of interest is the articulation of the elbow joint actuated by the biceps brachii muscle. In an effort to understand the bio-mechanics of the arm, a single degree of freedom crankslider mechanism is used to model the movement of the arm induced by the biceps brachii muscle. First, a purely kinematical analysis is performed on a rigid body crank-slider. Force analysis is also done modeling the muscle as a simple linear spring. Torque, rocking angle, and energy are calculated for a range of crank-slider geometries. The SMA wire characteristics are experimentally determined for the martensite detwinned and full austenite phases. Using the experimental data, an idealized actuator characteristic curve is produced for the SMA wire. Kinematic and force analyses are performed on the nonlinear wire characteristic curve and a linearized wire curve; both cases are applied to the crankslider mechanism. Performance metrics for both cases are compared, followed by discussion.

Combination TS-1 plus EGFR-tyrosine kinase inhibitors (TKIs) for the treatment of non-small cell lung cancer after progression on first-line or further EGFR-TKIs: A phase II, single-arm trial.

PubMed

Yang, Lu; Yang, Sheng; Liu, Yutao; Li, Junling; Hu, Xingsheng; Wang, Yalei; Zhang, Yan; Wang, Yan

2018-06-01

EGFR-tyrosine kinase inhibitors (TKIs) combined with TS-1 might overcome EGFR-TKI resistance, which has been indicated by several preclinical studies. We investigated the synergistic efficacy and safety of the combination therapy of EGFR-TKIs and TS-1 in non-small cell lung cancer (NSCLC) patients with acquired resistance to previous EGFR-TKI therapy. This was a phase II, single-arm and single-center prospective study. Stage IIIB-IV NSCLC patients with acquired resistance to prior EGFR-TKI treatment were enrolled. All patients were administered combination therapy of TS-1 and continuing EGFR-TKIs in this study. The primary endpoints were progression-free survival (PFS), while overall survival (OS), disease control rate (DCR), and safety were secondary endpoints. A total of 42 patients with acquired resistance to EGFR-TKIs were eligible for this study. The median PFS for all patients was five months (95% confidence interval [CI] 3.6-5.4). The OS and DCR were 31.9 (95% CI 17.8-46.0) months and 69.0% (29/42), respectively. No grade 4 toxicity or grade 3 hematologic toxicity was observed in this study. One patient (2%) experienced grade 3 elevated total serum bilirubin. The combination treatment of TS-1 and EGFR-TKIs was effective and well tolerated by patients who had experienced prior EGFR-TKI treatment failure. Our results need to be validated by larger prospective clinical trials. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Phase 1/2 Study of the CD56-Targeting Antibody-Drug Conjugate Lorvotuzumab Mertansine (IMGN901) in Combination With Carboplatin/Etoposide in Small-Cell Lung Cancer Patients With Extensive-Stage Disease.

PubMed

Socinski, Mark A; Kaye, Frederic J; Spigel, David R; Kudrik, Fred J; Ponce, Santiago; Ellis, Peter M; Majem, Margarita; Lorigan, Paul; Gandhi, Leena; Gutierrez, Martin E; Nepert, Dale; Corral, Jesus; Ares, Luis Paz

2017-01-01

This trial assessed the safety and efficacy of LM in combination with carboplatin/etoposide therapy compared to carboplatin/etoposide treatment alone in patients with previously untreated extensive-disease small-cell lung cancer (ED-SCLC). A run-in phase 1 stage was used to determine the recommended phase 2 dose and characterize the dose-limiting toxicities of LM in combination with carboplatin/etoposide followed by LM alone in patients with CD56-positive solid tumors. In phase 2, chemotherapy-naive ED-SCLC patients were randomized 2:1 to carboplatin AUC (area under the plasma concentration vs. time curve) of 5 day 1 + etoposide 100 mg/m 2 days 1 to 3 plus LM (arm 1) or alone (arm 2). In the phase 1 study (n = 33), a dose of LM at 112 mg/m 2 with carboplatin/etoposide was identified as the recommended phase 2 dose. However, because of an increased incidence of peripheral neuropathy events during early phase 2, this dose was reduced to 90 mg/m 2 . In phase 2, a total of 94 and 47 evaluable patients were assigned to arms 1 and 2, respectively. No difference in median progression-free survival was observed between arms 1 and 2 (6.2 vs. 6.7 months). The most common treatment-emergent adverse event leading to discontinuation was peripheral neuropathy (29%). A total of 21 patients had a treatment-emergent adverse event leading to death (18 in arm 1 and 3 in arm 2); for 10 individuals, this was an infection (pneumonia or sepsis) deemed to be related to the study drug. The combination of LM plus carboplatin/etoposide did not improve efficacy over standard carboplatin/etoposide doublet therapy in ED-SCLC patients and showed increased toxicity, including a higher incidence of serious infections with fatal outcomes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

McKenzie, Kirk; Spero, Robert E.; Shaddock, Daniel A.

For the Laser Interferometer Space Antenna (LISA) to reach its design sensitivity, the coupling of the free-running laser frequency noise to the signal readout must be reduced by more than 14 orders of magnitude. One technique employed to reduce the laser frequency noise will be arm locking, where the laser frequency is locked to the LISA arm length. In this paper we detail an implementation of arm locking. We investigate orbital effects (changing arm lengths and Doppler frequencies), the impact of errors in the Doppler knowledge that can cause pulling of the laser frequency, and the noise limit of armmore » locking. Laser frequency pulling is examined in two regimes: at lock acquisition and in steady state. The noise performance of arm locking is calculated with the inclusion of the dominant expected noise sources: ultrastable oscillator (clock) noise, spacecraft motion, and shot noise. We find that clock noise and spacecraft motion limit the performance of dual arm locking in the LISA science band. Studying these issues reveals that although dual arm locking [A. Sutton and D. A. Shaddock, Phys. Rev. D 78, 082001 (2008)] has advantages over single (or common) arm locking in terms of allowing high gain, it has disadvantages in both laser frequency pulling and noise performance. We address this by proposing a modification to the dual arm-locking sensor, a hybrid of common and dual arm-locking sensors. This modified dual arm-locking sensor has the laser frequency pulling characteristics and low-frequency noise coupling of common arm locking, but retains the control system advantages of dual arm locking. We present a detailed design of an arm-locking controller and perform an analysis of the expected performance when used with and without laser prestabilization. We observe that the sensor phase changes beneficially near unity-gain frequencies of the arm-locking controller, allowing a factor of 10 more gain than previously believed, without degrading stability. With a time-delay error of 3 ns (equivalent of 1 m interspacecraft ranging error), time-delay interferometry (TDI) is capable of suppressing 300 Hz/{radical}(Hz) of laser frequency noise to the required level. We show that if no interspacecraft laser links fail, arm locking alone surpasses this noise performance for the entire mission. If one interspacecraft laser link fails, arm locking alone will achieve this performance for all but approximately 1 h per year, when the arm length mismatch of the two remaining arms passes through zero. Therefore, the LISA sensitivity can be realized with arm locking and time-delay interferometry only, without any form of prestabilization.« less

Selecting promising treatments in randomized Phase II cancer trials with an active control.

PubMed

Cheung, Ying Kuen

2009-01-01

The primary objective of Phase II cancer trials is to evaluate the potential efficacy of a new regimen in terms of its antitumor activity in a given type of cancer. Due to advances in oncology therapeutics and heterogeneity in the patient population, such evaluation can be interpreted objectively only in the presence of a prospective control group of an active standard treatment. This paper deals with the design problem of Phase II selection trials in which several experimental regimens are compared to an active control, with an objective to identify an experimental arm that is more effective than the control or to declare futility if no such treatment exists. Conducting a multi-arm randomized selection trial is a useful strategy to prioritize experimental treatments for further testing when many candidates are available, but the sample size required in such a trial with an active control could raise feasibility concerns. In this study, we extend the sequential probability ratio test for normal observations to the multi-arm selection setting. The proposed methods, allowing frequent interim monitoring, offer high likelihood of early trial termination, and as such enhance enrollment feasibility. The termination and selection criteria have closed form solutions and are easy to compute with respect to any given set of error constraints. The proposed methods are applied to design a selection trial in which combinations of sorafenib and erlotinib are compared to a control group in patients with non-small-cell lung cancer using a continuous endpoint of change in tumor size. The operating characteristics of the proposed methods are compared to that of a single-stage design via simulations: The sample size requirement is reduced substantially and is feasible at an early stage of drug development.

Wide single-mode tuning in quantum cascade lasers with asymmetric Mach-Zehnder interferometer type cavities with separately biased arms

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

Zheng, Mei C., E-mail: meizheng@princeton.edu; Gmachl, Claire F.; Liu, Peter Q.

2013-11-18

We report on the experimental demonstration of a widely tunable single mode quantum cascade laser with Asymmetric Mach-Zehnder (AMZ) interferometer type cavities with separately biased arms. Current and, consequently, temperature tuning of the two arms of the AMZ type cavity resulted in a single mode tuning range of 20 cm{sup −1} at 80 K in continuous-wave mode operation, a ten-fold improvement from the lasers under a single bias current. In addition, we also observed a five fold increase in the tuning rate as compared to the AMZ cavities controlled by one bias current.

Successful Completion of the Pilot Phase of a Randomized Controlled Trial Comparing Sentinel Lymph Node Biopsy to No Further Axillary Staging in Patients with Clinical T1-T2 N0 Breast Cancer and Normal Axillary Ultrasound.

PubMed

Cyr, Amy E; Tucker, Natalia; Ademuyiwa, Foluso; Margenthaler, Julie A; Aft, Rebecca L; Eberlein, Timothy J; Appleton, Catherine M; Zoberi, Imran; Thomas, Maria A; Gao, Feng; Gillanders, William E

2016-08-01

Axillary surgery is not considered therapeutic in patients with clinical T1-T2 N0 breast cancer. The importance of axillary staging is eroding in an era in which tumor biology, as defined by biomarker and gene expression profile, is increasingly important in medical decision making. We hypothesized that axillary ultrasound (AUS) is a noninvasive alternative to sentinel lymph node biopsy (SLNB), and AUS could replace SLNB without compromising patient care. Patients with clinical T1-T2 N0 breast cancer and normal AUS were eligible for enrollment. Subjects were randomized to no further axillary staging (arm 1) vs SLNB (arm 2). Descriptive statistics were used to describe the results of the pilot phase of the randomized controlled trial. Sixty-eight subjects were enrolled in the pilot phase of the trial (34 subjects in arm 1, no further staging; 32 subjects in arm 2, SLNB; and 2 subjects voluntarily withdrew from the trial). The median age was 61 years (range 40 to 80 years) in arm 1 and 59 years (range 31 to 81 years) in arm 2, and there were no significant clinical or pathologic differences between the arms. Median follow-up was 17 months (range 1 to 32 months). The negative predictive value (NPV) of AUS for identification of clinically significant axillary disease (>2.0 mm) was 96.9%. No axillary recurrences have been observed in either arm. Successful completion of the pilot phase of the randomized controlled trial confirms the feasibility of the study design, and provides prospective evidence supporting the ability of AUS to exclude clinically significant disease in the axilla. The results provide strong support for a phase 2 randomized controlled trial. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Successful Completion of the Pilot Phase of a Randomized Controlled Trial Comparing Sentinel Lymph Node Biopsy to No Further Axillary Staging in Patients with Clinical T1-T2 N0 Breast Cancer and Normal Axillary Ultrasound

PubMed Central

Cyr, Amy E; Tucker, Natalia; Ademuyiwa, Foluso; Margenthaler, Julie A; Aft, Rebecca L; Eberlein, Timothy J; Appleton, Catherine M; Zoberi, Imran; Thomas, Maria A; Gao, Feng; Gillanders, William E

2016-01-01

Background Axillary surgery is not considered therapeutic in patients with clinical T1-T2 N0 breast cancer. The importance of axillary staging is eroding in an era where tumor biology, as defined by biomarker and gene expression profile, is increasingly important in medical decision making. We hypothesize that axillary ultrasound (AUS) is a noninvasive alternative to sentinel lymph node biopsy (SLNB), and AUS could replace SLNB without compromising patient care. Study Design Patients with clinical T1-T2 N0 breast cancer and normal AUS were eligible for enrollment. Subjects were randomized to no further axillary staging (Arm 1) versus SLNB (Arm 2). Descriptive statistics were used to describe the results of the pilot phase of the randomized controlled trial. Results 68 subjects were enrolled in the pilot phase of the trial (34 subjects in Arm 1, no further staging; 32 subjects in Arm 2, SLNB, and 2 subjects voluntarily withdrew from the trial). The median age was 61 years (range 40-80) in Arm 1 and 59 years (range 31-81) in Arm 2, and there were no significant clinical or pathologic differences between the arms. Median follow-up was 17 months (range 1-32). The negative predictive value (NPV) of AUS for identification of clinically significant axillary disease (> 2.0 mm) was 96.9%. No axillary recurrences have been observed in either arm. Conclusions Successful completion of the pilot phase of the randomized controlled trial confirms the feasibility of the study design, and provides prospective evidence supporting the ability of AUS to exclude clinically significant disease in the axilla. The results provide strong support for a phase 2 randomized controlled trial. PMID:27212005

A Bayesian pick-the-winner design in a randomized phase II clinical trial.

PubMed

Chen, Dung-Tsa; Huang, Po-Yu; Lin, Hui-Yi; Chiappori, Alberto A; Gabrilovich, Dmitry I; Haura, Eric B; Antonia, Scott J; Gray, Jhanelle E

2017-10-24

Many phase II clinical trials evaluate unique experimental drugs/combinations through multi-arm design to expedite the screening process (early termination of ineffective drugs) and to identify the most effective drug (pick the winner) to warrant a phase III trial. Various statistical approaches have been developed for the pick-the-winner design but have been criticized for lack of objective comparison among the drug agents. We developed a Bayesian pick-the-winner design by integrating a Bayesian posterior probability with Simon two-stage design in a randomized two-arm clinical trial. The Bayesian posterior probability, as the rule to pick the winner, is defined as probability of the response rate in one arm higher than in the other arm. The posterior probability aims to determine the winner when both arms pass the second stage of the Simon two-stage design. When both arms are competitive (i.e., both passing the second stage), the Bayesian posterior probability performs better to correctly identify the winner compared with the Fisher exact test in the simulation study. In comparison to a standard two-arm randomized design, the Bayesian pick-the-winner design has a higher power to determine a clear winner. In application to two studies, the approach is able to perform statistical comparison of two treatment arms and provides a winner probability (Bayesian posterior probability) to statistically justify the winning arm. We developed an integrated design that utilizes Bayesian posterior probability, Simon two-stage design, and randomization into a unique setting. It gives objective comparisons between the arms to determine the winner.

A phase III, open-label, single-arm study of tenecteplase for restoration of function in dysfunctional central venous catheters.

PubMed

Tebbi, Cameron; Costanzi, John; Shulman, Robert; Dreisbach, Luke; Jacobs, Brian R; Blaney, Martha; Ashby, Mark; Gillespie, Barbara S; Begelman, Susan M

2011-08-01

To evaluate, in a phase III, single-arm study, the safety and efficacy of the thrombolytic agent tenecteplase in restoring function to dysfunctional central venous catheters (CVCs). Pediatric and adult patients with dysfunctional CVCs were eligible to receive as much as 2 mL (2 mg) of intraluminal tenecteplase, which was left to dwell in the CVC lumen for a maximum of 120 minutes. If CVC function was not restored at 120 minutes, a second dose was instilled for an additional 120 minutes. Tenecteplase was administered to 246 patients. Mean patient age was 44 years (range, 0-92 y); 72 patients (29%) were younger than 17 years of age. Chemotherapy was the most common reason for catheter insertion. Restoration of CVC function was achieved in 177 patients (72%) within 120 minutes after the first dose. After instillation of a maximum of two doses of tenecteplase, CVC function was restored in 200 patients (81%), with similar frequencies in pediatric (83%) and adult (80%) patients. Adverse events (AEs) were reported in 31 patients (13%); fever (2%), neutropenia (1%), and nausea (0.8%) were most common. One serious AE, an allergic hypersensitivity reaction, was judged to be related to tenecteplase and/or a chemotherapeutic agent that the patient was receiving concurrently. Consecutive administration of one or two doses of tenecteplase into CVCs showed efficacy in the restoration of catheter function in patients with dysfunctional CVCs. Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.

The effect of an arm sling used for shoulder support on gait efficiency in hemiplegic patients with stroke using walking aids.

PubMed

Jeong, Yeon-Gyu; Jeong, Yeon-Jae; Koo, Jung-Wan

2017-06-01

The effects of an arm sling on the physiological costs of walking are not known. Even though a previous study reported that an arm sling can improve gait efficiency, its entrance criteria was only hemiparetic patients able to walk without walking aids independently. The aim of this study was to investigate the effect of shoulder support by an arm sling on gait efficiency in hemiplegic stroke patients using walking aids. Randomized crossover design. Rehabilitation department of a university hospital. A total of 57 hemiplegic patients with shoulder subluxation dependent on canes were grouped into single cane (N.=30) and quad cane groups (N.=27) as walking aids. All patients performed a walk with their own walking aid with and without an arm sling in randomized order, on the same day. We measured the energy cost and energy expenditure using a portable gas analyzer and heart rate during a 6-minutes Walk Test and a 10-m Walk Test. We analyzed all outcomes measures with and without an arm sling between the patients who were grouped according to their walking aids using 2-way repeated ANOVA. The energy cost (0.068±0.023 mL/kg/m) and oxygen expenditure (8.609±2.155 mL/kg/minutes) were lower with the arm sling (P<0.05) than without the arm sling (0.074±0.029 mL/kg/m, and 9.109±2.406 mL/kg/minutes, respectively), and the walking endurance (138.942±47.043 m) were longer (P<0.05) with the arm sling among the hemiplegic patients with single cane. Among the hemiplegic patients with a single cane, the walking endurance achieved with an arm sling significantly improved than those achieved without an arm sling, and the energy expenditure and energy cost was significantly lower. The hemiplegic arm support with an arm sling may be beneficial for gait efficiency in hemiplegic patients using a single cane, which lead to decreased oxygen use at a given speed.

A Simple Configuration for Quantitative Phase Contrast Microscopy of Transmissible Samples

NASA Astrophysics Data System (ADS)

Sengupta, Chandan; Dasgupta, Koustav; Bhattacharya, K.

Phase microscopy attempts to visualize and quantify the phase distribution of samples which are otherwise invisible under microscope without the use of stains. The two principal approaches to phase microscopy are essentially those of Fourier plane modulation and interferometric techniques. Although the former, first proposed by Zernike, had been the harbinger of phase microscopy, it was the latter that allowed for quantitative evaluation of phase samples. However interferometric techniques are fraught with associated problems such as complicated setup involving mirrors and beam-splitters, the need for a matched objective in the reference arm and also the need for vibration isolation. The present work proposes a single element cube beam-splitter (CBS) interferometer combined with a microscope objective (MO) for interference microscopy. Because of the monolithic nature of the interferometer, the system is almost insensitive to vibrations and relatively simple to align. It will be shown that phase shifting properties may also be introduced by suitable and proper use of polarizing devices. Initial results showing the quantitative three dimensional phase profiles of simulated and actual biological specimens are presented.

In Vivo Orientation of Single Myosin Lever Arms in Zebrafish Skeletal Muscle

PubMed Central

Sun, Xiaojing; Ekker, Stephen C.; Shelden, Eric A.; Takubo, Naoko; Wang, Yihua; Burghardt, Thomas P.

2014-01-01

Cardiac and skeletal myosin assembled in the muscle lattice power contraction by transducing ATP free energy into the mechanical work of moving actin. Myosin catalytic/lever-arm domains comprise the transduction/mechanical coupling machinery that move actin by lever-arm rotation. In vivo, myosin is crowded and constrained by the fiber lattice as side chains are mutated and otherwise modified under normal, diseased, or aging conditions that collectively define the native myosin environment. Single-myosin detection uniquely defines bottom-up characterization of myosin functionality. The marriage of in vivo and single-myosin detection to study zebrafish embryo models of human muscle disease is a multiscaled technology that allows one-to-one registration of a selected myosin molecular alteration with muscle filament-sarcomere-cell-fiber-tissue-organ- and organism level phenotypes. In vivo single-myosin lever-arm orientation was observed at superresolution using a photoactivatable-green-fluorescent-protein (PAGFP)-tagged myosin light chain expressed in zebrafish skeletal muscle. By simultaneous observation of multiphoton excitation fluorescence emission and second harmonic generation from myosin, we demonstrated tag specificity for the lever arm. Single-molecule detection used highly inclined parallel beam illumination and was verified by quantized photoactivation and photobleaching. Single-molecule emission patterns from relaxed muscle in vivo provided extensive superresolved dipole orientation constraints that were modeled using docking scenarios generated for the myosin (S1) and GFP crystal structures. The dipole orientation data provided sufficient constraints to estimate S1/GFP coordination. The S1/GFP coordination in vivo is rigid and the lever-arm orientation distribution is well-ordered in relaxed muscle. For comparison, single myosins in relaxed permeabilized porcine papillary muscle fibers indicated slightly differently oriented lever arms and rigid S1/GFP coordination. Lever arms in both muscles indicated one preferred spherical polar orientation and widely distributed azimuthal orientations relative to the fiber symmetry axis. Cardiac myosin is more radially displaced from the fiber axis. Probe rigidity implies the PAGFP tag reliably indicates cross-bridge orientation in situ and in vivo. PMID:25229148

Octopus arm movements under constrained conditions: adaptation, modification and plasticity of motor primitives.

PubMed

Richter, Jonas N; Hochner, Binyamin; Kuba, Michael J

2015-04-01

The motor control of the eight highly flexible arms of the common octopus (Octopus vulgaris) has been the focus of several recent studies. Our study is the first to manage to introduce a physical constraint to an octopus arm and investigate the adaptability of stereotypical bend propagation in reaching movements and the pseudo-limb articulation during fetching. Subjects (N=6) were placed inside a transparent Perspex box with a hole at the center that allowed the insertion of a single arm. Animals had to reach out through the hole toward a target, to retrieve a food reward and fetch it. All subjects successfully adjusted their movements to the constraint without an adaptation phase. During reaching tasks, the animals showed two movement strategies: stereotypical bend propagation reachings, which were established at the hole of the Perspex box and variant waving-like movements that showed no bend propagations. During fetching movements, no complete pseudo-joint fetching was observed outside the box and subjects pulled their arms through the hole in a pull-in like movement. Our findings show that there is some flexibility in the octopus motor system to adapt to a novel situation. However, at present, it seems that these changes are more an effect of random choices between different alternative motor programs, without showing clear learning effects in the choice between the alternatives. Interestingly, animals were able to adapt the fetching movements to the physical constraint, or as an alternative explanation, they could switch the motor primitive fetching to a different motor primitive 'arm pulling'. © 2015. Published by The Company of Biologists Ltd.

Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: two phase 2 single-arm trials

PubMed Central

Lawson, Jeffrey H; Glickman, Marc H; Ilzecki, Marek; Jakimowicz, Tomasz; Jaroszynski, Andrzej; Peden, Eric K; Pilgrim, Alison J; Prichard, Heather L; Guziewicz, Malgorzata; Przywara, Stanisław; Szmidt, Jacek; Turek, Jakub; Witkiewicz, Wojciech; Zapotoczny, Norbert; Zubilewicz, Tomasz; Niklason, Laura E

2016-01-01

Summary Background For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access. Methods We did two single-arm phase 2 trials at six centres in the USA and Poland. We enrolled adults with end-stage renal disease. A novel bioengineered human acellular vessel was implanted into the arms of patients for haemodialysis access. Primary endpoints were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months. All patients were followed up for at least 1 year, or had a censoring event. These trials are registered with ClinicalTrials.gov, NCT01744418 and NCT01840956. Findings Human acellular vessels were implanted into 60 patients. Mean follow-up was 16 months (SD 7·6). One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. At 6 months, 63% (95% CI 47–72) of patients had primary patency, 73% (57–81) had primary assisted patency, and 97% (85–98) had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% (17–40) had primary patency, 38% (26–51) had primary assisted patency, and 89% (74–93) had secondary patency. Interpretation Bioengineered human acellular vessels seem to provide safe and functional haemodialysis access, and warrant further study in randomised controlled trials. Funding Humacyte and US National Institutes of Health. PMID:27203778

The influence of mixed and phase clouds on surface shortwave irradiance during the Arctic spring

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

Lubin D.; Vogelmann A.

2011-10-13

The influence of mixed-phase stratiform clouds on the surface shortwave irradiance is examined using unique spectral shortwave irradiance measurements made during the Indirect and Semi-Direct Aerosol Campaign (ISDAC), supported by the U.S. Department of Energy Atmospheric Radiation Measurement (ARM) program. An Analytical Spectral Devices (ASD, Inc.) spectroradiometer measured downwelling spectral irradiance from 350 to 2200 nm in one-minute averages throughout April-May 2008 from the ARM Climate Research Facility's North Slope of Alaska (NSA) site at Barrow. This study examines spectral irradiance measurements made under single-layer, overcast cloud decks having geometric thickness < 3000 m. Cloud optical depth is retrieved frommore » irradiance in the interval 1022-1033 nm. The contrasting surface radiative influences of mixed-phase clouds and liquid-water clouds are discerned using irradiances in the 1.6-{micro}m window. Compared with liquid-water clouds, mixed-phase clouds during the Arctic spring cause a greater reduction of shortwave irradiance at the surface. At fixed conservative-scattering optical depth (constant optical depth for wavelengths {lambda} < 1100 nm), the presence of ice water in cloud reduces the near-IR surface irradiance by an additional several watts-per-meter-squared. This additional reduction, or supplemental ice absorption, is typically {approx}5 W m{sup -2} near solar noon over Barrow, and decreases with increasing solar zenith angle. However, for some cloud decks this additional absorption can be as large as 8-10 W m{sup -2}.« less

Activity and Safety of Cetuximab Plus Modified FOLFOXIRI Followed by Maintenance With Cetuximab or Bevacizumab for RAS and BRAF Wild-type Metastatic Colorectal Cancer: A Randomized Phase 2 Clinical Trial.

PubMed

Cremolini, Chiara; Antoniotti, Carlotta; Lonardi, Sara; Aprile, Giuseppe; Bergamo, Francesca; Masi, Gianluca; Grande, Roberta; Tonini, Giuseppe; Mescoli, Claudia; Cardellino, Giovanni Gerardo; Coltelli, Luigi; Salvatore, Lisa; Corsi, Domenico Cristiano; Lupi, Cristiana; Gemma, Donatello; Ronzoni, Monica; Dell'Aquila, Emanuela; Marmorino, Federica; Di Fabio, Francesca; Mancini, Maria Laura; Marcucci, Lorenzo; Fontanini, Gabriella; Zagonel, Vittorina; Boni, Luca; Falcone, Alfredo

2018-04-01

The combination of a triple-drug chemotherapy regimen with an anti-epidermal growth factor receptor (EGFR) agent as a first-line treatment of metastatic colorectal cancer (mCRC) showed promising activity along with safety concerns in single-arm phase 2 trials. The role of maintenance following chemotherapy and anti-EGFR and the optimal regimen to be adopted are not established. To evaluate the activity and safety of cetuximab plus modified FOLFOXIRI (mFOLFOXIRI) and explore the role of maintenance with cetuximab or bevacizumab in RAS and BRAF wild-type mCRC. In a prospective, noncomparative, open-label, multicenter, randomized phase 2 trial, patients aged 18 to 75 years with unresectable, previously untreated RAS and BRAF wild-type (before amendment, KRAS wild-type) mCRC were recruited from 21 oncology units in Italy from October 19, 2011, to March 1, 2015 (followed up through May 31, 2017). In total, 323 patients were screened and 143 were randomized to 2 treatment arms to receive as a first-line induction a regimen of mFOLFOXIRI plus cetuximab followed by cetuximab (arm A) or bevacizumab (arm B) until disease progression. Primary analyses were conducted in a modified intention-to-treat population. mFOLFOXIRI plus cetuximab repeated every 2 weeks for up to 8 cycles, followed by maintenance with cetuximab or bevacizumab until disease progression. The primary end point was the 10-month progression-free rate (PFR); secondary end points included progression-free and overall survival, response rate, rate of metastases resection, and adverse events. Of 143 patients randomized, 116 (81.1%) (median [interquartile range (IQR)] age, 59.5 [53-67] years; 34 [29.3%] women) had RAS and BRAF wild-type mCRC. At a median (IQR) follow-up of 44.0 (30.5-52.1) months, 10-month PFRs were 50.8% (90% CI, 39.5%-62.2%) in arm A and 40.4% (90% CI, 29.4%-52.1%) in arm B. The overall response rate was 71.6% (95% CI, 62.4%-79.5%). Main grade 3/4 adverse events were neutropenia (occurring in 36 patients [31%]), diarrhea (in 21 patients [18%]), skin toxic effects (in 18 patients [16%]), asthenia (in 11 patients [9%]), stomatitis (in 7 patients [6%]), and febrile neutropenia (in 3 patients [3%]). Although neither of the 2 arms met the primary end point, the findings indicate that a 4-month induction regimen of mFOLFOXIRI plus cetuximab is feasible and provides relevant activity results, leading to a high surgical resection rate. clinicaltrials.gov Identifier: NCT02295930.

Microswitch-aided programs to support physical exercise or adequate ambulation in persons with multiple disabilities.

PubMed

Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Alberti, Gloria; Perilli, Viviana; Oliva, Doretta; Buono, Serafino

2014-09-01

Three microswitch-aided programs were assessed in three single-case studies to enhance physical exercise or ambulation in participants with multiple disabilities. Study I was aimed at helping a woman who tended to have the head bending forward and the arms down to exercise a combination of appropriate head and arms movements. Study II was aimed at promoting ambulation continuity with a man who tended to have ambulation breaks. Study III was aimed at promoting ambulation with appropriate foot position in a girl who usually showed toe walking. The experimental designs of the studies consisted of a multiple probe across responses (Study I), an ABAB sequence (Study II), and an ABABB(1) sequence (Study III). The last phase of each study was followed by a post-intervention check. The microswitches monitored the target responses selected for the participants and triggered a computer system to provide preferred stimuli contingent on those responses during the intervention phases of the studies. Data showed that the programs were effective with each of the participants who learned to exercise head and arms movements, increased ambulation continuity, and acquired high levels of appropriate foot position during ambulation, respectively. The positive performance levels were retained during the post-intervention checks. The discussion focused on (a) the potential of technology-aided programs for persons with multiple disabilities and (b) the need of replication studies to extend the evidence available in the area. Copyright © 2014 Elsevier Ltd. All rights reserved.

CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1-2 study.

PubMed

Seto, Takashi; Kiura, Katsuyuki; Nishio, Makoto; Nakagawa, Kazuhiko; Maemondo, Makoto; Inoue, Akira; Hida, Toyoaki; Yamamoto, Nobuyuki; Yoshioka, Hiroshige; Harada, Masao; Ohe, Yuichiro; Nogami, Naoyuki; Takeuchi, Kengo; Shimada, Tadashi; Tanaka, Tomohiro; Tamura, Tomohide

2013-06-01

Currently, crizotinib is the only drug that has been approved for treatment of ALK-rearranged non-small-cell lung cancer (NSCLC). We aimed to study the activity and safety of CH5424802, a potent, selective, and orally available ALK inhibitor. In this multicentre, single-arm, open-label, phase 1-2 study of CH5424802, we recruited ALK inhibitor-naive patients with ALK-rearranged advanced NSCLC from 13 hospitals in Japan. In the phase 1 portion of the study, patients received CH5424802 orally twice daily by dose escalation. The primary endpoints of the phase 1 were dose limiting toxicity (DLT), maximum tolerated dose (MTD), and pharmacokinetic parameters. In the phase 2 portion of the study, patients received CH5424802 at the recommended dose identified in the phase 1 portion of the study orally twice a day. The primary endpoint of the phase 2 was the proportion of patients who had an objective response. Treatment was continued in 21-day cycles until disease progression, intolerable adverse events, or withdrawal of consent. The analysis was done by intent to treat. This study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-101264. Patients were enrolled between Sept 10, 2010, and April 18, 2012. The data cutoff date was July 31, 2012. In the phase 1 portion, 24 patients were treated at doses of 20-300 mg twice daily. No DLTs or adverse events of grade 4 were noted up to the highest dose; thus 300 mg twice daily was the recommended phase 2 dose. In the phase 2 portion of the study, 46 patients were treated with the recommended dose, of whom 43 achieved an objective response (93.5%, 95% CI 82.1-98.6) including two complete responses (4.3%, 0.5-14.8) and 41 partial responses (89.1%, 76.4-96.4). Treatment-related adverse events of grade 3 were recorded in 12 (26%) of 46 patients, including two patients each experiencing decreased neutrophil count and increased blood creatine phosphokinase. Serious adverse events occurred in five patients (11%). No grade 4 adverse events or deaths were reported. The study is still ongoing, since 40 of the 46 patients in the phase 2 portion remain on treatment. CH5424802 is well tolerated and highly active in patients with advanced ALK-rearranged NSCLC. Chugai Pharmaceutical Co, Ltd. Copyright © 2013 Elsevier Ltd. All rights reserved.

Wrist muscle activity of khatrah approach in Mameluke technique using traditional bow archery

NASA Astrophysics Data System (ADS)

Ariffin, Muhammad Shahimi; Rambely, Azmin Sham; Ariff, Noratiqah Mohd

2018-04-01

An investigation of khatrah technique in archery was carried out. An electromyography (EMG) experiment was conducted towards six wrist muscles which are flexor carpi radialis, extensor carpi ulnaris and extensor digitorum communis for both arms. The maximum voluntary contraction (MVC) and activity data were recorded. The bow arm produced a higher muscle force compared to draw arm muscles during release phase. However, the muscle forces produced by bow arm had a consistency in term of pattern throughout the phases. In conclusion, the forces generated by the professional archer produced a force benchmark at the wrist joint to alleviate the risk of injury.

Memory systems in the rat: effects of reward probability, context, and congruency between working and reference memory.

PubMed

Roberts, William A; Guitar, Nicole A; Marsh, Heidi L; MacDonald, Hayden

2016-05-01

The interaction of working and reference memory was studied in rats on an eight-arm radial maze. In two experiments, rats were trained to perform working memory and reference memory tasks. On working memory trials, they were allowed to enter four randomly chosen arms for reward in a study phase and then had to choose the unentered arms for reward in a test phase. On reference memory trials, they had to learn to visit the same four arms on the maze on every trial for reward. Retention was tested on working memory trials in which the interval between the study and test phase was 15 s, 15 min, or 30 min. At each retention interval, tests were performed in which the correct WM arms were either congruent or incongruent with the correct RM arms. Both experiments showed that congruency interacted with retention interval, yielding more forgetting at 30 min on incongruent trials than on congruent trials. The effect of reference memory strength on the congruency effect was examined in Experiment 1, and the effect of associating different contexts with working and reference memory on the congruency effect was studied in Experiment 2.

eLISA Telescope In-field Pointing and Scattered Light Study

NASA Astrophysics Data System (ADS)

Livas, J.; Sankar, S.; West, G.; Seals, L.; Howard, J.; Fitzsimons, E.

2017-05-01

The orbital motion of the three spacecraft that make up the eLISA Observatory constellation causes long-arm line of sight variations of approximately ± one degree over the course of a year. The baseline solution is to package the telescope, the optical bench, and the gravitational reference sensor (GRS) into an optical assembly at each end of the measurement arm, and then to articulate the assembly. An optical phase reference is exchanged between the moving optical benches with a single mode optical fiber (“backlink” fiber). An alternative solution, referred to as in-field pointing, embeds a steering mirror into the optical design, fixing the optical benches and eliminating the backlink fiber, but requiring the additional complication of a two-stage optical design for the telescope. We examine the impact of an in-field pointing design on the scattered light performance.

Magnetoplasmonic RF mixing and nonlinear frequency generation

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

Firby, C. J., E-mail: firby@ualberta.ca; Elezzabi, A. Y.

2016-07-04

We present the design of a magnetoplasmonic Mach-Zehnder interferometer (MZI) modulator facilitating radio-frequency (RF) mixing and nonlinear frequency generation. This is achieved by forming the MZI arms from long-range dielectric-loaded plasmonic waveguides containing bismuth-substituted yttrium iron garnet (Bi:YIG). The magnetization of the Bi:YIG can be driven in the nonlinear regime by RF magnetic fields produced around adjacent transmission lines. Correspondingly, the nonlinear temporal dynamics of the transverse magnetization component are mapped onto the nonreciprocal phase shift in the MZI arms, and onto the output optical intensity signal. We show that this tunable mechanism can generate harmonics, frequency splitting, and frequencymore » down-conversion with a single RF excitation, as well as RF mixing when driven by two RF signals. This magnetoplasmonic component can reduce the number of electrical sources required to generate distinct optical modulation frequencies and is anticipated to satisfy important applications in integrated optics.« less

The RAndomized Placebo Phase Study Of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis (RAPPORT)

PubMed Central

Ilowite, Norman T.; Prather, Kristi; Lokhnygina, Yuliya; Schanberg, Laura E.; Elder, Melissa; Milojevic, Diana; Verbsky, James W.; Spalding, Steven J.; Kimura, Yukiko; Imundo, Lisa F.; Punaro, Marilynn G.; Sherry, David D.; Tarvin, Stacey E.; Zemel, Lawrence S.; Birmingham, James D.; Gottlieb, Beth S.; Miller, Michael L.; O'Neil, Kathleen; Ruth, Natasha M.; Wallace, Carol A.; Singer, Nora G.; Sandborg, Christy I.

2015-01-01

Background Interleukin-1 plays a pivotal role in in the pathogenesis of systemic juvenile idiopathic arthritis (sJIA). We assessed the efficacy and safety of rilonacept (IL-1 trap), an IL-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. Methods An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multi-center design, followed by an open label phase. We randomized 71 children with at least 2 active joints 1:1 to 2 arms of the study. Patients in the rilonacept arm received rilonacept (4.4mg/kg loading dose followed by 2.2mg/kg weekly, subcutaneously) from day 0; patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary endpoint was time to response, using adapted JIA ACR30 response criteria coupled with absence of fever and taper of systemic corticosteroids using pre-specified criteria. Results Time to response was shorter in the rilonacept arm than in the placebo arm (Chi-square 7.235, P=.007). Secondary analysis showed 20/35 (57%) of patients in the rilonacept arm responded at week 4 compared to 9/33 (27%) in the placebo arm (P=.016) using the same response criteria. Exacerbation of sJIA (4) was the most common SAE. More patients in the rilonacept arm had elevated liver transaminases, including more than three times the upper limits of normal, as compared to those in the placebo arm. Adverse events were similar in the two arms of the study. Conclusions Rilonacept was generally well tolerated and demonstrated efficacy in active sJIA. PMID:24839206

French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC)

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

Bensadoun, Rene-Jean; Benezery, Karen; Dassonville, Olivier

Background: Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002. Methods: Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1{sup {yields}}D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m{sup 2} (D1, D22, D43); 5FU, continuous infusion (D1{sup {yields}}D5), 750 mg/m{sup 2}/day cycle 1; 430 mg/m{sup 2}/day cycles 2 and 3. Results: A total of 163 evaluablemore » patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years. Conclusion: For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an 'aggressive' dose-intensity radiotherapy schedule.« less

Thouless dephasing and amplitude modulation of Aharonov-Bohm oscillations in mesoscopic InGaAs/InAlAs interferometers

NASA Astrophysics Data System (ADS)

Heremans, J. J.; Ren, S. L.; Zhang, Yao; Gaspe, C. K.; Vijeyaragunathan, S.; Mishima, T. D.; Santos, M. B.

2014-03-01

Aharonov-Bohm oscillations in the low-temperature magnetoresistance of mesoscopic interferometric rings are investigated for their dependence on bias current and temperature, and to explore origins of the observed amplitude modulation in magnetic field. Single-ring interferometers of radius 650 nm and lithographic arm width 300 nm were fabricated on a high-mobility high-density InGaAs/InAlAs heterostructure. The rings show interference oscillations over a wide range of magnetic fields, with amplitudes subject to modulation with applied magnetic field. The quantum phase coherence length is extracted by analysis of the fundamental and higher Fourier components of the oscillations, and by comparative study of the amplitude. The variation of the amplitude with bias current and temperature shows the existence of a critical excitation energy consistent with the Thouless energy for quantum phase smearing. Autocorrelation and Fourier analysis are used to determine the quasi-period of the amplitude modulation, which is found to be consistent with an origin in the magnetic flux threading the finite width of the interferometer arms, changing the mesoscopic realization of the system. Supported by DOE DE-FG02-08ER46532 (VT) and NSF DMR-0520550 (UoO).

Oxygen vacancies controlled multiple magnetic phases in epitaxial single crystal Co 0.5(Mg 0.55Zn 0.45) 0.5O 1-v thin films

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

Zhu, Dapeng; Cao, Qiang; Qiao, Ruimin

2016-04-11

High quality single-crystal fcc-Co x (Mg y Zn 1-y ) 1-x O 1-v epitaxial thin films with high Co concentration up to x = 0.5 have been fabricated by molecular beam epitaxy. Systematic magnetic property characterization and soft X-ray absorption spectroscopy analysis indicate that the coexistence of ferromagnetic regions, superparamagnetic clusters, and non-magnetic boundaries in the as-prepared Co x (Mg y Zn 1-y ) 1-x O 1-v films is a consequence of the intrinsic inhomogeneous distribution of oxygen vacancies. Furthermore, the relative strength of multiple phases could be modulated by controlling the oxygen partial pressure during sample preparation. Armed withmore » both controllable magnetic properties and tunable band-gap, Co x (Mg y Zn 1-y ) 1-x O 1-v films may have promising applications in future spintronics.« less

Randomized Phase III Clinical Trial of Five Different Arms of Treatment in 332 Patients with Cancer Cachexia

PubMed Central

Macciò, Antonio; Madeddu, Clelia; Serpe, Roberto; Massa, Elena; Dessì, Mariele; Panzone, Filomena; Contu, Paolo

2010-01-01

Purpose. A phase III, randomized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia—lean body mass (LBM), resting energy expenditure (REE), and fatigue—and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines. Patients and Methods. Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were randomly assigned to one of five treatment arms: arm 1, medroxyprogesterone (500 mg/day) or megestrol acetate (320 mg/day); arm 2, oral supplementation with eicosapentaenoic acid; arm 3, L-carnitine (4 g/day); arm 4, thalidomide (200 mg/day); and arm 5, a combination of the above. Treatment duration was 4 months. Results. Analysis of variance showed a significant difference between treatment arms. A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints. An analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) significantly increased in arm 5. REE decreased significantly and fatigue improved significantly in arm 5. Appetite increased significantly in arm 5; interleukin (IL)-6 decreased significantly in arm 5 and arm 4; GPS and Eastern Cooperative Oncology Group performance status (ECOG PS) score decreased significantly in arm 5, arm 4, and arm 3. Toxicity was quite negligible, and was comparable between arms. Conclusion. The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite, IL-6, GPS, and ECOG PS score was the combination regimen that included all selected agents. PMID:20156909

Arctic Mixed-phase Clouds Simulated by a Cloud-Resolving Model: Comparison with ARM Observations and Sensitivity to Microphysics Parameterizations

NASA Technical Reports Server (NTRS)

Xu, Kuan-Man; Luo, Yali; Morrison, Hugh; Mcfarquhar, G.M.

2008-01-01

Single-layer mixed-phase stratiform (MPS) Arctic clouds, which formed under conditions of large surface heat flux combined with general subsidence during a subperiod of the Atmospheric Radiation Measurement (ARM) Program Mixed-Phase Arctic Cloud Experiment (M-PACE), are simulated with a cloud resolving model (CRM). The CRM is implemented with either an advanced two-moment (M05) or a commonly used one-moment (L83) bulk microphysics scheme and a state-of-the-art radiative transfer scheme. The CONTROL simulation, that uses the M05 scheme and observed aerosol size distribution and ice nulei (IN) number concentration, reproduces the magnitudes and vertical structures of cloud liquid water content (LWC), total ice water content (IWC), number concentration and effective radius of cloud droplets as suggested by the M-PACE observations. It underestimates ice crystal number concentrations by an order of magnitude and overestimates effective radius of ice crystals by a factor of 2-3. The OneM experiment, that uses the L83 scheme, produces values of liquid water path (LWP) and ice plus snow water path (ISWP) that were about 30% and 4 times, respectively, of those produced by the CONTROL. Its vertical profile of IWC exhibits a bimodal distribution in contrast to the constant distribution of IWC produced in the CONTROL and observations.

A radiation closure study of Arctic stratus cloud microphysical properties using the collocated satellite-surface data and Fu-Liou radiative transfer model

NASA Astrophysics Data System (ADS)

Dong, Xiquan; Xi, Baike; Qiu, Shaoyue; Minnis, Patrick; Sun-Mack, Sunny; Rose, Fred

2016-09-01

Retrievals of cloud microphysical properties based on passive satellite imagery are especially difficult over snow-covered surfaces because of the bright and cold surface. To help quantify their uncertainties, single-layered overcast liquid-phase Arctic stratus cloud microphysical properties retrieved by using the Clouds and the Earth's Radiant Energy System Edition 2 and Edition 4 (CERES Ed2 and Ed4) algorithms are compared with ground-based retrievals at the Atmospheric Radiation Measurement North Slope of Alaska (ARM NSA) site at Barrow, AK, during the period from March 2000 to December 2006. A total of 206 and 140 snow-free cases (Rsfc ≤ 0.3), and 108 and 106 snow cases (Rsfc > 0.3), respectively, were selected from Terra and Aqua satellite passes over the ARM NSA site. The CERES Ed4 and Ed2 optical depth (τ) and liquid water path (LWP) retrievals from both Terra and Aqua are almost identical and have excellent agreement with ARM retrievals under snow-free and snow conditions. In order to reach a radiation closure study for both the surface and top of atmosphere (TOA) radiation budgets, the ARM precision spectral pyranometer-measured surface albedos were adjusted (63.6% and 80% of the ARM surface albedos for snow-free and snow cases, respectively) to account for the water and land components of the domain of 30 km × 30 km. Most of the radiative transfer model calculated SW↓sfc and SW↑TOA fluxes by using ARM and CERES cloud retrievals and the domain mean albedos as input agree with the ARM and CERES flux observations within 10 W m-2 for both snow-free and snow conditions. Sensitivity studies show that the ARM LWP and re retrievals are less dependent on solar zenith angle (SZA), but all retrieved optical depths increase with SZA.

Exercise capacity in young adults with hypertension and systolic blood pressure difference between right arm and leg after repair of coarctation of the aorta.

PubMed

Instebø, Arne; Norgård, Gunnar; Helgheim, Vegard; Røksund, Ola Drange; Segadal, Leidulf; Greve, Gottfried

2004-10-01

Coarctation of the aorta represents 5-7% of congenital heart defects. Symptoms and prognosis depend on the degree of stenosis, age at surgery, surgical method and the presence of other heart defects. Postoperative complications are hypertension, restenosis and an abnormal blood pressure response during exercise. This study includes 41 patients, 15-40 years old, operated in the period 1975-1996. All were exercised on a treadmill until maximal oxygen consumption was achieved. Blood pressure was measured in the right arm and leg before and immediately after exercise, and in the right arm during exercise. Oxygen consumption was monitored and we defined an aerobic phase, an isocapnic buffering phase and a hypocapnic hyperventilation phase. The resting systolic blood pressure correlates with the resting systolic blood pressure difference between right arm and leg. A resting systolic blood pressure difference between the right arm and leg of 0.13 kPa (1 mmHg) to 2.67 kPa (20 mmHg) corresponds with a slight increase in resting systolic blood pressure. This rise in blood pressure increases the aerobic phase of the exercise test, helping the patients to achieve higher maximal oxygen consumption. A resting systolic blood pressure difference of more than 2.67 kPa (20 mmHg) corresponds with severe hypertension and causes reduction in the aerobic phase and maximal oxygen consumption. Resting systolic blood pressure and resting systolic blood pressure difference between the right arm and leg are not indicators for blood pressure response during exercise. Exercise testing is important to reveal exercise-induced hypertension and to monitor changes in transition from aerobic to anaerobic exercise and limitation to exercise capacity.

Coordinate measuring machine test standard apparatus and method

DOEpatents

Bieg, L.F.

1994-08-30

A coordinate measuring machine test standard apparatus and method are disclosed which includes a rotary spindle having an upper phase plate and an axis of rotation, a kinematic ball mount attached to the phase plate concentric with the axis of rotation of the phase plate, a groove mounted at the circumference of the phase plate, and an arm assembly which rests in the groove. The arm assembly has a small sphere at one end and a large sphere at the other end. The small sphere may be a coordinate measuring machine probe tip and may have variable diameters. The large sphere is secured in the kinematic ball mount and the arm is held in the groove. The kinematic ball mount includes at least three mounting spheres and the groove is an angular locating groove including at least two locking spheres. The arm may have a hollow inner core and an outer layer. The rotary spindle may be a ratio reducer. The device is used to evaluate the measuring performance of a coordinate measuring machine for periodic recertification, including 2 and 3 dimensional accuracy, squareness, straightness, and angular accuracy. 5 figs.

Coordinate measuring machine test standard apparatus and method

DOEpatents

Bieg, Lothar F.

1994-08-30

A coordinate measuring machine test standard apparatus and method which iudes a rotary spindle having an upper phase plate and an axis of rotation, a kinematic ball mount attached to the phase plate concentric with the axis of rotation of the phase plate, a groove mounted at the circumference of the phase plate, and an arm assembly which rests in the groove. The arm assembly has a small sphere at one end and a large sphere at the other end. The small sphere may be a coordinate measuring machine probe tip and may have variable diameters. The large sphere is secured in the kinematic ball mount and the arm is held in the groove. The kinematic ball mount includes at least three mounting spheres and the groove is an angular locating groove including at least two locking spheres. The arm may have a hollow inner core and an outer layer. The rotary spindle may be a ratio reducer. The device is used to evaluate the measuring performance of a coordinate measuring machine for periodic recertification, including 2 and 3 dimensional accuracy, squareness, straightness, and angular accuracy.

Antibody-ribosome-mRNA (ARM) complexes as efficient selection particles for in vitro display and evolution of antibody combining sites.

PubMed Central

He, M; Taussig, M J

1997-01-01

We describe a rapid, eukaryotic, in vitro method for selection and evolution of antibody combining sites using antibody-ribosome-mRNA (ARM) complexes as selection particles. ARMs carrying single-chain (VH/K) binding fragments specific for progesterone were selected using antigen-coupled magnetic beads; selection simultaneously captured the genetic information as mRNA, making it possible to generate and amplify cDNA by single-step RT-PCR on the ribosome-bound mRNA for further manipulation. Using mutant libraries, antigen-binding ARMs were enriched by a factor of 10(4)-10(5)-fold in a single cycle, with further enrichment in repeated cycles. While demonstrated here for antibodies, the method has the potential to be applied equally for selection of receptors or peptides from libraries. PMID:9396828

Antibody-ribosome-mRNA (ARM) complexes as efficient selection particles for in vitro display and evolution of antibody combining sites.

PubMed

He, M; Taussig, M J

1997-12-15

We describe a rapid, eukaryotic, in vitro method for selection and evolution of antibody combining sites using antibody-ribosome-mRNA (ARM) complexes as selection particles. ARMs carrying single-chain (VH/K) binding fragments specific for progesterone were selected using antigen-coupled magnetic beads; selection simultaneously captured the genetic information as mRNA, making it possible to generate and amplify cDNA by single-step RT-PCR on the ribosome-bound mRNA for further manipulation. Using mutant libraries, antigen-binding ARMs were enriched by a factor of 10(4)-10(5)-fold in a single cycle, with further enrichment in repeated cycles. While demonstrated here for antibodies, the method has the potential to be applied equally for selection of receptors or peptides from libraries.

A novel robotic platform for single-port abdominal surgery

NASA Astrophysics Data System (ADS)

Singh, Satwinder; Cheung, Jo L. K.; Sreedhar, Biji; Hoa, Xuyen Dai; Ng, Hoi Pang; Yeung, Chung Kwong

2018-03-01

In this paper, a novel robot-assisted platform for single-port minimally invasive surgery is presented. A miniaturized seven degrees of freedom (dof) fully internalized in-vivo actuated robotic arm is designed. Due to in-vivo actuation, the system has a smaller footprint and can generate 20 N of gripping force. The complete work envelop of the robotic arms is 252 mm × 192 mm × 322 m. With the assistance of the cannula-swivel system, the robotic arms can also be re-positioned and have multi-quadrant reachability without any additional incision. Surgical tasks, such as lifting, gripping suturing and knot tying that are commonly used in a standard surgical procedure, were performed to verify the dexterity of the robotic arms. A single-port trans-abdominal cholecystectomy in a porcine model was successfully performed to further validate its functionality.

Sequential therapy in metastatic clear cell renal carcinoma: TKI-TKI vs TKI-mTOR.

PubMed

Felici, Alessandra; Bria, Emilio; Tortora, Giampaolo; Cognetti, Francesco; Milella, Michele

2012-12-01

With seven targeted agents, directed against the VEGF/VEGF receptor (VEGFR) axis or the mTOR pathway, approved for the treatment of metastatic renal cell carcinoma and more active agents in advanced phase of clinical testing, questions have arisen with regard to their optimal use, either in combination or in sequence. One of the most compelling (and debated) issues is whether continued VEGF/VEGFR inhibition with agents hitting the same targets (TKI-TKI) affords better results than switching mechanisms of action by alternating VEGFR and mTOR inhibition (TKI-mTOR). In this article, the authors review the (little) available evidence coming from randomized Phase III clinical trials and try to fill in the (many) remaining gaps using evidence from small-size, single-arm Phase II studies and retrospective series, as well as reviewing preclinical evidence supporting either strategy.

Quality of reporting in oncology phase II trials: A 5-year assessment through systematic review.

PubMed

Langrand-Escure, Julien; Rivoirard, Romain; Oriol, Mathieu; Tinquaut, Fabien; Rancoule, Chloé; Chauvin, Frank; Magné, Nicolas; Bourmaud, Aurélie

2017-01-01

Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal. Objective The present study aims at estimating the quality of reporting in published oncology phase II clinical trials. A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010-2015). All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer. Quality of reporting was assessed using the Key Methodological Score. 557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001). Screening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate. This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles.

Quality of reporting in oncology phase II trials: A 5-year assessment through systematic review

PubMed Central

Langrand-Escure, Julien; Rivoirard, Romain; Oriol, Mathieu; Tinquaut, Fabien; Rancoule, Chloé; Chauvin, Frank; Magné, Nicolas; Bourmaud, Aurélie

2017-01-01

Background Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal. Objective The present study aims at estimating the quality of reporting in published oncology phase II clinical trials. Data sources A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010–2015). Study eligibility criteria All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer. Intervention Quality of reporting was assessed using the Key Methodological Score. Results 557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001). Limitations Screening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate. Conclusions & implications of key findings This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles. PMID:29216190

Monitoring acute phase proteins in retrovirus infected cats undergoing feline interferon-ω therapy.

PubMed

Leal, R O; Gil, S; Sepúlveda, N; McGahie, D; Duarte, A; Niza, M M R E; Tavares, L

2014-01-01

Recombinant feline interferon-ω therapy is an immunomodulator currently used in the treatment of different retroviral diseases including feline immune deficiency virus and feline leukaemia virus. Although its mechanism of action remains unclear, this drug appears to potentiate the innate response. Acute phase proteins are one of the key components of innate immunity and studies describing their use as a monitoring tool for the immune system in animals undergoing interferon-ω therapy are lacking. This study aimed to determine whether interferon-ω therapy influences acute phase protein concentrations namely serum amyloid-A, α-1-glycoprotein and C-reactive protein. A single-arm study was performed using 16 cats, living in an animal shelter, naturally infected with retroviruses and subjected to the interferon-ω therapy licensed protocol. Samples were collected before (D0), during (D10 and D30) and after therapy (D65). Serum amyloid-A and C-reactive protein were measured by specific enzyme-linked immunosorbent assay kits and α-1-glycoprotein by single radial immunodiffusion. All the acute phase proteins significantly increased in cats undergoing interferon-ω therapy (D0/D65: P<0·05) CLINICAL SIGNIFICANCE: Acute phase proteins appear to be reasonable predictors of innate-immune stimulation and may be useful in the individual monitoring of naturally retroviral infected cats undergoing interferon-ω therapy. © 2013 British Small Animal Veterinary Association.

Evaluation of inertial devices for the control of large, flexible, space-based telerobotic arms

NASA Technical Reports Server (NTRS)

Montgomery, Raymond C.; Kenny, Sean P.; Ghosh, Dave; Shenhar, Joram

1993-01-01

Inertial devices, including sensors and actuators, offer the potential of improving the tracking of telerobotic commands for space-based robots by smoothing payload motions and suppressing vibrations. In this paper, inertial actuators (specifically, torque-wheels and reaction-masses) are studied for that potential application. Batch simulation studies are presented which show that torque-wheels can reduce the overshoot in abrupt stop commands by 82 percent for a two-link arm. For man-in-the-loop evaluation, a real-time simulator has been developed which samples a hand-controller, solves the nonlinear equations of motion, and graphically displays the resulting motion on a computer workstation. Currently, two manipulator models, a two-link, rigid arm and a single-link, flexible arm, have been studied. Results are presented which show that, for a single-link arm, a reaction-mass/torque-wheel combination at the payload end can yield a settling time of 3 s for disturbances in the first flexible mode as opposed to 10 s using only a hub motor. A hardware apparatus, which consists of a single-link, highly flexible arm with a hub motor and a torque-wheel, has been assembled to evaluate the concept and is described herein.

Evaluation of inertial devices for the control of large, flexible, space-based telerobotic arms

NASA Astrophysics Data System (ADS)

Montgomery, Raymond C.; Kenny, Sean P.; Ghosh, Dave; Shenhar, Joram

1993-02-01

Inertial devices, including sensors and actuators, offer the potential of improving the tracking of telerobotic commands for space-based robots by smoothing payload motions and suppressing vibrations. In this paper, inertial actuators (specifically, torque-wheels and reaction-masses) are studied for that potential application. Batch simulation studies are presented which show that torque-wheels can reduce the overshoot in abrupt stop commands by 82 percent for a two-link arm. For man-in-the-loop evaluation, a real-time simulator has been developed which samples a hand-controller, solves the nonlinear equations of motion, and graphically displays the resulting motion on a computer workstation. Currently, two manipulator models, a two-link, rigid arm and a single-link, flexible arm, have been studied. Results are presented which show that, for a single-link arm, a reaction-mass/torque-wheel combination at the payload end can yield a settling time of 3 s for disturbances in the first flexible mode as opposed to 10 s using only a hub motor. A hardware apparatus, which consists of a single-link, highly flexible arm with a hub motor and a torque-wheel, has been assembled to evaluate the concept and is described herein.

Octopus vulgaris uses visual information to determine the location of its arm.

PubMed

Gutnick, Tamar; Byrne, Ruth A; Hochner, Binyamin; Kuba, Michael

2011-03-22

Octopuses are intelligent, soft-bodied animals with keen senses that perform reliably in a variety of visual and tactile learning tasks. However, researchers have found them disappointing in that they consistently fail in operant tasks that require them to combine central nervous system reward information with visual and peripheral knowledge of the location of their arms. Wells claimed that in order to filter and integrate an abundance of multisensory inputs that might inform the animal of the position of a single arm, octopuses would need an exceptional computing mechanism, and "There is no evidence that such a system exists in Octopus, or in any other soft bodied animal." Recent electrophysiological experiments, which found no clear somatotopic organization in the higher motor centers, support this claim. We developed a three-choice maze that required an octopus to use a single arm to reach a visually marked goal compartment. Using this operant task, we show for the first time that Octopus vulgaris is capable of guiding a single arm in a complex movement to a location. Thus, we claim that octopuses can combine peripheral arm location information with visual input to control goal-directed complex movements. Copyright © 2011 Elsevier Ltd. All rights reserved.

Hyperthermia and Radiation Therapy in Locoregional Recurrent Breast Cancers: A Systematic Review and Meta-analysis

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

Datta, Niloy R., E-mail: niloyranjan.datta@ksa.ch; Puric, Emsad; Klingbiel, Dirk

Purpose: To conduct a systematic review and meta-analysis to evaluate the outcome of hyperthermia (HT) and radiation therapy (RT) in locally recurrent breast cancers (LRBCs). Methods and Materials: A total of 708 abstracts were screened from 8 databases according to the PRISMA guidelines. Single-arm and 2-arm studies, treating LRBCs with HT and RT but without surgery (for local recurrence) or concurrent chemotherapy were considered. The evaluated endpoint was complete response (CR). Results: Thirty-one full text articles, pertaining to 34 studies, were shortlisted for the meta-analysis. Eight were 2-arm (randomized, n=5; nonrandomized, n=3), whereas 26 were single-arm studies. In all, 627more » patients were enrolled in 2-arm and 1483 in single-arm studies. Patients were treated with a median of 7 HT sessions, and an average temperature of 42.5°C was attained. Mean RT dose was 38.2 Gy (range, 26-60 Gy). Hyperthermia was most frequently applied after RT. In the 2-arm studies, a CR of 60.2% was achieved with RT + HT versus 38.1% with RT alone (odds ratio 2.64, 95% confidence interval [CI] 1.66-4.18, P<.0001). Risk ratio and risk difference were 1.57 (95% CI 1.25-1.96, P<.0001) and 0.22 (95% CI 0.11-0.33, P<.0001), respectively. In 26 single-arm studies, RT + HT attained a CR of 63.4% (event rate 0.62, 95% CI 0.57-0.66). Moreover, 779 patients had been previously irradiated (696 from single-arm and 83 from 2-arm studies). A CR of 66.6% (event rate 0.64, 95% CI 0.58-0.70) was achieved with HT and reirradiation (mean ± SD dose: 36.7 ± 7.7 Gy). Mean acute and late grade 3/4 toxicities with RT + HT were 14.4% and 5.2%, respectively. Conclusions: Thermoradiation therapy enhances the likelihood of CR rates in LRBCs over RT alone by 22% with minimal acute and late morbidities. For even those previously irradiated, reirradiation with HT provides locoregional control in two-thirds of the patients. Thermoradiation therapy could therefore be considered as an effective and safe palliative treatment option for LRBCs.« less

Self-Administered, Home-Based SMART (Sensorimotor Active Rehabilitation Training) Arm Training: A Single-Case Report.

PubMed

Hayward, Kathryn S; Neibling, Bridee A; Barker, Ruth N

2015-01-01

This single-case, mixed-method study explored the feasibility of self-administered, home-based SMART (sensorimotor active rehabilitation training) Arm training for a 57-yr-old man with severe upper-limb disability after a right frontoparietal hemorrhagic stroke 9 mo earlier. Over 4 wk of self-administered, home-based SMART Arm training, the participant completed 2,100 repetitions unassisted. His wife provided support for equipment set-up and training progressions. Clinically meaningful improvements in arm impairment (strength), activity (arm and hand tasks), and participation (use of arm in everyday tasks) occurred after training (at 4 wk) and at follow-up (at 16 wk). Areas for refinement of SMART Arm training derived from thematic analysis of the participant's and researchers' journals focused on enabling independence, ensuring home and user friendliness, maintaining the motivation to persevere, progressing toward everyday tasks, and integrating practice into daily routine. These findings suggest that further investigation of self-administered, home-based SMART Arm training is warranted for people with stroke who have severe upper-limb disability. Copyright © 2015 by the American Occupational Therapy Association, Inc.

Hybrid STTR intervention for heterosexuals using anonymous HIV testing and confidential linkage to care: a single arm exploratory trial using respondent-driven sampling.

PubMed

Gwadz, Marya; Cleland, Charles M; Leonard, Noelle R; Kutnick, Alexandra; Ritchie, Amanda S; Banfield, Angela; Hagan, Holly; Perlman, David C; McCright-Gill, Talaya; Sherpa, Dawa; Martinez, Belkis Y

2015-11-16

An estimated 14 % of the 1.2 million individuals living with HIV in the U.S. are unaware of their status. Yet this modest proportion of individuals with undiagnosed HIV is linked to 44-66 % of all new infections. Thus innovative intervention approaches are needed to seek out and test those with undiagnosed HIV, and link them to HIV treatment with high retention, an approach referred to as "Seek, Test, Treat, and Retain" (STTR). The present protocol describes a creative "hybrid" STTR approach that uses anonymous HIV testing followed by confidential care linkage, focused on heterosexuals at high risk (HHR) for HIV, who do not test as frequently as, and are diagnosed later, than other risk groups. This is a single-arm exploratory intervention efficacy trial. The study has two phases: one to seek out and test HHR, and another to link those found infected to HIV treatment in a timely fashion, with high retention. We will recruit African American/Black and Latino adult HHR who reside in urban locations with high poverty and HIV prevalence. Participants will be recruited with respondent-driven sampling, a peer recruitment method. The "Seek and Test" phase is comprised of a brief, convenient, single-session, anonymous HIV counseling and testing session. The "Treat and Retain" component will engage those newly diagnosed with HIV into a confidential research phase and use a set of procedures called care navigation to link them to HIV primary care. Participants will be followed for 6 months with objective assessment of outcomes (using medical records and biomarkers). Undiagnosed HIV infection is a major public health problem. While anonymous HIV testing is an important part of the HIV testing portfolio, it does not typically include linkage to care. The present study has potential to produce an innovative, brief, cost-effective, and replicable STTR intervention, and thereby reduce racial/ethnic disparities in HIV/AIDS. ClinicalTrials.gov, NCT02421159 , Registered April 15, 2015.

Multiple vaccinations, health, and recall bias within UK armed forces deployed to Iraq: cohort study.

PubMed

Murphy, Dominic; Hotopf, Matthew; Wessely, Simon

2008-06-30

To assess the relation between self reported number of vaccinations received and health, and between numbers of vaccinations recorded from individuals' medical records and health. First phase of a cohort study. UK armed forces personnel. 4882 randomly selected military personnel deployed to Iraq since 2003 and a subset of 378 whose vaccination records were accessed. Psychological distress, fatigue, symptoms of post-traumatic stress disorder, health perception, and multiple physical symptoms. Personnel who reported receiving two or more vaccinations on a single day were more likely to report symptoms of fatigue (adjusted risk ratio 1.17, 95% confidence interval 1.05 to 1.30), show caseness according to the general health questionnaire (1.31, 1.13 to 1.53), and have multiple physical symptoms (1.32, 1.08 to 1.60). These associations were no longer significant when number of vaccinations recorded in individuals' medical records was used as the independent variable. Multiple vaccinations given to personnel in the UK armed forces in preparation for deployment to Iraq are not associated with adverse health consequences when vaccinations are recorded objectively from medical records. Adverse health consequences associated with self reported multiple vaccinations could be explained by recall bias.

De novo assembly and phasing of a Korean human genome.

PubMed

Seo, Jeong-Sun; Rhie, Arang; Kim, Junsoo; Lee, Sangjin; Sohn, Min-Hwan; Kim, Chang-Uk; Hastie, Alex; Cao, Han; Yun, Ji-Young; Kim, Jihye; Kuk, Junho; Park, Gun Hwa; Kim, Juhyeok; Ryu, Hanna; Kim, Jongbum; Roh, Mira; Baek, Jeonghun; Hunkapiller, Michael W; Korlach, Jonas; Shin, Jong-Yeon; Kim, Changhoon

2016-10-13

Advances in genome assembly and phasing provide an opportunity to investigate the diploid architecture of the human genome and reveal the full range of structural variation across population groups. Here we report the de novo assembly and haplotype phasing of the Korean individual AK1 (ref. 1) using single-molecule real-time sequencing, next-generation mapping, microfluidics-based linked reads, and bacterial artificial chromosome (BAC) sequencing approaches. Single-molecule sequencing coupled with next-generation mapping generated a highly contiguous assembly, with a contig N50 size of 17.9 Mb and a scaffold N50 size of 44.8 Mb, resolving 8 chromosomal arms into single scaffolds. The de novo assembly, along with local assemblies and spanning long reads, closes 105 and extends into 72 out of 190 euchromatic gaps in the reference genome, adding 1.03 Mb of previously intractable sequence. High concordance between the assembly and paired-end sequences from 62,758 BAC clones provides strong support for the robustness of the assembly. We identify 18,210 structural variants by direct comparison of the assembly with the human reference, identifying thousands of breakpoints that, to our knowledge, have not been reported before. Many of the insertions are reflected in the transcriptome and are shared across the Asian population. We performed haplotype phasing of the assembly with short reads, long reads and linked reads from whole-genome sequencing and with short reads from 31,719 BAC clones, thereby achieving phased blocks with an N50 size of 11.6 Mb. Haplotigs assembled from single-molecule real-time reads assigned to haplotypes on phased blocks covered 89% of genes. The haplotigs accurately characterized the hypervariable major histocompatability complex region as well as demonstrating allele configuration in clinically relevant genes such as CYP2D6. This work presents the most contiguous diploid human genome assembly so far, with extensive investigation of unreported and Asian-specific structural variants, and high-quality haplotyping of clinically relevant alleles for precision medicine.

First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study

PubMed Central

Douillard, J-Y; Ostoros, G; Cobo, M; Ciuleanu, T; McCormack, R; Webster, A; Milenkova, T

2014-01-01

Background: Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Methods: Treatment: gefitinib 250 mg day−1 until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. Results: Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8% adenocarcinoma 97.2% never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5–77.7), DCR 90.6% (95% CI 83.5–94.8), median PFS 9.7 months (95% CI 8.5–11.0), median OS 19.2 months (95% CI 17.0–NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15% SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8–74.7). Conclusion: First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable. PMID:24263064

An Assessment of ECMWF Analyses and Model Forecasts over the North Slope of Alaska Using Observations from the ARM Mixed-Phase Arctic Cloud Experiment

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

Xie, Shaocheng; Klein, Stephen A.; Yio, J. John

2006-03-11

European Centre for Medium-Range Weather Forecasts (ECMWF) analysis and model forecast data are evaluated using observations collected during the Atmospheric Radiation Measurement (ARM) October 2004 Mixed-Phase Arctic Cloud Experiment (M-PACE) at its North Slope of Alaska (NSA) site. It is shown that the ECMWF analysis reasonably represents the dynamic and thermodynamic structures of the large-scale systems that affected the NSA during M-PACE. The model-analyzed near-surface horizontal winds, temperature, and relative humidity also agree well with the M-PACE surface measurements. Given the well-represented large-scale fields, the model shows overall good skill in predicting various cloud types observed during M-PACE; however, themore » physical properties of single-layer boundary layer clouds are in substantial error. At these times, the model substantially underestimates the liquid water path in these clouds, with the concomitant result that the model largely underpredicts the downwelling longwave radiation at the surface and overpredicts the outgoing longwave radiation at the top of the atmosphere. The model also overestimates the net surface shortwave radiation, mainly because of the underestimation of the surface albedo. The problem in the surface albedo is primarily associated with errors in the surface snow prediction. Principally because of the underestimation of the surface downwelling longwave radiation at the times of single-layer boundary layer clouds, the model shows a much larger energy loss (-20.9 W m-2) than the observation (-9.6 W m-2) at the surface during the M-PACE period.« less

First-Line XELOX Plus Bevacizumab Followed by XELOX Plus Bevacizumab or Single-Agent Bevacizumab as Maintenance Therapy in Patients with Metastatic Colorectal Cancer: The Phase III MACRO TTD Study

PubMed Central

Gómez-España, Auxiliadora; Massutí, Bartomeu; Sastre, Javier; Abad, Albert; Valladares, Manuel; Rivera, Fernando; Safont, Maria J.; Martínez de Prado, Purificación; Gallén, Manuel; González, Encarnación; Marcuello, Eugenio; Benavides, Manuel; Fernández-Martos, Carlos; Losa, Ferrán; Escudero, Pilar; Arrivi, Antonio; Cervantes, Andrés; Dueñas, Rosario; López-Ladrón, Amelia; Lacasta, Adelaida; Llanos, Marta; Tabernero, Jose M.; Antón, Antonio; Aranda, Enrique

2012-01-01

Purpose. The aim of this phase III trial was to compare the efficacy and safety of bevacizumab alone with those of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first-line treatment of patients with metastatic colorectal cancer (mCRC). Patients and Methods. Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression-free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety. Results. The intent-to-treat population comprised 480 patients (XELOX plus bevacizumab, n = 239; bevacizumab, n = 241); there were no significant differences in baseline characteristics. The median follow-up was 29.0 months (range, 0–53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand–foot syndrome, and neuropathy. Conclusion. Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with single-agent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients. PMID:22234633

Randomized phase 2/3 trial of CpG oligodeoxynucleotide PF-3512676 alone or with dacarbazine for patients with unresectable stage III and IV melanoma.

PubMed

Weber, Jeffrey S; Zarour, Hassan; Redman, Bruce; Trefzer, Uwe; O'Day, Steven; van den Eertwegh, Alfons J M; Marshall, Ernest; Wagner, Stefan

2009-09-01

The primary objective of this phase 2 study was to assess the objective response rate (complete response [CR] + partial responses [PR]), by Response Evaluation Criteria in Solid Tumors, of PF-3512676, a CpG oligodeoxynucleotide, alone in 2 doses or in combination with dacarbazine (DTIC) in patients with unresectable stage IIIB/C or stage IV malignant melanoma, with the aim of selecting an arm to take forward to a phase 3 portion of the study. A total of 184 patients were randomized to 1 of 4 treatments: PF-3512676 10 mg (low dose), at 40 mg (high dose), 40 mg plus DTIC (850 mg/m(2)), or DTIC (850 mg/m(2)) alone. Patients received PF-3512676 subcutaneously weekly in a 3-week cycle and received DTIC intravenously on the first week of the cycle. The objective response rate (PR or CR, confirmed or unconfirmed) in the 40 mg + DTIC arm was 16% (7 patients) compared with 8% (3 patients) with DTIC alone. One (2%) patient in the 10-mg and 0 patients in the 40-mg arms achieved an objective response. Best response of CR or PR or stable disease (SD), with no minimum duration defined for SD, was achieved by 15 (33%) patients in the 40 mg + DTIC arm, 15 (38%) patients in the DTIC-only arm, 8 (17%) patients in the 10-mg arm, and 9 (20%) patients in the 40-mg arm. The most frequently reported adverse events were classified as local injection site reactions or systemic flu-like symptoms, specifically fatigue, rigors, and pyrexia. PF-3512676 at the doses used was generally well tolerated. The modest objective response rates observed in all arms did not warrant continuation to the phase 3 portion of the study.

Gaia DR1 Evidence of Disrupting the Perseus Arm

NASA Astrophysics Data System (ADS)

Baba, Junichi; Kawata, Daisuke; Matsunaga, Noriyuki; Grand, Robert J. J.; Hunt, Jason A. S.

2018-02-01

We have discovered a clear sign of the disruption phase of the Perseus arm in the Milky Way using Cepheid variables, taking advantage of the accurately measured distances of Cepheids and the proper motions from Gaia Data Release 1. Both the Galactocentric radial and rotation velocities of 77 Cepheids within 1.5 kpc of the Perseus arm are correlated with their distances from the locus of the Perseus arm, as the trailing side is rotating faster and moving inward compared to the leading side. We also found a negative vertex deviation for the Cepheids on the trailing side, ‑27.°6 ± 2.°4, in contrast to the positive vertex deviation in the solar neighborhood. This is, to our knowledge, the first direct evidence that the vertex deviation around the Perseus arm is affected by the spiral arm. We compared these observational trends with our N-body/hydrodynamics simulations based on a static density-wave spiral scenario and with those based on a transient dynamic spiral scenario. Although our comparisons are limited to qualitative trends, they strongly favor the conclusion that the Perseus arm is in the disruption phase of a transient arm.

Transforaminal lumbar interbody graft placement using an articulating delivery arm facilitates increased segmental lordosis with superior anterior and midline graft placement.

PubMed

Shau, David N; Parker, Scott L; Mendenhall, Stephen K; Zuckerman, Scott L; Godil, Saniya S; Devin, Clinton J; McGirt, Matthew J

2015-05-01

Transforaminal lumbar interbody fusion (TLIF) is a frequently performed method of lumbar arthrodesis in patients failing medical management of back and leg pain. Accurate placement of the interbody graft and restoration of lordosis has been shown to be crucial when performing lumbar fusion procedures. We performed a single-surgeon, prospective, randomized study to determine whether a novel articulating versus traditional straight graft delivery arm system allows for superior graft placement and increased lordosis for single-level TLIF. Thirty consecutive patients undergoing single-level TLIF were included and prospectively randomized to one of the 2 groups (articulated vs. straight delivery arm system). Three radiographic characteristics were evaluated at 6-week follow-up: (1) degree of segmental lumbar lordosis at the fused level; (2) the percent anterior location of the interbody graft in disk space; and (3) the distance (mm) off midline of the interbody graft placement. Randomization yielded 16 patients in the articulated delivery arm cohort and 14 in the straight delivery arm cohort. The articulating delivery arm system yielded an average of 14.7-degree segmental lordosis at fused level, 35% anterior location, and 3.6 mm off midline. The straight delivery arm system yielded an average of 10.7-degree segmental lordosis at fused level, 46% anterior location, and 7.0 mm off midline. All 3 comparisons were statistically significant (P<0.05). The study suggests that an articulating delivery arm system facilitates superior anterior and midline TLIF graft placement allowing for increased segmental lordosis compared with a traditional straight delivery arm system.

Intra-Cyclic Phases of Arm-Leg Movement and Index of Coordination in Relation to Sprint Breaststroke Swimming in Young Swimmers

PubMed Central

Strzala, Marek; Krezalek, Piotr; Glab, Grzegorz; Kaca, Marcin; Ostrowski, Andrzej; Stanula, Arkadiusz; Tyka, Anna K.

2013-01-01

Despite the limitations set by FINA regulations, execution technique in breaststroke swimming is being improved thanks to more and more advanced analyses of the efficiency of the swimmer’s movements. The aim of this study was to detect the parameters of the time structure of the cycle correlated with the maximal swimming speed at the of 50 meters distance, in order to focus to specific technical aspects in the breaststroke training. In the group of 23 participants, between the age of 15.0 ± 1.17, the breaststroke cycle movement of the arms and legs was divided into two phases: propulsive or non-propulsive. In addition, indices characterizing the temporal coordination of movements of the upper limbs in relation to the lower limbs were distinguished: 1) Arm-Leg Lag - determines the interval between the phases of propulsion generated by upper and lower limbs; 2) Glide or Overlap - the inter-cyclic glide or overlap of the propulsive movement of the upper on lower limbs. Significant dependence was noted between the swim speed (V50surface breast) and the percentage of time of the arm propulsive in-sweep phase 0.64, p < 0.01. A significant correlation was observed between the V50surface breast with the percentage of partially surfaced hand phase of arm recovery 0.54, p < 0.01. Correlation between total leg propulsion and non-propulsion phases with V50surface breast was 0.49 and -0.49 respectively, both p < 0.01. The Glide or Overlap index was significantly related to the swimming speed V50surface breast 0.48, p < 0.05. This type of analysis suggests how to refine the swimming technique, with the goal to improve the current speed capabilities; furthermore the results also indicate the direction of its development in the future swimmers of the group studied. Key Points This study investigated the influence of the inter- and intra-cyclic time structure of the movements in sprint breaststroke swimming. The distinction of the operations phases of the upper limbs in the propulsive movement shows significant correlation 0.64, p <0.01 between the swimming speed V50surface breast and the execution time of the in-sweep phase in the movement cycle. Significant relationship was noted between minimizing the first non-propulsive phase of arm recovery with higher contribution of the next, partially immersed sliding phase of arm recovery. The specification of the inter-cyclic coordination index of the upper and lower limbs during the movement cycle shows influence of the overlap of the propulsive movement of the upper limbs on the propulsive movement of the lower limbs on V50surface breast with correlation 0.48, p <0.05 for young swimmers. PMID:24421728

A case study of microphysical structures and hydrometeor phase in convection using radar Doppler spectra at Darwin, Australia

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

Riihimaki, Laura D.; Comstock, Jennifer M.; Luke, Edward

To understand the microphysical processes that impact diabatic heating and cloud lifetimes in convection, we need to characterize the spatial distribution of supercooled liquid water. To address this observational challenge, vertically pointing active sensors at the Darwin Atmospheric Radiation Measurement (ARM) site are used to classify cloud phase within a deep convective cloud in a shallow to deep convection transitional case. The cloud cannot be fully observed by a lidar due to signal attenuation. Thus we develop an objective method for identifying hydrometeor classes, including mixed-phase conditions, using k-means clustering on parameters that describe the shape of the Doppler spectramore » from vertically pointing Ka band cloud radar. This approach shows that multiple, overlapping mixed-phase layers exist within the cloud, rather than a single region of supercooled liquid, indicating complexity to how ice growth and diabatic heating occurs in the vertical structure of the cloud.« less

Off-axis digital holographic camera for quantitative phase microscopy.

PubMed

Monemhaghdoust, Zahra; Montfort, Frédéric; Emery, Yves; Depeursinge, Christian; Moser, Christophe

2014-06-01

We propose and experimentally demonstrate a digital holographic camera which can be attached to the camera port of a conventional microscope for obtaining digital holograms in a self-reference configuration, under short coherence illumination and in a single shot. A thick holographic grating filters the beam containing the sample information in two dimensions through diffraction. The filtered beam creates the reference arm of the interferometer. The spatial filtering method, based on the high angular selectivity of the thick grating, reduces the alignment sensitivity to angular displacements compared with pinhole based Fourier filtering. The addition of a thin holographic grating alters the coherence plane tilt introduced by the thick grating so as to create high-visibility interference over the entire field of view. The acquired full-field off-axis holograms are processed to retrieve the amplitude and phase information of the sample. The system produces phase images of cheek cells qualitatively similar to phase images extracted with a standard commercial DHM.

Grand-design Spiral Arms in a Young Forming Circumstellar Disk

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

Tomida, Kengo; Lin, Chia Hui; Machida, Masahiro N.

We study formation and long-term evolution of a circumstellar disk in a collapsing molecular cloud core using a resistive magnetohydrodynamic simulation. While the formed circumstellar disk is initially small, it grows as accretion continues, and its radius becomes as large as 200 au toward the end of the Class-I phase. A pair of grand-design spiral arms form due to gravitational instability in the disk, and they transfer angular momentum in the highly resistive disk. Although the spiral arms disappear in a few rotations as expected in a classical theory, new spiral arms form recurrently as the disk, soon becoming unstablemore » again by gas accretion. Such recurrent spiral arms persist throughout the Class-0 and I phases. We then perform synthetic observations and compare our model with a recent high-resolution observation of a young stellar object Elias 2–27, whose circumstellar disk has grand-design spiral arms. We find good agreement between our theoretical model and the observation. Our model suggests that the grand-design spiral arms around Elias 2–27 are consistent with material arms formed by gravitational instability. If such spiral arms commonly exist in young circumstellar disks, it implies that young circumstellar disks are considerably massive and gravitational instability is the key process of angular momentum transport.« less

Cost-Effectiveness of Initiating Antiretroviral Therapy at Different Points in TB Treatment in HIV-TB Coinfected Ambulatory Patients in South Africa.

PubMed

Naidoo, Kogieleum; Grobler, Anneke C; Deghaye, Nicola; Reddy, Tarylee; Gengiah, Santhanalakshmi; Gray, Andrew; Abdool Karim, Salim

2015-08-15

Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment improves survival in TB-HIV coinfected patients. In patients with CD4 counts <50 cells per cubic millimeter, there is a substantial clinical and survival benefit of early ART initiation. The purpose of this study was to assess the costs and cost-effectiveness of starting ART at various time points during TB treatment in patients with CD4 counts ≥50 cells per cubic millimeter. In the SAPiT trial, 642 HIV-TB coinfected patients were randomized to 3 arms: receiving ART within 4 weeks of starting TB treatment (early treatment arm; Arm-1), after the intensive phase of TB treatment (late treatment arm; Arm-2), or after completing TB treatment (sequential arm; Arm-3). Direct health care costs were measured from a provider perspective using a micro-costing approach. The incremental cost per death averted was calculated using the trial outcomes. For patients with CD4 count ≥50 cells per cubic millimeter, median monthly variable costs per patient were US $116, US $113, and US $102 in Arm-1, Arm-2 and Arm-3, respectively. There were 12 deaths in 177 patients in Arm-1, 8 deaths in 180 patients in the Arm-2, and 19 deaths in 172 patients in Arm-3. Although the costs were lower in Arm-3, it had a substantially higher mortality rate. The incremental cost per death averted associated with moving from Arm-3 to Arm-2 was US $4199. There was no difference in mortality between Arm-1 and Arm-2, but Arm-1 was slightly more expensive. Initiation of ART after the completion of the intensive phase of TB treatment is cost-effective for patients with CD4 counts ≥50 cells per cubic millimeter.

Comprehensive classification test of scapular dyskinesis: A reliability study.

PubMed

Huang, Tsun-Shun; Huang, Han-Yi; Wang, Tyng-Guey; Tsai, Yung-Shen; Lin, Jiu-Jenq

2015-06-01

Assessment of scapular dyskinesis (SD) is of clinical interest, as SD is believed to be related to shoulder pathology. However, no clinical assessment with sufficient reliability to identify SD and provide treatment strategies is available. The purpose of this study was to investigate the reliability of the comprehensive SD classification method. Cross-sectional reliability study. Sixty subjects with unilateral shoulder pain were evaluated by two independent physiotherapists with a visual-based palpation method. SD was classified as single abnormal scapular pattern [inferior angle (pattern I), medial border (pattern II), superior border of scapula prominence or abnormal scapulohumeral rhythm (pattern III)], a mixture of the above abnormal scapular patterns, or normal pattern (pattern IV). The assessment of SD was evaluated as subjects performed bilateral arm raising/lowering movements with a weighted load in the scapular plane. Percentage of agreement and kappa coefficients were calculated to determine reliability. Agreement between the 2 independent physiotherapists was 83% (50/60, 6 subjects as pattern III and 44 subjects as pattern IV) in the raising phase and 68% (41/60, 5 subjects as pattern I, 12 subjects as pattern II, 12 subjects as pattern IV, 12 subjects as mixed patterns I and II) in the lowering phase. The kappa coefficients were 0.49-0.64. We concluded that the visual-based palpation classification method for SD had moderate to substantial inter-rater reliability. The appearance of different types of SD was more pronounced in the lowering phase than in the raising phase of arm movements. Copyright © 2014 Elsevier Ltd. All rights reserved.

Individuals with chronic hemiparetic stroke can correctly match forearm positions within a single arm

PubMed Central

Gurari, Netta; Drogos, Justin M.; Dewald, Julius P.A.

2017-01-01

Objective Previous studies determined, using between arms position matching assessments, that at least one-half of individuals with stroke have an impaired position sense. We investigated whether individuals with chronic stroke who have impairments mirroring arm positions also have impairments identifying the location of each arm in space. Methods Participants with chronic hemiparetic stroke and age-matched participants without neurological impairments (controls) performed a between forearms position matching task based on a clinical assessment and a single forearm position matching task, using passive and active movements, based on a robotic assessment. Results 12 out of our 14 participants with stroke who had clinically determined between forearms position matching impairments had greater errors than the controls in both their paretic and non-paretic arm when matching positions during passive movements; yet stroke participants performed comparable to the controls during active movements. Conclusions Many individuals with chronic stroke may have impairments matching positions in both their paretic and non-paretic arm if their arm is moved for them, yet not within either arm if these individuals control their own movements. Significance The neural mechanisms governing arm location perception in the stroke population may differ depending on whether arm movements are made passively versus actively. PMID:27866116

High resolution neutron Larmor diffraction using superconducting magnetic Wollaston prisms

DOE PAGES

Li, Fankang; Feng, Hao; Thaler, Alexander N.; ...

2017-04-13

The neutron Larmor diffraction technique has been implemented using superconducting magnetic Wollaston prisms in both single-arm and double-arm configurations. Successful measurements of the coefficient of thermal expansion of a single-crystal copper sample demonstrates that the method works as expected. Our experiment involves a new method of tuning by varying the magnetic field configurations in the device and the tuning results agree well with previous measurements. The difference between single-arm and double-arm configurations has been investigated experimentally. Here, we conclude that this measurement benchmarks the applications of magnetic Wollaston prisms in Larmor diffraction and shows in principle that the setup canmore » be used for inelastic phonon line-width measurements. The achievable resolution for Larmor diffraction is comparable to that using Neutron Resonance Spin Echo (NRSE) coils. Furthermore, the use of superconducting materials in the prisms allows high neutron polarization and transmission efficiency to be achieved.« less

Recognizing upper limb movements with wrist worn inertial sensors using k-means clustering classification.

PubMed

Biswas, Dwaipayan; Cranny, Andy; Gupta, Nayaab; Maharatna, Koushik; Achner, Josy; Klemke, Jasmin; Jöbges, Michael; Ortmann, Steffen

2015-04-01

In this paper we present a methodology for recognizing three fundamental movements of the human forearm (extension, flexion and rotation) using pattern recognition applied to the data from a single wrist-worn, inertial sensor. We propose that this technique could be used as a clinical tool to assess rehabilitation progress in neurodegenerative pathologies such as stroke or cerebral palsy by tracking the number of times a patient performs specific arm movements (e.g. prescribed exercises) with their paretic arm throughout the day. We demonstrate this with healthy subjects and stroke patients in a simple proof of concept study in which these arm movements are detected during an archetypal activity of daily-living (ADL) - 'making-a-cup-of-tea'. Data is collected from a tri-axial accelerometer and a tri-axial gyroscope located proximal to the wrist. In a training phase, movements are initially performed in a controlled environment which are represented by a ranked set of 30 time-domain features. Using a sequential forward selection technique, for each set of feature combinations three clusters are formed using k-means clustering followed by 10 runs of 10-fold cross validation on the training data to determine the best feature combinations. For the testing phase, movements performed during the ADL are associated with each cluster label using a minimum distance classifier in a multi-dimensional feature space, comprised of the best ranked features, using Euclidean or Mahalanobis distance as the metric. Experiments were performed with four healthy subjects and four stroke survivors and our results show that the proposed methodology can detect the three movements performed during the ADL with an overall average accuracy of 88% using the accelerometer data and 83% using the gyroscope data across all healthy subjects and arm movement types. The average accuracy across all stroke survivors was 70% using accelerometer data and 66% using gyroscope data. We also use a Linear Discriminant Analysis (LDA) classifier and a Support Vector Machine (SVM) classifier in association with the same set of features to detect the three arm movements and compare the results to demonstrate the effectiveness of our proposed methodology. Copyright © 2014 Elsevier B.V. All rights reserved.

The current status of neoadjuvant therapy for esophageal cancer.

PubMed

Lin, Daniel; Leichman, Lawrence

2014-01-01

Through the contribution of a very large number of single-arm phase II trials and many less randomized phase III trials, the standard of care for locally advanced esophageal cancer has evolved to either combination chemotherapy plus radiation or combination chemotherapy. In this review, we focus on the key findings of these studies and selected meta-analyses that have led to this evolution. We note differences in outcomes for adenocarcinomas of the esophagus when compared to squamous cell esophageal cancers. Despite progress in developing a consensus for therapy, the outcome for patients with locally advanced remains poor. We complete the review by noting newer areas of investigation seeking to provide targeted and more personalized therapy to patients with esophageal cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors.

PubMed

Molife, L Rhoda; Yan, Li; Vitfell-Rasmussen, Joanna; Zernhelt, Adriane M; Sullivan, Daniel M; Cassier, Philippe A; Chen, Eric; Biondo, Andrea; Tetteh, Ernestina; Siu, Lillian L; Patnaik, Amita; Papadopoulos, Kyriakos P; de Bono, Johann S; Tolcher, Anthony W; Minton, Susan

2014-01-03

Inhibition of AKT with MK-2206 has demonstrated synergism with anticancer agents. This phase 1 study assessed the MTD, DLTs, PK, and efficacy of MK-2206 in combination with cytotoxic and targeted therapies. Advanced solid tumor patients received oral MK-2206 45 or 60 mg (QOD) with either carboplatin (AUC 6.0) and paclitaxel 200 mg/m2 (arm 1), docetaxel 75 mg/m2 (arm 2), or erlotinib 100 or 150 mg daily (arm 3); alternative schedules of MK-2206 135-200 mg QW or 90-250 mg Q3W were also tested. MTD of MK-2206 (N = 72) was 45 mg QOD or 200 mg Q3W (arm 1); MAD was 200 mg Q3W (arm 2) and 135 mg QW (arm 3). DLTs included skin rash (arms 1, 3), febrile neutropenia (QOD, arms 1, 2), tinnitus (Q3W, arm 2), and stomatitis (QOD, arm 3). Common drug-related toxicities included fatigue (68%), nausea (49%), and rash (47%). Two patients with squamous cell carcinoma of the head and neck (arm 1; Q3W) demonstrated a complete and partial response (PR); additional PRs were observed in patients (1 each) with melanoma, endometrial, neuroendocrine prostate, NSCLC, and cervical cancers. Six patients had stable disease ≥6 months. MK-2206 plus carboplatin and paclitaxel, docetaxel, or erlotinib was well-tolerated, with early evidence of antitumor activity.

Peg-in-Hole Assembly Based on Two-phase Scheme and F/T Sensor for Dual-arm Robot

PubMed Central

Zhang, Xianmin; Zheng, Yanglong; Ota, Jun; Huang, Yanjiang

2017-01-01

This paper focuses on peg-in-hole assembly based on a two-phase scheme and force/torque sensor (F/T sensor) for a compliant dual-arm robot, the Baxter robot. The coordinated operations of human beings in assembly applications are applied to the behaviors of the robot. A two-phase assembly scheme is proposed to overcome the inaccurate positioning of the compliant dual-arm robot. The position and orientation of assembly pieces are adjusted respectively in an active compliant manner according to the forces and torques derived by a six degrees-of-freedom (6-DOF) F/T sensor. Experiments are conducted to verify the effectiveness and efficiency of the proposed assembly scheme. The performances of the dual-arm robot are consistent with those of human beings in the peg-in-hole assembly process. The peg and hole with 0.5 mm clearance for round pieces and square pieces can be assembled successfully. PMID:28862691

Peg-in-Hole Assembly Based on Two-phase Scheme and F/T Sensor for Dual-arm Robot.

PubMed

Zhang, Xianmin; Zheng, Yanglong; Ota, Jun; Huang, Yanjiang

2017-09-01

This paper focuses on peg-in-hole assembly based on a two-phase scheme and force/torque sensor (F/T sensor) for a compliant dual-arm robot, the Baxter robot. The coordinated operations of human beings in assembly applications are applied to the behaviors of the robot. A two-phase assembly scheme is proposed to overcome the inaccurate positioning of the compliant dual-arm robot. The position and orientation of assembly pieces are adjusted respectively in an active compliant manner according to the forces and torques derived by a six degrees-of-freedom (6-DOF) F/T sensor. Experiments are conducted to verify the effectiveness and efficiency of the proposed assembly scheme. The performances of the dual-arm robot are consistent with those of human beings in the peg-in-hole assembly process. The peg and hole with 0.5 mm clearance for round pieces and square pieces can be assembled successfully.

Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer.

PubMed

Del Campo, J M; Roszak, A; Bidzinski, M; Ciuleanu, T E; Hogberg, T; Wojtukiewicz, M Z; Poveda, A; Boman, K; Westermann, A M; Lebedinsky, C

2009-11-01

This randomized, open-label, phase II clinical trial evaluated the optimal regimen of trabectedin administered every 3 weeks in patients with platinum-sensitive, relapsed, advanced ovarian cancer (AOC). Patients previously treated with less than two or two previous chemotherapy lines were randomized to receive trabectedin 1.5 mg/m(2) 24 h (arm A, n = 54) or 1.3 mg/m(2) 3 h (arm B, n = 53). Objective response rate (ORR) per RECIST was the primary efficacy end point. Toxic effects were graded according to the National Cancer Institute-Common Toxicity Criteria v. 2.0. ORR was 38.9% [95% confidence interval (CI) 25.9% to 53.1%; arm A] and 35.8% (95% CI 23.1% to 50.2%; arm B) (intention-to-treat primary analysis). Median time to progression was 6.2 months (95% CI 5.3-8.6 months; arm A) and 6.8 months (95% CI 4.6-7.4 months; arm B). Frequent severe adverse events were nausea/vomiting (24%, arm A; 15%, arm B) and fatigue (15%, arm A; 10%, arm B). Common severe laboratory abnormalities were transient, noncumulative neutropenia (55%, arm A; 37%, arm B) and transaminase increases (alanine aminotransferase, 55%, arm A; 59%, arm B). Both every-3-weeks trabectedin regimes, 1.5 mg/m(2) 24 h and 1.3 mg/m(2) 3 h, were active and reasonably well tolerated in AOC platinum-sensitive patients. Trabectedin every-3-weeks has promising activity and deserves to be further evaluated in relapsed AOC.

Autoantigen-specific regulatory T cells induced in patients with Type 1 Diabetes Mellitus by Insulin B-chain immunotherapy

PubMed Central

Orban, Tihamer; Farkas, Klara; Jalahej, Heyam; Kis, Janos; Treszl, Andras; Falk, Ben; Reijonen, Helena; Wolfsdorf, Joseph; Ricker, Alyne; Matthews, Jeffrey B.; Tchao, Nadio; Sayre, Peter; Bianchine, Pete

2009-01-01

There is a growing body of evidence to suggest that the autoimmunity observed in type 1 diabetes mellitus (T1DM) is the result of an imbalance between autoaggressive and regulatory cell subsets. Therapeutics that supplement or enhance the existing regulatory subset are therefore a much sought after goal in this indication. Here, we report the results of a double blind, placebo controlled, phase I clinical trial of a novel antigen-specific therapeutic in 12 subjects with recently diagnosed T1DM. Our primary objective was to test its safety. The study drug, human insulin B-chain in incomplete Freund’s adjuvant (IFA) was administered as a single intramuscular injection, with subjects followed for 2 years. All subjects completed therapy and all follow-up visits. The therapy was generally safe and well-tolerated. Mixed meal stimulated C-peptide responses, measured every 6 months, showed no statistical differences between arms. All patients vaccinated with the autoantigen, but none who received placebo, developed robust insulin-specific humoral and T cell responses. Up to two years following the single injection, in peripheral blood from subjects in the experimental arm, but not the control arm, insulin B-chain-specific CD4+ T cells could be isolated and cloned that showed phenotypic and functional characteristics of regulatory T cells. The induction of a lasting, robust immune response generating autoantigen-specific regulatory T cells provides strong justification for further testing of this therapy in type 1 diabetes. (clinicaltrials.gov identifier NCT00057499). PMID:19931408

Time-Delay Interferometry for Space-based Gravitational Wave Searches

NASA Technical Reports Server (NTRS)

Armstrong, J.; Estabrook, F.; Tinto, M.

1999-01-01

Ground-based, equal-arm-length laser interferometers are being built to measure high-frequency astrophysical graviatational waves. Because of the arm-length equality, laser light experiences the same delay in each arm and thus phase or frequency noise from the laser itself precisely cancels at the photodetector.

Adding bevacizumab to single agent chemotherapy for the treatment of platinum-resistant recurrent ovarian cancer: A cost effectiveness analysis of the AURELIA trial.

PubMed

Wysham, Weiya Z; Schaffer, Elisabeth M; Coles, Theresa; Roque, Dario R; Wheeler, Stephanie B; Kim, Kenneth H

2017-05-01

AURELIA, a randomized phase III trial of adding bevacizumab (B) to single agent chemotherapy (CT) for the treatment of platinum-resistant recurrent ovarian cancer, demonstrated improved progression free survival (PFS) in the B+CT arm compared to CT alone. We aimed to evaluate the cost effectiveness of adding B to CT in the treatment of platinum-resistant recurrent ovarian cancer. A decision tree model was constructed to evaluate the cost effectiveness of adding bevacizumab (B) to single agent chemotherapy (CT) based on the arms of the AURELIA trial. Costs, quality-adjusted life years (QALYs), and progression free survival (PFS) were modeled over fifteen months. Model inputs were extracted from published literature and public sources. Incremental cost effectiveness ratios (ICERs) per QALY gained and ICERs per progression free life year saved (PF-LYS) were calculated. One-way sensitivity analyses were performed to evaluate the robustness of results. The ICER associated with B+CT is $410,455 per QALY gained and $217,080 per PF-LYS. At a willingness to pay (WTP) threshold of $50,000/QALY, adding B to single agent CT is not cost effective for this patient population. Even at a WTP threshold of $100,000/QALY, B+CT is not cost effective. These findings are robust to sensitivity analyses. Despite gains in QALY and PFS, the addition of B to single agent CT for treatment of platinum-resistant recurrent ovarian cancer is not cost effective. Benefits, risks, and costs associated with treatment should be taken into consideration when prescribing chemotherapy for this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

EMG analysis of human postural responses during parabolic flight microgravity episodes

NASA Technical Reports Server (NTRS)

Layne, Charles S.; Spooner, Brian S.

1990-01-01

Anticipatory postural activity in the trunk and legs precedes rapid shoulder flexion in unit gravity. The hypothesis that anticipatory activity is a component of a single neural command for arm movement was tested by monitoring the surface electromyographic activity of the biceps femoris, paraspinals, and deltoid muscles of three subjects during the microgravity phase of parabolic flight. If part of a single command, anticipatory postural activity would be expected to remain intact despite the absence of the body's center of gravity in a reduced gravity environment. However, in at least 75 percent of the microgravity trials anticipatory biceps femoris activity was absent, indicating a separation of postural and agonist muscle activity. Such a finding suggests that anticipatory postural biceps femoris activity may be initiated independently of agonist (deltoid) activity.

Brief Report: Dolutegravir Plus Abacavir/Lamivudine for the Treatment of HIV-1 Infection in Antiretroviral Therapy-Naive Patients: Week 96 and Week 144 Results From the SINGLE Randomized Clinical Trial.

PubMed

Walmsley, Sharon; Baumgarten, Axel; Berenguer, Juan; Felizarta, Franco; Florence, Eric; Khuong-Josses, Marie-Aude; Kilby, J Michael; Lutz, Thomas; Podzamczer, Daniel; Portilla, Joaquin; Roth, Norman; Wong, Deborah; Granier, Catherine; Wynne, Brian; Pappa, Keith

2015-12-15

The SINGLE study was a randomized, double-blind, noninferiority study that evaluated the safety and efficacy of 50 mg dolutegravir + abacavir/lamivudine versus efavirenz/tenofovir/emtricitabine in 833 ART-naive HIV-1 + participants. Of 833 randomized participants, 71% in the dolutegravir + abacavir/lamivudine arm and 63% in the efavirenz/tenofovir/emtricitabine arm maintained viral loads of <50 copies per milliliter through W144 (P = 0.01). Superior efficacy was primarily driven by fewer discontinuations due to adverse events in the dolutegravir + abacavir/lamivudine arm [dolutegravir + abacavir/lamivudine arm, 16 (4%); efavirenz/tenofovir/emtricitabine arm, 58 (14%)] through W144 [corrected]. No treatment-emergent integrase or nucleoside resistance was observed in dolutegravir + abacavir/lamivudine recipients through W144.

Arterial blood pressure response to heavy resistance exercise.

PubMed

MacDougall, J D; Tuxen, D; Sale, D G; Moroz, J R; Sutton, J R

1985-03-01

The purpose of this study was to record the blood pressure response to heavy weight-lifting exercise in five experienced body builders. Blood pressure was directly recorded by means of a capacitance transducer connected to a catheter in the brachial artery. Intrathoracic pressure with the Valsalva maneuver was recorded as mouth pressure by having the subject maintain an open glottis while expiring against a column of Hg during the lifts. Exercises included single-arm curls, overhead presses, and both double- and single-leg presses performed to failure at 80, 90, 95, and 100% of maximum. Systolic and diastolic blood pressures rose rapidly to extremely high values during the concentric contraction phase for each lift and declined with the eccentric contraction. The greatest peak pressures occurred during the double-leg press where the mean value for the group was 320/250 mmHg, with pressures in one subject exceeding 480/350 mmHg. Peak pressures with the single-arm curl exercise reached a mean group value of 255/190 mmHg when repetitions were continued to failure. Mouth pressures of 30-50 Torr during a single maximum lift, or as subjects approached failure with a submaximal weight, indicate that a portion of the observed increase in blood pressure was caused by a Valsalva maneuver. It was concluded that when healthy young subjects perform weight-lifting exercises the mechanical compression of blood vessels combines with a potent pressor response and a Valsalva response to produce extreme elevations in blood pressure. Pressures are extreme even when exercise is performed with a relatively small muscle mass.

Meta-analyses and adaptive group sequential designs in the clinical development process.

PubMed

Jennison, Christopher; Turnbull, Bruce W

2005-01-01

The clinical development process can be viewed as a succession of trials, possibly overlapping in calendar time. The design of each trial may be influenced by results from previous studies and other currently proceeding trials, as well as by external information. Results from all of these trials must be considered together in order to assess the efficacy and safety of the proposed new treatment. Meta-analysis techniques provide a formal way of combining the information. We examine how such methods can be used in combining results from: (1) a collection of separate studies, (2) a sequence of studies in an organized development program, and (3) stages within a single study using a (possibly adaptive) group sequential design. We present two examples. The first example concerns the combining of results from a Phase IIb trial using several dose levels or treatment arms with those of the Phase III trial comparing the treatment selected in Phase IIb against a control This enables a "seamless transition" from Phase IIb to Phase III. The second example examines the use of combination tests to analyze data from an adaptive group sequential trial.

On the false lock behavior of polarity-type Costas loops with Manchester coded input. [for Space Shuttle Orbiter communication

NASA Technical Reports Server (NTRS)

Simon, M. K.

1977-01-01

A modification of a Costas loop is described, and the false lock behavior of this system is studied. The modified Costas loop hard limits the output of the in-phase channel, replaces the analog multiplier with a chopper-type device, and is equipped with single-pole arm filters in the loop. The false lock behavior associated with the use of Manchester coded data is investigated; the results can be applied to the assessment of the false lock margin on the Ku-band uplink to the Space Shuttle Orbiter through the TURSS.

Cost-effectiveness of initiating antiretroviral therapy at different points in TB treatment in HIV-TB co-infected ambulatory patients in South Africa

PubMed Central

Naidoo, Kogieleum; Grobler, Anneke C; Deghaye, Nicola; Reddy, Tarylee; Gengiah, Santhanalakshmi; Gray, Andrew; Karim, Salim Abdool

2015-01-01

Objective Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment improves survival in TB-HIV co-infected patients. In patients with CD4+ counts <50cells/mm3, there is a substantial clinical and survival benefit of early ART initiation. The purpose of this study was to assess the costs and cost effectiveness of starting ART at various time points during TB treatment in patients with CD4+ counts ≥50cells/mm3. Methods In the SAPiT trial, 642 HIV-TB co-infected patients were randomized to three arms, either receiving ART within 4 weeks of starting TB treatment (early treatment arm; Arm-1), after the intensive phase of TB treatment (late treatment arm; Arm-2), or after completing TB treatment (sequential arm; Arm-3). Direct healthcare costs were measured from a provider perspective using a micro-costing approach. The incremental cost per death averted was calculated using the trial outcomes. Results For patients with CD4+ count≥50cells/mm3, median monthly variable costs per patient were $116, $113 and $102 in Arms-1, -2 and -3, respectively. There were 12 deaths in 177 patients in Arm-1, 8 deaths in 180 patients in the Arm-2 and 19 deaths in 172 patients in Arm-3. While the costs were lower in Arm-3, it had a substantially higher mortality rate. The incremental cost per death averted associated with moving from Arm-3 to Arm-2 was $4199. There was no difference in mortality between Arm-1 and Arm-2, but Arm-1 was slightly more expensive. Conclusions Initiation of ART after the completion of the intensive phase of TB treatment is cost effective for patients with CD4+ counts≥50cells/mm3. PMID:26167618

Structural Studies of Three-Arm Star Block Copolymers Exposed to Extreme Stretch Suggests a Persistent Polymer Tube

NASA Astrophysics Data System (ADS)

Mortensen, Kell; Borger, Anine L.; Kirkensgaard, Jacob J. K.; Garvey, Christopher J.; Almdal, Kristoffer; Dorokhin, Andriy; Huang, Qian; Hassager, Ole

2018-05-01

We present structural small-angle neutron scattering studies of a three-armed polystyrene star polymer with short deuterated segments at the end of each arm. We show that the form factor of the three-armed star molecules in the relaxed state agrees with that of the random phase approximation of Gaussian chains. Upon exposure to large extensional flow conditions, the star polymers change conformation resulting in a highly stretched structure that mimics a fully extended three-armed tube model. All three arms are parallel to the flow, one arm being either in positive or negative stretching direction, while the two other arms are oriented parallel, right next to each other in the direction opposite to the first arm.

Simulating mixed-phase Arctic stratus clouds: sensitivity to ice initiation mechanisms

NASA Astrophysics Data System (ADS)

Sednev, I.; Menon, S.; McFarquhar, G.

2008-06-01

The importance of Arctic mixed-phase clouds on radiation and the Arctic climate is well known. However, the development of mixed-phase cloud parameterization for use in large scale models is limited by lack of both related observations and numerical studies using multidimensional models with advanced microphysics that provide the basis for understanding the relative importance of different microphysical processes that take place in mixed-phase clouds. To improve the representation of mixed-phase cloud processes in the GISS GCM we use the GISS single-column model coupled to a bin resolved microphysics (BRM) scheme that was specially designed to simulate mixed-phase clouds and aerosol-cloud interactions. Using this model with the microphysical measurements obtained from the DOE ARM Mixed-Phase Arctic Cloud Experiment (MPACE) campaign in October 2004 at the North Slope of Alaska, we investigate the effect of ice initiation processes and Bergeron-Findeisen process (BFP) on glaciation time and longevity of single-layer stratiform mixed-phase clouds. We focus on observations taken during 9th-10th October, which indicated the presence of a single-layer mixed-phase clouds. We performed several sets of 12-h simulations to examine model sensitivity to different ice initiation mechanisms and evaluate model output (hydrometeors' concentrations, contents, effective radii, precipitation fluxes, and radar reflectivity) against measurements from the MPACE Intensive Observing Period. Overall, the model qualitatively simulates ice crystal concentration and hydrometeors content, but it fails to predict quantitatively the effective radii of ice particles and their vertical profiles. In particular, the ice effective radii are overestimated by at least 50%. However, using the same definition as used for observations, the effective radii simulated and that observed were more comparable. We find that for the single-layer stratiform mixed-phase clouds simulated, process of ice phase initiation due to freezing of supercooled water in both saturated and undersaturated (w.r.t. water) environments is as important as primary ice crystal origination from water vapor. We also find that the BFP is a process mainly responsible for the rates of glaciation of simulated clouds. These glaciation rates cannot be adequately represented by a water-ice saturation adjustment scheme that only depends on temperature and liquid and solid hydrometeors' contents as is widely used in bulk microphysics schemes and are better represented by processes that also account for supersaturation changes as the hydrometeors grow.

Simulating mixed-phase Arctic stratus clouds: sensitivity to ice initiation mechanisms

NASA Astrophysics Data System (ADS)

Sednev, I.; Menon, S.; McFarquhar, G.

2009-07-01

The importance of Arctic mixed-phase clouds on radiation and the Arctic climate is well known. However, the development of mixed-phase cloud parameterization for use in large scale models is limited by lack of both related observations and numerical studies using multidimensional models with advanced microphysics that provide the basis for understanding the relative importance of different microphysical processes that take place in mixed-phase clouds. To improve the representation of mixed-phase cloud processes in the GISS GCM we use the GISS single-column model coupled to a bin resolved microphysics (BRM) scheme that was specially designed to simulate mixed-phase clouds and aerosol-cloud interactions. Using this model with the microphysical measurements obtained from the DOE ARM Mixed-Phase Arctic Cloud Experiment (MPACE) campaign in October 2004 at the North Slope of Alaska, we investigate the effect of ice initiation processes and Bergeron-Findeisen process (BFP) on glaciation time and longevity of single-layer stratiform mixed-phase clouds. We focus on observations taken during 9-10 October, which indicated the presence of a single-layer mixed-phase clouds. We performed several sets of 12-h simulations to examine model sensitivity to different ice initiation mechanisms and evaluate model output (hydrometeors' concentrations, contents, effective radii, precipitation fluxes, and radar reflectivity) against measurements from the MPACE Intensive Observing Period. Overall, the model qualitatively simulates ice crystal concentration and hydrometeors content, but it fails to predict quantitatively the effective radii of ice particles and their vertical profiles. In particular, the ice effective radii are overestimated by at least 50%. However, using the same definition as used for observations, the effective radii simulated and that observed were more comparable. We find that for the single-layer stratiform mixed-phase clouds simulated, process of ice phase initiation due to freezing of supercooled water in both saturated and subsaturated (w.r.t. water) environments is as important as primary ice crystal origination from water vapor. We also find that the BFP is a process mainly responsible for the rates of glaciation of simulated clouds. These glaciation rates cannot be adequately represented by a water-ice saturation adjustment scheme that only depends on temperature and liquid and solid hydrometeors' contents as is widely used in bulk microphysics schemes and are better represented by processes that also account for supersaturation changes as the hydrometeors grow.

Potentiation of a p53-SLP vaccine by cyclophosphamide in ovarian cancer: a single-arm phase II study.

PubMed

Vermeij, Renee; Leffers, Ninke; Hoogeboom, Baukje-Nynke; Hamming, Ineke L E; Wolf, Rinze; Reyners, Anna K L; Molmans, Barbara H W; Hollema, Harry; Bart, Joost; Drijfhout, Jan W; Oostendorp, Jaap; van der Zee, Ate G J; Melief, Cornelis J; van der Burg, Sjoerd H; Daemen, Toos; Nijman, Hans W

2012-09-01

The purpose of the current phase II single-arm clinical trial was to evaluate whether pretreatment with low-dose cyclophosphamide improves immunogenicity of a p53-synthetic long peptide (SLP) vaccine in patients with recurrent ovarian cancer. Patients with ovarian cancer with elevated serum levels of CA-125 after primary treatment were immunized four times with the p53-SLP vaccine. Each immunization was preceded by administration of 300 mg/m2 intravenous cyclophosphamide as a means to affect regulatory T cells (Tregs). Vaccine-induced p53-specific interferon-gamma (IFN-γ)-producing T cells evaluated by IFN-γ ELISPOT were observed in 90% (9/10) and 87.5% (7/8) of evaluable patients after two and four immunizations, respectively. Proliferative p53-specific T cells, observed in 80.0% (8/10) and 62.5% (5/8) of patients, produced both T-helper 1 and T-helper-2 cytokines. Cyclophosphamide induced neither a quantitative reduction of Tregs determined by CD4+ FoxP3+ T cell levels nor a demonstrable qualitative difference in Treg function tested in vitro. Nonetheless, the number of vaccine-induced p53-specific IFN-γ-producing T cells was higher in our study compared to a study in which a similar patient group was treated with p53-SLP monotherapy (p≤0.012). Furthermore, the strong reduction in the number of circulating p53-specific T cells observed previously after four immunizations was currently absent. Stable disease was observed in 20.0% (2/10) of patients, and the remainder of patients (80.0%) showed clinical, biochemical and/or radiographic evidence of progressive disease. The outcome of this phase II trial warrants new studies on the use of low-dose cyclophosphamide to potentiate the immunogenicity of the p53-SLP vaccine or other antitumor vaccines. Copyright © 2011 UICC.

A phase II, multicenter, single-arm trial of eribulin as first- or second-line chemotherapy for HER2-negative advanced or metastatic breast cancer: evaluation of efficacy, safety, and patient-reported outcomes.

PubMed

Kimura, Kosei; Iwamoto, Mitsuhiko; Tanaka, Satoru; Yamamoto, Daigo; Yoshidome, Katsuhide; Ogura, Hiroyuki; Terasawa, Risa; Matsunami, Nobuki; Takahashi, Yuko; Nitta, Toshikatsu; Morimoto, Takashi; Fujioka, Hiroya; Kawaguchi, Kanako; Uchiyama, Kazuhisa

2018-05-01

Although eribulin is a suitable option for early-line treatment of metastatic breast cancer (MBC), data on first- or second-line use of eribulin for human epidermal growth factor receptor 2 (HER2)-negative MBC are still limited. Therefore, we conducted a phase II trial to investigate the efficacy and safety of eribulin for first- or second-line chemotherapy for HER2-negative MBC. We performed a phase II, open-label, single-arm, multicenter study in Japan. Eligible patients were women with histologically confirmed HER2-negative MBC without chemotherapy or only one chemotherapy line for MBC. The primary endpoint was the overall response rate (ORR) and the secondary endpoints included the clinical benefit rate (ORR + stable disease for 6 months; CBR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and health-related quality of life (HRQoL). A total of 35 patients with HER2-negative MBC were enrolled between March 2013 and February 2017 (data cut-off July 31, 2017). The ORR was 37.1% (95% CI 21.1-53.2%). The CBR was 54.3% (95% CI 37.8-70.8%). The median PFS was 6.2 months (95% CI 2.7-9.4 months) and median OS was 21.4 months (95% CI 11.5-32.9 months). Common grade 3/4 adverse events were neutropenia (42.9%) but febrile neutropenia (2.9%). Although the majority of non-hematological adverse events were mild in severity, one patient died of pneumonitis. In HRQoL analysis, eribulin appeared to maintain HRQoL of many patients. Eribulin as first- or second-line chemotherapy is effective and has manageable toxicity for patients with HER2-negative MBC.

Twelve-Month Efficacy and Safety Data for the "Stress Incontinence Control, Efficacy and Safety Study": A Phase III, Multicenter, Prospective, Randomized, Controlled Study Treating Female Stress Urinary Incontinence Using the Vesair Intravesical Balloon.

PubMed

Winkler, Harvey; Jacoby, Karny; Kalota, Susan; Snyder, Jeffrey; Cline, Kevin; Robertson, Kaiser; Kahan, Randall; Green, Lonny; McCammon, Kurt; Rovner, Eric; Rardin, Charles

The "Stress Incontinence Control, Efficacy and Safety Study" (SUCCESS) is a phase III study of the Vesair Balloon in women with stress urinary incontinence who had failed conservative therapy, and either failed surgery, were not candidates for surgery, or chose not to have surgery. The safety and efficacy of the balloon at 12 months is reported for those participants in the treatment arm who elected to continue with the SUCCESS trial beyond the primary end point at 3 months. The SUCCESS trial is a multicenter, prospective, single-blinded, randomized, sham-controlled study. Participants were randomized on a 2.33:1 basis to either Vesair Balloon placement or placebo. The primary efficacy end point was a composite of both a greater than 50% reduction from baseline on 1-hour provocative pad weight test and an at least 10-point improvement in symptoms on the Incontinence Quality of Life questionnaire assessed at the 3-month study visit. Patients in the treatment arm who opted to continue in the trial were followed up prospectively up to 12 months. A total of 221 participants were randomized, including 157 in the treatment arm and 64 in the control arm. Sixty-seven participants in the treatment arm (42.7% of participants enrolled) were evaluated at 12 months, with 56.3% achieving the composite end point and 78.7% having greater than 50% reduction in pad weight from baseline in a per-protocol analysis. In an intent-to-treat analysis treating all participants who did not continue with the balloon as failures, 24% of the participants achieved the composite end point and 33.6% had a greater than 50% reduction in pad weight from baseline. Treatment-related adverse events in this group included dysuria (40.1%), gross hematuria (36.9%), and urinary tract infection (26.1%). In this phase III trial, symptom relief was maintained for those participants who continued therapy for 12 months. The balloon was found to be safe with no device- or procedure-related serious adverse events reported. Additional studies are warranted to determine which patient populations are more tolerant of the balloon and to assess the efficacy and safety of its longer-term use. Additional screening methods, including screening patients for balloon tolerability, are warranted to reduce participant withdrawals.

Granulocyte-macrophage colony-stimulating factor alone or with dacarbazine in metastatic melanoma: a randomized phase II trial.

PubMed

Ravaud, A; Delaunay, M; Chevreau, C; Coulon, V; Debled, M; Bret-Dibat, C; Courbon, F; Gualde, N; Nguyen Bui, B

2001-11-16

The potential antitumoral effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) led us to evaluate GM-CSF alone or with dacarbazine (DTIC) in metastatic melanoma in first line randomized phase II. Treatment was arm A: GM-CSF: 5 microg kg(-1), bid, 14 consecutive days every 21 days and arm B: GM-CSF: 5 microg kg(-1), bid, day 2 to day 19 every 21 days and DTIC: 800 mg m(-2), day 1 of each cycle. 32 patients (pts) were included, 15 pts in arm A and 17 in arm B. All pts had visceral metastatic sites. 9 had only one metastatic site. The median number of cycles given was 2 in arm A and 3 in arm B. 100% and 89.4% of the planned dose of GM-CSF was given in arm A and arm B respectively. No objective response was obtained. 19 pts experienced at least WHO grade 3 toxicity. All pts had fever, 29 had a decrease in performance status and 23 had pain. Grade 3 toxicity were fever (38.7%), decrease in performance status (32.3%), pain (19.4%) and dyspnoea (12.5%). In this study, GM-CSF alone or in association with DTIC did not induce any antitumoral activity with subsequent toxicity.

Generalized optimal design for two-arm, randomized phase II clinical trials with endpoints from the exponential dispersion family.

PubMed

Jiang, Wei; Mahnken, Jonathan D; He, Jianghua; Mayo, Matthew S

2016-11-01

For two-arm randomized phase II clinical trials, previous literature proposed an optimal design that minimizes the total sample sizes subject to multiple constraints on the standard errors of the estimated event rates and their difference. The original design is limited to trials with dichotomous endpoints. This paper extends the original approach to be applicable to phase II clinical trials with endpoints from the exponential dispersion family distributions. The proposed optimal design minimizes the total sample sizes needed to provide estimates of population means of both arms and their difference with pre-specified precision. Its applications on data from specific distribution families are discussed under multiple design considerations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Perception and action in swimming: Effects of aquatic environment on upper limb inter-segmental coordination.

PubMed

Guignard, Brice; Rouard, Annie; Chollet, Didier; Ayad, Omar; Bonifazi, Marco; Dalla Vedova, Dario; Seifert, Ludovic

2017-10-01

This study assessed perception-action coupling in expert swimmers by focusing on their upper limb inter-segmental coordination in front crawl. To characterize this coupling, we manipulated the fluid flow and compared trials performed in a swimming pool and a swimming flume, both at a speed of 1.35ms -1 . The temporal structure of the stroke cycle and the spatial coordination and its variability for both hand/lower arm and lower arm/upper arm couplings of the right body side were analyzed as a function of fluid flow using inertial sensors positioned on the corresponding segments. Swimmers' perceptions in both environments were assessed using the Borg rating of perceived exertion scale. Results showed that manipulating the swimming environment impacts low-order (e.g., temporal, position, velocity or acceleration parameters) and high-order (i.e., spatial-temporal coordination) variables. The average stroke cycle duration and the relative duration of the catch and glide phases were reduced in the flume trial, which was perceived as very intense, whereas the pull and push phases were longer. Of the four coordination patterns (in-phase, anti-phase, proximal and distal: when the appropriate segment is leading the coordination of the other), flume swimming demonstrated more in-phase coordination for the catch and glide (between hand and lower arm) and recovery (hand/lower arm and lower arm/upper arm couplings). Conversely, the variability of the spatial coordination was not significantly different between the two environments, implying that expert swimmers maintain consistent and stable coordination despite constraints and whatever the swimming resistances. Investigations over a wider range of velocities are needed to better understand coordination dynamics when the aquatic environment is modified by a swimming flume. Since the design of flumes impacts significantly the hydrodynamics and turbulences of the fluid flow, previous results are mainly related to the characteristics of the flume used in the present study (or a similar one), and generalization is subject to additional investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

The Relationship of Throwing Arm Mechanics and Elbow Varus Torque: Within-Subject Variation for Professional Baseball Pitchers Across 82,000 Throws.

PubMed

Camp, Christopher L; Tubbs, Travis G; Fleisig, Glenn S; Dines, Joshua S; Dines, David M; Altchek, David W; Dowling, Brittany

2017-11-01

Likely due to the high level of strain exerted across the elbow during the throwing motion, elbow injuries are on the rise in baseball. To identify at-risk athletes and guide postinjury return-to-throw programs, a better understanding of the variables that influence elbow varus torque is desired. To describe the within-subject relationship between elbow varus torque and arm slot and arm rotation in professional baseball pitchers. Descriptive laboratory study. A total of 81 professional pitchers performed 82,000 throws while wearing a motusBASEBALL sensor and sleeve. These throws represented a combination of throw types, such as warm-up/catch, structured long-toss, bullpen throwing from a mound, and live game activity. Variables recorded for each throw included arm slot (angle of the forearm relative to the ground at ball release), arm speed (maximal rotational velocity of the forearm), arm rotation (maximal external rotation of the throwing arm relative to the ground), and elbow varus torque. Linear mixed-effects models and likelihood ratio tests were used to estimate the relationship between elbow varus torque and arm slot, arm speed, and arm rotation within individual pitchers. All 3 metrics-arm slot (χ 2 = 428, P < .001), arm speed (χ 2 = 57,683, P < .001), and arm rotation (χ 2 = 1392, P < .001)-were found to have a significant relationship with elbow varus torque. Within individual athletes, a 1-N.m increase in elbow varus torque was associated with a 13° decrease in arm slot, a 116 deg/s increase in arm speed, and an 8° increase in arm rotation. Elbow varus torque increased significantly as pitchers increased their arm rotation during the arm cocking phase, increased the rotational velocity of their arm during the arm acceleration phase of throwing, and decreased arm slot at ball release. Thus, shoulder flexibility, arm speed, and elbow varus torque (and likely injury risk) are interrelated and should be considered collectively when treating pitchers. It is well established that elbow varus torque is related to ulnar collateral ligament injuries in overhead throwers. This study describes the relationship of arm slot, arm speed, and arm rotation to elbow varus torque in an attempt to identify modifiable risk factors for injury.

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

PubMed

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

2010-07-01

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

Comparison of the pharmacokinetics and safety of three formulations of infliximab (CT-P13, EU-approved reference infliximab and the US-licensed reference infliximab) in healthy subjects: a randomized, double-blind, three-arm, parallel-group, single-dose, Phase I study.

PubMed

Park, Won; Lee, Sang Joon; Yun, Jihye; Yoo, Dae Hyun

2015-01-01

To compare the pharmacokinetics (PK), safety and tolerability of biosimilar infliximab (CT-P13 [Remsima(®), Inflectra(®)]) with two formulations of the reference medicinal product (RMP) (Remicade(®)) from either Europe (EU-RMP) or the USA (US-RMP). This was a double-blind, three-arm, parallel-group study (EudraCT number: 2013-003173-10). Healthy subjects received single doses (5 mg/kg) of CT-P13 (n = 71), EU-RMP (n = 71) or US-RMP (n = 71). The primary objective was to compare the PK profiles for the three formulations. Assessments of comparative safety and tolerability were secondary objectives. Baseline demographics were well balanced across the three groups. Primary end points (Cmax, AUClast and AUCinf) were equivalent between all formulations (CT-P13 vs EU-RMP; CT-P13 vs US-RMP; EU-RMP vs US-RMP). All other PK end points supported the high similarity of the three treatments. Tolerability profiles of the formulations were similar. The PK profile of CT-P13 is highly similar to EU-RMP and US-RMP. All three formulations were equally well tolerated.

Practice makes transfer of motor skills imperfect.

PubMed

Boutin, Arnaud; Badets, Arnaud; Salesse, Robin N; Fries, Udo; Panzer, Stefan; Blandin, Yannick

2012-09-01

We investigated the practice-effects on motor skill transfer and the associated representational memory changes that occur during the within-practice and between-practice phases. In two experiments, participants produced extension-flexion movements with their dominant right arm for a limited or prolonged practice session arranged in either a single- or multi-session format. We tested the ability of participants to transfer the original pattern (extrinsic transformation) or the mirrored one (intrinsic transformation) to the non-dominant left arm, 10 min and 24 h after the practice sessions. Results showed that practice induces rapid motor skill improvements that are non-transferable irrespective of the amount of acquisition trials. Furthermore, the extrinsic component of the skill develops early and remains the dominant coding system during practice. Conversely, we found distinct between-practice memory changes: a limited practice induces an off-line development of the extrinsic component, whereas a prolonged practice session subserves the off-line development of the intrinsic component (experiment 2). We provided further evidence that the long-term representation of the motor skill also depends on the nature of the practice session itself: the parsing of practice into multiple sessions narrows the effector-transfer capacities in comparison to a single session (experiment 1). These findings yield theoretical and practical implications that are discussed in the context of recent motor skill learning models.

Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors

PubMed Central

2014-01-01

Background Inhibition of AKT with MK-2206 has demonstrated synergism with anticancer agents. This phase 1 study assessed the MTD, DLTs, PK, and efficacy of MK-2206 in combination with cytotoxic and targeted therapies. Methods Advanced solid tumor patients received oral MK-2206 45 or 60 mg (QOD) with either carboplatin (AUC 6.0) and paclitaxel 200 mg/m2 (arm 1), docetaxel 75 mg/m2 (arm 2), or erlotinib 100 or 150 mg daily (arm 3); alternative schedules of MK-2206 135-200 mg QW or 90-250 mg Q3W were also tested. Results MTD of MK-2206 (N = 72) was 45 mg QOD or 200 mg Q3W (arm 1); MAD was 200 mg Q3W (arm 2) and 135 mg QW (arm 3). DLTs included skin rash (arms 1, 3), febrile neutropenia (QOD, arms 1, 2), tinnitus (Q3W, arm 2), and stomatitis (QOD, arm 3). Common drug-related toxicities included fatigue (68%), nausea (49%), and rash (47%). Two patients with squamous cell carcinoma of the head and neck (arm 1; Q3W) demonstrated a complete and partial response (PR); additional PRs were observed in patients (1 each) with melanoma, endometrial, neuroendocrine prostate, NSCLC, and cervical cancers. Six patients had stable disease ≥6 months. Conclusion MK-2206 plus carboplatin and paclitaxel, docetaxel, or erlotinib was well-tolerated, with early evidence of antitumor activity. Trial registration ClinicalTrials.gov: NCT00848718. PMID:24387695

Analysis of allelic expression patterns in clonal somatic cells by single-cell RNA-seq

PubMed Central

Ramsköld, Daniel; Deng, Qiaolin; Johnsson, Per; Michaëlsson, Jakob; Frisén, Jonas; Sandberg, Rickard

2016-01-01

Cellular heterogeneity can emerge from the expression of only one parental allele. However, it has remained controversial whether, or to what degree, random monoallelic expression of autosomal genes (aRME) is mitotically inherited (clonal) or stochastic (dynamic) in somatic cells, particularly in vivo. Here, we used allele-sensitive single-cell RNA-seq on clonal primary mouse fibroblasts and in vivo human CD8+ T-cells to dissect clonal and dynamic monoallelic expression patterns. Dynamic aRME affected a considerable portion of the cells’ transcriptomes, with levels dependent on the cells’ transcriptional activity. Importantly, clonal aRME was detected but was surprisingly scarce (<1% of genes) and affected mainly the most low-expressed genes. Consequently, the overwhelming portion of aRME occurs transiently within individual cells and patterns of aRME are thus primarily scattered throughout somatic cell populations rather than, as previously hypothesized, confined to patches of clonally related cells. PMID:27668657

Analysis of allelic expression patterns in clonal somatic cells by single-cell RNA-seq.

PubMed

Reinius, Björn; Mold, Jeff E; Ramsköld, Daniel; Deng, Qiaolin; Johnsson, Per; Michaëlsson, Jakob; Frisén, Jonas; Sandberg, Rickard

2016-11-01

Cellular heterogeneity can emerge from the expression of only one parental allele. However, it has remained controversial whether, or to what degree, random monoallelic expression of autosomal genes (aRME) is mitotically inherited (clonal) or stochastic (dynamic) in somatic cells, particularly in vivo. Here we used allele-sensitive single-cell RNA-seq on clonal primary mouse fibroblasts and freshly isolated human CD8 + T cells to dissect clonal and dynamic monoallelic expression patterns. Dynamic aRME affected a considerable portion of the cells' transcriptomes, with levels dependent on the cells' transcriptional activity. Notably, clonal aRME was detected, but it was surprisingly scarce (<1% of genes) and mainly affected the most weakly expressed genes. Consequently, the overwhelming majority of aRME occurs transiently within individual cells, and patterns of aRME are thus primarily scattered throughout somatic cell populations rather than, as previously hypothesized, confined to patches of clonally related cells.

Step-by-step design of a single phase 3.3 kV/200 a resistive type superconducting fault current limiter (R-SFCL) and cryostat

NASA Astrophysics Data System (ADS)

Kar, Soumen; Rao, V. V.

2018-07-01

In our first attempt to design a single phase R-SFCL in India, we have chosen the typical rating of a medium voltage level (3.3 kVrms, 200 Arms, 1Φ) R-SFCL. The step-by-step design procedure for the R-SFCL involves conductor selection, time dependent electro-thermal simulations and recovery time optimization after fault removal. In the numerical analysis, effective fault limitation for a fault current of 5 kA for the medium voltage level R-SFCL are simulated. Maximum normal state resistance and maximum temperature rise in the SFCL coil during current limitation are estimated using one-dimensional energy balance equation. Further, a cryogenic system is conceptually designed for aforesaid MV level R-SFCL by considering inner and outer vessel materials, wall-thickness and thermal insulation which can be used for R-SFCL system. Finally, the total thermal load is calculated for the designed R-SFCL cryostat to select a suitable cryo-refrigerator for LN2 re-condensation.

Simple and fast spectral domain algorithm for quantitative phase imaging of living cells with digital holographic microscopy

NASA Astrophysics Data System (ADS)

Min, Junwei; Yao, Baoli; Ketelhut, Steffi; Kemper, Björn

2017-02-01

The modular combination of optical microscopes with digital holographic microscopy (DHM) has been proven to be a powerful tool for quantitative live cell imaging. The introduction of condenser and different microscope objectives (MO) simplifies the usage of the technique and makes it easier to measure different kinds of specimens with different magnifications. However, the high flexibility of illumination and imaging also causes variable phase aberrations that need to be eliminated for high resolution quantitative phase imaging. The existent phase aberrations compensation methods either require add additional elements into the reference arm or need specimen free reference areas or separate reference holograms to build up suitable digital phase masks. These inherent requirements make them unpractical for usage with highly variable illumination and imaging systems and prevent on-line monitoring of living cells. In this paper, we present a simple numerical method for phase aberration compensation based on the analysis of holograms in spatial frequency domain with capabilities for on-line quantitative phase imaging. From a single shot off-axis hologram, the whole phase aberration can be eliminated automatically without numerical fitting or pre-knowledge of the setup. The capabilities and robustness for quantitative phase imaging of living cancer cells are demonstrated.

Split-arm swinging: the effect of arm swinging manipulation on interlimb coordination during walking.

PubMed

Bondi, Moshe; Zeilig, Gabi; Bloch, Ayala; Fasano, Alfonso; Plotnik, Meir

2017-08-01

Human locomotion is defined by bilateral coordination of gait (BCG) and shared features with the fore-hindlimb coordination of quadrupeds. The objective of the present study is to explore the influence of arm swinging (AS) on BCG. Sixteen young, healthy individuals (eight women; eight right motor-dominant, eight left-motor dominant) participated. Participants performed 10 walking trials (2 min). In each of the trials AS was unilaterally manipulated (e.g., arm restriction, weight on the wrist), bilaterally manipulated, or not manipulated. The order of trials was random. Walking trials were performed on a treadmill. Gait kinematics were recorded by a motion capture system. Using feedback-controlled belt speed allowed the participants to walk at a self-determined gait speed. Effects of the manipulations were assessed by AS amplitudes and the phase coordination index (PCI), which quantifies the left-right anti-phased stepping pattern. Most of the AS manipulations caused an increase in PCI values (i.e., reduced lower limb coordination). Unilateral AS manipulation had a reciprocal effect on the AS amplitude of the other arm such that, for example, over-swinging of the right arm led to a decrease in the AS amplitude of the left arm. Side of motor dominance was not found to have a significant impact on PCI and AS amplitude. The present findings suggest that lower limb BCG is markedly influenced by the rhythmic AS during walking. It may thus be important for gait rehabilitation programs targeting BCG to take AS into account. NEW & NOTEWORTHY Control mechanisms for four-limb coordination in human locomotion are not fully known. To study the influence of arm swinging (AS) on bilateral coordination of the lower limbs during walking, we introduced a split-AS paradigm in young, healthy adults. AS manipulations caused deterioration in the anti-phased stepping pattern and impacted the AS amplitudes for the contralateral arm, suggesting that lower limb coordination is markedly influenced by the rhythmic AS during walking. Copyright © 2017 the American Physiological Society.

Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel.

PubMed

Hoskins, P; Vergote, I; Cervantes, A; Tu, D; Stuart, G; Zola, P; Poveda, A; Provencher, D; Katsaros, D; Ojeda, B; Ghatage, P; Grimshaw, R; Casado, A; Elit, L; Mendiola, C; Sugimoto, A; D'Hondt, V; Oza, A; Germa, J R; Roy, M; Brotto, L; Chen, D; Eisenhauer, E A

2010-10-20

Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy. Women aged 75 years or younger with newly diagnosed stage IIB or greater ovarian cancer, Eastern Cooperative Oncology Group Performance Status of 1 or less, were stratified by type of primary surgery and residual disease, treatment center, and age; then randomly assigned to one of the two 21-day intravenous regimens. Patients in arm 1 (n = 409) were administered four cycles of cisplatin 50 mg/m(2) on day 1 and topotecan 0.75 mg/m(2) on days 1-5, then four cycles of paclitaxel 175 mg/m(2) over 3 hours on day 1 followed by carboplatin (area under the curve = 5) on day 1. Patients in arm 2 (n = 410) were given paclitaxel plus carboplatin as in arm 1 for eight cycles. We compared progression-free survival (PFS), overall survival, and cancer antigen-125 normalization rates in the two treatment arms. A stratified log-rank test was used to assess the primary endpoint, PFS. All statistical tests were two-sided. A total of 819 patients were randomly assigned. At baseline, the median age of the patients was 57 years (range = 28-78); 81% had received debulking surgery, and of these, 55% had less than 1 cm residual disease; 66% of patients were stage III and 388 (47.4%) patients had measurable disease. After a median follow-up of 43 months, 650 patients had disease progression or died without documented progression and 406 had died. Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 (hazard ratio = 1.10, 95% confidence interval = 0.94 to 1.28, P = .25). Among patients with elevated baseline cancer antigen-125, fewer in arm 1 than in arm 2 had levels return to normal by 3 months after random assignment (51.6% vs 63.3%, P = .007) Topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and paclitaxel alone, but without improved efficacy. Carboplatin plus paclitaxel remains the standard of care for advanced epithelial ovarian cancer.

Prospective Randomized Phase 2 Trial of Intensity Modulated Radiation Therapy With or Without Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Intermediate-Risk Prostate Cancer

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

Freytag, Svend O., E-mail: sfreyta1@hfhs.org; Stricker, Hans; Lu, Mei

Purpose: To assess the safety and efficacy of combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer. Methods and Materials: Forty-four men with intermediate-risk prostate cancer were randomly assigned to receive either OAMCGT plus IMRT (arm 1; n=21) or IMRT only (arm 2; n=23). The primary phase 2 endpoint was acute (≤90 days) toxicity. Secondary endpoints included quality of life (QOL), prostate biopsy (12-core) positivity at 2 years, freedom from biochemical/clinical failure (FFF), freedom from metastases, and survival. Results: Men in arm 1 exhibited a greater incidence of low-grade influenza-like symptoms, transaminitis,more » neutropenia, and thrombocytopenia than men in arm 2. There were no significant differences in gastrointestinal or genitourinary events or QOL between the 2 arms. Two-year prostate biopsies were obtained from 37 men (84%). Thirty-three percent of men in arm 1 were biopsy-positive versus 58% in arm 2, representing a 42% relative reduction in biopsy positivity in the investigational arm (P=.13). There was a 60% relative reduction in biopsy positivity in the investigational arm in men with <50% positive biopsy cores at baseline (P=.07). To date, 1 patient in each arm exhibited biochemical failure (arm 1, 4.8%; arm 2, 4.3%). No patient developed hormone-refractory or metastatic disease, and none has died from prostate cancer. Conclusions: Combining OAMCGT with IMRT does not exacerbate the most common side effects of prostate radiation therapy and suggests a clinically meaningful reduction in positive biopsy results at 2 years in men with intermediate-risk prostate cancer.« less

Prediction of Imagined Single-Joint Movements in a Person with High Level Tetraplegia

PubMed Central

Simeral, John D.; Donoghue, John P.; Hochberg, Leigh R.; Kirsch, Robert F.

2013-01-01

Cortical neuroprostheses for movement restoration require developing models for relating neural activity to desired movement. Previous studies have focused on correlating single-unit activities (SUA) in primary motor cortex to volitional arm movements in able-bodied primates. The extent of the cortical information relevant to arm movements remaining in severely paralyzed individuals is largely unknown. We record intracortical signals using a microelectrode array chronically implanted in the precentral gyrus of a person with tetraplegia, and estimate positions of imagined single-joint arm movements. Using visually guided motor imagery, the participant imagined performing eight distinct single-joint arm movements while SUA, multi-spike trains (MSP), multi-unit activity (MUA), and local field potential time (LFPrms) and frequency signals (LFPstft) were recorded. Using linear system identification, imagined joint trajectories were estimated with 20 – 60% variance explained, with wrist flexion/extension predicted the best and pronation/supination the poorest. Statistically, decoding of MSP and LFPstft yielded estimates that equaled those of SUA. Including multiple signal types in a decoder increased prediction accuracy in all cases. We conclude that signals recorded from a single restricted region of the precentral gyrus in this person with tetraplegia contained useful information regarding the intended movements of upper extremity joints. PMID:22851229

Understanding rapid changes in phase partitioning between cloud liquid and ice in an Arctic stratiform mixed-phase cloud

NASA Astrophysics Data System (ADS)

Kalesse, Heike; de Boer, Gijs; Solomon, Amy; Oue, Mariko; Ahlgrimm, Maike; Zhang, Damao; Shupe, Matthew; Luke, Edward; Protat, Alain

2016-04-01

In the Arctic, a region particularly sensitive to climate change, mixed-phase clouds occur as persistent single or multiple stratiform layers. For many climate models, the correct partitioning of hydrometeor phase (liquid vs. ice) remains a challenge. However, this phase partitioning plays an important role for precipitation processes and the radiation budget. To better understand the partitioning of phase in Arctic clouds, observations using a combination of surface-based remote sensors are useful. In this study, the focus is on a persistent low-level single-layer stratiform Arctic mixed-phase cloud observed during March 11-12, 2013 at the US Department of Energy's (DOE) Atmospheric Radiation Measurement (ARM) North Slope of Alaska (NSA) permanent site in Barrow, Alaska. This case is of particular interest due to two significant shifts in observed precipitation intensity over a 36 hour period. For the first 12 hours of this case, the observed liquid portion of the cloud cover featured a stable cloud top height with a gradually descending liquid cloud base and continuous ice precipitation. Then the ice precipitation intensity significantly decreased. A second decrease in ice precipitation intensity was observed a few hours later coinciding with the advection of a cirrus over the site. Through analysis of the data collected by extensive ground-based remote-sensing and in-situ observing systems as well as Nested Weather Research and Forecasting (WRF) simulations and ECMWF radiation scheme simulations, we try to shed light on the processes responsible for these rapid changes in precipitation rates. A variety of parameters such as the evolution of the internal dynamics and microphysics of the low-level mixed-phase cloud and the influence of the cirrus cloud are evaluated.

Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial.

PubMed

Dunning, Jake; Sahr, Foday; Rojek, Amanda; Gannon, Fiona; Carson, Gail; Idriss, Baimba; Massaquoi, Thomas; Gandi, Regina; Joseph, Sebatu; Osman, Hassan K; Brooks, Timothy J G; Simpson, Andrew J H; Goodfellow, Ian; Thorne, Lucy; Arias, Armando; Merson, Laura; Castle, Lyndsey; Howell-Jones, Rebecca; Pardinaz-Solis, Raul; Hope-Gill, Benjamin; Ferri, Mauricio; Grove, Jennifer; Kowalski, Mark; Stepniewska, Kasia; Lang, Trudie; Whitehead, John; Olliaro, Piero; Samai, Mohammed; Horby, Peter W

2016-04-01

TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. Pan African Clinical Trials Registry PACTR201501000997429.

Simeprevir in combination with sofosbuvir in treatment-naïve and -experienced patients with hepatitis C virus genotype 4 infection: a Phase III, open-label, single-arm study (PLUTO).

PubMed

Buti, M; Calleja, J L; Lens, S; Diago, M; Ortega, E; Crespo, J; Planas, R; Romero-Gómez, M; Rodríguez, F G; Pascasio, J M; Fevery, B; Kurland, D; Corbett, C; Kalmeijer, R; Jessner, W

2017-02-01

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and subsequent hepatocellular carcinoma. HCV genotype 4 is found widely in the Middle East, Egypt and Africa, and has also spread into Europe. There are limited data available regarding the use of direct-acting antiviral agents in HCV genotype 4-infected patients with cirrhosis. To evaluate in the phase III, open-label, single-arm PLUTO study the efficacy and safety of 12 weeks of simeprevir (HCV NS3/4A protease inhibitor) plus sofosbuvir (HCV nucleotide-analogue NS5B polymerase inhibitor) in treatment-naïve and (peg)interferon ± ribavirin-experienced HCV genotype 4-infected patients, with or without compensated cirrhosis. Adult patients with chronic HCV genotype 4 infection received simeprevir 150 mg once-daily and sofosbuvir 400 mg once-daily for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety was also assessed. Forty patients received treatment; the majority were male (73%) and treatment-experienced (68%). Overall, 7/40 (18%) patients had compensated cirrhosis. All patients achieved SVR12 [100% (Clopper-Pearson 95% confidence interval: 91-100%)]. Adverse events, all Grade 1 or 2, were reported in 20/40 (50%) patients. No serious adverse events were reported and no patients discontinued study treatment. Grade 3 treatment-emergent laboratory abnormalities were noted in 2/40 (5%) patients. Treatment with simeprevir plus sofosbuvir for 12 weeks resulted in SVR12 rates of 100% in treatment-naïve and -experienced patients with HCV genotype 4 infection with or without compensated cirrhosis, and was well tolerated. [NCT02250807]. © 2016 John Wiley & Sons Ltd.

Drug-conjugated antibodies for the treatment of cancer

PubMed Central

Lambert, John M

2013-01-01

Despite considerable effort, application of monoclonal antibody technology has had only modest success in improving treatment outcomes in patients with solid tumours. Enhancing the cancer cell-killing activity of antibodies through conjugation to highly potent cytotoxic ‘payloads’ to create antibody–drug conjuates (ADCs) offers a strategy for developing anti-cancer drugs of great promise. Early ADCs exhibited side-effect profiles similar to those of ‘classical’ chemotherapeutic agents and their performance in clinical trials in cancer patients was generally poor. However, the recent clinical development of ADCs that have highly potent tubulin-acting agents as their payloads have profoundly changed the outlook for ADC technology. Twenty-five such ADCs are in clinical development and one, brentuximab vedotin, was approved by the FDA in August, 2011, for the treatment of patients with Hodgkin's lymphoma and patients with anaplastic large cell lymphoma, based on a high rate of durable responses in single arm phase II clinical trials. More recently, a second ADC, trastuzumab emtansine, has shown excellent anti-tumour activity with the presentation of results of a 991-patient randomized phase III trial in patients with HER2-positive metastatic breast cancer. Treatment with this ADC (single agent) resulted in a significantly improved progression-free survival of 9.6 months compared with 6.4 months for lapatinib plus capecitabine in the comparator arm and significantly prolonged overall survival. Besides demonstrating excellent efficacy, these ADCs were remarkably well tolerated. Thus these, and other ADCs in development, promise to achieve the long sought goal of ADC technology, that is, of having compounds with high anti-tumour activity at doses where adverse effects are generally mild. PMID:23173552

[A multicenter, randomized, controlled, phase Ⅳ clinical study of PEG-rhG-CSF for preventing chemotherapy induced neutropenia in patients with breast cancer].

PubMed

Jiang, Z F; Xu, F R; Fan, J; Li, B J; Gao, J N; Hu, J W; Wang, X J; Zhang, Y Q; Wang, J H; Li, F; Liu, Q; Liu, Y H; Wang, S; Wang, Y S; Ouyang, Q C; Hu, B; Sun, G P; Zhang, Y; Zang, A M; Fan, P Z; Wu, C P; Liu, J; Zhang, H W; Wang, W; Hu, X C; Tang, L L; Zhang, J; Bao, Y Y; Geng, C Z; Sun, Q; Zhang, F; Yin, Y M; Jiang, H C; An, Y H

2018-04-24

Objective: To explore the efficacy and safety of polyethylene glycal recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patiens with breast cancer. Methods: There were two parts in the present phase Ⅳ clinical study. One was a randomized, controlled clinical study. Patients in this study received PEG-rhG-CSF or rhG-CSF in the first cycle and followed with both PEG-rhG-CSF in the rest of 3 cycles. The other one was a single arm study. Patients who developed Ⅲ/Ⅳ grade neutropenia in the screening cycle received PEG-rhG-CSF in the rest of 3 cycles chemotherapy. Results: In the first cycle of randomized, controlled study, the incidence of Ⅳ grade neutropenia are 31.48% and 35.58% respectively in PEG-rhG-CSF and rhG-CSF group, with no statistically significant differences ( P =0.527 6). The duration of Ⅳ grade neutropenia respectively are 2.22±1.58 and 3.00±1.59 days, with a statistically significant difference ( P =0.016 6). In the single arm study, the incidence of Ⅳ grade neutropenia was 57.76% in screening cycle. And the incidence decreased to 16.35%, 10%, and 8.57% in the followed 3 cycle after the use of PEG-rhG-CSF. The incidence of adverse effects was 5.06%, and the major adverse effect was bone pain which with an incidence of 2.8%. Conclusion: The fixed 6mg dose of PEG-rhG-CSF can effectively prevent neutropenia in patients with breast cancer in multicycle chemotherapy and it has a low incidence of adverse events and mild adverse reaction.

Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes.

PubMed

Kaminskas, Edvardas; Farrell, Ann; Abraham, Sophia; Baird, Amy; Hsieh, Li-Shan; Lee, Shwu-Luan; Leighton, John K; Patel, Hasmukh; Rahman, Atiqur; Sridhara, Rajeshwara; Wang, Yong-Cheng; Pazdur, Richard

2005-05-15

This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome. In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks. In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths. On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda.gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.

Professional tennis players' serve: correlation between segmental angular momentums and ball velocity.

PubMed

Martin, Caroline; Kulpa, Richard; Delamarche, Paul; Bideau, Benoit

2013-03-01

The purpose of the study was to identify the relationships between segmental angular momentum and ball velocity between the following events: ball toss, maximal elbow flexion (MEF), racket lowest point (RLP), maximal shoulder external rotation (MER), and ball impact (BI). Ten tennis players performed serves recorded with a real-time motion capture. Mean angular momentums of the trunk, upper arm, forearm, and the hand-racket were calculated. The anteroposterior axis angular momentum of the trunk was significantly related with ball velocity during the MEF-RLP, RLP-MER, and MER-BI phases. The strongest relationships between the transverse-axis angular momentums and ball velocity followed a proximal-to-distal timing sequence that allows the transfer of angular momentum from the trunk (MEF-RLP and RLP-MER phases) to the upper arm (RLP-MER phase), forearm (RLP-MER and MER-BI phases), and the hand-racket (MER-BI phase). Since sequence is crucial for ball velocity, players should increase angular momentums of the trunk during MEF-MER, upper arm during RLP-MER, forearm during RLP-BI, and the hand-racket during MER-BI.

Four-dimensional key design in amplitude, phase, polarization and distance for optical encryption based on polarization digital holography and QR code.

PubMed

Lin, Chao; Shen, Xueju; Li, Baochen

2014-08-25

We demonstrate that all parameters of optical lightwave can be simultaneously designed as keys in security system. This multi-dimensional property of key can significantly enlarge the key space and further enhance the security level of the system. The single-shot off-axis digital holography with orthogonal polarized reference waves is employed to perform polarization state recording on object wave. Two pieces of polarization holograms are calculated and fabricated to be arranged in reference arms to generate random amplitude and phase distribution respectively. When reconstruction, original information which is represented with QR code can be retrieved using Fresnel diffraction with decryption keys and read out noise-free. Numerical simulation results for this cryptosystem are presented. An analysis on the key sensitivity and fault tolerance properties are also provided.

Intelligent Robotic Systems Study (IRSS), phase 4

NASA Technical Reports Server (NTRS)

1991-01-01

Under the Intelligent Robotics Systems Study (IRSS), a generalized robotic control architecture was developed for use with the ProtoFlight Manipulator Arm (PFMA). Based upon the NASREM system design concept, the controller built for the PFMA provides localized position based force control, teleoperation, and advanced path recording and playback capabilities. The PFMA has six computer controllable degrees of freedom (DOF) plus a 7th manually indexable DOF, making the manipulator a pseudo 7 DOF mechanism. Joints on the PFMA are driven via 7 pulse width modulated amplifiers. Digital control of the PFMA is implemented using a variety of single board computers. There were two major activities under the IRSS phase 4 study: (1) enhancement of the PFMA control system software functionality; and (2) evaluation of operating modes via a teleoperation performance study. These activities are described and results are given.

LISA Long-Arm Interferometry

NASA Technical Reports Server (NTRS)

Thorpe, James I.

2009-01-01

An overview of LISA Long-Arm Interferometry is presented. The contents include: 1) LISA Interferometry; 2) Constellation Design; 3) Telescope Design; 4) Constellation Acquisition; 5) Mechanisms; 6) Optical Bench Design; 7) Phase Measurement Subsystem; 8) Phasemeter Demonstration; 9) Time Delay Interferometry; 10) TDI Limitations; 11) Active Frequency Stabilization; 12) Spacecraft Level Stabilization; 13) Arm-Locking; and 14) Embarassment of Riches.

Macroscopic Hematuria After Conventional or Hypofractionated Radiation Therapy: Results From a Prospective Phase 3 Study

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

Sanguineti, Giuseppe, E-mail: sanguineti@ifo.it; Arcidiacono, Fabio; Landoni, Valeria

2016-10-01

Purpose: To assess the macroscopic hematuria rates within a single-institution randomized phase 3 trial comparing dose-escalated, conventionally fractionated radiation therapy (CFRT) and moderately hypofractionated radiation therapy (MHRT) for localized prostate cancer. Methods and Materials: Patients with intermediate- to high-risk localized prostate cancer were treated with conformal RT and short-course androgen deprivation. Both the prostate and the entire seminal vesicles were treated to 80 Gy in 40 fractions over 8 weeks (CFRT) or 62 Gy in 20 fractions over 5 weeks (MHRT). The endpoint of the present study was the development of any episode or grade of macroscopic hematuria. The median follow-up period was 93 monthsmore » (range 6-143). Results: Macroscopic hematuria was reported by 25 of 168 patients (14.9%). The actuarial estimate of hematuria at 8 years was 17.0% (95% confidence interval [CI] 10.7%-23.3%). The number of patients with hematuria was 6 and 19 in the CFRT and MHRT arms, respectively, for an actuarial 8-year estimate of 9.7% and 24.3%, respectively (hazard ratio 3.468, 95% CI 1.385-8.684; P=.008). Overall, 8 of 25 patients were found to have biopsy-proven urothelial carcinoma (3 in the CFRT arm and 5 in the MHRT arm; P=.27). Thus, the 8-year actuarial incidence of macroscopic hematuria (after censoring urothelial cancer–related episodes) was 4.1% and 18.2% after CFRT and MHRT, respectively (hazard ratio 4.961, 95% CI 1.426-17.263; P=.012). The results were confirmed by multivariate analysis after accounting for several patient-, treatment-, and tumor-related covariates. Conclusions: MHRT was associated with a statistically significant increased risk of macroscopic hematuria compared with CFRT.« less

Analysis of phase II methodologies for single-arm clinical trials with multiple endpoints in rare cancers: An example in Ewing's sarcoma.

PubMed

Dutton, P; Love, S B; Billingham, L; Hassan, A B

2018-05-01

Trials run in either rare diseases, such as rare cancers, or rare sub-populations of common diseases are challenging in terms of identifying, recruiting and treating sufficient patients in a sensible period. Treatments for rare diseases are often designed for other disease areas and then later proposed as possible treatments for the rare disease after initial phase I testing is complete. To ensure the trial is in the best interests of the patient participants, frequent interim analyses are needed to force the trial to stop promptly if the treatment is futile or toxic. These non-definitive phase II trials should also be stopped for efficacy to accelerate research progress if the treatment proves to be particularly promising. In this paper, we review frequentist and Bayesian methods that have been adapted to incorporate two binary endpoints and frequent interim analyses. The Eurosarc Trial of Linsitinib in advanced Ewing Sarcoma (LINES) is used as a motivating example and provides a suitable platform to compare these approaches. The Bayesian approach provides greater design flexibility, but does not provide additional value over the frequentist approaches in a single trial setting when the prior is non-informative. However, Bayesian designs are able to borrow from any previous experience, using prior information to improve efficiency.

Apolipoprotein E genotyping by multiplex tetra-primer amplification refractory mutation system PCR in single reaction tube.

PubMed

Yang, Young Geun; Kim, Jong Yeol; Park, Su Jeong; Kim, Suhng Wook; Jeon, Ok-Hee; Kim, Doo-Sik

2007-08-31

Apolipoprotein E (APOE) plays a critical role in lipoprotein metabolism by binding to both low-density lipoprotein and APOE receptors. The APOE gene has three allelic forms, epsilon2, epsilon3, and epsilon4, which encode different isoforms of the APOE protein. In this study, we have developed a new genotyping method for APOE. Our multiplex tetra-primer amplification refractory mutation system (multiplex T-ARMS) polymerase chain reaction (PCR) was performed in a single reaction tube with six primers consisting of two common primers and two specific primers for each of two single nucleotide polymorphism (SNP) sites. We obtained definitive electropherograms that showed three (epsilon2/epsilon2, epsilon3/epsilon3, and epsilon4/epsilon4), four (epsilon2/epsilon3 and epsilon3/epsilon4), and five (epsilon2/epsilon4) amplicons by multiplex T-ARMS PCR in a single reaction tube. Multiplex T-ARMS PCR for APOE genotyping is a simple and accurate method that requires only a single PCR reaction, without any another treatments or expensive instrumentation, to simultaneously identify two sites of single nucleotide polymorphisms.

On-chip beamsplitter operation on single photons from quasi-resonantly excited quantum dots embedded in GaAs rib waveguides

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

Rengstl, U.; Schwartz, M.; Herzog, T.

2015-07-13

We present an on-chip beamsplitter operating on a single-photon level by means of a quasi-resonantly driven InGaAs/GaAs quantum dot. The single photons are guided by rib waveguides and split into two arms by an evanescent field coupler. Although the waveguides themselves support the fundamental TE and TM modes, the measured degree of polarization (∼90%) reveals the main excitation and propagation of the TE mode. We observe the preserved single-photon nature of a quasi-resonantly excited quantum dot by performing a cross-correlation measurement on the two output arms of the beamsplitter. Additionally, the same quantum dot is investigated under resonant excitation, wheremore » the same splitting ratio is observed. An autocorrelation measurement with an off-chip beamsplitter on a single output arm reveal the single-photon nature after evanescent coupling inside the on-chip splitter. Due to their robustness, adjustable splitting ratio, and their easy implementation, rib waveguide beamsplitters with embedded quantum dots provide a promising step towards fully integrated quantum circuits.« less

Stochastic estimation of human arm impedance under nonlinear friction in robot joints: a model study.

PubMed

Chang, Pyung Hun; Kang, Sang Hoon

2010-05-30

The basic assumption of stochastic human arm impedance estimation methods is that the human arm and robot behave linearly for small perturbations. In the present work, we have identified the degree of influence of nonlinear friction in robot joints to the stochastic human arm impedance estimation. Internal model based impedance control (IMBIC) is then proposed as a means to make the estimation accurate by compensating for the nonlinear friction. From simulations with a nonlinear Lugre friction model, it is observed that the reliability and accuracy of the estimation are severely degraded with nonlinear friction: below 2 Hz, multiple and partial coherence functions are far less than unity; estimated magnitudes and phases are severely deviated from that of a real human arm throughout the frequency range of interest; and the accuracy is not enhanced with an increase of magnitude of the force perturbations. In contrast, the combined use of stochastic estimation and IMBIC provides with accurate estimation results even with large friction: the multiple coherence functions are larger than 0.9 throughout the frequency range of interest and the estimated magnitudes and phases are well matched with that of a real human arm. Furthermore, the performance of suggested method is independent of human arm and robot posture, and human arm impedance. Therefore, the IMBIC will be useful in measuring human arm impedance with conventional robot, as well as in designing a spatial impedance measuring robot, which requires gearing. (c) 2010 Elsevier B.V. All rights reserved.

Granulocyte-macrophage colony-stimulating factor alone or with dacarbazine in metastatic melanoma: a randomized phase II trial

PubMed Central

Ravaud, A; Delaunay, M; Chevreau, C; Coulon, V; Debled, M; Bret-Dibat, C; Courbon, F; Gualde, N; Bui, B Nguyen

2001-01-01

The potential antitumoural effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) led us to evaluate GM-CSF alone or with dacarbazine (DTIC) in metastatic melanoma in first line randomized phase II. Treatment was arm A: GM-CSF: 5 μg kg−1, bid, 14 consecutive days every 21 days and arm B: GM-CSF: 5 μg kg−1, bid, day 2 to day 19 every 21 days and DTIC: 800 mg m−2, day 1 of each cycle. 32 patients (pts) were included, 15 pts in arm A and 17 in arm B. All pts had visceral metastatic sites. 9 had only one metastatic site. The median number of cycles given was 2 in arm A and 3 in arm B. 100% and 89.4% of the planned dose of GM-CSF was given in arm A and arm B respectively. No objective response was obtained. 19 pts experienced at least WHO grade 3 toxicity. All pts had fever, 29 had a decrease in performance status and 23 had pain. Grade 3 toxicity were fever (38.7%), decrease in performance status (32.3%), pain (19.4%) and dyspnoea (12.5%). In this study, GM-CSF alone or in association with DTIC did not induce any antitumoural activity with subsequent toxicity. © 2001 Cancer Research Campaign   http://www.bjcancer.com PMID:11720430

Multicolour versus monocolour inking specimens after pancreaticoduodenectomy for periampullary cancer: A single centre prospective randomised clinical trial.

PubMed

Casadei, Riccardo; Ricci, Claudio; Taffurelli, Giovanni; Pacilio, Carlo Alberto; Santini, Donatella; Di Marco, Mariacristina; Minni, Francesco

2018-03-01

R status represents an important prognostic factors in periampullary cancers. Thus, it is useful to verify if it can be influenced by different techniques of margination. Single-centre, randomised clinical trial of patients affected by periampullary cancer who underwent pancreaticoduodenectomies which included two different types of margination: arm A (multicolour inking) and arm B (monocolour inking). The primary endpoint was the overall R1 resection rate and its difference between the two arms. The secondary endpoints were the R1 resection rate in each margin and its difference between the two arms, and the impact of margin status on survival. Fifty patients were randomised, 41 analysed: 22 in arm A, 19 arm B. The overall R1 status was 61%, without significant differences between the two arms. The margin most commonly involved was the superior mesenteric artery (SMA) (36.6%). A trend in favour of arm B was shown for the superior mesenteric artery margin (arm A = 22.7% versus arm B = 52.6%; P = 0.060). The anterior surface (P = 0.015), SMA (P = 0.047) and pancreatic remnant (P = 0.018) margins significantly influenced disease-free survival. The R status was not influenced by different techniques of margination using a standardised pathological protocol. The SMA margin seemed to be the most important margin for evaluating both R status and disease-free survival. Copyright © 2018. Published by Elsevier Ltd.

Phase I study of cediranib in combination with cisplatin plus fluoropyrimidine (S-1 or capecitabine) in Japanese patients with previously untreated advanced gastric cancer.

PubMed

Satoh, Taroh; Yamada, Yasuhide; Muro, Kei; Hayashi, Hidetoshi; Shimada, Yasuhiro; Takahari, Daisuke; Taku, Keisei; Nakajima, Takako Eguchi; Shi, Xiaojin; Brown, Kathryn H; Boku, Narikazu

2012-02-01

The primary objective of this Phase I study was to assess the safety and tolerability of the vascular endothelial growth factor signalling inhibitor cediranib in combination with cisplatin plus an oral fluoropyrimidine, in Japanese patients with previously untreated advanced gastric cancer. Patients received continuous, once-daily oral doses of cediranib 20 mg in combination with either cisplatin (60 mg/m(2) iv day 1) plus S-1 (40-60 mg bid, days 1-21) every 5 weeks for a maximum of eight cycles [Arm A]; or cisplatin (80 mg/m(2) iv, day 1) plus capecitabine (1,000 mg/m(2) bid, days 1-14) every 3 weeks for a maximum of six cycles [Arm B]. In both arms, the assessment period for dose-limiting toxicities (DLTs) was the first 21 days of cycle 1. Fourteen patients (Arm A, n = 6; Arm B, n = 8) were enrolled and received at least one dose of cediranib. One patient in each arm experienced a DLT (Arm A; decreased appetite, grade 3; Arm B, decreased appetite, fatigue and hyponatraemia, all grade 3). Overall, the most common adverse events were decreased appetite, fatigue and nausea (all n = 13 [92.9%]). Preliminary efficacy evaluation showed one confirmed (Arm A) and three unconfirmed (Arm A, n = 1; Arm B, n = 2) partial responses that were ongoing at data cut-off. Cediranib 20 mg/day in combination with cisplatin and S-1 or capecitabine was tolerable, with no new toxicities identified, and showed preliminary evidence of antitumour activity.

Induction of a pathological complete response by four courses of neoadjuvant chemotherapy for gastric cancer: early results of the randomized phase II COMPASS trial.

PubMed

Yoshikawa, Takaki; Tanabe, Kazuaki; Nishikawa, Kazuhiro; Ito, Yuichi; Matsui, Takanori; Kimura, Yutaka; Hirabayashi, Naoki; Mikata, Shoki; Iwahashi, Makoto; Fukushima, Ryoji; Takiguchi, Nobuhiro; Miyashiro, Isao; Morita, Satoshi; Miyashita, Yumi; Tsuburaya, Aakira; Sakamoto, Junichi

2014-01-01

The prognosis for stage 3 gastric cancer is not satisfactory, even with S-1 adjuvant chemotherapy. A randomized phase II trial was conducted to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) using a two-by-two factorial design for locally advanced gastric cancer. The primary endpoint was overall survival. We clarified the impact of these regimens on the secondary endpoints, including the clinical and pathological responses, chemotherapy-related toxicities, and surgical results. Patients received S-1 (80 mg/m(2) for 21 days with 1 week's rest)/cisplatin (60 mg/m(2) at day 8) or paclitaxel/cisplatin (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week's rest) as neoadjuvant chemotherapy. Eighty-three patients were assigned to arm A (two courses of SC, n = 21), arm B (four courses of SC, n = 20), arm C (two courses of PC, n = 21), and arm D (four courses of PC, n = 21). Pathological response rate was 43 % in arm A, 40 % in arm B, 29 % in arm C, and 38 % in arm D. Pathological complete response was only observed in arms B (10 %) and D (10 %). Most bone marrow toxicities, nausea, vomiting, alopecia, and fatigue were slightly higher but acceptable in arms B and D. Grade 3/4 surgical morbidities were not commonly observed in all four arms. Pathological complete response could be induced by four courses of neoadjuvant chemotherapy without a marked increase of toxicities, regardless of a SC or PC regimen.

Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease and Multiorgan Failure after Stem Cell Transplantation: A Multicenter, Randomized, Dose-Finding Trial

PubMed Central

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

2010-01-01

Therapeutic options for severe hepatic veno-occlusive disease (VOD) are limited and outcomes are dismal, but early phase I/II studies have suggested promising activity and acceptable toxicity using the novel polydisperse oligonucleotide defibrotide. This randomized phase II dose-finding trial determined the efficacy of defibrotide in patients with severe VOD following hematopoietic stem cell transplantation (HSCT) and identified an appropriate dose for future trials. Adult and pediatric patients received either lower-dose (arm A: 25 mg/kg/day; n = 75) or higher-dose (arm B: 40 mg/kg/day; n = 74) i.v. defibrotide administered in divided doses every 6 hours for ≥ 14 days or until complete response, VOD progression, or any unacceptable toxicity occurred. Overall complete response and day + 100 post-HSCT survival rates were 46% and 42%, respectively, with no significant difference between treatment arms. The incidence of treatment-related adverse events was low (8% overall; 7% in arm A, 10% in arm B); there was no significant difference in the overall rate of adverse events between treatment arms. Early stabilization or decreased bilirubin was associated with better response and day + 100 survival, and decreased plasminogen activator inhibitor type 1 (PAI-1) during treatment was associated with better outcome; changes were similar in both treatment arms. Defibrotide 25 or 40 mg/kg/day also appears effective in treating severe VOD following HSCT. In the absence of any differences in activity, toxicity or changes in PAI-1 level, defibrotide 25 mg/kg/day was selected for ongoing phase III trials in VOD. PMID:20167278

Evaluation of NASA GISS post-CMIP5 single column model simulated clouds and precipitation using ARM Southern Great Plains observations

NASA Astrophysics Data System (ADS)

Zhang, Lei; Dong, Xiquan; Kennedy, Aaron; Xi, Baike; Li, Zhanqing

2017-03-01

The planetary boundary layer turbulence and moist convection parameterizations have been modified recently in the NASA Goddard Institute for Space Studies (GISS) Model E2 atmospheric general circulation model (GCM; post-CMIP5, hereafter P5). In this study, single column model (SCM P5) simulated cloud fractions (CFs), cloud liquid water paths (LWPs) and precipitation were compared with Atmospheric Radiation Measurement (ARM) Southern Great Plains (SGP) groundbased observations made during the period 2002-08. CMIP5 SCM simulations and GCM outputs over the ARM SGP region were also used in the comparison to identify whether the causes of cloud and precipitation biases resulted from either the physical parameterization or the dynamic scheme. The comparison showed that the CMIP5 SCM has difficulties in simulating the vertical structure and seasonal variation of low-level clouds. The new scheme implemented in the turbulence parameterization led to significantly improved cloud simulations in P5. It was found that the SCM is sensitive to the relaxation time scale. When the relaxation time increased from 3 to 24 h, SCM P5-simulated CFs and LWPs showed a moderate increase (10%-20%) but precipitation increased significantly (56%), which agreed better with observations despite the less accurate atmospheric state. Annual averages among the GCM and SCM simulations were almost the same, but their respective seasonal variations were out of phase. This suggests that the same physical cloud parameterization can generate similar statistical results over a long time period, but different dynamics drive the differences in seasonal variations. This study can potentially provide guidance for the further development of the GISS model.

Estimating outcomes and cost effectiveness using a single-arm clinical trial: ofatumumab for double-refractory chronic lymphocytic leukemia.

PubMed

Hatswell, Anthony J; Thompson, Gwilym J; Maroudas, Penny A; Sofrygin, Oleg; Delea, Thomas E

2017-01-01

Ofatumumab (Arzerra ® , Novartis) is a treatment for chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab [double refractory (DR-CLL)]. Ofatumumab was licensed on the basis of an uncontrolled Phase II study, Hx-CD20-406, in which patients receiving ofatumumab survived for a median of 13.9 months. However, the lack of an internal control arm presents an obstacle for the estimation of comparative effectiveness. The objective of the study was to present a method to estimate the cost effectiveness of ofatumumab in the treatment of DR-CLL. As no suitable historical control was available for modelling, the outcomes from non-responders to ofatumumab were used to model the effect of best supportive care (BSC). This was done via a Cox regression to control for differences in baseline characteristics between groups. This analysis was included in a partitioned survival model built in Microsoft ® Excel with utilities and costs taken from published sources, with costs and quality-adjusted life years (QALYs) were discounted at a rate of 3.5% per annum. Using the outcomes seen in non-responders, ofatumumab is expected to add approximately 0.62 life years (1.50 vs. 0.88). Using published utility values this translates to an additional 0.30 QALYs (0.77 vs. 0.47). At the list price, ofatumumab had a cost per QALY of £130,563, and a cost per life year of £63,542. The model was sensitive to changes in assumptions regarding overall survival estimates and utility values. This study demonstrates the potential of using data for non-responders to model outcomes for BSC in cost-effectiveness evaluations based on single-arm trials. Further research is needed on the estimation of comparative effectiveness using uncontrolled clinical studies.

Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study.

PubMed

Hochhaus, A; Masszi, T; Giles, F J; Radich, J P; Ross, D M; Gómez Casares, M T; Hellmann, A; Stentoft, J; Conneally, E; García-Gutiérrez, V; Gattermann, N; Wiktor-Jedrzejczak, W; le Coutre, P D; Martino, B; Saussele, S; Menssen, H D; Deng, W; Krunic, N; Bedoucha, V; Saglio, G

2017-07-01

The single-arm, phase 2 ENESTfreedom trial assessed the potential for treatment-free remission (TFR; i.e., the ability to maintain a molecular response after stopping therapy) following frontline nilotinib treatment. Patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase with MR 4.5 (BCR-ABL1⩽0.0032% on the International Scale (BCR-ABL1 IS )) and ⩾2 years of frontline nilotinib therapy were enrolled. Patients with sustained deep molecular response during the 1-year nilotinib consolidation phase were eligible to stop treatment and enter the TFR phase. Patients with loss of major molecular response (MMR; BCR-ABL1 IS ⩽0.1%) during the TFR phase reinitiated nilotinib. In total, 215 patients entered the consolidation phase, of whom 190 entered the TFR phase. The median duration of nilotinib before stopping treatment was 43.5 months. At 48 weeks after stopping nilotinib, 98 patients (51.6%; 95% confidence interval, 44.2-58.9%) remained in MMR or better (primary end point). Of the 86 patients who restarted nilotinib in the treatment reinitiation phase after loss of MMR, 98.8% and 88.4%, respectively, regained MMR and MR 4.5 by the data cutoff date. Consistent with prior reports of imatinib-treated patients, musculoskeletal pain-related events were reported in 24.7% of patients in the TFR phase (consolidation phase, 16.3%).

An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle-invasive bladder cancer: Interim results.

PubMed

Packiam, Vignesh T; Lamm, Donald L; Barocas, Daniel A; Trainer, Andrew; Fand, Benjamin; Davis, Ronald L; Clark, William; Kroeger, Michael; Dumbadze, Igor; Chamie, Karim; Kader, A Karim; Curran, Dominic; Gutheil, John; Kuan, Arthur; Yeung, Alex W; Steinberg, Gary D

2017-07-26

CG0070 is a replication-competent oncolytic adenovirus that targets bladder tumor cells through their defective retinoblastoma pathway. Prior reports of intravesical CG0070 have shown promising activity in patients with high-grade non-muscle invasive bladder cancer (NMIBC) who previously did not respond to bacillus Calmette-Guérin (BCG). However, limited accrual has hindered analysis of efficacy, particularly for pathologic subsets. We evaluated interim results of a phase II trial for intravesical CG0070 in patients with BCG-unresponsive NMIBC who refused cystectomy. At interim analysis (April 2017), 45 patients with residual high-grade Ta, T1, or carcinoma-in-situ (CIS) ± Ta/T1 had evaluable 6-month follow-up in this phase II single-arm multicenter trial (NCT02365818). All patients received at least 2 prior courses of intravesical therapy for CIS, with at least 1 being a course of BCG. Patients had either failed BCG induction therapy within 6 months or had been successfully treated with BCG with subsequent recurrence. Complete response (CR) at 6 months was defined as absence of disease on cytology, cystoscopy, and random biopsies. Of 45 patients, there were 24 pure CIS, 8 CIS + Ta, 4 CIS + T1, 6 Ta, 3 T1. Overall 6-month CR (95% CI) was 47% (32%-62%). Considering 6-month CR for pathologic subsets, pure CIS was 58% (37%-78%), CIS ± Ta/T1 50% (33%-67%), and pure Ta/T1 33% (8%-70%). At 6 months, the single patient that progressed to muscle-invasive disease had Ta and T1 tumors at baseline. No patients with pure T1 had 6-month CR. Treatment-related adverse events (AEs) at 6 months were most commonly urinary bladder spasms (36%), hematuria (28%), dysuria (25%), and urgency (22%). Immunologic treatment-related AEs included flu-like symptoms (12%) and fatigue (6%). Grade III treatment-related AEs included dysuria (3%) and hypotension (1.5%). There were no Grade IV/V treatment-related AEs. This phase II study demonstrates that intravesical CG0070 yielded an overall 47% CR rate at 6 months for all patients and 50% for patients with CIS, with an acceptable level of toxicity for patients with high-risk BCG-unresponsive NMIBC. There is a particularly strong response and limited progression in patients with pure CIS. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial

PubMed Central

2011-01-01

Background To evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer. Methods Patients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed. Results From February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03); patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p < 0.001). Neutropenia and stomatitis were worse in the 3-weekly arm, where two toxic deaths were observed. Overall response rate was 39.1% and 33.3% in 3-weekly and weekly arms; hazard ratio of progression was 1.29 (95% CI: 0.84-1.97) and hazard ratio of death was 1.38 (95% CI: 0.82-2.30) in the weekly arm. Conclusions In this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer. Trial registration ClinicalTrials.gov NCT00540800. PMID:21324184

Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial.

PubMed

Nuzzo, Francesco; Morabito, Alessandro; Gravina, Adriano; Di Rella, Francesca; Landi, Gabriella; Pacilio, Carmen; Labonia, Vincenzo; Rossi, Emanuela; De Maio, Ermelinda; Piccirillo, Maria Carmela; D'Aiuto, Giuseppe; Thomas, Renato; Rinaldo, Massimo; Botti, Gerardo; Di Bonito, Maurizio; Di Maio, Massimo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2011-02-16

To evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer. Patients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed. From February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03); patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p < 0.001). Neutropenia and stomatitis were worse in the 3-weekly arm, where two toxic deaths were observed. Overall response rate was 39.1% and 33.3% in 3-weekly and weekly arms; hazard ratio of progression was 1.29 (95% CI: 0.84-1.97) and hazard ratio of death was 1.38 (95% CI: 0.82-2.30) in the weekly arm. In this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer. ClinicalTrials.gov NCT00540800.

Coordinated control of a space manipulator tested by means of an air bearing free floating platform

NASA Astrophysics Data System (ADS)

Sabatini, Marco; Gasbarri, Paolo; Palmerini, Giovanni B.

2017-10-01

A typical approach studied for the guidance of next generation space manipulators (satellites with robotic arms aimed at autonomously performing on-orbit operations) is to decouple the platform and the arm maneuvers, which are supposed to happen sequentially, mainly because of safety concerns. This control is implemented in this work as a two-stage Sequential control, where a first stage calls for the motion of the platform and the second stage calls for the motion of the manipulator. A second novel strategy is proposed, considering the platform and the manipulator as a single multibody system subject to a Coordinated control, with the goal of approaching and grasping a target spacecraft. At the scope, a region that the end effector can reach by means of the arm motion with limited reactions on the platform is identified (the so called Reaction Null workspace). The Coordinated control algorithm performs a gain modulation (finalized to a balanced contribution of the platform and arm motion) as a function of the target position within this Reaction Null map. The result is a coordinated maneuver in which the end effector moves thanks to the platform motion, predominant in a first phase, and to the arm motion, predominant when the Reaction-Null workspace is reached. In this way the collision avoidance and attitude over-control issues are automatically considered, without the need of splitting the mission in independent (and overall sub-optimal) segments. The guidance and control algorithms are first simulated by means of a multibody code, and successively tested in the lab by means of a free floating platform equipped with a robotic arm, moving frictionless on a flat granite table thanks to air bearings and on-off thrusters; the results will be discussed in terms of optimality of the fuel consumption and final accuracy.

Can an electronic device with a single cuff be accurate in a wide range of arm size? Validation of the Visomat Comfort 20/40 device for home blood pressure monitoring.

PubMed

Stergiou, G S; Tzamouranis, D; Nasothimiou, E G; Protogerou, A D

2008-11-01

An appropriate cuff according to the individual's arm circumference is recommended with all blood pressure (BP) monitors. An electronic device for home monitoring has been developed (Visomat Comfort 20/40) that estimates the individual's arm circumference by measuring the cuff filing volume and makes an adjustment of measured BP taking into account the estimated arm circumference. Thus the manufacturer recommends the use of a single cuff for arm circumference 23-43 cm. The device accuracy was assessed using the European Society of Hypertension International Protocol. Simultaneous BP measurements were obtained in 33 adults by two observers (connected mercury sphygmomanometers) four times, sequentially with three measurements taken using the tested device. Absolute device-observer BP differences were classified into < or =5, < or =10 and < or =15 mm Hg zones. For each participant the number of measurements with a difference < or =5 mm Hg was calculated. The device produced 60/89/97 measurements within 5/10/15 mm Hg respectively for systolic BP, and 72/97/98 for diastolic. Twenty-three subjects had at least two of their systolic BP differences < or =5 mm Hg and three had no differences < or =5 mm Hg (for diastolic 27 and 1, respectively). Mean device-observer BP difference (systolic/diastolic) was 3.7 +/- 5.6/-1.5 +/- 4.7 mm Hg (4.7 +/- 4.9/ - 1.7 +/- 4.3 in arm circumference 23-29 cm [39 readings] and 3.1 +/- 5.9/-1.4 +/- 5.0 in arm 30-34 cm [60 readings], P=NS). In conclusion, the device fulfils the International Protocol requirements and can be recommended for clinical use. Interestingly, the device was accurate using a single cuff in a wide range of arm circumference (23-34 cm). This study provides no information about the device accuracy in larger arms.

West Antarctica as a Natural Laboratory for Single- and Mixed-Phase Cloud Microphysics

NASA Astrophysics Data System (ADS)

Wilson, A.; Scott, R. C.; Lubin, D.

2016-12-01

As part of the ARM West Antarctic Radiation Experiment (AWARE), a micropulse lidar (MPL) and a shortwave spectroradiometer were deployed to the West Antarctic Ice Sheet (WAIS) Divide Ice Camp during December 2015 and January 2016. Contrasting meteorological conditions gave rise to several distinct episodes of mixed-phase clouds, liquid water clouds, and entirely glaciated clouds. These phases were readily distinguished in the polarization signature from the MPL. The spectroradiometer measured downwelling hemispheric irradiance in the wavelength interval 0.35-2.2 microns, with 3-nanometer resolution at visible and 10-nanometer resolution at near-infrared wavelengths. Under overcast sky conditions, this measured irradiance is sensitive to total cloud optical depth for wavelengths shorter than 1.1 microns, and is sensitive at both cloud phase and effective particle size in the 1.6-micron window. For single-phase clouds, the spectral irradiance in the 1.6-micron window shows marked contrasts between liquid and ice water. For mixed phase clouds, this spectral dependence of the 1.6-micron irradiance is consistent with the prevailing phase, but in all cases the irradiance is small than that under a liquid water cloud having the same total optical depth. Radiative transfer retrievals of effective particle size from the 1.6-micron irradiance data reveal liquid water effective radii typically 2 microns smaller than found in the spring and summertime high Arctic. Most of the clouds sampled here were within 2 km of the surface, and there are comprehensive ancillary data including sondes four times daily, additional microwave radiometer data, and broadband radiometry. This AWARE data set from WAIS Divide provides a unique opportunity for testing and improving cloud microphysical parameterizations in extreme cold and pristine conditions.

Neutral B-meson Mixing and CP Violation at LHCb

NASA Astrophysics Data System (ADS)

Oblakowska-Mucha, A.; LHCb Collaboration

2016-11-01

The LHCb detector is a single-arm forward spectrometer that collects data at the LHC, designed for studies of flavour physics with high precision. We present a selection of recent measurements of mixing and CP-violating parameters, including sin 2β and weak phase ϕ s, using several decays. A good understanding of the pollution from sub-leading penguin to pologies in these measurements can be achieved by measuring CP violation and polarization in the decay Bs 0→Jψ⁄K 0* and B 0→Jψ⁄ ρ 0. All results here presented are obtained using the full Run I dataset.

Early superoxide dismutase alterations during SV40-transformation of human fibroblasts.

PubMed

Bravard, A; Hoffschir, F; Sabatier, L; Ricoul, M; Pinton, A; Cassingena, R; Estrade, S; Luccioni, C; Dutrillaux, B

1992-11-11

The expression of superoxide dismutases (SOD) 1 and 2 was studied in 4 clones of human fibroblasts after their infection by simian virus 40 (SV40), in parallel with the alterations of chromosomes 21 and chromosome 6q arms, carrying the genes that encode for SOD1 and SOD2 respectively. For all clones, a similar scheme with 2 main phases was observed for both chromosome and SOD variations. The first phase, defined as the pre-crisis phase, was characterized by chromosomal instability, but maintenance of normal numbers of chromosome 6q arms and chromosomes 21. The level of SOD2 mRNA was high, while SOD2 activity and immunoreactive protein were low. SOD1 protein and activity were decreased. In the second phase, defined as the post-crisis phase, the accumulation of clonal chromosomal rearrangements led to the loss of 6q arms, while the number of chromosomes 21 remained normal. SOD2 mRNA level was decreased and SOD2 immunoreactive protein and activity remained low. SOD1 protein and activity increased with passages, reaching values similar to those of control cells at late passages. As in established SV40-transformed human fibroblast cell lines, good correlation was found between SOD2 activity and the relative number of 6q arms. These results allow us to reconstruct the sequence of events leading to the decrease of SOD2, a possible tumor-suppressor gene, during the process of SV40-transformation of human fibroblasts.

A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO).

PubMed

Sehouli, Jalid; Tomè, Oliver; Dimitrova, Desislava; Camara, Oumar; Runnebaum, Ingo Bernhard; Tessen, Hans Werner; Rautenberg, Beate; Chekerov, Radoslav; Muallem, Mustafa Zelal; Lux, Michael Patrick; Trarbach, Tanja; Gitsch, Gerald

2017-03-01

In recurrent ovarian cancer (ROC), there is a high demand on effective therapies with a mild toxicity profile. Treosulfan is an alkylating agent approved as oral (p.o.) and intravenous (i.v.) formulation for the treatment of recurrent ovarian cancer. Data on safety and efficacy for either formulation are rare. For the first time we conducted a randomized phase III study comparing both formulations in women with ROC. Patients having received at least two previous lines of chemotherapy were randomly assigned to one of two treatment arms: treosulfan i.v. 7000 mg/m 2 d1 q4w or treosulfan p.o. 600 mg/m 2 d1-28 q8w. Primary endpoint was safety regarding hematological and gastrointestinal toxicity grade III/IV, secondary endpoints were other toxicities, clinical benefit rate (CBR), time to progression (TTP), overall survival (OS) and quality of life. 250 patients were treated with treosulfan i.v. (128) or treosulfan p.o. (122). In general treosulfan therapy was well tolerated in both treatment arms. Leukopenia grade III/IV occurred significantly more frequently in the p.o. arm (3.9% i.v. arm, 14.8% p.o. arm, p = 0.002). Other toxicities were similar in both arms. CBR was comparable between arms (41.4% i.v. arm, 36.9% p.o. arm). No difference in TTP (3.7 months i.v. arm, 3.5 months p.o. arm) or OS (13.6 months i.v. arm, 10.4 months p.o. arm, p = 0.087) occurred. Given the safety and efficacy results treosulfan is an acceptable option for heavily pretreated OC patients. Regarding the toxicity profile the i.v. application was better tolerated with less grade III and IV toxicities.

Radio frequency reflectometry and charge sensing of a precision placed donor in silicon

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

Hile, Samuel J., E-mail: samhile@gmail.com; House, Matthew G.; Peretz, Eldad

2015-08-31

We compare charge transitions on a deterministic single P donor in silicon using radio frequency reflectometry measurements with a tunnel coupled reservoir and DC charge sensing using a capacitively coupled single electron transistor (SET). By measuring the conductance through the SET and comparing this with the phase shift of the reflected radio frequency (RF) excitation from the reservoir, we can discriminate between charge transfer within the SET channel and tunneling between the donor and reservoir. The RF measurement allows observation of donor electron transitions at every charge degeneracy point in contrast to the SET conductance signal where charge transitions aremore » only observed at triple points. The tunnel coupled reservoir has the advantage of a large effective lever arm (∼35%), allowing us to independently extract a neutral donor charging energy ∼62 ± 17 meV. These results demonstrate that we can replace three terminal transistors by a single terminal dispersive reservoir, promising for high bandwidth scalable donor control and readout.« less

Single shot imaging through turbid medium and around corner using coherent light

NASA Astrophysics Data System (ADS)

Li, Guowei; Li, Dayan; Situ, Guohai

2018-01-01

Optical imaging through turbid media and around corner is a difficult challenge. Even a very thin layer of a turbid media, which randomly scatters the probe light, can appear opaque and hide any objects behind it. Despite many recent advances, no current method can image the object behind turbid media with single record using coherent laser illumination. Here we report a method that allows non-invasive single-shot optical imaging through turbid media and around corner via speckle correlation. Instead of being as an obstacle in forming diffractionlimited images, speckle actually can be a carrier that encodes sufficient information to imaging through visually opaque layers. Optical imaging through turbid media and around corner is experimentally demonstrated using traditional imaging system with the aid of iterative phase retrieval algorithm. Our method require neither scan of illumination nor two-arm interferometry or long-time exposure in acquisition, which has new implications in optical sensing through common obscurants such as fog, smoke and haze.

Single-camera visual odometry to track a surgical X-ray C-arm base.

PubMed

Esfandiari, Hooman; Lichti, Derek; Anglin, Carolyn

2017-12-01

This study provides a framework for a single-camera odometry system for localizing a surgical C-arm base. An application-specific monocular visual odometry system (a downward-looking consumer-grade camera rigidly attached to the C-arm base) is proposed in this research. The cumulative dead-reckoning estimation of the base is extracted based on frame-to-frame homography estimation. Optical-flow results are utilized to feed the odometry. Online positional and orientation parameters are then reported. Positional accuracy of better than 2% (of the total traveled distance) for most of the cases and 4% for all the cases studied and angular accuracy of better than 2% (of absolute cumulative changes in orientation) were achieved with this method. This study provides a robust and accurate tracking framework that not only can be integrated with the current C-arm joint-tracking system (i.e. TC-arm) but also is capable of being employed for similar applications in other fields (e.g. robotics).

Using shape to turn off blinking for two-colour multiexciton emission in CdSe/CdS tetrapods

NASA Astrophysics Data System (ADS)

Mishra, Nimai; Orfield, Noah J.; Wang, Feng; Hu, Zhongjian; Krishnamurthy, Sachidananda; Malko, Anton V.; Casson, Joanna L.; Htoon, Han; Sykora, Milan; Hollingsworth, Jennifer A.

2017-05-01

Semiconductor nanostructures capable of emitting from two excited states and thereby of producing two photoluminescence colours are of fundamental and potential technological significance. In this limited class of nanocrystals, CdSe/CdS core/arm tetrapods exhibit the unusual trait of two-colour (red and green) multiexcitonic emission, with green emission from the CdS arms emerging only at high excitation fluences. Here we show that by synthetic shape-tuning, both this multi-colour emission process, and blinking and photobleaching behaviours of single tetrapods can be controlled. Specifically, we find that the properties of dual emission and single-nanostructure photostability depend on different structural parameters--arm length and arm diameter, respectively--but that both properties can be realized in the same nanostructure. Furthermore, based on results of correlated photoluminescence and transient absorption measurements, we conclude that hole-trap filling in the arms and partial state-filling in the core are necessary preconditions for the observation of multiexciton multi-colour emission.

Beam rider for an Articulated Robot Manipulator (ARM) accurate positioning of long flexible manipulators

NASA Technical Reports Server (NTRS)

Malachowski, M. J.

1990-01-01

Laser beam positioning and beam rider modules were incorporated into the long hollow flexible segment of an articulated robot manipulator (ARM). Using a single laser beam, the system determined the position of the distal ARM endtip, with millimetric precision, in six degrees of freedom, at distances of up to 10 meters. Preliminary designs, using space rated technology for the critical systems, of a two segmented physical ARM, with a single and a dual degree of freedom articulation, were developed, prototyped, and tested. To control the positioning of the physical ARM, an indirect adaptive controller, which used the mismatch between the position of the laser beam under static and dynamic conditions, was devised. To predict the behavior of the system and test the concept, a computer simulation model was constructed. A hierarchical artificially intelligent real time ADA operating system program structure was created. The software was designed for implementation on a dedicated VME bus based Intel 80386 administered parallel processing multi-tasking computer system.

Using shape to turn off blinking for two-colour multiexciton emission in CdSe/CdS tetrapods

PubMed Central

Mishra, Nimai; Orfield, Noah J.; Wang, Feng; Hu, Zhongjian; Krishnamurthy, Sachidananda; Malko, Anton V.; Casson, Joanna L.; Htoon, Han; Sykora, Milan; Hollingsworth, Jennifer A.

2017-01-01

Semiconductor nanostructures capable of emitting from two excited states and thereby of producing two photoluminescence colours are of fundamental and potential technological significance. In this limited class of nanocrystals, CdSe/CdS core/arm tetrapods exhibit the unusual trait of two-colour (red and green) multiexcitonic emission, with green emission from the CdS arms emerging only at high excitation fluences. Here we show that by synthetic shape-tuning, both this multi-colour emission process, and blinking and photobleaching behaviours of single tetrapods can be controlled. Specifically, we find that the properties of dual emission and single-nanostructure photostability depend on different structural parameters—arm length and arm diameter, respectively—but that both properties can be realized in the same nanostructure. Furthermore, based on results of correlated photoluminescence and transient absorption measurements, we conclude that hole-trap filling in the arms and partial state-filling in the core are necessary preconditions for the observation of multiexciton multi-colour emission. PMID:28497776

Application of System Identification Methods for Decoding Imagined Single-Joint Movements in an Individual with High Tetraplegia

PubMed Central

Ajiboye, A. Bolu; Hochberg, Leigh R.; Donoghue, John P.; Kirsch, Robert F.

2013-01-01

This study investigated the decoding of imagined arm movements from M1 in an individual with high level tetraplegia. The participant was instructed to imagine herself performing a series of single-joint arm movements, aided by the visual cue of an animate character performing these movements. System identification was used offline to predict the trajectories of the imagined movements and compare these predictions to the trajectories of the actual movements. We report rates of 25 – 50% for predicting completely imagined arm movements in the absence of a priori movements to aid in decoder building. PMID:21096197

Brain-Machine Interface Enables Bimanual Arm Movements in Monkeys

PubMed Central

Ifft, Peter J.; Shokur, Solaiman; Li, Zheng; Lebedev, Mikhail A.; Nicolelis, Miguel A. L.

2014-01-01

Brain-machine interfaces (BMIs) are artificial systems that aim to restore sensation and movement to severely paralyzed patients. However, previous BMIs enabled only single arm functionality, and control of bimanual movements was a major challenge. Here, we developed and tested a bimanual BMI that enabled rhesus monkeys to control two avatar arms simultaneously. The bimanual BMI was based on the extracellular activity of 374–497 neurons recorded from several frontal and parietal cortical areas of both cerebral hemispheres. Cortical activity was transformed into movements of the two arms with a decoding algorithm called a 5th order unscented Kalman filter (UKF). The UKF is well-suited for BMI decoding because it accounts for both characteristics of reaching movements and their representation by cortical neurons. The UKF was trained either during a manual task performed with two joysticks or by having the monkeys passively observe the movements of avatar arms. Most cortical neurons changed their modulation patterns when both arms were engaged simultaneously. Representing the two arms jointly in a single UKF decoder resulted in improved decoding performance compared with using separate decoders for each arm. As the animals’ performance in bimanual BMI control improved over time, we observed widespread plasticity in frontal and parietal cortical areas. Neuronal representation of the avatar and reach targets was enhanced with learning, whereas pairwise correlations between neurons initially increased and then decreased. These results suggest that cortical networks may assimilate the two avatar arms through BMI control. PMID:24197735

Neural control of rhythmic arm cycling after stroke

PubMed Central

Loadman, Pamela M.; Hundza, Sandra R.

2012-01-01

Disordered reflex activity and alterations in the neural control of walking have been observed after stroke. In addition to impairments in leg movement that affect locomotor ability after stroke, significant impairments are also seen in the arms. Altered neural control in the upper limb can often lead to altered tone and spasticity resulting in impaired coordination and flexion contractures. We sought to address the extent to which the neural control of movement is disordered after stroke by examining the modulation pattern of cutaneous reflexes in arm muscles during arm cycling. Twenty-five stroke participants who were at least 6 mo postinfarction and clinically stable, performed rhythmic arm cycling while cutaneous reflexes were evoked with trains (5 × 1.0-ms pulses at 300 Hz) of constant-current electrical stimulation to the superficial radial (SR) nerve at the wrist. Both the more (MA) and less affected (LA) arms were stimulated in separate trials. Bilateral electromyography (EMG) activity was recorded from muscles acting at the shoulder, elbow, and wrist. Analysis was conducted on averaged reflexes in 12 equidistant phases of the movement cycle. Phase-modulated cutaneous reflexes were present, but altered, in both MA and LA arms after stroke. Notably, the pattern was “blunted” in the MA arm in stroke compared with control participants. Differences between stroke and control were progressively more evident moving from shoulder to wrist. The results suggest that a reduced pattern of cutaneous reflex modulation persists during rhythmic arm movement after stroke. The overall implication of this result is that the putative spinal contributions to rhythmic human arm movement remain accessible after stroke, which has translational implications for rehabilitation. PMID:22572949

Comparison of VRX CT scanners geometries

NASA Astrophysics Data System (ADS)

DiBianca, Frank A.; Melnyk, Roman; Duckworth, Christopher N.; Russ, Stephan; Jordan, Lawrence M.; Laughter, Joseph S.

2001-06-01

A technique called Variable-Resolution X-ray (VRX) detection greatly increases the spatial resolution in computed tomography (CT) and digital radiography (DR) as the field size decreases. The technique is based on a principle called `projective compression' that allows both the resolution element and the sampling distance of a CT detector to scale with the subject or field size. For very large (40 - 50 cm) field sizes, resolution exceeding 2 cy/mm is possible and for very small fields, microscopy is attainable with resolution exceeding 100 cy/mm. This paper compares the benefits obtainable with two different VRX detector geometries: the single-arm geometry and the dual-arm geometry. The analysis is based on Monte Carlo simulations and direct calculations. The results of this study indicate that the dual-arm system appears to have more advantages than the single-arm technique.

Large Scale Ice Water Path and 3-D Ice Water Content

DOE Data Explorer

Liu, Guosheng

2008-01-15

Cloud ice water concentration is one of the most important, yet poorly observed, cloud properties. Developing physical parameterizations used in general circulation models through single-column modeling is one of the key foci of the ARM program. In addition to the vertical profiles of temperature, water vapor and condensed water at the model grids, large-scale horizontal advective tendencies of these variables are also required as forcing terms in the single-column models. Observed horizontal advection of condensed water has not been available because the radar/lidar/radiometer observations at the ARM site are single-point measurement, therefore, do not provide horizontal distribution of condensed water. The intention of this product is to provide large-scale distribution of cloud ice water by merging available surface and satellite measurements. The satellite cloud ice water algorithm uses ARM ground-based measurements as baseline, produces datasets for 3-D cloud ice water distributions in a 10 deg x 10 deg area near ARM site. The approach of the study is to expand a (surface) point measurement to an (satellite) areal measurement. That is, this study takes the advantage of the high quality cloud measurements at the point of ARM site. We use the cloud characteristics derived from the point measurement to guide/constrain satellite retrieval, then use the satellite algorithm to derive the cloud ice water distributions within an area, i.e., 10 deg x 10 deg centered at ARM site.

Spatially varying geometric phase in classically entangled vector beams of light

NASA Astrophysics Data System (ADS)

King-Smith, Andrew; Leary, Cody

We present theoretical results describing a spatially varying geometric (Pancharatnam) phase present in vector modes of light, in which the polarization and transverse spatial mode degrees of freedom exhibit classical entanglement. We propose an experimental setup capable of characterizing this effect, in which a vector mode propagates through a Mach-Zehnder interferometer with a birefringent phase retarder present in one arm. Since the polarization state of a classically entangled light beam exhibits spatial variation across the transverse mode profile, the phase retarder gives rise to a spatially varying geometric phase in the beam propagating through it. When recombined with the reference beam from the other interferometer arm, the presence of the geometric phase is exhibited in the resulting interference pattern. We acknowledge funding from the Research Corporation for Science Advancement by means of a Cottrell College Science Award.

Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial

PubMed Central

Van Coevorden, Frits; Punt, Cornelis J. A.; Pierie, Jean-Pierre E. N.; Borel-Rinkes, Inne; Ledermann, Jonathan A.; Poston, Graeme; Bechstein, Wolf; Lentz, Marie-Ange; Mauer, Murielle; Folprecht, Gunnar; Van Cutsem, Eric; Ducreux, Michel; Nordlinger, Bernard

2017-01-01

Background: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. Methods: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n < 10 and no extrahepatic disease) received systemic treatment alone or systemic treatment plus aggressive local treatment by radiofrequency ablation ± resection. Previously, we reported that the primary end point (30-month overall survival [OS] > 38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. Results: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. Conclusions: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases. PMID:28376151

Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial.

PubMed

Ruers, Theo; Van Coevorden, Frits; Punt, Cornelis J A; Pierie, Jean-Pierre E N; Borel-Rinkes, Inne; Ledermann, Jonathan A; Poston, Graeme; Bechstein, Wolf; Lentz, Marie-Ange; Mauer, Murielle; Folprecht, Gunnar; Van Cutsem, Eric; Ducreux, Michel; Nordlinger, Bernard

2017-09-01

Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n < 10 and no extrahepatic disease) received systemic treatment alone or systemic treatment plus aggressive local treatment by radiofrequency ablation ± resection. Previously, we reported that the primary end point (30-month overall survival [OS] > 38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases. © The Author 2017. Published by Oxford University Press.

Effects of spiral arms on star formation in nuclear rings of barred-spiral galaxies

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

Seo, Woo-Young; Kim, Woong-Tae, E-mail: seowy@astro.snu.ac.kr, E-mail: wkim@astro.snu.ac.kr

2014-09-01

We use hydrodynamic simulations to study the effect of spiral arms on the star formation rate (SFR) in nuclear rings of barred-spiral galaxies. We find that spiral arms can be an efficient means of gas transport from the outskirts to the central parts, provided that the arms are rotating slower than the bar. While the ring star formation in models with no arms or corotating arms is active only during around the bar growth phase, arm-driven gas accretion both significantly enhances and prolongs the ring star formation in models with slow-rotating arms. The arm-enhanced SFR is larger by a factormore » of ∼3-20 than in the no-arm model, with larger values corresponding to stronger and slower arms. Arm-induced mass inflows also make dust lanes stronger. Nuclear rings in slow-arm models are ∼45% larger than in the no-arm counterparts. Star clusters that form in a nuclear ring exhibit an age gradient in the azimuthal direction only when the SFR is small, whereas no notable age gradient is found in the radial direction for models with arm-induced star formation.« less

Pacing the phasing of leg and arm movements in breaststroke swimming to minimize intra-cyclic velocity fluctuations

PubMed Central

Roerdink, Melvyn; Huibers, Alja V.; Evers, Lotte L. W.; Beek, Peter J.

2017-01-01

In swimming propelling efficiency is partly determined by intra-cyclic velocity fluctuations. The higher these fluctuations are at a given average swimming velocity, the less efficient is the propulsion. This study explored whether the leg-arm coordination (i.e. phase relation ϕ) within the breaststroke cycle can be influenced with acoustic pacing, and whether the so induced changes are accompanied by changes in intra-cyclic velocity fluctuations. Twenty-six participants were asked to couple their propulsive leg and arm movements to a double-tone metronome beat and to keep their average swimming velocity constant over trials. The metronome imposed five different phase relations ϕi (90, 135, 180, 225 and 270°) of leg-arm coordination. Swimmers adjusted their technique under the influence of the metronome, but failed to comply to the velocity requirement for ϕ = 90 and 135°. For imposed ϕ = 180, 225 and 270°, the intra-cyclic velocity fluctuations increased with increasing ϕ, while average swimming velocity did not differ. This suggests that acoustic pacing may be used to adjust ϕ and thereby performance of breaststroke swimming given the dependence of propelling efficiency on ϕ. PMID:29023496

Pacing the phasing of leg and arm movements in breaststroke swimming to minimize intra-cyclic velocity fluctuations.

PubMed

van Houwelingen, Josje; Roerdink, Melvyn; Huibers, Alja V; Evers, Lotte L W; Beek, Peter J

2017-01-01

In swimming propelling efficiency is partly determined by intra-cyclic velocity fluctuations. The higher these fluctuations are at a given average swimming velocity, the less efficient is the propulsion. This study explored whether the leg-arm coordination (i.e. phase relation ϕ) within the breaststroke cycle can be influenced with acoustic pacing, and whether the so induced changes are accompanied by changes in intra-cyclic velocity fluctuations. Twenty-six participants were asked to couple their propulsive leg and arm movements to a double-tone metronome beat and to keep their average swimming velocity constant over trials. The metronome imposed five different phase relations ϕi (90, 135, 180, 225 and 270°) of leg-arm coordination. Swimmers adjusted their technique under the influence of the metronome, but failed to comply to the velocity requirement for ϕ = 90 and 135°. For imposed ϕ = 180, 225 and 270°, the intra-cyclic velocity fluctuations increased with increasing ϕ, while average swimming velocity did not differ. This suggests that acoustic pacing may be used to adjust ϕ and thereby performance of breaststroke swimming given the dependence of propelling efficiency on ϕ.

Broadband Achromatic Phase Shifter for a Nulling Interferometer

NASA Technical Reports Server (NTRS)

Bolcar, Matthew R.; Lyon, Richard G.

2011-01-01

Nulling interferometry is a technique for imaging exoplanets in which light from the parent star is suppressed using destructive interference. Light from the star is divided into two beams and a phase shift of radians is introduced into one of the beams. When the beams are recombined, they destructively interfere to produce a deep null. For monochromatic light, this is implemented by introducing an optical path difference (OPD) between the two beams equal to lambda/2, where lambda is the wavelength of the light. For broadband light, however, a different phase shift will be introduced at each wavelength and the two beams will not effectively null when recombined. Various techniques have been devised to introduce an achromatic phase shift a phase shift that is uniform across a particular bandwidth. One popular technique is to use a series of dispersive elements to introduce a wavelength-dependent optical path in one or both of the arms of the interferometer. By intelligently choosing the number, material and thickness of a series of glass plates, a nearly uniform, arbitrary phase shift can be introduced between two arms of an interferometer. There are several constraints that make choosing the number, type, and thickness of materials a difficult problem, such as the size of the bandwidth to be nulled. Several solutions have been found for bandwidths on the order of 20 to 30 percent (Delta(lambda)/lambda(sub c)) in the mid-infrared region. However, uniform phase shifts over a larger bandwidth in the visible regime between 480 to 960 nm (67 percent) remain difficult to obtain at the tolerances necessary for exoplanet detection. A configuration of 10 dispersive glass plates was developed to be used as an achromatic phase shifter in nulling interferometry. Five glass plates were placed in each arm of the interferometer and an additional vacuum distance was also included in the second arm of the interferometer. This configuration creates a phase shift of pi radians with an average error of 5.97 x 10(exp -8) radians and standard deviation of 3.07 x 10(exp -4) radians. To reduce ghost reflections and interference effects from neighboring elements, the glass plates are tilted such that the beam does not strike each plate at normal incidence. Reflections will therefore walk out of the system and not contribute to the intensity when the beams are recombined. Tilting the glass plates, however, introduces several other problems that must be mitigated: (1) the polarization of a beam changes when refracted at an interface at non-normal incidence; (2) the beam experiences lateral chromatic spread as it traverses multiple glass plates; (3) at each surface, wavelength- dependent intensity losses will occur due to reflection. For a fixed angle of incidence, each of these effects must be balanced between each arm of the interferometer in order to ensure a deep null. The solution was found using a nonlinear optimization routine that minimized an objective function relating phase shift, intensity difference, chromatic beam spread, and polarization difference to the desired parameters: glass plate material and thickness. In addition to providing a uniform, broadband phase shift, the configuration achieves an average difference in intensity transmission between the two arms of the interferometer of 0.016 percent with a standard deviation of 3.64 x 10(exp -4) percent, an average difference in polarization between the two arms of the interferometer of 5.47 x 10(exp -5) percent with a standard deviation of 1.57 x 10(exp -6) percent, and an average chromatic beam shift between the two arms of the interferometer of -47.53 microns with a wavelength-by-wavelength spread of 0.389 microns.

The Mixed-Phase Arctic Cloud Experiment (M-PACE)

NASA Technical Reports Server (NTRS)

Verlinde, J.; Harrington, J. Y.; McFarquhar, G. M.; Yannuzzi, V. T.; Avramov, A.; Greenberg, S.; Johnson, N.; Zhang, G.; Poellot, M. R.; Mather, J. H.;

A limit-cycle self-organizing map architecture for stable arm control.

PubMed

Huang, Di-Wei; Gentili, Rodolphe J; Katz, Garrett E; Reggia, James A

2017-01-01

Inspired by the oscillatory nature of cerebral cortex activity, we recently proposed and studied self-organizing maps (SOMs) based on limit cycle neural activity in an attempt to improve the information efficiency and robustness of conventional single-node, single-pattern representations. Here we explore for the first time the use of limit cycle SOMs to build a neural architecture that controls a robotic arm by solving inverse kinematics in reach-and-hold tasks. This multi-map architecture integrates open-loop and closed-loop controls that learn to self-organize oscillatory neural representations and to harness non-fixed-point neural activity even for fixed-point arm reaching tasks. We show through computer simulations that our architecture generalizes well, achieves accurate, fast, and smooth arm movements, and is robust in the face of arm perturbations, map damage, and variations of internal timing parameters controlling the flow of activity. A robotic implementation is evaluated successfully without further training, demonstrating for the first time that limit cycle maps can control a physical robot arm. We conclude that architectures based on limit cycle maps can be organized to function effectively as neural controllers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhanced arm swing alters interlimb coordination during overground walking in individuals with traumatic brain injury.

PubMed

Ustinova, Ksenia I; Langenderfer, Joseph E; Balendra, Nilanthy

2017-04-01

The current study investigated interlimb coordination in individuals with traumatic brain injury (TBI) during overground walking. The study involved 10 participants with coordination, balance, and gait abnormalities post-TBI, as well as 10 sex- and age-matched healthy control individuals. Participants walked 12m under two experimental conditions: 1) at self-selected comfortable walking speeds; and 2) with instructions to increase the amplitude and out-of-phase coordination of arm swinging. The gait was assessed with a set of spatiotemporal and kinematic parameters including the gait velocity, step length and width, double support time, lateral displacement of the center of mass, the amplitude of horizontal trunk rotation, and angular motions at shoulder and hip joints in sagittal plane. Interlimb coordination (coupling) was analyzed as the relative phase angles between the left and right shoulders, hips, and contralateral shoulders and hips, with an ideal out-of-phase coupling of 180° and ideal in-phase coupling of 0°. The TBI group showed much less interlimb coupling of the above pairs of joint motions than the control group. When participants were required to increase and synchronize arm swinging, coupling between shoulder and hip motions was significantly improved in both groups. Enhanced arm swinging was associated with greater hip and shoulder motion amplitudes, and greater step length. No other significant changes in spatiotemporal or kinematic gait characteristics were found in either group. The results suggest that arm swinging may be a gait parameter that, if controlled properly, can improve interlimb coordination during overground walking in patients with TBI. Copyright © 2017 Elsevier B.V. All rights reserved.

Gating of tactile information through gamma band during passive arm movement in awake primates

PubMed Central

Song, Weiguo; Francis, Joseph T.

2015-01-01

To make precise and prompt action in a dynamic environment, the sensorimotor system needs to integrate all related information. The inflow of somatosensory information to the cerebral cortex is regulated and mostly suppressed by movement, which is commonly referred to as sensory gating or gating. Sensory gating plays an important role in preventing redundant information from reaching the cortex, which should be considered when designing somatosensory neuroprosthetics. Gating can occur at several levels within the sensorimotor pathway, while the underlying mechanism is not yet fully understood. The average sensory evoked potential is commonly used to assess sensory information processing, however the assumption of a stereotyped response to each stimulus is still an open question. Event related spectral perturbation (ERSP), which is the power spectrum after time-frequency decomposition on single trial evoked potentials (total power), could overcome this limitation of averaging and provide additional information for understanding the underlying mechanism. To this aim, neural activities in primary somatosensory cortex (S1), primary motor cortex (M1), and ventral posterolateral (VPL) nucleus of thalamus were recorded simultaneously in two areas (S1 and M1 or S1 and VPL) during passive arm movement and rest in awake monkeys. Our results showed that neural activity at different recording areas demonstrated specific and unique response frequency characteristics. Tactile input induced early high frequency responses followed by low frequency oscillations within sensorimotor circuits, and passive movement suppressed these oscillations either in a phase-locked or non-phase-locked manner. Sensory gating by movement was non-phase-locked in M1, and complex in sensory areas. VPL showed gating of non-phase-locked at gamma band and mix of phase-locked and non-phase-locked at low frequency, while S1 showed gating of phase-locked and non-phase-locked at gamma band and an early phase-locked elevation followed by non-phase-locked gating at low frequency. Granger causality (GC) analysis showed bidirectional coupling between VPL and S1, while GC between M1 and S1 was not responsive to tactile input. Thus, these results suggest that tactile input is dominantly transmitted along the ascending direction from VPL to S1, and the sensory input is suppressed during movement through a bottom-up strategy within the gamma-band during passive movement. PMID:26578892

Control strategy for a dual-arm maneuverable space robot

NASA Technical Reports Server (NTRS)

Wang, P. K. C.

1987-01-01

A simple strategy for the attitude control and arm coordination of a maneuverable space robot with dual arms is proposed. The basic task for the robot consists of the placement of marked rigid solid objects with specified pairs of gripping points and a specified direction of approach for gripping. The strategy consists of three phases each of which involves only elementary rotational and translational collision-free maneuvers of the robot body. Control laws for these elementary maneuvers are derived by using a body-referenced dynamic model of the dual-arm robot.

Exploring the statistical and clinical impact of two interim analyses on the Phase II design with option for direct assignment.

PubMed

An, Ming-Wen; Mandrekar, Sumithra J; Edelman, Martin J; Sargent, Daniel J

2014-07-01

The primary goal of Phase II clinical trials is to understand better a treatment's safety and efficacy to inform a Phase III go/no-go decision. Many Phase II designs have been proposed, incorporating randomization, interim analyses, adaptation, and patient selection. The Phase II design with an option for direct assignment (i.e. stop randomization and assign all patients to the experimental arm based on a single interim analysis (IA) at 50% accrual) was recently proposed [An et al., 2012]. We discuss this design in the context of existing designs, and extend it from a single-IA to a two-IA design. We compared the statistical properties and clinical relevance of the direct assignment design with two IA (DAD-2) versus a balanced randomized design with two IA (BRD-2) and a direct assignment design with one IA (DAD-1), over a range of response rate ratios (2.0-3.0). The DAD-2 has minimal loss in power (<2.2%) and minimal increase in T1ER (<1.6%) compared to a BRD-2. As many as 80% more patients were treated with experimental vs. control in the DAD-2 than with the BRD-2 (experimental vs. control ratio: 1.8 vs. 1.0), and as many as 64% more in the DAD-2 than with the DAD-1 (1.8 vs. 1.1). We illustrate the DAD-2 using a case study in lung cancer. In the spectrum of Phase II designs, the direct assignment design, especially with two IA, provides a middle ground with desirable statistical properties and likely appeal to both clinicians and patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Speckle-free and halo-free low coherent Mach-Zehnder quantitative-phase-imaging module as a replacement of objective lens in conventional inverted microscopes

NASA Astrophysics Data System (ADS)

Yamauchi, Toyohiko; Yamada, Hidenao; Matsui, Hisayuki; Yasuhiko, Osamu; Ueda, Yukio

2018-02-01

We developed a compact Mach-Zehnder interferometer module to be used as a replacement of the objective lens in a conventional inverted microscope (Nikon, TS100-F) in order to make them quantitative phase microscopes. The module has a 90-degree-flipped U-shape; the dimensions of the module are 160 mm by 120 mm by 40 mm and the weight is 380 grams. The Mach-Zehnder interferometer equipped with the separate reference and sample arms was implemented in this U-shaped housing and the path-length difference between the two arms was manually adjustable. The sample under test was put on the stage of the microscope and a sample light went through it. Both arms had identical achromatic lenses for image formation and the lateral positions of them were also manually adjustable. Therefore, temporally and spatially low coherent illumination was applicable because the users were able to balance precisely the path length of the two arms and to overlap the two wavefronts. In the experiment, spectrally filtered LED light for illumination (wavelength = 633 nm and bandwidth = 3 nm) was input to the interferometer module via a 50 micrometer core optical fiber. We have successfully captured full-field interference images by a camera put on the trinocular tube of the microscope and constructed quantitative phase images of the cultured cells by means of the quarter-wavelength phase shifting algorithm. The resultant quantitative phase images were speckle-free and halo-free due to spectrally and spatially low coherent illumination.

Military Education: Implementation of Recommendations at the Armed Forces Staff College. Report to the Chairman, Panel on Military Education, Committee on Armed Services, House of Representatives.

ERIC Educational Resources Information Center

General Accounting Office, Washington, DC. National Security and International Affairs Div.

This study evaluates the Armed Forces Staff College's implementation of selected recommendations from the April 1989 report of the Panel on Military Education. In particular, this report discusses Phase II officer professional military education (PME) programs taught at the Joint and Combined Staff Officer School in Norfolk, Virginia. The study…

Synthesis, spectroscopy, X-ray crystallography, DFT calculations, DNA binding and molecular docking of a propargyl arms containing Schiff base.

PubMed

Balakrishnan, C; Subha, L; Neelakantan, M A; Mariappan, S S

2015-11-05

A propargyl arms containing Schiff base (L) was synthesized by the condensation of 1-[2-hydroxy-4-(prop-2-yn-1-yloxy)phenyl]ethanone with trans-1,2-diaminocyclohexane. The structure of L was characterized by IR, (1)H NMR, (13)C NMR and UV-Vis spectroscopy and by single crystal X-ray diffraction analysis. The UV-Visible spectral behavior of L in different solvents exhibits positive solvatochromism. Density functional calculation of the L in gas phase was performed by using DFT (B3LYP) method with 6-31G basis set. The computed vibrational frequencies and NMR signals of L were compared with the experimental data. Tautomeric stability study inferred that the enolimine is more stable than the ketoamine form. The charge delocalization has been analyzed using natural bond orbital (NBO) analysis. Electronic absorption and emission spectral studies were used to study the binding of L with CT-DNA. The molecular docking was done to identify the interaction of L with A-DNA and B-DNA. Copyright © 2015 Elsevier B.V. All rights reserved.

Phase II randomized trial of carboplatin, paclitaxel, bevacizumab with or without cixutumumab (IMC-A12) in patients with advanced non-squamous, non-small-cell lung cancer: a trial of the ECOG-ACRIN Cancer Research Group (E3508).

PubMed

Argiris, A; Lee, J W; Stevenson, J; Sulecki, M G; Hugec, V; Choong, N W; Saltzman, J N; Song, W; Hansen, R M; Evans, T L; Ramalingam, S S; Schiller, J H

2017-12-01

Cixutumumab is a fully human IgG1 monoclonal antibody to the insulin-like growth factor type I receptor that can potentially reverse resistance and enhance the efficacy of chemotherapy. Bevacizumab-eligible patients with stage IV or recurrent non-squamous, non-small-cell lung cancer and good performance status were randomized to receive standard doses of paclitaxel, carboplatin, and bevacizumab to a maximum of six cycles followed by bevacizumab maintenance (CPB) until progression (arm A) or CPB plus cixutumumab 6 mg/kg i.v. weekly (arm B). Of 175 patients randomized, 153 were eligible and treated (78 in arm A; 75 in arm B). The median progression-free survival was 5.8 months (95% CI 5.4-7.1) in arm A versus 7 months (95% CI 5.7-7.6) in arm B (P = 0.33); hazard ratio 0.92 (95% CI 0.65-1.31). Objective response was 46.2% versus 58.7% in arm A versus arm B (P = 0.15). The median overall survival was 16.2 months in arm A versus 16.1 months in arm B (P = 0.95). Grade 3/4 neutropenia and febrile neutropenia, thrombocytopenia, fatigue, and hyperglycemia were increased with cixutumumab. The addition of cixutumumab to CPB increased toxicity without improving efficacy and is not recommended for further development in non-small-cell lung cancer. Both treatment groups had longer OS than historical controls which may be attributed to several factors, and emphasizes the value of a comparator arm in phase II trials. NCT00955305. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Effectiveness of robot-assisted training added to conventional rehabilitation in patients with humeral fracture early after surgical treatment: protocol of a randomised, controlled, multicentre trial.

PubMed

Nerz, Corinna; Schwickert, Lars; Becker, Clemens; Studier-Fischer, Stefan; Müßig, Janina Anna; Augat, Peter

2017-12-06

The incidence of proximal humeral fractures increases with age. The functional recovery of the upper arm after such fractures is slow, and results are often disappointing. Treatment is associated with long immobilisation periods. Evidence-based exercise guidelines are missing. Loss of muscle mass as well as reduced range of motion and motor performance are common consequences. These losses could be partly counteracted by training interventions using robot-assisted arm support of the affected arm derived from neurorehabilitation. Thus, shorter immobilisation could be reached. Thus far, this approach has been tested in only a few small studies. The aim of the present study is to examine whether assistive robotic training augmenting conventional occupational and physical therapy can improve functional shoulder outcomes. Patients aged between 35 and 66 years with proximal humeral fracture and surgical treatment will be recruited at three different clinics in Germany and randomised into an intervention group and a control group. Participants will be assessed before randomisation and followed after completing an intervention period of 3 weeks and additionally after 3, 6 and 12 months. The baseline assessment will include cognition (Short Orientation-Memory-Concentration Test); level of pain in the affected arm; ability to work; gait speed (10-m walk); disability of the arm, shoulder and hand (Disabilities of the Arm, Shoulder and Hand Outcome Measure [DASH]); range of motion of the affected arm (goniometer measurement); visual acuity; and motor function of orthopaedic patients (Wolf Motor Function Test-Orthopaedic version [WMFT-O]). Clinical follow-up directly after the intervention will include assessment of disability of the arm, shoulder and hand (DASH) as well as range of motion and motor function (WMFT-O). The primary outcome parameter will be the DASH, and the secondary outcome parameter will be the WMFT-O. The long-term results will be assessed prospectively by postal follow-up. All patients will receive conventional occupational and physical therapy. The intervention group will receive additional robot-assisted training using the Armeo®Spring robot for 3 weeks. This study protocol describes a phase II, randomised, controlled, single-blind, multicentre intervention study. The results will guide and possibly improve methods of rehabilitation after proximal humeral fracture. Clinicaltrials.gov, NCT03100201 . Registered on 28 March 2017.

Role of Surgical Versus Clinical Staging in Chemoradiated FIGO Stage IIB-IVA Cervical Cancer Patients-Acute Toxicity and Treatment Quality of the Uterus-11 Multicenter Phase III Intergroup Trial of the German Radiation Oncology Group and the Gynecologic Cancer Group.

PubMed

Marnitz, Simone; Martus, Peter; Köhler, Christhardt; Stromberger, Carmen; Asse, Elke; Mallmann, Peter; Schmidberger, Heinz; Affonso Júnior, Renato José; Nunes, João Soares; Sehouli, Jalid; Budach, Volker

2016-02-01

The Uterus-11 trial was designed to evaluate the role of surgical staging in patients with cervical cancer before primary chemoradiation therapy (CRT). The present report provides the toxicity data stratified by the treatment arm and technique. A total of 255 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics stage IIB-IVA) were randomized to either surgical staging followed by CRT (arm A) or clinical staging followed by CRT (arm B). Patients with para-aortic metastases underwent extended field radiation therapy (RT). Brachytherapy was mandatory. The present report presents the acute therapy-related toxicities stratified by treatment arm and radiation technique. A total of 240 patients were eligible (n=121 in arm A; n=119 in arm B). Of the 240 patients, 236 (98.3%) underwent external beam RT with a median total dose of 50.4 Gy. The mean treatment duration was 53 days. Of the patients, 60% underwent intensity modulated RT (IMRT). A total of 234 patients (97.5%) underwent chemotherapy, and 231 (96.3%) underwent brachytherapy, with a median single dose of 6 Gy covering the tumor to a median nominal total dose of 28 Gy. Treatment was well tolerated, with 0% grade ≥3 genitourinary and gastrointestinal toxicity, 6% grade 3 nausea, 3% grade 3 vomiting, and <2% grade 3 diarrhea. More patients after surgical staging experienced grade 2 anemia (54.3% in arm A vs 45.3% in arm B; P=.074) and grade 2 leukocytopenia (41.4% vs 31.6%; P=.56). Of the patients who received IMRT versus a 3-dimensional technique, 65.3% versus 33.7% presented with grade 2 anemia. Grade 3 gastrointestinal and grade 2 bladder toxicity were significantly reduced with the use of IMRT. The incidence and severity of acute therapy-related toxicity compared favorably with those from other randomized trials. Excellent adherence to treatment and treatment quality was achieved compared with patterns of care analyses. Surgical staging led to a doubled number of patients treated with extended field RT. The question of whether surgical staging is beneficial in the context of primary CRT requires further study. Copyright © 2016 Elsevier Inc. All rights reserved.

Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: Grupo cancer de recto 3 study.

PubMed

Fernández-Martos, Carlos; Pericay, Carles; Aparicio, Jorge; Salud, Antonieta; Safont, Mariajose; Massuti, Bertomeu; Vera, Ruth; Escudero, Pilar; Maurel, Joan; Marcuello, Eugenio; Mengual, Jose Luis; Saigi, Eugenio; Estevan, Rafael; Mira, Moises; Polo, Sonia; Hernandez, Ana; Gallen, Manuel; Arias, Fernando; Serra, Javier; Alonso, Vicente

2010-02-10

PURPOSE The optimal therapeutic sequence of the adjuvant chemotherapy component of preoperative chemoradiotherapy (CRT) for patients with locally advanced rectal cancer is controversial. Induction chemotherapy before preoperative CRT may be associated with better efficacy and compliance. PATIENTS AND METHODS A total of 108 patients with locally advanced rectal cancer were randomly assigned to arm A-preoperative CRT with capecitabine, oxaliplatin, and concurrent radiation followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-induction CAPOX followed by CRT and surgery. The primary end point was pathologic complete response rate (pCR). Results On an intention-to-treat basis, the pCR for arms A and B were 13.5% (95% CI, 5.6% to 25.8%) and 14.3% (95% CI, 6.4% to 26.2%), respectively. There were no statistically significant differences in other end points, including downstaging, tumor regression, and R0 resection. Overall, chemotherapy treatment exposure was higher in arm B than in arm A for both oxaliplatin (P < .0001) and capecitabine (P < .0001). During CRT, grades 3 to 4 adverse events were similar in both arms but were significantly higher in arm A during postoperative adjuvant CT than with induction CT in arm B. There were three deaths in each arm during the treatment period. CONCLUSION Compared with postoperative adjuvant CAPOX, induction CAPOX before CRT had similar pCR and complete resection rates. It did achieve more favorable compliance and toxicity profiles. On the basis of these findings, a phase III study to definitively test the induction strategy is warranted.

Arm to leg coordination in elite butterfly swimmers.

PubMed

Chollet, D; Seifert, L; Boulesteix, L; Carter, M

2006-04-01

This study proposed the use of four time gaps to assess arm-to-leg coordination in the butterfly stroke at increasing race paces. Fourteen elite male swimmers swam at four velocities corresponding to the appropriate paces for, respectively, the 400-m, 200-m, 100-m, and 50-m events. The different stroke phases of the arm and leg were identified by video analysis and then used to calculate four time gaps (T1: time gap between entry of the hands in the water and the high break-even point of the first undulation; T2: time gap between the beginning of the hands' backward movement and the low break-even point of the first undulation; T3: time gap between the hands' arrival in a vertical plane to the shoulders and the high break-even point of the second undulation; T4: time gap between the hands' release from the water and the low break-even point of the second undulation), the values of which described the changing relationship of arm to leg movements over an entire stroke cycle. With increases in pace, elite swimmers increased the stroke rate, the relative duration of the arm pull, the recovery and the first downward movement of the legs, and decreased the stroke length, the relative duration of the arm catch phase and the body glide with arms forward (measured by T2), until continuity in the propulsive actions was achieved. Whatever the paces, the T1, T3, and T4 values were close to zero and revealed a high degree of synchronisation at key motor points of the arm and leg actions. This new method to assess butterfly coordination could facilitate learning and coaching by situating the place of the leg undulation in relation with the arm stroke.

Design of a multi-arm randomized clinical trial with no control arm.

PubMed

Magaret, Amalia; Angus, Derek C; Adhikari, Neill K J; Banura, Patrick; Kissoon, Niranjan; Lawler, James V; Jacob, Shevin T

2016-01-01

Clinical trial designs that include multiple treatments are currently limited to those that perform pairwise comparisons of each investigational treatment to a single control. However, there are settings, such as the recent Ebola outbreak, in which no treatment has been demonstrated to be effective; and therefore, no standard of care exists which would serve as an appropriate control. For illustrative purposes, we focused on the care of patients presenting in austere settings with critically ill 'sepsis-like' syndromes. Our approach involves a novel algorithm for comparing mortality among arms without requiring a single fixed control. The algorithm allows poorly-performing arms to be dropped during interim analyses. Consequently, the study may be completed earlier than planned. We used simulation to determine operating characteristics for the trial and to estimate the required sample size. We present a potential study design targeting a minimal effect size of a 23% relative reduction in mortality between any pair of arms. Using estimated power and spurious significance rates from the simulated scenarios, we show that such a trial would require 2550 participants. Over a range of scenarios, our study has 80 to 99% power to select the optimal treatment. Using a fixed control design, if the control arm is least efficacious, 640 subjects would be enrolled into the least efficacious arm, while our algorithm would enroll between 170 and 430. This simulation method can be easily extended to other settings or other binary outcomes. Early dropping of arms is efficient and ethical when conducting clinical trials with multiple arms. Copyright © 2015 Elsevier Inc. All rights reserved.

Central implementation strategies outperform local ones in improving HIV testing in Veterans Healthcare Administration facilities.

PubMed

Goetz, Matthew Bidwell; Hoang, Tuyen; Knapp, Herschel; Burgess, Jane; Fletcher, Michael D; Gifford, Allen L; Asch, Steven M

2013-10-01

Pilot data suggest that a multifaceted approach may increase HIV testing rates, but the scalability of this approach and the level of support needed for successful implementation remain unknown. To evaluate the effectiveness of a scaled-up multi-component intervention in increasing the rate of risk-based and routine HIV diagnostic testing in primary care clinics and the impact of differing levels of program support. Three arm, quasi-experimental implementation research study. Veterans Health Administration (VHA) facilities. Persons receiving primary care between June 2009 and September 2011 INTERVENTION: A multimodal program, including a real-time electronic clinical reminder to facilitate HIV testing, provider feedback reports and provider education, was implemented in Central and Local Arm Sites; sites in the Central Arm also received ongoing programmatic support. Control Arm sites had no intervention Frequency of performing HIV testing during the 6 months before and after implementation of a risk-based clinical reminder (phase I) or routine clinical reminder (phase II). The adjusted rate of risk-based testing increased by 0.4 %, 5.6 % and 10.1 % in the Control, Local and Central Arms, respectively (all comparisons, p < 0.01). During phase II, the adjusted rate of routine testing increased by 1.1 %, 6.3 % and 9.2 % in the Control, Local and Central Arms, respectively (all comparisons, p < 0.01). At study end, 70-80 % of patients had been offered an HIV test. Use of clinical reminders, provider feedback, education and social marketing significantly increased the frequency at which HIV testing is offered and performed in VHA facilities. These findings support a multimodal approach toward achieving the goal of having every American know their HIV status as a matter of routine clinical practice.

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.

A single-arm phase III study exploring the efficacy and safety of LNG-IUS 8, a low-dose levonorgestrel intrauterine contraceptive system (total content 13.5 mg), in an Asia-Pacific population.

PubMed

Fan, Guangsheng; Kang, Sukho; Ren, Mulan; Weisberg, Edith; Lukkari-Lax, Eeva; Roth, Katrin; Shin, SoYoung

2017-04-01

The objective was to evaluate the efficacy and safety of a low-dose levonorgestrel intrauterine system with total content 13.5 mg (average approximately 8 μg/24 h over the first year; LNG-IUS 8; Jaydess®) in an Asia-Pacific population. An open-label, single-arm phase III study conducted at 25 centers in China, Australia and Korea assessed LNG-IUS 8 use over 3 years in nulliparous and parous women (N=1114) aged 18-40 years with regular menstrual cycles (21-35 days). Primary outcome was pregnancy rate, expressed as the Pearl Index. Secondary outcomes included 3-year cumulative failure rate, treatment-emergent adverse events (TEAEs), discontinuation rate, bleeding profile and placement pain. The full analysis set comprised 925 women (mean age 31.6 years, 6.4% nulliparous). Overall unadjusted Pearl Index was 0.35 (95% confidence interval 0.15-0.70); the 3-year cumulative failure rate was 0.9% (95% confidence interval 0.4-1.9). TEAEs and study drug-related TEAEs were reported in 70.1% and 31.2% of women, respectively. Overall, 27.9% of women discontinued the study, 16.9% due to adverse events. Frequent or prolonged bleeding (World Health Organization criteria) decreased from the first to the twelfth 90-day reference intervals (from 5.0% to 0.7% and from 44.1% to 3.0%, respectively), and the percentage of women with amenorrhea increased over time (from 0.4% to 10.8%). Pain on placement was reported as "none" or "mild" in 91.9% of women. LNG-IUS 8 was an effective and well-tolerated contraceptive method, providing another option for women in the Asia-Pacific region. In this phase III study, LNG-IUS 8 was shown to be highly effective and well tolerated in an Asia-Pacific population and was not associated with any new or unexpected safety events. LNG-IUS 8 provides another contraceptive option for women in the Asia-Pacific region. Copyright © 2016. Published by Elsevier Inc.

Primary reaction control system/remote manipulator system interaction with loaded arm. Space shuttle engineering and operations support

NASA Technical Reports Server (NTRS)

Taylor, E. C.; Davis, J. D.

1978-01-01

A study of the interaction between the orbiter primary reaction control system (PRCS) and the remote manipulator system (RMS) with a loaded arm is documented. This analysis was performed with the Payload Deployment and Retrieval Systems Simulation (PDRSS) program with the passive arm bending option. The passive-arm model simulates the arm as massless elastic links with locked joints. The study was divided into two parts. The first part was the evaluation of the response of the arm to step inputs (i.e. constant jet torques) about each of the orbiter body axes. The second part of the study was the evaluation of the response of the arm to minimum impulse primary RCS jet firings with both single pulse and pulse train inputs.

Analysis of phase II methodologies for single-arm clinical trials with multiple endpoints in rare cancers: An example in Ewing’s sarcoma

PubMed Central

Dutton, P; Love, SB; Billingham, L; Hassan, AB

2016-01-01

Trials run in either rare diseases, such as rare cancers, or rare sub-populations of common diseases are challenging in terms of identifying, recruiting and treating sufficient patients in a sensible period. Treatments for rare diseases are often designed for other disease areas and then later proposed as possible treatments for the rare disease after initial phase I testing is complete. To ensure the trial is in the best interests of the patient participants, frequent interim analyses are needed to force the trial to stop promptly if the treatment is futile or toxic. These non-definitive phase II trials should also be stopped for efficacy to accelerate research progress if the treatment proves to be particularly promising. In this paper, we review frequentist and Bayesian methods that have been adapted to incorporate two binary endpoints and frequent interim analyses. The Eurosarc Trial of Linsitinib in advanced Ewing Sarcoma (LINES) is used as a motivating example and provides a suitable platform to compare these approaches. The Bayesian approach provides greater design flexibility, but does not provide additional value over the frequentist approaches in a single trial setting when the prior is non-informative. However, Bayesian designs are able to borrow from any previous experience, using prior information to improve efficiency. PMID:27587590

Extrinsic fiber optic displacement sensors and displacement sensing systems

DOEpatents

Murphy, K.A.; Gunther, M.F.; Vengsarkar, A.M.; Claus, R.O.

1994-04-05

An extrinsic Fizeau fiber optic sensor comprises a single-mode fiber, used as an input/output fiber, and a multimode fiber, used purely as a reflector, to form an air gap within a silica tube that acts as a Fizeau cavity. The Fresnel reflection from the glass/air interface at the front of the air gap (reference reflection) and the reflection from the air/glass interface at the far end of the air gap (sensing reflection) interfere in the input/output fiber. The two fibers are allowed to move in the silica tube, and changes in the air gap length cause changes in the phase difference between the reference reflection and the sensing reflection. This phase difference is observed as changes in intensity of the light monitored at the output arm of a fused biconical tapered coupler. The extrinsic Fizeau fiber optic sensor behaves identically whether it is surface mounted or embedded, which is unique to the extrinsic sensor in contrast to intrinsic Fabry-Perot sensors. The sensor may be modified to provide a quadrature phase shift extrinsic Fizeau fiber optic sensor for the detection of both the amplitude and the relative polarity of dynamically varying strain. The quadrature light signals may be generated by either mechanical or optical means. A plurality of the extrinsic sensors may connected in cascade and multiplexed to allow monitoring by a single analyzer. 14 figures.

Extrinsic fiber optic displacement sensors and displacement sensing systems

DOEpatents

Murphy, Kent A.; Gunther, Michael F.; Vengsarkar, Ashish M.; Claus, Richard O.

1994-01-01

An extrinsic Fizeau fiber optic sensor comprises a single-mode fiber, used as an input/output fiber, and a multimode fiber, used purely as a reflector, to form an air gap within a silica tube that acts as a Fizeau cavity. The Fresnel reflection from the glass/air interface at the front of the air gap (reference reflection) and the reflection from the air/glass interface at the far end of the air gap (sensing reflection) interfere in the input/output fiber. The two fibers are allowed to move in the silica tube, and changes in the air gap length cause changes in the phase difference between the reference reflection and the sensing reflection. This phase difference is observed as changes in intensity of the light monitored at the output arm of a fused biconical tapered coupler. The extrinsic Fizeau fiber optic sensor behaves identically whether it is surface mounted or embedded, which is unique to the extrinsic sensor in contrast to intrinsic Fabry-Perot sensors. The sensor may be modified to provide a quadrature phase shift extrinsic Fizeau fiber optic sensor for the detection of both the amplitude and the relative polarity of dynamically varying strain. The quadrature light signals may be generated by either mechanical or optical means. A plurality of the extrinsic sensors may connected in cascade and multiplexed to allow monitoring by a single analyzer.

The influence of polymer architecture on the assembly of poly(ethylene oxide) grafted C60 fullerene clusters in aqueous solution: a molecular dynamics simulation study.

PubMed

Hooper, Justin B; Bedrov, Dmitry; Smith, Grant D

2009-03-28

The effect of polymer architecture on the aggregation behavior of C60 fullerenes tethered with a single chain of poly(ethylene oxide) (PEO) in aqueous solution has been investigated using coarse-grained, implicit solvent molecular dynamics simulations. The PEO-grafted fullerenes were comprised of a single tether of 60 repeat units represented as a linear polymer, a three-arm star (20 repeat units/arm) or a six-arm star (10 repeat units/arm). Additionally, the influence of arm length on self-assembly of the PEO-fullerene conjugates was investigated for the three-arm stars. Self-assembly is driven by favorable fullerene-fullerene and fullerene-PEO interactions. Our simulations reveal that it should be possible to control the size and geometry of the self-assembled fullerene aggregates in water through variation of PEO architecture and PEO molecular weight. We found that aggregate size and shape could be understood qualitatively in terms of the packing parameter concept that has been employed for diblock polymer and surfactant self-assembly. Higher molecular weight PEO (longer arms) and more compact PEO (more arms for the same molecular weight) resulted in greater steric repulsion between fullerenes, engendering greater aggregate surface curvature and hence the formation of smaller, more spherically shaped aggregates. Finally, weak attractive interactions between PEO and the fullerenes were found to play an important role in determining aggregate shape, size and the dynamics of self-assembly.

Stress Management and Resiliency Training (SMART) program among Department of Radiology faculty: a pilot randomized clinical trial.

PubMed

Sood, Amit; Sharma, Varun; Schroeder, Darrell R; Gorman, Brian

2014-01-01

To test the efficacy of a Stress Management and Resiliency Training (SMART) program for decreasing stress and anxiety and improving resilience and quality of life among Department of Radiology physicians. The study was approved by the institutional review board. A total of 26 Department of Radiology physicians were randomized in a single-blind trial to either the SMART program or a wait-list control arm for 12 weeks. The program involved a single 90-min group session in the SMART training with two follow-up phone calls. Primary outcomes measured at baseline and week 12 included the Perceived Stress Scale, Linear Analog Self-Assessment Scale, Mindful Attention Awareness Scale, and Connor-Davidson Resilience Scale. A total of 22 physicians completed the study. A statistically significant improvement in perceived stress, anxiety, quality of life, and mindfulness at 12 weeks was observed in the study arm compared to the wait-list control arm; resilience also improved in the active arm, but the changes were not statistically significant when compared to the control arm. A single session to decrease stress among radiologists using the SMART program is feasible. Furthermore, the intervention afforded statistically significant and clinically meaningful improvement in anxiety, stress, quality of life, and mindful attention. Further studies including larger sample size and longer follow-up are warranted. Copyright © 2014. Published by Elsevier Inc.

Neuromuscular-skeletal origins of predominant patterns of coordination in rhythmic two-joint arm movement.

PubMed

de Rugy, Aymar; Riek, Stephan; Carson, Richard G

2006-01-01

The authors tested for predominant patterns of coordination in the combination of rhythmic flexion-extension (FE) and supination- (SP) at the elbow-joint complex. Participants (N=10) spontaneously established in-phase (supination synchronized with flexion) and antiphase (pronation synchronized with flexion) patterns. In addition, the authors used a motorized robot arm to generate involuntary SP movements with different phase relations with respect to voluntary FE. The involuntarily induced in-phase pattern was accentuated and was more consistent than other patterns. The result provides evidence that the predominance of the in-phase pattern originates in the influence of neuromuscular-skeletal constraints rather than in a preference dictated by perceptual-cognitive factors implicated in voluntary control. Neuromuscular-skeletal constraints involved in the predominance of the in-phase and the antiphase patterns are discussed.

Butterfly Sprint Swimming Technique, Analysis of Somatic and Spatial-Temporal Coordination Variables

PubMed Central

Stanula, Arkadiusz; Krężałek, Piotr; Ostrowski, Andrzej; Kaca, Marcin; Głąb, Grzegorz

2017-01-01

Abstract The aim of this study was to investigate somatic properties and force production of leg extensor muscles measured in the countermovement jump test (CMJ), as well as to analyse kinematic variables of sprint surface butterfly swimming. Thirty-four male competitive swimmers were recruited with an average age of 19.3 ± 1.83 years. Their average body height (BH) was 183.7 ± 5.93 cm, body fat content 10.8 ± 2.64% and body mass (BM) 78.3 ± 5.0 kg. Length measurements of particular body segments were taken and a counter movement jump (CMJ) as well as an all-out 50 m butterfly speed test were completed. The underwater movements of the swimmers’ bodies were recorded with a digital camera providing side-shots. We registered a significant relationship between body mass (r = 0.46), lean body mass (r = 0.48) and sprint surface butterfly swimming (VSBF). The anaerobic power measured in the CMJ test, total body length (TBL) as well as upper and lower extremity length indices did not influence swimming speed significantly. The temporal entry-kick index (the time ratio between the first kick and arm entry) significantly influenced VSBF (r = -0.45). Similarly, medium power of the coefficient was indicated between a) stroke rate kinematics (SR), b) duration of the first leg kick (LP1), c) air phase duration of arm recovery (Fly-arm), and VSBF (r = 0.40; r = 0.40 and r = 0.41, respectively). The entry-kick temporal index showed that, in the butterfly cycle, an appropriately early executed initial kick when compared to arm entry was associated with a longer arm propulsion phase, which in turn was associated with minimizing resistive gliding phases and enabled relatively longer and less resistive air arm recovery (higher value of the fly-arm index). The higher value of SR kinematic was another important element of the best butterfly results in this study. PMID:29339985

Fighting fire with fire: attacking the complexity of human tumors with armed therapeutic viruses.

PubMed

Hermiston, Terry

2002-08-01

Cancer gene therapies have centered on the use of a single gene, directed against a particular property or single aspect of tumor biology, to treat neoplastic disease. These therapies have met with limited clinical success. This is, perhaps, not surprising given the complex and heterogeneous nature of solid tumors. Treatments targeted at confronting multiple dimensions of human tumors are needed. Armed therapeutic viruses (oncolytic viruses carrying therapeutic genes) represent a system where the concerted action of multiple therapeutics can be joined into a single agent, and represent a promising avenue for developing future cancer therapies.

Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study.

PubMed

Giaccone, Giuseppe; Kim, Chul; Thompson, Jillian; McGuire, Colleen; Kallakury, Bhaskar; Chahine, Joeffrey J; Manning, Maria; Mogg, Robin; Blumenschein, Wendy M; Tan, Ming T; Subramaniam, Deepa S; Liu, Stephen V; Kaplan, Ian M; McCutcheon, Justine N

2018-03-01

Treatment options are limited for patients with thymic carcinoma. These aggressive tumours are not typically associated with paraneoplastic autoimmune disorders, and strong PD-L1 expression has been reported in thymic epithelial tumours. We aimed to assess the activity of pembrolizumab, a monoclonal antibody that targets PD-1, in patients with advanced thymic carcinoma. We completed a single-arm phase 2 study of pembrolizumab in patients with recurrent thymic carcinoma who had progressed after at least one line of chemotherapy. This was a single-centre study performed at Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. Key inclusion criteria were an Eastern Cooperative Oncology Group performance status of 0-2, no history of autoimmune disease or other malignancy requiring treatment or laboratory abnormality, and adequate organ function. Patients received 200 mg of pembrolizumab every 3 weeks for up to 2 years. The primary objective of the study was the proportion of patients who had achieved a response assessed with Response Evaluation Criteria in Solid Tumors version 1.1. Analysis was per protocol, in all eligible patients. The study is registered with ClinicalTrials.gov, number NCT02364076, and is closed to accrual; we report the final analysis. 41 patients were enrolled from March 12, 2015, to Dec 16, 2016, of whom 40 were eligible and evaluable and one was excluded because of elevated liver enzymes at screening. The median follow-up was 20 months (IQR 14-26). The proportion of patients who achieved a response was 22·5% (95% CI 10·8-38·5); one (3%) patient achieved a complete response, eight (20%) patients achieved partial responses, and 21 (53%) patients achieved stable disease. The most common grade 3 or 4 adverse events were increased aspartate aminotransferase and alanine aminotransferase (five [13%] patients each). Six (15%) patients developed severe autoimmune toxicity, including two (5%) patients with myocarditis. There were 17 deaths at the time of analysis, but no deaths due to toxicity. Pembrolizumab is a promising treatment option in patients with thymic carcinoma. Because severe autoimmune disorders are more frequent in thymic carcinoma than in other tumour types, careful monitoring is essential. Merck & Co. Copyright © 2018 Elsevier Ltd. All rights reserved.

Group refractive index reconstruction with broadband interferometric confocal microscopy

PubMed Central

Marks, Daniel L.; Schlachter, Simon C.; Zysk, Adam M.; Boppart, Stephen A.

2010-01-01

We propose a novel method of measuring the group refractive index of biological tissues at the micrometer scale. The technique utilizes a broadband confocal microscope embedded into a Mach–Zehnder interferometer, with which spectral interferograms are measured as the sample is translated through the focus of the beam. The method does not require phase unwrapping and is insensitive to vibrations in the sample and reference arms. High measurement stability is achieved because a single spectral interferogram contains all the information necessary to compute the optical path delay of the beam transmitted through the sample. Included are a physical framework defining the forward problem, linear solutions to the inverse problem, and simulated images of biologically relevant phantoms. PMID:18451922

A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN).

PubMed

Bellmunt, J; Kerst, J M; Vázquez, F; Morales-Barrera, R; Grande, E; Medina, A; González Graguera, M B; Rubio, G; Anido, U; Fernández Calvo, O; González-Billalabeitia, E; Van den Eertwegh, A J M; Pujol, E; Perez-Gracia, J L; González Larriba, J L; Collado, R; Los, M; Maciá, S; De Wit, R

2017-07-01

Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second lines. Vinflunine is the only treatment approved in this setting by the European Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy versus vinflunine. This is a multicenter, randomized, open-label, phase II/III study, following a Simon's optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II. ECOG Performance Status, anaemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and overall survival for the phase III. Seventy patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and six patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median progression-free survival for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P = 0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found favouring vinflunine (median 7.6 versus 5.5 months). Grade 3- to 4-related adverse events were seen in 41% patients with no difference between the two arms. This phase II/III second line bladder study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those known previously. NCT01830231. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

All optical coherent receiver for self-homodyne detection of digitally phase modulated optical signals

NASA Astrophysics Data System (ADS)

Kiasaleh, Kamran

1994-02-01

A novel optical phase-locked loop (OPLL) system for the self-homodyne detection of digitally phase modulated optical signals is introduced. A Mach-Zehnder type interferometer is used to self-homodyne binary phase-modulated optical signals with an external phase modulator inserted in the control arm of the interferometer.

Phase transition of social learning collectives and the echo chamber.

PubMed

Mori, Shintaro; Nakayama, Kazuaki; Hisakado, Masato

2016-11-01

We study a simple model for social learning agents in a restless multiarmed bandit. There are N agents, and the bandit has M good arms that change to bad with the probability q_{c}/N. If the agents do not know a good arm, they look for it by a random search (with the success probability q_{I}) or copy the information of other agents' good arms (with the success probability q_{O}) with probabilities 1-p or p, respectively. The distribution of the agents in M good arms obeys the Yule distribution with the power-law exponent 1+γ in the limit N,M→∞, and γ=1+(1-p)q_{I}/pq_{O}. The system shows a phase transition at p_{c}=q_{I}/q_{I}+q_{o}. For pp_{c}), the variance of N_{1} per agent is finite (diverges as ∝N^{2-γ} with N). There is a threshold value N_{s} for the system size that scales as lnN_{s}∝1/(γ-1). The expected value of the number of the agents with a good arm N_{1} increases with p for N>N_{s}. For p>p_{c} and N

Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A

PubMed Central

Mahlangu, Johnny; Powell, Jerry S.; Ragni, Margaret V.; Chowdary, Pratima; Josephson, Neil C.; Pabinger, Ingrid; Hanabusa, Hideji; Gupta, Naresh; Kulkarni, Roshni; Fogarty, Patrick; Perry, David; Shapiro, Amy; Pasi, K. John; Apte, Shashikant; Nestorov, Ivan; Jiang, Haiyan; Li, Shuanglian; Neelakantan, Srividya; Cristiano, Lynda M.; Goyal, Jaya; Sommer, Jurg M.; Dumont, Jennifer A.; Dodd, Nigel; Nugent, Karen; Vigliani, Gloria; Luk, Alvin; Brennan, Aoife

2014-01-01

This phase 3 pivotal study evaluated the safety, efficacy, and pharmacokinetics of a recombinant FVIII Fc fusion protein (rFVIIIFc) for prophylaxis, treatment of acute bleeding, and perioperative hemostatic control in 165 previously treated males aged ≥12 years with severe hemophilia A. The study had 3 treatment arms: arm 1, individualized prophylaxis (25-65 IU/kg every 3-5 days, n = 118); arm 2, weekly prophylaxis (65 IU/kg, n = 24); and arm 3, episodic treatment (10-50 IU/kg, n = 23). A subgroup compared recombinant FVIII (rFVIII) and rFVIIIFc pharmacokinetics. End points included annualized bleeding rate (ABR), inhibitor development, and adverse events. The terminal half-life of rFVIIIFc (19.0 hours) was extended 1.5-fold vs rFVIII (12.4 hours; P < .001). Median ABRs observed in arms 1, 2, and 3 were 1.6, 3.6, and 33.6, respectively. In arm 1, the median weekly dose was 77.9 IU/kg; approximately 30% of subjects achieved a 5-day dosing interval (last 3 months on study). Across arms, 87.3% of bleeding episodes resolved with 1 injection. Adverse events were consistent with those expected in this population; no subjects developed inhibitors. rFVIIIFc was well-tolerated, had a prolonged half-life compared with rFVIII, and resulted in low ABRs when dosed prophylactically 1 to 2 times per week. This trial was registered at www.clinicaltrials.gov as #NCT01181128. PMID:24227821

Imaging Organ of Corti Vibration Using Fourier-Domain OCT

NASA Astrophysics Data System (ADS)

Choudhury, Niloy; Chen, Fangyi; Fridberger, Anders; Zha, Dingjun; Jacques, Steven L.; Wang, Ruikang K.; Nuttall, Alfred L.

2011-11-01

Measuring the sound stimulated vibration from various structures in the organ of Corti is important in understanding how the small vibrations are amplified and detected. In this study we examine the feasibility of using phase-sensitive Fourier domain optical coherence tomography (PSFD-OCT) to measure vibration of the cellular structures of the organ of Corti. PSFD-OCT is a low coherence interferrometry system where the interferrogram is detected as a function of wavelength. The phase of the Fourier transformation of the detected spectra contains path deference (between the sample arm and the reference arm) information of the interferometer. In PSFD-OCT this phase is measured as a function of time and thus any time dependent change in the path difference between the sample arm and the reference arm can be detected. In the experiment, we used an in vitro preparation of the guinea pig cochlea and made a surgical opening at the apical end to access the organ of Corti. By applying tones with different frequencies via the intact middle ear, we recorded the structural vibration inside the organ of Corti. Vibration amplitude and phase of different substructures were mapped on a cross-section view of the organ of Corti. Although the measurements were made at the apical turn of the cochlea, it will be possible to make vibration measurement from various turns of the cochlea. The noise floor of the system was 0.3 nm, calibrated using a piezo stack as a calibrator.

A Randomized Multicenter Phase III Study of Single Administration of Mecapegfilgrastim (HHPG-19K), a Pegfilgrastim Biosimilar, for Prophylaxis of Chemotherapy-Induced Neutropenia in Patients With Advanced Non-Small-Cell Lung Cancer (NSCLC).

PubMed

Zhou, Caicun; Huang, Yunchao; Wang, Donglin; An, Changshan; Zhou, Fuxiang; Li, Yali; Chen, Gongyan; Wu, Changping; He, Jianxing; Wu, Gang; Song, Xia; Gao, Jianfei; Liu, Wei; Li, Baolan; Shi, Jianhua; Huang, Cheng; Yu, Jingrui; Feng, Jueping; Yue, Hongmei; Shi, Meiqi; Xia, Jielai

2016-03-01

Mecapegfilgrastim (code name HHPG-19K) is a biosimilar to pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF). The efficacy and safety of mecapegfilgrastim, using a regimen of once-per-cycle injection of 100-μg/kg or a fixed 6-mg dose, were evaluated for the prophylactic therapy for neutropenia in patients with advanced non-small-cell lung cancer (NSCLC) who were treated with myelosuppressive chemotherapy. Patients were randomized (1:1:1) blindly to 3 treatment arms to receive a single injection of mecapegfilgrastim 100 μg/kg, a 6-mg fixed dose of mecapegfilgrastim, or saline (control) in cycle 1. In cycles 2 to 4 following unblinding at the end of cycle 1, patients in the control arm received daily injections of short-acting rhG-CSF at a dose of 5 μg/kg, whereas patients in the 2 mecapegfilgrastim arms continued the same treatment as in cycle 1. All patients received 4 chemotherapy cycles of docetaxel combined with cisplatin or carboplatin every 21 days. The primary endpoint was the incidence of grade ≥ 3 neutropenia in cycle 1. A single dose of 100 μg/kg or a fixed 6-mg dose of mecapegfilgrastim per cycle effectively reduced chemotherapy-induced neutropenia and was comparable to daily rhG-CSF with regard to all efficacy endpoints, including incidence of grade ≥ 3 neutropenia, incidence of febrile neutropenia, duration of grade ≥ 3 neutropenia, and time to neutrophil recovery. No difference in efficacy parameters was observed between the 2-dose regimens of mecapegfilgrastim across all cycles. Mecapegfilgrastim was well-tolerated and was as safe as daily rhG-CSF. Once-per-cycle injection of mecapegfilgrastim is as effective and safe as daily rhG-CSF for prophylaxis of chemotherapy-induced neutropenia in patients with NSCLC. Mecapegfilgrastim (fixed 6-mg dose) is recommended in clinical practice for its convenient dose management. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Coordination of rapid stepping with arm pointing: anticipatory changes and step adaptation.

PubMed

Yiou, Eric; Schneider, Cyril; Roussel, Didier

2007-06-01

The present study explored whether rapid stepping is influenced by the coordination of an arm pointing task. Nine participants were instructed to (a) point the index finger of the dominant arm towards a target from the standing posture, (b) initiate a rapid forward step with the contralateral leg, and (c) synchronize stepping and pointing (combined task). Force plate and ankle muscle electromyography (EMG) recordings were contrasted between (b) and (c). In the combined task, the arm acceleration trace most often peaked around foot-off, coinciding with a 15% increase in the forward acceleration of the center of gravity (CoG). Backward displacement of the center of foot pressure at foot-off, duration of anticipatory postural adjustments (APAs) and ankle muscle EMG activity remained unchanged. In contrast, durations of swing phase and whole step were reduced and step length was smaller in the combined task. A reduction in the swing phase was correlated with an increased CoG forward acceleration at foot-off. Changes in the biomechanics of step initiation during the combined task might be ascribed to the postural dynamics elicited by arm pointing, and not to a modulation of the step APAs programming.

A Phase II Study of the Central European Society of Anticancer-Drug Research (CESAR) Group: Results of an Open-Label Study of Gemcitabine plus Cisplatin with or without Concomitant or Sequential Gefitinib in Patients with Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium.

PubMed

Miller, Kurt; Morant, Rudolf; Stenzl, Arnulf; Zuna, Ivan; Wirth, Manfred

2016-01-01

This phase II trial evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, in combination with first-line chemotherapy in advanced urothelial cancer. Chemotherapy-naïve patients with advanced or metastatic urothelial carcinoma were randomized 1:1:1 to receive six cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8, and cisplatin 70 mg/m2 on day 1 of every cycle) concomitantly with gefitinib 250 mg/day (arm A); or with sequential gefitinib (arm B); or alone (arm C). The primary endpoint was the time to progression (TTP). A total of 105 patients received study treatment. Median TTP for arms A, B, and C were 6.1, 6.3, and 7.8 months, respectively. There were no significant differences between treatment arms for any outcomes measured. The most common adverse events were nausea and vomiting. Gefitinib in combination with chemotherapy did not improve efficacy in advanced urothelial cancer. © 2015 S. Karger AG, Basel.

Effect of an Arm Swing on Countermovement Vertical Jump Performance in Elite Volleyball Players: FINAL.

PubMed

Vaverka, Frantisek; Jandačka, Daniel; Zahradník, David; Uchytil, Jaroslav; Farana, Roman; Supej, Matej; Vodičar, Janez

2016-12-01

The aim of this study was to determine how elite volleyball players employed the arm swing (AS) to enhance their jump performance. The study assessed how the AS influenced the duration and magnitude of the vertical ground reaction force (VGRF) during the main phases (preparatory, braking and accelerating) of the countermovement vertical jump (CMVJ), the starting position of the body at the beginning of the accelerating phase and the moment when the AS began contributing to increasing the jump height. Eighteen elite volleyball players performed three CMVJs with and without an AS. Kinetics and kinematics data were collected using two Kistler force plates and the C-motion system. The time and force variables were evaluated based on the VGRF, and the position of the body and the trajectory of the arm movement were determined using kinematic analysis. The AS improved the CMVJ by increasing the jump height by 38% relative to jumping without an AS. The AS significantly shortened the braking phase and prolonged the accelerating phase, however, it did not influence the preparatory phase or the overall jump duration. The AS also significantly increased the average force during the accelerating phase as well as the accelerating impulse. The AS upward began at 76% into the overall jump duration. The AS did not influence the body position at the beginning of the accelerating phase. These findings can be used to improve performance of the CMVJ with the AS and in teaching beginning volleyball players proper jumping technique.

Starbursts and Wispy Drops : Surfactants Spreading on Gel Substrates

NASA Astrophysics Data System (ADS)

Mukhopadhyay, Shomeek; Daniels, Karen; Behringer, Robert

2005-11-01

We report a phase diagram for a novel instability seen in drops of nonionic surfactant solution (Triton X-305) spreading on viscoelastic agar gel substrate . This system allows us to examine the effect of varying the effective fluidity/stiffness of aqueous substrates. The morphology is strongly affected by the substrate fluidity, ranging from spreading starbursts of arms on weak gels, to wispy drops on intermediate strength gels, to circular drops on stiff gels. We analyze the dynamics of spreading in the starburst phase, where the arm length grows as t ^3/4 at early times, independent of the gel strength and surfactant concentration. The number of arms is proportional to the surfactant concentration and inversely proportional to the gel strength. Ongoing work is exploring the effects of changing the drop volume.

Arms Control, Disarmament, and Peace Newsletters.

ERIC Educational Resources Information Center

Atkins, Stephen

1986-01-01

Considers the research value of four types of newsletters on arms control, disarmament, and peace: direct-action, informational, scholarly, and single-issue. An annotated list of 58 newsletters includes those considered most significant of their type and recommended for library collections. (EM)

Influence of French Air Power Strategy in the European Union’s Military Operations in Africa (2003-2009)

DTIC Science & Technology

2011-06-01

Patrick Facon, Histoire de l’Armée de l’Air, provides the context of French operations in Africa in the broadest history of the French Air Force. 3 In...during the 2000s, including its 3 Patrick Facon, Histoire de L’armée de L’air (Paris: La...34, 8. 5 Facon, Histoire de L’armée de L’air, 451. 6 Facon, Histoire de L’armée de L’air, 458. The third phase began in 1994 after the Rwanda

Microstrip Antennas with Broadband Integrated Phase Shifting

NASA Technical Reports Server (NTRS)

Bernhard, Jennifer T.; Romanofsky, Robert R. (Technical Monitor)

2001-01-01

The goal of this research was to investigate the feasibility of using a spiral microstrip antenna that incorporates a thin ferroelectric layer to achieve both radiation and phase shifting. This material is placed between the conductive spiral antenna structure and the grounded substrate. Application of a DC bias between the two arms of the spiral antenna will change the effective permittivity of the radiating structure and the degree of coupling between contiguous spiral arms, therefore changing the phase of the RF signal transmitted or received by the antenna. This could eliminate the need for a separate phase shifter apart from the antenna structure. The potential benefits of such an antenna element compared to traditional phased array elements include: continuous, broadband phase shifting at the antenna, lower overall system losses, lighter, more efficient, and more compact phased arrays, and simpler control algorithms. Professor Jennifer Bernhard, graduate student Gregory Huff, and undergraduate student Brian Huang participated in this effort from March 1, 2000 to February 28, 2001. No inventions resulted from the research undertaken in this cooperative agreement.

Control of nausea with palonosetron versus granisetron, both combined with dexamethasone, in patients receiving cisplatin- or anthracycline plus cyclophosphamide-based regimens.

PubMed

Kubota, Kaoru; Saito, Mitsue; Aogi, Kenjiro; Sekine, Ikuo; Yoshizawa, Hirohisa; Yanagita, Yasuhiro; Sakai, Hiroshi; Inoue, Kenichi; Kitagawa, Chiyoe; Ogura, Takashi

2016-09-01

In a comparative phase 3 study involving 1114 Japanese patients receiving highly emetogenic chemotherapy (HEC), palonosetron (PALO) was found to be superior to granisetron (GRA) for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in the delayed phase. This post hoc analysis of the phase 3 study evaluated the efficacy of PALO for the control of nausea. The proportion of patients without nausea was assessed at 24-h intervals during the acute phase (0-24 h), delayed phase (24-120 h), and overall (0-120 h). No nausea rates were also evaluated by sex, type of chemotherapy (cisplatin or doxorubicin/epirubicin plus cyclophosphamide [AC/EC]), and age (<55 vs. ≥55 years). Nausea severity was categorized using a 4-point Likert scale (0 = no nausea to 3 = severe nausea). The proportion of patients without nausea was significantly higher in the PALO arm than in the GRA arm in the delayed phase (37.8 % vs. 27.2 %; p = 0.002) and overall (31.9 % vs. 25.0 %; p = 0.0117). When analyzed by stratification factors, the proportion of patients without nausea was significantly higher in the PALO arm in the delayed phase and overall in patients who were female, younger, or treated with cisplatin and in the delayed phase in patients who were older or treated with doxorubicin or epirubicin plus cyclophosphamide (all p < 0.05). PALO was more effective than GRA in prophylaxis of HEC-induced nausea in the delayed phase and overall. In addition, PALO was more effective than GRA in young and female patients, who are at high risk of CINV, both in the delayed phase and overall.

Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE: a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma.

PubMed

Baertsch, Marc-Andrea; Schlenzka, Jana; Mai, Elias K; Merz, Maximilian; Hillengaß, Jens; Raab, Marc S; Hose, Dirk; Wuchter, Patrick; Ho, Anthony D; Jauch, Anna; Hielscher, Thomas; Kunz, Christina; Luntz, Steffen; Klein, Stefan; Schmidt-Wolf, Ingo G H; Goerner, Martin; Schmidt-Hieber, Martin; Reimer, Peter; Graeven, Ullrich; Fenk, Roland; Salwender, Hans; Scheid, Christof; Nogai, Axel; Haenel, Mathias; Lindemann, Hans W; Martin, Hans; Noppeney, Richard; Weisel, Katja; Goldschmidt, Hartmut

2016-04-25

Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients. ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and--in absence of available stem cells from earlier harvesting--undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3(rd) (arm A + B) and the 5(th) lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary endpoints include overall survival (OS), RR, time to best response and the influence of early versus late salvage high dose chemotherapy plus autologous stem cell transplantation on OS. This phase III trial is designed to evaluate whether high dose chemotherapy plus autologous stem cell transplantation and lenalidomide maintenance after lenalidomide/dexamethasone induction improves PFS compared with the well-established continued lenalidomide/dexamethasone regimen in RMM patients. ISRCTN16345835 (date of registration 2010-08-24).

The microstructure and fracture behavior of the dissimilar alloy 690-SUS 304L joint with various Nb addition

NASA Astrophysics Data System (ADS)

Lee, H. T.; Jeng, S. L.; Kuo, T. Y.

2003-05-01

This study investigates the microstructure and fracture behavior of dissimilar weldments of alloy 690 and SUS 304L for various additions of niobium (0.1, 1.03, 2.49, and 3.35 wt pct) in the flux. With identical parameters and procedures, weldments were butt welded by the shielding metal arc welding (SMAW) process using three layers, with each layer being deposited in a single pass. The results indicate that the microstructure of the fusion zone was primarily dendritic and that the contents of Ni, Cr, and Fe within this zone remain relatively constant and resemble alloy 690. With Nb addition, it is noted that the microstructure changes from a cellular to columnar dendrite and equiaxed dendrite. Meanwhile, the dendrite arm spacing reduces and the secondary arms grow longer. Moreover, the composition of the interdendritic phase, whose precipitate volume percentage increases from 5 to 25 pct, changes from Al-Ti-O to Nb rich. The spread of the interdendritic phase is less in the root bead than in the cap bead due to the greater influence of base metal dilution in this region. Mechanical tests indicate that Nb addition increases the average hardness of the weldment and reduces its elongation prior to rupture. However, the tensile strength is essentially unchanged by Nb addition. It is found that the average hardness of the root bead is generally lower than the cap bead, and that the tensile specimens all rupture in the fusion zone, with the fracture surfaces exhibiting ductile features. It is noted that the cap bead tends to rupture interdendritically with increasing Nb addition. Finally, fractography shows that the dimples in the root become larger and shallower with Nb addition and are rich with an interdendritic phase.

Randomized, phase II study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 in patients with advanced soft tissue sarcoma.

PubMed

Baker, Laurence H; Rowinsky, Eric K; Mendelson, David; Humerickhouse, Rod A; Knight, Raymond A; Qian, Jiang; Carr, Robert A; Gordon, Gary B; Demetri, George D

2008-12-01

Sarcomas are among the most proangiogenic malignancies in preclinical models. Phase I study results for ABT-510, which inhibits angiogenesis via a novel thrombospondin-mimetic mechanism, suggested activity in soft tissue sarcoma (STS) patients. This phase II study further evaluated the safety and efficacy of ABT-510 in advanced STS patients. Patients with metastatic or unresectable STS were randomly assigned to treatment with one of two ABT-510 dose schedules (20 mg once a day [20 mg], n = 42; or 100 mg twice a day [200 mg], n = 46), which were self-administered subcutaneously in 28-day treatment periods. End points included progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and safety. Median PFS for the 20-mg arm was 94 days, with 4- and 6-month PFS rate estimates of 42% and 24%, respectively. Median PFS for the 200-mg arm was 64 days, with 4- and 6-month PFS rate estimates of 41% and 32%, respectively. Although only one objective response was noted, stable disease was observed in 52% (20 mg) and 48% (200 mg) of patients. Median OS was 431 days (20 mg) and 295 days (200 mg). ABT-510 was well tolerated. Rare treatment-related grade 3 or 4 adverse events were one event each of hypotension, deep vein thrombosis, and hypophosphatemia. ABT-510 pharmacokinetics were dose proportional, time independent, and consistent with those in previous studies. ABT-510 had a favorable safety profile, and the rate of disease control and OS times were encouraging. However, with low ORR and lack of dose response, the study failed to yield compelling evidence of strong single-agent activity in STS.

Phase II trial of pirfenidone in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas.

PubMed

Widemann, Brigitte C; Babovic-Vuksanovic, Dusica; Dombi, Eva; Wolters, Pamela L; Goldman, Stewart; Martin, Staci; Goodwin, Anne; Goodspeed, Wendy; Kieran, Mark W; Cohen, Bruce; Blaney, Susan M; King, Allison; Solomon, Jeffrey; Patronas, Nicholas; Balis, Frank M; Fox, Elizabeth; Steinberg, Seth M; Packer, Roger J

2014-09-01

Pirfenidone, an oral anti-inflammatory, antifibrotic agent with activity in idiopathic pulmonary fibrosis, may mediate anti-tumor activity in neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PN) by inhibition of fibroblast proliferation and collagen synthesis. The primary objective of this open label, single arm phase II trial was to evaluate the activity of pirfenidone in children and young adults with inoperable PN. Patients (3-21 years) with NF1-related progressive PN received pirfenidone at the previously determined optimal dose (500 mg/m(2) orally, q8h) on a continuous dosing schedule (one cycle = 28 days). Volumetric MRI analysis was used to assess response. Progression was defined as ≥ 20% PN volume increase compared to baseline. Pirfenidone would be considered active if it doubled the median time to progression (TTP) compared to the TTP on the placebo arm of a phase II trial with the farnesyltransferase inhibitor tipifarnib, which used near identical eligibility criteria. Toxicities, objective response rate, and quality of life (QOL) also were evaluated. Thirty-six patients were enrolled and tolerated pirfenidone well with intermittent nausea and vomiting as the most frequent toxicities. A dose reduction was required in only three patients. The median TTP for pirfenidone was 13.2 months compared to 10.6 months for the placebo control group from the tipifarnib trial (two-tailed P = 0.92; one-tailed P = 0.46). No objective responses were observed. Pirfenidone was well tolerated, but did not demonstrate activity as defined in this trial and does not warrant further evaluation in children with NF1 and progressive PN. © 2014 Wiley Periodicals, Inc.

Spectral-domain low-coherence interferometry for phase-sensitive measurement of Faraday rotation at multiple depths.

PubMed

Yeh, Yi-Jou; Black, Adam J; Akkin, Taner

2013-10-10

We describe a method for differential phase measurement of Faraday rotation from multiple depth locations simultaneously. A polarization-maintaining fiber-based spectral-domain interferometer that utilizes a low-coherent light source and a single camera is developed. Light decorrelated by the orthogonal channels of the fiber is launched on a sample as two oppositely polarized circular states. These states reflect from sample surfaces and interfere with the corresponding states of the reference arm. A custom spectrometer, which is designed to simplify camera alignment, separates the orthogonal channels and records the interference-related oscillations on both spectra. Inverse Fourier transform of the spectral oscillations in k-space yields complex depth profiles, whose amplitudes and phase difference are related to reflectivity and Faraday rotation within the sample, respectively. Information along a full depth profile is produced at the camera speed without performing an axial scan for a multisurface sample. System sensitivity for the Faraday rotation measurement is 0.86 min of arc. Verdet constants of clear liquids and turbid media are measured at 687 nm.

Galactic Spiral Shocks with Thermal Instability in Vertically Stratified Galactic Disks

NASA Astrophysics Data System (ADS)

Kim, Chang-Goo; Kim, Woong-Tae; Ostriker, Eve C.

2010-09-01

Galactic spiral shocks are dominant morphological features and believed to be responsible for substructure formation within spiral arms in disk galaxies. They can also contribute a substantial amount of kinetic energy to the interstellar gas by tapping the (differential) rotational motion. We use numerical hydrodynamic simulations to investigate dynamics and structure of spiral shocks with thermal instability (TI) in vertically stratified galactic disks, focusing on environmental conditions (of heating and the galactic potential) similar to the Solar neighborhood. We initially consider an isothermal disk in vertical hydrostatic equilibrium and let it evolve subject to interstellar cooling and heating as well as a stellar spiral potential. Due to TI, a disk with surface density Σ0 >= 6.7 M sun pc-2 rapidly turns to a thin dense slab near the midplane sandwiched between layers of rarefied gas. The imposed spiral potential leads to a vertically curved shock that exhibits strong flapping motions in the plane perpendicular to the arm. The overall flow structure at saturation is comprised of the arm, postshock expansion zone, and interarm regions that occupy typically 10%, 20%, and 70% of the arm-to-arm distance, in which the gas resides for 15%, 30%, and 55% of the arm-to-arm crossing time, respectively. The flows are characterized by transitions from rarefied to dense phases at the shock and from dense to rarefied phases in the postshock expansion zone, although gas with too-large postshock-density does not undergo this return phase transition, instead forming dense condensations. If self-gravity is omitted, the shock flapping drives random motions in the gas, but only up to ~2-3 km s-1 in the in-plane direction and less than 2 km s-1 in the vertical direction. Time-averaged shock profiles show that the spiral arms in stratified disks are broader and less dense compared to those in unstratified models, and that the vertical density distribution is overall consistent with local effective hydrostatic equilibrium. Inclusion of self-gravity increases the dense gas fraction by a factor of ~2 and raises the in-plane velocity dispersion to ~5-7 km s-1. When the disks are massive enough, with Σ0 >= 5 M sun pc-2, self-gravity promotes formation of bound clouds that repeatedly collide with each other in the arm and break up in the postshock expansion zone.

Docetaxel Alone or in Combination With a Therapeutic Cancer Vaccine (PANVAC) in Patients With Metastatic Breast Cancer: A Randomized Clinical Trial.

PubMed

Heery, Christopher R; Ibrahim, Nuhad K; Arlen, Philip M; Mohebtash, Mahsa; Murray, James L; Koenig, Kimberly; Madan, Ravi A; McMahon, Sheri; Marté, Jennifer L; Steinberg, Seth M; Donahue, Renee N; Grenga, Italia; Jochems, Caroline; Farsaci, Benedetto; Folio, Les R; Schlom, Jeffrey; Gulley, James L

2015-11-01

Previous phase 1 and 2 trials of PANVAC, a poxviral-based cancer vaccine, have suggested clinical efficacy in some patients with breast, ovarian, and colorectal cancer and have shown evidence of immunologic activity. Preclinical data have shown that docetaxel can modify tumor phenotype, making tumor cells more amenable to T cell-mediated killing. The goal of this study was to determine if the treatment combination of docetaxel and PANVAC improves clinical outcomes in patients with metastatic breast cancer compared with docetaxel treatment alone. Between May 2006 and February 2012, this open-label, phase 2 randomized clinical trial enrolled 48 patients with metastatic breast cancer of all subtypes, without limitation on other lines of previous therapy, to receive treatment with either docetaxel with PANVAC (arm A) or docetaxel alone (arm B). Final clinical data were collected on September 16, 2013. All patients were treated at either the National Cancer Institute or the Department of Breast Medical Oncology, MD Anderson Cancer Center. The primary end point was progression-free survival (PFS), using a phase 2.5 statistical design, with the intent of identifying a trend toward benefit (defined as 1-sided P≤.10) to guide a larger trial design. Secondary end points included safety and immunologic correlative studies. Forty-eight participants were enrolled: 25 were randomized to the combination treatment arm A, and 23 to arm B. No patient remained in the study at the time of the final analysis. Patient and tumor characteristics were well matched. Analysis of adverse events in both treatment arms demonstrated very little difference between the 2 groups. In the combination treatment arm (arm A), statistically significant increases were noted in the frequency of grades 1 and 2 edema (P=.02, likely related to greater median number of docetaxel cycles) and injection-site reactions (P<.001). In the final data analysis, median PFS was 7.9 months in arm A vs 3.9 months in arm B (hazard ratio, 0.65 [95% CI, 0.34-1.14]; P=.09). The results suggest that the combination of PANVAC with docetaxel in metastatic breast cancer may provide a clinical benefit. This study was hypothesis generating and provides both rationale and statistical assumptions for a larger definitive randomized study. clinicaltrials.gov Identifier: NCT00179309.

A randomized phase II study comparing paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches in patients with stage IV nonsquamous nonsmall-cell lung cancer: NVALT12 (NCT01171170)†.

PubMed

Dingemans, A-M C; Groen, H J M; Herder, G J M; Stigt, J A; Smit, E F; Bahce, I; Burgers, J A; van den Borne, B E E M; Biesma, B; Vincent, A; van der Noort, V; Aerts, J G

2015-11-01

Nitroglycerin (NTG) increases tumor blood flow and oxygenation by inhibiting hypoxia-inducible-factor (HIF)-1. A randomized phase II study has shown improved outcome when NTG patches were added to vinorelbine/cisplatin in patients with advanced nonsmall-cell lung cancer (NSCLC). In addition, there is evidence that the combination of bevacizumab and HIF-1 inhibitors increases antitumor activity. In this randomized phase II trial, chemo-naive patients with stage IV nonsquamous NSCLC were randomized to four cycles of carboplatin (area under the curve 6)-paclitaxel (200 mg/m(2))-bevacizumab 15 mg/kg on day 1 every 3 weeks with or without NTG patches 15 mg (day -2 to +2) followed by bevacizumab with or without NTG until progression. Response was assessed every two cycles. Primary end point was progression-free survival (PFS). The study was powered (80%) to detect a decrease in the hazard of tumor progression of 33% at α = 0.05 with a two-sided log-rank test when 222 patients were enrolled and followed until 195 events were observed. Between 1 January 2011 and 1 January 2013, a total of 223 patients were randomized; 112 control arm and 111 experimental arm; response rate was 54% in control arm and 38% in experimental arm. Median [95% confidence interval (CI)] PFS in control arm was 6.8 months (5.6-7.3) and 5.1 months (4.2-5.8) in experimental arm, hazard ratio (HR) 1.27 (95% CI 0.96-1.67). Overall survival (OS) was 11.6 months (8.8-13.6) in control arm and 9.4 months (7.8-11.3) in experimental arm, HR 1.02 (95% CI 0.71-1.46). In the experimental arm, no additional toxicity was observed except headache (6% versus 52% in patients treated with NTG). Adding NTG to first-line carboplatin-paclitaxel-bevacizumab did not improve PFS and OS in patients with stage IV nonsquamous NSCLC. © 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.

Flexural Stiffness of Myosin Va Subdomains as Measured from Tethered Particle Motion

PubMed Central

Michalek, Arthur J.; Kennedy, Guy G.; Warshaw, David M.; Ali, M. Yusuf

2015-01-01

Myosin Va (MyoVa) is a processive molecular motor involved in intracellular cargo transport on the actin cytoskeleton. The motor's processivity and ability to navigate actin intersections are believed to be governed by the stiffness of various parts of the motor's structure. Specifically, changes in calcium may regulate motor processivity by altering the motor's lever arm stiffness and thus its interhead communication. In order to measure the flexural stiffness of MyoVa subdomains, we use tethered particle microscopy, which relates the Brownian motion of fluorescent quantum dots, which are attached to various single- and double-headed MyoVa constructs bound to actin in rigor, to the motor's flexural stiffness. Based on these measurements, the MyoVa lever arm and coiled-coil rod domain have comparable flexural stiffness (0.034 pN/nm). Upon addition of calcium, the lever arm stiffness is reduced 40% as a result of calmodulins potentially dissociating from the lever arm. In addition, the flexural stiffness of the full-length MyoVa construct is an order of magnitude less stiff than both a single lever arm and the coiled-coil rod. This suggests that the MyoVa lever arm-rod junction provides a flexible hinge that would allow the motor to maneuver cargo through the complex intracellular actin network. PMID:26770194

Validation of the Omron M6 (HEM-7001-E) upper arm blood pressure measuring device according to the International Protocol in elderly patients.

PubMed

Altunkan, Sekip; Iliman, Nevzat; Altunkan, Erkan

2008-04-01

Despite the widespread use of automated self-measurement monitors, there is limited published evidence on their accuracy and reliability on different patient groups. The objective of this study was to evaluate the accuracy and reliability of the Omron M6 (HEM-7001-E) upper-arm blood pressure (BP) device against mercury sphygmomanometer on elderly patients according to the criteria of the International Protocol. Thirty-three patients above 65 years of age, who were classified based on the BP categories of the International Protocol, were recruited for the study. BP measurements at the upper arm with the Omron M6 were compared with the results obtained by two trained observers using a mercury sphygmomanometer. Nine sequential BP measurements were taken. During the validation study, 99 measurements were obtained from 33 patients for comparison. The first phase was carried out on 15 patients and if the device passed this phase, 18 more patients were selected. Mean discrepancies and standard deviations of the device sphygmomanometer were 1.4+/-5.3 mmHg for systolic BP (SBP) and -1.4+/-4.5 mmHg for diastolic BP (DBP) in the study group. The device passed phase 1 in 15 patients. In phase 2.1, from the total 99 comparisons, 76, 92, and 97 for SBP and 77, 94, and 99 for DBP were less than 5, 10, and 15 mmHg, respectively. The Omron M6 passed phases 2.1 and 2.2 in the elderly group of patients. The Omron M6 (HEM-7001-E) upper-arm BP monitor passed according to the International Protocol criteria and can be recommended for use in elderly patients.

A 19-Month Climatology of Marine Aerosol-Cloud-Radiation Properties Derived From DOE ARM AMF Deployment at the Azores: Part I: Cloud Fraction and Single-Layered MBL Cloud Properties

NASA Technical Reports Server (NTRS)

Dong, Xiquan; Xi, Baike; Kennedy, Aaron; Minnis, Patrick; Wood, Robert

2013-01-01

A 19-month record of total, and single-layered low (0-3 km), middle (3-6 km), and high (> 6 km) cloud fractions (CFs), and the single-layered marine boundary layer (MBL) cloud macrophysical and microphysical properties has been generated from ground-based measurements taken at the ARM Azores site between June 2009 and December 2010. It documents the most comprehensive and longest dataset on marine cloud fraction and MBL cloud properties to date. The annual means of total CF, and single-layered low, middle, and high CFs derived from ARM radar-lidar observations are 0.702, 0.271, 0.01 and 0.106, respectively. More total and single-layered high CFs occurred during winter, while single-layered low CFs were greatest during summer. The diurnal cycles for both total and low CFs are stronger during summer than during winter. The CFs are bimodally distributed in the vertical with a lower peak at approx. 1 km and higher one between 8 and 11 km during all seasons, except summer, when only the low peak occurs. The persistent high pressure and dry conditions produce more single-layered MBL clouds and fewer total clouds during summer, while the low pressure and moist air masses during winter generate more total and multilayered-clouds, and deep frontal clouds associated with midlatitude cyclones.

Noninvasive lifting of arm, thigh, and knee skin with transcutaneous intense focused ultrasound.

PubMed

Alster, Tina S; Tanzi, Elizabeth L

2012-05-01

Transcutaneous intense focused ultrasound is a novel Food and Drug Administration-approved technology for noninvasive skin tightening of the face and neck. No studies have reported on its safety and effectiveness on nonfacial areas. Eighteen paired areas (6 each) on the upper arms, medial thighs, and extensor knees were randomly treated with two different transducers (4.0 MHz, 4.5-mm focal depth and 7.0 MHz, 3.0-mm focal depth). One side was randomly assigned to receive a single pass (single plane) of microthermal coagulation zones over the involved area with the 4.0 MHz, 4.5-mm-depth transducer, and the contralateral side was assigned to receive consecutive single passes (dual plane) using both transducers (4.0 MHz, 4.5-mm depth followed by 7.0 MHz, 3.0-mm depth). Two independent masked assessors determined clinical improvement scores using comparative standardized photographs obtained at baseline and 3 and 6 months after treatment. Subjective assessments of clinical improvement and side effects of treatment were obtained. Global assessment scores revealed significant improvement in all treated areas, with the upper arms and knees demonstrating more skin lifting and tightening than the thighs. Areas receiving dual-plane treatment had slightly better clinical scores than those receiving single-plane treatment in all three sites. Clinical scores from single-plane and dual-plane treated areas continued to improve between 3 and 6 months after treatment. Side effects were mild and transient and included erythema, warmth, and skin tenderness. Rare focal bruising was noted in two patients on the upper arms that resolved within 7 days. No other side effects were reported or observed. Transcutaneous intense focused ultrasound can be safely and effectively used to improve the clinical appearance (texture and contour) of the upper arms, extensor knees, and medial thighs. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Super-global distortion correction for a rotational C-arm x-ray image intensifier.

PubMed

Liu, R R; Rudin, S; Bednarek, D R

1999-09-01

Image intensifier (II) distortion changes as a function of C-arm rotation angle because of changes in the orientation of the II with the earth's or other stray magnetic fields. For cone-beam computed tomography (CT), distortion correction for all angles is essential. The new super-global distortion correction consists of a model to continuously correct II distortion not only at each location in the image but for every rotational angle of the C arm. Calibration bead images were acquired with a standard C arm in 9 in. II mode. The super-global (SG) model is obtained from the single-plane global correction of the selected calibration images with given sampling angle interval. The fifth-order single-plane global corrections yielded a residual rms error of 0.20 pixels, while the SG model yielded a rms error of 0.21 pixels, a negligibly small difference. We evaluated the accuracy dependence of the SG model on various factors, such as the single-plane global fitting order, SG order, and angular sampling interval. We found that a good SG model can be obtained using a sixth-order SG polynomial fit based on the fifth-order single-plane global correction, and that a 10 degrees sampling interval was sufficient. Thus, the SG model saves processing resources and storage space. The residual errors from the mechanical errors of the x-ray system were also investigated, and found comparable with the SG residual error. Additionally, a single-plane global correction was done in the cylindrical coordinate system, and physical information about pincushion distortion and S distortion were observed and analyzed; however, this method is not recommended due to a lack of calculational efficiency. In conclusion, the SG model provides an accurate, fast, and simple correction for rotational C-arm images, which may be used for cone-beam CT.

Impairment-oriented training or Bobath therapy for severe arm paresis after stroke: a single-blind, multicentre randomized controlled trial.

PubMed

Platz, T; Eickhof, C; van Kaick, S; Engel, U; Pinkowski, C; Kalok, S; Pause, M

2005-10-01

To study the effects of augmented exercise therapy time for arm rehabilitation as either Bobath therapy or the impairment-oriented training (Arm BASIS training) in stroke patients with arm severe paresis. Single blind, multicentre randomized control trial. Three inpatient neurorehabilitation centres. Sixty-two anterior circulation ischaemic stroke patients. Random assignment to three group: (A) no augmented exercise therapy time, (B) augmented exercise therapy time as Bobath therapy and (C) augmented exercise therapy time as Arm BASIS training. Fugl-Meyer arm motor score. Secondary measure: Action Research Arm Test (ARA). Ancillary measures: Fugl-Meyer arm sensation and joint motion/pain scores and the Ashworth Scale (elbow flexors). An overall effect of augmented exercise therapy time on Fugl-Meyer scores after four weeks was not corroborated (mean and 95% confidence interval (CI) of change scores: no augmented exercise therapy time (n=20) 8.8, 5.2-12.3; augmented exercise therapy time (n=40) 9.9, 6.8-13.9; p = 0.2657). The group who received the augmented exercise therapy time as Arm BASIS training (n=20) had, however, higher gains than the group receiving the augmented exercise therapy time as Bobath therapy (n=20) (mean and 95% CI of change scores: Bobath 7.2, 2.6-11.8; BASIS 12.6, 8.4-16.8; p = 0.0432). Passive joint motion/pain deteriorated less in the group who received BASIS training (mean and 95% CI of change scores: Bobath -3.2, -5.2 to -1.1; BASIS 0.1, -1.8-2.0; p = 0.0090). ARA, Fugl-Meyer arm sensation, and Ashworth Scale scores were not differentially affected. The augmented exercise therapy time as Arm BASIS training enhanced selective motor control. Type of training was more relevant for recovery of motor control than therapeutic time spent.

HBOC-201 as an alternative to blood transfusion: efficacy and safety evaluation in a multicenter phase III trial in elective orthopedic surgery.

PubMed

Jahr, Jonathan S; Mackenzie, Colin; Pearce, L Bruce; Pitman, Arkadiy; Greenburg, A Gerson

2008-06-01

The ability of hemoglobin based oxygen carrier-201 (HBOC-201) to safely reduce and/or eliminate perioperative transfusion was studied in orthopedic surgery patients. A randomized, single-blind, packed red blood cell (PRBC)-controlled, parallel-group multicenter study was conducted. Six hundred eighty-eight patients were randomized to treatment with HBOC-201 (H, n = 350) or PRBC (R, n = 338) at the first transfusion decision. Primary endpoints were transfusion avoidance and blinded assessment [Mann-Whitney estimator (MW)] of safety noninferiority. Groups were compared directly and by paired/matching group analyses predicated on a prospectively defined dichotomy [treatment success (HH) vs. failure (HR)] in the H arm and an equivalently defined dichotomy [3 (R3+) units PRBC] in the R arm, based on need (moderate vs. high) for additional oxygen carrying capacity. A total of 59.4% of patients in the H arm avoided PRBC transfusion. Adverse events (8.47 vs. 5.88), and serious adverse events (SAEs) (0.35 vs. 0.25) per patient were higher in the H versus R arms (p < 0.001 and p < 0.01) with MW = 0.561 (95 CI 0.528-0.594). HH versus R3- had identical (0.14) serious adverse events/patient and a MW = 0.519 (95% confidence limit 0.481-0.558), whereas the incidence was higher (0.63 vs. 0.47) for HR versus R3+ with a MW = 0.605 (95% confidence limit 0.550-0.662). Age (>80 years), volume overload and undertreatment contributed to this imbalance. HBOC-201 eliminated transfusion in the majority of subjects. The between arms (H vs. R) safety analysis was unfavorable and likely related to patient age, volume overload, and undertreatment and was isolated to patients that could not be managed by HBOC-201 alone. However, patients <80 years old with moderate clinical need may safely avoid transfusion when treated with up to 10 units of HBOC-201.

Early manifestation of arm-leg coordination during stepping on a surface in human neonates.

PubMed

La Scaleia, Valentina; Ivanenko, Y; Fabiano, A; Sylos-Labini, F; Cappellini, G; Picone, S; Paolillo, P; Di Paolo, A; Lacquaniti, F

2018-04-01

The accomplishment of mature locomotor movements relies upon the integrated coordination of the lower and upper limbs and the trunk. Human adults normally swing their arms and a quadrupedal limb coordination persists during bipedal walking despite a strong corticospinal control of the upper extremities that allows to uncouple this connection during voluntary activities. Here we investigated arm-leg coordination during stepping responses on a surface in human neonates. In eight neonates, we found the overt presence of alternating arm-leg oscillations, the arms moving up and down in alternation with ipsilateral lower limb movements. These neonates moved the diagonal limbs together, and the peak of the arm-to-trunk angle (i.e., maximum vertical excursion of the arm) occurred around the end of the ipsilateral stance phase, as it occurs during typical adult walking. Although episodes of arm-leg coordination were sporadic in our sample of neonates, their presence provides significant evidence for a neural coupling between the upper and lower limbs during early ontogenesis of locomotion in humans.

Arm motion coupling during locomotion-like actions: An experimental study and a dynamic model

PubMed Central

Shapkova, E.Yu; Terekhov, A.V.; Latash, M.L.

2010-01-01

We studied the coordination of arm movements in standing persons who performed an out-of-phase arm-swinging task while stepping in place or while standing. The subjects were instructed to stop one of the arms in response to an auditory signal while trying to keep the rest of the movement pattern unchanged. A significant increase was observed in the amplitude of the arm that continued swinging under both the stepping and standing conditions. This increase was similar between the right and left arms. A dynamic model was developed including two coupled non-linear van der Pol oscillators. We assumed that stopping an arm did not eliminate the coupling but introduced a new constraint. Within the model, superposition of two factors, a command to stop the ongoing movement of one arm and the coupling between the two oscillators, has been able to account for the observed effects. The model makes predictions for future experiments. PMID:21628725

Prospective randomized phase II study of FOLFIRI versus FOLFOX7 in advanced gastric adenocarcinoma: a Chinese Western Cooperative Gastrointestinal Oncology Group Study

PubMed Central

Qiu, Meng; Liu, Jiyan; Chen, Jing; Yi, Cheng; Li, Zhiping; Luo, Deyun; Xu, Feng; Cai, Xiaohong; Bi, Feng

2017-01-01

Until now, no standard chemotherapy has been widely accepted for advanced gastric cancer (GC). The current research aimed to compare folinic acid, fluorouracil with irinotecan (mFOLFIRI) or with oxaliplatin (mFOLFOX7) as first-line treatments in patients with locally advanced GC in an open, randomized, phase II study. Previously untreated metastatic or recurrent GC patients with measurable disease received mFOLFIRI (arm A) or mFOLFOX7 (arm B) every 2 weeks. The defined second-line treatment was mFOLFOX7 for arm A and mFOLFIRI for arm B. Primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), disease control rate (DCR) and toxicity. The evaluable population consisted of 128 patients (54 in arm A; 74 in arm B). Median PFS of arm A was 2.9 months (m) (95% confidence interval, CI, 1.9 to 4.1 m) versus 4.1 m (95% CI, 3.2 to 4.8 m) for arm B (p = 0.109). Median OS was 9.9 months (95% CI, 6.0 to 13.5 m) for arm A versus 12.0 m for arm B (95% CI, 10.3 to 13.7m; p = 0.431). DCRs for arm A and arm B were 59.3% and 66.3%, respectively (p = 0.850). In subgroup analysis of the patients who completed both treatment lines per protocol, the median first-line PFS was 2.1 m for the mFOLFIRI/mFOLFOX7arm versus 8.0 m for the mFOLFOX7/mFOLFIRI arm (p = 0.053), and the median second-line PFS values were 1.2 m versus 5.1 m (p = 0.287). Total PFS and OS were 8.1m and 11.0 m for the mFOLFIRI/mFOLFOX7 group compared with 12.2m and 20.2 m for the mFOLFOX7/mFOLFIRI group (p = 0.008, p = 0.030). Both regimens were well-tolerated with acceptable and manageable toxicities. Hence, there was no significant difference in the PFS or DCR. However, mFOLFOX7 followed by mFOLFIRI might have a better OS. PMID:29228659

Prospective randomized phase II study of FOLFIRI versus FOLFOX7 in advanced gastric adenocarcinoma: a Chinese Western Cooperative Gastrointestinal Oncology Group Study.

PubMed

Li, Qiu; Wen, Feng; Zhou, Chengya; Qiu, Meng; Liu, Jiyan; Chen, Jing; Yi, Cheng; Li, Zhiping; Luo, Deyun; Xu, Feng; Cai, Xiaohong; Bi, Feng

2017-11-17

Until now, no standard chemotherapy has been widely accepted for advanced gastric cancer (GC). The current research aimed to compare folinic acid, fluorouracil with irinotecan (mFOLFIRI) or with oxaliplatin (mFOLFOX7) as first-line treatments in patients with locally advanced GC in an open, randomized, phase II study. Previously untreated metastatic or recurrent GC patients with measurable disease received mFOLFIRI (arm A) or mFOLFOX7 (arm B) every 2 weeks. The defined second-line treatment was mFOLFOX7 for arm A and mFOLFIRI for arm B. Primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), disease control rate (DCR) and toxicity. The evaluable population consisted of 128 patients (54 in arm A; 74 in arm B). Median PFS of arm A was 2.9 months (m) (95% confidence interval, CI , 1.9 to 4.1 m) versus 4.1 m (95% CI , 3.2 to 4.8 m) for arm B ( p = 0.109). Median OS was 9.9 months (95% CI , 6.0 to 13.5 m) for arm A versus 12.0 m for arm B (95% CI , 10.3 to 13.7m; p = 0.431). DCRs for arm A and arm B were 59.3% and 66.3%, respectively ( p = 0.850). In subgroup analysis of the patients who completed both treatment lines per protocol, the median first-line PFS was 2.1 m for the mFOLFIRI/mFOLFOX7arm versus 8.0 m for the mFOLFOX7/mFOLFIRI arm ( p = 0.053), and the median second-line PFS values were 1.2 m versus 5.1 m ( p = 0.287). Total PFS and OS were 8.1m and 11.0 m for the mFOLFIRI/mFOLFOX7 group compared with 12.2m and 20.2 m for the mFOLFOX7/mFOLFIRI group ( p = 0.008, p = 0.030). Both regimens were well-tolerated with acceptable and manageable toxicities. Hence, there was no significant difference in the PFS or DCR. However, mFOLFOX7 followed by mFOLFIRI might have a better OS.

Randomized Phase 2 Trial of S1 and Oxaliplatin-Based Chemoradiotherapy With or Without Induction Chemotherapy for Esophageal Cancer

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

Yoon, Dok Hyun; Jang, Geundoo; Department of Internal Medicine, Hallym Medical Center, Hallym University College of Medicine, Seoul

2015-03-01

Purpose: To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer. Patients and Methods: Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m{sup 2} on day 1 and S1 at 40 mg/m{sup 2} twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m{sup 2} on days 1 and 21 and S1 30 mg/m{sup 2} twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), ormore » the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate. Results: A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery. Conclusions: Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.« less

Randomized phase 2 trial of S1 and oxaliplatin-based chemoradiotherapy with or without induction chemotherapy for esophageal cancer.

PubMed

Yoon, Dok Hyun; Jang, Geundoo; Kim, Jong Hoon; Kim, Yong-Hee; Kim, Ji Youn; Kim, Hyeong Ryul; Jung, Hwoon-Yong; Lee, Gin-Hyug; Song, Ho Young; Cho, Kyung-Ja; Ryu, Jin-Sook; Kim, Sung-Bae

2015-03-01

To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer. Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m(2) on day 1 and S1 at 40 mg/m(2) twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m(2) on days 1 and 21 and S1 30 mg/m(2) twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate. A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery. Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate. Copyright © 2015 Elsevier Inc. All rights reserved.

Highly sensitive detection of individual HEAT and ARM repeats with HHpred and COACH.

PubMed

Kippert, Fred; Gerloff, Dietlind L

2009-09-24

HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. A protocol is presented for the identification of individual HEAT or ARM repeats which is straightforward to implement. It provides high sensitivity at a low false positive rate and will therefore greatly enhance the accuracy of predictions of HEAT and ARM domains.

Highly Sensitive Detection of Individual HEAT and ARM Repeats with HHpred and COACH

PubMed Central

Kippert, Fred; Gerloff, Dietlind L.

2009-01-01

Background HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. Methodology and Principal Findings Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. Significance A protocol is presented for the identification of individual HEAT or ARM repeats which is straightforward to implement. It provides high sensitivity at a low false positive rate and will therefore greatly enhance the accuracy of predictions of HEAT and ARM domains. PMID:19777061

Magnitude of blood pressure reduction in the placebo arms of modern hypertension trials: implications for trials of renal denervation.

PubMed

Patel, Hitesh C; Hayward, Carl; Ozdemir, Baris Ata; Rosen, Stuart D; Krum, Henry; Lyon, Alexander R; Francis, Darrel P; di Mario, Carlo

2015-02-01

Early phase studies of novel interventions for hypertension, such as renal sympathetic denervation, are sometimes single-armed (uncontrolled). We explored the wisdom of this by quantifying the blood pressure fall in the placebo arms of contemporary trials of hypertension. We searched Medline up to June 2014 and identified blinded, randomized trials of hypertension therapy in which the control arm received placebo medication or a sham (placebo) procedure. For nonresistant hypertension, we have identified all such trials of drugs licensed by the US Food and Drug Administration since 2000 (5 drugs). This US Food and Drug Administration-related restriction was not applied to resistant hypertension trials. This produced 7451 patients, who were allocated to a blinded control from 52 trials of nonresistant hypertension and 694 patients from 8 trials of resistant hypertension (3 drugs and 2 interventions). Systolic blood pressure fell by 5.92 mm Hg (95% confidence interval, 5.14-6.71; P<0.0001) in the nonresistant cohort and by 8.76 mm Hg (95% confidence interval, 4.83-12.70; P<0.0001) in the resistant cohort. Using metaregression, the falls were larger in trials that did not use ambulatory blood pressure monitoring as an inclusion criterion (z=2.84; P=0.0045), in those with higher baseline blood pressures (z=-0.3; P=0.0001), and in those where the patients were prescribed a continuous background of antihypertensives (z=-2.72; P=0.0065). The nontrivial magnitude of these apparent blood pressure reductions with perfectly ineffective intervention (placebo) illustrates that efficacy explorations of novel therapies for hypertension, once safety is established, should be performed with a randomized, appropriately controlled, and blinded design. © 2014 American Heart Association, Inc.

Ferric carboxymaltose with or without erythropoietin for the prevention of red-cell transfusions in the perioperative period of osteoporotic hip fractures: a randomized contolled trial. The PAHFRAC-01 project.

PubMed

Bernabeu-Wittel, Máximo; Aparicio, Reyes; Romero, Manuel; Murcia-Zaragoza, José; Monte-Secades, Rafael; Rosso, Clara; Montero, Abelardo; Ruiz-Cantero, Alberto; Melero-Bascones, María

2012-02-21

Around one third to one half of patients with hip fractures require red-cell pack transfusion. The increasing incidence of hip fracture has also raised the need for this scarce resource. Additionally, red-cell pack transfusions are not without complications which may involve excessive morbidity and mortality. This makes it necessary to develop blood-saving strategies. Our objective was to assess safety, efficacy, and cost-effictveness of combined treatment of i.v. ferric carboxymaltose and erythropoietin (EPOFE arm) versus i.v. ferric carboxymaltose (FE arm) versus a placebo (PLACEBO arm) in reducing the percentage of patients who receive blood transfusions, as well as mortality in the perioperative period of hip fracture intervention. Multicentric, phase III, randomized, controlled, double blinded, parallel groups clinical trial. Patients > 65 years admitted to hospital with a hip fracture will be eligible to participate. Patients will be treated with either a single dosage of i.v. ferric carboxymaltose of 1 g and subcutaneous erythropoietin (40.000 IU), or i.v. ferric carboxymaltose and subcutaneous placebo, or i.v. placebo and subcutaneous placebo. Follow-up will be performed until 60 days after discharge, assessing transfusion needs, morbidity, mortality, safety, costs, and health-related quality of life. Intention to treat, as well as per protocol, and incremental cost-effectiveness analysis will be performed. The number of recruited patients per arm is set at 102, a total of 306 patients. We think that this trial will contribute to the knowledge about the safety and efficacy of ferric carboxymaltose with/without erythropoietin in preventing red-cell pack transfusions in patients with hip fracture. CLINICALTRIALS.GOV IDENTIFIER: NCT01154491.

Equivalent-Groups versus Single-Group Equating Designs for the Accelerated CAT-ASVAB (Computerized Adaptive Test-Armed Services Vocational Aptitude Battery) Project.

DTIC Science & Technology

1987-01-01

DESIGNS FOR THE ACCELERATED CAT -ASVAB * PROJECT Peter H. Stoloff DTIC’- , " SELECTE -NOV 2 3 987 A Division of Hudson Institute CENTER FOR NAVAL ANALYSES...65153M C0031 SI TITLE (Include Security Classification) Equivalent-Groups Versus Single-Group Equating Designs For The Accelerated CAT -ASVAB Project...GROUP ACAP (Accelerated CAT -ASVAB Program), Aptitude tests, ASVAB (Armed 05 10 Services Vocational Aptitude Battery), CAT (Computerized Adaptive Test

Safety, pharmacokinetics, and antitumor response of depatuxizumab mafodotin as monotherapy or in combination with temozolomide in patients with glioblastoma.

PubMed

Gan, Hui K; Reardon, David A; Lassman, Andrew B; Merrell, Ryan; van den Bent, Martin; Butowski, Nicholas; Lwin, Zarnie; Wheeler, Helen; Fichtel, Lisa; Scott, Andrew M; Gomez, Erica J; Fischer, JuDee; Mandich, Helen; Xiong, Hao; Lee, Ho-Jin; Munasinghe, Wijith P; Roberts-Rapp, Lisa A; Ansell, Peter J; Holen, Kyle D; Kumthekar, Priya

2018-05-18

We recently reported an acceptable safety and pharmacokinetic profile of depatuxizumab mafodotin (depatux-m), formerly called ABT-414, plus radiation and temozolomide in newly diagnosed glioblastoma (arm A). The purpose of this study was to evaluate the safety and pharmacokinetics of depatux-m, either in combination with temozolomide in newly diagnosed or recurrent glioblastoma (arm B) or as monotherapy in recurrent glioblastoma (arm C). In this multicenter phase I dose escalation study, patients received depatux-m (0.5-1.5 mg/kg in arm B, 1.25 mg/kg in arm C) every 2 weeks by intravenous infusion. Maximum tolerated dose (MTD), recommended phase II dose (RP2D), and preliminary efficacy were also determined. Thirty-eight patients were enrolled as of March 1, 2016. The most frequent toxicities were ocular, occurring in 35/38 (92%) patients. Keratitis was the most common grade 3 adverse event observed in 6/38 (16%) patients; thrombocytopenia was the most common grade 4 event seen in 5/38 (13%) patients. The MTD was set at 1.5 mg/kg in arm B and was not reached in arm C. RP2D was declared as 1.25 mg/kg for both arms. Depatux-m demonstrated a linear pharmacokinetic profile. In recurrent glioblastoma patients, the progression-free survival (PFS) rate at 6 months was 30.8% and the median overall survival was 10.7 months. Best Response Assessment in Neuro-Oncology responses were 1 complete and 2 partial responses. Depatux-m alone or in combination with temozolomide demonstrated an acceptable safety and pharmacokinetic profile in glioblastoma. Further studies are currently under way to evaluate its efficacy in newly diagnosed (NCT02573324) and recurrent glioblastoma (NCT02343406).

Phase I Trial of Aflibercept (VEGF Trap) with Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients with High-Grade Gliomas

PubMed Central

Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred WK; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

2017-01-01

Background Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor (PlGF), depleting circulating levels of these growth factors. Methods The Adult Brain Tumor Consortium (ABTC) conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed high-grade gliomas (HGG) with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Results Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4mg/kg every 2 weeks. Dose limiting toxicities (DLTs) at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. Conclusions This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4mg/kg every 2 weeks. PMID:28116649

Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas.

PubMed

Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred W K; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

2017-03-01

Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor, depleting circulating levels of these growth factors. The Adult Brain Tumor Consortium conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed HGG with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4 mg/kg every 2 weeks. Dose limiting toxicities at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients) (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4 mg/kg every 2 weeks.

Proprioceptive Interaction between the Two Arms in a Single-Arm Pointing Task.

PubMed

Kigawa, Kazuyoshi; Izumizaki, Masahiko; Tsukada, Setsuro; Hakuta, Naoyuki

2015-01-01

Proprioceptive signals coming from both arms are used to determine the perceived position of one arm in a two-arm matching task. Here, we examined whether the perceived position of one arm is affected by proprioceptive signals from the other arm in a one-arm pointing task in which participants specified the perceived position of an unseen reference arm with an indicator paddle. Both arms were hidden from the participant's view throughout the study. In Experiment 1, with both arms placed in front of the body, the participants received 70-80 Hz vibration to the elbow flexors of the reference arm (= right arm) to induce the illusion of elbow extension. This extension illusion was compared with that when the left arm elbow flexors were vibrated or not. The degree of the vibration-induced extension illusion of the right arm was reduced in the presence of left arm vibration. In Experiment 2, we found that this kinesthetic interaction between the two arms did not occur when the left arm was vibrated in an abducted position. In Experiment 3, the vibration-induced extension illusion of one arm was fully developed when this arm was placed at an abducted position, indicating that the brain receives increased proprioceptive input from a vibrated arm even if the arm was abducted. Our results suggest that proprioceptive interaction between the two arms occurs in a one-arm pointing task when the two arms are aligned with one another. The position sense of one arm measured using a pointer appears to include the influences of incoming information from the other arm when both arms were placed in front of the body and parallel to one another.

Proprioceptive Interaction between the Two Arms in a Single-Arm Pointing Task

PubMed Central

Kigawa, Kazuyoshi; Izumizaki, Masahiko; Tsukada, Setsuro; Hakuta, Naoyuki

2015-01-01

Proprioceptive signals coming from both arms are used to determine the perceived position of one arm in a two-arm matching task. Here, we examined whether the perceived position of one arm is affected by proprioceptive signals from the other arm in a one-arm pointing task in which participants specified the perceived position of an unseen reference arm with an indicator paddle. Both arms were hidden from the participant’s view throughout the study. In Experiment 1, with both arms placed in front of the body, the participants received 70–80 Hz vibration to the elbow flexors of the reference arm (= right arm) to induce the illusion of elbow extension. This extension illusion was compared with that when the left arm elbow flexors were vibrated or not. The degree of the vibration-induced extension illusion of the right arm was reduced in the presence of left arm vibration. In Experiment 2, we found that this kinesthetic interaction between the two arms did not occur when the left arm was vibrated in an abducted position. In Experiment 3, the vibration-induced extension illusion of one arm was fully developed when this arm was placed at an abducted position, indicating that the brain receives increased proprioceptive input from a vibrated arm even if the arm was abducted. Our results suggest that proprioceptive interaction between the two arms occurs in a one-arm pointing task when the two arms are aligned with one another. The position sense of one arm measured using a pointer appears to include the influences of incoming information from the other arm when both arms were placed in front of the body and parallel to one another. PMID:26317518

Effects of a High Magnetic Field on the Microstructure of Ni-Based Single-Crystal Superalloys During Directional Solidification

NASA Astrophysics Data System (ADS)

Xuan, Weidong; Lan, Jian; Liu, Huan; Li, Chuanjun; Wang, Jiang; Ren, Weili; Zhong, Yunbo; Li, Xi; Ren, Zhongming

2017-08-01

High magnetic fields are widely used to improve the microstructure and properties of materials during the solidification process. During the preparation of single-crystal turbine blades, the microstructure of the superalloy is the main factor that determines its mechanical properties. In this work, the effects of a high magnetic field on the microstructure of Ni-based single-crystal superalloys PWA1483 and CMSX-4 during directional solidification were investigated experimentally. The results showed that the magnetic field modified the primary dendrite arm spacing, γ' phase size, and microsegregation of the superalloys. In addition, the size and volume fractions of γ/ γ' eutectic and the microporosity were decreased in a high magnetic field. Analysis of variance (ANOVA) results showed that the effect of a high magnetic field on the microstructure during directional solidification was significant ( p < 0.05). Based on both experimental results and theoretical analysis, the modification of microstructure was attributed to thermoelectric magnetic convection occurring in the interdendritic regions under a high magnetic field. The present work provides a new method to optimize the microstructure of Ni-based single-crystal superalloy blades by applying a high magnetic field.

Efficacy and safety of testosterone replacement gel for treating hypogonadism in men: Phase III open-label studies.

PubMed

Belkoff, L; Brock, G; Carrara, D; Neijber, A; Ando, M; Mitchel, J

2018-02-01

Efficacy and safety of testosterone gel 2% (TG) were evaluated in two phase 3, open-labelled, single-arm, multicentre studies (000023 and extension study 000077). Hypogonadal men having serum testosterone levels <300 ng/dl at two consecutive measurements were included. Study duration was 9 months (000023: 3 months; 000077: 6 months). Starting dose of TG (46 mg) was applied on upper arm/shoulder. The primary endpoint (000023) was responder rate (subjects with average 24-hour serum testosterone concentration 300-1050 ng/dl on Day 90). Study 000077 evaluated the safety of TG in patients rolling over from study 000023 over a period of 6 months. Of 180 subjects in 000023, 172 completed and 145 rolled over to 000077, with 127 completers. The responder rate was 85.5%. Fewer subjects in 000077 (12.7%) versus 000023 (31.8%) had maximum testosterone concentration (C max ) >1500 ng/dl, with no significant safety concerns. Significant improvements in sexual function and quality of life were noted in both studies. Subjects experienced few skin reactions without notable increases in prostate-specific antigen and haematocrit levels. TG was efficacious with an acceptable safety profile. C max >1500 ng/dl did not exhibit distinct impact on safety parameters. However, further optimisation of titration schema to reduce C max is warranted while maintaining the average steady state total testosterone concentration. © 2017 Blackwell Verlag GmbH.

Efficacy and safety of Privigen(®) in patients with chronic inflammatory demyelinating polyneuropathy: results of a prospective, single-arm, open-label Phase III study (the PRIMA study).

PubMed

Léger, Jean-Marc; De Bleecker, Jan L; Sommer, Claudia; Robberecht, Wim; Saarela, Mika; Kamienowski, Jerzy; Stelmasiak, Zbigniew; Mielke, Orell; Tackenberg, Björn; Shebl, Amgad; Bauhofer, Artur; Zenker, Othmar; Merkies, Ingemar S J

2013-06-01

This prospective, multicenter, single-arm, open-label Phase III study aimed to evaluate the efficacy and safety of Privigen(®) (10% liquid human intravenous immunoglobulin [IVIG], stabilized with L-proline) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Patients received one induction dose of Privigen (2 g/kg body weight [bw]) and up to seven maintenance doses (1 g/kg bw) at 3-week intervals. The primary efficacy endpoint was the responder rate at completion, defined as improvement of ≥1 point on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale. The preset success criterion was the responder rate being ≥35%. Of the 31 screened patients, 28 patients were enrolled including 13 (46.4%) IVIG-pretreated patients. The overall responder rate at completion was 60.7% (95% confidence interval [CI]: 42.41%-76.43%). IVIG-pretreated patients demonstrated a higher responder rate than IVIG-naïve patients (76.9% vs. 46.7%). The median (25%-75% quantile) INCAT score improved from 3.5 (3.0-4.5) points at baseline to 2.5 (1.0-3.0) points at completion, as did the mean (standard deviation [SD]) maximum grip strength (66.7 [37.24] kPa vs. 80.9 [31.06] kPa) and the median Medical Research Council sum score (67.0 [61.5-72.0] points vs. 75.5 [71.5-79.5] points). Of 108 adverse events (AEs; 0.417 AEs per infusion), 95 AEs (88.0%) were mild or moderate in intensity and resolved by the end of study. Two serious AEs of hemolysis were reported that resolved after discontinuation of treatment. Thus, Privigen provided efficacious and well-tolerated induction and maintenance treatment in patients with CIDP. © 2013 The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals, Inc. on behalf of Peripheral Nerve Society.

Skin toxicity and quality of life in patients with metastatic colorectal cancer during first-line panitumumab plus FOLFIRI treatment in a single-arm phase II study.

PubMed

Thaler, Josef; Karthaus, Meinolf; Mineur, Laurent; Greil, Richard; Letocha, Henry; Hofheinz, Ralf; Fernebro, Eva; Gamelin, Erick; Baños, Ana; Köhne, Claus-Henning

2012-09-29

Integument-related toxicities are common during epidermal growth factor receptor (EGFR)-targeted therapy. Panitumumab is a fully human monoclonal antibody targeting the EGFR that significantly improves progression-free survival when added to chemotherapy in patients with metastatic colorectal cancer who have wild-type (WT) KRAS tumours. Primary efficacy and tolerability results from a phase II single-arm study of first-line panitumumab plus FOLFIRI in patients with metastatic colorectal cancer have been reported. Here we report additional descriptive tolerability and quality of life data from this trial. Integument-related toxicities and quality of life were analysed; toxicities were graded using modified National Cancer Institute Common Toxicity Criteria. Kaplan-Meier estimates of time to and duration of first integument-related toxicity were prepared. Quality of life was measured using EuroQoL EQ-5D and EORTC QLQ-C30. Best overall response was analysed by skin toxicity grade and baseline quality of life. Change in quality of life was analysed by skin toxicity severity. 154 patients were enrolled (WT KRAS n = 86; mutant KRAS n = 59); most (98%) experienced integument-related toxicities (most commonly rash [42%], dry skin [40%] and acne [36%]). Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56%) compared with those with grade 0/1 (29%). Mean overall EQ-5D health state index scores (0.81 vs. 0.78), health rating scores (72.5 vs. 71.0) and QLQ-C30 global health status scores (65.8 vs. 66.7) were comparable at baseline vs. safety follow-up (8 weeks after completion), respectively and appeared unaffected by skin toxicity severity. First-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument-related toxicity. ClinicalTrials.gov NCT00508404.

Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial

PubMed Central

Rojek, Amanda; Gannon, Fiona; Carson, Gail; Idriss, Baimba; Massaquoi, Thomas; Gandi, Regina; Joseph, Sebatu; Osman, Hassan K.; Brooks, Timothy J. G.; Simpson, Andrew J. H.; Goodfellow, Ian; Thorne, Lucy; Arias, Armando; Merson, Laura; Castle, Lyndsey; Howell-Jones, Rebecca; Pardinaz-Solis, Raul; Hope-Gill, Benjamin; Ferri, Mauricio; Grove, Jennifer; Kowalski, Mark; Stepniewska, Kasia; Lang, Trudie; Whitehead, John; Olliaro, Piero; Samai, Mohammed; Horby, Peter W.

2016-01-01

Background TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. Methods and Findings In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. Conclusions Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. Trial registration Pan African Clinical Trials Registry PACTR201501000997429 PMID:27093560

Icotinib in Patients with Pretreated Advanced Esophageal Squamous Cell Carcinoma with EGFR Overexpression or EGFR Gene Amplification: A Single-Arm, Multicenter Phase 2 Study.

PubMed

Huang, Jing; Fan, Qingxia; Lu, Ping; Ying, Jianming; Ma, Changwu; Liu, Wei; Liu, Ying; Tan, Fenlai; Sun, Yan

2016-06-01

Epidermal growth factor receptor (EGFR) has been reported to be overexpressed and amplified in a high percentage of patients with esophageal squamous cell carcinoma (ESCC). The activity of icotinib, an EGFR tyrosine kinase inhibitor, was assessed in previously treated ESCC with EGFR overexpression or amplification. For this phase 2, single-arm, multicenter trial undertaken at six hospitals in China, we included Chinese patients with previously treated, histologically confirmed advanced ESCC and EGFR overexpression (immunohistochemical staining sore of 3+) or amplification (positive fluorescence in situ hybridization result). These patients received oral icotinib (250 mg, three times daily).The primary end point was the proportion of patients with objective responses as assessed by an independent radiology review committee. Between December 5, 2013, and May 28, 2015, a total of 281 patients were screened. Fifty-four eligible patients were enrolled. Nine responses were observed, including one complete response and eight partial responses, and 16 patients had stable disease, resulting in a 16.7% objective response rate (95% confidence interval [CI]: 6.7-26.6) and 46.3% disease control rate (95% CI: 33.0-59.6). The median progression-free survival and overall survival times were 52 (95% CI: 40-95) days and 153 (95% CI: 139-218) days, respectively. A total of 43 patients experienced at least one adverse event, but most were only grade 1 to 2 in severity. The most frequent was rash (48.1%), followed by diarrhea (22.2%). Icotinib showed favorable activity in patients with advanced, previously treated ESCC with EGFR overexpression or amplification. These findings suggest further research into EGFR overexpression or amplification for selecting responsive patients. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Sensitivity of Cirrus and Mixed-phase Clouds to the Ice Nuclei Spectra in McRAS-AC: Single Column Model Simulations

NASA Technical Reports Server (NTRS)

Betancourt, R. Morales; Lee, D.; Oreopoulos, L.; Sud, Y. C.; Barahona, D.; Nenes, A.

2012-01-01

The salient features of mixed-phase and ice clouds in a GCM cloud scheme are examined using the ice formation parameterizations of Liu and Penner (LP) and Barahona and Nenes (BN). The performance of LP and BN ice nucleation parameterizations were assessed in the GEOS-5 AGCM using the McRAS-AC cloud microphysics framework in single column mode. Four dimensional assimilated data from the intensive observation period of ARM TWP-ICE campaign was used to drive the fluxes and lateral forcing. Simulation experiments where established to test the impact of each parameterization in the resulting cloud fields. Three commonly used IN spectra were utilized in the BN parameterization to described the availability of IN for heterogeneous ice nucleation. The results show large similarities in the cirrus cloud regime between all the schemes tested, in which ice crystal concentrations were within a factor of 10 regardless of the parameterization used. In mixed-phase clouds there are some persistent differences in cloud particle number concentration and size, as well as in cloud fraction, ice water mixing ratio, and ice water path. Contact freezing in the simulated mixed-phase clouds contributed to transfer liquid to ice efficiently, so that on average, the clouds were fully glaciated at T approximately 260K, irrespective of the ice nucleation parameterization used. Comparison of simulated ice water path to available satellite derived observations were also performed, finding that all the schemes tested with the BN parameterization predicted 20 average values of IWP within plus or minus 15% of the observations.

The effect of arm sling on balance in patients with hemiplegia.

PubMed

Acar, Merve; Karatas, Gulcin Kaymak

2010-10-01

The aim of this study was to investigate the effect of an arm sling on balance in patients with, hemiplegia following a stroke. Twenty-six patients with hemiplegia (11 men, 15 women) who had, shoulder subluxation were enrolled in the study. Balance was evaluated by the Berg Balance Scale, the, Functional Reach test, and a static balance index which was measured by the Kinesthetic Ability, Trainer 3000. Balance tests were performed twice, with arm sling and without arm sling use. Results of, this study show that the Berg Balance Scores and static balance index ameliorated with arm sling use (p=0.005 and p=0.004, respectively). Likewise, the Functional Reach test was better when performed with an arm sling (p=0.039). In conclusion, arm slings have a beneficial effect on balance in patients, with hemiplegia. An arm sling may be applied for its possible beneficial effect on balance especially in, the early phases of stroke rehabilitation while the upper extremity is still flaccid and arm swing is, reduced. Copyright © 2010 Elsevier B.V. All rights reserved.

Using shape to turn off blinking for two-colour multiexciton emission in CdSe/CdS tetrapods

DOE PAGES

Mishra, Nimai; Orfield, Noah Jeremiah; Wang, Feng; ...

2017-05-12

Here, semiconductor nanostructures capable of emitting from two excited states and thereby of producing two photoluminescence colours are of fundamental and potential technological significance. In this limited class of nanocrystals, CdSe/CdS core/arm tetrapods exhibit the unusual trait of two-colour (red and green) multiexcitonic emission, with green emission from the CdS arms emerging only at high excitation fluences. Here we show that by synthetic shape-tuning, both this multi-colour emission process, and blinking and photobleaching behaviours of single tetrapods can be controlled. Specifically, we find that the properties of dual emission and single-nanostructure photostability depend on different structural parameters—arm length and armmore » diameter, respectively—but that both properties can be realized in the same nanostructure. Furthermore, based on results of correlated photoluminescence and transient absorption measurements, we conclude that hole-trap filling in the arms and partial state-filling in the core are necessary preconditions for the observation of multiexciton multi-colour emission.« less

Using shape to turn off blinking for two-colour multiexciton emission in CdSe/CdS tetrapods

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

Mishra, Nimai; Orfield, Noah Jeremiah; Wang, Feng

Here, semiconductor nanostructures capable of emitting from two excited states and thereby of producing two photoluminescence colours are of fundamental and potential technological significance. In this limited class of nanocrystals, CdSe/CdS core/arm tetrapods exhibit the unusual trait of two-colour (red and green) multiexcitonic emission, with green emission from the CdS arms emerging only at high excitation fluences. Here we show that by synthetic shape-tuning, both this multi-colour emission process, and blinking and photobleaching behaviours of single tetrapods can be controlled. Specifically, we find that the properties of dual emission and single-nanostructure photostability depend on different structural parameters—arm length and armmore » diameter, respectively—but that both properties can be realized in the same nanostructure. Furthermore, based on results of correlated photoluminescence and transient absorption measurements, we conclude that hole-trap filling in the arms and partial state-filling in the core are necessary preconditions for the observation of multiexciton multi-colour emission.« less

Experimental measure of arm stiffness during single reaching movements with a time-frequency analysis

PubMed Central

Pierobon, Alberto; DiZio, Paul; Lackner, James R.

2013-01-01

We tested an innovative method to estimate joint stiffness and damping during multijoint unfettered arm movements. The technique employs impulsive perturbations and a time-frequency analysis to estimate the arm's mechanical properties along a reaching trajectory. Each single impulsive perturbation provides a continuous estimation on a single-reach basis, making our method ideal to investigate motor adaptation in the presence of force fields and to study the control of movement in impaired individuals with limited kinematic repeatability. In contrast with previous dynamic stiffness studies, we found that stiffness varies during movement, achieving levels higher than during static postural control. High stiffness was associated with elevated reflexive activity. We observed a decrease in stiffness and a marked reduction in long-latency reflexes around the reaching movement velocity peak. This pattern could partly explain the difference between the high stiffness reported in postural studies and the low stiffness measured in dynamic estimation studies, where perturbations are typically applied near the peak velocity point. PMID:23945781

Observation of the quantum paradox of separation of a single photon from one of its properties

NASA Astrophysics Data System (ADS)

Ashby, James M.; Schwarz, Peter D.; Schlosshauer, Maximilian

2016-07-01

We report an experimental realization of the quantum paradox of the separation of a single photon from one of its properties (the so-called "quantum Cheshire cat"). We use a modified Sagnac interferometer with displaced paths to produce appropriately pre- and postselected states of heralded single photons. Weak measurements of photon presence and circular polarization are performed in each arm of the interferometer by introducing weak absorbers and small polarization rotations and analyzing changes in the postselected signal. The absorber is found to have an appreciable effect only in one arm of the interferometer, while the polarization rotation significantly affects the signal only when performed in the other arm. We carry out both sequential and simultaneous weak measurements and find good agreement between measured and predicted weak values. In the language of Aharonov et al. and in the sense of the ensemble averages described by weak values, the experiment establishes the separation of a particle from one its properties during the passage through the interferometer.

The globalization of the arms industry: The next proliferation challenge

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

Bitzinger, R.A.

1994-12-31

The globalization of the arms industry entails a significant shift away from traditional, single-country patterns of weapons production toward internationalization of the development, production, and marketing of arms. While wholly indigenous armaments production may be on the decline, multinational arms production - through collaboration on individual weapon systems and increasingly via interfirm linkages across the international arms industry - appears actually to be expanding. In several instances, in fact, multinational armaments production is increasingly supplementing or even supplanting indigenous or autonomous weapons production or arms imports. The emergence of an increasingly transnational defense technology and industrial base is fundamentally affectingmore » the shape and content of much of the global arms trade. This changing defense market, in turn, will have a profound impact on a number of national security issues concerning the Western industrialized nations. 3 figs., 2 tabs.« less

[Relationship of Ghrelin gene polymorphism with congenital anorectal malformation and Hirschsprung disease].

PubMed

Gao, Hong; Wang, Dajia; Zhao, Xiangxuan; Mi, Jie; Bai, Yuzuo; Wang, Weilin

2015-07-01

To explore the relationship of Ghrelin gene polymorphism with the occurrence of human anorectal malformations (ARMs) and Hirschsprung disease(HSCR). PCR and DNA sequencing were used to detect the single nucleotide polymorphism (SNPs) of 3 loci (rs139684563, rs149447194, rs186599567) genotype of Ghrelin gene in 100 children with ARMs, 100 children with HSCR, and 100 healthy children (normal group). Genovariation and gene mutation were analyzed with case-control method. Three loci SNPs were in accordance with Hardy-Weinberg genetic equilibrium. No significant differences were found in rs139684563 allele and genotype frequencies between the cases and the normal groups (P>0.05). The allele and genotype frequencies of rs149447194 and rs186599567 were significantly different between cases and normal group (P<0.05). DNA sequencing results showed that wild-type homozygous deletion (176th and 191th base A deletion, respectively) were found in rs149447194 and rs186599567of ARMs and HSCR children, and single base substitution was detected in rs149447194 of ARMs children (194th codon nucleotide CCT to CTC). The rs149447194 and the rs186599567 polymorphism changes may be associated with the pathogenesis of ARMs and HSCR.

BDNF Polymorphism Predicts General Intelligence after Penetrating Traumatic Brain Injury

PubMed Central

Rostami, Elham; Krueger, Frank; Zoubak, Serguei; Dal Monte, Olga; Raymont, Vanessa; Pardini, Matteo; Hodgkinson, Colin A.; Goldman, David; Risling, Mårten; Grafman, Jordan

2011-01-01

Neuronal plasticity is a fundamental factor in cognitive outcome following traumatic brain injury. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays an important role in this process. While there are many ways to measure cognitive outcome, general cognitive intelligence is a strong predictor of everyday decision-making, occupational attainment, social mobility and job performance. Thus it is an excellent measure of cognitive outcome following traumatic brain injury (TBI). Although the importance of the single-nucleotide polymorphisms polymorphism on cognitive function has been previously addressed, its role in recovery of general intelligence following TBI is unknown. We genotyped male Caucasian Vietnam combat veterans with focal penetrating TBI (pTBI) (n = 109) and non-head injured controls (n = 38) for 7 BDNF single-nucleotide polymorphisms. Subjects were administrated the Armed Forces Qualification Test (AFQT) at three different time periods: pre-injury on induction into the military, Phase II (10–15 years post-injury, and Phase III (30–35 years post-injury). Two single-nucleotide polymorphisms, rs7124442 and rs1519480, were significantly associated with post-injury recovery of general cognitive intelligence with the most pronounced effect at the Phase II time point, indicating lesion-induced plasticity. The genotypes accounted for 5% of the variance of the AFQT scores, independently of other significant predictors such as pre-injury intelligence and percentage of brain volume loss. These data indicate that genetic variations in BDNF play a significant role in lesion-induced recovery following pTBI. Identifying the underlying mechanism of this brain-derived neurotrophic factor effect could provide insight into an important aspect of post-traumatic cognitive recovery. PMID:22087305

Neoadjuvant Chemoradiation for Distal Rectal Cancer: 5-Year Updated Results of a Randomized Phase 2 Study of Neoadjuvant Combined Modality Chemoradiation for Distal Rectal Cancer

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

Mohiuddin, Mohammed, E-mail: asemuddin@gmail.com; Paulus, Rebecca; Mitchell, Edith

2013-07-01

Purpose: To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers. Methods and Materials: One hundred six patients with T3/T4 distal rectal cancers were randomized in a phase 2 study. Patients received either continuous venous infusion (CVI) of 5-Fluorouracil (5-FU), 225 mg/m{sup 2} per day, 7 days per week plus pelvic hyperfractionated radiation (HRT), 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers (Arm 1), or CVI of 5-FU, 225 mg/m{sup 2} per day, Monday to Friday, plus irinotecan, 50 mg/m{sup 2} once weeklymore » × 4, plus pelvic radiation therapy (RT), 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers (Arm 2). Surgery was performed 4 to 10 weeks later. Results: All eligible patients (n=103) are included in this analysis; 2 ineligible patients were excluded, and 1 patient withdrew consent. Ninety-eight of 103 patients (95%) underwent resection. Four patients did not undergo surgery for either disease progression or patient refusal, and 1 patient died during induction chemotherapy. The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2. The pathological complete response (pCR) rates were 30% in Arm 1 and 26% in Arm 2. Locoregional recurrence rates were 16% in Arm 1 and 17% in Arm 2. Five-year survival rates were 61% and 75% and Disease-specific survival rates were 78% and 85% for Arm1 and Arm 2, respectively. Five second primaries occurred in patients on Arm 1, and 1 second primary occurred in Arm 2. Conclusions: High rates of disease-specific survival were seen in each arm. Overall survival appears affected by the development of unrelated second cancers. The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival.« less

NGC 4622:. A clear example of spiral density wave star formation unused in textbooks.

NASA Astrophysics Data System (ADS)

Byrd, Gene G.

2018-06-01

Refer to the poster HST images or to http://heritage.stsci.edu/2002/03/index.html. The top northeastern (NE) arm of NGC 4622 winds outward clockwise (CW) showing beautiful “ beads on a string” blue stellar associations on the CONCAVE SIDE of the arm. These are nicely offset CW in position from the density concentration of old yellow stars in the arms. The displacement would result from aggregation of gas clouds as they orbit CW into a more slowly turning stellar disk arm pattern. There is a time delay until the associations form and light up on the concave side. Farther inward along the top NE arm, the lit-up associations occur in the MIDDLE of the stellar arm. This is characteristic of the co-rotation (CR) radius where the CW orbital angular rate of the gas clouds and the arm CW pattern speeds match. Just within CR, the association displacement from the stellar arm is opposite (CCW) onto the CONVEX SIDE of the arm. A similar displacement sequence from concave (outside CR), middle (at CR) to convex (inside CR) is seen along the lower southwestern arm. Why isn’t NGC 4622 featured in textbooks? A rather puzzling single stellar arm winds outward CCW from the center, opposite to the outer pair. The eastern edge of the disk (marked by dust cloud silhouettes) is the nearer edge. The NE portion radial velocity is away relative to the nucleus so the disk orbital motion is CW. The outer pair of arms thus winds outward to LEAD in the same direction as the CW orbital motion, contrary to typical arm winding. Actually, the leading pair of arms and single inner arm would make NGC 4622 even better for use in introductory astronomy texts. Students can debate the origin of this galaxy's strange arm pattern which, ironically, matches density wave predictions so well. This is better than simply reading a textbook and thinking that all is explained. See G. G. Byrd; T. Freeman; S. Howard; R. J. Buta (2008). Astron. J., 135, p. 408–413 and references there for observations and hypotheses about NGC 4622’s arms. This work was supported by NSAS/STScI grant 8707 to the Univ. of Alabama and NSF grant AST 02-0177 to Bevill State College, Fayette, AL. Also see https://www.researchgate.net/profile/Gene_Byrd2

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

PubMed Central

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

2014-01-01

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

Development of a 3D immersive videogame to improve arm-postural coordination in patients with TBI

PubMed Central

2011-01-01

Background Traumatic brain injury (TBI) disrupts the central and executive mechanisms of arm(s) and postural (trunk and legs) coordination. To address these issues, we developed a 3D immersive videogame-- Octopus. The game was developed using the basic principles of videogame design and previous experience of using videogames for rehabilitation of patients with acquired brain injuries. Unlike many other custom-designed virtual environments, Octopus included an actual gaming component with a system of multiple rewards, making the game challenging, competitive, motivating and fun. Effect of a short-term practice with the Octopus game on arm-postural coordination in patients with TBI was tested. Methods The game was developed using WorldViz Vizard software, integrated with the Qualysis system for motion analysis. Avatars of the participant's hands precisely reproducing the real-time kinematic patterns were synchronized with the simulated environment, presented in the first person 3D view on an 82-inch DLP screen. 13 individuals with mild-to-moderate manifestations of TBI participated in the study. While standing in front of the screen, the participants interacted with a computer-generated environment by popping bubbles blown by the Octopus. The bubbles followed a specific trajectory. Interception of the bubbles with the left or right hand avatar allowed flexible use of the postural segments for balance maintenance and arm transport. All participants practiced ten 90-s gaming trials during a single session, followed by a retention test. Arm-postural coordination was analysed using principal component analysis. Results As a result of the short-term practice, the participants improved in game performance, arm movement time, and precision. Improvements were achieved mostly by adapting efficient arm-postural coordination strategies. Of the 13 participants, 10 showed an immediate increase in arm forward reach and single-leg stance time. Conclusion These results support the feasibility of using the custom-made 3D game for retraining of arm-postural coordination disrupted as a result of TBI. PMID:22040301

Development of a 3D immersive videogame to improve arm-postural coordination in patients with TBI.

PubMed

Ustinova, Ksenia I; Leonard, Wesley A; Cassavaugh, Nicholas D; Ingersoll, Christopher D

2011-10-31

Traumatic brain injury (TBI) disrupts the central and executive mechanisms of arm(s) and postural (trunk and legs) coordination. To address these issues, we developed a 3D immersive videogame--Octopus. The game was developed using the basic principles of videogame design and previous experience of using videogames for rehabilitation of patients with acquired brain injuries. Unlike many other custom-designed virtual environments, Octopus included an actual gaming component with a system of multiple rewards, making the game challenging, competitive, motivating and fun. Effect of a short-term practice with the Octopus game on arm-postural coordination in patients with TBI was tested. The game was developed using WorldViz Vizard software, integrated with the Qualysis system for motion analysis. Avatars of the participant's hands precisely reproducing the real-time kinematic patterns were synchronized with the simulated environment, presented in the first person 3D view on an 82-inch DLP screen. 13 individuals with mild-to-moderate manifestations of TBI participated in the study. While standing in front of the screen, the participants interacted with a computer-generated environment by popping bubbles blown by the Octopus. The bubbles followed a specific trajectory. Interception of the bubbles with the left or right hand avatar allowed flexible use of the postural segments for balance maintenance and arm transport. All participants practiced ten 90-s gaming trials during a single session, followed by a retention test. Arm-postural coordination was analysed using principal component analysis. As a result of the short-term practice, the participants improved in game performance, arm movement time, and precision. Improvements were achieved mostly by adapting efficient arm-postural coordination strategies. Of the 13 participants, 10 showed an immediate increase in arm forward reach and single-leg stance time. These results support the feasibility of using the custom-made 3D game for retraining of arm-postural coordination disrupted as a result of TBI.

Role of arm motion in feet-in-place balance recovery.

PubMed

Cheng, Kuangyou B; Wang, Kuan-Mao; Kuo, Shih-Yu

2015-09-18

Although considerable arm movements have been observed at loss of balance, research on standing balance focused primarily on the ankle and hip strategies. This study aimed to investigate the effect of arm motion on feet-in-place balance recovery. Participants stood on a single force plate and leaned forward with a straight body posture. They were then released from three forward-lean angles and regained balance without moving their forefeet under arm-swing (AS) and arm-constrained (AC) conditions. Higher success rates and shorter recovery times were found with arm motion under moderate balance perturbations. Recovery time was significantly correlated with peak linear momentum of the arms. Circumduction arm motion caused initial shoulder extension (backward arm movement) to generate reaction forces to pull the body forward, but later forward linear momentum of the arms helped move the whole body backward to avoid forward falling. However, greater lean angles increased difficulty in balance recovery, making the influences of the arms less significant. Since arm motions were observed in all participants with significantly enhanced performance under moderate balance perturbation, it was concluded that moving the arms should also be considered (together with the ankles and hips) as an effective strategy for balance recovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

In vivo myosin step-size from zebrafish skeletal muscle

PubMed Central

Ajtai, Katalin; Sun, Xiaojing; Takubo, Naoko; Wang, Yihua

2016-01-01

Muscle myosins transduce ATP free energy into actin displacement to power contraction. In vivo, myosin side chains are modified post-translationally under native conditions, potentially impacting function. Single myosin detection provides the ‘bottom-up’ myosin characterization probing basic mechanisms without ambiguities inherent to ensemble observation. Macroscopic muscle physiological experimentation provides the definitive ‘top-down’ phenotype characterizations that are the concerns in translational medicine. In vivo single myosin detection in muscle from zebrafish embryo models for human muscle fulfils ambitions for both bottom-up and top-down experimentation. A photoactivatable green fluorescent protein (GFP)-tagged myosin light chain expressed in transgenic zebrafish skeletal muscle specifically modifies the myosin lever-arm. Strychnine induces the simultaneous contraction of the bilateral tail muscles in a live embryo, causing them to be isometric while active. Highly inclined thin illumination excites the GFP tag of single lever-arms and its super-resolution orientation is measured from an active isometric muscle over a time sequence covering many transduction cycles. Consecutive frame lever-arm angular displacement converts to step-size by its product with the estimated lever-arm length. About 17% of the active myosin steps that fall between 2 and 7 nm are implicated as powerstrokes because they are beyond displacements detected from either relaxed or ATP-depleted (rigor) muscle. PMID:27249818

Measurements of microhardness during transient horizontal directional solidification of Al-Rich Al-Cu alloys: Effect of thermal parameters, primary dendrite arm spacing and Al2Cu intermetallic phase

NASA Astrophysics Data System (ADS)

Barros, André Santos; Magno, Igor Alexsander; Souza, Fabrício Andrade; Mota, Carlos Alberto; Moreira, Antonio Luciano; Silva, Maria Adrina; Rocha, Otávio Lima

2015-05-01

In this work, the effect of the growth rate (VL) and cooling rate (TR), primary dendritic arm spacing (λ1) and Al2Cu intermetallic phase on the microhardness was investigated during transient horizontal directional solidification of Al-3wt%Cu and Al-8wt%Cu alloys. Microstructural characterization of the investigated alloys was performed using traditional techniques of metallography, optical and SEM microscopy and X-Ray diffraction. The microhardness evolution as a function of the thermal and microstructural parameters (VL, TR, and λ1) was evaluated using power and Hall-Petch type experimental laws, which were compared with other laws in the literature. In order to examine the effect of the Al2Cu intermetallic phase, microhardness measurements were performed in interdendritic regions. Finally, a comparative analysis was performed between the experimental data of this work and theoretical models from the literature that have been proposed to predict primary dendrite arm spacing, which have been tested in numerous works considering upward directional solidification.

Effect of stride length on overarm throwing delivery: A linear momentum response.

PubMed

Ramsey, Dan K; Crotin, Ryan L; White, Scott

2014-12-01

Changing stride length during overhand throwing delivery is thought to alter total body and throwing arm linear momentums, thereby altering the proportion of throwing arm momentum relative to the total body. Using a randomized cross-over design, nineteen pitchers (15 collegiate and 4 high school) were assigned to pitch two simulated 80-pitch games at ±25% of their desired stride length. An 8-camera motion capture system (240Hz) integrated with two force plates (960Hz) and radar gun tracked each throw. Segmental linear momentums in each plane of motion were summed yielding throwing arm and total body momentums, from which compensation ratio's (relative contribution between the two) were derived. Pairwise comparisons at hallmark events and phases identified significantly different linear momentum profiles, in particular, anteriorly directed total body, throwing arm, and momentum compensation ratios (P⩽.05) as a result of manipulating stride length. Pitchers with shorter strides generated lower forward (anterior) momentum before stride foot contact, whereas greater upward and lateral momentum (toward third base) were evident during the acceleration phase. The evidence suggests insufficient total body momentum in the intended throwing direction may potentially influence performance (velocity and accuracy) and perhaps precipitate throwing arm injuries. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of pH adjustment by mixing steroid for venous pain in colorectal cancer patients receiving oxaliplatin through peripheral vein: a multicenter randomized phase II study (APOLLO).

PubMed

Hata, Taishi; Honda, Michitaka; Kobayashi, Michiya; Toyokawa, Akihiro; Tsuda, Masahiro; Tokunaga, Yukihiko; Takase, Kozo; Miyake, Masakazu; Morita, Satoshi; Nagata, Naoki; Sakamoto, Junichi; Gosho, Masahiko; Mishima, Hideyuki

2015-12-01

The aim of this phase II clinical trial was to evaluate the preventive effect of dexamethasone mixing injection for venous pain in patients with colorectal cancer during chemotherapy. Patients were randomized to receive a 2-h intravenous infusion of oxaliplatin 130 mg/m(2) on day 1 followed by capecitabine 1000 mg/m(2) (or S-1 40-60 mg/m(2)) twice daily on days 1 through 14 of every 3 weeks with or without dexamethasone 1.65 mg at the infusion on day 1. A total of 53 patients were enrolled. The analysis population consisted of 49 patients (arm A, with dexamethasone N = 24; arm B, without dexamethasone N = 25). The incidence of venous pain ≥grade 2 based on the CTCAE version 4.0 was 33.3 % in arm A and 56.0 % in arm B (relative risk 0.60; 95 % CI 0.31-1.16). The incidences based on the verbal rating scale for arms A and B were 50.0 and 64.0 %, respectively (relative risk 0.78; 95 % CI 0.48-1.28). The primary endpoint was not met in this preliminary study.

Fixing methods for the use of optical fibers in interferometric arrangements

NASA Astrophysics Data System (ADS)

Cubik, Jakub; Kepak, Stanislav; Fajkus, Marcel; Zboril, Ondrej; Nedoma, Jan; Davidson, Alan; Vasinek, Vladimir

2016-12-01

Today interferometric sensors are among the most accurate available thanks to their inherent high sensitivity. These highly versatile sensors may be used to measure phenomena such as temperature, strain, fluid level, flow, vibration, stress, etc. This article concentrates on the composition of fiber-optic interferometers, in particular the Mach-Zehnder type. The Mach-Zehnder type is composed of two arms, one for measurement and a second serving as a reference. When light enters the interferometer, ideally the phase of the light is shifted only in the measurement arm while the phase in the second arm remains unchanged. Interference occurs when the light recombining at the output and the resulting light intensity is proportional to the measurand. A major issue in the application of fiber based sensors is laying and fixing the fibers effectively in real life environments. Different approaches are necessary for both arms. The reference arm should as far as possible be isolated from the measurand. In this paper, various isolating materials are considered, however there are almost unlimited materials that may be used for isolation purposes. Conventional construction methods and materials were used such as aluminum tubing, flexible PVC tubing, double sided tape, steel clinches, superglue, PVC strips and PVC strips filled by silicon.

Twist limits for late twisting double somersaults on trampoline.

PubMed

Yeadon, M R; Hiley, M J

2017-06-14

An angle-driven computer simulation model of aerial movement was used to determine the maximum amount of twist that could be produced in the second somersault of a double somersault on trampoline using asymmetrical movements of the arms and hips. Lower bounds were placed on the durations of arm and hip angle changes based on performances of a world trampoline champion whose inertia parameters were used in the simulations. The limiting movements were identified as the largest possible odd number of half twists for forward somersaulting takeoffs and even number of half twists for backward takeoffs. Simulations of these two limiting movements were found using simulated annealing optimisation to produce the required amounts of somersault, tilt and twist at landing after a flight time of 2.0s. Additional optimisations were then run to seek solutions with the arms less adducted during the twisting phase. It was found that 3½ twists could be produced in the second somersault of a forward piked double somersault with arms abducted 8° from full adduction during the twisting phase and that three twists could be produced in the second somersault of a backward straight double somersault with arms fully adducted to the body. These two movements are at the limits of performance for elite trampolinists. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quality of life analyses from the randomized, open-label, phase III PointBreak study of pemetrexed-carboplatin-bevacizumab followed by maintenance pemetrexed-bevacizumab versus paclitaxel-carboplatin-bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer.

PubMed

Spigel, David R; Patel, Jyoti D; Reynolds, Craig H; Garon, Edward B; Hermann, Robert C; Govindan, Ramaswamy; Olsen, Mark R; Winfree, Katherine B; Chen, Jian; Liu, Jingyi; Guba, Susan C; Socinski, Mark A; Bonomi, Philip

2015-02-01

Treatment impact on quality of life (QoL) informs treatment management decisions in advanced nonsquamous non-small-cell lung cancer (NS NSCLC). QoL outcomes from the phase III PointBreak trial are reported. Chemonaive patients (n = 939) with stage IIIB/IV nonsquamous non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status 0 to 1 were randomized (1:1) to pemetrexed-carboplatin-bevacizumab (pemetrexed arm) or paclitaxel-carboplatin-bevacizumab (paclitaxel arm). Patients without progressive disease received maintenance pemetrexed-bevacizumab (pemetrexed arm) or bevacizumab (paclitaxel arm). QoL was assessed using Functional Assessment of Cancer Therapy (FACT)-General (FACT-G), FACT-Lung (FACT-L), and FACT/Gynecologic Oncology Group-Neurotoxicity (FACT-Ntx) instruments. Subscale scores, total scores, and trial outcome indices were analyzed using linear mixed-effects models. Post hoc analyses examined the association between baseline FACT scores and overall survival (OS). Mean score differences in change from baseline significantly favored the pemetrexed arm for the neurotoxicity subscale score, FACT-Ntx total scores, and FACT-Ntx trial outcome index. They occurred at cycle 2 (p < 0.001) and persisted through induction cycles 2 to 4 and six maintenance cycles. Investigator-assessed, qualitative, drug-related differences in grade 2 (1.6% versus 10.6%) and grade 3 (0.0% versus 4.1%) sensory neuropathy and grade 3/4 fatigue (10.9% versus 5.0%, p = 0.0012) were observed between the pemetrexed and paclitaxel arms. Baseline FACT-G, FACT-L, and FACT-Ntx scores were significant prognostic factors for OS (p < 0.001). Randomized patients reported similar changes in QoL, except for less change from baseline in neurotoxicity on the pemetrexed arm; investigators reported greater neurotoxicity on the paclitaxel arm and greater fatigue on the pemetrexed arm. Higher baseline FACT scores were favorable prognostic factors for OS.

Phase III noninferiority trial comparing irinotecan with oxaliplatin, fluorouracil, and leucovorin in patients with advanced colorectal carcinoma previously treated with fluorouracil: N9841.

PubMed

Kim, George P; Sargent, Daniel J; Mahoney, Michelle R; Rowland, Kendrith M; Philip, Philip A; Mitchell, Edith; Mathews, Abraham P; Fitch, Tom R; Goldberg, Richard M; Alberts, Steven R; Pitot, Henry C

2009-06-10

The primary goal of this multicenter phase III trial was to determine whether overall survival (OS) of fluorouracil (FU) -refractory patients was noninferior when treated with second-line infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4; arm B) versus irinotecan (arm A). Cross-over to the other treatment on disease progression was mandated. Patients who experienced treatment failure with one prior FU-based therapy and had not received prior irinotecan or oxaliplatin, either for metastatic disease or within 6 months of adjuvant FU therapy, were randomly assigned to arm A (irinotecan 350 or 300 mg/m(2) every 3 weeks) or arm B (FOLFOX4). A total of 491 patients were randomly assigned (arm A, n = 245; arm B, n = 246); 288 (59%) had experienced treatment failure with FU for metastatic colorectal cancer. Two hundred twenty-seven patients (46%) received protocol-mandated third-line therapy (arm A, 43%; arm B, 57%). Median survival was 13.8 months (95% CI, 12.2 to 15.0 months) for initial treatment with FOLFOX4 and 14.3 months (95% CI, 12.0 to 15.9 months) for irinotecan (P = .38; hazard ratio = 0.92; 95% CI, 0.8 to 1.1). Response rates (RR; 28% v 15.5%; P = .0009) and time to progression (TTP; 6.2 v 4.4 months; P = .0009) were significantly superior with FOLFOX4. In the nonrandom subset of patients who crossed over, RR and TTP improvements with FOLFOX4 continued into third-line treatment. Irinotecan therapy was associated with more grade 3 nausea, vomiting, diarrhea, and febrile neutropenia; FOLFOX4 was associated with more neutropenia and paresthesias. In patients who experienced treatment failure with front-line FU therapy, OS does not significantly differ whether second-line therapy begins with irinotecan or FOLFOX4. FOLFOX4 produces higher RR and longer TTP. Both arms had notable OS in patients who experienced treatment failure with first-line FU therapy.

Effect of the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation Therapy for Patients With Esophageal Cancer: The NRG Oncology RTOG 0436 Phase 3 Randomized Clinical Trial.

PubMed

Suntharalingam, Mohan; Winter, Kathryn; Ilson, David; Dicker, Adam P; Kachnic, Lisa; Konski, André; Chakravarthy, A Bapsi; Anker, Christopher J; Thakrar, Harish; Horiba, Naomi; Dubey, Ajay; Greenberger, Joel S; Raben, Adam; Giguere, Jeffrey; Roof, Kevin; Videtic, Gregory; Pollock, Jondavid; Safran, Howard; Crane, Christopher H

2017-11-01

The role of epidermal growth factor receptor (EGFR) inhibition in chemoradiation strategies in the nonoperative treatment of patients with esophageal cancer remains uncertain. To evaluate the benefit of cetuximab added to concurrent chemoradiation therapy for patients undergoing nonoperative treatment of esophageal carcinoma. A National Cancer Institute (NCI) sponsored, multicenter, phase 3, randomized clinical trial open to patients with biopsy-proven carcinoma of the esophagus. The study accrued 344 patients from 2008 to 2013. Patients were randomized to weekly concurrent cisplatin (50 mg/m2), paclitaxel (25 mg/m2), and daily radiation of 50.4 Gy/1.8 Gy fractions with or without weekly cetuximab (400 mg/m2 on day 1 then 250 mg/m2 weekly). Overall survival (OS) was the primary endpoint, with a study designed to detect an increase in 2-year OS from 41% to 53%; 80% power and 1-sided α = .025. Between June 30, 2008, and February 8, 2013, 344 patients were enrolled. This analysis used all data received at NRG Oncology through April 12, 2015. Sixteen patients were ineligible, resulting in 328 evaluable patients, 159 in the experimental arm and 169 in the control arm. Patients were well matched between the treatment arms for patient and tumor characteristics: 263 (80%) with T3 or T4 disease, 215 (66%) N1, and 62 (19%) with celiac nodal involvement. Incidence of grade 3, 4, or 5 treatment-related adverse events at any time was 71 (46%), 35 (23%), or 6 (4%) in the experimental arm and 83 (50%), 28 (17%), or 2 (1%) in the control arm, respectively. A clinical complete response (cCR) rate of 81 (56%) was observed in the experimental arm vs 92 (58%) in the control arm (Fisher exact test, P = .66). No differences were seen in cCR between treatment arms for either histology (adenocarcinoma or squamous cell). Median follow-up for all patients was 18.6 months. The 24- and 36-month local failure for the experimental arm was 47% (95% CI, 38%-57%) and 49% (95% CI, 40%-59%) vs 49% (95% CI, 41%-58%) and 49% (95% CI, 41%-58%) for the control arm (HR, 0.92; 95% CI, 0.66-1.28; P = .65). The 24- and 36-month OS rates for the experimental arm were 45% (95% CI, 37%-53%) and 34% (95% CI, 26%-41%) vs 44% (95% CI, 36%-51%) and 28% (95% CI, 21%-35%) for the control arm (HR, 0.90; 95% CI, 0.70-1.16; P = .47). The addition of cetuximab to concurrent chemoradiation did not improve OS. These phase 3 trial results point to little benefit to current EGFR-targeted agents in an unselected patient population, and highlight the need for predictive biomarkers in the treatment of esophageal cancer. clinicaltrials.gov Identifier: NCT00655876.

No Clinically Relevant Drug-Drug Interactions between Methadone or Buprenorphine-Naloxone and Antiviral Combination Glecaprevir and Pibrentasvir

PubMed Central

Kosloski, Matthew P.; Zhao, Weihan; Asatryan, Armen; Kort, Jens; Geoffroy, Pierre

2017-01-01

ABSTRACT The combination of glecaprevir (formerly ABT-493), a nonstructural protein 3/4A (NS3/4A) protease inhibitor, and pibrentasvir (formerly ABT-530), an NS5A protein inhibitor, is being developed as treatment for HCV genotype 1 to 6 infection. The pharmacokinetics, pharmacodynamics, safety, and tolerability of methadone or buprenorphine-naloxone when coadministered with the glecaprevir-pibrentasvir combination in HCV-negative subjects on stable opioid maintenance therapy were investigated in a phase 1, single-center, two-arm, multiple-dose, open-label sequential study. Subjects received methadone (arm 1) or buprenorphine-naloxone (arm 2) once daily (QD) per their existing individual prescriptions alone (days 1 to 9) and then in combination with glecaprevir at 300 mg QD and pibrentasvir at 120 mg QD (days 10 to 16) each morning. Dose-normalized exposures were similar with and without glecaprevir and pibrentasvir for (R)- and (S)-methadone (≤5% difference) and for buprenorphine and naloxone (≤24% difference); the norbuprenorphine area under the curve was 30% higher with glecaprevir and pibrentasvir, consistent with maximum and trough plasma concentrations that increased by 21% to 25%. No changes in pupil response, short opiate withdrawal scale score, or desire for drugs questionnaire were observed when glecaprevir and pibrentasvir were added to methadone or buprenorphine-naloxone therapy. No dose adjustment is required when glecaprevir and pibrentasvir are coadministered with methadone or buprenorphine-naloxone. PMID:28807904

Rotational foot placement specifies the lever arm of the ground reaction force during the push-off phase of walking initiation.

PubMed

Erdemir, Ahmet; Piazza, Stephen J

2002-06-01

The lever arm of the ground reaction force (GRF) about the talocrural joint axis is a functionally important indicator of the nature of foot loading. Walking initiation experiments (ten subjects; age, 23-29 years) were completed to demonstrate that rotational foot placement is a possible strategy to specify the lever arm. Externally-rotated foot placement resulted in larger lever arms during push-off. A computer simulation of push-off revealed that a decreased lever arm reduces the plantarflexion moment necessary to maintain a constant forward velocity, while increasing the required plantarflexion velocity. Shortening of the foot thus diminishes the muscular force demand but also requires high muscle fiber shortening velocities that may limit the force generating capacity of plantar flexors. Decreased plantar flexion moment and slow walking previously noted in partial-foot amputees may result from shortened lever arms in this manner.

Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: study protocol for a prospective, multicenter, randomized, open-label, phase II trial.

PubMed

Lee, Ji Yeon; Kim, Deog Kyeom; Lee, Jung-Kyu; Yoon, Ho Il; Jeong, Ina; Heo, Eunyoung; Park, Young Sik; Lee, Jae Ho; Park, Sung Soo; Lee, Sang-Min; Lee, Chang-Hoon; Lee, Jinwoo; Choi, Sun Mi; Park, Jong Sun; Joh, Joon-Sung; Cho, Young-Jae; Lee, Yeon Joo; Kim, Se Joong; Hwang, Young Ran; Kim, Hyeonjeong; Ki, Jongeun; Choi, Hyungsook; Han, Jiyeon; Ahn, Heejung; Hahn, Seokyung; Yim, Jae-Joon

2017-02-13

Linezolid, an oxazolidinone, substantially improves treatment outcomes of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. We started a trial to test whether the use of linezolid instead of ethambutol could increase the rate of sputum culture conversion as of 8 weeks of treatment in patients with drug-susceptible tuberculosis. This is a phase II, multicenter, randomized study with three arms. We are enrolling patients with pulmonary tuberculosis without rifampicin resistance screened by the Xpert MTB/RIF® assay. The standard treatment arm uses isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months). Experimental arm 1 uses linezolid (600 mg/day) for 4 weeks instead of ethambutol. Experimental arm 2 uses linezolid (600 mg/day) for 2 weeks instead of ethambutol. The primary outcome is the sputum culture conversion rate on liquid media after 2 months of treatment. Secondary outcomes include the sputum culture conversion rate on solid media after 2 months of treatment, time to sputum culture conversion on liquid and solid media, cure rate, and treatment success rate. The frequencies of total adverse events (AEs) and serious AEs will be described and documented. Based on an α = 0.05 level of significance, a power of 85%, a 15% difference in the culture conversion rate after 2 months between the control arm and experimental arm 1 (75% vs. 90%), a 10% default (loss to follow-up) rate, and a 10% culture failure, the required number per arm was calculated to be 143 (429 in total). This trial will reveal the effectiveness and safety of 2 or 4 weeks of use of linezolid instead of ethambutol for patients with drug-susceptible pulmonary tuberculosis. If a new regimen including linezolid shows a higher culture conversion rate by week 8, and is safe, it could be tested as a 4-month antituberculosis treatment regimen in the future. ClincalTrials.gov, NCT01994460 . Registered on 13 November 2013.

An international phase 3 trial in head and neck cancer: quality of life and symptom results: EORTC 24954 on behalf of the EORTC Head and Neck and the EORTC Radiation Oncology Group.

PubMed

Bottomley, Andrew; Tridello, Gloria; Coens, Corneel; Rolland, Frederic; Tesselaar, Margot E T; Leemans, C Rene; Hupperets, Pierre; Licitra, Lisa; Vermorken, Jan B; Van Den Weyngaert, Danielle; Truc, Gilles; Barillot, Isabelle; Lefebvre, Jean-Louis

2014-02-01

The European Organization for Research and Treatment of Cancer (EORTC) 24954 phase 3 randomized clinical trial compared 2 schemes of combined chemotherapy for patients with resectable cancers of the hypopharynx and larynx: sequential induction chemotherapy and radiotherapy versus alternating chemoradiotherapy. The current study reports detailed effects of both treatment arms on health-related quality of life (HRQOL) and symptoms. A total of 450 patients aged 35 years to 76 years (World Health Organization performance status (WHO PS) ≤ 2) with untreated, resectable advanced squamous cell carcinoma of the larynx (tumor classification of T3-T4) or hypopharynx (tumor classification of T2-T3-T4) with regional lymph nodes in the neck classified as N0 to N2 with no metastases were randomized in this prospective phase 3 trial into either the sequential arm (control) or the alternating arm (experimental). QOL assessment was performed at randomization; at baseline; at 42 days; and at 6, 12, 24, 36, and 48 months. There were no observed differences with regard to the primary endpoint of Fatigue and secondary endpoint of Dyspnea. Significant differences were found in the secondary endpoints of Swallowing and Speech problems at 42 days after randomization in favor of patients in the sequential arm. Explanatory and sensitivity analysis revealed that the primary analysis favored the sequential arm, but the majority of differences in HRQOL did not exist at the end of treatment, and returned to baseline levels. In the current study, a trend toward worse scores was noted in the patients treated on the alternating chemoradiotherapy arm but very few differences reached the level of statistical significance. The HRQOL scores of the majority of patients returned to baseline after therapy. © 2013 American Cancer Society.

Validation of the Omron M6 (HEM-7001-E) upper-arm blood pressure measuring device according to the International Protocol in adults and obese adults.

PubMed

Altunkan, Sekip; Ilman, Nevzat; Kayatürk, Nur; Altunkan, Erkan

2007-08-01

Electronic blood pressure (BP) measurement devices are the preferred choice of patients owing to their user-friendly nature; however, there is a requirement to investigate the accuracy and reliability of these devices. The objective of this study is to evaluate the accuracy of the Omron M6 upper-arm BP device against the mercury sphygmomanometer in adults and obese adults according to the International Protocol criteria. One hundred and twenty-one patients, older than 30 years of age, were studied and classified on the basis of the range of the International Protocol. BP measurements at the upper arm with the Omron M6 were compared with the results obtained by two trained observers using a mercury sphygmomanometer. Nine sequential BP measurements were taken. A total of 33 participants were selected for each validation study. During the validation study, 99 measurements were performed on 33 participants for comparison. The first phase was performed on 15 participants, and if the device passed this phase, 18 more participants were selected. Having a two-fold purpose, this study was conducted on both adult and obese adult patients. Mean discrepancies and standard deviations of the monitor-mercury sphygmomanometer were 1.1+/-4.0 mmHg for systolic BP (SBP) and -0.5+/-3.5 mmHg for diastolic BP (DBP) in the adult group. The device passed phase 1 in 15 participants. In phase 2.1, out of a total of 99 comparisons, 88, 96, and 97 for SBP, and 88, 98, and 99 for DBP were <5, <10, and <15 mmHg, respectively. Mean discrepancies and standard deviations of the monitor-mercury sphygmomanometer were 1.7+/-4.8 mmHg for SBP and -0.8+/-4.3 mmHg for DBP in the obese adult group. The device passed phase 1 in 15 participants. In phase 2.1, out of a total of 99 comparisons, 82, 90, and 97 for SBP, and 80, 97, and 99 for DBP were <5, <10, and <15 mmHg, respectively. It was found that the Omron M6 automatic monitor, which measures BP at the upper arm, produced results in accordance with the criteria of phases 2.1 and 2.2 in both SBP and DBP, when applied to adults and to obese adults. It was concluded that the Omron M6 device, which measures BP at the upper arm, was deemed to be in accordance with the International Protocol criteria and can be recommended for use by adults and obese adults.

Testing cloud microphysics parameterizations in NCAR CAM5 with ISDAC and M-PACE observations

NASA Astrophysics Data System (ADS)

Liu, Xiaohong; Xie, Shaocheng; Boyle, James; Klein, Stephen A.; Shi, Xiangjun; Wang, Zhien; Lin, Wuyin; Ghan, Steven J.; Earle, Michael; Liu, Peter S. K.; Zelenyuk, Alla

2011-01-01

Arctic clouds simulated by the National Center for Atmospheric Research (NCAR) Community Atmospheric Model version 5 (CAM5) are evaluated with observations from the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Indirect and Semi-Direct Aerosol Campaign (ISDAC) and Mixed-Phase Arctic Cloud Experiment (M-PACE), which were conducted at its North Slope of Alaska site in April 2008 and October 2004, respectively. Model forecasts for the Arctic spring and fall seasons performed under the Cloud-Associated Parameterizations Testbed framework generally reproduce the spatial distributions of cloud fraction for single-layer boundary-layer mixed-phase stratocumulus and multilayer or deep frontal clouds. However, for low-level stratocumulus, the model significantly underestimates the observed cloud liquid water content in both seasons. As a result, CAM5 significantly underestimates the surface downward longwave radiative fluxes by 20-40 W m-2. Introducing a new ice nucleation parameterization slightly improves the model performance for low-level mixed-phase clouds by increasing cloud liquid water content through the reduction of the conversion rate from cloud liquid to ice by the Wegener-Bergeron-Findeisen process. The CAM5 single-column model testing shows that changing the instantaneous freezing temperature of rain to form snow from -5°C to -40°C causes a large increase in modeled cloud liquid water content through the slowing down of cloud liquid and rain-related processes (e.g., autoconversion of cloud liquid to rain). The underestimation of aerosol concentrations in CAM5 in the Arctic also plays an important role in the low bias of cloud liquid water in the single-layer mixed-phase clouds. In addition, numerical issues related to the coupling of model physics and time stepping in CAM5 are responsible for the model biases and will be explored in future studies.

SINGLE AGENT CARBOPLATIN VERSUS CARBOPLATIN PLUS PEGYLATED LIPOSOMAL DOXORUBICIN IN RECURRENT OVARIAN CANCER: FINAL SURVIVAL RESULTS OF A SWOG (S0200) PHASE 3 RANDOMIZED TRIAL

PubMed Central

Markman, Maurie; Moon, James; Wilczynski, Sharon; Lopez, Ana Maria; Rowland, Kendrith M.; Michelin, David P.; Lanzotti, Victor J.; Anderson, Garnet L.; Alberts, David S.

2009-01-01

Objectives Randomized phase 3 trials have demonstrated the utility of a regimen of carboplatin plus pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer, and have provided provocative data suggesting a substantially lower risk of carboplatin-associated hypersensitivity if PDL is delivered in combination with the platinum agent. Methods To further examine both of these clinically-relevant issues, the survival outcome (with longer follow-up) and hypersensitivity reaction profile of a previously reported phase 3 trial that compared single agent carboplatin (AUC 5) to carboplatin (AUC 5) plus PLD (30 mg/m2) delivered on an every 4-week schedule in recurrent ovarian cancer (SWOG 0200) were re-analyzed. Results In the limited number of patients (n=61) entered into this phase 3 study before closure by the SWOG Data Safety and Monitoring Committee due to insufficient accrual, there was an initially reported improvement in outcome associated with the combination regimen. With longer follow-up and additional events there is still a statistically-significant improved progression-free survival (median: 12 versus 8 months, p=0.02), but the previously observed impact of the two-drug regimen on overall survival is no longer apparent (median: 31 versus 18 months; p=0.2). While no hypersensitivity reactions were reported in the carboplatin plus PLD arm (0/31), 9 of 30 patients (30%) of women randomized to single agent carboplatin experienced an allergic episode (p=0.0008), with 5 being ≥ grade 3 in severity. Conclusion Despite a favorable impact of carboplatin and PLD on progression-free survival in this trial, the effect on overall survival is not statistically significant. For currently unknown reasons, administering PLD with carboplatin appears to substantially reduce the incidence of platinum-associated hypersensitivity reactions. PMID:20044128

Upper Arm Central Venous Port Implantation: A 6-Year Single Institutional Retrospective Analysis and Pictorial Essay of Procedures for Insertion

PubMed Central

Shiono, Masatoshi; Takahashi, Shin; Kakudo, Yuichi; Takahashi, Masanobu; Shimodaira, Hideki; Kato, Shunsuke; Ishioka, Chikashi

2014-01-01

Background The requirement of central venous (CV) port implantation is increasing with the increase in the number of cancer patients and advancement in chemotherapy. In our division, medical oncologists have implanted all CV ports to save time and consultation costs to other departments. Recently, upper arm implantation has become the first choice as a safe and comfortable method in our unit. Here we report our experience and discuss the procedure and its potential advantages. Methods All CV port implantations (n = 599) performed in our unit from January 2006 to December 2011 were analyzed. Procedural success and complication rates between subclavian and upper arm groups were compared. Results Both groups had similar patient characteristics. Upper arm CV port and subclavian implantations were equivalently successful and safe. Although we only retrospectively analyzed data from a single center, the upper arm group had a significantly lower overall postprocedural complication rate than the subclavian group. No pneumothorax risk, less risk of arterial puncture by ultrasound, feasibility of stopping potential arterial bleeding, and prevention of accidental arterial cannulation by targeting the characteristic solitary basilic vein were the identified advantages of upper arm CV port implantation. In addition to the aforementioned advantages, there is no risk of “pinch-off syndrome,” possibly less patient fear of manipulation, no scars on the neck and chest, easier accessibility, and compatibility with the “peripherally inserted central catheter” technique. Conclusions Upper arm implantation may benefit clinicians and patients with respect to safety and comfort. We also introduce our methods for upper arm CV port implantation with the videos. PMID:24614412

SpArcFiRe: Scalable automated detection of spiral galaxy arm segments

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

Davis, Darren R.; Hayes, Wayne B., E-mail: drdavis@uci.edu, E-mail: whayes@uci.edu

Given an approximately centered image of a spiral galaxy, we describe an entirely automated method that finds, centers, and sizes the galaxy (possibly masking nearby stars and other objects if necessary in order to isolate the galaxy itself) and then automatically extracts structural information about the spiral arms. For each arm segment found, we list the pixels in that segment, allowing image analysis on a per-arm-segment basis. We also perform a least-squares fit of a logarithmic spiral arc to the pixels in that segment, giving per-arc parameters, such as the pitch angle, arm segment length, location, etc. The algorithm takesmore » about one minute per galaxies, and can easily be scaled using parallelism. We have run it on all ∼644,000 Sloan objects that are larger than 40 pixels across and classified as 'galaxies'. We find a very good correlation between our quantitative description of a spiral structure and the qualitative description provided by Galaxy Zoo humans. Our objective, quantitative measures of structure demonstrate the difficulty in defining exactly what constitutes a spiral 'arm', leading us to prefer the term 'arm segment'. We find that pitch angle often varies significantly segment-to-segment in a single spiral galaxy, making it difficult to define the pitch angle for a single galaxy. We demonstrate how our new database of arm segments can be queried to find galaxies satisfying specific quantitative visual criteria. For example, even though our code does not explicitly find rings, a good surrogate is to look for galaxies having one long, low-pitch-angle arm—which is how our code views ring galaxies. SpArcFiRe is available at http://sparcfire.ics.uci.edu.« less

Venetoclax in Patients with Previously Treated Chronic Lymphocytic Leukemia.

PubMed

Roberts, Andrew W; Stilgenbauer, Stephan; Seymour, John F; Huang, David C S

2017-08-15

Venetoclax is the first BCL2 inhibitor to enter routine clinical practice. It is an orally bioavailable small molecule that binds BCL2 very specifically. Acting as a pharmacologic mimic of the proteins that initiate apoptosis (a so-called BH3 mimetic), venetoclax rapidly induces apoptosis in chronic lymphocytic leukemia (CLL) cells, which express high levels of BCL2 and rely on it to maintain their survival. As a single agent, daily venetoclax treatment induced durable responses in 79% of patients with relapsed or refractory CLL or small lymphocytic lymphoma in a phase I study, including complete remissions in 20% of patients. Its use was approved by the FDA in April 2016 for patients with previously treated del(17p) CLL on the basis of a single-arm phase II trial demonstrating a 79% response rate and an estimated 1-year progression-free survival of 72% with 400 mg/day continuous therapy. This review focuses on venetoclax, its mechanism of action, pharmacology, and clinical trial data and seeks to place it in the context of rapid advances in therapy for patients with relapsed CLL, especially those with del(17p) CLL. Clin Cancer Res; 23(16); 4527-33. ©2017 AACR . ©2017 American Association for Cancer Research.

High-Power X-Band Semiconductor RF Switch for Pulse Compression Systems of Future Colliders

NASA Astrophysics Data System (ADS)

Tantawi, Sami G.; Tamura, Fumihiko

2000-04-01

We describe the potential of semiconductor X-band RF switch arrays as a means of developing high power RF pulse compression systems for future linear colliders. The switch systems described here have two designs. Both designs consist of two 3dB hybrids and active modules. In the first design the module is composed of a cascaded active phase shifter. In the second design the module uses arrays of SPST (Single Pole Single Throw) switches. Each cascaded element of the phase shifter and the SPST switch has similar design. The active element consists of symmetrical three-port tee-junctions and an active waveguide window in the symmetrical arm of the tee-junction. The design methodology of the elements and the architecture of the whole switch system are presented. We describe the scaling law that governs the relation between power handling capability and number of elements. The design of the active waveguide window is presented. The waveguide window is a silicon wafer with an array of four hundred PIN/NIP diodes covering the surface of the window. This waveguide window is located in an over-moded TE01 circular waveguide. The results of high power RF measurements of the active waveguide window are presented. The experiment is performed at power levels of tens of megawatts at X-band.

Recovery in the Severely Impaired Arm Post-stroke after Mirror Therapy - a Randomized Controlled Study.

PubMed

Chan, Wing Chiu; Au-Yeung, Stephanie Suk Yin

2018-03-09

This study aimed to examine the effectiveness of mirror therapy (MT) on recovery in the severely impaired arm after stroke. Using single-blind randomized controlled design, patients with severely impaired arm within 1-month post-stroke were assigned to received MT (n=20) or control therapy (CT) (n=21), 30min. twice daily for 4 weeks in addition to conventional rehabilitation. During MT and CT, subjects practiced similar structured exercises in both arms, except that mirror reflection of the unaffected arm was the visual feedback for MT, but mirror was absent for CT so that subjects could watch both arms in exercise. Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) were the outcome measurements. After the intervention, both MT and CT groups had significant arm recovery similarly in FMA (p=0.867), WMFT-Time (p=0.947) and WMFT-Functional Ability Scale (p=0.676). MT or CT which involved exercises concurrently for the paretic and unaffected arms during subacute stroke promoted similar motor recovery in the severely impaired arm.

Theoretical model of an optothermal microactuator directly driven by laser beams

NASA Astrophysics Data System (ADS)

Han, Xu; Zhang, Haijun; Xu, Rui; Wang, Shuying; Qin, Chun

2015-07-01

This paper proposes a novel method of optothermal microactuation based on single and dual laser beams (spots). The theoretical model of the optothermal temperature distribution of an expansion arm is established and simulated, indicating that the maximum temperature of the arm irradiated by dual laser spots, at the same laser power level, is much lower than that irradiated by one single spot, and thus the risk of burning out and damaging the optothermal microactuator (OTMA) can be effectively avoided. To verify the presented method, a 750 μm long OTMA with a 100 μm wide expansion arm is designed and microfabricated, and single/dual laser beams with a wavelength of 650 nm are adopted to carry out experiments. The experimental results showed that the optothermal deflection of the OTMA under the irradiation of dual laser spots is larger than that under the irradiation of a single spot with the same power, which is in accordance with theoretical prediction. This method of optothermal microactuation may expand the practical applications of microactuators, which serve as critical units in micromechanical devices and micro-opto-electro-mechanical systems (MOEMS).

Development of Hybrid Computer Programs for AAFSS/COBRA/COIN Weapons Effectiveness Studies. Volume I. Simulating Aircraft Maneuvers and Weapon Firing Runs.

DTIC Science & Technology

for the game. Subsequent duels , flown with single armed escorts, calculated reduction in losses and damage states. For the study, hybrid computer...6) a duel between a ground weapon, armed escort, and formation of lift aircraft. (Author)

Role of Surgical Versus Clinical Staging in Chemoradiated FIGO Stage IIB-IVA Cervical Cancer Patients—Acute Toxicity and Treatment Quality of the Uterus-11 Multicenter Phase III Intergroup Trial of the German Radiation Oncology Group and the Gynecologic Cancer Group

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

Marnitz, Simone, E-mail: simone.marnitz-schulze@uk-koeln.de; Martus, Peter; Köhler, Christhardt

Purpose: The Uterus-11 trial was designed to evaluate the role of surgical staging in patients with cervical cancer before primary chemoradiation therapy (CRT). The present report provides the toxicity data stratified by the treatment arm and technique. Methods and Materials: A total of 255 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics stage IIB-IVA) were randomized to either surgical staging followed by CRT (arm A) or clinical staging followed by CRT (arm B). Patients with para-aortic metastases underwent extended field radiation therapy (RT). Brachytherapy was mandatory. The present report presents the acute therapy-related toxicities stratifiedmore » by treatment arm and radiation technique. Results: A total of 240 patients were eligible (n=121 in arm A; n=119 in arm B). Of the 240 patients, 236 (98.3%) underwent external beam RT with a median total dose of 50.4 Gy. The mean treatment duration was 53 days. Of the patients, 60% underwent intensity modulated RT (IMRT). A total of 234 patients (97.5%) underwent chemotherapy, and 231 (96.3%) underwent brachytherapy, with a median single dose of 6 Gy covering the tumor to a median nominal total dose of 28 Gy. Treatment was well tolerated, with 0% grade ≥3 genitourinary and gastrointestinal toxicity, 6% grade 3 nausea, 3% grade 3 vomiting, and <2% grade 3 diarrhea. More patients after surgical staging experienced grade 2 anemia (54.3% in arm A vs 45.3% in arm B; P=.074) and grade 2 leukocytopenia (41.4% vs 31.6%; P=.56). Of the patients who received IMRT versus a 3-dimensional technique, 65.3% versus 33.7% presented with grade 2 anemia. Grade 3 gastrointestinal and grade 2 bladder toxicity were significantly reduced with the use of IMRT. Conclusions: The incidence and severity of acute therapy-related toxicity compared favorably with those from other randomized trials. Excellent adherence to treatment and treatment quality was achieved compared with patterns of care analyses. Surgical staging led to a doubled number of patients treated with extended field RT. The question of whether surgical staging is beneficial in the context of primary CRT requires further study.« less

The effects of a rhythm and music-based therapy program and therapeutic riding in late recovery phase following stroke: a study protocol for a three-armed randomized controlled trial

PubMed Central

2012-01-01

Background Stroke represents one of the most costly and long-term disabling conditions in adulthood worldwide and there is a need to determine the effectiveness of rehabilitation programs in the late phase after stroke. Limited scientific support exists for training incorporating rhythm and music as well as therapeutic riding and well-designed trials to determine the effectiveness of these treatment modalities are warranted. Methods/Design A single blinded three-armed randomized controlled trial is described with the aim to evaluate whether it is possible to improve the overall health status and functioning of individuals in the late phase of stroke (1-5 years after stroke) through a rhythm and music-based therapy program or therapeutic riding. About 120 individuals will be consecutively and randomly allocated to one of three groups: (T1) rhythm and music-based therapy program; (T2) therapeutic riding; or (T3) control group receiving the T1 training program a year later. Evaluation is conducted prior to and after the 12-week long intervention as well as three and six months later. The evaluation comprises a comprehensive functional and cognitive assessment (both qualitative and quantitative), and questionnaires. Based on the International classification of functioning, disability, and health (ICF), the outcome measures are classified into six comprehensive domains, with participation as the primary outcome measure assessed by the Stroke Impact Scale (SIS, version 2.0.). The secondary outcome measures are grouped within the following domains: body function, activity, environmental factors and personal factors. Life satisfaction and health related quality of life constitute an additional domain. Current status A total of 84 participants were randomised and have completed the intervention. Recruitment proceeds and follow-up is on-going, trial results are expected in early 2014. Discussion This study will ascertain whether any of the two intervention programs can improve overall health status and functioning in the late phase of stroke. A positive outcome would increase the scientific basis for the use of such interventions in the late phase after stroke. Trial registration Clinical Trials.gov Identifier: NCT01372059 PMID:23171380

The effects of a rhythm and music-based therapy program and therapeutic riding in late recovery phase following stroke: a study protocol for a three-armed randomized controlled trial.

PubMed

Bunketorp Käll, Lina; Lundgren-Nilsson, Åsa; Blomstrand, Christian; Pekna, Marcela; Pekny, Milos; Nilsson, Michael

2012-11-21

Stroke represents one of the most costly and long-term disabling conditions in adulthood worldwide and there is a need to determine the effectiveness of rehabilitation programs in the late phase after stroke. Limited scientific support exists for training incorporating rhythm and music as well as therapeutic riding and well-designed trials to determine the effectiveness of these treatment modalities are warranted. A single blinded three-armed randomized controlled trial is described with the aim to evaluate whether it is possible to improve the overall health status and functioning of individuals in the late phase of stroke (1-5 years after stroke) through a rhythm and music-based therapy program or therapeutic riding. About 120 individuals will be consecutively and randomly allocated to one of three groups: (T1) rhythm and music-based therapy program; (T2) therapeutic riding; or (T3) control group receiving the T1 training program a year later. Evaluation is conducted prior to and after the 12-week long intervention as well as three and six months later. The evaluation comprises a comprehensive functional and cognitive assessment (both qualitative and quantitative), and questionnaires. Based on the International classification of functioning, disability, and health (ICF), the outcome measures are classified into six comprehensive domains, with participation as the primary outcome measure assessed by the Stroke Impact Scale (SIS, version 2.0.). The secondary outcome measures are grouped within the following domains: body function, activity, environmental factors and personal factors. Life satisfaction and health related quality of life constitute an additional domain. A total of 84 participants were randomised and have completed the intervention. Recruitment proceeds and follow-up is on-going, trial results are expected in early 2014. This study will ascertain whether any of the two intervention programs can improve overall health status and functioning in the late phase of stroke. A positive outcome would increase the scientific basis for the use of such interventions in the late phase after stroke. Clinical Trials.gov Identifier: NCT01372059.

The Coherent Backscattering Opposition Effect: Measurements at Very Small Phase Angles

NASA Technical Reports Server (NTRS)

Nelson, R.; Hapke, B.; Smythe, W.; Horn, L.; Herrera, P.; Gharakanian, V.

1993-01-01

This oral presentation explains that measurements of the opposition surge (the nonlinear increase in reflectance seen in particulate materials when observed at small phase angles) are the first ever made using the JPL long-arm goniometer, which permits very small phase angle measuremnets to be made.

Combined vemurafenib and fotemustine in patients with BRAF V600 melanoma progressing on vemurafenib.

PubMed

Queirolo, Paola; Spagnolo, Francesco; Picasso, Virginia; Spano, Laura; Tanda, Enrica; Fontana, Valeria; Giorello, Laura; Merlo, Domenico Franco; Simeone, Ester; Grimaldi, Antonio Maria; Curvietto, Marcello; Del Vecchio, Michele; Bruzzi, Paolo; Ascierto, Paolo Antonio

2018-02-23

BRAF inhibitor vemurafenib achieves high response rate and an improvement in survival in patients with BRAF-mutated metastatic melanoma. However, median progression-free survival is only 6.9 months in the phase 3 study. Retrospective analyses suggest that treatment with BRAF inhibitors beyond initial progression might be associated with improved overall survival. We aimed to prospectively investigate the activity of prolonged treatment with vemurafenib and the addition of fotemustine in patients with systemic progression on prior single-agent BRAF inhibitor. In this two-centres, single-arm Phase 2 trial, we enrolled patients with systemic progressive disease during single-agent vemurafenib treatment. Participants received vemurafenib 960 mg twice daily or dose administered at time of disease progression with vemurafenib previous treatment and fotemustine 100 mg/m2 intravenously every three weeks. The primary endpoint was PFS. Thirty-one patients were enrolled in the study; 16 patients had brain metastases at baseline. Median PFS was 3.9 months and 19 patients (61.3%) achieved disease control (1 CR, 4 PR, 14 SD). For patients achieving disease control, median duration of treatment was 6 months. Median OS was 5.8 months from enrolment and 15.4 months from start of previous vemurafenib. Five patients (16.1%) had a G3-4 AE, the most common being thrombocytopenia, which occurred in 3 patients.This trial is registered with ClinicalTrials.gov number NCT01983124. The combination of vemurafenib plus fotemustine has clinical activity and an acceptable safety profile in BRAF-refractory patients.

Randomized, double-blind, phase III trial of palonosetron versus granisetron in the triplet regimen for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy: TRIPLE study.

PubMed

Suzuki, K; Yamanaka, T; Hashimoto, H; Shimada, Y; Arata, K; Matsui, R; Goto, K; Takiguchi, T; Ohyanagi, F; Kogure, Y; Nogami, N; Nakao, M; Takeda, K; Azuma, K; Nagase, S; Hayashi, T; Fujiwara, K; Shimada, T; Seki, N; Yamamoto, N

2016-08-01

There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC). Patients with a malignant solid tumor who would receive HEC containing 50 mg/m(2) or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2-4) and aprepitant (125 mg on day 1 and 80 mg on days 2-3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0-120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea). Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0-120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0-24 h) period, while at the delayed (24-120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0-120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369). The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point. UMIN000004863. © 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.

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

PubMed

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

2016-11-01

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

Modeling of biodynamic responses distributed at the fingers and the palm of the human hand-arm system.

PubMed

Dong, Ren G; Dong, Jennie H; Wu, John Z; Rakheja, Subhash

2007-01-01

The objective of this study is to develop analytical models for simulating driving-point biodynamic responses distributed at the fingers and palm of the hand under vibration along the forearm direction (z(h)-axis). Two different clamp-like model structures are formulated to analyze the distributed responses at the fingers-handle and palm-handle interfaces, as opposed to the single driving point invariably considered in the reported models. The parameters of the proposed four- and five degrees-of-freedom models are identified through minimization of an rms error function of the model and measured responses under different hand actions, namely, fingers pull, push only, grip only, and combined push and grip. The results show that the responses predicted from both models agree reasonably well with the measured data in terms of distributed as well total impedance magnitude and phase. The variations in the identified model parameters under different hand actions are further discussed in view of the biological system behavior. The proposed models are considered to serve as useful tools for design and assessment of vibration isolation methods, and for developing a hand-arm simulator for vibration analysis of power tools.

A phase I/pharmacokinetic study of sunitinib in combination with highly active antiretroviral therapy (HAART) in HIV-positive patients with cancer: AIDS Malignancy Consortium Trial AMC 061

PubMed Central

Rudek, Michelle A; Moore, Page C.; Mitsuyasu, Ronald T.; Dezube, Bruce J.; Aboulafia, David; Gerecitano, John; Sullivan, Ryan; Cianfrocca, Mary E.; Henry, David H.; Ratner, Lee; Haigentz, Missak; Dowlati, Afshin; Little, Richard F.; Ivy, S. Percy; Deeken, John F.

2014-01-01

Background Treatment of non-AIDS defining cancers (NADCs) may be complicated by drug interactions between highly active antiretroviral therapy (HAART) and chemotherapy. This trial is the first by the AIDS Malignancy Consortium assessing targeted therapies and HAART in HIV+ cancer patients (ClinicalTrials.gov NCT00890747). Methods Patients were stratified into two arms based on whether they were taking ritonavir, a potent CYP3A4 inhibitor, in a modified phase I study of sunitinib. Patients in arm 1 (non-ritonavir HAART) received standard sunitinib dosing (50mg/day). Arm 2 (ritonavir-based HAART) used a phase I, 3+3 dose escalation design (from 25 to 50mg/day). Cycles were with four weeks on treatment followed by a two week break (6 weeks total). Pharmacokinetics of sunitinib and its active metabolite (N-desethyl sunitinib) were assessed. Results Nineteen patients were enrolled and evaluable. Patients on Arm 1 tolerated treatment with one observed dose limiting toxicity (DLT). In Arm 2, a DLT was experienced at 37.5mg, and an additional 3 of 5 patients experienced grade 3 neutropenia, an uncommon toxicity of sunitinib. No patient had a response, but 10 had stable disease, including 8 with prolonged disease stability. Efavirenz, a potent inducer of CYP3A4, resulted in increased exposure of N-desethyl sunitinib, whereas ritonavir caused decreased exposure of the metabolite. Hand-foot syndrome was associated with higher steady-state trough concentrations of sunitinib. Conclusions Patients on non-ritonavir based HAART regimens tolerated standard dosing of sunitinib. Patients on ritonavir-based therapy treated with 37.5mg/day experienced higher toxicities. Dose reduction of sunitinib to 37.5mg may be warranted in patients on ritonavir. PMID:24474568

Dasatinib 100 mg Once Daily Minimizes the Occurrence of Pleural Effusion in Patients With Chronic Myeloid Leukemia in Chronic Phase and Efficacy Is Unaffected in Patients who Develop Pleural Effusion

PubMed Central

Porkka, Kimmo; Khoury, H. Jean; Paquette, Ronald L.; Matloub, Yousif; Sinha, Ritwik; Cortes, Jorge E.

2014-01-01

BACKGROUND Dasatinib, a highly potent BCR-ABL inhibitor, is an effective treatment for patients with chronic myeloid leukemia in chronic phase (CML CP) after resistance, suboptimal response, or intolerance to prior imatinib. In a phase 3 dose optimization trial in patients with CML CP (CA180-034), the occurrence of pleural effusion was significantly minimized with dasatinib 100 mg once daily (QD) compared with other treatment arms (70 mg twice daily [twice daily], 140 mg QD, or 50 mg twice daily). METHODS To investigate the occurrence and management of pleural effusion during dasatinib treatment, and efficacy in patients with or without pleural effusion, data from CA180-034 were analyzed. RESULTS With 24-month minimum follow-up, 14% of patients treated with dasatinib 100 mg QD incurred pleural effusion (grade 3: 2%; grade 4: 0%) compared with 23% to 26% in other study arms. The pleural effusion rate showed only a minimal increment from 12 to 24 months. In the 100 mg QD study arm, median time to pleural effusion (any grade) was 315 days, and after pleural effusion, 52% of patients had a transient dose interruption, 35% had a dose reduction, 57% received a diuretic, and 26% received a corticosteroid. Three patients in the 100 mg QD study arm discontinued treatment after pleural effusion. Across all study arms, patients with or without pleural effusion demonstrated similar progression-free and overall survival, and cytogenetic response rates were higher in patients with a pleural effusion. CONCLUSIONS Pleural effusion is minimized with dasatinib 100 mg QD dosing and its occurrence does not affect short- or long-term efficacy. PMID:19924787

Iron-Magnesium Hydroxycarbonate (Fermagate): A Novel Non-Calcium-Containing Phosphate Binder for the Treatment of Hyperphosphatemia in Chronic Hemodialysis Patients

PubMed Central

McIntyre, Christopher W.; Pai, Pearl; Warwick, Graham; Wilkie, Martin; Toft, Alex J.; Hutchison, Alastair J.

2009-01-01

Background and objectives: This phase II study tested the safety and efficacy of fermagate, a calcium-free iron and magnesium hydroxycarbonate binder, for treating hyperphosphatemia in hemodialysis patients. Design, setting, participants, & measurements: A randomized, double-blind, three-arm, parallel-group study compared two doses of fermagate (1 g three times daily or 2 g three times daily with placebo). Sixty-three patients who had been on a stable hemodialysis regimen for ≥3 mo were randomized to the treatment phase. Study medication was administered three times daily just before meals for 21 d. The primary endpoint was reduction in serum phosphate over this period. Results: In the intention-to-treat analysis, mean baseline serum phosphate was 2.16 mmol/L. The fermagate 1- and 2-g three-times-daily treatment arms were associated with statistical reductions in mean serum phosphate to 1.71 and 1.47 mmol/L, respectively. Adverse event (AE) incidence in the 1-g fermagate arm was statistically comparable to the placebo group. The 2-g arm was associated with a statistically higher number of patients reporting AEs than the 1-g arm, particularly gastrointestinal AEs, as well as a higher number of discontinuations, complicating interpretation of this dose's efficacy. Both doses were associated with elevations of prehemodialysis serum magnesium levels. Conclusions: The efficacy and tolerability of fermagate were dose dependent. Fermagate showed promising efficacy in the treatment of hyperphosphatemia in chronic hemodialysis patients as compared with placebo in this initial phase II study. The optimal balance between efficacy and tolerability needs to be determined from future dose-titration studies, or fixed-dose comparisons of more doses. PMID:19158369

[Multiple-Victimisation due to Armed Conflict and Emotional Distress in the State of Magdalena, Colombia].

PubMed

Campo-Arias, Adalberto; Sanabria, Adriana R; Ospino, Anyelly; Guerra, Valeria M; Caamaño, Beatriz H

Emotional distress is common in Colombian armed conflict victims. Multiple-victimisation is associated with an increase in emotional distress than victimisation due a single event. However, the association between poly-victimisation and emotional distress among victims of the armed conflict in Colombia has not been documented. To study the association between multiple-victimisation and emotional distress in victims of armed conflict in the State of Magdalena, Colombia. A cross-sectional study was designed, with a secondary analysis of registration of the Psychosocial Care Program and Victim Integral Health (PAPSIVI) in the State of Magdalena, from 2013 to 2014. The profile formula grouped demographic variables, victimising events, and a set of symptoms of emotional distress (perceived discrimination, depressive and anxiety-stress). Odds ratio (OR, 95%CI) were established as measures of association. A total of 943 people were included, with 67.4% women, and ages between18 and 94 years (mean 47.9±14.2). A total of 109 (11.7%) suffered from multiple victimisation. Multiple victimisation events were associated with more emotional distress, depressive symptoms (OR=1.5; 95%CI, 1.3-1.8), perceived stigma (OR=1.3; 95%CI, 1.1-1.5), and anxiety-stress (OR=1.2; 95%CI 1.0-1.4) than a single event. There is more emotional distress in multiple victimisations than in a single victimisation event during armed conflict in this region of Colombia. Further studies are required on this topic. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

The Tendril Plot-a novel visual summary of the incidence, significance and temporal aspects of adverse events in clinical trials.

PubMed

Karpefors, Martin; Weatherall, James

2018-03-21

In contrast to efficacy, safety hypotheses of clinical trials are not always pre-specified, and therefore, the safety interpretation work of a trial tends to be more exploratory, often reactive, and the analysis more statistically and graphically challenging. We introduce a new means of visualizing the adverse event data across an entire clinical trial. The approach overcomes some of the current limitations of adverse event analysis and streamlines the way safety data can be explored, interpreted and analyzed. Using a phase II study, we describe and exemplify how the tendril plot effectively summarizes the time-resolved safety profile of two treatment arms in a single plot and how that can provide scientists with a trial safety overview that can support medical decision making. To our knowledge, the tendril plot is the only way to graphically show important treatment differences with preserved temporal information, across an entire clinical trial, in a single view.

Reach-to-grasp movement as a minimization process.

PubMed

Yang, Fang; Feldman, Anatol G

2010-02-01

It is known that hand transport and grasping are functionally different but spatially coordinated components of reach-to-grasp (RTG) movements. As an extension of this notion, we suggested that body segments involved in RTG movements are controlled as a coherent ensemble by a global minimization process associated with the necessity for the hand to reach the motor goal. Different RTG components emerge following this process without pre-programming. Specifically, the minimization process may result from the tendency of neuromuscular elements to diminish the spatial gap between the actual arm-hand configuration and its virtual (referent) configuration specified by the brain. The referent configuration is specified depending on the object shape, localization, and orientation. Since the minimization process is gradual, it can be interrupted and resumed following mechanical perturbations, at any phase during RTG movements, including hand closure. To test this prediction of the minimization hypothesis, we asked subjects to reach and grasp a cube placed within the reach of the arm. Vision was prevented during movement until the hand returned to its initial position. As predicted, by arresting wrist motion at different points of hand transport in randomly selected trials, it was possible to halt changes in hand aperture at any phase, not only during hand opening but also during hand closure. Aperture changes resumed soon after the wrist was released. Another test of the minimization hypothesis was made in RTG movements to an object placed beyond the reach of the arm. It has previously been shown (Rossi et al. in J Physiol 538:659-671, 2002) that in such movements, the trunk motion begins to contribute to hand transport only after a critical phase when the shifts in the referent arm configuration have finished (at about the time when hand velocity is maximal). The minimization rule suggests that when the virtual contribution of the arm to hand transport is completed, guidance of hand aperture switches from the arm to the trunk control system. As a consequence, hand aperture changes can be halted by trunk arrests but only if they are prolonged beyond a critical phase. As predicted, hand transport and hand aperture in RTG movements beyond the reach of the arm were halted by trunk arrests only if they were prolonged beyond the time of peak hand velocity. Hand motion and aperture changes resumed only when the trunk was released. While supporting the minimization hypothesis, our findings imply that not only spatial but also temporal characteristics of each component, including the shortest, hand closure component of RTG movements, are controlled in a flexible, task-specific way.

Acute Toxicity and Quality of Life in Patients With Prostate Cancer Treated With Protons or Carbon Ions in a Prospective Randomized Phase II Study—The IPI Trial

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

Habl, Gregor; Department of Radiation Oncology, Technische Universität München, Munich; Uhl, Matthias

Purpose: The purpose of this study was to compare safety and feasibility of proton therapy with that of carbon ion therapy in hypofractionated raster-scanned irradiation of the prostate, in a prospective randomized phase 2 trial. Methods and Materials: In this trial, 92 patients with localized prostate cancer were enrolled. Patients were randomized to receive either proton therapy (arm A) or carbon ion therapy (arm B) and treated with a total dose of 66 Gy(relative biological effectiveness [RBE]) administered in 20 fractions (single dose of 3.3 Gy[RBE]). Patients were stratified by the use of antihormone therapy. Primary endpoint was the combined assessment ofmore » safety and feasibility. Secondary endpoints were specific toxicities, prostate-specific antigen progression-free survival (PFS), overall survival (OS), and quality of life (QoL). Results: Ninety-one patients completed therapy and have had a median follow-up of 22.3 months. Among acute genitourinary toxicities, grade 1 cystitis rates were 34.1% (39.1% in A; 28.9% in B) and 17.6% grade 2 (21.7% in A; 13.3% in B). Seven patients (8%) required urinary catheterization during treatment due to urinary retention, 5 of whom were in arm A. Regarding acute gastrointestinal toxicities, 2 patients treated with protons developed grade 3 rectal fistulas. Grade 1 radiation proctitis occurred in 12.1% (13.0% in A; 11.1% in B) and grade 2 in 5.5% (8.7% in A; 2.2% in B). No statistically significant differences in toxicity profiles between arms were found. Reduced QoL was evident mainly in fatigue, pain, and urinary symptoms during therapy and 6 weeks thereafter. All European Organization for Research and Treatment of Cancer QLQ-C30 and -PR25 scores improved during follow-up. Conclusions: Hypofractionated irradiation using either carbon ions or protons results in comparable acute toxicities and QoL parameters. We found that hypofractionated particle irradiation is feasible and may be safe. Due to the occurrence of gel in the rectal wall and the consecutive occurrence of 2 rectal fistulas, we stopped using the insertion of spacer gel. Longer follow-up is necessary for evaluation of PFS and OS. (Ion Prostate Irradiation (IPI); (NCT01641185); (ClinicalTrials.gov).)« less

PedVacc 002: a phase I/II randomized clinical trial of MVA.HIVA vaccine administered to infants born to human immunodeficiency virus type 1-positive mothers in Nairobi.

PubMed

Njuguna, Irene N; Ambler, Gwen; Reilly, Marie; Ondondo, Beatrice; Kanyugo, Mercy; Lohman-Payne, Barbara; Gichuhi, Christine; Borthwick, Nicola; Black, Antony; Mehedi, Shams-Rony; Sun, Jiyu; Maleche-Obimbo, Elizabeth; Chohan, Bhavna; John-Stewart, Grace C; Jaoko, Walter; Hanke, Tomáš

2014-10-07

A safe, effective vaccine for breastfeeding infants born to HIV-1-positive mothers could complement antiretroviral therapy (ART) for prevention of mother-to-child transmission of HIV-1. To date, only a few HIV-1 vaccine candidates have been tested in infants. A phase I/II randomized controlled trial PedVacc 002 was conducted to determine the safety and immunogenicity of a single, low dose of MVA.HIVA vaccine delivered intramuscularly to healthy 20-week-old infants born to HIV-1-positive mothers in Nairobi, Kenya. Pregnant HIV-1-positive women in the 2nd/3rd trimester of gestation were enrolled, provided with ART and self-selected their infant-feeding modality. Infants received nevirapine and cotrimoxazole prophylaxis. At 20 weeks of age, eligible HIV-1-negative infants were randomized to vaccine versus no-treatment arms and followed to 48 weeks of age for assessments of vaccine safety, HIV-1-specific T-cell responses and antibodies to routine childhood vaccines. Between February and November 2010, 182 mothers were screened, 104 were eligible and followed on ART during pregnancy/postpartum, of whom 73 had eligible infants at 20 weeks postpartum. Thirty-six infants were randomized to vaccine and 37 to no treatment. Eighty-four percent of infants breastfed, and retention at 48 weeks was 99%. Adverse events were rare and similar between the two arms. HIV-1-specific T-cell frequencies in interferon-γ ELISPOT assay were transiently higher in the MVA.HIVA arm (p=0.002), but not above the threshold for a positive assay. Protective antibody levels were adequate and similar between arms for all routine childhood vaccines except HBV, where 71% of MVA.HIVA subjects compared to 92% of control subjects were protected (p=0.05). This trial tested for the first time an MVA-vectored candidate HIV-1 vaccine in HIV-1-exposed infants in Africa, demonstrating trial feasibility and vaccine safety, low immunogenicity, and compatibility with routine childhood vaccinations. These results are reassuring for use of the MVA vector in more potent prime-boost regimens. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Phase II Study of Adjuvant Immunotherapy with the CSF-470 Vaccine Plus Bacillus Calmette-Guerin Plus Recombinant Human Granulocyte Macrophage-Colony Stimulating Factor vs Medium-Dose Interferon Alpha 2B in Stages IIB, IIC, and III Cutaneous Melanoma Patients: A Single Institution, Randomized Study.

PubMed

Mordoh, José; Pampena, María Betina; Aris, Mariana; Blanco, Paula Alejandra; Lombardo, Mónica; von Euw, Erika María; Mac Keon, Soledad; Yépez Crow, Michelle; Bravo, Alicia Inés; O'Connor, Juan Manuel; Orlando, Ana Gabriela; Ramello, Franco; Levy, Estrella Mariel; Barrio, María Marcela

2017-01-01

The irradiated, allogeneic, cellular CSF-470 vaccine plus Bacillus Calmette-Guerin (BCG) and recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) is being tested against medium-dose IFN-α2b in stages IIB-III cutaneous melanoma (CM) patients (pts) after surgery in an open, randomized, Phase II/III study. We present the results of the Phase II part of the ongoing CASVAC-0401 study (ClinicalTrials.gov: NCT01729663). Thirty-one pts were randomized to the CSF-470 vaccine ( n  = 20) or to the IFN-α2b arm ( n  = 11). During the 2-year treatment, immunized pts should receive 13 vaccinations. On day 1 of each visit, 1.6 × 10 7 irradiated CSF-470 cells plus 10 6 colony-forming units BCG plus 100 µg rhGM-CSF were administered intradermally, followed on days 2-4 by 100 µg rhGM-CSF. IFN-α2b pts should receive 10 million units (MU)/day/5 days a week for 4 weeks; then 5 MU thrice weekly for 23 months. Toxicity and quality of life (QOL) were evaluated at each visit. With a mean and a maximum follow-up of 39.4 and 83 months, respectively, a significant benefit in the distant metastasis-free survival (DMFS) for CSF-470 was observed ( p  = 0.022). Immune monitoring showed an increase in antitumoral cellular and humoral response in vaccinated pts. CSF-470 was well tolerated; 20/20 pts presented grades 1-2 dermic reactions at the vaccination site; 3/20 pts presented grade 3 allergic reactions. Other adverse events (AEs) were grade 1. Pts in the IFN-α2b arm presented grades 2-3 hematological (7/11), hepatic (2/11), and cardiac (1/11) toxicity; AEs in 9/11 pts forced treatment interruptions. QOL was significantly superior in the vaccine arm ( p  < 0.0001). Our results suggest that CSF-470 vaccine plus BCG plus GM-CSF can significantly prolong, with lower toxicity, the DMFS of high-risk CM pts with respect to medium-dose IFN-α2b. The continuation of a Phase III part of the CASVAC-0401 study is encouraged.

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial.

PubMed

Liang, J; Bi, N; Wu, S; Chen, M; Lv, C; Zhao, L; Shi, A; Jiang, W; Xu, Y; Zhou, Z; Wang, W; Chen, D; Hui, Z; Lv, J; Zhang, H; Feng, Q; Xiao, Z; Wang, X; Liu, L; Zhang, T; Du, L; Chen, W; Shyr, Y; Yin, W; Li, J; He, J; Wang, L

2017-04-01

The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer (NSCLC) remains unclear. A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin (EP) or carboplatin/paclitaxel (PC) in patients with stage III NSCLC. Patients were randomly received 60-66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m2 on days 1-5 and cisplatin 50 mg/m2 on days 1 and 8 every 4 weeks for two cycles (EP arm), or paclitaxel 45 mg/m2 and carboplatin (AUC 2) on day 1 weekly (PC arm). The primary end point was overall survival (OS). The study was designed with 80% power to detect a 17% superiority in 3-year OS with a type I error rate of 0.05. A total of 200 patients were randomized and 191 patients were treated (95 in the EP arm and 96 in the PC arm). With a median follow-up time of 73 months, the 3-year OS was significantly higher in the EP arm than that of the PC arm. The estimated difference was 15.0% (95% CI 2.0%-28.0%) and P value of 0.024. Median survival times were 23.3 months in the EP arm and 20.7 months in the PC arm (log-rank test P = 0.095, HR 0.76, 95%CI 0.55-1.05). The incidence of Grade ≥2 radiation pneumonitis was higher in the PC arm (33.3% versus 18.9%, P = 0.036), while the incidence of Grade ≥3 esophagitis was higher in the EP arm (20.0% versus 6.3%, P = 0.009). EP might be superior to weekly PC in terms of OS in the setting of concurrent chemoradiation for unresectable stage III NSCLC. NCT01494558. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A new index of flat breaststroke propulsion: a comparison of elite men and women.

PubMed

Seifert, L; Chollet, D

2005-03-01

This study examined arm and leg coordination and propulsion during the flat breaststroke in nine elite male and eight elite female swimmers over three race paces (200 m, 100 m and 50 m). Coordination was expressed using four temporal gaps (T1, T2, T3, T4), which described the continuity between the propulsive phases of the limbs, as recorded on a video device (50 Hz). Glide duration was denoted T1, the time between the beginning of arm and leg recovery was denoted T2, the time between the end of arm and the leg recovery was denoted T3, and the time between 90 degrees of flexion during arm recovery and 90 degrees during leg recovery was denoted T4. Using these temporal gaps, four stroke phases (propulsion, glide, recovery and leg insweep) could be followed over a complete arm and leg stroke. The total duration of arm and leg propulsion was assessed by a new index of flat breaststroke propulsion (IFBP). Velocity, stroke rate and stroke length were also calculated for each pace. The elite swimmers showed short T2, T3 and T4; moreover, T1 decreased when the pace increased. Expertise in the flat breaststroke was thus characterized by synchronized arm and leg recoveries and increased continuity in the arm and leg propulsions with increasing velocity. Differences between the sexes in the spatio-temporal parameters were possibly due to anthropometric differences (the men were heavier, older and taller than the women) and different motor organization linked to arm and leg coordination (shorter T3, body glide and body recovery, and greater body propulsion and higher IFBP in the men). The men's propulsive actions showed greater continuity, particularly in the sprint. The best men adopted a superposition coordination and thus had the ability to overcome very great active drag. Temporal gap measurement and the IFBP are practical indicators of arm and leg coordination and propulsion that can be exploited by coaches and swimmers to increase the continuity between propulsive actions during the flat breaststroke.

SAKK 24/09: safety and tolerability of bevacizumab plus paclitaxel vs. bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer - a multicenter, randomized phase III trial.

PubMed

Rochlitz, Christoph; Bigler, Martin; von Moos, Roger; Bernhard, Jürg; Matter-Walstra, Klazien; Wicki, Andreas; Zaman, Khalil; Anchisi, Sandro; Küng, Marc; Na, Kyung-Jae; Bärtschi, Daniela; Borner, Markus; Rordorf, Tamara; Rauch, Daniel; Müller, Andreas; Ruhstaller, Thomas; Vetter, Marcus; Trojan, Andreas; Hasler-Strub, Ursula; Cathomas, Richard; Winterhalder, Ralph

2016-10-10

Adding bevacizumab to chemotherapy improves response rates and progression-free survival (PFS) in metastatic breast cancer (mBC). We aimed to demonstrate decreased toxicity with metronomic chemotherapy/bevacizumab compared with paclitaxel/bevacizumab. This multicenter, randomized phase III trial compared bevacizumab with either paclitaxel (arm A) or daily oral capecitabine-cyclophosphamide (arm B) as first-line treatment in patients with HER2-negative advanced breast cancer. The primary endpoint was the incidence of selected grade 3-5 adverse events (AE) including: febrile neutropenia, infection, sensory/motor neuropathy, and mucositis. Secondary endpoints included objective response rate, disease control rate, PFS, overall survival (OS), quality of life (QoL), and pharmacoeconomics. The study was registered prospectively with ClinicalTrials.gov, number NCT01131195 on May 25, 2010. Between September 2010 and December 2012, 147 patients were included at 22 centers. The incidence of primary endpoint-defining AEs was similar in arm A (25 % [18/71]; 95 % CI 15-35 %) and arm B (24 % [16/68]; 95 % CI 13-34 %; P = 0.96). Objective response rates were 58 % (42/73; 95 % CI 0.46-0.69) and 50 % (37/74; 95 % CI 0.39-0.61) in arms A and B, respectively (P = 0.45). Median PFS was 10.3 months (95 % CI 8.7-11.3) in arm A and 8.5 months (95 % CI 6.5-11.9) in arm B (P = 0.90). Other secondary efficacy endpoints were not significantly different between study arms. The only statistically significant differences in QoL were less hair loss and less numbness in arm B. Treatment costs between the two arms were equivalent. This trial failed to meet its primary endpoint of a reduced rate of prespecified grade 3-5 AEs with metronomic bevacizumab, cyclophosphamide and capecitabine.

Decision-theoretic designs for a series of trials with correlated treatment effects using the Sarmanov multivariate beta-binomial distribution.

PubMed

Hee, Siew Wan; Parsons, Nicholas; Stallard, Nigel

2018-03-01

The motivation for the work in this article is the setting in which a number of treatments are available for evaluation in phase II clinical trials and where it may be infeasible to try them concurrently because the intended population is small. This paper introduces an extension of previous work on decision-theoretic designs for a series of phase II trials. The program encompasses a series of sequential phase II trials with interim decision making and a single two-arm phase III trial. The design is based on a hybrid approach where the final analysis of the phase III data is based on a classical frequentist hypothesis test, whereas the trials are designed using a Bayesian decision-theoretic approach in which the unknown treatment effect is assumed to follow a known prior distribution. In addition, as treatments are intended for the same population it is not unrealistic to consider treatment effects to be correlated. Thus, the prior distribution will reflect this. Data from a randomized trial of severe arthritis of the hip are used to test the application of the design. We show that the design on average requires fewer patients in phase II than when the correlation is ignored. Correspondingly, the time required to recommend an efficacious treatment for phase III is quicker. © 2017 The Author. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Arms control and The President's Strategic Defense Initiative

NASA Astrophysics Data System (ADS)

Bon, J. J.

1985-04-01

The President's Strategic Defense Initiative (SDI) provides the hope for eliminating the threat from ballistic missiles. This study evaluates the impact of SDI on existing and future arms control agreements. Because new or modified space-related treaties are a probable result of the SDI, this study concludes that the best single strategy for arms control negotiations is to preserve overall US interests and maintain open technological options vice severely limiting any space technology that might some day become part of a space-based defensive system.

Erlotinib 150 mg daily plus chemotherapy in advanced pancreatic cancer: an interim safety analysis of a multicenter, randomized, cross-over phase III trial of the 'Arbeitsgemeinschaft Internistische Onkologie'.

PubMed

Boeck, Stefan; Vehling-Kaiser, Ursula; Waldschmidt, Dirk; Kettner, Erika; Märten, Angela; Winkelmann, Cornelia; Klein, Stefan; Kojouharoff, Georgi; Gauler, Thomas; Fischer von Weikersthal, Ludwig; Clemens, Michael R; Geissler, Michael; Greten, Tim F; Hegewisch-Becker, Susanna; Neugebauer, Sascha; Heinemann, Volker

2010-01-01

To date, only limited toxicity data are available for the combination of erlotinib with either capecitabine or gemcitabine as front-line therapy for advanced pancreatic cancer. Within a randomized phase III trial, 281 treatment-naive patients were randomly assigned between capecitabine (2000 mg/m/day, for 14 days, once every 3 weeks) plus erlotinib (150 mg/day, arm A) and gemcitabine (1000 mg/m as a 30-min infusion) plus erlotinib (150 mg/day, arm B). In case of treatment failure, patients were crossed over to a second-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was the time to treatment failure of second-line therapy (TTF2). This interim analysis of toxicity contains safety data from the first 127 randomized patients. During first-line therapy, patients received a median number of three treatment cycles (range 0-13) in both the arms. Regarding chemotherapy, a treatment delay was observed in 12% of the cycles in arm A and in 22% of the cycles in arm B. Dose reductions of the cytostatic drug were performed in 18 and 27% of treatment cycles, respectively. Erlotinib dose reductions were performed in 6 and 11% of all cycles. Grade 3/4 hematological toxicity was <10% in both the arms; major grade 3/4 toxicities in arms A and B were diarrhea (9 vs. 7%), skin rash (4 vs. 12%), and hand-foot syndrome (7 vs. 0%). No treatment-related death was observed. In conclusion, this interim safety analysis suggests that treatment with erlotinib 150 mg/day is feasible in combination with capecitabine or gemcitabine.

Kinematic and kinetic comparisons between American and Korean professional baseball pitchers.

PubMed

Escamilla, Rafael; Fleisig, Glen; Barrentine, Steven; Andrews, James; Moorman, Claude

2002-07-01

The purpose of this study was to quantify and compare kinematic, temporal, and kinetic characteristics of American and Korean professional pitchers in order to investigate differences in pitching mechanics, performance, and injury risks among two different cultures and populations of baseball pitchers. Eleven American and eight Korean healthy professional baseball pitchers threw multiple fastball pitches off an indoor throwing mound positioned at regulation distance from home plate. A Motion Analysis three-dimensional automatic digitizing system was used to collect 200 Hz video data from four electronically synchronized cameras. Twenty kinematic, six temporal, and 11 kinetic variables were analyzed at lead foot contact, during the arm cocking and arm acceleration phases, at ball release, and during the arm deceleration phase. A radar gun was used to quantify ball velocity. At lead foot contact, the American pitchers had significantly greater horizontal abduction of the throwing shoulder, while Korean pitchers exhibited significantly greater abduction and external rotation of the throwing shoulder. During arm cocking, the American pitchers displayed significantly greater maximum shoulder external rotation and maximum pelvis angular velocity. At the instant of ball release, the American pitchers had significantly greater forward trunk tilt and ball velocity and significantly less knee flexion, which help explain why the American pitchers had 10% greater ball velocity compared to the Korean pitchers. The American pitchers had significantly greater maximum shoulder internal rotation torque and maximum elbow varus torque during arm cocking, significantly greater elbow flexion torque during arm acceleration, and significantly greater shoulder and elbow proximal forces during arm deceleration. While greater shoulder and elbow forces and torques generated in the American pitchers helped generate greater ball velocity for the American group, these greater kinetics may predispose this group to a higher risk of shoulder and elbow injuries.

Effective seat-to-head transmissibility in whole-body vibration: Effects of posture and arm position

NASA Astrophysics Data System (ADS)

Rahmatalla, Salam; DeShaw, Jonathan

2011-12-01

Seat-to-head transmissibility is a biomechanical measure that has been widely used for many decades to evaluate seat dynamics and human response to vibration. Traditionally, transmissibility has been used to correlate single-input or multiple-input with single-output motion; it has not been effectively used for multiple-input and multiple-output scenarios due to the complexity of dealing with the coupled motions caused by the cross-axis effect. This work presents a novel approach to use transmissibility effectively for single- and multiple-input and multiple-output whole-body vibrations. In this regard, the full transmissibility matrix is transformed into a single graph, such as those for single-input and single-output motions. Singular value decomposition and maximum distortion energy theory were used to achieve the latter goal. Seat-to-head transmissibility matrices for single-input/multiple-output in the fore-aft direction, single-input/multiple-output in the vertical direction, and multiple-input/multiple-output directions are investigated in this work. A total of ten subjects participated in this study. Discrete frequencies of 0.5-16 Hz were used for the fore-aft direction using supported and unsupported back postures. Random ride files from a dozer machine were used for the vertical and multiple-axis scenarios considering two arm postures: using the armrests or grasping the steering wheel. For single-input/multiple-output, the results showed that the proposed method was very effective in showing the frequencies where the transmissibility is mostly sensitive for the two sitting postures and two arm positions. For multiple-input/multiple-output, the results showed that the proposed effective transmissibility indicated higher values for the armrest-supported posture than for the steering-wheel-supported posture.

Robotics Offer Newfound Surgical Capabilities

NASA Technical Reports Server (NTRS)

2008-01-01

Barrett Technology Inc., of Cambridge, Massachusetts, completed three Phase II Small Business Innovation Research (SBIR) contracts with Johnson Space Center, during which the company developed and commercialized three core technologies: a robotic arm, a hand that functions atop the arm, and a motor driver to operate the robotics. Among many industry uses, recently, an adaptation of the arm has been cleared by the U.S. Food and Drug Administration (FDA) for use in a minimally invasive knee surgery procedure, where its precision control makes it ideal for inserting a very small implant.

A four-way junction with triple-helical arms: design, characterization, and stability.

PubMed

Makube, N; Klump, H H

2000-05-01

The formation of the four-way junction containing four triple-helical arms has been demonstrated using chemical methods (polyacrylamide gel electrophoresis and chemical footprinting using OsO(4) as a probe) and physical methods (UV absorbance melting and DSC). The junction J(T1T3) was assembled from two 20-mer purine strands and two 44-mer pyrimidine strands. To determine the contribution of the different arms to the stability of the complete structure of J(T1T3), the junction was compared to two simplified substructures, J(T1) and J(T3), respectively. Common to these complexes is the underlying double-helical four-way junction Js. Addition of Na(+) had a profound effect on stabilizing and subsequently folding the junctions into the stacked X-structures. The following results support the structure present: (i) The native polyacrylamide electrophoresis exhibits only a single band(s) corresponding to one species present when all four single strands are mixed in equal amounts. (ii) OsO(4) modifications were investigated at pH 5.0 and in the presence of 10 mM Mg(2+) and 100 mM Na(+). There is no cleavage of thymine residues at the branch point and throughout the structure. (iii) The thermal unfolding of J(T1) and J(T3) illustrates that the triple-helical arms are more stable than the double-helical arms which are contained in these junctions and that J(T1T3) with four triple-helical arms is slightly more stable than J(T1) and J(T3). (iv) The calorimetric transition enthalpies determined for the arms of J(T1T3) are comparable to those associated with the unfolding of its corresponding arms in J(T1) and J(T3). The results also illustrate that the formation of the junctions is not restricted by the pH, [Na(+)], sequence composition of the arms, and/or the loop position. Copyright 2000 Academic Press.

Randomized phase II study of sequential carboplatin plus paclitaxel and gefitinib in chemotherapy-naïve patients with advanced or metastatic non-small-cell lung cancer: Long-term follow-up results.

PubMed

Kubo, Emi; Yamamoto, Noboru; Nokihara, Hiroshi; Fujiwara, Yutaka; Horinouchi, Hidehito; Kanda, Shintaro; Goto, Yasushi; Ohe, Yuichiro

2017-01-01

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib was initially approved in Japan in 2002 for the treatment of advanced or metastatic non-small-cell lung cancer (NSCLC); however, the optimal order of conventional cytotoxic chemotherapy (carboplatin and paclitaxel) and gefitinib administration has not been determined. We conducted a randomized phase II study of carboplatin and paclitaxel followed by gefitinib vs. gefitinib followed by carboplatin and paclitaxel to select a candidate for further development in a phase III study of chemotherapy-naïve patients with advanced or metastatic NSCLC, regardless of their EGFR mutation status. A total of 97 patients meeting this description were randomly assigned to arm A (carboplatin and paclitaxel followed by gefitinib; n=49) or B (gefitinib followed by carboplatin and paclitaxel; n=48) from June, 2003 to October, 2005. Carboplatin and paclitaxel were administered in 4 cycles every 3 weeks; gefitinib was continued until disease progression or development of unacceptable toxicity. The primary endpoint was overall survival; the secondary endpoints were response rate and adverse event prevalence. The median overall follow-up was 65.1 months (range, 28.7-75.1 months). The major toxicities were hematological (carboplatin and paclitaxel) or skin rash, diarrhea and hepatic dysfunction (gefitinib). Interstitial lung disease was observed in 1 patient from each arm. In arms A and B, the carboplatin and paclitaxel response rate, gefitinib response rate, and median survival durations were 34.8 and 26.5%, 33.3 and 35.7%, and 18.8 and 17.2 months, respectively. Arm A was selected for a subsequent phase III study.

Bilateral coupling facilitates recovery of rhythmical movements from perturbation in healthy and post-stroke subjects.

PubMed

Ustinova, Ksenia I; Feldman, Anatol G; Levin, Mindy F

2013-06-01

The paretic arm of subjects with stroke has a decreased ability to quickly adapt to and recover from perturbations during rhythmical arm swinging. We investigated whether bilateral coupling in the synchronous motion of two arms may facilitate the restoration of rhythmical movement of the paretic arm in subjects with chronic hemiparesis due to stroke. While standing, stroke and age-matched healthy (control) subjects swung one or both arms synchronously at ~0.8 Hz from the shoulder joints. In randomly selected cycles, one arm was transiently arrested by an electromagnetic device when moving forward or backward. In the control group, bilateral swinging resumed faster than unilateral swinging regardless of which arm was perturbed. In the stroke group, this effect was observed only when the perturbation was applied to the paretic arm, suggesting that the motion of the non-paretic arm accelerated the recovery from perturbation of the paretic arm. In addition, bilateral swinging resumed after reduced anterior-posterior excursions of both arms in stroke subjects. Results confirm previous findings that bilateral swinging is normally guided by central changes in the referent configuration of the two arms that function as a single unit. As a consequence, both arms cooperate in recovery from perturbation of motion applied to one arm. Results also suggest that stroke-related brain damage alters the symmetry of bilateral interaction, resulting in deficits of inter-manual cooperative action. The involvement of the non-paretic arm could be beneficial for the recovery of swinging of both arms and may also facilitate movements of the paretic arm in certain tasks.

Design and pilot evaluation of competitive and cooperative exercise games for arm rehabilitation at home.

PubMed

Gorsic, Maja; Novak, Domen

2016-08-01

People with chronic arm impairment should exercise intensely at home after completing their clinical rehabilitation program, but frequently lack motivation. To address this issue, we present a home rehabilitation system that motivates patients by allowing them to perform arm exercises together with friends or relatives in competitive and cooperative games. Inertial sensors are used to track the patient's arm and control the game. The system was tested with seven adults with arm impairment as well as their friends or spouses. They tested four exercise games (single-player, competitive and two different cooperative games) for 3 minutes each. Of the 7 participants, 4 preferred the competitive game, 2 preferred a cooperative game, and 1 preferred to exercise alone. Competition also increased exercise intensity (measured using inertial sensors) compared to exercising alone. Though preliminary, these results indicate that competitive exercise games could improve arm rehabilitation at home for survivors of neurological and orthopedic injuries.

Wheelchair-mounted robotic arm to hold and move a communication device - final design.

PubMed

Barrett, Graham; Kurley, Kyle; Brauchie, Casey; Morton, Scott; Barrett, Steven

2015-01-01

At the 51st Rocky Mountain Bioengineering Symposium we presented a preliminary design for a robotic arm to assist an individual living within an assistive technology smart home. The individual controls much of their environment with a Dynavox Maestro communication device. However, the device obstructs the individual’s line of site when navigating about the smart home. A robotic arm was developed to move the communication device in and out of the user’s field of view as desired. The robotic arm is controlled by a conveniently mounted jelly switch. The jelly switch sends control signals to a four state (up, off, down, off) single-axis robotic arm interfaced to a DC motor by high power electronic relays. This paper describes the system, control circuitry, and multiple safety features. The arm will be delivered for use later in 2015.

Robust coordinated control of a dual-arm space robot

NASA Astrophysics Data System (ADS)

Shi, Lingling; Kayastha, Sharmila; Katupitiya, Jay

2017-09-01

Dual-arm space robots are more capable of implementing complex space tasks compared with single arm space robots. However, the dynamic coupling between the arms and the base will have a serious impact on the spacecraft attitude and the hand motion of each arm. Instead of considering one arm as the mission arm and the other as the balance arm, in this work two arms of the space robot perform as mission arms aimed at accomplishing secure capture of a floating target. The paper investigates coordinated control of the base's attitude and the arms' motion in the task space in the presence of system uncertainties. Two types of controllers, i.e. a Sliding Mode Controller (SMC) and a nonlinear Model Predictive Controller (MPC) are verified and compared with a conventional Computed-Torque Controller (CTC) through numerical simulations in terms of control accuracy and system robustness. Both controllers eliminate the need to linearly parameterize the dynamic equations. The MPC has been shown to achieve performance with higher accuracy than CTC and SMC in the absence of system uncertainties under the condition that they consume comparable energy. When the system uncertainties are included, SMC and CTC present advantageous robustness than MPC. Specifically, in a case where system inertia increases, SMC delivers higher accuracy than CTC and costs the least amount of energy.

LRRC6 Mutation Causes Primary Ciliary Dyskinesia with Dynein Arm Defects

PubMed Central

Horani, Amjad; Ferkol, Thomas W.; Shoseyov, David; Wasserman, Mollie G.; Oren, Yifat S.; Kerem, Batsheva; Amirav, Israel; Cohen-Cymberknoh, Malena; Dutcher, Susan K.; Brody, Steven L.; Elpeleg, Orly; Kerem, Eitan

2013-01-01

Despite recent progress in defining the ciliome, the genetic basis for many cases of primary ciliary dyskinesia (PCD) remains elusive. We evaluated five children from two unrelated, consanguineous Palestinian families who had PCD with typical clinical features, reduced nasal nitric oxide concentrations, and absent dynein arms. Linkage analyses revealed a single common homozygous region on chromosome 8 and one candidate was conserved in organisms with motile cilia. Sequencing revealed a single novel mutation in LRRC6 (Leucine-rich repeat containing protein 6) that fit the model of autosomal recessive genetic transmission, leading to a change of a highly conserved amino acid from aspartic acid to histidine (Asp146His). LRRC6 was localized to the cytoplasm and was up-regulated during ciliogenesis in human airway epithelial cells in a Foxj1-dependent fashion. Nasal epithelial cells isolated from affected individuals and shRNA-mediated silencing in human airway epithelial cells, showed reduced LRRC6 expression, absent dynein arms, and slowed cilia beat frequency. Dynein arm proteins were either absent or mislocalized to the cytoplasm in airway epithelial cells from a primary ciliary dyskinesia subject. These findings suggest that LRRC6 plays a role in dynein arm assembly or trafficking and when mutated leads to primary ciliary dyskinesia with laterality defects. PMID:23527195

The Michelson Stellar Interferometer Error Budget for Triple Triple-Satellite Configuration

NASA Technical Reports Server (NTRS)

Marathay, Arvind S.; Shiefman, Joe

1996-01-01

This report presents the results of a study of the instrumentation tolerances for a conventional style Michelson stellar interferometer (MSI). The method used to determine the tolerances was to determine the change, due to the instrument errors, in the measured fringe visibility and phase relative to the ideal values. The ideal values are those values of fringe visibility and phase that would be measured by a perfect MSI and are attributable solely to the object being detected. Once the functional relationship for changes in visibility and phase as a function of various instrument errors is understood it is then possible to set limits on the instrument errors in order to ensure that the measured visibility and phase are different from the ideal values by no more than some specified amount. This was done as part of this study. The limits we obtained are based on a visibility error of no more than 1% and a phase error of no more than 0.063 radians (this comes from 1% of 2(pi) radians). The choice of these 1% limits is supported in the literture. The approach employed in the study involved the use of ASAP (Advanced System Analysis Program) software provided by Breault Research Organization, Inc., in conjunction with parallel analytical calculations. The interferometer accepts object radiation into two separate arms each consisting of an outer mirror, an inner mirror, a delay line (made up of two moveable mirrors and two static mirrors), and a 10:1 afocal reduction telescope. The radiation coming out of both arms is incident on a slit plane which is opaque with two openings (slits). One of the two slits is centered directly under one of the two arms of the interferometer and the other slit is centered directly under the other arm. The slit plane is followed immediately by an ideal combining lens which images the radiation in the fringe plane (also referred to subsequently as the detector plane).

Piezoelectric micromotor based on the structure of serial bending arms.

PubMed

Tong, Jianhua; Cui, Tianhong; Shao, Peige; Wang, Liding

2003-09-01

This paper presents a new piezoelectric micromotor based on the structure of serial bending arms. Serial bending arms are composed of two piezoelectric bimorphs with one end fixed and the other end free, driven by two signals of a biased square wave with a phase difference of pi/2. The free end of a cantilever arm will move along an elliptic orbit so that the cantilever is used to drive a cylinder rotor. The rotor's end surface contacts the free end of the cantilever, resulting in the rotor's rotation. There are six serial bending arms anchored on the base. The driving mechanism of the micromotor is proposed and analyzed. A new micromotor prototype, 5 mm in diameter, has been fabricated and characterized. The maximum rotational speed reaches 325 rpm, and the output torque is about 36.5 microNm.

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

PubMed

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

2017-09-01

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

A Phase 2 Open Label, Single-Arm Trial to Evaluate the Combination of Cetuximab Plus Taxotere, Cisplatin, and 5-Flurouracil as an Induction Regimen in Patients With Unresectable Squamous Cell Carcinoma of the Head and Neck

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

Mesía, Ricard, E-mail: rmesia@iconcologia.net; Vázquez, Silvia; Grau, Juan J.

Purpose: Despite treatment, prognosis of unresectable squamous cell carcinoma of the head and neck (SCCHC) is dismal. Cetuximab therapy has proven to increase the clinical activity of radiation therapy and chemotherapy in patients with locoregional advanced disease with an acceptable toxicity profile. We designed a phase 2 trial to evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil (TPF) plus cetuximab (C-TPF) as an induction regimen in patients with unresectable SCCHN. Methods and Materials: A single-arm phase 2 trial was conducted. Eligible patients included those with untreated unresectable SCCHC, World Health Organization performance status of 0 to 1, 18 to 70 yearsmore » of age. Treatment consisted of four 21-day cycles of TPF (docetaxel, 75 mg/m{sup 2} day 1; cisplatin, 75 mg/m{sup 2} day 1; 5-fluorouracil [5-FU], 750 mg/m{sup 2} day 1-5) and cetuximab, 250 mg/m{sup 2} weekly (loading dose of 400 mg/m{sup 2}). Prophylactic granulocyte colony-stimulating factor and antibiotic support were given. After induction, sequential accelerated radiation therapy with concomitant boost (69.9 Gy) and weekly cetuximab therapy were delivered in the absence of disease progression. The primary endpoint was objective response rate (ORR) to C-TPF. Results: Fifty patients were enrolled across 8 centers. Median age was 54 years; disease was stage IV; oropharynx and hypopharynx were the most common primary sites. Eighty-two percent received 4 cycles of C-TPF, and 86% started sequential treatment based on radiation therapy and cetuximab. ORR after C-TPF was 86% (95% confidence interval [CI]: 73%-94%) and 24% had complete response (CR). With a median follow-up of 40.7 months, median overall survival (OS) was 40.7 months. The 2-year actuarial locoregional control (LRC) rate was 57%. The most common drug-related grade 3 or 4 toxicities during induction were neutropenia (24%), neutropenic fever (24%), and diarrhea (20%). There were 3 treatment-related deaths (6%). Conclusions: C-TPF yields high ORR and CR as induction treatment in unresectable SCCHN. However, hematologic toxicity is too high to recommend this regimen at the current dose.« less

Sequential FOLFIRI.3 + Gemcitabine Improves Health-Related Quality of Life Deterioration-Free Survival of Patients with Metastatic Pancreatic Adenocarcinoma: A Randomized Phase II Trial

PubMed Central

Anota, Amélie; Mouillet, Guillaume; Trouilloud, Isabelle; Dupont-Gossart, Anne-Claire; Artru, Pascal; Lecomte, Thierry; Zaanan, Aziz; Gauthier, Mélanie; Fein, Francine; Dubreuil, Olivier; Paget-Bailly, Sophie; Taieb, Julien; Bonnetain, Franck

2015-01-01

Background A randomized multicenter phase II trial was conducted to assess the sequential treatment strategy using FOLFIRI.3 and gemcitabine alternately (Arm 2) compared to gemcitabine alone (Arm 1) in patients with metastatic non pre-treated pancreatic adenocarcinoma. The primary endpoint was the progression-free survival (PFS) rate at 6 months. It concludes that the sequential treatment strategy appears to be feasible and effective with a PFS rate of 43.5% in Arm 2 at 6 months (26.1% in Arm 1). This paper reports the results of the longitudinal analysis of the health-related quality of life (HRQoL) as a secondary endpoint of this study. Methods HRQoL was evaluated using the EORTC QLQ-C30 at baseline and every two months until the end of the study or death. HRQoL deterioration-free survival (QFS) was defined as the time from randomization to a first significant deterioration as compared to the baseline score with no further significant improvement, or death. A propensity score was estimated comparing characteristics of partial and complete responders. Analyses were repeated with inverse probability weighting method using the propensity score. Multivariate Cox regression analyses were performed to identify independent factors influencing QFS. Results 98 patients were included between 2007 and 2011. Adjusting on the propensity score, patients of Arm 2 presented a longer QFS of Global Health Status (Hazard Ratio: 0.52 [0.31-0.85]), emotional functioning (0.35 [0.21–0.59]) and pain (0.50 [0.31 – 0.81]) than those of Arm 1. Conclusion Patients of Arm 2 presented a better HRQoL with a longer QFS than those of Arm 1. Moreover, the propensity score method allows to take into account the missing data depending on patients’ characteristics. Trial registration information Eudract N° 2006-005703-34. (Name of the Trial: FIRGEM). PMID:26010884

Arm Activity During Daily Life in Individuals With Chronic Obstructive Pulmonary Disease.

PubMed

Janaudis-Ferreira, Tania; Mathur, Sunita; Romano, Julia Marie; Goldstein, Roger Samuel; Brooks, Dina

2016-01-01

To determine whether individuals with chronic obstructive pulmonary disease (COPD) have decreased arm activity during daily life compared with healthy controls and explore the relationships between arm activity during daily life and arm functional measures in individuals with COPD. This was a prospective cross-sectional study that included 30 people with COPD and 14 healthy controls. Subjects attended a single assessment session in which measurements of arm exercise capacity, arm functional performance, self-perception of performance during activities of daily living (ADL), shoulder and elbow flexion force and biceps and triceps thickness were performed. On completion of this session, participants were issued a wrist actigraph and asked to wear the device on the dominant arm for 24 hours for 7 consecutive days. Compared with healthy controls, patients with COPD presented decreased total activity level in daily life (P = .001). When corrected for walking, the level of arm activity did not differ between individuals with COPD and healthy controls (P = .62). No correlations were found between arm activity and arm exercise capacity, arm functional performance, upper limb muscle strength, and self-perception of performance during ADL (r =-0.20 to 0.14; all P ≥ .10). Arm activity intensity in individuals with COPD did not differ from that of healthy controls when measured by a wrist actigraph. Moreover, arm activity was not associated with other clinical outcomes of arm function. Disability during ADL is multifactorial, and only limited inferences of function can be made from accelerometer data.

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial.

PubMed

Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin; Räty, Riikka; Wader, Karin Fahl; Laurell, Anna; Toldbod, Helle; Pedersen, Lone Bredo; Niemann, Carsten Utoft; Dahl, Christina; Kuitunen, Hanne; Geisler, Christian H; Grønbæk, Kirsten; Kolstad, Arne

2018-03-01

Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone. In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients aged 18 years or older with relapsed or refractory mantle cell lymphoma who had previously been treated with at least one rituximab-containing regimen, an Eastern Cooperative Oncology Group performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56 days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m 2 ) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle, whereas oral lenalidomide (15 mg once a day) was given on days 1-21. The primary endpoint was overall response assessed in the intention-to-treat population according to Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment. The trial is ongoing, but is no longer accruing patients, and is registered with ClinicalTrials.gov, number NCT02460276. Between April 30, 2015, and June 1, 2016, we enrolled 50 patients with relapsed or refractory mantle cell lymphoma at ten centres in Sweden, Finland, Norway, and Denmark. At a median follow-up of 17·8 months (IQR 14·7-20·9), 38 (76%, 95% CI 63-86) patients had an overall response, including 28 (56%, 42-69) patients who had a complete response and ten (20%, 11-33) who had a partial response. The most common grade 3-4 adverse events were neutropenia (in 19 [38%] of 50 patients), infections (in 11 [22%] patients), and cutaneous toxicity (in seven [14%] patients). There were three treatment-related deaths during the study, two due to sepsis and one due to embolic stroke. Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomised controlled trial. Janssen and Celgene. Copyright © 2018 Elsevier Ltd. All rights reserved.

Efficacy and cost-effectiveness of octenidine wound gel in the treatment of chronic venous leg ulcers in comparison to modern wound dressings.

PubMed

Hämmerle, Gilbert; Strohal, Robert

2016-04-01

The aim of this study was to determine the efficacy, safety and cost-effectiveness of an octenidine-based wound gel in the treatment of chronic venous leg ulcers. For this purpose, 49 wounds were treated with either modern wound-phase-adapted dressings alone (treatment arm 1; n = 17), octenidine wound gel plus modern wound-phase-adapted dressings (treatment arm 2; n = 17) or octenidine wound gel alone (treatment arm 3; n = 15). During the study period of 42 days with dressing changes every 3-5 days, wound healing characteristics and treatment costs of different dressings were analysed. Wound size reduction was significantly better (P = 0·028) in both octenidine wound gel treatment arms compared to modern dressings alone with total reductions of 14·6%, 64·1% and 96·2% in treatment arms 1-3. Early wound healing was merely observed under octenidine wound gel treatment (n = 9), whereby lowest treatment costs were generated by octenidine wound gel alone (€20·34/dressing change). As a result, the octenidine wound gel is cost-effective and well suitable for the treatment of chronic venous leg ulcers, considering both safety and promotion of wound healing. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Intracyclic Velocity Variation of the Center of Mass and Hip in Breaststroke Swimming With Maximal Intensity.

PubMed

Gourgoulis, Vassilios; Koulexidis, Stylianos; Gketzenis, Panagiotis; Tzouras, Grigoris

2018-03-01

Gourgoulis, V, Koulexidis, S, Gketzenis, P, and Tzouras, G. Intra-cyclic velocity variation of the center of mass and hip in breaststroke swimming with maximal intensity. J Strength Cond Res 32(3): 830-840, 2018-The aim of the study was to compare the center of mass (CM) and hip (HIP) intracyclic velocity variation in breaststroke swimming using 3-dimensional kinematic analysis. Nine male breaststrokes, of moderate performance level, swam 25-m breaststroke with maximal intensity, and their movements were recorded, both under and above the water surface, using 8 digital cameras. Their CM and HIP velocities and their intracyclic variations were estimated after manual digitization of 28 selected points on the body in a complete arm and leg breaststroke cycle. Paired sample t-tests or Wilcoxon tests, when the assumption of normality was broken, were used for statistical analyses. In both, CM and HIP velocity-time curves, the results revealed a similar pattern of 2 clear peaks associated with the leg and arm propulsive phases and 2 minimal velocities that corresponded to the arm and leg recovery phase and the lag time between the leg and arm propulsive phases, respectively. However, despite this similar general pattern, the HIP minimum resultant velocity was significantly lower, whereas its maximal value was significantly greater, than the corresponding CM values. Consequently, the HIP intracyclic swimming velocity fluctuation significantly overestimates the actual variation of the swimmer's velocity in breaststroke swimming.

A Randomized Trial of Displaying Paid Price Information on Imaging Study and Procedure Ordering Rates.

PubMed

Chien, Alyna T; Lehmann, Lisa Soleymani; Hatfield, Laura A; Koplan, Kate E; Petty, Carter R; Sinaiko, Anna D; Rosenthal, Meredith B; Sequist, Thomas D

2017-04-01

Prior studies have demonstrated how price transparency lowers the test-ordering rates of trainees in hospitals, and physician-targeted price transparency efforts have been viewed as a promising cost-controlling strategy. To examine the effect of displaying paid-price information on test-ordering rates for common imaging studies and procedures within an accountable care organization (ACO). Block randomized controlled trial for 1 year. A total of 1205 fully licensed clinicians (728 primary care, 477 specialists). Starting January 2014, clinicians in the Control arm received no price display; those in the intervention arms received Single or Paired Internal/External Median Prices in the test-ordering screen of their electronic health record. Internal prices were the amounts paid by insurers for the ACO's services; external paid prices were the amounts paid by insurers for the same services when delivered by unaffiliated providers. Ordering rates (orders per 100 face-to-face encounters with adult patients): overall, designated to be completed internally within the ACO, considered "inappropriate" (e.g., MRI for simple headache), and thought to be "appropriate" (e.g., screening colonoscopy). We found no significant difference in overall ordering rates across the Control, Single Median Price, or Paired Internal/External Median Prices study arms. For every 100 encounters, clinicians in the Control arm ordered 15.0 (SD 31.1) tests, those in the Single Median Price arm ordered 15.0 (SD 16.2) tests, and those in the Paired Prices arms ordered 15.7 (SD 20.5) tests (one-way ANOVA p-value 0.88). There was no difference in ordering rates for tests designated to be completed internally or considered to be inappropriate or appropriate. Displaying paid-price information did not alter how frequently primary care and specialist clinicians ordered imaging studies and procedures within an ACO. Those with a particular interest in removing waste from the health care system may want to consider a variety of contextual factors that can affect physician-targeted price transparency.

Association between CFH, CFB, ARMS2, SERPINF1, VEGFR1 and VEGF polymorphisms and anatomical and functional response to ranibizumab treatment in neovascular age-related macular degeneration.

PubMed

Cobos, Estefania; Recalde, Sergio; Anter, Jaouad; Hernandez-Sanchez, Maria; Barreales, Carla; Olavarrieta, Leticia; Valverde, Alicia; Suarez-Figueroa, Marta; Cruz, Fernando; Abraldes, Maximino; Pérez-Pérez, Julian; Fernández-Robredo, Patricia; Arias, Luis; García-Layana, Alfredo

2018-03-01

We sought to determine if specific genetic single nucleotide polymorphisms (SNPs) influence vascular endothelial growth factor inhibition response to ranibizumab in neovascular age-related macular degeneration (AMD). A total of 403 Caucasian patients diagnosed with exudative AMD were included. After a three-injection loading phase, a pro re nata regimen was followed. Nine SNPs from six different genes (CFH, CFB, ARMS2, SERPINF1, VEGFR1, VEGF) were genotyped. Non-genetic risk factors (gender, smoking habit and hypertension) were also assessed. Patients were classified as good or poor responders (GR or PR) according to functional (visual acuity), anatomical (foveal thickness measured by OCT) and fluid criteria (fluid/no fluid measured by OCT). Hypertension was the environmental factor with the strongest poor response association with ranibizumab in the anatomical measure after the loading phase (p = 0.0004; OR 3.7; 95% CI, 2.4-5.8) and after 12 months of treatment (p = 10 -5 ; OR 2.3; 95% CI, 1.5-3.4). The genetic variants rs12614 (CFB), rs699947 (VEGFA) and rs7993418 (VEGFR1) predisposed patients to a good response, while rs12603486 and rs1136287 (SERPINF1) were associated with a poor response. The protective genotype of rs800292 variant (CFH) was also associated with a poor anatomical response (p 0.0048). All these data suggest that genetics play an important role in treatment response in AMD patients. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Optical Sensors Based on Single on Arm Thin Film Waveguide Interferometer

NASA Technical Reports Server (NTRS)

Sarkisov, S. S.; Diggs, D.; Curley, M.; Adamovsky, Grigory (Technical Monitor)

2000-01-01

Single-arm dual-mode optical waveguide interferometer utilizes interference between two modes of different order. Sensing effect results from the change in propagation conditions of the modes caused by the environment. The waveguide is made as an open asymmetric structure containing a dye-doped polymer film onto a quartz substrate. It is more sensitive to the change of environment than its conventional polarimetric analog using orthogonal modes (TE and TM) of the same order. The sensor still preserves the option of operating in polarimetric regime using a variety of mode combinations such as TE(sub 0)/TM(sub 0) (conventional) TE(sub 0)/TM(sub 1), TE(sub 1)/TM(sub 0), or TE(sub 1)/TM(sub 1) but can also work in nonpolarimetric regime using combinations TE(sub 0)/TE(sub 1) or TM(sub 0)/TM(sub 1). Utilization of different mode combinations simultaneously makes the device more versatile. Application of the sensor to gas sensing is based on doping polymer film with an organic indicator dye targeting a particular gaseous reagent. Change of the optical absorption spectrum of the dye caused by the gaseous pollutant results in change of the reactive index of the dye-doped polymer film that can be detected by the sensor. As indicator dyes we utilize Bromocresol Purple doped into polymer poly(methyl) methacrylate that is sensitive to small concentrations of ammonia. The indicator dye demonstrated an irreversible increase in optical absorption near the peak at 350 nm being exposed to 5% ammonia in pure nitrogen at 600 Torr. The dye also showed reversible growth of the absorption peak near 600 nm after exposure to a vapor of standard medical ammonia spirit (65% alcohol). We have built a breadboard prototype of the sensor with He-Ne laser as a light source and with a single mode fiber input and a multimode fiber output. The prototype showed a sensitivity to temperature change of the order of 2 C per 2pi phase shift. The sensitivity of the sensor to the presence of dTy ammonia is not less than 300 ppm per 2pi phase shift. The proposed sensor can be used as a robust stand-alone instrument for continuous environment pollution monitoring.

Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study.

PubMed

Topp, Max S; Gökbuget, Nicola; Stein, Anthony S; Zugmaier, Gerhard; O'Brien, Susan; Bargou, Ralf C; Dombret, Hervé; Fielding, Adele K; Heffner, Leonard; Larson, Richard A; Neumann, Svenja; Foà, Robin; Litzow, Mark; Ribera, Josep-Maria; Rambaldi, Alessandro; Schiller, Gary; Brüggemann, Monika; Horst, Heinz A; Holland, Chris; Jia, Catherine; Maniar, Tapan; Huber, Birgit; Nagorsen, Dirk; Forman, Stephen J; Kantarjian, Hagop M

2015-01-01

Adults with relapsed or refractory B-precursor acute lymphoblastic leukaemia have an unfavourable prognosis. Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19, an antigen consistently expressed on B-lineage acute lymphoblastic leukaemia cells. We aimed to confirm the activity and safety profile of blinatumomab for acute lymphoblastic leukaemia. In a multicentre, single-arm, open-label phase 2 study, we enrolled adult patients with Philadelphia-chromosome-negative, primary refractory or relapsed (first relapse within 12 months of first remission, relapse within 12 months after allogeneic haemopoietic stem-cell transplantation [HSCT], or no response to or relapse after first salvage therapy or beyond) leukaemia. Patients received blinatumomab (9 μg/day for the first 7 days and 28 μg/day thereafter) by continuous intravenous infusion over 4 weeks every 6 weeks (up to five cycles), per protocol. The primary endpoint was complete remission (CR) or CR with partial haematological recovery of peripheral blood counts (CRh) within the first two cycles. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT01466179. Between Jan 13, 2012, and Oct 10, 2013, 189 patients were enrolled and treated with blinatumomab. After two cycles, 81 (43%, 95% CI 36-50) patients had achieved a CR or CRh: 63 (33%) patients had a CR and 18 (10%) patients had a CRh. 32 (40%) of patients who achieved CR/CRh underwent subsequent allogeneic HSCT. The most frequent grade 3 or worse adverse events were febrile neutropenia (48 patients, 25%), neutropenia (30 patients, 16%), and anaemia (27 patients, 14%). Three (2%) patients had grade 3 cytokine release syndrome. Neurologic events of worst grade 3 or 4 occurred in 20 (11%) and four (2%) patients, respectively. Three deaths (due to sepsis, Escherichia coli sepsis, and Candida infection) were thought to be treatment-related by the investigators. Single-agent blinatumomab showed antileukaemia activity in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia characterised by negative prognostic factors. Further assessment of blinatumomab treatment earlier in the course of the disease and in combination with other treatment approaches is warranted. Amgen. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biomass Burning Emissions of Black Carbon from African Sources

NASA Astrophysics Data System (ADS)

Aiken, A. C.; Leone, O.; Nitschke, K. L.; Dubey, M. K.; Carrico, C.; Springston, S. R.; Sedlacek, A. J., III; Watson, T. B.; Kuang, C.; Uin, J.; McMeeking, G. R.; DeMott, P. J.; Kreidenweis, S. M.; Robinson, A. L.; Yokelson, R. J.; Zuidema, P.

2016-12-01

Biomass burning (BB) emissions are a large source of carbon to the atmosphere via particles and gas phase species. Carbonaceous aerosols are emitted along with gas-phase carbon monoxide (CO) and carbon dioxide (CO2) that can be used to determine particulate emission ratios and modified combustion efficiencies. Black carbon (BC) aerosols are potentially underestimated in global models and are considered to be one of the most important global warming factors behind CO2. Half or more BC in the atmosphere is from BB, estimated at 6-9 Tg/yr (IPCC, 5AR) and contributing up to 0.6 W/m2 atmospheric warming (Bond et al., 2013). With a potential rise in drought and extreme events in the future due to climate change, these numbers are expected to increase. For this reason, we focus on BC and organic carbon aerosol species that are emitted from forest fires and compare their emission ratios, physical and optical properties to those from controlled laboratory studies of single-source BB fuels to understand BB carbonaceous aerosols in the atmosphere. We investigate BC in concentrated BB plumes as sampled from the new U.S. DOE ARM Program campaign, Layered Atlantic Smoke Interactions with Clouds (LASIC). The ARM Aerosol Mobile Facility 1 (AMF1) and Mobile Aerosol Observing System (MAOS) are currently located on Ascension Island in the South Atlantic Ocean, located midway between Angola and Brazil. The location was chosen for sampling maximum aerosol outflow from Africa. The far-field aged BC from LASIC is compared to BC from indoor generation from single-source fuels, e.g. African grass, sampled during Fire Lab At Missoula Experiments IV (FLAME-IV). BC is measured with a single-particle soot photometer (SP2) alongside numerous supporting instrumentation, e.g. particle counters, CO and CO2 detectors, aerosol scattering and absorption measurements, etc. FLAME-IV includes both direct emissions and well-mixed aerosol samples that have undergone dilution, cooling, and condensation. BC physical and optical properties change as particles are transported in the atmosphere due to oxidation, coagulation, and condensation which is observed in the laboratory BC data. Laboratory BC emissions and emission ratios are compared with those from LASIC to improve model treatment of BB BC emissions and aging in global climate models.

Impacts of Subgrid Heterogeneous Mixing between Cloud Liquid and Ice on the Wegner-Bergeron-Findeisen Process and Mixed-phase Clouds in NCAR CAM5

NASA Astrophysics Data System (ADS)

Liu, X.; Zhang, M.; Zhang, D.; Wang, Z.; Wang, Y.

2017-12-01

Mixed-phase clouds are persistently observed over the Arctic and the phase partitioning between cloud liquid and ice hydrometeors in mixed-phase clouds has important impacts on the surface energy budget and Arctic climate. In this study, we test the NCAR Community Atmosphere Model Version 5 (CAM5) with the single-column and weather forecast configurations and evaluate the model performance against observation data from the DOE Atmospheric Radiation Measurement (ARM) Program's M-PACE field campaign in October 2004 and long-term ground-based multi-sensor remote sensing measurements. Like most global climate models, we find that CAM5 also poorly simulates the phase partitioning in mixed-phase clouds by significantly underestimating the cloud liquid water content. Assuming pocket structures in the distribution of cloud liquid and ice in mixed-phase clouds as suggested by in situ observations provides a plausible solution to improve the model performance by reducing the Wegner-Bergeron-Findeisen (WBF) process rate. In this study, the modification of the WBF process in the CAM5 model has been achieved with applying a stochastic perturbation to the time scale of the WBF process relevant to both ice and snow to account for the heterogeneous mixture of cloud liquid and ice. Our results show that this modification of WBF process improves the modeled phase partitioning in the mixed-phase clouds. The seasonal variation of mixed-phase cloud properties is also better reproduced in the model in comparison with the long-term ground-based remote sensing observations. Furthermore, the phase partitioning is insensitive to the reassignment time step of perturbations.

Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study

PubMed Central

Beer, Tomasz M.; Armstrong, Andrew J.; Rathkopf, Dana; Loriot, Yohann; Sternberg, Cora N.; Higano, Celestia S.; Iversen, Peter; Evans, Christopher P.; Kim, Choung-Soo; Kimura, Go; Miller, Kurt; Saad, Fred; Bjartell, Anders S.; Borre, Michael; Mulders, Peter; Tammela, Teuvo L.; Parli, Teresa; Sari, Suha; van Os, Steve; Theeuwes, Ad; Tombal, Bertrand

2017-01-01

Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic progression or death by 68% (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.28–0.37; p < 0.0001) and the risk of death by 23% (HR 0.77, 95% CI 0.67–0.88; p = 0.0002). Median investigator-assessed rPFS was 20.0 mo (95% CI 18.9–22.1) in the enzalutamide arm and 5.4 mo (95% CI 4.1–5.6) in the placebo arm. Median OS was 35.3 mo (95% CI 32.2–not yet reached) in the enzalutamide arm and 31.3 mo (95% CI 28.8–34.2) in the placebo arm. At the time of the OS analysis, 167 patients in the placebo arm had crossed over to receive enzalutamide. The most common adverse events in the enzalutamide arm were fatigue, back pain, constipation, and arthralgia. This final analysis of PREVAIL provides more complete assessment of the clinical benefit of enzalutamide. PMID:27477525

The development of a fiber optics communication network for controlling a Multidegree-Of-Freedom Serpentine Truss

NASA Astrophysics Data System (ADS)

Andrawis, Alfred S.

1994-10-01

The problem addressed by this report is the large size and heavy weight of the cable bundle, used for controlling a Multidegree-Of-Freedom Serpentine Truss Manipulator arm, which imposes limitations on the manipulator arm maneuverability. This report covers a design of an optical fiber network to replace the existing copper wire network of the Serpentine Truss Manipulator. This report proposes a fiber network design which significantly reduces the bundle size into two phases. The first phase does not require any modifications for the manipulator architecture, while the other requires major modifications. Design philosophy, hardware details and schematic diagrams are presented.

The development of a fiber optics communication network for controlling a Multidegree-Of-Freedom Serpentine Truss

NASA Technical Reports Server (NTRS)

Andrawis, Alfred S.

1994-01-01

The problem addressed by this report is the large size and heavy weight of the cable bundle, used for controlling a Multidegree-Of-Freedom Serpentine Truss Manipulator arm, which imposes limitations on the manipulator arm maneuverability. This report covers a design of an optical fiber network to replace the existing copper wire network of the Serpentine Truss Manipulator. This report proposes a fiber network design which significantly reduces the bundle size into two phases. The first phase does not require any modifications for the manipulator architecture, while the other requires major modifications. Design philosophy, hardware details and schematic diagrams are presented.

Measurements of morphology and refractive indexes on human downy hairs using three-dimensional quantitative phase imaging.

PubMed

Lee, SangYun; Kim, Kyoohyun; Lee, Yuhyun; Park, Sungjin; Shin, Heejae; Yang, Jongwon; Ko, Kwanhong; Park, HyunJoo; Park, YongKeun

2015-01-01

We present optical measurements of morphology and refractive indexes (RIs) of human downy arm hairs using three-dimensional (3-D) quantitative phase imaging techniques. 3-D RI tomograms and high-resolution two-dimensional synthetic aperture images of individual downy arm hairs were measured using a Mach–Zehnder laser interferometric microscopy equipped with a two-axis galvanometer mirror. From the measured quantitative images, the RIs and morphological parameters of downy hairs were noninvasively quantified including the mean RI, volume, cylinder, and effective radius of individual hairs. In addition, the effects of hydrogen peroxide on individual downy hairs were investigated.

Ternary eutectic dendrites: Pattern formation and scaling properties

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

Rátkai, László; Szállás, Attila; Pusztai, Tamás

2015-04-21

Extending previous work [Pusztai et al., Phys. Rev. E 87, 032401 (2013)], we have studied the formation of eutectic dendrites in a model ternary system within the framework of the phase-field theory. We have mapped out the domain in which two-phase dendritic structures grow. With increasing pulling velocity, the following sequence of growth morphologies is observed: flat front lamellae → eutectic colonies → eutectic dendrites → dendrites with target pattern → partitionless dendrites → partitionless flat front. We confirm that the two-phase and one-phase dendrites have similar forms and display a similar scaling of the dendrite tip radius with themore » interface free energy. It is also found that the possible eutectic patterns include the target pattern, and single- and multiarm spirals, of which the thermal fluctuations choose. The most probable number of spiral arms increases with increasing tip radius and with decreasing kinetic anisotropy. Our numerical simulations confirm that in agreement with the assumptions of a recent analysis of two-phase dendrites [Akamatsu et al., Phys. Rev. Lett. 112, 105502 (2014)], the Jackson-Hunt scaling of the eutectic wavelength with pulling velocity is obeyed in the parameter domain explored, and that the natural eutectic wavelength is proportional to the tip radius of the two-phase dendrites. Finally, we find that it is very difficult/virtually impossible to form spiraling two-phase dendrites without anisotropy, an observation that seems to contradict the expectations of Akamatsu et al. Yet, it cannot be excluded that in isotropic systems, two-phase dendrites are rare events difficult to observe in simulations.« less

Dabigatran after Short Heparin Anticoagulation for Acute Intermediate-Risk Pulmonary Embolism: Rationale and Design of the Single-Arm PEITHO-2 Study.

PubMed

Klok, Frederikus A; Ageno, Walter; Barco, Stefano; Binder, Harald; Brenner, Benjamin; Duerschmied, Daniel; Empen, Klaus; Faggiano, Pompilio; Ficker, Joachim H; Galiè, Nazzareno; Ghuysen, Alexandre; Held, Matthias; Heydenreich, Nadine; Huisman, Menno V; Jiménez, David; Kozak, Matija; Lang, Irene M; Lankeit, Mareike; Münzel, Thomas; Petris, Antoniu; Pruszczyk, Piotr; Quitzau, Kurt; Schellong, Sebastian; Schmidt, Kai-Helge; Stefanovic, Branislav S; Verschuren, Franck; Wolf-Puetz, Anamaria; Meyer, Guy; Konstantinides, Stavros V

2017-12-01

Patients with intermediate-risk pulmonary embolism (PE) may, depending on the method and cut-off values used for definition, account for up to 60% of all patients with PE and have an 8% or higher risk of short-term adverse outcome. Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have been approved for the treatment of venous thromboembolism, their safety and efficacy as well as the optimal anticoagulation regimen using these drugs have not been systematically investigated in intermediate-risk PE. Moreover, it remains unknown how many patients with intermediate-high-risk and intermediate-low-risk PE were included in most of the phase III NOAC trials. The ongoing Pulmonary Embolism International Thrombolysis 2 (PEITHO-2) study is a prospective, multicentre, multinational, single-arm trial investigating whether treatment of acute intermediate-risk PE with parenteral heparin anticoagulation over the first 72 hours, followed by the direct oral thrombin inhibitor dabigatran over 6 months, is effective and safe. The primary efficacy outcome is recurrent symptomatic venous thromboembolism or death related to PE within the first 6 months. The primary safety outcome is major bleeding as defined by the International Society on Thrombosis and Haemostasis. Secondary outcomes include all-cause mortality, the overall duration of hospital stay (index event and repeated hospitalizations) and the temporal pattern of recovery of right ventricular function over the 6-month follow-up period. By applying and evaluating a contemporary risk-tailored treatment strategy for acute PE, PEITHO-2 will implement the recommendations of current guidelines and contribute to their further evolution.

Intra-operative 3D guidance in prostate brachytherapy using a non-isocentric C-arm.

PubMed

Jain, A; Deguet, A; Iordachita, I; Chintalapani, G; Blevins, J; Le, Y; Armour, E; Burdette, C; Song, D; Fichtinger, G

2007-01-01

Intra-operative guidance in Transrectal Ultrasound (TRUS) guided prostate brachytherapy requires localization of inserted radioactive seeds relative to the prostate. Seeds were reconstructed using a typical C-arm, and exported to a commercial brachytherapy system for dosimetry analysis. Technical obstacles for 3D reconstruction on a non-isocentric C-arm included pose-dependent C-arm calibration; distortion correction; pose estimation of C-arm images; seed reconstruction; and C-arm to TRUS registration. In precision-machined hard phantoms with 40-100 seeds, we correctly reconstructed 99.8% seeds with a mean 3D accuracy of 0.68 mm. In soft tissue phantoms with 45-87 seeds and clinically realistic 15 degrees C-arm motion, we correctly reconstructed 100% seeds with an accuracy of 1.3 mm. The reconstructed 3D seed positions were then registered to the prostate segmented from TRUS. In a Phase-1 clinical trial, so far on 4 patients with 66-84 seeds, we achieved intra-operative monitoring of seed distribution and dosimetry. We optimized the 100% prescribed iso-dose contour by inserting an average of 3.75 additional seeds, making intra-operative dosimetry possible on a typical C-arm, at negligible additional cost to the existing clinical installation.

Feasibility of school-based computer-assisted robotic gaming technology for upper limb rehabilitation of children with cerebral palsy.

PubMed

Preston, Nick; Weightman, Andrew; Gallagher, Justin; Holt, Raymond; Clarke, Michael; Mon-Williams, Mark; Levesley, Martin; Bhakta, Bipinchandra

2016-01-01

We investigated the feasibility of using computer-assisted arm rehabilitation (CAAR) computer games in schools. Outcomes were children's preference for single player or dual player mode, and changes in arm activity and kinematics. Nine boys and two girls with cerebral palsy (6-12 years, mean 9 years) played assistive technology computer games in single-user mode or with school friends in an AB-BA design. Preference was determined by recording the time spent playing each mode and by qualitative feedback. We used the ABILHAND-kids and Canadian Occupational Performance Measure to evaluate activity limitation, and a portable laptop-based device to capture arm kinematics. No difference was recorded between single-user and dual-user modes (median daily use 9.27 versus 11.2 min, p = 0.214). Children reported dual-user mode was preferable. There were no changes in activity limitation (ABILHAND-kids, p = 0.424; COPM, p = 0.484) but we found significant improvements in hand speed (p = 0.028), smoothness (p = 0.005) and accuracy (p = 0.007). School timetables prohibit extensive use of rehabilitation technology but there is potential for its short-term use to supplement a rehabilitation program. The restricted access to the rehabilitation games was sufficient to improve arm kinematics but not arm activity. Implications for Rehabilitation School premises and teaching staff present no obstacles to the installation of rehabilitation gaming technology. Twelve minutes per day is the average amount of time that the school time table permits children to use rehabilitation gaming equipment (without disruption to academic attendance). The use of rehabilitation gaming technology for an average of 12 minutes daily does not appear to benefit children's functional performance, but there are improvements in the kinematics of children's upper limb.

Second-line single-agent versus doublet chemotherapy as salvage therapy for metastatic urothelial cancer: a systematic review and meta-analysis.

PubMed

Raggi, D; Miceli, R; Sonpavde, G; Giannatempo, P; Mariani, L; Galsky, M D; Bellmunt, J; Necchi, A

2016-01-01

The efficacy and safety of a combination of chemotherapeutic agent compared with single-agent chemotherapy in the second-line setting of advanced urothelial carcinoma (UC) are unclear. We aimed to study the survival impact of single-agent compared with doublet chemotherapy as second-line chemotherapy of advanced UC. Literature was searched for studies including single-agent or doublet chemotherapy in the second-line setting after platinum-based chemotherapy. Random-effects models were used to pool trial-level data according to treatment arm, including median progression-free survival (PFS), overall survival (OS), objective response rate (ORR) probability, and grade 3-4 toxicity. Univariable and multivariable analyses, including sensitivity analyses, were carried out, adjusting for the percent of patients with ECOG performance status ≥1 and hepatic metastases. Forty-six arms of trials including 1910 patients were selected: 22 arms with single agent (n = 1202) and 24 arms with doublets (n = 708). The pooled ORR with single agents was 14.2% [95% confidence interval (CI) 11.1-17.9] versus 31.9% [95% CI 27.3-36.9] with doublet chemotherapy. Pooled median PFS was 2.69 and 4.05 months, respectively. The pooled median OS was 6.98 and 8.50 months, respectively. Multivariably, the odds ratio for ORR and the pooled median difference of PFS were statistically significant (P < 0.001 and P = 0.002) whereas the median difference in OS was not (P = 0.284). When including single-agent vinflunine or taxanes only, differences were significant only for ORR (P < 0.001) favoring doublet chemotherapy. No statistically significant differences in grade 3-4 toxicity were seen between the two groups. Despite significant improvements in ORR and PFS, doublet regimens did not extend OS compared with single agents for the second-line chemotherapy of UC. Prospective trials are necessary to elucidate the role of combination chemotherapy, with or without targeted agents, in the salvage setting. Currently, improvements in this field should be pursued considering single-agent chemotherapy as the foundation for new more active combinations. © 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.

Dasatinib, high-dose imatinib and nilotinib for the treatment of imatinib-resistant chronic myeloid leukaemia: a systematic review and economic evaluation.

PubMed

Loveman, E; Cooper, K; Bryant, J; Colquitt, J L; Frampton, G K; Clegg, A

2012-01-01

The present report was commissioned as a supplement to an existing technology assessment report produced by the Peninsula Technology Assessment Group (PenTAG), which evaluated the clinical effectiveness and cost-effectiveness of dasatinib and nilotinib in patients who are either resistant or intolerant to standard-dose imatinib. This report evaluates the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and high-dose imatinib within their licensed indications for the treatment of people with chronic myeloid leukaemia (CML) who are resistant to standard-dose imatinib. Bibliographic databases were searched from inception to January 2011, including The Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), and MEDLINE In-Process & Other Non-Indexed Citations. Bibliographies of related papers were screened, key conferences were searched, and experts were contacted to identify additional published and unpublished references. This report includes systematic reviews of clinical effectiveness and cost-effectiveness studies, an independent appraisal of information submitted by drug manufacturers to the National Institute for Health and Clinical Excellence (NICE), an independent appraisal of the PenTAG economic evaluation, and new economic analyses adapting the PenTAG economic model. Standard systematic procedures involving two reviewers to maintain impartiality and transparency, and to minimise bias, were conducted. Eleven studies met the inclusion criteria. Four of these studies included new data published since the PenTAG report; all of these were in chronic-phase CML. No relevant studies on the clinical effectiveness of nilotinib were found. The clinical effectiveness studies on dasatinib [one arm of a randomised controlled trial (RCT)] and high-dose imatinib (one arm of a RCT and three single-arm cohort studies) had major methodological limitations. These limitations precluded a comparison of the different arms within the RCT. Data from the studies are summarised in this report, but caution in interpretation is required. One economic evaluation was identified that compared dasatinib with high-dose imatinib in patients with chronic-phase CML who were CML resistant to standard-dose imatinib. Two industry submissions and the PenTAG economic evaluation were critiqued and differences in the assumptions and results were identified. The PenTAG economic model was adapted and new analyses conducted for the interventions dasatinib, nilotinib and high-dose imatinib and the comparators interferon alfa, standard-dose imatinib, stem cell transplantation and hydroxycarbamide. The results suggest that the three interventions, dasatinib, nilotinib and high-dose imatinib, have similar costs and cost-effectiveness compared with hydroxycarbamide, with a cost-effectiveness of around £30,000 per quality-adjusted life-year gained. However, it is not possible to derive firm conclusions about the relative cost-effectiveness of the three interventions owing to great uncertainty around data inputs. Uncertainty was explored using deterministic sensitivity analyses, threshold analyses and probabilistic sensitivity analyses. The paucity of good-quality evidence should be considered when interpreting this report. This review has identified very limited new information on clinical effectiveness of the interventions over that already shown in the PenTAG report. Limitations in the data exist; however, the results of single-arm studies suggest that the interventions can lead to improvements in haematological and cytogenetic responses in people with imatinib-resistant CML. The economic analyses do not highlight any one of the interventions as being the most cost-effective; however, the analysis results are highly uncertain owing to lack of agreement on appropriate assumptions. Recommendations for future research made by PenTAG, for a good-quality RCT comparing the three treatments remain.

A common neural element receiving rhythmic arm and leg activity as assessed by reflex modulation in arm muscles

PubMed Central

Tazoe, Toshiki; Nakajima, Tsuyoshi; Futatsubashi, Genki; Ohtsuka, Hiroyuki; Suzuki, Shinya; Zehr, E. Paul; Komiyama, Tomoyoshi

2016-01-01

Neural interactions between regulatory systems for rhythmic arm and leg movements are an intriguing issue in locomotor neuroscience. Amplitudes of early latency cutaneous reflexes (ELCRs) in stationary arm muscles are modulated during rhythmic leg or arm cycling but not during limb positioning or voluntary contraction. This suggests that interneurons mediating ELCRs to arm muscles integrate outputs from neural systems controlling rhythmic limb movements. Alternatively, outputs could be integrated at the motoneuron and/or supraspinal levels. We examined whether a separate effect on the ELCR pathways and cortico-motoneuronal excitability during arm and leg cycling is integrated by neural elements common to the lumbo-sacral and cervical spinal cord. The subjects performed bilateral leg cycling (LEG), contralateral arm cycling (ARM), and simultaneous contralateral arm and bilateral leg cycling (A&L), while ELCRs in the wrist flexor and shoulder flexor muscles were evoked by superficial radial (SR) nerve stimulation. ELCR amplitudes were facilitated by cycling tasks and were larger during A&L than during ARM and LEG. A low stimulus intensity during ARM or LEG generated a larger ELCR during A&L than the sum of ELCRs during ARM and LEG. We confirmed this nonlinear increase in single motor unit firing probability following SR nerve stimulation during A&L. Furthermore, motor-evoked potentials following transcranial magnetic and electrical stimulation did not show nonlinear potentiation during A&L. These findings suggest the existence of a common neural element of the ELCR reflex pathway that is active only during rhythmic arm and leg movement and receives convergent input from contralateral arms and legs. PMID:26961103

Future of robotic surgery in urology.

PubMed

Rassweiler, Jens J; Autorino, Riccardo; Klein, Jan; Mottrie, Alex; Goezen, Ali Serdar; Stolzenburg, Jens-Uwe; Rha, Koon H; Schurr, Marc; Kaouk, Jihad; Patel, Vipul; Dasgupta, Prokar; Liatsikos, Evangelos

2017-12-01

To provide a comprehensive overview of the current status of the field of robotic systems for urological surgery and discuss future perspectives. A non-systematic literature review was performed using PubMed/Medline search electronic engines. Existing patents for robotic devices were researched using the Google search engine. Findings were also critically analysed taking into account the personal experience of the authors. The relevant patents for the first generation of the da Vinci platform will expire in 2019. New robotic systems are coming onto the stage. These can be classified according to type of console, arrangement of robotic arms, handles and instruments, and other specific features (haptic feedback, eye-tracking). The Telelap ALF-X robot uses an open console with eye-tracking, laparoscopy-like handles with haptic feedback, and arms mounted on separate carts; first clinical trials with this system were reported in 2016. The Medtronic robot provides an open console using three-dimensional high-definition video technology and three arms. The Avatera robot features a closed console with microscope-like oculars, four arms arranged on one cart, and 5-mm instruments with six degrees of freedom. The REVO-I consists of an open console and a four-arm arrangement on one cart; the first experiments with this system were published in 2016. Medicaroid uses a semi-open console and three robot arms attached to the operating table. Clinical trials of the SP 1098-platform using the da Vinci Xi for console-based single-port surgery were reported in 2015. The SPORT robot has been tested in animal experiments for single-port surgery. The SurgiBot represents a bedside solution for single-port surgery providing flexible tube-guided instruments. The Avicenna Roboflex has been developed for robotic flexible ureteroscopy, with promising early clinical results. Several console-based robots for laparoscopic multi- and single-port surgery are expected to come to market within the next 5 years. Future developments in the field of robotic surgery are likely to focus on the specific features of robotic arms, instruments, console, and video technology. The high technical standards of four da Vinci generations have set a high bar for upcoming devices. Ultimately, the implementation of these upcoming systems will depend on their clinical applicability and costs. How these technical developments will facilitate surgery and whether their use will translate into better outcomes for our patients remains to be determined. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Regulatory light chain mutants linked to heart disease modify the cardiac myosin lever arm.

PubMed

Burghardt, Thomas P; Sikkink, Laura A

2013-02-19

Myosin is the chemomechanical energy transducer in striated heart muscle. The myosin cross-bridge applies impulsive force to actin while consuming ATP chemical energy to propel myosin thick filaments relative to actin thin filaments in the fiber. Transduction begins with ATP hydrolysis in the cross-bridge driving rotary movement of a lever arm converting torque into linear displacement. Myosin regulatory light chain (RLC) binds to the lever arm and modifies its ability to translate actin. Gene sequencing implicated several RLC mutations in heart disease, and three of them are investigated here using photoactivatable GFP-tagged RLC (RLC-PAGFP) exchanged into permeabilized papillary muscle fibers. A single-lever arm probe orientation is detected in the crowded environment of the muscle fiber by using RLC-PAGFP with dipole orientation deduced from the three-spatial dimension fluorescence emission pattern of the single molecule. Symmetry and selection rules locate dipoles in their half-sarcomere, identify those at the minimal free energy, and specify active dipole contraction intermediates. Experiments were performed in a microfluidic chamber designed for isometric contraction, total internal reflection fluorescence detection, and two-photon excitation second harmonic generation to evaluate sarcomere length. The RLC-PAGFP reports apparently discretized lever arm orientation intermediates in active isometric fibers that on average produce the stall force. Disease-linked mutants introduced into RLC move intermediate occupancy further down the free energy gradient, implying lever arms rotate more to reach stall force because mutant RLC increases lever arm shear strain. A lower free energy intermediate occupancy involves a lower energy conversion efficiency in the fiber relating a specific myosin function modification to the disease-implicated mutant.

Cuff Pressure Pain Detection Is Associated with Both Sex and Physical Activity Level in Nonathletic Healthy Subjects.

PubMed

Lemming, Dag; Börsbo, Björn; Sjörs, Anna; Lind, Eva-Britt; Arendt-Nielsen, Lars; Graven-Nielsen, Thomas; Gerdle, Björn

2017-08-01

The aim of this study was to evaluate pressure pain sensitivity on leg and arm in 98 healthy persons (50 women) using cuff algometry. Furthermore, associations with sex and physical activity level were investigated. Normal physical activity level was defined as Godin Leisure-Time Exercise Questionnaire (GLTEQ) score ≤ 45 and high activity level as GLTEQ > 45. A pneumatic double-chamber cuff was placed around the arm or leg where a single chamber was inflated. The cuff inflation rate (1 kPa/s) was constant, and pain intensity was registered continuously on a 10 cm electronic visual analogue scale (VAS). The pain detection threshold (PDT) was defined as when the pressure was perceived as painful, and pain tolerance (PTT) was when the subject terminated the cuff inflation. For PTT, the corresponding VAS score was recorded (VAS-PTT). The protocol was repeated with two chambers inflated. Only single cuff results are given. For women compared with men, the PDT was lower when assessed in the arm ( P = 0.002), PTTs were lower in the arm and leg ( P < 0.001), and the VAS-PTT was higher in the arm and leg ( P < 0.033). Highly active participants compared with less active had higher PDT ( P = 0.027) in the leg. Women showed facilitated spatial summation ( P < 0.014) in the arm and leg and a steeper VAS slope (i.e., the slope of the VAS pressure curve between PDT and PPT) in the arm and leg ( P < 0.003). This study indicates that reduced pressure pain sensitivity is associated both with male sex and physical activity level. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Ribociclib plus letrozole in early breast cancer: A presurgical, window-of-opportunity study.

PubMed

Curigliano, G; Gómez Pardo, P; Meric-Bernstam, F; Conte, P; Lolkema, M P; Beck, J T; Bardia, A; Martínez García, M; Penault-Llorca, F; Dhuria, S; Tang, Z; Solovieff, N; Miller, M; Di Tomaso, E; Hurvitz, S A

2016-08-01

Cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4/6-retinoblastoma (Rb) pathway hyperactivation is associated with hormone receptor-positive (HR+) breast cancer (BC). This study assessed the biological activity of ribociclib (LEE011; CDK4/6 inhibitor) plus letrozole compared with single-agent letrozole in the presurgical setting. Postmenopausal women (N = 14) with resectable, HR+, human epidermal growth factor receptor 2-negative (HER2-) early BC were randomized 1:1:1 to receive 2.5 mg/day letrozole alone (Arm 1), or with 400 or 600 mg/day ribociclib (Arm 2 or 3). Circulating tumor DNA and tumor biopsies were collected at baseline and, following 14 days of treatment, prior to or during surgery. The primary objective was to assess antiproliferative response per Ki67 levels in Arms 2 and 3 compared with Arm 1. Additional assessments included safety, pharmacokinetics, and genetic profiling. Mean decreases in the Ki67-positive cell fraction from baseline were: Arm 1 69% (range 38-100%; n = 2), Arm 2 96% (range 78-100%; n = 6), Arm 3 92% (range 75-100%; n = 3). Decreased phosphorylated Rb levels and CDK4, CDK6, CCND2, CCND3, and CCNE1 gene expression were observed following ribociclib treatment. Ribociclib and letrozole pharmacokinetic parameters were consistent with single-agent data. The ribociclib plus letrozole combination was well tolerated, with no Grade 3/4 adverse events over the treatment. The results suggest absence of a drug-drug interaction between ribociclib and letrozole and indicate ribociclib plus letrozole may reduce Ki67 expression in HR+, HER2- BC (NCT01919229). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission.

PubMed

Church, Jessica D; Omer, Saad B; Guay, Laura A; Huang, Wei; Lidstrom, Jessica; Musoke, Philippa; Mmiro, Francis; Jackson, J Brooks; Eshleman, Susan H

2008-10-01

Single-dose nevirapine (SD NVP) at birth plus NVP prophylaxis for the infant up to 6 weeks of age is superior to SD NVP alone for prevention of vertical transmission of human immunodeficiency virus (HIV) through breastfeeding. We analyzed NVP resistance in HIV-infected Ugandan infants who received either SD NVP or extended NVP prophylaxis. We tested plasma HIV by using a genotyping assay (ViroSeq; Celera Diagnostics), a phenotypic resistance assay (PhenoSense; Monogram Biosciences), and sensitive point mutation assay (LigAmp, for K103N, Y181C, and G190A). When infants were 6 weeks old, ViroSeq detected NVP resistance in a higher proportion of infants in the extended NVP arm than in the SD NVP arm (21 of 25 [84%] vs. 12 of 24 [50%]; P = .01). Similar results were obtained with LigAmp and PhenoSense. In both study arms, infants who were HIV infected at birth frequently had NVP resistance detected. In contrast, infants in the extended NVP arm who were HIV infected after birth were more likely to have resistance detected at 6 weeks, compared with infants in the SD NVP arm. The use of extended NVP prophylaxis was also associated with detection of NVP resistance by ViroSeq at 6 months (7 of 7 [100%] infants in the extended NVP arm had resistance detected, compared with 1 of 6 [16.7%] infants in the SD NVP arm; P = .005). The use of extended NVP prophylaxis was associated with increased selection for and persistence of NVP resistance in HIV-infected Ugandan infants.

Evolutionary disarmament in interspecific competition.

PubMed

Kisdi, E; Geritz, S A

2001-12-22

Competitive asymmetry, which is the advantage of having a larger body or stronger weaponry than a contestant, drives spectacular evolutionary arms races in intraspecific competition. Similar asymmetries are well documented in interspecific competition, yet they seldom lead to exaggerated traits. Here we demonstrate that two species with substantially different size may undergo parallel coevolution towards a smaller size under the same ecological conditions where a single species would exhibit an evolutionary arms race. We show that disarmament occurs for a wide range of parameters in an ecologically explicit model of competition for a single shared resource; disarmament also occurs in a simple Lotka-Volterra competition model. A key property of both models is the interplay between evolutionary dynamics and population density. The mechanism does not rely on very specific features of the model. Thus, evolutionary disarmament may be widespread and may help to explain the lack of interspecific arms races.

Evolutionary disarmament in interspecific competition.

PubMed Central

Kisdi, E.; Geritz, S. A.

2001-01-01

Competitive asymmetry, which is the advantage of having a larger body or stronger weaponry than a contestant, drives spectacular evolutionary arms races in intraspecific competition. Similar asymmetries are well documented in interspecific competition, yet they seldom lead to exaggerated traits. Here we demonstrate that two species with substantially different size may undergo parallel coevolution towards a smaller size under the same ecological conditions where a single species would exhibit an evolutionary arms race. We show that disarmament occurs for a wide range of parameters in an ecologically explicit model of competition for a single shared resource; disarmament also occurs in a simple Lotka-Volterra competition model. A key property of both models is the interplay between evolutionary dynamics and population density. The mechanism does not rely on very specific features of the model. Thus, evolutionary disarmament may be widespread and may help to explain the lack of interspecific arms races. PMID:11749715

Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial.

PubMed

Hochhaus, A; Saglio, G; Hughes, T P; Larson, R A; Kim, D-W; Issaragrisil, S; le Coutre, P D; Etienne, G; Dorlhiac-Llacer, P E; Clark, R E; Flinn, I W; Nakamae, H; Donohue, B; Deng, W; Dalal, D; Menssen, H D; Kantarjian, H M

2016-05-01

In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients' long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54%; 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR(4.5); BCR-ABL⩽0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP.

Single-primer fluorescent sequencing

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

Ruth, J.L.; Morgan, C.A.; Middendorf, L.R.

Modified linker arm oligonucleotides complementary to standard M13 priming sites were synthesized, labelled with either one, two, or three fluoresceins, and purified by reverse-phase HPLC. When used as primers in standard dideoxy M13 sequencing with /sup 32/P-dNTPs, normal autoradiographic patterns were obtained. To eliminate the radioactivity, direct on-line fluorescence detection was achieved by the use of a scanning 10 mW Argon laser emitting 488 nm light. Fluorescent bands were detected directly in standard 0.2 or 0.35 mm thick polyacrylamide gels at a distance of 24 cm from the loading wells by a photomultiplier tube filtered at 520 nm. Horizontal andmore » temporal location of each band was displayed by computer as a band in real time, providing visual appearance similar to normal 4-lane autoradiograms. Using a single primer labelled with two fluoresceins, sequences of between 500 and 600 bases have been read in a single loading with better than 98% accuracy; up to 400 bases can be read reproducibly with no errors. More than 50 sequences have been determined by this method. This approach requires only 1-2 ug of cloned template, and produces continuous sequence data at about one band per minute.« less

Phase III Noninferiority Trial Comparing Irinotecan With Oxaliplatin, Fluorouracil, and Leucovorin in Patients With Advanced Colorectal Carcinoma Previously Treated With Fluorouracil: N9841

PubMed Central

Kim, George P.; Sargent, Daniel J.; Mahoney, Michelle R.; Rowland, Kendrith M.; Philip, Philip A.; Mitchell, Edith; Mathews, Abraham P.; Fitch, Tom R.; Goldberg, Richard M.; Alberts, Steven R.; Pitot, Henry C.

2009-01-01

Purpose The primary goal of this multicenter phase III trial was to determine whether overall survival (OS) of fluorouracil (FU) -refractory patients was noninferior when treated with second-line infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4; arm B) versus irinotecan (arm A). Cross-over to the other treatment on disease progression was mandated. Patients and Methods Patients who experienced treatment failure with one prior FU-based therapy and had not received prior irinotecan or oxaliplatin, either for metastatic disease or within 6 months of adjuvant FU therapy, were randomly assigned to arm A (irinotecan 350 or 300 mg/m2 every 3 weeks) or arm B (FOLFOX4). Results A total of 491 patients were randomly assigned (arm A, n = 245; arm B, n = 246); 288 (59%) had experienced treatment failure with FU for metastatic colorectal cancer. Two hundred twenty-seven patients (46%) received protocol-mandated third-line therapy (arm A, 43%; arm B, 57%). Median survival was 13.8 months (95% CI, 12.2 to 15.0 months) for initial treatment with FOLFOX4 and 14.3 months (95% CI, 12.0 to 15.9 months) for irinotecan (P = .38; hazard ratio = 0.92; 95% CI, 0.8 to 1.1). Response rates (RR; 28% v 15.5%; P = .0009) and time to progression (TTP; 6.2 v 4.4 months; P = .0009) were significantly superior with FOLFOX4. In the nonrandom subset of patients who crossed over, RR and TTP improvements with FOLFOX4 continued into third-line treatment. Irinotecan therapy was associated with more grade 3 nausea, vomiting, diarrhea, and febrile neutropenia; FOLFOX4 was associated with more neutropenia and paresthesias. Conclusion In patients who experienced treatment failure with front-line FU therapy, OS does not significantly differ whether second-line therapy begins with irinotecan or FOLFOX4. FOLFOX4 produces higher RR and longer TTP. Both arms had notable OS in patients who experienced treatment failure with first-line FU therapy. PMID:19380443

Endoscopic endonasal transsphenoidal surgery using the iArmS operation support robot: initial experience in 43 patients.

PubMed

Ogiwara, Toshihiro; Goto, Tetsuya; Nagm, Alhusain; Hongo, Kazuhiro

2017-05-01

Objective The intelligent arm-support system, iArmS, which follows the surgeon's arm and automatically fixes it at an adequate position, was developed as an operation support robot. iArmS was designed to support the surgeon's forearm to prevent hand trembling and to alleviate fatigue during surgery with a microscope. In this study, the authors report on application of this robotic device to endoscopic endonasal transsphenoidal surgery (ETSS) and evaluate their initial experiences. Methods The study population consisted of 43 patients: 29 with pituitary adenoma, 3 with meningioma, 3 with Rathke's cleft cyst, 2 with craniopharyngioma, 2 with chordoma, and 4 with other conditions. All patients underwent surgery via the endonasal transsphenoidal approach using a rigid endoscope. During the nasal and sphenoid phases, iArmS was used to support the surgeon's nondominant arm, which held the endoscope. The details of the iArmS and clinical results were collected. Results iArmS followed the surgeon's arm movement automatically. It reduced the surgeon's fatigue and stabilized the surgeon's hand during ETSS. Shaking of the video image decreased due to the steadying of the surgeon's scope-holding hand with iArmS. There were no complications related to use of the device. Conclusions The intelligent armrest, iArmS, seems to be safe and effective during ETSS. iArmS is helpful for improving the precision and safety not only for microscopic neurosurgery, but also for ETSS. Ongoing advances in robotics ensure the continued evolution of neurosurgery.

Final Report: Investigations of Mixed-Phase Cloud Microphysical, Radiative, and Dynamical Processes

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

Shupe, Matthew

2016-08-18

This project supported the principle investigator’s work on a number of studies regarding mixed-phase clouds and in various related collaborations with ARM and related scientists. This project has contributed to numerous publications and conference/meeting presentations.

A self-assembled nanoscale robotic arm controlled by electric fields

NASA Astrophysics Data System (ADS)

Kopperger, Enzo; List, Jonathan; Madhira, Sushi; Rothfischer, Florian; Lamb, Don C.; Simmel, Friedrich C.

2018-01-01

The use of dynamic, self-assembled DNA nanostructures in the context of nanorobotics requires fast and reliable actuation mechanisms. We therefore created a 55-nanometer–by–55-nanometer DNA-based molecular platform with an integrated robotic arm of length 25 nanometers, which can be extended to more than 400 nanometers and actuated with externally applied electrical fields. Precise, computer-controlled switching of the arm between arbitrary positions on the platform can be achieved within milliseconds, as demonstrated with single-pair Förster resonance energy transfer experiments and fluorescence microscopy. The arm can be used for electrically driven transport of molecules or nanoparticles over tens of nanometers, which is useful for the control of photonic and plasmonic processes. Application of piconewton forces by the robot arm is demonstrated in force-induced DNA duplex melting experiments.

Application of adaptive design and decision making to a phase II trial of a phosphodiesterase inhibitor for the treatment of intermittent claudication.

PubMed

Lewis, Roger J; Connor, Jason T; Teerlink, John R; Murphy, James R; Cooper, Leslie T; Hiatt, William R; Brass, Eric P

2011-05-25

Claudication secondary to peripheral artery disease (PAD) is associated with substantial functional impairment. Phosphodiesterase (PDE) inhibitors have been shown to increase walking performance in these patients. K-134 is a selective PDE 3 inhibitor being developed as a potential treatment for claudication. The use of K-134, as with other PDE 3 inhibitors, in patients with PAD raises important safety and tolerability concerns, including the induction of cardiac ischemia, tachycardia, and hypotension. We describe the design, oversight, and implementation of an adaptive, phase II, dose-finding trial evaluating K-134 for the treatment of stable, intermittent claudication. The study design was a double-blind, multi-dose (25 mg, 50 mg, and 100 mg of K-134), randomized trial with both placebo and active comparator arms conducted in the United States and Russia. The primary objective of the study was to compare the highest tolerable dose of K-134 versus placebo using peak walking time after 26 weeks of therapy as the primary outcome. Study visits with intensive safety assessments were included early in the study period to provide data for adaptive decision making. The trial used an adaptive, dose-finding strategy to efficiently identify the highest dose(s) most likely to be safe and well tolerated, based on the side effect profiles observed within the trial, so that less promising doses could be abandoned. Protocol specified criteria for safety and tolerability endpoints were used and modeled prior to the adaptive decision making. The maximum target sample size was 85 subjects in each of the retained treatment arms. When 199 subjects had been randomized and 28-day data were available from 143, the Data Monitoring Committee (DMC) recommended termination of the lowest dose (25 mg) treatment arm. Safety evaluations performed during 14- and 28-day visits which included in-clinic dosing and assessments at peak drug concentrations provided core data for the DMC review. At the time of review, no subject in any of the five treatment arms (placebo, three K-134-containing arms, and cilostazol) had met pre-specified definitions for resting tachycardia or ischemic changes on exercise ECG. If, instead of dropping the 25-mg K-134 treatment arm, all arms had been continued to full enrollment, then approximately 43 additional research subjects would have been required to complete the trial. In this phase II, dose-finding trial of K-134 in the treatment of stable intermittent claudication, no concerning safety signals were seen at interim analysis, allowing the discontinuation of the lowest-dose-containing arm and the retention of the two highest-dose-containing arms. The adaptive design facilitated safe and efficient evaluation of K-134 in this high-risk cardiovascular population. ClinicalTrials.gov: NCT00783081.

Simultaneous Genotyping of the rs4762 and rs699 Polymorphisms in Angiotensinogen Gene and Correlation with Iranian CAD Patients with Novel Hexa-primer ARMS-PCR

PubMed Central

KHATAMI, Mehri; HEIDARI, Mohammad Mehdi; HADADZADEH, Mehdi; SCHEIBER-MOJDEHKAR, Barbara; BITARAF SANI, Morteza; HOUSHMAND, Massoud

2017-01-01

Background: A significant role of Renin-angiotensin system (RAS) genetic variants in the pathogenesis of essential hypertension and cardiovascular diseases has been proved. This study aimed to develop a new, fast and cheap method for the simultaneous detection of two missense single nucleotide polymorphisms (T207M or rs4762 and M268T orrs699) of angiotensinogen (AGT) in single-step Multiplex Hexa-Primer Amplification Refractory Mutation System - polymerase chain reaction (H-ARMS-PCR). Methods: In this case-control study, 148 patients with coronary artery disease (CAD) and 135 controls were included. The patients were referred to cardiac centers in Afshar Hospital (Yazd, Iran) from 2012 to 2015. Two sets of inner primer (for each SNP) and one set outer primer pairs were designed for genotyping of rs4762 and rs699 in single tube H-ARMS-PCR. Direct sequencing of all samples was also performed to assess the accuracy of this method. DNA sequencing method validated the results of single tube H-ARMS-PCR. Results: We found full accordance for genotype adscription by sequencing method. The frequency of the AGT T521 and C702 alleles was significantly higher in CAD patients than in the control group (OR: 0.551, 95% CI: 0.359–0.846, P=0.008 and OR: 0.629, 95% CI: 0.422–0.936, P=0.028, respectively). Conclusion: This is the first work describing a rapid, low-cost, high-throughput simultaneous detection of rs4762 and rs699 polymorphisms in AGT gene, used in large clinical studies. PMID:28828324

Quantum Photonics Beyond Conventional Computing

DTIC Science & Technology

2015-07-10

polarisation using a half- wave plate (HWP), the two arms are combined by a polarising beam splitter (PBS). The resulting state is passed through the...phase-matched for Type-I SPDC, creating non -collinear degenerate horizontally polarised photon pairs at 808 nm. After converting one arm to vertical...For the case of non -interacting fermions, the transition probabilities for states under unitary evolution are governed by matrix determinants, which are

Army Special Operations Forces (ARSOF): How Can ARSOF Redirect Efforts in Colombia from Tactical to Operational Level Support Due to the Recent Transition of the Fuerzas Armadas Revolucionarias Colombianas (FARC)

DTIC Science & Technology

The remodeling of Army Special Operations Forces (ARSOF) support to Colombian Security Forces during the transition phase of the Revolutionary Armed ...Forces of Colombia needs to be revised at to retain stability in the country. The Fuerzas Armadas Revolucionarias Colombianas (Revolutionary Armed

'TXT2BFiT' a mobile phone-based healthy lifestyle program for preventing unhealthy weight gain in young adults: study protocol for a randomized controlled trial.

PubMed

Hebden, Lana; Balestracci, Kate; McGeechan, Kevin; Denney-Wilson, Elizabeth; Harris, Mark; Bauman, Adrian; Allman-Farinelli, Margaret

2013-03-18

Despite international efforts to arrest increasing rates of overweight and obesity, many population strategies have neglected young adults as a target group. Young adults are at high risk for unhealthy weight gain which tends to persist throughout adulthood with associated chronic disease health risks. TXT2BFiT is a nine month two-arm parallel-group randomized controlled trial aimed at improving weight management and weight-related dietary and physical activity behaviors among young adults. Participants are recruited via general practice (primary medical care) clinics in Sydney, New South Wales, Australia. All participants receive a mailed resource outlining national physical activity and dietary guidelines and access to the study website. Additional resources accessible to the intervention arm via the study website include Smartphone mobile applications, printable handouts, an interactive healthy weight tracker chart, and a community blog. The study consists of two phases: (1) Intensive phase (weeks 1 to 12): the control arm receives four short message service (SMS) text messages; the intervention arm receives eight SMS messages/week tailored to their baseline stage-of-change, one Email/week, and personalized coaching calls during weeks 0, 2, 5, 8, and 11; and (2) Maintenance phase (weeks 14 to 36): the intervention arm receives one SMS message/month, one Email/month and booster coaching calls during months 5 and 8. A sample of N = 354 (177 per arm) is required to detect differences in primary outcomes: body weight (kg) and body mass index (kg/m2), and secondary outcomes: physical activity, sitting time, intake of specific foods, beverages and nutrients, stage-of-change, self-efficacy and participant well-being, at three and nine months. Program reach, costs, implementation and participant engagement will also be assessed. This mobile phone based program addresses an important gap in obesity prevention efforts to date. The method of intervention delivery is via platforms that are highly accessible and appropriate for this population group. If effective, further translational research will be required to assess how this program might operate in the broader community. Australian New Zealand Clinical Trials Registry ACTRN12612000924853.

A Novel Strategy for Continuation ECT in Geriatric Depression: Phase 2 of the PRIDE Study.

PubMed

Kellner, Charles H; Husain, Mustafa M; Knapp, Rebecca G; McCall, W Vaughn; Petrides, Georgios; Rudorfer, Matthew V; Young, Robert C; Sampson, Shirlene; McClintock, Shawn M; Mueller, Martina; Prudic, Joan; Greenberg, Robert M; Weiner, Richard D; Bailine, Samuel H; Rosenquist, Peter B; Raza, Ahmad; Kaliora, Styliani; Latoussakis, Vassilios; Tobias, Kristen G; Briggs, Mimi C; Liebman, Lauren S; Geduldig, Emma T; Teklehaimanot, Abeba A; Dooley, Mary; Lisanby, Sarah H

2016-11-01

The randomized phase (phase 2) of the Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy and tolerability of continuation ECT plus medication compared with medication alone in depressed geriatric patients after a successful course of ECT (phase 1). PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, augmented with venlafaxine. Phase 2 compared two randomized treatment arms: a medication only arm (venlafaxine plus lithium, over 24 weeks) and an ECT plus medication arm (four continuation ECT treatments over 1 month, plus additional ECT as needed, using the Symptom-Titrated, Algorithm-Based Longitudinal ECT [STABLE] algorithm, while continuing venlafaxine plus lithium). The intent-to-treat sample comprised 120 remitters from phase 1. The primary efficacy outcome measure was score on the 24-item Hamilton Depression Rating Scale (HAM-D), and the secondary efficacy outcome was score on the Clinical Global Impressions severity scale (CGI-S). Tolerability as measured by neurocognitive performance (reported elsewhere) was assessed using an extensive test battery; global cognitive functioning as assessed by the Mini-Mental State Examination (MMSE) is reported here. Longitudinal mixed-effects repeated-measures modeling was used to compare ECT plus medication and medication alone for efficacy and global cognitive function outcomes. At 24 weeks, the ECT plus medication group had statistically significantly lower HAM-D scores than the medication only group. The difference in adjusted mean HAM-D scores at study end was 4.2 (95% CI=1.6, 6.9). Significantly more patients in the ECT plus medication group were rated "not ill at all" on the CGI-S compared with the medication only group. There was no statistically significant difference between groups in MMSE score. Additional ECT after remission (here operationalized as four continuation ECT treatments followed by further ECT only as needed) was beneficial in sustaining mood improvement for most patients.

Gain dependent self-phasing in a two-core coherently combined fiber laser.

PubMed

Kunkel, W Minster; Leger, James R

2018-04-16

The influence of the Kramers-Kronig phase is demonstrated in a coherently combined fiber laser where other passive phasing mechanisms such as wavelength tuning have been suppressed. A mathematical model is developed to predict the lasing supermode and is supported by experimental measurements of the gain, phase, and power. The results show that the difference in Kramers-Kronig phase arising from a difference in gain between the two arms partially compensates for an externally applied phase error.

A Phase 2 Randomized Study of Ramucirumab (IMC-1121B) with or without Dacarbazine in Patients with Metastatic Melanoma

PubMed Central

Carvajal, Richard D.; Wong, Michael K.; Thompson, John A.; Gordon, Michael S.; Lewis, Karl D.; Pavlick, Anna C.; Wolchok, Jedd D.; Rojas, Patrick B.; Schwartz, Jonathan D.; Bedikian, Agop Y.

2017-01-01

SUMMARY Background To evaluate the efficacy and safety of ramucirumab (IMC-1121B; LY3009806), a fully human monoclonal antibody targeting the vascular endothelial growth factor receptor-2, alone and in combination with dacarbazine in chemotherapy-naïve patients with metastatic melanoma (MM). Methods Eligible patients received ramucirumab (10 mg/kg) + dacarbazine (1000 mg/m2) (Arm A) or ramucirumab only (10 mg/kg) (Arm B) every 3 weeks. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response, and safety. Findings Of 106 randomized patients, 102 received study treatment (Arm A, N = 52; Arm B, N = 50). Baseline characteristics were similar in both arms. Median PFS was 2·6 months (Arm A) and 1·7 months (Arm B); median 6-month PFS rates were 30·7% and 17·9% and 12-month PFS rates were 23·7% and 15·6%, respectively. In Arm A, 9 (17·3%) patients had partial response (PR) and 19 (36·5%), stable disease (SD); PR and SD in Arm B were 2 (4·0%) and 21 (42·0%), respectively. Median OS was 8·7 months in Arm A and 11·1 months in Arm B. Patients in both arms tolerated the treatment with limited grade 3/4 toxicities. Interpretation Ramucirumab alone or in combination with dacarbazine was associated with an acceptable safety profile in patients with MM. Although the study was not powered for comparison between treatment arms, PFS appeared greater with combination therapy. Sustained disease control was observed on both study arm Funding Funded by ImClone Systems LLC, a wholly-owned subsidiary of Eli Lilly and Company, Bridgewater, NJ PMID:24930625

Intelligent Robotic Systems Study (IRSS), phase 3

NASA Technical Reports Server (NTRS)

1991-01-01

This phase of the Intelligent Robotic Systems Study (IRSS) examines some basic dynamics and control issues for a space manipulator attached to its worksite through a compliant base. One example of this scenario is depicted, which is a simplified, planar representation of the Flight Telerobotic Servicer (FTS) Development Test Flight 2 (DTF-2) experiment. The system consists of 4 major components: (1) dual FTS arms to perform dextrous tasks; (2) the main body to house power and electronics; (3) an Attachment Stabilization and Positioning Subsystem (ASPS) to provide coarse positioning and stabilization of the arms, and (4) the Worksite Attachment Mechanism (WAM) which anchors the system to its worksite, such as a Space Station truss node or Shuttle bay platform. The analysis is limited to the DTF-2 scenario. The goal is to understand the basic interaction dynamics between the arm, the positioner and/or stabilizer, and the worksite. The dynamics and controls simulation model are described. Analysis and simulation results are presented.

Randomized phase II study of a bendamustine monotherapy schedule for relapsed or refractory low-grade B-cell non-Hodgkin lymphoma or mantle cell lymphoma (RABBIT-14).

PubMed

Itoh, Kuniaki; Igarashi, Tadahiko; Irisawa, Hiroyuki; Aotsuka, Nobuyuki; Masuda, Shinichi; Utsu, Yoshikazu; Tsujimura, Hideki; Tsukasaki, Kunihiro; Wakita, Hisashi

2017-10-30

The aim of this randomized phase II study was to improve the treatment delays and discontinuations associated with bendamustine use by comparing the effect of Benda-14 (intravenous bendamustine, 120 mg/m 2 on days 1 and 15, repeated every 4 weeks for a total of 6 cycles) with those of the standard treatment in relapsed indolent lymphoma and/or mantle cell lymphoma. Forty-six patients were randomly assigned to the treatments from September 2012 to February 2016. Treatment accomplishment rate and median relative dose intensity were similar in both arms: 38 and 63.4% in the Benda-14 arm and 41 and 66.3% in the standard treatment arm, respectively. The overall response rate and median progression-free survival, respectively, were 83% and 21.0 months for Benda-14, and 77% and 15.5 months for the standard treatment. Benda-14 induced favorable responses with less frequent hematological toxicities.

First-in-human phase I study of oral S49076, a unique MET/AXL/FGFR inhibitor, in advanced solid tumours.

PubMed

Rodon, Jordi; Postel-Vinay, Sophie; Hollebecque, Antoine; Nuciforo, Paolo; Azaro, Analia; Cattan, Valérie; Marfai, Lucie; Sudey, Isabelle; Brendel, Karl; Delmas, Audrey; Malasse, Stéphanie; Soria, Jean-Charles

2017-08-01

S49076 is a novel ATP-competitive tyrosine kinase inhibitor of MET, AXL and FGFR with a unique selectivity profile. A phase I open-label study was undertaken to establish the tolerability profile and determine the recommended dose (RD) and administration schedule. Patients with advanced solid tumours received S49076 orally once-daily (qd) or twice-daily (bid) in continuous 21-day cycles at escalating doses guided by a 3 + 3 design and followed by an expansion phase at the RD. Pharmacokinetic (PK) parameters were assessed and pharmacodynamic end-points were evaluated in pre- and post-treatment tumour biopsies. Preliminary anti-tumour activity was evaluated as per the Response Evaluation Criteria In Solid Tumours 1.1 criteria. A total of 103 patients were treated: 79 in the dose-escalation and 24 in the expansion. Doses from 15 to 900 mg were evaluated. Dose-limiting toxicities were reported in 9 patients and occurred at 30, 760 and 900 mg in the qd arm and at 180, 225 and 285 mg in the bid arm. The RD was defined at 600 mg qd. Adverse events (AEs) occurred with similar frequency in both regimens at an equivalent total daily dose. Overall, 83 patients (81.4%) had drug-related AEs, the majority (93%) of which were grade I-II (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0) and only 3% led to drug discontinuation. Intratumoural PK analysis at the RD suggested hitting of MET, AXL and FGFR. S49076 demonstrated a tolerable safety profile with limited single-agent activity. PK/pharmacodynamic readouts of S49076 are encouraging for further investigation of S49076 in combination therapies. ISRCTN00759419. Copyright © 2017 Elsevier Ltd. All rights reserved.

A randomized open-label study of guideline-driven antiemetic therapy versus single agent antiemetic therapy in patients with advanced cancer and nausea not related to anticancer treatment.

PubMed

Hardy, Janet; Skerman, Helen; Glare, Paul; Philip, Jennifer; Hudson, Peter; Mitchell, Geoffrey; Martin, Peter; Spruyt, Odette; Currow, David; Yates, Patsy

2018-05-02

Nausea/vomiting (N/V) not related to anti-cancer treatment is common in patients with advanced cancer. The standard approach to management is to define a dominant cause, and treat with an antiemetic selected through pathophysiologic knowledge of emetic pathways. High rates of N/V control have been reported using both etiology-based guideline-driven antiemetic regimens and an empiric approach using single agents in uncontrolled studies. These different approaches had never been formally compared. This randomized, prospective, open label, dose-escalating study used readily available antiemetics in accordance with etiology-based guidelines or single agent therapy with haloperidol. Participants had a baseline average nausea score of ≥3/10. Response was defined as a ≥ 2/10 point reduction on a numerical rating scale of average nausea score with a final score < 3/10 at 72 h. Nausea scores and distress from nausea improved over time in the majority of the 185 patients randomized. For those who completed each treatment day, a greater response rate was seen in the guideline arm than the single agent arm at 24 h (49% vs 32%; p = 0.02), but not at 48 or 72 h. Response rates at 72 h in the intention to treat analysis were 49 and 53% respectively, with no significant difference between arms (0·04; 95% CI: -0·11, 0·19; p = 0·59). Over 80% of all participants reported an improved global impression of change. There were few adverse events worse than baseline in either arm. An etiology-based, guideline-directed approach to antiemetic therapy may offer more rapid benefit, but is no better than single agent treatment with haloperidol at 72 h. Australian New Zealand Clinical Trials Registry: ANZCTRN12610000481077 .

Fine-scale Horizontal Structure of Arctic Mixed-Phase Clouds.

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

Rambukkange,M.; Verlinde, J.; Elorante, E.

2006-07-10

Recent in situ observations in stratiform clouds suggest that mixed phase regimes, here defined as limited cloud volumes containing both liquid and solid water, are constrained to narrow layers (order 100 m) separating all-liquid and fully glaciated volumes (Hallett and Viddaurre, 2005). The Department of Energy Atmospheric Radiation Measurement Program's (DOE-ARM, Ackerman and Stokes, 2003) North Slope of Alaska (NSA) ARM Climate Research Facility (ACRF) recently started collecting routine measurement of radar Doppler velocity power spectra from the Millimeter Cloud Radar (MMCR). Shupe et al. (2004) showed that Doppler spectra has potential to separate the contributions to the total reflectivitymore » of the liquid and solid water in the radar volume, and thus to investigate further Hallett and Viddaurre's findings. The Mixed-Phase Arctic Cloud Experiment (MPACE) was conducted along the NSA to investigate the properties of Arctic mixed phase clouds (Verlinde et al., 2006). We present surface based remote sensing data from MPACE to discuss the fine-scale structure of the mixed-phase clouds observed during this experiment.« less

Large-scale Chromosomal Movements During Interphase Progression in Drosophila

PubMed Central

Csink, Amy K.; Henikoff, Steven

1998-01-01

We examined the effect of cell cycle progression on various levels of chromosome organization in Drosophila. Using bromodeoxyuridine incorporation and DNA quantitation in combination with fluorescence in situ hybridization, we detected gross chromosomal movements in diploid interphase nuclei of larvae. At the onset of S-phase, an increased separation was seen between proximal and distal positions of a long chromsome arm. Progression through S-phase disrupted heterochromatic associations that have been correlated with gene silencing. Additionally, we have found that large-scale G1 nuclear architecture is continually dynamic. Nuclei display a Rabl configuration for only ∼2 h after mitosis, and with further progression of G1-phase can establish heterochromatic interactions between distal and proximal parts of the chromosome arm. We also find evidence that somatic pairing of homologous chromosomes is disrupted during S-phase more rapidly for a euchromatic than for a heterochromatic region. Such interphase chromosome movements suggest a possible mechanism that links gene regulation via nuclear positioning to the cell cycle: delayed maturation of heterochromatin during G1-phase delays establishment of a silent chromatin state. PMID:9763417

Approaches for Achieving Broadband Achromatic Phase Shifts for Visible Nulling Coronagraphy

NASA Technical Reports Server (NTRS)

Bolcar, Matthew R.; Lyon, Richard G.

2012-01-01

Visible nulling coronagraphy is one of the few approaches to the direct detection and characterization of Jovian and Terrestrial exoplanets that works with segmented aperture telescopes. Jovian and Terrestrial planets require at least 10(exp -9) and 10(exp -10) image plane contrasts, respectively, within the spectral bandpass and thus require a nearly achromatic pi-phase difference between the arms of the interferometer. An achromatic pi-phase shift can be achieved by several techniques, including sequential angled thick glass plates of varying dispersive materials, distributed thin-film multilayer coatings, and techniques that leverage the polarization-dependent phase shift of total-internal reflections. Herein we describe two such techniques: sequential thick glass plates and Fresnel rhomb prisms. A viable technique must achieve the achromatic phase shift while simultaneously minimizing the intensity difference, chromatic beam spread and polarization variation between each arm. In this paper we describe the above techniques and report on efforts to design, model, fabricate, align the trades associated with each technique that will lead to an implementations of the most promising one in Goddard's Visible Nulling Coronagraph (VNC).

A pilot single-blind multicentre randomized controlled trial to evaluate the potential benefits of computer-assisted arm rehabilitation gaming technology on the arm function of children with spastic cerebral palsy.

PubMed

Preston, Nick; Weightman, Andrew; Gallagher, Justin; Levesley, Martin; Mon-Williams, Mark; Clarke, Mike; O'Connor, Rory J

2016-10-01

To evaluate the potential benefits of computer-assisted arm rehabilitation gaming technology on arm function of children with spastic cerebral palsy. A single-blind randomized controlled trial design. Power calculations indicated that 58 children would be required to demonstrate a clinically important difference. Intervention was home-based; recruitment took place in regional spasticity clinics. A total of 15 children with cerebral palsy aged five to 12 years were recruited; eight to the device group. Both study groups received 'usual follow-up treatment' following spasticity treatment with botulinum toxin; the intervention group also received a rehabilitation gaming device. ABILHAND-kids and Canadian Occupational Performance Measure were performed by blinded assessors at baseline, six and 12 weeks. An analysis of covariance showed no group differences in mean ABILHAND-kids scores between time points. A non-parametric analysis of variance on Canadian Occupational Performance Measure scores showed a statistically significant improvement across time points (χ 2 (2,15) = 6.778, p = 0.031), but this improvement did not reach minimal clinically important difference. Mean daily device use was seven minutes. Recruitment did not reach target owing to unanticipated staff shortages in clinical services. Feedback from children and their families indicated that the games were not sufficiently engaging to promote sufficient use that was likely to result in functional benefits. This study suggests that computer-assisted arm rehabilitation gaming does not benefit arm function, but a Type II error cannot be ruled out. © The Author(s) 2015.

Relaxation near Supermassive Black Holes Driven by Nuclear Spiral Arms: Anisotropic Hypervelocity Stars, S-stars, and Tidal Disruption Events

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

Hamers, Adrian S.; Perets, Hagai B., E-mail: hamers@ias.edu

Nuclear spiral arms are small-scale transient spiral structures found in the centers of galaxies. Similarly to their galactic-scale counterparts, nuclear spiral arms can perturb the orbits of stars. In the case of the Galactic center (GC), these perturbations can affect the orbits of stars and binaries in a region extending to several hundred parsecs around the supermassive black hole (SMBH), causing diffusion in orbital energy and angular momentum. This diffusion process can drive stars and binaries to close approaches with the SMBH, disrupting single stars in tidal disruption events (TDEs), or disrupting binaries, leaving a star tightly bound to themore » SMBH and an unbound star escaping the galaxy, i.e., a hypervelocity star (HVS). Here, we consider diffusion by nuclear spiral arms in galactic nuclei, specifically the Milky Way GC. We determine nuclear-spiral-arm-driven diffusion rates using test-particle integrations and compute disruption rates. Our TDE rates are up to 20% higher compared to relaxation by single stars. For binaries, the enhancement is up to a factor of ∼100, and our rates are comparable to the observed numbers of HVSs and S-stars. Our scenario is complementary to relaxation driven by massive perturbers. In addition, our rates depend on the inclination of the binary with respect to the Galactic plane. Therefore, our scenario provides a novel potential source for the observed anisotropic distribution of HVSs. Nuclear spiral arms may also be important for accelerating the coalescence of binary SMBHs and for supplying nuclear star clusters with stars and gas.« less

A common neural element receiving rhythmic arm and leg activity as assessed by reflex modulation in arm muscles.

PubMed

Sasada, Syusaku; Tazoe, Toshiki; Nakajima, Tsuyoshi; Futatsubashi, Genki; Ohtsuka, Hiroyuki; Suzuki, Shinya; Zehr, E Paul; Komiyama, Tomoyoshi

2016-04-01

Neural interactions between regulatory systems for rhythmic arm and leg movements are an intriguing issue in locomotor neuroscience. Amplitudes of early latency cutaneous reflexes (ELCRs) in stationary arm muscles are modulated during rhythmic leg or arm cycling but not during limb positioning or voluntary contraction. This suggests that interneurons mediating ELCRs to arm muscles integrate outputs from neural systems controlling rhythmic limb movements. Alternatively, outputs could be integrated at the motoneuron and/or supraspinal levels. We examined whether a separate effect on the ELCR pathways and cortico-motoneuronal excitability during arm and leg cycling is integrated by neural elements common to the lumbo-sacral and cervical spinal cord. The subjects performed bilateral leg cycling (LEG), contralateral arm cycling (ARM), and simultaneous contralateral arm and bilateral leg cycling (A&L), while ELCRs in the wrist flexor and shoulder flexor muscles were evoked by superficial radial (SR) nerve stimulation. ELCR amplitudes were facilitated by cycling tasks and were larger during A&L than during ARM and LEG. A low stimulus intensity during ARM or LEG generated a larger ELCR during A&L than the sum of ELCRs during ARM and LEG. We confirmed this nonlinear increase in single motor unit firing probability following SR nerve stimulation during A&L. Furthermore, motor-evoked potentials following transcranial magnetic and electrical stimulation did not show nonlinear potentiation during A&L. These findings suggest the existence of a common neural element of the ELCR reflex pathway that is active only during rhythmic arm and leg movement and receives convergent input from contralateral arms and legs. Copyright © 2016 the American Physiological Society.

Ca2+-Induced Rigidity Change of the Myosin VIIa IQ Motif-Single α Helix Lever Arm Extension.

PubMed

Li, Jianchao; Chen, Yiyun; Deng, Yisong; Unarta, Ilona Christy; Lu, Qing; Huang, Xuhui; Zhang, Mingjie

2017-04-04

Several unconventional myosins contain a highly charged single α helix (SAH) immediately following the calmodulin (CaM) binding IQ motifs, functioning to extend lever arms of these myosins. How such SAH is connected to the IQ motifs and whether the conformation of the IQ motifs-SAH segments are regulated by Ca 2+ fluctuations are not known. Here, we demonstrate by solving its crystal structure that the predicted SAH of myosin VIIa (Myo7a) forms a stable SAH. The structure of Myo7a IQ5-SAH segment in complex with apo-CaM reveals that the SAH sequence can extend the length of the Myo7a lever arm. Although Ca 2+ -CaM remains bound to IQ5-SAH, the Ca 2+ -induced CaM binding mode change softens the conformation of the IQ5-SAH junction, revealing a Ca 2+ -induced lever arm flexibility change for Myo7a. We further demonstrate that the last IQ motif of several other myosins also binds to both apo- and Ca 2+ -CaM, suggesting a common Ca 2+ -induced conformational regulation mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

An Intergroup Randomized Phase II Study of Bevacizumab or Cetuximab in Combination with Gemcitabine and in Combination with Chemoradiation in Patients with Resected Pancreatic Carcinoma: A Trial of the ECOG-ACRIN Cancer Research Group (E2204).

PubMed

Berlin, Jordan D; Feng, Yang; Catalano, Paul; Abbruzzese, James L; Philip, Philip A; McWilliams, Robert R; Lowy, Andrew M; Benson, Al B; Blackstock, A William

2018-01-01

Evaluate toxicity of two treatment arms, A (cetuximab) and B (bevacizumab), when combined with gemcitabine, and chemoradiation in patients with completely resected pancreatic carcinoma. Secondary objectives included overall survival (OS) and disease-free survival (DFS). Patients with R0/R1 resection were randomized 1:1 to cetuximab or bevacizumab administered in combination with gemcitabine for two treatment cycles. Next three cycles included concurrent cetuximab/bevacizumab plus chemoradiation, followed by one cycle of cetuximab/bevacizumab. Cycles 7-12 included cetuximab/bevacizumab with gemcitabine. Cycles were 2 weeks. Frequency of specific toxicities was summarized for each treatment arm at two times during the study, after chemotherapy but prior to chemoradiation and after all therapy. A total of 127 patients were randomized (A, n = 65; B, n = 62). Prior to chemoradiation, the overall rate for toxicities of interest was 10% for arm A and 2% for arm B. After all therapy, the overall rates for toxicities of interest were 30 and 25% for arms A and B, respectively. Overall median OS and DFS were 17 and 11 months, respectively, which is not a significant improvement over expected survival rates for historical controls. Both treatments were tolerable with manageable toxicities, and were safe enough for a phase III trial had this been indicated. © 2017 S. Karger AG, Basel.

Robotic Characterization of Ipsilesional Motor Function in Subacute Stroke.

PubMed

Semrau, Jennifer A; Herter, Troy M; Kenzie, Jeffrey M; Findlater, Sonja E; Scott, Stephen H; Dukelow, Sean P

2017-06-01

Poststroke impairments of the ipsilesional arm are often discussed, but rarely receive focused rehabilitation. Ipsilesional deficits may affect daily function and although many studies have investigated them in chronic stroke, few characterizations have been made in the subacute phase. Furthermore, most studies have quantified ipsilesional deficits using clinical measures that can fail to detect subtle, but important deficits in motor function. We aimed to quantify reaching deficits of the contra- and ipsilesional limbs in the subacute phase poststroke. A total of 227 subjects with first-time, unilateral stroke completed a unilateral assessment of motor function (visually guided reaching) using a KINARM robot. Subjects completed the task with both the ipsi- and contralesional arms. Subjects were assessed on a variety of traditional clinical measures (Functional Independence Measure, Chedoke-McMaster Stroke Assessment, Purdue Pegboard, Behavioral Inattention Test) to compare with robotic measures of motor function. Ipsilesional deficits were common and occurred in 37% (n = 84) of subjects. Impairments of the ipsilesional and contralesional arm were weakly to moderately correlated on robotic measures. Magnitude of impairment of the contralesional arm was similar for subjects with and without ipsilesional deficits. Furthermore, we found that a higher percentage of subjects with right-hemisphere stroke had ipsilesional deficits and more subjects with left-hemisphere subcortical strokes did not have ipsilesional deficits. Magnitude of contralesional impairment and lesion location may be poor predictors of individuals with ipsilesional impairments after stroke. Careful characterization of ipsilesional deficits could identify individuals who may benefit from rehabilitation of the less affected arm.

Effort, success, and nonuse determine arm choice

PubMed Central

Xiao, Yupeng; Kim, Sujin; Yoshioka, Toshinori; Gordon, James; Osu, Rieko

2015-01-01

How do humans choose one arm or the other to reach single targets in front of the body? Current theories of reward-driven decisionmaking predict that choice results from a comparison of “action values,” which are the expected rewards for possible actions in a given state. In addition, current theories of motor control predict that in planning arm movements, humans minimize an expected motor cost that balances motor effort and endpoint accuracy. Here, we test the hypotheses that arm choice is determined by comparison of action values comprising expected effort and expected task success for each arm, as well as a handedness bias. Right-handed subjects, in either a large or small target condition, were first instructed to use each hand in turn to shoot through an array of targets and then to choose either hand to shoot through the same targets. Effort was estimated via inverse kinematics and dynamics. A mixed-effects logistic-regression analysis showed that, as predicted, both expected effort and expected success predicted choice, as did arm use in the preceding trial. Finally, individual parameter estimation showed that the handedness bias correlated with mean difference between right- and left-arm success, leading to overall lower use of the left arm. We discuss our results in light of arm nonuse in individuals' poststroke. PMID:25948869

The effect of arm support combined with rehabilitation games on upper-extremity function in subacute stroke: a randomized controlled trial.

PubMed

Prange, Gerdienke B; Kottink, Anke I R; Buurke, Jaap H; Eckhardt, Martine M E M; van Keulen-Rouweler, Bianca J; Ribbers, Gerard M; Rietman, Johan S

2015-02-01

Use of rehabilitation technology, such as (electro)mechanical devices or robotics, could partly relieve the increasing strain on stroke rehabilitation caused by an increasing prevalence of stroke. Arm support (AS) training showed improvement of unsupported arm function in chronic stroke. To examine the effect of weight-supported arm training combined with computerized exercises on arm function and capacity, compared with dose-matched conventional reach training in subacute stroke patients. In a single-blind, multicenter, randomized controlled trial, 70 subacute stroke patients received 6 weeks of training with either an AS device combined with computerized exercises or dose-matched conventional training (CON). Arm function was evaluated pretraining and posttraining by Fugl-Meyer assessment (FM), maximal reach distance, Stroke Upper Limb Capacity Scale (SULCS), and arm pain via Visual Analogue Scale, in addition to perceived motivation by Intrinsic Motivation Inventory posttraining. FM and SULCS scores and reach distance improved significantly within both groups. These improvements and experienced pain did not differ between groups. The AS group reported higher interest/enjoyment during training than the CON group. AS training with computerized exercises is as effective as conventional therapy dedicated to the arm to improve arm function and activity in subacute stroke rehabilitation, when applied at the same dose. © The Author(s) 2014.

Spatiotemporal distribution of location and object effects in reach-to-grasp kinematics

PubMed Central

Rouse, Adam G.

2015-01-01

In reaching to grasp an object, the arm transports the hand to the intended location as the hand shapes to grasp the object. Prior studies that tracked arm endpoint and grip aperture have shown that reaching and grasping, while proceeding in parallel, are interdependent to some degree. Other studies of reaching and grasping that have examined the joint angles of all five digits as the hand shapes to grasp various objects have not tracked the joint angles of the arm as well. We, therefore, examined 22 joint angles from the shoulder to the five digits as monkeys reached, grasped, and manipulated in a task that dissociated location and object. We quantified the extent to which each angle varied depending on location, on object, and on their interaction, all as a function of time. Although joint angles varied depending on both location and object beginning early in the movement, an early phase of location effects in joint angles from the shoulder to the digits was followed by a later phase in which object effects predominated at all joint angles distal to the shoulder. Interaction effects were relatively small throughout the reach-to-grasp. Whereas reach trajectory was influenced substantially by the object, grasp shape was comparatively invariant to location. Our observations suggest that neural control of reach-to-grasp may occur largely in two sequential phases: the first determining the location to which the arm transports the hand, and the second shaping the entire upper extremity to grasp and manipulate the object. PMID:26445870

Samarium-153-EDTMP (Quadramet®) with or without vaccine in metastatic castration-resistant prostate cancer: A randomized Phase 2 trial.

PubMed

Heery, Christopher R; Madan, Ravi A; Stein, Mark N; Stadler, Walter M; Di Paola, Robert S; Rauckhorst, Myrna; Steinberg, Seth M; Marté, Jennifer L; Chen, Clara C; Grenga, Italia; Donahue, Renee N; Jochems, Caroline; Dahut, William L; Schlom, Jeffrey; Gulley, James L

2016-10-18

PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine tetramethylene phosphonate (Sm-153-EDTMP; Quadramet®), a radiopharmaceutical, binds osteoblastic bone lesions and emits beta particles causing local tumor cell destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating immune-mediated killing. This phase 2 multi-center trial randomized patients to Sm-153-EDTMP alone or with PSA-TRICOM vaccine. Eligibility required mCRPC, bone metastases, prior docetaxel and no visceral disease. The primary endpoint was the proportion of patients without radiographic disease progression at 4 months. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and immune responses. Forty-four patients enrolled. Eighteen and 21 patients were evaluable for the primary endpoint in Sm-153-EDTMP alone and combination arms, respectively. There was no statistical difference in the primary endpoint, with two of 18 (11.1%) and five of 21 (23.8%) in Sm-153-EDTMP alone and combination arms, respectively, having stable disease at approximately the 4-month evaluation time point (P = 0.27). Median PFS was 1.7 vs. 3.7 months in the Sm-153-EDTMP alone and combination arms (P = 0.041, HR = 0.51, P = 0.046). No patient in the Sm-153-EDTMP alone arm achieved prostate-specific antigen (PSA) decline > 30% compared with four patients (of 21) in the combination arm, including three with PSA decline > 50%. Toxicities were similar between arms and related to number of Sm-153-EDTMP doses administered. These results provide the rationale for clinical evaluation of new radiopharmaceuticals, such as Ra-223, in combination with PSA-TRICOM.

Samarium-153-EDTMP (Quadramet®) with or without vaccine in metastatic castration-resistant prostate cancer: A randomized Phase 2 trial

PubMed Central

Heery, Christopher R.; Madan, Ravi A.; Stein, Mark N.; Stadler, Walter M.; Di Paola, Robert S.; Rauckhorst, Myrna; Steinberg, Seth M.; Marté, Jennifer L.; Chen, Clara C.; Grenga, Italia; Donahue, Renee N.; Jochems, Caroline; Dahut, William L.; Schlom, Jeffrey; Gulley, James L.

2016-01-01

PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine tetramethylene phosphonate (Sm-153-EDTMP; Quadramet®), a radiopharmaceutical, binds osteoblastic bone lesions and emits beta particles causing local tumor cell destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating immune-mediated killing. This phase 2 multi-center trial randomized patients to Sm-153-EDTMP alone or with PSA-TRICOM vaccine. Eligibility required mCRPC, bone metastases, prior docetaxel and no visceral disease. The primary endpoint was the proportion of patients without radiographic disease progression at 4 months. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and immune responses. Forty-four patients enrolled. Eighteen and 21 patients were evaluable for the primary endpoint in Sm-153-EDTMP alone and combination arms, respectively. There was no statistical difference in the primary endpoint, with two of 18 (11.1%) and five of 21 (23.8%) in Sm-153-EDTMP alone and combination arms, respectively, having stable disease at approximately the 4-month evaluation time point (P = 0.27). Median PFS was 1.7 vs. 3.7 months in the Sm-153-EDTMP alone and combination arms (P = 0.041, HR = 0.51, P = 0.046). No patient in the Sm-153-EDTMP alone arm achieved prostate-specific antigen (PSA) decline > 30% compared with four patients (of 21) in the combination arm, including three with PSA decline > 50%. Toxicities were similar between arms and related to number of Sm-153-EDTMP doses administered. These results provide the rationale for clinical evaluation of new radiopharmaceuticals, such as Ra-223, in combination with PSA-TRICOM. PMID:27486817

Maintenance sunitinib or observation in metastatic pancreatic adenocarcinoma: a phase II randomised trial.

PubMed

Reni, Michele; Cereda, Stefano; Milella, Michele; Novarino, Anna; Passardi, Alessandro; Mambrini, Andrea; Di Lucca, Giuseppe; Aprile, Giuseppe; Belli, Carmen; Danova, Marco; Bergamo, Francesca; Franceschi, Enrico; Fugazza, Clara; Ceraulo, Domenica; Villa, Eugenio

2013-11-01

New strategies to prolong disease control warrant investigation in patients with metastatic pancreatic adenocarcinoma. This open-label, randomised, multi-centre phase II trial explored the role of maintenance sunitinib after first-line chemotherapy in this setting. Patients with pathologic diagnosis of metastatic pancreatic adenocarcinoma, performance status >50%, no progression after 6 months of chemotherapy were centrally randomised by an independent contract research organisation, which was also responsible for data collection and monitoring, to observation (arm A) or sunitinib at 37.5mg daily until progression or a maximum of 6 months (arm B). The primary outcome measure was the probability of being progression-free at 6 months (PFS-6) from randomisation. Assuming P0 = 10%; P1 = 30%, α .10; β .10, the target accrual was 26 patients per arm. 28 per arm were randomised. One arm B patient had kidney cancer and was excluded. Sunitinib was given for a median of 91 days (7-186). Main grade 3-4 toxicity was thrombocytopenia, neutropenia and hand-foot syndrome (12%), diarrhoea 8%. In arm A versus B, PFS-6 was 3.6% (95% confidence interval (CI): 0-10.6%) and 22.2% (95% CI: 6.2-38.2%; P<0.01); 2 y overall survival was 7.1% (95% CI: 0-16.8%) and 22.9% (95% CI: 5.8-40.0%; P = 0.11), stable disease 21.4% and 51.9% (P = 0.02). This is the first randomised trial on maintenance therapy in metastatic pancreatic adenocarcinoma. The primary end-point was fulfilled and 2 y overall survival was remarkably high, suggesting that maintenance sunitinib is promising and should be further explored in this patient population. Copyright © 2013 Elsevier Ltd. All rights reserved.

A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: Final results

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

Rouesse, Jacques; Lande, Brigitte de la; Bertheault-Cvitkovic, Frederique

Purpose: To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients. Methods and Materials: This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m{sup 2} 5-fluorouracil, 12 mg/m{sup 2} mitoxantrone, and 500 mg/m{sup 2} cyclophosphamide, with concomitant radiotherapy (50 Gy {+-} 10-20-Gy boost). Patients in Arm B received 500 mg/m{sup 2} 5-fluorouracil, 60 mg/m{sup 2} epirubicin, and 500 mg/m{sup 2} cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles. Results: Medianmore » treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02). Conclusions: Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.« less

Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial.

PubMed

Gilbert, Mark R; Wang, Meihua; Aldape, Kenneth D; Stupp, Roger; Hegi, Monika E; Jaeckle, Kurt A; Armstrong, Terri S; Wefel, Jeffrey S; Won, Minhee; Blumenthal, Deborah T; Mahajan, Anita; Schultz, Christopher J; Erridge, Sara; Baumert, Brigitta; Hopkins, Kristen I; Tzuk-Shina, Tzahala; Brown, Paul D; Chakravarti, Arnab; Curran, Walter J; Mehta, Minesh P

2013-11-10

Radiotherapy with concomitant and adjuvant temozolomide is the standard of care for newly diagnosed glioblastoma (GBM). O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status may be an important determinant of treatment response. Dose-dense (DD) temozolomide results in prolonged depletion of MGMT in blood mononuclear cells and possibly in tumor. This trial tested whether DD temozolomide improves overall survival (OS) or progression-free survival (PFS) in patients with newly diagnosed GBM. This phase III trial enrolled patients older than age 18 years with a Karnofsky performance score of ≥ 60 with adequate tissue. Stratification included clinical factors and tumor MGMT methylation status. Patients were randomly assigned to standard temozolomide (arm 1) or DD temozolomide (arm 2) for 6 to 12 cycles. The primary end point was OS. Secondary analyses evaluated the impact of MGMT status. A total of 833 patients were randomly assigned to either arm 1 or arm 2 (1,173 registered). No statistically significant difference was observed between arms for median OS (16.6 v 14.9 months, respectively; hazard ratio [HR], 1.03; P = .63) or median PFS (5.5 v 6.7 months; HR, 0.87; P = .06). Efficacy did not differ by methylation status. MGMT methylation was associated with improved OS (21.2 v 14 months; HR, 1.74; P < .001), PFS (8.7 v 5.7 months; HR, 1.63; P < .001), and response (P = .012). There was increased grade ≥ 3 toxicity in arm 2 (34% v 53%; P < .001), mostly lymphopenia and fatigue. This study did not demonstrate improved efficacy for DD temozolomide for newly diagnosed GBM, regardless of methylation status. However, it did confirm the prognostic significance of MGMT methylation. Feasibility of large-scale accrual, prospective tumor collection, and molecular stratification was demonstrated.

A simple integrated ratiometric wavelength monitor based on multimode interference structure

NASA Astrophysics Data System (ADS)

Hatta, Agus Muhamad; Farrell, Gerald; Wang, Qian

2008-09-01

Wavelength measurement or monitoring can be implemented using a ratiometric power measurement technique. A ratiometric wavelength monitor normally consists of a Y-branch splitter with two arms: an edge filter arm with a well defined spectral response and a reference arm or alternatively, two edge filters arms with opposite slope spectral responses. In this paper, a simple configuration for an integrated ratiometric wavelength monitor based on a single multimode interference structure is proposed. By optimizing the length of the MMI and the two output port positions, opposite spectral responses for the two output ports can be achieved. The designed structure demonstrates a spectral response suitable for wavelength measurement with potentially a 10 pm resolution over a 100 nm wavelength range.

The ARAMIS project: a concept robot and technical design.

PubMed

Colizzi, Lucio; Lidonnici, Antonio; Pignolo, Loris

2009-11-01

To describe the ARAMIS (Automatic Recovery Arm Motility Integrated System) project, a concept robot applicable in the neuro-rehabilitation of the paretic upper limb after stroke. Methods, results and conclusion: The rationale and engineering of a state-of-the-art, hardware/software integrated robot system, its mechanics, ergonomics, electric/electronics features providing control, safety and suitability of use are described. An ARAMIS prototype has been built and is now available for clinical tests. It allows the therapist to design neuro-rehabilitative (synchronous or asynchronous) training protocols in which sample exercises are generated by a single exoskeleton (operated by the patient's unaffected arm or by the therapist's arm) and mirrored in real-time or offline by the exoskeleton supporting the paretic arm.

Open-loop frequency acquisition for suppressed-carrier biphase signals using one-pole arm filters

NASA Technical Reports Server (NTRS)

Shah, B.; Holmes, J. K.

1991-01-01

Open loop frequency acquisition performance is discussed for suppressed carrier binary phase shift keyed signals in terms of the probability of detecting the carrier frequency offset when the arms of the Costas loop detector have one pole filters. The approach, which does not require symbol timing, uses fast Fourier transforms (FFTs) to detect the carrier frequency offset. The detection probability, which depends on both the 3 dB arm filter bandwidth and the received symbol signal to noise ratio, is derived and is shown to be independent of symbol timing. It is shown that the performance of this technique is slightly better that other open loop acquisition techniques which use integrators in the arms and whose detection performance varies with symbol timing.

A randomized, blinded, multicenter trial of a gentamicin vancomycin gel (DFA-02) in patients undergoing abdominal surgery.

PubMed

Bennett-Guerrero, Elliott; Berry, Scott M; Bergese, Sergio D; Fleshner, Phillip R; Minkowitz, Harold S; Segura-Vasi, Alvaro M; Itani, Kamal M F; Henderson, Karen W; Rackowski, Felicia P; Aberle, Laura H; Stryjewski, Martin E; Corey, G Ralph; Allenby, Kent S

2017-06-01

SI is a significant medical problem. DFA-02 is an investigational bioresorbable modified release gel consisting of both gentamicin (16.8 mg/mL) and vancomycin (18.8 mg/mL). A Phase 2a study, where the drug was applied during surgical incision closure, suggested safety and tolerability but was not designed to assess its efficacy. In a Phase 2b randomized, blinded trial patients undergoing abdominal, primarily colorectal, surgery were randomized (4:1:1) to one of three study arms: DFA-02, matching placebo gel, or standard of care (SOC) involving irrigation of the wound with normal saline. The DFA-02 and placebo gel groups received up to 20 mL of study drug inserted above the fascia during wound closure, and were treated in a double-blind manner; the SOC group was treated in a single-blind manner. The primary endpoint was SSI (adjudicated centrally by a blinded committee) through postoperative day 30. Overall, 445 subjects (intention-to-treat) were randomized at 35 centers with 425 subjects completing the study and being evaluable. There were 67 SSIs (15.8%): 64.2% superficial, 7.5% deep, and 28.4% organ space. The incidence of SSI was not statistically significantly different between the DFA-02 and the placebo gel/SOC arms combined, 42/287 = 14.6% vs 25/138 = 18.1% (p = 0.36), respectively. Rehospitalization within 30 days was also similar between study groups (DFA-02 28.6%, placebo gel 21.4%, SOC 27.3%). In this multicenter, blinded, randomized trial with central adjudication, the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. Patients undergoing abdominal surgery were randomized to one of three study arms: DFA-02 gel consisting of both gentamicin and vancomycin, matching placebo gel, or standard of care (SOC). Of 425 patients completing the study at 35 sites the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of OPD in wavelength-shifting interferometry

NASA Astrophysics Data System (ADS)

Wang, Hongjun; Tian, Ailing; Liu, Bingcai; Dang, Juanjuan

2009-12-01

Phase-shifting interferometry is a powerful tool for high accuracy optical measurement. It operates by change the optical path length in the reference arm or test arm. This method practices by move optical device. So it has much problem when the optical device is very large and heavy. For solve this problem, the wavelength-shifting interferometry was put forwarded. In wavelength-shifting interferometry, the phase shifting angle was achieved by change the wavelength of optical source. The phase shifting angle was decided by wavelength and OPD (Optical Path Difference) between test and reference wavefront. So the OPD is an important factor to measure results. But in measurement, because the positional error and profile error of under testing optical element is exist, the phase shifting angle is different in different test point when wavelength scanning, it will introduce phase shifting angle error, so it will introduce optical surface measure error. For analysis influence of OPD on optical surface error, the relation between surface error and OPD was researched. By simulation, the relation between phase shifting error and OPD was established. By analysis, the error compensation method was put forward. After error compensation, the measure results can be improved to great extend.

Influence of OPD in wavelength-shifting interferometry

NASA Astrophysics Data System (ADS)

Wang, Hongjun; Tian, Ailing; Liu, Bingcai; Dang, Juanjuan

2010-03-01

Phase-shifting interferometry is a powerful tool for high accuracy optical measurement. It operates by change the optical path length in the reference arm or test arm. This method practices by move optical device. So it has much problem when the optical device is very large and heavy. For solve this problem, the wavelength-shifting interferometry was put forwarded. In wavelength-shifting interferometry, the phase shifting angle was achieved by change the wavelength of optical source. The phase shifting angle was decided by wavelength and OPD (Optical Path Difference) between test and reference wavefront. So the OPD is an important factor to measure results. But in measurement, because the positional error and profile error of under testing optical element is exist, the phase shifting angle is different in different test point when wavelength scanning, it will introduce phase shifting angle error, so it will introduce optical surface measure error. For analysis influence of OPD on optical surface error, the relation between surface error and OPD was researched. By simulation, the relation between phase shifting error and OPD was established. By analysis, the error compensation method was put forward. After error compensation, the measure results can be improved to great extend.

Heat shock protein peptide complex-96 vaccination for newly diagnosed glioblastoma: a phase I, single-arm trial.

PubMed

Ji, Nan; Zhang, Yang; Liu, Yunpeng; Xie, Jian; Wang, Yi; Hao, Shuyu; Gao, Zhixian

2018-05-17

Heat shock protein peptide complex-96 (HSPPC-96) triggers adaptive and innate antitumor immune responses. The safety and efficacy of HSPPC-96 vaccination was examined in patients with newly diagnosed glioblastoma multiforme (GBM). In this open-label, single-arm, phase I study, adult patients were vaccinated with HSPPC-96 in combination with the standard treatment for newly diagnosed GBM after surgical resection. Primary endpoints were frequency of adverse events and progression-free survival (PFS) at 6 months. Secondary endpoints included overall survival (OS), PFS, and tumor-specific immune response (TSIR). A total of 20 patients with newly diagnosed GBM were enrolled from September 2013 to February 2015. No grade 3 or 4 vaccine-related adverse events were noted. After a median follow-up of 42.3 months, PFS was 89.5% (95% CI, 66.9%-98.7%) at 6 months, median PFS was 11.0 months (95% CI, 8.2-13.8), and median OS was 31.4 months (95% CI, 14.9-47.9). TSIR was significantly increased by 2.3-fold (95% CI, 1.7-3.2) after vaccination. Median OS for patients with high TSIR after vaccination was >40.5 months (95% CI, incalculable) as compared with 14.6 months (95% CI, 7.0-22.2) for patients with low TSIR after vaccination (hazard ratio, 0.25; 95% CI, 0.071-0.90; P = 0.034). A multivariate Cox regression model revealed TSIR after vaccination as a primary independent predicator for survival. The HSPPC-96 vaccination, combined with the standard therapy, is a safe and effective strategy for treatment of newly diagnosed GBM patients. TSIR after vaccination would be a good indicator predicting the vaccine efficacy. ClinicalTrials.gov NCT02122822. National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2014BAI04B01, 2014BAI04B02), Beijing Natural Science Foundation (7164253), Beijing Talents Fund (2014000021469G257), and Shenzhen Science and Technology Innovation Committee (JSGG20170413151359491).

Pemetrexed-Erlotinib, Pemetrexed Alone, or Erlotinib Alone as Second-Line Treatment for East Asian and Non-East Asian Never-Smokers with Locally Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer: Exploratory Subgroup Analysis of a Phase II Trial

PubMed Central

Lee, Dae Ho; Lee, Jung Shin; Wang, Jie; Hsia, Te-Chun; Wang, Xin; Kim, Jongseok; Orlando, Mauro

2015-01-01

Purpose This subgroup analysis of a phase II trial was conducted to assess possible ethnicity-based trends in efficacy and safety in East Asian (EA) and non-EA populations with nonsquamous non-small cell lung cancer (NSCLC). Materials and Methods Never-smoker patients (n=240) with locally advanced or metastatic nonsquamous NSCLC included 133 EA patients randomized to pemetrexed supplemented with dexamethasone, folic acid, and vitamin B12 plus erlotinib (pemetrexed-erlotinib) (n=41), erlotinib (n=49), or pemetrexed (n=43), and 107 non-EA patients randomized to pemetrexed-erlotinib (n=37), erlotinib (n=33), or pemetrexed (n=37). The primary endpoint, progression-free survival (PFS), was analyzed using a multivariate Cox model. Results Consistent with the results of the overall study, a statistically significant difference in PFS among the three arms was noted in the EA population favoring pemetrexed-erlotinib (overall p=0.003) as compared with either single-agent arm (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29 to 0.79; p=0.004 vs. erlotinib; HR, 0.40; 95% CI, 0.23 to 0.70; p=0.001 vs. pemetrexed). The EA patients treated with pemetrexed-erlotinib achieved a longer median PFS (7.4 months) compared with erlotinib (4.5 months) and pemetrexed (4.0 months). The PFS results also numerically favored pemetrexed-erlotinib in the non-EA population (overall p=0.210) (HR, 0.62; 95% CI, 0.37 to 1.05; p=0.078 vs. erlotinib; HR, 0.75; 95% CI, 0.42 to 1.32; p=0.320 vs. pemetrexed) (median PFS: pemetrexed-erlotinib, 6.7 months; erlotinib, 3.0 months; pemetrexed, 4.4 months). Conclusion The PFS results from this subset analysis in both EA and non-EA populations are consistent with the results in the overall population. The PFS advantage for pemetrexed-erlotinib is significant compared with the single agents in EA patients. PMID:25672577

Electro-mechanical control of an on-chip optical beam splitter containing an embedded quantum emitter.

PubMed

Bishop, Z K; Foster, A P; Royall, B; Bentham, C; Clarke, E; Skolnick, M S; Wilson, L R

2018-05-01

We demonstrate electro-mechanical control of an on-chip GaAs optical beam splitter containing a quantum dot single-photon source. The beam splitter consists of two nanobeam waveguides, which form a directional coupler (DC). The splitting ratio of the DC is controlled by varying the out-of-plane separation of the two waveguides using electromechanical actuation. We reversibly tune the beam splitter between an initial state, with emission into both output arms, and a final state with photons emitted into a single output arm. The device represents a compact and scalable tuning approach for use in III-V semiconductor integrated quantum optical circuits.

Multipoint sensing with a low-coherence source using single-arm frequency-shifted interferometry

DOE PAGES

Zhang, Yiwei; Ye, Fei; Qi, Bing; ...

2016-07-12

We demonstrate that multiple-site sensing along an optical fiber can be done with incoherent continuous-wave light. Here, using a broadband low-coherence noise source, a slow detector, and an optical modulator, we construct a single-arm frequency-shifted interferometer (SA-FSI) capable of simultaneously sensing multiple weak-reflection sites distributed either in parallel or in series along fiber links. By scanning the driving frequency of an electro-optic amplitude modulator in the range of 2.7–3.2 GHz at steps of 41.7 KHz, we demonstrate a spatial resolution of 0.3 m and a measurement range of over 1 km.

Acoustic ranging of small arms fire using a single sensor node collocated with the target.

PubMed

Lo, Kam W; Ferguson, Brian G

2015-06-01

A ballistic model-based method, which builds upon previous work by Lo and Ferguson [J. Acoust. Soc. Am. 132, 2997-3017 (2012)], is described for ranging small arms fire using a single acoustic sensor node collocated with the target, without a priori knowledge of the muzzle speed and ballistic constant of the bullet except that they belong to a known two-dimensional parameter space. The method requires measurements of the differential time of arrival and differential angle of arrival of the muzzle blast and ballistic shock wave at the sensor node. Its performance is evaluated using both simulated and real data.

Changes in arm-hand function and arm-hand skill performance in patients after stroke during and after rehabilitation.

PubMed

Franck, Johan Anton; Smeets, Rob Johannes Elise Marie; Seelen, Henk Alexander Maria

2017-01-01

Arm-hand rehabilitation programs applied in stroke rehabilitation frequently target specific populations and thus are less applicable in heterogeneous patient populations. Besides, changes in arm-hand function (AHF) and arm-hand skill performance (AHSP) during and after a specific and well-described rehabilitation treatment are often not well evaluated. This single-armed prospective cohort study featured three subgroups of stroke patients with either a severely, moderately or mildly impaired AHF. Rehabilitation treatment consisted of a Concise_Arm_and_hand_ Rehabilitation_Approach_in_Stroke (CARAS). Measurements at function and activity level were performed at admission, clinical discharge, 3, 6, 9 and 12 months after clinical discharge. Eighty-nine stroke patients (M/F:63/23; mean age:57.6yr (+/-10.6); post-stroke time:29.8 days (+/-20.1)) participated. All patients improved on AHF and arm-hand capacity during and after rehabilitation, except on grip strength in the severely affected subgroup. Largest gains occurred in patients with a moderately affected AHF. As to self-perceived AHSP, on average, all subgroups improved over time. A small percentage of patients declined regarding self-perceived AHSP post-rehabilitation. A majority of stroke patients across the whole arm-hand impairment severity spectrum significantly improved on AHF, arm-hand capacity and self-perceived AHSP. These were maintained up to one year post-rehabilitation. Results may serve as a control condition in future studies.

Lateralized Motor Control Processes Determine Asymmetry of Interlimb Transfer

PubMed Central

Sainburg, Robert L.; Schaefer, Sydney Y.; Yadav, Vivek

2016-01-01

This experiment tested the hypothesis that interlimb transfer of motor performance depends on recruitment of motor control processes that are specialized to the hemisphere contralateral to the arm that is initially trained. Right-handed participants performed a single-joint task, in which reaches were targeted to 4 different distances. While the speed and accuracy was similar for both hands, the underlying control mechanisms used to vary movement speed with distance were systematically different between the arms: The amplitude of the initial acceleration profiles scaled greater with movement speed for the right-dominant arm, while the duration of the initial acceleration profile scaled greater with movement speed for the left-non-dominant arm. These two processes were previously shown to be differentially disrupted by left and right hemisphere damage, respectively. We now hypothesize that task practice with the right arm might reinforce left-hemisphere mechanisms that vary acceleration amplitude with distance, while practice with the left arm might reinforce right-hemisphere mechanisms that vary acceleration duration with distance. We thus predict that following right arm practice, the left arm should show increased contributions of acceleration amplitude to peak velocities, and following left arm practice, the right arm should show increased contributions of acceleration duration to peak velocities. Our findings support these predictions, indicating that asymmetry in interlimb transfer of motor performance, at least in the task used here, depends on recruitment of lateralized motor control processes. PMID:27491479

Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Randomized Phase 2 Trial of Neoadjuvant Preoperative Paclitaxel/Cisplatin/Radiation Therapy (RT) or Irinotecan/Cisplatin/RT in Esophageal Adenocarcinoma: Long-Term Outcome and Implications for Trial Design

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

Kleinberg, Lawrence R., E-mail: kleinla@jhmi.edu; Catalano, Paul J.; Forastiere, Arlene A.

Purpose: Toxicity, pathologic complete response, and long-term outcomes are reported for the neoadjuvant therapies assessed in a randomized phase 2 Eastern Cooperative Oncology Group and American College of Radiology Imaging Network trial for operable esophageal adenocarcinoma, staged as II-IVa by endoscopy/ultrasonography (EUS). Methods and Materials: A total of 86 eligible patients began treatment. For arm A, preoperative chemotherapy was cisplatin, 30 mg/m{sup 2}, and irinotecan, 50 mg/m{sup 2}, on day 1, 8, 22, 29 during 45 Gy radiation therapy (RT), 1.8 Gy per day over 5 weeks. Adjuvant therapy was cisplatin, 30 mg/m{sup 2}, and irinotecan, 65 mg/m{sup 2} daymore » 1, 8 every 21 days for 3 cycles. Arm B therapy was cisplatin, 30 mg/m{sup 2}, and paclitaxel, 50 mg/m{sup 2}, day 1, 8, 15, 22, 29 with RT, followed by adjuvant cisplatin, 75 mg/m{sup 2}, and paclitaxel, 175 mg/m{sup 2}, day 1 every 21 days for 3 cycles. Stratification included EUS stage and performance status. Results: In arm A, median overall survival was 35 months, and 5-, 6-, and 7-year survival rates were 46%, 39%, and 35%, respectively, whereas for arm B, they were 21 months and 27%, 27%, and 23%, respectively. Median progression- or recurrence-free survival (PFS) was 39.8 months with a 3-year PFS of 50% for arm A and 12.4 months (P=.046) with 3-year PFS of 28% for arm B. Eighty percent of the observed incidents of progression occurred within 19 months. Survival did not differ significantly by EUS and performance status strata. Conclusions: Long-term survival was similar for both arms and did not appear superior to results achieved with other standard regimens.« less

Interprofessional, psycho-social intervention to facilitate resilience and reduce supportive care needs for patients with cancer: Results of a noncomparative, randomized phase II trial.

PubMed

Eicher, Manuela; Ribi, Karin; Senn-Dubey, Catherine; Senn, Stefanie; Ballabeni, Pierluigi; Betticher, Daniel

2018-04-14

We developed 2 intensity levels of a complex intervention for interprofessional supportive care in cancer (IPSC-C) to facilitate resilience and reduce unmet supportive care needs. We aimed to test the feasibility, acceptability, and preliminary effectiveness of both intensity levels in routine practice. In a randomized, noncomparative phase II trial, newly diagnosed patients received either low (LI-IPSC-C) or high (HI-IPSC-C) intensity interventions. Low-intensity-interprofessional supportive care in cancer (LI-IPSC-C) consisted of 3 electronic assessments of resilience, unmet supportive care needs, mood, and coping effort over 16 weeks with an immediate feedback to clinicians including tailored intervention recommendations to facilitate resilience and supportive care. High-intensity-interprofessional supportive care in cancer (HI-IPSC-C) added 5 structured consultations (face-to-face and telephone) provided by specialized nurses. Primary outcome was a change ≥5 in resilience score on the Connor-Davidson Resilience Scale (CD-RISC). Secondary outcomes were unmet supportive care needs, mood, and coping effort. We assessed feasibility by clinician-provided tailored interventions as recommended and acceptability through qualitative interviews with clinicians and patients. In the LI-IPSC-C arm, 11 of 41, in the HI-IPSC-C arm 17 of 43, patients increased resilience scores by ≥5. Relatively more patients decreased unmet needs in HI-IPSC-C arm. Mood, in both arms, and coping effort, in HI-IPSC-C arm, improved meaningfully. Feasibility was limited for the LI-IPSC-C arm, mainly due to lack of time; acceptability was high in both arms. Neither LI-IPSC-C nor HI-IPSC-C interventions reached the desired threshold. HI-IPSC-C showed positive effects on secondary outcomes and was feasible. Resilience as measured by the CD-RISC may not be the optimal outcome measure for this intervention. Copyright © 2018 John Wiley & Sons, Ltd.

Phase II randomized study of whole-brain radiation therapy with or without concurrent temozolomide for brain metastases from breast cancer.

PubMed

Cao, K I; Lebas, N; Gerber, S; Levy, C; Le Scodan, R; Bourgier, C; Pierga, J-Y; Gobillion, A; Savignoni, A; Kirova, Y M

2015-01-01

To improve the therapeutic index of whole-brain radiation therapy (WBRT) in the treatment of brain metastases (BM) from breast cancer, we investigated the efficacy and safety of WBRT combined with temozolomide (TMZ) in this population. This phase II multicenter prospective randomized study included patients with newly diagnosed intraparenchymal BMs from breast cancer, unsuitable for surgery or radiosurgery. All patients received conformal WBRT (3 Gy × 10-30 Gy), with or without concomitant TMZ administered at a dosage of 75 mg/m(2)/day during the irradiation period. The primary end point was objective response rate (ORR) 6 weeks after the end of treatment, defined as a partial or complete response on systematic brain MRI (modified WHO criteria). Secondary end points were progression-free survival (PFS) and overall survival (OS), neurologic symptoms, and tolerability. Between February 2008 and November 2010, 100 patients were enrolled in the study (50 in the WBRT + TMZ arm, 50 in the WBRT arm). Median age was 55 years (29-79). Median follow-up was 9.4 months [1.0-68.1]. ORRs at 6 weeks were 36% in the WBRT arm and 30% in the WBRT + TMZ arm (NS). In the WBRT arm, median PFS was 7.4 months and median OS was 11.1 months. In the WBRT + TMZ arm, median PFS was 6.9 months and median OS was 9.4 months. Treatment was well tolerated in this arm: the most common ≥grade 2 acute toxicity was reversible lymphopenia. WBRT combined with TMZ did not significantly improve local control and survival in patients with BMs from breast cancer. CLINICALTRIALS.GOV: NCT00875355. © The Author 2014. 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.

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial

PubMed Central

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan

2015-01-01

Purpose Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. Methods This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m2 intravenously on day 1 plus oral capecitabine 825 mg/m2 twice daily during LDRBT and EBRT. Results The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. Conclusion A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer. PMID:26361613

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial.

PubMed

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan; Mohammadianpanah, Mohammad

2015-08-01

Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m(2) intravenously on day 1 plus oral capecitabine 825 mg/m(2) twice daily during LDRBT and EBRT. The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer.

Determining Best Estimates and Uncertainties in Cloud Microphysical Parameters from ARM Field Data: Implications for Models, Retrieval Schemes and Aerosol-Cloud-Radiation Interactions

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

McFarquhar, Greg

We proposed to analyze in-situ cloud data collected during ARM/ASR field campaigns to create databases of cloud microphysical properties and their uncertainties as needed for the development of improved cloud parameterizations for models and remote sensing retrievals, and for evaluation of model simulations and retrievals. In particular, we proposed to analyze data collected over the Southern Great Plains (SGP) during the Mid-latitude Continental Convective Clouds Experiment (MC3E), the Storm Peak Laboratory Cloud Property Validation Experiment (STORMVEX), the Small Particles in Cirrus (SPARTICUS) Experiment and the Routine AAF Clouds with Low Optical Water Depths (CLOWD) Optical Radiative Observations (RACORO) field campaign,more » over the North Slope of Alaska during the Indirect and Semi-Direct Aerosol Campaign (ISDAC) and the Mixed-Phase Arctic Cloud Experiment (M-PACE), and over the Tropical Western Pacific (TWP) during The Tropical Warm Pool International Cloud Experiment (TWP-ICE), to meet the following 3 objectives; derive statistical databases of single ice particle properties (aspect ratio AR, dominant habit, mass, projected area) and distributions of ice crystals (size distributions SDs, mass-dimension m-D, area-dimension A-D relations, mass-weighted fall speeds, single-scattering properties, total concentrations N, ice mass contents IWC), complete with uncertainty estimates; assess processes by which aerosols modulate cloud properties in arctic stratus and mid-latitude cumuli, and quantify aerosol’s influence in context of varying meteorological and surface conditions; and determine how ice cloud microphysical, single-scattering and fall-out properties and contributions of small ice crystals to such properties vary according to location, environment, surface, meteorological and aerosol conditions, and develop parameterizations of such effects.In this report we describe the accomplishments that we made on all 3 research objectives.« less

A robot arm simulation with a shared memory multiprocessor machine

NASA Technical Reports Server (NTRS)

Kim, Sung-Soo; Chuang, Li-Ping

1989-01-01

A parallel processing scheme for a single chain robot arm is presented for high speed computation on a shared memory multiprocessor. A recursive formulation that is derived from a virtual work form of the d'Alembert equations of motion is utilized for robot arm dynamics. A joint drive system that consists of a motor rotor and gears is included in the arm dynamics model, in order to take into account gyroscopic effects due to the spinning of the rotor. The fine grain parallelism of mechanical and control subsystem models is exploited, based on independent computation associated with bodies, joint drive systems, and controllers. Efficiency and effectiveness of the parallel scheme are demonstrated through simulations of a telerobotic manipulator arm. Two different mechanical subsystem models, i.e., with and without gyroscopic effects, are compared, to show the trade-off between efficiency and accuracy.

Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone: a proof of concept trial.

PubMed

Andersen, Claus Yding; Elbaek, Helle Olesen; Alsbjerg, Birgit; Laursen, Rita Jakubcionyte; Povlsen, Betina Boel; Thomsen, Lise; Humaidan, Peter

2015-10-01

Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care? Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can replace the traditional used luteal phase support with exogenous progesterone. A bolus of hCG for final maturation of follicles in connection with COS may induce the risk of OHSS and the luteal phase progesterone levels rise very abruptly in the early luteal phase. This is a proof-of-concept study conducted as a three arm RCT with a total of 93 patients. First patient enrolled in January 2012 and the study finished in January 2014. Normal responder women undergoing IVF/ICSI treatment in a university hospital. One arm served as control, where women followed a standard antagonist protocol. Two study arms were included both having 125 IU hCG daily for luteal phase support without exogenous progesterone after using a GnRHa trigger for ovulation induction. In both study arms exogenous FSH was stopped on stimulation day 6 and replaced by exogenous hCG that was initiated on either stimulation day 2 or day 6. Blood samples were obtained on the day of ovulation induction, on the day of oocyte pickup (OPU) and day OPU + 7. The mean serum levels of hCG did not exceeded the normal physiological range of LH activity in any samples. Mid-luteal progesterone levels were significantly higher in the two study groups receiving daily low-dose hCG for luteal phase support as compared with the control group (control group: 177 ± 27 nmol/l; study group 1: 334 ± 42 nmol/l; study group 2: 277 ± 27 nmol/l; (mean ± SEM). No differences in reproductive outcome were seen between groups. The number of patients included is limited and conclusions need to be verified in a larger RCT. Endogenous production of progesterone may become more attractive as the luteal phase support with levels of LH-like activity only in the physiological range and may, from the patients' point of view, replace inconvenient exogenous progesterone preparation. Further hCG may reduce the cost of stimulation and may collectively be used for stimulation of the follicular phase, ovulation induction and for luteal phase support. An unrestricted grant from ARTS Biologics made this study possible. None of the authors has any competing interests to declare. ClinicalTrial.gov number: NCT01504139. 28 December 2011. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Was it less painful for knights? Influence of appearance on pain perception.

PubMed

Weeth, A; Mühlberger, A; Shiban, Y

2017-11-01

Pain perception is a subjective experience shaped by different factors. In this study, we investigated the influence of a visually manipulated appearance of a virtual arm on pain perception. Specifically, we investigated how pain perception and vegetative skin responses were modified by inducing a virtual protection on the right arm by a virtual armour. Participants (n = 32) immersed in virtual reality embodied a virtual arm, which appeared in three different versions (uncovered, neutral or protected). During the virtual reality simulation, the participants received electrical stimulations of varying intensities. Skin conductance level (SCL) was analysed for the phase anticipation (from the moment the arm appeared until the electric stimulation) and perception of pain (after the electric stimulation). Pain ratings were acquired after the painful stimuli occurred. The sense of embodiment was positive for the unprotected and neutral condition and lower for the protected than for the neutral arm. Pain ratings were significantly decreased in the protected arm condition compared with both the unprotected arm and the neutral arm conditions. The SCL measurements showed no significant differences for the three arm types. According to the pain ratings, participants felt significantly less pain in the covered arm condition compared with the unprotected and the neutral arm condition. Subjective pain perception was decreased by a virtual protection of the arm in VR. The simplicity of the manipulation suggests possible practical uses in pain therapy by strengthening the patients' own capacities to influence their pain using simple cognitive manipulations via virtual reality. A virtual, covered arm causes differences in reported pain ratings. Physiological measurements do not confirm the findings. Visual information about body protection can have an impact on pain perception. © 2017 European Pain Federation - EFIC®.

COMAP: a new computational interpretation of human movement planning level based on coordinated minimum angle jerk policies and six universal movement elements.

PubMed

Emadi Andani, Mehran; Bahrami, Fariba

2012-10-01

Flash and Hogan (1985) suggested that the CNS employs a minimum jerk strategy when planning any given movement. Later, Nakano et al. (1999) showed that minimum angle jerk predicts the actual arm trajectory curvature better than the minimum jerk model. Friedman and Flash (2009) confirmed this claim. Besides the behavioral support that we will discuss, we will show that this model allows simplicity in planning any given movement. In particular, we prove mathematically that each movement that satisfies the minimum joint angle jerk condition is reproducible by a linear combination of six functions. These functions are calculated independent of the type of the movement and are normalized in the time domain. Hence, we call these six universal functions the Movement Elements (ME). We also show that the kinematic information at the beginning and end of the movement determines the coefficients of the linear combination. On the other hand, in analyzing recorded data from sit-to-stand (STS) transfer, arm-reaching movement (ARM) and gait, we observed that minimum joint angle jerk condition is satisfied only during different successive phases of these movements and not for the entire movement. Driven by these observations, we assumed that any given ballistic movement may be decomposed into several successive phases without overlap, such that for each phase the minimum joint angle jerk condition is satisfied. At the boundaries of each phase the angular acceleration of each joint should obtain its extremum (zero third derivative). As a consequence, joint angles at each phase will be linear combinations of the introduced MEs. Coefficients of the linear combination at each phase are the values of the joint kinematics at the boundaries of that phase. Finally, we conclude that these observations may constitute the basis of a computational interpretation, put differently, of the strategy used by the Central Nervous System (CNS) for motor planning. We call this possible interpretation "Coordinated Minimum Angle jerk Policy" or COMAP. Based on this policy, the function of the CNS in generating the desired pattern of any given task (like STS, ARM or gait) can be described computationally using three factors: (1) the kinematics of the motor system at given body states, i.e., at certain movement events/instances, (2) the time length of each phase, and (3) the proposed MEs. From a computational point of view, this model significantly simplifies the processes of movement planning as well as feature abstraction for saving characterizing information of any given movement in memory. Copyright © 2012 Elsevier B.V. All rights reserved.