Science.gov

Sample records for randomized multicentre phase

  1. Tretinoin Nanogel 0.025% Versus Conventional Gel 0.025% in Patients with Acne Vulgaris: A Randomized, Active Controlled, Multicentre, Parallel Group, Phase IV Clinical Trial

    PubMed Central

    Chandrashekhar, B S; Anitha, M.; Ruparelia, Mukesh; Vaidya, Pradyumna; Aamir, Riyaz; Shah, Sunil; Thilak, S; Aurangabadkar, Sanjeev; Pal, Sandeep; Saraswat, Abir

    2015-01-01

    Background: Conventional topical tretinoin formulation is often associated with local adverse events. Nanogel formulation of tretinoin has good physical stability and enables good penetration of tretinoin into the pilo-sebaceous glands. Aim: The present study was conducted to assess the efficacy and safety of a nanogel formulation of tretinoin as compared to its conventional gel formulation in the treatment of acne vulgaris of the face. Materials and Methods: This randomized, active controlled, multicentric, phase IV clinical trial evaluated the treatment of patients with acne vulgaris of the face by the two gel formulations locally applied once daily at night for 12 wk. Acne lesion counts (inflammatory, non-inflammatory & total) and severity grading were carried out on the monthly scheduled visits along with the tolerability assessments. Results: A total of 207 patients were randomized in the study. Reductions in the total (72.9% vs. 65.0%; p = 0.03) and inflammatory (78.1% vs. 66.9%; p = 0.02) acne lesions were reported to be significantly greater with the nanogel formulation as compared to the conventional gel formulation. Local adverse events were significantly less (p = 0.04) in the nanogel group (13.3%) as compared to the conventional gel group (24.7%). Dryness was the most common adverse event reported in both the treatment groups while peeling of skin, burning sensation and photosensitivity were reported in patients using the conventional gel only. Conclusion: In the treatment of acne vulgaris of the face, tretinoin nanogel formulation appears to be more effective and better tolerated than the conventional gel formulation. PMID:25738069

  2. Clindamycin 1% Nano-emulsion Gel Formulation for the Treatment of Acne Vulgaris: Results of a Randomized, Active Controlled, Multicentre, Phase IV Clinical Trial

    PubMed Central

    Bhavsar, Bhavik; Choksi, Bimal; Dogra, Alka; Haq, Rizwan; Mehta, Sudhanshu; Mukherjee, Santanu; Subramanian, V; Sheikh, Shafiq; Mittal, Ravindra

    2014-01-01

    Background: Acne vulgaris of the face is a common dermatological disease with a significant impact on the quality of life, psychosocial development as well as self-esteem of the patients. Nano emulsion gel formulations are said to have various advantages over the conventional formulations. Aim: The present study was conducted to assess the comparative efficacy and safety of a nano-emulsion gel formulation of clindamycin with its conventional formulation in the treatment of acne vulgaris of the face. Materials and Methods: This prospective, active controlled, multicentric, phase IV clinical trial evaluated the treatment of patients with acne vulgaris of the face by a nano emulsion gel formulation or conventional gel formulation of clindamycin (as phosphate) 1% locally applied twice daily for 12 weeks as per random allocation. Acne lesion counts (inflammatory, non-inflammatory and total) and severity grading were carried out on the monthly scheduled visits along with tolerability assessments. Results: A total of 200 patients (97 males) were included for Intention to Treat analysis in the trial with 100 patients in each group. Reductions in total (69.3 vs. 51.9%; p<0.001), inflammatory (73.4 vs. 60.6%; p<0.005) and non inflammatory (65.1 vs. 43.7%; p<0.001) acne lesions were reported to be significantly greater with the nano-emulsion gel formulation as compared to the conventional gel formulation. Significantly more reduction in the mean acne severity score was noticeable with the nano-emulsion gel formulation (-1.6 ± 0.9 vs. -1.0 ± 0.8; p<0.001) than the comparator. A trend towards better safety profile of the nano emulsion gel formulation was reported. Conclusion: In the treatment of acne vulgaris of the face, clindamycin nano emulsion gel formulation appears to be more effective than the conventional gel formulation and is also well tolerated. PMID:25302253

  3. Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase‐4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24‐week multicentre, randomized, double‐blind, placebo‐controlled phase III trial

    PubMed Central

    Hong, S.; Park, C.‐Y.; Han, K. A.; Chung, C. H.; Ku, B. J.; Jang, H. C.; Ahn, C. W.; Lee, M.‐K.; Moon, M. K.; Son, H. S.; Lee, C. B.; Cho, Y.‐W.

    2016-01-01

    We assessed the 24‐week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase‐4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were −0.94% [least‐squares (LS) mean −1.22, −0.65] and −1.21 mmol/l (−1.72, −0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo‐controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM. PMID:26749529

  4. Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24-week multicentre, randomized, double-blind, placebo-controlled phase III trial.

    PubMed

    Hong, S; Park, C-Y; Han, K A; Chung, C H; Ku, B J; Jang, H C; Ahn, C W; Lee, M-K; Moon, M K; Son, H S; Lee, C B; Cho, Y-W; Park, S-W

    2016-05-01

    We assessed the 24-week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were -0.94% [least-squares (LS) mean -1.22, -0.65] and -1.21 mmol/l (-1.72, -0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo-controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM.

  5. Efficacy and safety of sucroferric oxyhydroxide compared with sevelamer hydrochloride in Japanese haemodialysis patients with hyperphosphataemia: A randomized, open‐label, multicentre, 12‐week phase III study

    PubMed Central

    Yokoyama, Keitaro; Fukagawa, Masafumi; Terao, Akira; Akizawa, Tadao

    2017-01-01

    Abstract Aim We aimed to investigate the non‐inferiority of PA21 (sucroferric oxyhydroxide) to sevelamer hydrochloride (sevelamer) in terms of efficacy and safety in Japanese haemodialysis patients with hyperphosphataemia. Methods In this Phase III, open‐label, multicentre study, 213 haemodialysis patients with hyperphosphataemia were randomized to PA21 or sevelamer treatment for 12 weeks. The primary outcome was adjusted serum phosphorus concentration at the end of treatment; the non‐inferiority of PA21 was confirmed if the upper limit of the two‐sided 95% confidence interval (CI) is ≤0.32 mmol/L. Secondary outcomes were corrected serum calcium and intact‐parathyroid hormone concentrations. Adverse events (AEs) and adverse drug reactions (ADRs) were evaluated. Results The adjusted mean serum phosphorus concentration at the end of treatment confirmed the non‐inferiority of PA21 for lowering serum phosphorus compared with sevelamer (1.62 vs 1.72 mmol/L; difference, −0.11 mmol/L; 95% CI, −0.20 to −0.02 mmol/L). The mean daily tablet intake was 5.6 ± 2.6 and 18.7 ± 7.1 tablets in the PA21 and sevelamer groups, respectively. The incidences of AEs and ADRs were not significantly different between the two groups. Conclusion The non‐inferiority of PA21 to sevelamer was confirmed for the treatment of Japanese haemodialysis patients with hyperphosphataemia. PA21 was effective, safe, and well tolerated, while having a considerably lower pill burden than sevelamer. PMID:27496336

  6. Fluvoxamine CR in the long-term treatment of social anxiety disorder: the 12- to 24-week extension phase of a multicentre, randomized, placebo-controlled trial.

    PubMed

    Stein, Dan J; Westenberg, Herman G M; Yang, Haichen; Li, David; Barbato, Luigi M

    2003-12-01

    Fluvoxamine CR has been reported effective in the short-term (12-wk) treatment of generalized social anxiety disorder (social phobia). Social anxiety disorder (SAD) is, however, a chronic disorder thought to require maintenance treatment. We report on data from the extension phase of a short-term study, in order to explore the efficacy and safety profile of fluvoxamine CR (100-300 mg/d) in the longer-term treatment of this disorder. Adult outpatients with generalized social anxiety disorder (GSAD) at 35 centres in Europe, South Africa, and USA were included in an acute phase study (12 wk). Subjects who demonstrated at least minimal improvement by endpoint (n=112), were offered participation in an extension phase, in which medication was continued for a further 12 wk under double-blind conditions. Efficacy was assessed using the Liebowitz Social Anxiety Disorder Scale (LSAS), the Clinical Global Impression Global Improvement score (CGI-I), the Clinical Global Impressions Severity of Illness score (CGI-S), and the Sheehan Disability Scale (SDS). Safety and tolerability assessments were also performed at regular intervals. Subjects treated with fluvoxamine CR had a numerically greater decrease in LSAS total scores than subjects treated with placebo at endpoint. Analysis of data from baseline (day 1) to endpoint (last observation carried forward) demonstrated that this difference tended towards significance, while severity of illness on the CGI-S and disability on the SDS were significantly lower in the fluvoxamine CR group than in the placebo group. The same trends were observed when only data from weeks 12-24 were included in the analysis; although the magnitude of changes was smaller in the extension phase than in the acute phase, fluvoxamine CR-treated subjects continued to show improvement compared to placebo-treated subjects. Most treatment-emergent signs and symptoms (TESS) were mild to moderate in severity. No unexpected abnormalities were reported on vital

  7. Evaluation of safety and immunogenicity of HNVAC, an MDCK-based H1N1 pandemic influenza vaccine, in Phase I single centre and Phase II/III multi-centre, double-blind, randomized, placebo-controlled, parallel assignment studies.

    PubMed

    Basavaraj, V H; Sampath, G; Hegde, Nagendra R; Mohan, V Krishna; Ella, Krishna M

    2014-07-31

    The clinical evaluation of the MDCK-based H1N1 pandemic influenza vaccine HNVAC in adults aged 18-65 years is reported. In the Phase I randomized, double-blind, placebo-controlled, single-centre study, 160 subjects were parallelly assigned 3:1 to vaccine:placebo groups (n=60:20) with both the aluminium hydroxide adjuvanted and non-adjuvanted vaccine formulations. A single dose of both the formulations containing 15 μg of haemagglutinin protein showed minimal adverse reactions, the most common of which were pain at injection site (11.67%) and fever (10.00%). Both formulations produced 74-81% seroprotection (SRP: titre of ≥40), 67-70% seroconversion (SRC: four-fold increase in titres between days 0 and 21), and a four-fold increase in geometric mean titres (GMT). Aluminium hydroxide did not have a significant effect either on immunogenicity or on reactogenicity. Nevertheless, based on its recognized positive effects on the stability and immunogenicity of many vaccines, and its marginal benefit in both pre-clinical and Phase I studies of HNVAC, alum adjuvanted HNVAC was further tested in a staggered Phase II/III randomized, double-blind, placebo-controlled, multi-centre study of 200 and 195 subjects, respectively, parallelly assigned 4:1 to adjuvanted vaccine and placebo groups. In these studies, the most common adverse reactions were pain at injection site (6.88% and 5.77% in Stage 1 and Stage 2, respectively) and fever (7.50% and 7.05%, respectively), and a single dose resulted in 87-90% SRP, 85-86% SRC, and a nearly six-fold increase in GMT, meeting or exceeding licensing criteria. It is concluded that HNVAC is safe and immunogenic to adults of 18-65 years.

  8. Relative efficiency of unequal cluster sizes for variance component estimation in cluster randomized and multicentre trials.

    PubMed

    van Breukelen, Gerard Jp; Candel, Math Jjm; Berger, Martijn Pf

    2008-08-01

    Cluster randomized and multicentre trials evaluate the effect of a treatment on persons nested within clusters, for instance patients within clinics or pupils within schools. Although equal sample sizes per cluster are generally optimal for parameter estimation, they are rarely feasible. This paper addresses the relative efficiency (RE) of unequal versus equal cluster sizes for estimating variance components in cluster randomized trials and in multicentre trials with person randomization within centres, assuming a quantitative outcome. Starting from maximum likelihood estimation, the RE is investigated numerically for a range of cluster size distributions. An approximate formula is presented for computing the RE as a function of the mean and variance of cluster sizes and the intraclass correlation. The accuracy of this approximation is checked and found to be good. It is concluded that the loss of efficiency for variance component estimation due to variation of cluster sizes rarely exceeds 20% and can be compensated by sampling 25% more clusters.

  9. Tetrodotoxin alleviates acute heroin withdrawal syndrome: a multicentre, randomized, double-blind, placebo-controlled study.

    PubMed

    Song, Hui; Li, Jing; Lu, Chang-Li; Kang, Lin; Xie, Liang; Zhang, Yang-Yang; Zhou, Xiao-Bo; Zhong, Sheng

    2011-08-01

    1. Tetrodotoxin (TTX) is a powerful sodium channel blocker extracted from the puffer fish. The efficacy and safety of TTX as monotherapy for the treatment of acute heroin withdrawal syndrome were evaluated in the present study. This 7-day, multicentre, randomized, double-blind, placebo-controlled study was carried out between December 2008 and October 2009. In total, 216 patients who met the Diagnostic and Statistical Manual of Mental Disorders IV diagnosis of heroin addiction were recruited. After providing written informed consent, subjects were randomly assigned to double-blind treatment in one of the following groups: 5 μg TTX group (group 1), 10 μg TTX group (group 2) or the placebo group (group 3). 2. Evidence suggests that both 5 and 10 μg TTX significantly reduced withdrawal symptoms by day 3 compared with placebo, and there was no significant difference in the incidence of adverse events in the three groups. 3. In conclusion, this clinical trial shows that TTX (5 and 10 μg given t.i.d.) is effective in alleviating opiate withdrawal symptoms with few side-effects.

  10. Randomized multicentric Italian study on two treatment regimens for marrow relapse in childhood acute lymphoblastic leukemia.

    PubMed

    Rossi, M R; Masera, G; Zurlo, M G; Amadori, S; Mandelli, F; Bagnulo, S; Carli, M; Zanesco, L; Dini, G; Guazzelli, C

    1986-01-01

    This paper reports the results of a multicentric randomized clinical trial on the treatment of first hematological relapse in childhood ALL. Induction treatment consisted of vincristine, adriamycin, L-asparaginase, and prednisone. Patients achieving complete remission were randomized to two maintenance regimens (A and B). Regimen A consisted of five different drug associations including VM26 and IDMTX in a sequential schedule; Regimen B was essentially classical Spiers schedule for the first year, followed by a milder treatment. Eighty-four of 102 evaluable patients (82%) achieved second complete remission. The two maintenance regimens were similar as regards duration of second complete remission (median duration A, 32 weeks; B, 37 weeks) and toxicity. Better results were obtained in patients relapsing after 12 months from suspension of treatment in first complete remission than in those relapsing within the first year off therapy (82.8% vs. 31.4%). In group A fewer CNS relapses were reported. The two regimens produced results similar to those reported by other authors. The good prognosis in patients relapsing at least 1 year after treatment suspension in first complete remission must be emphasized.

  11. Lobeglitazone and pioglitazone as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, parallel-group, active-controlled, phase III clinical trial with a 28-week extension.

    PubMed

    Jin, S-M; Park, C-Y; Cho, Y M; Ku, B J; Ahn, C W; Cha, B-S; Min, K W; Sung, Y A; Baik, S H; Lee, K W; Yoon, K-H; Lee, M-K; Park, S W

    2015-06-01

    We aimed to compare the efficacy and safety of lobeglitazone and pioglitazone as add-ons to metformin in patients with type 2 diabetes. Patients who were inadequately controlled by metformin were randomized and treated once daily with either lobeglitazone (0.5 mg, n = 128) or pioglitazone (15 mg, n = 125) for 24 weeks, with a 28-week extension trial of lobeglitazone treatment in patients who consented. The primary endpoint was the change in glycated haemoglobin (HbA1c) concentration from baseline to week 24. At week 24, the mean change from baseline in HbA1c was -0.74% for the lobeglitazone group and -0.74% for the pioglitazone group, with a mean difference of 0.01% [95% confidence interval (CI) of difference, -0.16 to 0.18]. The effects of lobeglitazone on lipid variables and the adverse events associated with lobeglitazone were similar to those observed with pioglitazone. Lobeglitazone was not inferior to pioglitazone as an add-on to metformin in terms of their efficacy and safety.

  12. Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial): A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial

    PubMed Central

    Heidrich, Benjamin; Cordes, Hans-Jörg; Klinker, Hartwig; Möller, Bernd; Naumann, Uwe; Rössle, Martin; Kraus, Michael R.; Böker, Klaus H.; Roggel, Christoph; Schuchmann, Marcus; Stoehr, Albrecht; Trein, Andreas; Hardtke, Svenja; Gonnermann, Andrea; Koch, Armin; Wedemeyer, Heiner; Manns, Michael P.; Cornberg, Markus

    2015-01-01

    Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoing response after 24 weeks P-2b/R qualified for OPTEX, a randomized trial investigating treatment extension of additional 24 weeks (total 48 weeks, Group A) or additional 12 weeks (total 36 weeks, group B) of 1.5 μg/kg P-2b and 800-1400 mg R. Due to the low number of patients without RVR, the number of 150 anticipated study patients was not met and only 99 non-RVR patients (n=50 Group A, n=49 Group B) could be enrolled into the OPTEX trial. Baseline factors did not differ between groups. Sixteen patients had G2 and 83 patients G3. Based on the ITT (intention-to-treat) analysis, 68% [55%; 81%] in Group A and 57% [43%; 71%] in Group B achieved SVR (p= 0.31). The primary endpoint of better SVR rates in Group A compared to a historical control group (SVR 70%) was not met. In conclusion, approximately 23% of G2/3 patients did not achieve RVR in a real world setting. However, subsequent recruitment in a treatment-extension study was difficult. Prolonged therapy beyond 24 weeks did not result in higher SVR compared to a historical control group. Trial Registration ClinicalTrials.gov NCT00803309 PMID:26057627

  13. Whole body vibration for older persons: an open randomized, multicentre, parallel, clinical trial

    PubMed Central

    2011-01-01

    Background Institutionalized older persons have a poor functional capacity. Including physical exercise in their routine activities decreases their frailty and improves their quality of life. Whole-body vibration (WBV) training is a type of exercise that seems beneficial in frail older persons to improve their functional mobility, but the evidence is inconclusive. This trial will compare the results of exercise with WBV and exercise without WBV in improving body balance, muscle performance and fall prevention in institutionalized older persons. Methods/Design An open, multicentre and parallel randomized clinical trial with blinded assessment. 160 nursing home residents aged over 65 years and of both sexes will be identified to participate in the study. Participants will be centrally randomised and allocated to interventions (vibration or exercise group) by telephone. The vibration group will perform static/dynamic exercises (balance and resistance training) on a vibratory platform (Frequency: 30-35 Hz; Amplitude: 2-4 mm) over a six-week training period (3 sessions/week). The exercise group will perform the same exercise protocol but without a vibration stimuli platform. The primary outcome measure is the static/dynamic body balance. Secondary outcomes are muscle strength and, number of new falls. Follow-up measurements will be collected at 6 weeks and at 6 months after randomization. Efficacy will be analysed on an intention-to-treat (ITT) basis and 'per protocol'. The effects of the intervention will be evaluated using the "t" test, Mann-Witney test, or Chi-square test, depending on the type of outcome. The final analysis will be performed 6 weeks and 6 months after randomization. Discussion This study will help to clarify whether WBV training improves body balance, gait mobility and muscle strength in frail older persons living in nursing homes. As far as we know, this will be the first study to evaluate the efficacy of WBV for the prevention of falls. Trial

  14. Efficacy and safety of foscarnet for recurrent orolabial herpes: a multicentre randomized double-blind study.

    PubMed Central

    Lawee, D; Rosenthal, D; Aoki, F Y; Portnoy, J

    1988-01-01

    Foscarnet sodium (trisodium phosphonoformate hexahydrate) has been shown to inhibit herpes simplex virus (HSV) in vitro and to be efficacious for topical treatment of experimental HSV infection in animals. To assess its clinical efficacy in the treatment of recurrent orolabial herpes a multicentre collaborative, double-blind, placebo-controlled trial was conducted. The study patients were randomly assigned to receive either 3% foscarnet cream (78 patients) or placebo (cream vehicle) (75 patients) and were asked to start treatment at the earliest indication of a recurrence. Efficacy was evaluated in 143 patients (74 in the foscarnet group and 69 in the placebo group). There was no significant difference in time to healing or duration of virus shedding between the two groups. However, in the subgroup of patients who started treatment before vesicles appeared, the duration of virus shedding was shorter in the foscarnet group than in the placebo group (p = 0.04), and the proportion of lesions that evolved to the vesicular stage was smaller (p = 0.03). No significant difference in the incidence of local or systemic adverse effects was noted between the two groups. We conclude that the beneficial effect of foscarnet was limited to a subgroup of patients who started treatment in the prevesicular stage. PMID:2962712

  15. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN) - a randomized multicentre trial

    PubMed Central

    2012-01-01

    Background Cachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia. Findings We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g) or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2,5 (SEM) kg. During treatment body-mass-index increased by 3,4 ± 1,4% under L-Carnitine and decreased (−1,5 ± 1,4%) in controls (p < 0,05). Moreover, nutritional status (body cell mass, body fat) and quality-of-life parameters improved under L-Carnitine. There was a trend towards an increased overall survival in the L-Carnitine group (median 519 ± 50 d versus 399 ± 43 d, not significant) and towards a reduced hospital-stay (36 ± 4d versus 41 ± 9d,n.s.). Conclusion While these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinically relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine. PMID:22824168

  16. Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomized clinical trial.

    PubMed

    de Vos, Cecile C; Meier, Kaare; Zaalberg, Paul Brocades; Nijhuis, Harold J A; Duyvendak, Wim; Vesper, Jan; Enggaard, Thomas P; Lenders, Mathieu W P M

    2014-11-01

    Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet effectiveness of SCS treatment for PDN is not well established. To our knowledge, ours is the first multicentre randomized controlled trial investigating the effectiveness of SCS in patients with PDN. Sixty patients with PDN in the lower extremities refractory to conventional medical therapy were enrolled and followed for 6 months. They were randomized 2:1 to best conventional medical practice with (SCS group) or without (control group) additional SCS therapy, and both groups were assessed at regular intervals. At each follow-up visit, the EuroQoL 5D, the short form McGill Pain Questionnaire (SF-MPQ) and a visual analogue scale (VAS, ranging 0-100) to measure pain intensity were recorded. The average VAS score for pain intensity was 73 in the SCS group and 67 in the control group at baseline. After 6 months of treatment, the average VAS score was significantly reduced to 31 in the SCS group (P<.001) and remained 67 (P=.97) in the control group. The SF-MPQ and EuroQoL 5D questionnaires also showed that patients in the SCS group, unlike those in the control group, experienced reduced pain and improved health and quality of life after 6 months of treatment. In patients with refractory painful diabetic neuropathy, spinal cord stimulation therapy significantly reduced pain and improved quality of life.

  17. An integrated approach to consumer representation and involvement in a multicentre randomized controlled trial.

    PubMed

    Langston, Anne L; McCallum, Marilyn; Campbell, Marion K; Robertson, Clare; Ralston, Stuart H

    2005-01-01

    Although, consumer involvement in individual studies is often limited, their involvement in guiding health research is generally considered to be beneficial. This paper outlines our experiences of an integrated relationship between the organisers of a clinical trial and a consumer organisation. The PRISM trial is a UK multicentre, randomized controlled trial comparing treatment strategies for Paget's disease of the bone. The National Association for the Relief of Paget's Disease (NARPD) is the only UK support group for sufferers of Paget's disease and has worked closely with the PRISM team from the outset. NARPD involvement is integral to the conduct of the trial and specific roles have included: peer-review; trial steering committee membership; provision of advice to participants, and promotion of the trial amongst Paget's disease patients. The integrated relationship has yielded benefits to both the trial and the consumer organisation. The benefits for the trial have included: recruitment of participants via NARPD contacts; well-informed participants; unsolicited patient advocacy of the trial; and interested and pro-active collaborators. For the NARPD and Paget's disease sufferers, benefits have included: increased awareness of Paget's disease; increased access to relevant health research; increased awareness of the NARPD services; and wider transfer of diagnosis and management knowledge to/from health care professionals. Our experience has shown that an integrated approach between a trial team and a consumer organisation is worthwhile. Adoption of such an approach in other trials may yield significant improvements in recruitment and quality of participant information flow. There are, however, resource implications for both parties.

  18. Remifentanil patient controlled analgesia versus epidural analgesia in labour. A multicentre randomized controlled trial

    PubMed Central

    2012-01-01

    Background Pain relief during labour is a topic of major interest in the Netherlands. Epidural analgesia is considered to be the most effective method of pain relief and recommended as first choice. However its uptake by pregnant women is limited compared to other western countries, partly as a result of non-availability due to logistic problems. Remifentanil, a synthetic opioid, is very suitable for patient controlled analgesia. Recent studies show that epidural analgesia is superior to remifentanil patient controlled analgesia in terms of pain intensity score; however there was no difference in satisfaction with pain relief between both treatments. Methods/design The proposed study is a multicentre randomized controlled study that assesses the cost-effectiveness of remifentanil patient controlled analgesia compared to epidural analgesia. We hypothesize that remifentanil patient controlled analgesia is as effective in improving pain appreciation scores as epidural analgesia, with lower costs and easier achievement of 24 hours availability of pain relief for women in labour and efficient pain relief for those with a contraindication for epidural analgesia. Eligible women will be informed about the study and randomized before active labour has started. Women will be randomly allocated to a strategy based on epidural analgesia or on remifentanil patient controlled analgesia when they request pain relief during labour. Primary outcome is the pain appreciation score, i.e. satisfaction with pain relief. Secondary outcome parameters are costs, patient satisfaction, pain scores (pain-intensity), mode of delivery and maternal and neonatal side effects. The economic analysis will be performed from a short-term healthcare perspective. For both strategies the cost of perinatal care for mother and child, starting at the onset of labour and ending ten days after delivery, will be registered and compared. Discussion This study, considering cost effectiveness of remifentanil as

  19. A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

    PubMed Central

    Nowak, A K; Byrne, M J; Williamson, R; Ryan, G; Segal, A; Fielding, D; Mitchell, P; Musk, A W; Robinson, B W S

    2002-01-01

    Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2–69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m−2 i.v. day 1 and gemcitabine 1000 mg m−2 i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20–46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life. British Journal of Cancer (2002) 87, 491–496. doi:10.1038/sj.bjc.6600505 www.bjcancer.com © 2002 Cancer Research UK PMID:12189542

  20. Efficacy and safety of pioglitazone added to alogliptin in Japanese patients with type 2 diabetes mellitus: a multicentre, randomized, double-blind, parallel-group, comparative study.

    PubMed

    Kaku, K; Katou, M; Igeta, M; Ohira, T; Sano, H

    2015-12-01

    A phase IV, multicentre, randomized, double-blind, parallel-group, comparative study was conducted in Japanese subjects with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control, despite treatment with alogliptin in addition to diet and/or exercise therapy. Subjects with glycated haemoglobin (HbA1c) concentrations of 6.9-10.5% were randomized to receive 16 weeks' double-blind treatment with pioglitazone 15 mg, 30 mg once daily or placebo added to alogliptin 25 mg once daily. The primary endpoint was the change in HbA1c from baseline at the end of treatment period (week 16). Both pioglitazone 15 and 30 mg combination therapy resulted in a significantly greater reduction in HbA1c than alogliptin monotherapy [-0.80 and -0.90% vs 0.00% (the least squares mean using analysis of covariance model); p < 0.0001, respectively]. The overall incidence rates of treatment-emergent adverse events were similar among the treatment groups. Pioglitazone/alogliptin combination therapy was effective and generally well tolerated in Japanese subjects with T2DM and is considered to be useful in clinical settings.

  1. The effect of bright light therapy on sleep and circadian rhythms in renal transplant recipients: a pilot randomized, multicentre wait-list controlled trial.

    PubMed

    Burkhalter, Hanna; Wirz-Justice, Anna; Denhaerynck, Kris; Fehr, Thomas; Steiger, Jürg; Venzin, Reto Martin; Cajochen, Christian; Weaver, Terri Elisabeth; De Geest, Sabina

    2015-01-01

    This study assessed the effect and feasibility of morning bright light therapy (BLT) on sleep, circadian rhythms, subjective feelings, depressive symptomatology and cognition in renal transplant recipients (RTx) diagnosed with sleep-wake disturbances (SWD). This pilot randomized multicentre wait-list controlled trial included 30 home-dwelling RTx randomly assigned 1:1 to either 3 weeks of BLT or a wait-list control group. Morning BLT (10 000 lux) was individually scheduled for 30 min daily for 3 weeks. Wrist actimetry (measuring sleep and circadian rhythms), validated instruments (subjective feelings and cognition) and melatonin assay (circadian timing) were used. Data were analysed via a random-intercept regression model. Of 30 RTx recipients (aged 58 ± 15, transplanted 15 ± 6 years ago), 26 completed the study. While BLT had no significant effect on circadian and sleep measures, sleep timing improved significantly. The intervention group showed a significant get-up time phase advance from baseline to intervention (+24 min) [(standardized estimates (SE): -0.23 (-0.42; -0.03)] and a small (+14 min) but significant bedtime phase advance from intervention to follow-up (SE: -0.25 (-0.41; -0.09). Improvement in subjective feelings and depressive symptomatology was observed but was not statistically significant. Bright light therapy showed preliminary indications of a beneficial effect in RTx with sleep-wake disturbances. (ClinicalTrials.gov number: NCT01256983).

  2. Randomized Grain Boundary Liquid Crystal Phase

    NASA Astrophysics Data System (ADS)

    Chen, D.; Wang, H.; Li, M.; Glaser, M.; Maclennan, J.; Clark, N.

    2012-02-01

    The formation of macroscopic, chiral domains, in the B4 and dark conglomerate phases, for example, is a feature of bent-core liquid crystals resulting from the interplay of chirality, molecular bend and molecular tilt. We report a new, chiral phase observed in a hockey stick-like liquid crystal molecule. This phase appears below a smectic A phase and cools to a crystal phase. TEM images of the free surface of the chiral phase show hundreds of randomly oriented smectic blocks several hundred nanometers in size, similar to those seen in the twist grain boundary (TGB) phase. However, in contrast to the TGB phase, these blocks are randomly oriented. The characteristic defects in this phase are revealed by freeze-fracture TEM images. We will show how these defects mediate the randomized orientation and discuss the intrinsic mechanism driving the formation of this phase. This work is supported by NSF MRSEC Grant DMR0820579 and NSF Grant DMR0606528.

  3. A prospective, randomized, multicentre trial for the treatment of refractory status epilepticus; experiences from evaluating the effect of the novel drug candidate, NS1209.

    PubMed

    Sabers, Anne; Wolf, Peter; Møller, Arne; Rysgaard, Karen; Ben-Menachem, Elinor

    2013-09-01

    Refractory status epilepticus (RSE) is a life-threatening condition that requires immediate and aggressive treatment. Unfortunately, sometimes standard antiepileptic treatment is insufficient. Furthermore, alternative therapeutic options are limited by low evidence of efficacy. The primary objective of this study was to evaluate the effects of the novel drug candidate, NS1209 versus third-line standard treatment (phenytoin/valproate) for RSE. Having not reached the study end-points, the purpose of this paper is to discuss the challenges that are encountered in conducting a controlled study of RSE. This was a phase II, prospective, multicentre, single-blinded, randomized clinical trial and included patients to two separate protocols for convulsive and non-convulsive RSE (NS1209-006 and NS1209-007). In total, 28 patients were included and 14 patients were exposed to NS1209. At study conclusion, the study was insufficiently powered to detect any statistically significant difference between the two treatment groups. This was especially true for the convulsive RSE protocol. We conclude that high-quality studies in RSE are difficult to conduct owing to a number of ethical and practical problems associated with this critical illness. Challenges for further studies are discussed.

  4. Emedastine difumarate versus loratadine in chronic idiopathic urticaria: a randomized, double-blind, controlled European multicentre clinical trial.

    PubMed

    Pons-Guiraud, Annik; Nekam, Kristof; Lahovsky, J; Costa, Angela; Piacentini, Andrea

    2006-01-01

    Emedastine difumarate (2 mg b.i.d.) was compared to loratadine (10 mg o.d.) in a randomized, double-blind, multicentre trial for 4 weeks in 192 patients with idiopathic chronic urticaria. After one week of treatment significant differences were recorded: body skin involvement diminished to 0-10% in 57.1% of emedastine patients vs. 38.2% of loratadine patients (p = 0.0019) and 83.3% had a total urticaria symptom score of 0-1 vs. 64.5% with loratadine (p = 0.0134). After 4 weeks of treatment the efficacy of the two drugs was similar in terms of mean change in total urticaria symptom score (- 5.57 +/- 3.15 with emedastine - 5.67 +/- 3.26 with loratadine), proportion of symptom-free patients (52.4% vs. 54.5%), intensity of erythema, number of hives, size of the largest hive, extent of skin area involved and overall assessment of urticaria symptoms.Twenty-three emedastine patients (23.9%) and 17 loratadine patients (17.7%) experienced an adverse event. Nineteen events in 15 emedastine patients and 9 in 9 loratadine patients were related to treatment (p = 0.0294). Only one event caused discontinuation in both treatment groups. The most common adverse event was sleepiness (7 patients with emedastine and 2 with loratadine). Emedastine is well tolerated, and as effective as loratadine in the short-term treatment of chronic idiopathic urticaria.

  5. Azithromycin for Indigenous children with bronchiectasis: study protocol for a multi-centre randomized controlled trial

    PubMed Central

    2012-01-01

    Background The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis. Methods/design We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12–24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV1; for children ≥6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4

  6. Phase transitions on random lattices: how random is topological disorder?

    PubMed

    Barghathi, Hatem; Vojta, Thomas

    2014-09-19

    We study the effects of topological (connectivity) disorder on phase transitions. We identify a broad class of random lattices whose disorder fluctuations decay much faster with increasing length scale than those of generic random systems, yielding a wandering exponent of ω=(d-1)/(2d) in d dimensions. The stability of clean critical points is thus governed by the criterion (d+1)ν>2 rather than the usual Harris criterion dν>2, making topological disorder less relevant than generic randomness. The Imry-Ma criterion is also modified, allowing first-order transitions to survive in all dimensions d>1. These results explain a host of puzzling violations of the original criteria for equilibrium and nonequilibrium phase transitions on random lattices. We discuss applications, and we illustrate our theory by computer simulations of random Voronoi and other lattices.

  7. Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre, double-blind randomized controlled trial

    PubMed Central

    de Jonghe, Annemarieke; van Munster, Barbara C.; Goslings, J. Carel; Kloen, Peter; van Rees, Carolien; Wolvius, Reinder; van Velde, Romuald; Levi, Marcel; de Haan, Rob J.; de Rooij, Sophia E.

    2014-01-01

    Background: Disturbance of the sleep–wake cycle is a characteristic of delirium. In addition, changes in melatonin rhythm influence the circadian rhythm and are associated with delirium. We compared the effect of melatonin and placebo on the incidence and duration of delirium. Methods: We performed this multicentre, double-blind, randomized controlled trial between November 2008 and May 2012 in 1 academic and 2 nonacademic hospitals. Patients aged 65 years or older who were scheduled for acute hip surgery were eligible for inclusion. Patients received melatonin 3 mg or placebo in the evening for 5 consecutive days, starting within 24 hours after admission. The primary outcome was incidence of delirium within 8 days of admission. We also monitored the duration of delirium. Results: A total of 452 patients were randomly assigned to the 2 study groups. We subsequently excluded 74 patients for whom the primary end point could not be measured or who had delirium before the second day of the study. After these postrandomization exclusions, data for 378 patients were included in the main analysis. The overall mean age was 84 years, 238 (63.0%) of the patients lived at home before admission, and 210 (55.6%) had cognitive impairment. We observed no effect of melatonin on the incidence of delirium: 55/186 (29.6%) in the melatonin group v. 49/192 (25.5%) in the placebo group; difference 4.1 (95% confidence interval −0.05 to 13.1) percentage points. There were no between-group differences in mortality or in cognitive or functional outcomes at 3-month follow-up. Interpretation: In this older population with hip fracture, treatment with melatonin did not reduce the incidence of delirium. Trial registration: Netherlands Trial Registry, NTR1576: MAPLE (Melatonin Against PLacebo in Elderly patients) study; www.trialregister.nl/trialreg/admin/rctview.asp?TC=1576 PMID:25183726

  8. A comparison of topical application of penciclovir 1% cream with acyclovir 3% cream for treatment of genital herpes: a randomized, double-blind, multicentre trial.

    PubMed

    Chen, X S; Han, G Z; Guo, Z P; Lu, N Z; Chen, J; Wang, J B

    2000-09-01

    Genital herpes simplex virus (HSV) infection, a sexually transmitted disease (STD), is the commonest cause of ulcerative genital infections among the young and adult population. The significant association of genital ulceration and transmission of human immunodeficiency virus (HIV) has been shown in many studies. To explore the potential efficacy of topical treatment of genital herpes with penciclovir cream, a randomized, double-blind, multicentre, acyclovir-controlled Phase II clinical trial of penciclovir 1% cream 5 times daily up to 7 days for suppression of genital herpes was conducted in China. A total of 205 patients aged 20-59 years (mean age 36.0+/-8.8 years for acyclovir and 34.8+/-8.4 years for penciclovir) with a clinical diagnosis of genital herpes were randomly allocated to one of the 2 parallel treatment groups and used for analysis. Clinical assessment were made before treatment and followed up at every visit during the study. Our results show that there was an encouraging improvement simultaneously in the 2 groups although no significant differences in clinical efficacy with respect to clinical cure rate, and times to healing, resolution of all symptoms, absence of blisters, cessation of new blisters, crusting, and loss of crust between penciclovir and acyclovir groups in terms of primary, non-primary and total patients were found. However a significantly shorter time to crusting was found in primary penciclovir group when compared with primary acyclovir group. Adverse experience was generally infrequent and mild, and was comparable in the 2 treatment groups. Based on these preliminary clinical findings, further evaluation of penciclovir 3% cream for topical treatment of genital herpes is planned.

  9. Video-based feedback of oral clinical presentations reduces the anxiety of ICU medical students: a multicentre, prospective, randomized study

    PubMed Central

    2014-01-01

    Background Oral presentations of clinical cases by medical students during medical rounds in hospital wards are a source of anxiety and little is known about how this anxiety can be alleviated. The objective of this study was to investigate whether video-based feedback of public oral presentations can reduce anxiety in 4th year medical students. Methods Multicentre randomized study conducted in six intensive care units (ICU) and emergency departments (ED) in France over a 9-month period in 2012. One hundred and forty two 4th year medical students were randomized to two groups: intervention and control. Students in the intervention group were recorded while making an oral presentation of a patient during morning ward rounds, followed by video-based feedback. Students in the control group conducted presented classical oral presentations without being filmed and with no formal feedback. Anxiety levels during a public oral presentation were assessed using the Spielberger State Anxiety Inventory (STAI-S). The primary outcome was the difference in STAI-S scores between groups at the beginning and at the end of a 3-month ICU or ED internship. Results Seventy four students were randomized to the ‘video-based feedback’ group and 68 were randomized to the control group. In both groups, STAI-S scores were significantly lower after 3 months of internship. However, the reduction in STAI-S scores was significantly greater in the “video-based feedback” group than in controls (-9.2 ± 9.3 vs. –4.6 ± 8.2, p = 0.024. Compared to the control group, significantly fewer students with high-level anxiety were observed in the “video-based feedback” group after 3 months of internship (68 vs. 28%, p <0.001). Conclusions Compared to “usual practice”, video-assisted oral feedback reduced anxiety and significantly decreased the proportion of students experiencing severe anxiety. PMID:24885005

  10. Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial

    PubMed Central

    Shaw, E; Miró, J M; Puig-Asensio, M; Pigrau, C; Barcenilla, F; Murillas, J; Garcia-Pardo, G; Espejo, E; Padilla, B; Garcia-Reyne, A; Pasquau, J; Rodriguez-Baño, J; López-Contreras, J; Montero, M; de la Calle, C; Pintado, V; Calbo, E; Gasch, O; Montejo, M; Salavert, M; Garcia-Pais, M J; Carratalà, J; Pujol, M

    2015-01-01

    Introduction Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. Methods and analysis A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. Ethics and dissemination The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals

  11. Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial

    PubMed Central

    2015-01-01

    Summary Background A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. Methods Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with the randomisation number. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score between the baseline and 44 weeks, analysed by intention to treat. The primary null hypothesis for each dose group was that the mean change in UPDRS was 3 points less than the mean change in the placebo group. The alternative hypothesis (of futility) was that pioglitazone is not meaningfully different from placebo. We rejected the null if there was significant evidence of futility at the one-sided alpha level of 0.10. The study is registered at ClinicalTrials.gov, number NCT01280123. Findings 210 patients from 35 sites in the USA were enrolled between May 10, 2011, and July 31, 2013. The primary analysis included 72 patients in the 15 mg group, 67 in the 45 mg group, and 71 in the placebo group. The mean total UPDRS change at 44 weeks was 4.42 (95% CI 2.55–6.28) for 15 mg pioglitazone, 5.13 (95% CI 3.17–7.08) for 45 mg pioglitazone, and 6.25 (95% CI 4.35–8.15) for placebo (higher change scores are worse). The mean difference between the 15 mg and placebo groups was −1.83 (80% CI −3.56 to −0.10) and the null hypothesis could not be rejected (p=0.19). The mean difference between the 45 mg and placebo

  12. Short-course eflornithine in Gambian trypanosomiasis: a multicentre randomized controlled trial.

    PubMed Central

    Pépin, J.; Khonde, N.; Maiso, F.; Doua, F.; Jaffar, S.; Ngampo, S.; Mpia, B.; Mbulamberi, D.; Kuzoe, F.

    2000-01-01

    OBJECTIVE: A randomized controlled trial was conducted to determine whether 7 days of intravenous eflornithine (100 mg/kg every 6 h) was as effective as the standard 14-day regimen in the treatment of late-stage Trypanosoma brucei gambiense trypanosomiasis. METHODS: A total of 321 patients (274 new cases, 47 relapsing cases) were randomized at four participating centres in Congo, Côte d'Ivoire, the Democratic Republic of the Congo, and Uganda to one of these treatment regimens and followed up for 2 years. RESULTS: Six patients died during treatment, one of whom was on the 7-day regimen, whereas the other five had been on the 14-day regimen (P = 0.2). The response to eflornithine differed markedly between Uganda and other countries. Among new cases in Uganda, the 2-year probability of cure was 73% on the 14-day course compared with 62% on the 7-day regimen (hazard ratio (HR) for treatment failure, 7-day versus 14-day regimen: 1.45, 95% CI: 0.7, 3.1, P = 0.3). Among new cases in Côte d'Ivoire, Congo, and the Democratic Republic of the Congo combined, the 2-year probability of cure was 97% on the 14-day course compared with 86.5% on the 7-day regimen (HR for treatment failure, 7-day vs 14-day: 6.72, 95% confidence interval (CI): 1.5, 31.0, P = 0.003). Among relapsing cases in all four countries, the 2-year probability of cure was 94% with 7 days and 100% with 14 days of treatment. Factors associated with a higher risk of treatment failure were: a positive lymph node aspirate (HR 4.1; 95% CI: 1.8-9.4), a cerebrospinal fluid (CSF) white cell count > or = 100/mm3 (HR 3.5; 95% CI: 1.1-10.9), being treated in Uganda (HR 2.9; 95% CI: 1.4-5.9), and CSF trypanosomes (HR 1.9; 95% CI: 0.9-4.1). Being stuporous on admission was associated with a lower risk of treatment failure (HR 0.18; 95% CI: 0.02-1.4) as was increasing age (HR 0.977; 95% CI: 0.95-1.0, for each additional year of age). DISCUSSION: The 7-day course of eflornithine is an effective treatment of relapsing cases

  13. Quantum walks with random phase shifts

    SciTech Connect

    Kosik, Jozef; Buzek, Vladimir; Hillery, Mark

    2006-08-15

    We investigate quantum walks in multiple dimensions with different quantum coins. We augment the model by assuming that at each step the amplitudes of the coin state are multiplied by random phases. This model enables us to study in detail the role of decoherence in quantum walks and to investigate the quantum-to-classical transition. We also provide classical analog of the quantum random walks studied. Interestingly enough, it turns out that the classical counterparts of some quantum random walks are classical random walks with a memory and biased coin. In addition random phase shifts 'simplify' the dynamics (the cross-interference terms of different paths vanish on average) and enable us to give a compact formula for the dispersion of such walks.

  14. Efficacy of Propolis on the Denture Stomatitis Treatment in Older Adults: A Multicentric Randomized Trial

    PubMed Central

    Pina, Gisela de M. S.; Lia, Erica N.; Berretta, Andresa A.; Nascimento, Andresa P.; Torres, Elina C.; Buszinski, Andrei F. M.; de Campos, Tatiana A.; Martins, Vicente de P.

    2017-01-01

    Our hypothesis tested the efficacy and safety of a mucoadhesive oral gel formulation of Brazilian propolis extract compared to miconazole oral gel for the treatment of denture stomatitis due to Candida spp. infection in older adults. Forty patients were randomly allocated in a noninferiority clinical trial into two groups. The control group (MIC) received 20 mg/g miconazole oral gel and the study group (PROP) received mucoadhesive formulation containing standardized extract of 2% (20 mg/g) propolis (EPP-AF®) during 14 days. Patients were examined on days 1, 7, and 14. The Newton's score was used to classify the severity of denture stomatitis. The colony forming unity count (CFU/mL) was quantified and identified (CHROMagar Candida®) before and after the treatment. Baseline characteristics did not differ between groups. Both treatments reduced Newton's score (P < 0.0001), indicating a clinical improvement of the symptoms of candidiasis with a clinical cure rate of 70%. The microbiological cure with significant reduction in fungal burden on T14 was 70% in the miconazole group and 25% in the EPP-AF group. The EPP-AF appears to be noninferior to miconazole considering the clinical cure rate and could be recommended as an alternative treatment in older patients.

  15. Comparison of tinzaparin and acenocoumarol for the secondary prevention of venous thromboembolism: a multicentre, randomized study.

    PubMed

    Pérez-de-Llano, Luis A; Leiro-Fernández, Virginia; Golpe, Rafael; Núñez-Delgado, Jose M; Palacios-Bartolomé, Ana; Méndez-Marote, Lidia; Colomé-Nafria, Esteve

    2010-12-01

    The objective of the present study was to evaluate the efficacy, safety and healthcare resource utilization of long-term treatment with tinzaparin in symptomatic patients with acute pulmonary embolism as compared to standard therapy. In this open-label trial, 102 patients with objectively confirmed pulmonary embolism were randomized to receive, after initial treatment with tinzaparin, either tinzaparin (175 IU/kg/day) or international normalized ratio-adjusted acenocoumarol for 6 months. Clinical endpoints were assessed during the 6 months of treatment. A pharmacoeconomic analysis was carried out to evaluate the cost of the long-term treatment with tinzaparin in comparison with the standard one. In an intention-to-treat analysis, one of 52 patients developed recurrent venous thromboembolism in the tinzaparin group compared with none of the 50 patients in the acenocoumarol group. One patient in each group had a major haemorrhagic complication. Six patients in the acenocoumarol group had minor bleeding compared with none in the tinzaparin group (P = 0.027). Median hospital length of stay was shorter in the tinzaparin group compared to the acenocoumarol group (7 versus 9 days; P = 0.014). When all the direct and indirect cost components were combined for the entire population, we found a slight, nonstatistically significant (mean difference €345; 95% CI 1382-2071; P = 0.69) reduction in total cost with tinzaparin. Symptomatic acute pulmonary embolism treatment with full therapeutic doses of tinzaparin for 6 months is a feasible alternative to conventional treatment with vitamin K antagonists.

  16. Random-phase metasurfaces at optical wavelengths

    PubMed Central

    Pors, Anders; Ding, Fei; Chen, Yiting; Radko, Ilya P.; Bozhevolnyi, Sergey I.

    2016-01-01

    Random-phase metasurfaces, in which the constituents scatter light with random phases, have the property that an incident plane wave will diffusely scatter, hereby leading to a complex far-field response that is most suitably described by statistical means. In this work, we present and exemplify the statistical description of the far-field response, particularly highlighting how the response for polarised and unpolarised light might be alike or different depending on the correlation of scattering phases for two orthogonal polarisations. By utilizing gap plasmon-based metasurfaces, consisting of an optically thick gold film overlaid by a subwavelength thin glass spacer and an array of gold nanobricks, we design and realize random-phase metasurfaces at a wavelength of 800 nm. Optical characterisation of the fabricated samples convincingly demonstrates the diffuse scattering of reflected light, with statistics obeying the theoretical predictions. We foresee the use of random-phase metasurfaces for camouflage applications and as high-quality reference structures in dark-field microscopy, while the control of the statistics for polarised and unpolarised light might find usage in security applications. Finally, by incorporating a certain correlation between scattering by neighbouring metasurface constituents new types of functionalities can be realised, such as a Lambertian reflector. PMID:27328635

  17. Random-phase metasurfaces at optical wavelengths

    NASA Astrophysics Data System (ADS)

    Pors, Anders; Ding, Fei; Chen, Yiting; Radko, Ilya P.; Bozhevolnyi, Sergey I.

    2016-06-01

    Random-phase metasurfaces, in which the constituents scatter light with random phases, have the property that an incident plane wave will diffusely scatter, hereby leading to a complex far-field response that is most suitably described by statistical means. In this work, we present and exemplify the statistical description of the far-field response, particularly highlighting how the response for polarised and unpolarised light might be alike or different depending on the correlation of scattering phases for two orthogonal polarisations. By utilizing gap plasmon-based metasurfaces, consisting of an optically thick gold film overlaid by a subwavelength thin glass spacer and an array of gold nanobricks, we design and realize random-phase metasurfaces at a wavelength of 800 nm. Optical characterisation of the fabricated samples convincingly demonstrates the diffuse scattering of reflected light, with statistics obeying the theoretical predictions. We foresee the use of random-phase metasurfaces for camouflage applications and as high-quality reference structures in dark-field microscopy, while the control of the statistics for polarised and unpolarised light might find usage in security applications. Finally, by incorporating a certain correlation between scattering by neighbouring metasurface constituents new types of functionalities can be realised, such as a Lambertian reflector.

  18. Random fields at a nonequilibrium phase transition.

    PubMed

    Barghathi, Hatem; Vojta, Thomas

    2012-10-26

    We study nonequilibrium phase transitions in the presence of disorder that locally breaks the symmetry between two equivalent macroscopic states. In low-dimensional equilibrium systems, such random-field disorder is known to have dramatic effects: it prevents spontaneous symmetry breaking and completely destroys the phase transition. In contrast, we show that the phase transition of the one-dimensional generalized contact process persists in the presence of random-field disorder. The ultraslow dynamics in the symmetry-broken phase is described by a Sinai walk of the domain walls between two different absorbing states. We discuss the generality and limitations of our theory, and we illustrate our results by large-scale Monte Carlo simulations.

  19. Fast phase randomization via two-folds.

    PubMed

    Simpson, D J W; Jeffrey, M R

    2016-02-01

    A two-fold is a singular point on the discontinuity surface of a piecewise-smooth vector field, at which the vector field is tangent to the discontinuity surface on both sides. If an orbit passes through an invisible two-fold (also known as a Teixeira singularity) before settling to regular periodic motion, then the phase of that motion cannot be determined from initial conditions, and, in the presence of small noise, the asymptotic phase of a large number of sample solutions is highly random. In this paper, we show how the probability distribution of the asymptotic phase depends on the global nonlinear dynamics. We also show how the phase of a smooth oscillator can be randomized by applying a simple discontinuous control law that generates an invisible two-fold. We propose that such a control law can be used to desynchronize a collection of oscillators, and that this manner of phase randomization is fast compared with existing methods (which use fixed points as phase singularities), because there is no slowing of the dynamics near a two-fold.

  20. Near zerO fluoroscopic exPosure during catheter ablAtion of supRavenTricular arrhYthmias: the NO-PARTY multicentre randomized trial

    PubMed Central

    Casella, Michela; Dello Russo, Antonio; Pelargonio, Gemma; Del Greco, Maurizio; Zingarini, Gianluca; Piacenti, Marcello; Di Cori, Andrea; Casula, Victor; Marini, Massimiliano; Pizzamiglio, Francesca; Zucchetti, Martina; Riva, Stefania; Russo, Eleonora; Narducci, Maria Lucia; Soldati, Ezio; Panchetti, Luca; Startari, Umberto; Bencardino, Gianluigi; Perna, Francesco; Santangeli, Pasquale; Di Biase, Luigi; Cichocki, Fabrizio; Fattore, Giovanni; Bongiorni, Mariagrazia; Picano, Eugenio; Natale, Andrea; Tondo, Claudio

    2016-01-01

    Aims Aim of this study was to compare a minimally fluoroscopic radiofrequency catheter ablation with conventional fluoroscopy-guided ablation for supraventricular tachycardias (SVTs) in terms of ionizing radiation exposure for patient and operator and to estimate patients' lifetime attributable risks associated with such exposure. Methods and results We performed a prospective, multicentre, randomized controlled trial in six electrophysiology (EP) laboratories in Italy. A total of 262 patients undergoing EP studies for SVT were randomized to perform a minimally fluoroscopic approach (MFA) procedure with the EnSiteTMNavXTM navigation system or a conventional approach (ConvA) procedure. The MFA was associated with a significant reduction in patients' radiation dose (0 mSv, iqr 0–0.08 vs. 8.87 mSv, iqr 3.67–22.01; P < 0.00001), total fluoroscopy time (0 s, iqr 0–12 vs. 859 s, iqr 545–1346; P < 0.00001), and operator radiation dose (1.55 vs. 25.33 µS per procedure; P < 0.001). In the MFA group, X-ray was not used at all in 72% (96/134) of cases. The acute success and complication rates were not different between the two groups (P = ns). The reduction in patients' exposure shows a 96% reduction in the estimated risks of cancer incidence and mortality and an important reduction in estimated years of life lost and years of life affected. Based on economic considerations, the benefits of MFA for patients and professionals are likely to justify its additional costs. Conclusion This is the first multicentre randomized trial showing that a MFA in the ablation of SVTs dramatically reduces patients' exposure, risks of cancer incidence and mortality, and years of life affected and lost, keeping safety and efficacy. Trial registration clinicaltrials.gov Identifier: NCT01132274. PMID:26559916

  1. Double random phase encoding using phase reservation and compression

    NASA Astrophysics Data System (ADS)

    Chen, Wen; Chen, Xudong

    2014-02-01

    In recent years, various studies have been conducted to illustrate the vulnerability of double random phase encoding (DRPE). In this paper, we propose a novel method via phase reservation and compression to enhance DRPE security. Only a compressed phase distribution is available in the CCD plane, and the amplitude component is not available or requested for optical decryption. Since only noise-like distributions can be obtained by using the correct security keys during optical decryption, a nonlinear correlation algorithm is further applied for authenticating the decrypted image. It is demonstrated that valid conditions for attack algorithms are broken and high security can be achieved for the DRPE system.

  2. Multicentre phase II trial of trastuzumab and capecitabine in patients with HER2 overexpressing metastatic pancreatic cancer

    PubMed Central

    Harder, J; Ihorst, G; Heinemann, V; Hofheinz, R; Moehler, M; Buechler, P; Kloeppel, G; Röcken, C; Bitzer, M; Boeck, S; Endlicher, E; Reinacher-Schick, A; Schmoor, C; Geissler, M

    2012-01-01

    Background: New therapeutic options for metastatic pancreatic cancer are urgently needed. In pancreatic cancer, overexpression of the epidermal growth factor receptor 2 (HER2) has been reported in up to 45%. This multicentre phase II study investigated the efficacy and toxicity of the HER2 antibody trastuzumab combined with capecitabine in the patients with pancreatic cancer and HER2 overexpression. Methods: Primary endpoint was progression-free survival (PFS) after 12 weeks. A total of 212 patients were screened for HER2 expression. Results: Immunohistochemical (IHC) HER2 expression was: 83 (40%) grade 0, 71 (34%) grade 1, 31 (15%) grade 2, 22 (11%) grade 3. A total of 17 patients with IHC +3 HER2 expression or gene amplification could be assessed for the treatment response. Grade 3/4 treatment toxicities were: each 7% leucopenia, diarrhoea, nausea and hand-foot syndrome. Progression-free survival after 12 weeks was 23.5%, median overall survival (OS) 6.9 months. Conclusion: This study demonstrates +3 HER2 expression or gene amplification in 11% of patients. Contrary to breast and gastric cancer, only 7 out of 11 (64%) patients with IHC +3 HER2 expression showed gene amplification. Although the therapy was well tolerated, PFS and OS did not perform favourably compared with standard chemotherapy. Together, we do not recommend further evaluation of anti-HER2 treatment in patients with metastatic pancreatic cancer. PMID:22374460

  3. Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study

    PubMed Central

    De Placido, S; Lopez, M; Carlomagno, C; Paoletti, G; Palazzo, S; Manzione, L; Iannace, C; Ianniello, G P; De Vita, F; Ficorella, C; Farris, A; Pistillucci, G; Gemini, M; Cortesi, E; Adamo, V; Gebbia, N; Palmeri, S; Gallo, C; Perrone, F; Persico, G; Bianco, A R

    2005-01-01

    The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2 × 2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival advantage. The hazard ratio (HR) of relapse was 0.89 (95% confidence intervals (CI): 0.73–1.09) for patients receiving FA and 0.99 (95% CI 0.80–1.21) for those receiving LEV; corresponding HRs of death were 1.02 (95% CI: 0.80–1.30) and 0.94 (95% CI 0.73–1.20). Nonhaematological toxicity (all grade vomiting, diarrhoea, mucositis, congiuntivitis, skin, fever and fatigue) was significantly worse with FA, while all other toxicities were similar. In the present trial, there was no evidence that the addition of FA or LEV significantly prolongs DFS and OAS of radically resected colorectal cancer patients. PMID:16222322

  4. Efficacy of a standardized herbal preparation (Roidosanal®) in the treatment of hemorrhoids: A randomized, controlled, open-label multicentre study

    PubMed Central

    Aggrawal, Kapil; Satija, Naveen; Dasgupta, Gita; Dasgupta, Partha; Nain, Parul; Sahu, Aditya R.

    2014-01-01

    Background: Catechins and epicatechins are monomers of naturally occurring proanthocyanidins, which have been reported with free radical scavenging, antioxidant, antiinflammatory, antiallergic, and vasodilatory properties. Plant parts rich in proanthocyanidins have been used for years in treatment of various ano-rectal diseases. This study compares the efficacy of two herbal preparations, Daflon® 500 mg and Roidosanal®, in ameliorating the signs and symptoms associated with hemorrhoids. Objective: To evaluate the safety and to compare the efficacy of a herbal preparation, Roidosanal® versus Daflon® 500 mg, on signs and symptoms of hemorrhoidal disease. Materials and Methods: In this pilot, active controlled, open-labeled multicentre study, 73 patients with proctoscopy proven hemorrhoids (Grade I to III) were randomly assigned to receive either Roidosanal® (Gr R; n = 37) or Daflon® 500 mg (Gr D; n = 36), for 15 days, at three centers in India. Assessment of hemorrhoidal symptoms was carried out in all patients at different time points. Intent-to-treat analysis was performed for both primary and secondary endpoints. Results: Baseline characteristics were comparable between the two groups. Both products were found to be equally effective in improving the ano-rectal conditions in Grade I and Grade II hemorrhoids; however, Roidosanal® demonstrated better efficacy in patients with Grade III hemorrhoids. Hemorrhoids associated symptoms like bleeding, pain, etc., improved in both groups, although intergroup comparisons were comparable. Conclusion: Both Roidosanal® and Daflon® 500 mg were equally effective in resolving signs and symptoms of hemorrhoids. Roidosanal® can be tried as a safe and effective treatment option for treatment of hemorrhoids. Further randomized, double-blind and large multicentre studies are recommended. PMID:24948863

  5. Relativistic Random Phase Approximation At Finite Temperature

    SciTech Connect

    Niu, Y. F.; Paar, N.; Vretenar, D.; Meng, J.

    2009-08-26

    The fully self-consistent finite temperature relativistic random phase approximation (FTRRPA) has been established in the single-nucleon basis of the temperature dependent Dirac-Hartree model (FTDH) based on effective Lagrangian with density dependent meson-nucleon couplings. Illustrative calculations in the FTRRPA framework show the evolution of multipole responses of {sup 132}Sn with temperature. With increased temperature, in both monopole and dipole strength distributions additional transitions appear in the low energy region due to the new opened particle-particle and hole-hole transition channels.

  6. Clinical efficacy and mechanistic evaluation of aflibercept for proliferative diabetic retinopathy (acronym CLARITY): a multicentre phase IIb randomised active-controlled clinical trial

    PubMed Central

    Sivaprasad, Sobha; Prevost, A Toby; Bainbridge, James; Edwards, Rhiannon Tudor; Hopkins, David; Kelly, Joanna; Luthert, Phil; Murphy, Caroline; Ramu, Jayashree; Sarafraz-Shekary, Negin; Vasconcelos, Joana; White-Alao, Beverley; Hykin, Philip

    2015-01-01

    Introduction Proliferative diabetic retinopathy (PDR) is the main cause of severe visual loss in people with diabetes mellitus. The standard treatment for this condition is panretinal photocoagulation (PRP). This laser treatment is inherently destructive, with predictable adverse effects on visual function, and a safer alternative is required. Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors can induce short-term regression of retinal neovascularisation. The aim of this randomised controlled trial is to determine the efficacy, safety and cost-effectiveness of intravitreal aflibercept, an inhibitor of VEGF-A, VEGF-B and placental growth factor (PLGF), in PDR, and to investigate the impact on local oxygenation. Methods and analysis This is a phase IIb randomised controlled single-masked multicentre clinical trial to determine the impact of repeated intravitreal aflibercept injections in the treatment and prevention of PDR. 220 participants with treatment-naïve or treated but active retinal neovascularisation in at least one eye will be randomly allocated 1:1 to intravitreal aflibercept injections or PRP for a period of 52 weeks. The primary outcome is the change in best-corrected visual acuity in the study eye at 52 weeks. Secondary outcomes include changes from baseline in other visual functions, anatomical changes and cost-effectiveness. Ocular and non-ocular adverse events will also be reported over 52 weeks. Ethics and dissemination The study has been approved by the National Research Ethics Service (NRES) committee with respect to scientific content and compliance with applicable research and human subjects’ regulations. Findings will be reported through scientific publications and research conferences. The results of this study will provide clinical evidence for the feasibility, efficacy safety and cost-effectiveness of intravitreal aflibercept for PDR. Trial registration number ISRCTN 32207582. PMID:26369798

  7. Early hormonal data from a multicentre phase II trial using transdermal oestrogen patches as first-line hormonal therapy in patients with locally advanced or metastatic prostate cancer

    PubMed Central

    Langley, Ruth E.; Godsland, Ian F.; Kynaston, Howard; Clarke, Noel W.; Rosen, Stuart D.; Morgan, Rachel C.; Pollock, Philip; Kockelbergh, Roger; Lalani, El-Nasir; Dearnaley, David; Parmar, Mahesh; Abel, Paul D.

    2008-01-01

    OBJECTIVE To assess the hormonal effects of Fem7® (Merck, KGaA, Darmstadt, Germany) 100 μg transdermal oestrogen patches on men undergoing first-line androgen-deprivation therapy for prostate cancer. PATIENTS AND METHODS PATCH is a multicentre, randomized, phase II trial for men with locally advanced or metastatic prostate cancer, comparing luteinizing hormone-releasing hormone agonist therapy with oestrogen patches. To assess the dosing schedule for the patches, as this was the first time that this brand of patch had been used in men, and to reassure patients and participating clinicians, the Independent Data Monitoring Committee agreed to early release of hormonal data from this study. RESULTS Oestradiol, testosterone and prostate-specific antigen (PSA) levels are presented for the first group of 14 patients who received the patches (with 1 withdrawal) and for whom there were ≥12 weeks of follow-up by March 2007. After 12 weeks, testosterone levels (nmol/L) in eight of the 13 patients were <1.7, two were 1.7–2 and three were >2. The median (range) serum oestradiol levels was 442 (52.1–1542) pmol/L and all patients had a PSA response, with eight having a PSA level of <4 ng/mL. CONCLUSION These results confirm that oestrogen patches produce castrate levels of testosterone and concomitant PSA responses. They also highlighted the potential differences between different brands of oestrogen patches, and the need to monitor hormonal response, toxicity and efficacy until more experience with oestrogen patches for this clinical indication is obtained. The number of patches recommended in the PATCH study has now been increased. PMID:18422771

  8. Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD) plus interferon alpha for metastatic melanoma: a multicentre phase II study.

    PubMed Central

    Punt, C. J.; van Herpen, C. M.; Jansen, R. L.; Vreugdenhil, G.; Muller, E. W.; de Mulder, P. H.

    1997-01-01

    High response rates in patients with metastatic melanoma have been achieved with combination chemoimmunotherapy. A response rate of 62% in 45 patients has been reported for treatment with dacarbazine, bleomycin, vincristine, lomustine (BOLD) plus interferon alpha (IFN-alpha). We conducted a multicentre phase II study to confirm these results. Melanoma patients with distant metastases were treated as outpatients with dacarbazine 200 mg m(-2) on days 1-5, vincristine 1 mg m(-2) on days 1 and 4, bleomycin 15 mg on days 2 and 5 i.v. and lomustine 80 mg orally on day 1, repeated every 4 weeks. IFN-alpha-2b was initiated s.c. on day 8 at 3 MU daily for 6 weeks, and 6 MU t.i.w. thereafter. Forty-three patients entered the study. The median number of metastatic sites was three (range 1-5), and 81% of patients had visceral metastases. Nine patients had brain metastases, and seven patients were systemically pretreated. Among the 41 patients that were evaluable for response, the response rate was 27% (95% CI 14-3%), with one complete and ten partial remissions. The response rate in 25 previously untreated patients without brain metastases was 40% (95% CI 21-61%). Median duration of response was 6 (range 2-14+) months; median overall survival was 5 (1-26) months. The main toxicity was malaise/fatigue. We confirm that BOLD plus IFN-alpha has activity in metastatic melanoma. The lower response rate in our study compared with the previous report is probably related to patient selection, as in the previous study 46% of patients had stage III disease, whereas all our patients had stage IV disease, which is associated with a worse prognosis. PMID:9231931

  9. Random bilayer phases of dilute surfactant solutions

    NASA Astrophysics Data System (ADS)

    Cates, M. E.; Roux, D.

    1990-12-01

    Surfactant molecules in dilute solution may aggregate reversibly into extended structures. For suitably chosen molecules, the preferred packing involves a locally flat bilayer which tends to wander entropically at large distances. At low temperatures (and/or high concentrations) the system forms a stack of flat sheets with one-dimensional quasi-long range order (a smectic liquid crystal), but at high temperatures or low concentrations, the stack can melt into a random surface structure that resembles a multiply connected labyrinth or 'sponge' of bilayer in a sea of solvent. Recent theoretical and experimental progress in understanding the properties of the sponge is reviewed. The authors argue that the sponge phase may provide a good system for the study of various liquid-state critical phenomena.

  10. Phase transitions in random quantum satisfiability

    NASA Astrophysics Data System (ADS)

    Laumann, Chris; Moessner, Roderich; Scardicchio, Antonello; Sondhi, Shivaji

    2009-03-01

    The potential power of quantum computers is a subject of great current interest and the raison d'etre for the intense effort and progress to build them. Naturally much theoretical interest has focused on algorithms that outperform their classical counterpart but recent developments in quantum complexity theory suggest that we already know problems, those shown to be QMA-complete, whose worst case instances would take a quantum computer exponentially long to solve. As in classical complexity theory the supposed difficulty of QMA complete problems follows from the existence of polynomial transformations relating any of the large class of QMA problems to instances of QMA-complete questions. This does not directly address the question of why this problem has hard instances and what features they posses. In this work we attempt to investigate the features of hard instances of a QMA complete problem introduced by S. Bravyi: quantum k-SAT. We use techniques of statistical physics of disordered systems in order to study a random ensemble of quantum k-SAT instances parametrized by clause density α in a program that is analogous to recent studies of classical random k-SAT. We establish a phase transition in satisfiability as a function of clause density and show that the problem almost always reduces to identifying a classical graph property.

  11. Coulomb glass in the random phase approximation

    NASA Astrophysics Data System (ADS)

    Basylko, S. A.; Onischouk, V. A.; Rosengren, A.

    2002-01-01

    A three-dimensional model of the electrons localized on randomly distributed donor sites of density n and with the acceptor charge uniformly smeared on these sites, -Ke on each, is considered in the random phase approximation (RPA). For the case K=1/2 the free energy, the density of the one-site energies (DOSE) ɛ, and the pair OSE correlators are found. In the high-temperature region (e2n1/3/T)<1 (T is the temperature) RPA energies and DOSE are in a good agreement with the corresponding data of Monte Carlo simulations. Thermodynamics of the model in this region is similar to the one of an electrolyte in the regime of Debye screening. In the vicinity of the Fermi level μ=0 the OSE correlations, depending on sgn(ɛ1.ɛ2) and with very slow decoupling law, have been found. The main result is that even in the temperature range where the energy of a Coulomb glass is determined by Debye screening effects, the correlations of the long-range nature between the OSE still exist.

  12. [Multicentric reticulohistiocytosis].

    PubMed

    Sokolović, Sekib; Kasumagić, Sida

    2009-01-01

    A very rare inflammatory systemic rheumatic disorder--Multicentric reticulohistiocytosis--was described as a case report in this paper. A 22 year old female patient was presented with a destructive polyarthritis and prominent multiple skin nodules that pointed to possible presence of this rare disease. The final diagnosis was made based on the biopsy finding. Application of the cytotoxic drug Metotrexate in the therapy, besides non-steroidal anti-inflammatory drugs and corticosteroids, leaded to full remission with disappearance of skin changes.

  13. Effect of lansoprazole on the epigastric symptoms of functional dyspepsia (ELF study): A multicentre, prospective, randomized, double-blind, placebo-controlled clinical trial

    PubMed Central

    Kusunoki, Hiroaki; Kamiya, Takeshi; Futagami, Seiji; Yamaguchi, Yasuharu; Nishizawa, Toshihiro; Iwasaki, Eisuke; Matsuzaki, Juntaro; Takahashi, Shinichi; Sakamoto, Choitsu; Haruma, Ken; Joh, Takashi; Asakura, Keiko; Hibi, Toshifumi

    2013-01-01

    Background: Since the publication of the Rome III criteria for functional dyspepsia (FD), the evidence about the efficacy of half-dose of proton pump inhibitors for dyspepsia symptoms have been limited. Objective: To examine the efficacy of lansoprazole for functional dyspepsia (FD) diagnosed with the Rome III criteria by the multicentre, double-blind, randomized, placebo-controlled study in Japan. Methods: A total of 54 FD participants were randomized to lansoprazole 15 mg once daily or placebo for a 4-week double-blind treatment period. The primary efficacy endpoint was an overall dyspeptic symptom relief rate evaluated by 5-point Likert scale scores. The alteration of dyspeptic symptom scores during the study period was also assessed. Results: At week 4, the overall dyspeptic symptom relief rates were higher in the lansoprazole group (30.4%) than in the placebo group (6.7%) (p = 0.045). The scores for epigastric pain (p = 0.045) and epigastric burning (p = 0.03) were significantly improved in the lansoprazole group compared to the placebo group, whereas the improvement of the scores for postprandial fullness (p = 0.81) and early satiation (p = 0.33) was not different between lansoprazole and placebo groups. Conclusions: Lansoprazole 15 mg ameliorates dyspeptic symptoms, particularly the epigastric pain syndrome-related symptoms of FD. PMID:24917996

  14. The addition of sirolimus to the graft-versus-host disease prophylaxis regimen in reduced intensity allogeneic stem cell transplantation for lymphoma: a multicentre randomized trial.

    PubMed

    Armand, Philippe; Kim, Haesook T; Sainvil, Marie-Michele; Lange, Paulina B; Giardino, Angela A; Bachanova, Veronika; Devine, Steven M; Waller, Edmund K; Jagirdar, Neera; Herrera, Alex F; Cutler, Corey; Ho, Vincent T; Koreth, John; Alyea, Edwin P; McAfee, Steven L; Soiffer, Robert J; Chen, Yi-Bin; Antin, Joseph H

    2016-04-01

    Inhibition of the mechanistic target of rapamycin (mTOR) pathway has clinical activity in lymphoma. The mTOR inhibitor sirolimus has been used in the prevention and treatment of graft-versus-host disease (GVHD) after allogeneic haematopoietic stem cell transplantation (HSCT). A retrospective study suggested that patients with lymphoma undergoing reduced intensity conditioning (RIC) HSCT who received sirolimus as part of their GVHD prophylaxis regimen had a lower rate of relapse. We therefore performed a multicentre randomized trial comparing tacrolimus, sirolimus and methotrexate to standard regimens in adult patients undergoing RIC HSCT for lymphoma in order to assess the possible benefit of sirolimus on HSCT outcome. 139 patients were randomized. There was no difference overall in 2-year overall survival, progression-free survival, relapse, non-relapse mortality or chronic GVHD. However, the sirolimus-containing arm had a significantly lower incidence of grade II-IV acute GVHD (9% vs. 25%, P = 0·015), which was more marked for unrelated donor grafts. In conclusion, the addition of sirolimus for GVHD prophylaxis in RIC HSCT is associated with no increased overall toxicity and a lower risk of acute GVHD, although it does not improve survival; this regimen is an acceptable option for GVHD prevention in RIC HSCT. This trial is registered at clinicaltrials.gov (NCT00928018).

  15. Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study

    PubMed Central

    Lauria, Giuseppe; Dalla Bella, Eleonora; Antonini, Giovanni; Borghero, Giuseppe; Capasso, Margherita; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Eleopra, Roberto; Fazio, Raffaella; Filosto, Massimiliano; Giannini, Fabio; Granieri, Enrico; La Bella, Vincenzo; Logroscino, Giancarlo; Mandrioli, Jessica; Mazzini, Letizia; Monsurrò, Maria Rosaria; Mora, Gabriele; Pietrini, Vladimiro; Quatrale, Rocco; Rizzi, Romana; Salvi, Fabrizio; Siciliano, Gabriele; Sorarù, Gianni; Volanti, Paolo; Tramacere, Irene; Filippini, Graziella

    2015-01-01

    Objective To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Methods Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40 000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intention-to-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. Results We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. Conclusions RhEPO 40 000 IU fortnightly did not change the course of ALS. PMID:25595151

  16. Four-phase rhinomanometry: a multicentric retrospective analysis of 36,563 clinical measurements.

    PubMed

    Vogt, Klaus; Wernecke, Klaus-Dieter; Behrbohm, Hans; Gubisch, Wolfgang; Argale, Mara

    2016-05-01

    Rhinomanometry can still be considered as the standard technique for the objective assessment of the ventilatory function of the nose. Reliable technical requirements are given by fast digital sensors and modern information technology. However, the xyimaging of the pressure-flow relation typically shows loops as a sign of hysteresis, with the need for resolution of the breath in four phases. The three pillars of 4-phase rhinomanometry (4PR) are the replacement of estimations by measurements, the introduction of parameters related to the subjective sensing of obstruction, and the graphical information regarding the disturbed function of the nasal valve. In a meta-analysis of 36,563 clinical measurements, we analyze the errors of the "classic" parameters (flow in 150 Pa) and reject the further use of these parameters as obsolete, because they correspond to an inaccurate estimation rather than proper measurement. In a pre-study of 1580 measurements, the logarithmic effective resistance (Reff) was found to have the highest correlation with values obtained from a visual analog scale. Next, we classify the inspiratory effective resistance in 20,069 measurements without treatment and 16,494 measurements after decongestion with xylometazoline 0.1 % spray in 20 % percentiles. The gradation of obstruction delivers not only "normal" values but also indications for the severity of the obstruction in adult Caucasian noses. Adoption of the distribution for the growing nose and analysis of the total nasal resistance is addressed, and typical findings of nasal valve phenomena are outlined.

  17. Implementation phase of a multicentre prehospital telemedicine system to support paramedics: feasibility and possible limitations

    PubMed Central

    2013-01-01

    Background Legal regulations often limit the medical care that paramedics can provide. Telemedical solutions could overcome these limitations by remotely providing expert support. Therefore, a mobile telemedicine system to support paramedics was developed. During the implementation phase of this system in four German emergency medical services (EMS), the feasibility and possible limitations of this system were evaluated. Methods After obtaining ethical approval and providing a structured training program for all medical professionals, the system was implemented on three paramedic-staffed ambulances on August 1st, 2012. Two more ambulances were included subsequently during this month. The paramedics could initiate a consultation with EMS physicians at a teleconsultation centre. Telemedical functionalities included audio communication, real-time vital data transmission, 12-lead electrocardiogram, picture transmission on demand, and video streaming from a camera embedded into the ceiling of each ambulance. After each consultation, telephone-based debriefings were conducted. Data were retrieved from the documentation protocols of the teleconsultation centre and the EMS. Results During a one month period, teleconsultations were conducted during 35 (11.8%) of 296 emergency missions with a mean duration of 24.9 min (SD 12.5). Trauma, acute coronary syndromes, and circulatory emergencies represented 20 (57%) of the consultation cases. Diagnostic support was provided in 34 (97%) cases, and the administration of 50 individual medications, including opioids, was delegated by the teleconsultation centre to the paramedics in 21 (60%) missions (range: 1–7 per mission). No medical complications or negative interpersonal effects were reported. All applications functioned as expected except in one case in which the connection failed due to the lack of a viable mobile network. Conclusion The feasibility of the telemedical approach was demonstrated. Teleconsultation enabled early

  18. Multicentre, randomized, open-label study of on-demand treatment with two prophylaxis regimens of recombinant coagulation factor IX in haemophilia B subjects.

    PubMed

    Valentino, L A; Rusen, L; Elezovic, I; Smith, L M; Korth-Bradley, J M; Rendo, P

    2014-05-01

    Few randomized studies have reported on the use of factor IX (FIX) for secondary prophylaxis in haemophilia B patients. This study aimed to evaluate the efficacy and safety of two secondary prophylaxis regimens of recombinant coagulation FIX, nonacog alfa, compared with on-demand therapy. Male subjects aged 6-65 years with severe or moderately severe haemophilia B (FIX:C ≤ 2, n = 50) and ≥12 bleeding episodes (including ≥6 haemarthroses episodes) within 12 months of study participation were enrolled in this multicentre, randomized, open-label, four-period crossover trial. The primary measure was the annualized bleeding rate (ABR) of two prophylactic regimens vs. on-demand therapy. In the intent-to-treat group, mean ABR values were 35.1, 2.6 and 4.6 for the first on-demand period, the 50 IU kg(-1) twice-weekly period, and the 100 IU kg(-1) once-weekly period respectively. Differences in ABR between the first on-demand period and both prophylaxis regimens were significant (P < 0.0001); no significant differences were observed between prophylaxis regimens (P = 0.22). Seven serious adverse events occurred in five subjects, none related to study drug. Results demonstrated that secondary prophylaxis therapy with nonacog alfa 50 IU kg(-1) twice weekly or 100 IU kg(-1) once weekly reduced ABR by 89.4% relative to on-demand treatment. Both prophylaxis regimens demonstrated favourable safety profiles in subjects with haemophilia B.

  19. A multicentre, prospective, randomized, controlled trial comparing EVARREST™ fibrin sealant patch to standard of care in controlling bleeding following elective hepatectomy: anatomic versus non-anatomic resection

    PubMed Central

    Koea, Jonathan B.; Batiller, Jonathan; Aguirre, Nicolas; Shen, Jessica; Kocharian, Richard; Bochicchio, Grant; Garden, O. James

    2016-01-01

    Background This multicentre, randomized clinical trial assessed the safety and effectiveness of the EVARREST™ Fibrin Sealant Patch (FP) in treating parenchymal bleeding following anatomic and non-anatomic liver resections. Methods One hundred and two patients were stratified according to the type of hepatic resection (anatomic/non-anatomic), and randomized (1:1) after identification of an appropriate bleeding site, to FP vs Standard of Care (SoC, manual compression ± topical haemostat). The primary endpoint was haemostasis at 4 min from bleeding site identification with no re-bleeding requiring re-treatment. Results The FP was superior in achieving haemostasis at 4 min (96%, 48/50) to SoC (46%, 24/52; p < 0.001). Stratification for resection type showed treatment differences for primary endpoint for anatomic (24/25 FP vs 13/23 SoC; p = 0.001) and non-anatomic liver resections (24/25FP vs 11/29 SoC; p < 0.001). Adverse events related to the study procedure were reported in 40/50 patients (80%) in the FP group and 43/52 patients (83%) in the SoC group. One (2%) adverse event (infected intra-abdominal fluid collection) was possibly related to study treatment. Conclusion This clinical trial confirms that the FP is safe and highly effective in controlling parenchymal bleeding following hepatectomy regardless of the type of resection. ClinicalTrials.gov NCT01993888. PMID:27017161

  20. Catheter ablation vs. antiarrhythmic drug treatment of persistent atrial fibrillation: a multicentre, randomized, controlled trial (SARA study)

    PubMed Central

    Mont, Lluís; Bisbal, Felipe; Hernández-Madrid, Antonio; Pérez-Castellano, Nicasio; Viñolas, Xavier; Arenal, Angel; Arribas, Fernando; Fernández-Lozano, Ignacio; Bodegas, Andrés; Cobos, Albert; Matía, Roberto; Pérez-Villacastín, Julián; Guerra, José M.; Ávila, Pablo; López-Gil, María; Castro, Victor; Arana, José Ignacio; Brugada, Josep

    2014-01-01

    Background Catheter ablation (CA) is a highly effective therapy for the treatment of paroxysmal atrial fibrillation (AF) when compared with antiarrhythmic drug therapy (ADT). No randomized studies have compared the two strategies in persistent AF. The present randomized trial aimed to compare the effectiveness of CA vs. ADT in treating persistent AF. Methods and results Patients with persistent AF were randomly assigned to CA or ADT (excluding patients with long-standing persistent AF). Primary endpoint at 12-month follow-up was defined as any episode of AF or atrial flutter lasting >24 h that occurred after a 3-month blanking period. Secondary endpoints were any atrial tachyarrhythmia lasting >30 s, hospitalization, and electrical cardioversion. In total, 146 patients were included (aged 55 ± 9 years, 77% male). The ADT group received class Ic (43.8%) or class III drugs (56.3%). In an intention-to-treat analysis, 69 of 98 patients (70.4%) in the CA group and 21 of 48 patients (43.7%) in the ADT group were free of the primary endpoint (P = 0.002), implying an absolute risk difference of 26.6% (95% CI 10.0–43.3) in favour of CA. The proportion of patients free of any recurrence (>30 s) was higher in the CA group than in the ADT group (60.2 vs. 29.2%; P < 0.001) and cardioversion was less frequent (34.7 vs. 50%, respectively; P = 0.018). Conclusion Catheter ablation is superior to medical therapy for the maintenance of sinus rhythm in patients with persistent AF at 12-month follow-up. Clinical Trial Registration Information NCT00863213 (http://clinicaltrials.gov/ct2/show/NCT00863213). PMID:24135832

  1. Randomized multi-centre trial of the effects of a catheter coated with hydrogel and silver salts on the incidence of hospital-acquired urinary tract infections.

    PubMed

    Thibon, P; Le Coutour, X; Leroyer, R; Fabry, J

    2000-06-01

    Catheters coated with hydrogel and silver salts have been proposed to prevent hospital-acquired urinary tract infections (UTI). We carried out a randomized, prospective, double-blind multi-centre trial to compare those catheters with classical urinary tract catheters. We included in the study 199 patients requiring urethral catheterization for more than three days: 109 in group 1 (classical catheter) and 90 in group 2 (catheter coated with hydrogel and silver salts). Urine from the patients was tested for 10 days after the insertion of the catheter (reactive dipsticks each day and diagnostic urinalysis every two days). The UTI associated with catheterization was defined on the basis of bacterial and cytological criteria (>10(5)cfu bacteria per mL and >10 leucocytes per mm(3)). Twenty-two UTIs were recorded: 13 in group 1 and nine in group 2. The cumulative incidence of UTI associated with catheterization was 11.1% overall, 11.9% for group 1 and 10% for group 2; the odds ratio was 0.82 (95% confidence interval: 0.30 to 2. 20); the cumulative incidence for UTI, calculated by the Kaplan-Meier method was 36.3 overall, 35.2 in group 1 and 36.0 in group 2; the overall incidence density was 19 per thousand days of catheterization, 21 in group 1 and 18 in group 2. The differences between the two groups were not significant. Overall, we feel that there is not enough evidence to conclude that catheters coated with silver salts and hydrogel give greater protection than classical catheters and to recommend widespread use.

  2. Optimization of ventilator setting by flow and pressure waveforms analysis during noninvasive ventilation for acute exacerbations of COPD: a multicentric randomized controlled trial

    PubMed Central

    2011-01-01

    Introduction The analysis of flow and pressure waveforms generated by ventilators can be useful in the optimization of patient-ventilator interactions, notably in chronic obstructive pulmonary disease (COPD) patients. To date, however, a real clinical benefit of this approach has not been proven. Methods The aim of the present randomized, multi-centric, controlled study was to compare optimized ventilation, driven by the analysis of flow and pressure waveforms, to standard ventilation (same physician, same initial ventilator setting, same time spent at the bedside while the ventilator screen was obscured with numerical data always available). The primary aim was the rate of pH normalization at two hours, while secondary aims were changes in PaCO2, respiratory rate and the patient's tolerance to ventilation (all parameters evaluated at baseline, 30, 120, 360 minutes and 24 hours after the beginning of ventilation). Seventy patients (35 for each group) with acute exacerbation of COPD were enrolled. Results Optimized ventilation led to a more rapid normalization of pH at two hours (51 vs. 26% of patients), to a significant improvement of the patient's tolerance to ventilation at two hours, and to a higher decrease of PaCO2 at two and six hours. Optimized ventilation induced physicians to use higher levels of external positive end-expiratory pressure, more sensitive inspiratory triggers and a faster speed of pressurization. Conclusions The analysis of the waveforms generated by ventilators has a significant positive effect on physiological and patient-centered outcomes during acute exacerbation of COPD. The acquisition of specific skills in this field should be encouraged. Trial registration ClinicalTrials.gov NCT01291303. PMID:22115190

  3. Azathioprine versus Beta Interferons for Relapsing-Remitting Multiple Sclerosis: A Multicentre Randomized Non-Inferiority Trial

    PubMed Central

    Massacesi, Luca; Tramacere, Irene; Amoroso, Salvatore; Battaglia, Mario A.; Benedetti, Maria Donata; Filippini, Graziella; La Mantia, Loredana; Repice, Anna; Solari, Alessandra; Tedeschi, Gioacchino; Milanese, Clara

    2014-01-01

    For almost three decades in many countries azathioprine has been used to treat relapsing-remitting multiple sclerosis. However its efficacy was usually considered marginal and following approval of β interferons for this indication it was no longer recommended as first line treatment, even if presently no conclusive direct β interferon-azathioprine comparison exists. To compare azathioprine efficacy versus the currently available β interferons in relapsing-remitting multiple sclerosis, a multicenter, randomized, controlled, single-blinded, non-inferiority trial was conducted in 30 Italian multiple sclerosis centers. Eligible patients (relapsing-remitting course; ≥2 relapses in the last 2 years) were randomly assigned to azathioprine or β interferons. The primary outcome was annualized relapse rate ratio (RR) over 2 years. Key secondary outcome was number of new brain MRI lesions. Patients (n = 150) were randomized in 2 groups (77 azathioprine, 73 β interferons). At 2 years, clinical evaluation was completed in 127 patients (62 azathioprine, 65 β interferons). Annualized relapse rate was 0.26 (95% Confidence Interval, CI, 0.19–0.37) in the azathioprine and 0.39 (95% CI 0.30–0.51) in the interferon group. Non-inferiority analysis showed that azathioprine was at least as effective as β interferons (relapse RRAZA/IFN 0.67, one-sided 95% CI 0.96; p<0.01). MRI outcomes were analyzed in 97 patients (50 azathioprine and 47 β interferons). Annualized new T2 lesion rate was 0.76 (95% CI 0.61–0.95) in the azathioprine and 0.69 (95% CI 0.54–0.88) in the interferon group. Treatment discontinuations due to adverse events were higher (20.3% vs. 7.8%, p = 0.03) in the azathioprine than in the interferon group, and concentrated within the first months of treatment, whereas in the interferon group discontinuations occurred mainly during the second year. The results of this study indicate that efficacy of azathioprine is not inferior to that of

  4. Randomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection

    PubMed Central

    Tsaganos, Thomas; Tseti, Ioulia K.; Tziolos, Nikolaos; Soumelas, Georgios‐Stefanos; Koupetori, Marina; Pyrpasopoulou, Athina; Akinosoglou, Karolina; Gogos, Charalambos; Tsokos, Nikolaos; Karagiannis, Asterios; Sympardi, Styliani

    2016-01-01

    Aim No randomized study has been conducted to investigate the use of intravenous paracetamol (acetaminophen, APAP) for the management of fever due to infection. The present study evaluated a new ready‐made infusion of paracetamol. Methods Eighty patients with a body temperature onset ≥38.5°C in the previous 24 h due to infection were randomized to a single administration of placebo (n = 39) or 1 g paracetamol (n = 41), and their temperature was recorded at standard intervals. Rescue medication with 1 g paracetamol was allowed. Serum samples were collected for the measurement of APAP and its metabolites. The primary endpoint was defervescence, defined as a core temperature ≤37.1°C. Results During the first 6 h, defervescence was achieved in 15 (38.5%) patients treated with placebo compared with 33 (80.5%) patients treated with paracetamol 1 g (P < 0.0001). The median time to defervescence with paracetamol 1 g was 3 h. Rescue medication was given to 15 (38.5%) and five (12.2%) patients allocated to placebo and paracetamol, respectively (P = 0.007); nine (60.0%) and two (40.0%) of these patients, respectively, experienced defervescence. No further antipyretic medication was needed for patients becoming afebrile with rescue medication. Serum glucuronide‐APAP concentrations were significantly greater in the serum of patients who did not experience defervescence with paracetamol. The efficacy of paracetamol was not affected by serum creatinine. No drug‐related adverse events were reported. Conclusions The 1 g paracetamol formulation has a rapid and sustainable antipyretic effect on fever due to infection. Its efficacy is dependent on hepatic metabolism. PMID:27792836

  5. Ordering and phase transitions in random-field Ising systems

    NASA Technical Reports Server (NTRS)

    Maritan, Amos; Swift, Michael R.; Cieplak, Marek; Chan, Moses H. W.; Cole, Milton W.; Banavar, Jayanth R.

    1991-01-01

    An exact analysis of the Ising model with infinite-range interactions in a random field and a local mean-field theory in three dimensions is carried out leading to a phase diagram with several coexistence surfaces and lines of critical points. The results show that the phase diagram depends crucially on whether the distribution of random fields is symmetric or not. Thus, Ising-like phase transitions in a porous medium (the asymmetric case) are in a different universality class from the conventional random-field model (symmetric case).

  6. Fusion and failure following anterior cervical plating with dynamic or rigid plates: 6-months results of a multi-centric, prospective, randomized, controlled study

    PubMed Central

    Stulik, Jan; Chrobok, Jan; Ruffing, Sabine; Drumm, Jörg; Sova, Laurentius; Kucera, Ravel; Vyskocil, Tomas; Steudel, Wolf Ingo

    2007-01-01

    Anterior cervical plate fixation is an approved surgical technique for cervical spine stabilization in the presence of anterior cervical instability. Rigid plate design with screws rigidly locked to the plate is widely used and is thought to provide a better fixation for the treated spinal segment than a dynamic design in which the screws may slide when the graft is settling. Recent biomechanical studies showed that dynamic anterior plates provide a better graft loading possibly leading to accelerated spinal fusion with a lower incidence of implant complications. This, however, was investigated in vitro and does not necessarily mean to be the case in vivo, as well. Thus, the two major aspects of this study were to compare the speed of bone fusion and the rate of implant complications using either rigid- or dynamic plates. The study design is prospective, randomized, controlled, and multi-centric, having been approved by respective ethic committees of all participating sites. One hundred and thirty-two patients were included in this study and randomly assigned to one of the two groups, both undergoing routine level-1- or level-2 anterior cervical discectomy with autograft fusion receiving either a dynamic plate with screws being locked in ap - position (ABC, Aesculap, Germany), or a rigid plate (CSLP, Synthes, Switzerland). Segmental mobility and implant complications were compared after 3- and 6 months, respectively. All measurements were performed by an independent radiologist. Mobility results after 6 months were available for 77 patients (43 ABC/34 CSLP). Mean segmental mobility for the ABC group was 1.7 mm at the time of discharge, 1.4 mm after 3 months, and 0.8 mm after 6 months. For the CSLP- group the measurements were 1.0, 1.8, and 1.7 mm, respectively. The differences of mean segmental mobility were statistically significant between both groups after 6 months (P = 0.02). Four patients of the CSLP-group demonstrated surgical hardware complications

  7. Early class III protraction facemask treatment reduces the need for orthognathic surgery: a multi-centre, two-arm parallel randomized, controlled trial

    PubMed Central

    Mandall, Nicky; Cousley, Richard; DiBiase, Andrew; Dyer, Fiona; Littlewood, Simon; Mattick, Rye; Nute, Spencer J.; Doherty, Barbara; Stivaros, Nadia; McDowall, Ross; Shargill, Inderjit; Worthington, Helen V.

    2016-01-01

    Objective: To evaluate whether patients who had received early class III protraction facemask treatment were less likely to need orthognathic surgery compared with untreated controls. This paper is a 6-year follow-up of a previous clinical trial. Design: Multi-centre 2-arm parallel randomized controlled trial. Setting: Eight United Kingdom hospital orthodontic departments. Participants: Seventy three 7- to 9–year-old children. Method: Patients were randomly allocated, stratified for gender, into an early class III protraction facemask group (PFG) (n = 35) and a control/no treatment group (CG) (n = 38). The primary outcome, need for orthognathic surgery was assessed by panel consensus. Secondary outcomes were changed in skeletal pattern, overjet, Peer Assessment Rating (PAR), self-esteem and the oral aesthetic impact of malocclusion. The data were compared between baseline (DC1) and 6-year follow-up (DC4). A per-protocol analysis was carried out with n = 32 in the CG and n = 33 in the PFG. Results: Thirty six percent of the PFG needed orthognathic surgery, compared with 66% of the CG (P = 0.027). The odds of needing surgery was 3.5 times more likely when protraction facemask treatment was not used (odds ratio = 3.34 95% CI 1.21–9.24). The PFG exhibited a clockwise rotation and the CG an anti-clockwise rotation in the maxilla (regression coefficient 8.24 (SE 0.75); 95% CI 6.73–9.75; P < 0.001) and the mandible (regression coefficient 6.72 (SE 0.73); 95% CI 5.27–8.18; P < 0.001). Sixty eight per cent of the PFG maintained a positive overjet at 6-year follow-up. There were no statistically significant differences between the PFG and CG for skeletal/occlusal improvement, self-esteem or oral aesthetic impact. Conclusions: Early class III protraction facemask treatment reduces the need for orthognathic surgery. However, this effect cannot be explained by the maintenance of skeletal cephalometric change. PMID:27564126

  8. Treatment of severe, nonfulminant acute hepatitis B with lamivudine vs placebo: a prospective randomized double-blinded multicentre trial.

    PubMed

    Wiegand, J; Wedemeyer, H; Franke, A; Rößler, S; Zeuzem, S; Teuber, G; Wächtler, M; Römmele, U; Ruf, B; Spengler, U; Trautwein, C; Bock, C T; Fiedler, G M; Thiery, J; Manns, M P; Brosteanu, O; Tillmann, H L

    2014-10-01

    Acute hepatitis B virus (aHBV) infection can lead to fulminant liver failure, which likely is prevented by early lamivudine therapy. Even nonfulminant but severe acute hepatitis B can lead to significant morbidity and impaired quality of life. Therefore, lamivudine was evaluated in patients with severe aHBV in a placebo-controlled trial. Patients with severe aHBV infection (ALT >10× ULN, bilirubin >85 μm, prothrombin time >50%) were prospectively treated with lamivudine 100 mg/day or with placebo within 8 days after the diagnosis. The primary end point was time to bilirubin <34.2 μm. Secondary end points were time to clear HBsAg and HBV-DNA, development of anti-HBs and normalization of ALT. Eighteen cases were randomized to lamivudine, 17 to placebo. 94% of patients were hospitalized. No individual progressed to hepatic failure; all but one patient achieved the primary end point. Due to smaller than expected patient numbers, all study end points did not become statistically significant between treatment arms. Median time end points [in days] were bilirubin <34.2 μm (26.5 vs 32), ALT normalization (35 vs 48) and HBsAg clearance (48 vs 67) referring to earlier recovery under lamivudine, in contrast to loss of HBV-DNA (62 vs 54) and development of anti-HBs (119 vs 109). In all but two patients (one in every group), HBsAg clearance was reached in the study. Adverse events occurred more frequently during lamivudine therapy, but did not reach statistical significance. Lamivudine may ameliorate severe aHBV infection, but limited patient numbers prevented definite conclusions.

  9. Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Negative Women: A Multicentre Randomized Controlled Trial

    PubMed Central

    Abdulla, Salim; Accrombessi, Manfred; Aponte, John J.; Akerey-Diop, Daisy; Basra, Arti; Briand, Valérie; Capan, Meskure; Cot, Michel; Kabanywanyi, Abdunoor M.; Kleine, Christian; Kremsner, Peter G.; Macete, Eusebio; Mackanga, Jean-Rodolphe; Massougbodgi, Achille; Mayor, Alfredo; Nhacolo, Arsenio; Pahlavan, Golbahar; Ramharter, Michael; Rupérez, María; Sevene, Esperança; Vala, Anifa; Zoleko-Manego, Rella; Menéndez, Clara

    2014-01-01

    Background Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women. Methods and Findings A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 [13.0%]) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio [RR], 1.02 (95% CI 0.86–1.22; p = 0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 [4.6%] in the SP group and 88/2,737 [3.2%] in the MQ group; RR, 0.70 [95% CI 0.51–0.96]; p = 0.03) and anemia at delivery (609/1,380 [44.1%] in the SP group and 1,110/2743 [40.5%] in the MQ group; RR, 0.92 [95% CI 0.85–0.99]; p = 0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year [PYAR] in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 [95% CI 0.52–0.88]; p = 0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 [0.78–0.95]; p = 0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP

  10. [Occult multicentric breast cancer].

    PubMed

    Vtorushin, S V; Zab'ialova, M V; Glushchenko, S A; Perel'muter, V M; Slonimskaia, E M

    2009-01-01

    The study included 92 patients with invasive ductal breast cancer (T2-4N0-2M0-1). In 38 cases, tumor growth was unicentric while histologically identifiable ones as multicentric in 44. Multicentricity mostly occurred in cases of macroscopically-identifiable nodes located in the central segments of the breast. Clinically-identifiable nodes of multicentric tumor growth measured more than 3 cm. Multicentric tumors were mostly grade III, featured lower expression of sex hormone receptors and positive Her2 status.

  11. Effects of Blockiness on the phase behavior of random copolymers

    NASA Astrophysics Data System (ADS)

    Vanderwoude, Gordon; Shi, An-Chang

    Theoretical study of random block copolymers remains a challenging topic due in part to the sheer enormity of their phase space. In this study we use the self-consistent field theory to investigate the phase behaviour of linear (AB)n-type and (AB)n-C-type multiblock copolymers with randomly distributed A and B blocks. In particular, we examine the effect of ``blockiness'' of the random copolymers on the formation of ordered phases. The blockiness can be quantified by the average length of individual A or B blocks, which can be taken as a measure of the heterogeneity of the random copolymers. We observed that the critical value of the χ parameter, at which the order-disorder transition occurs, decreases with increasing blockiness in the (AB)n copolymers. We also observed that the phase behaviour of the (AB)n-C copolymers depends strongly on the blockiness of the random chain. In particular, the blockiness governs whether or not the A/B blocks can phase separate within the A/B domains, thus dictating whether the (AB)n-C behaves as A/B-C diblock copolymers or as ABC terpolymers. The theoretical phase diagrams will be compared with available experiments.

  12. Single-exposure phase-shifting digital holography using a random-phase reference wave.

    PubMed

    Nomura, Takanori; Imbe, Masatoshi

    2010-07-01

    We propose a single-exposure phase-shifting digital holography based on a wave-splitting method using a random-phase reference wave. A random-phase reference wave gives random-phase distribution on the digital hologram. Using the amplitude and the phase distributions of the reference wave, the fully complex amplitude of the object wave is obtained. The proposed method requires not devised optical systems but ordinary imaging devices, such as CCD cameras. A preliminary experimental result is given to confirm the proposed method.

  13. The Condensation Phase Transition in Random Graph Coloring

    NASA Astrophysics Data System (ADS)

    Bapst, Victor; Coja-Oghlan, Amin; Hetterich, Samuel; Raßmann, Felicia; Vilenchik, Dan

    2016-01-01

    Based on a non-rigorous formalism called the "cavity method", physicists have put forward intriguing predictions on phase transitions in diluted mean-field models, in which the geometry of interactions is induced by a sparse random graph or hypergraph. One example of such a model is the graph coloring problem on the Erdős-Renyi random graph G( n, d/ n), which can be viewed as the zero temperature case of the Potts antiferromagnet. The cavity method predicts that in addition to the k-colorability phase transition studied intensively in combinatorics, there exists a second phase transition called the condensation phase transition (Krzakala et al. in Proc Natl Acad Sci 104:10318-10323, 2007). In fact, there is a conjecture as to the precise location of this phase transition in terms of a certain distributional fixed point problem. In this paper we prove this conjecture for k exceeding a certain constant k 0.

  14. Nonequilibrium phase transition on a randomly diluted lattice.

    PubMed

    Vojta, Thomas; Lee, Man Young

    2006-01-27

    We show that the interplay between geometric criticality and dynamical fluctuations leads to a novel universality class of the contact process on a randomly diluted lattice. The nonequilibrium phase transition across the percolation threshold of the lattice is characterized by unconventional activated (exponential) dynamical scaling and strong Griffiths effects. We calculate the critical behavior in two and three space dimensions, and we also relate our results to the recently found infinite-randomness fixed point in the disordered one-dimensional contact process.

  15. Phase transitions for information diffusion in random clustered networks

    NASA Astrophysics Data System (ADS)

    Lim, Sungsu; Shin, Joongbo; Kwak, Namju; Jung, Kyomin

    2016-09-01

    We study the conditions for the phase transitions of information diffusion in complex networks. Using the random clustered network model, a generalisation of the Chung-Lu random network model incorporating clustering, we examine the effect of clustering under the Susceptible-Infected-Recovered (SIR) epidemic diffusion model with heterogeneous contact rates. For this purpose, we exploit the branching process to analyse information diffusion in random unclustered networks with arbitrary contact rates, and provide novel iterative algorithms for estimating the conditions and sizes of global cascades, respectively. Showing that a random clustered network can be mapped into a factor graph, which is a locally tree-like structure, we successfully extend our analysis to random clustered networks with heterogeneous contact rates. We then identify the conditions for phase transitions of information diffusion using our method. Interestingly, for various contact rates, we prove that random clustered networks with higher clustering coefficients have strictly lower phase transition points for any given degree sequence. Finally, we confirm our analytical results with numerical simulations of both synthetically-generated and real-world networks.

  16. Ultrafast quantum random number generation based on quantum phase fluctuations.

    PubMed

    Xu, Feihu; Qi, Bing; Ma, Xiongfeng; Xu, He; Zheng, Haoxuan; Lo, Hoi-Kwong

    2012-05-21

    A quantum random number generator (QRNG) can generate true randomness by exploiting the fundamental indeterminism of quantum mechanics. Most approaches to QRNG employ single-photon detection technologies and are limited in speed. Here, we experimentally demonstrate an ultrafast QRNG at a rate over 6 Gbits/s based on the quantum phase fluctuations of a laser operating near threshold. Moreover, we consider a potential adversary who has partial knowledge on the raw data and discuss how one can rigorously remove such partial knowledge with postprocessing. We quantify the quantum randomness through min-entropy by modeling our system and employ two randomness extractors--Trevisan's extractor and Toeplitz-hashing--to distill the randomness, which is information-theoretically provable. The simplicity and high-speed of our experimental setup show the feasibility of a robust, low-cost, high-speed QRNG.

  17. Random phase-free computer holography and its applications

    NASA Astrophysics Data System (ADS)

    Shimobaba, Tomoyoshi; Kakue, Takashi; Ito, Tomoyoshi

    2016-06-01

    Random phase is required in computer-generated hologram (CGH) to widely diffuse object light and to avoid its concentration on the CGH; however, the random phase causes considerable speckle noise in the reconstructed image and degrades the image quality. We introduce a simple and computationally inexpensive method that improves the image quality and reduces the speckle noise by multiplying the object light with the designed convergence light. We furthermore propose the improved method of the designed convergence light with iterative method to reduce ringing artifacts. Subsequently, as the application, a lensless zoomable holographic projection is introduced.

  18. Single-random-phase holographic encryption of images

    NASA Astrophysics Data System (ADS)

    Tsang, P. W. M.

    2017-02-01

    In this paper, a method is proposed for encrypting an optical image onto a phase-only hologram, utilizing a single random phase mask as the private encryption key. The encryption process can be divided into 3 stages. First the source image to be encrypted is scaled in size, and pasted onto an arbitrary position in a larger global image. The remaining areas of the global image that are not occupied by the source image could be filled with randomly generated contents. As such, the global image as a whole is very different from the source image, but at the same time the visual quality of the source image is preserved. Second, a digital Fresnel hologram is generated from the new image, and converted into a phase-only hologram based on bi-directional error diffusion. In the final stage, a fixed random phase mask is added to the phase-only hologram as the private encryption key. In the decryption process, the global image together with the source image it contained, can be reconstructed from the phase-only hologram if it is overlaid with the correct decryption key. The proposed method is highly resistant to different forms of Plain-Text-Attacks, which are commonly used to deduce the encryption key in existing holographic encryption process. In addition, both the encryption and the decryption processes are simple and easy to implement.

  19. A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma.

    PubMed

    Ogura, Michinori; Ando, Kiyoshi; Suzuki, Tatsuya; Ishizawa, Kenichi; Oh, Sung Yong; Itoh, Kuniaki; Yamamoto, Kazuhito; Au, Wing Yan; Tien, Hwei-Fang; Matsuno, Yoshihiro; Terauchi, Takashi; Yamamoto, Keiko; Mori, Masahiko; Tanaka, Yoshinobu; Shimamoto, Takashi; Tobinai, Kensei; Kim, Won Seog

    2014-06-01

    Although initial rituximab-containing chemotherapies achieve high response rates, indolent B-cell non-Hodgkin lymphoma (B-NHL), such as follicular lymphoma (FL), is still incurable. Therefore, new effective agents with novel mechanisms are anticipated. In this multicentre phase II study, patients with relapsed/refractory indolent B-NHL and mantle cell lymphoma (MCL) received vorinostat 200 mg twice daily for 14 consecutive days in a 21-d cycle until disease progression or unacceptable toxicity occurred. The primary endpoint was overall response rate (ORR) in FL patients and safety and tolerability in all patients. Secondary endpoints included progression-free survival (PFS). Fifty-six eligible patients were enrolled; 50 patients (39 with FL, seven with other B-NHL, and four with MCL) were evaluable for ORR, and 40 patients had received rituximab-containing prior chemotherapeutic regimens. For the 39 patients with FL, the ORR was 49% [95% confidence interval (CI): 32·4, 65·2] and the median PFS was 20 months (95% CI: 11·2, 29·7). Major toxicities were manageable grade 3/4 thrombocytopenia and neutropenia. Vorinostat offers sustained antitumour activity in patients with relapsed or refractory FL with an acceptable safety profile. Further investigation of vorinostat for clinical efficacy is warranted.

  20. Calcium supplementation reducing the risk of hypertensive disorders of pregnancy and related problems: A meta-analysis of multicentre randomized controlled trials.

    PubMed

    An, Li-bin; Li, Wen-tao; Xie, Tie-nan; Peng, Xin; Li, Bo; Xie, Shu-hong; Xu, Jing; Zhou, Xiao-hua; Guo, Shao-ning

    2015-05-01

    Hypertensive disorders of pregnancy are closely related to maternal mortality and morbidity. Calcium supplementation during pregnancy seems to reduce the risk of hypertensive disorders. No systematic review on multicentre RCTs of calcium supplementation during pregnancy has been published. The purpose of this study was to report a quantitative systematic review of the effectiveness of calcium supplementation during pregnancy on reducing the risk of hypertensive disorders of pregnancy and related problems. Publications over the years of 1991-2012 were searched through PubMed, Science Direct, EMBASE, CINAHL and Web of Science. The literatures were selected of the multicentre RCTs on calcium supplementation during pregnancy in prevention of hypertensive disorders and related problems. Reference lists from the studies were also examined for additional references. Studies were critically appraised by three independent reviewers, and the Cochrane Handbook was used to assess the quality of those included trials. Four studies were included in this systematic review. All included studies were high quality, with low risk of bias. There was an observed risk reduction in hypertension in calcium group. However, there was no reduction in the risk of severe gestational hypertension, pre-eclampsia, severe pre-eclampsia, preterm birth and low birthweight. Calcium supplementation appears to reduce the risk of hypertension in pregnancy.

  1. Noise radar using random phase and frequency modulation

    NASA Astrophysics Data System (ADS)

    Axelsson, Sune R. J.

    2004-01-01

    Pulse compression radar is used in a great number of radar applications. Excellent range resolution and high ECCM performance can be achieved by wide-band modulated long pulses, which spread out the transmitted energy in frequency and time. By using random noise as waveform, the range ambiguity can be suppressed as well. The same limit in doppler resolution is achieved as for a coherent doppler radar when the time compression of the reference is tuned to that of the target. Mostly, the random signal is transmitted directly from a noise generating HF-source. A sine wave, which is phase or frequency modulated by random noise, is an alternative giving similar performance but higher transmitted mean power when peak-limited transmitters are applied. A narrower modulation noise bandwidth can also be applied to generate the same output bandwidth. For phase modulation, the bandwidth amplifying factor is simply the rms value of the phase modulation, and for a frequency modulating waveform the output rms bandwidth equals the rms value of the frequency modulation. The results also show that the range sidelobes can be highly suppressed compared with the sidelobes of the modulating signal. The mean and variance of the correlation integral are derived in terms of the autocorrelation function of the modulation. Finally, random bi-phase modulation and the effects of low-bit ADC at the correlation processing are analyzed and described. The advantages of low range sidelobes and enhanced range resolution make frequency and phase modulation attractive for a great number of applications.

  2. Correlation Energies from the Two-Component Random Phase Approximation.

    PubMed

    Kühn, Michael

    2014-02-11

    The correlation energy within the two-component random phase approximation accounting for spin-orbit effects is derived. The resulting plasmon equation is rewritten-analogously to the scalar relativistic case-in terms of the trace of two Hermitian matrices for (Kramers-restricted) closed-shell systems and then represented as an integral over imaginary frequency using the resolution of the identity approximation. The final expression is implemented in the TURBOMOLE program suite. The code is applied to the computation of equilibrium distances and vibrational frequencies of heavy diatomic molecules. The efficiency is demonstrated by calculation of the relative energies of the Oh-, D4h-, and C5v-symmetric isomers of Pb6. Results within the random phase approximation are obtained based on two-component Kohn-Sham reference-state calculations, using effective-core potentials. These values are finally compared to other two-component and scalar relativistic methods, as well as experimental data.

  3. Autocorrelations of Random Fractal Apertures and Phase Screens

    NASA Astrophysics Data System (ADS)

    Schonfeld, Jonathan F.

    We introduce a new product representation for general random binary fractal apertures defined by removing voids from Euclidean space, and use it to derive a simple closed-form expression for ensemble-averaged correlations. Power-law scaling at short distance follows almost immediately. Similar techniques provide easy constructions of objects with fractional Brownian short-distance behavior for phase screens and other applications.

  4. Pegylated liposomal doxorubicin and gemcitabine in the front-line treatment of recurrent/metastatic breast cancer: a multicentre phase II study.

    PubMed

    Adamo, V; Lorusso, V; Rossello, R; Adamo, B; Ferraro, G; Lorusso, D; Condemi, G; Priolo, D; Di Lullo, L; Paglia, A; Pisconti, S; Scambia, G; Ferrandina, G

    2008-06-17

    This multicentre phase II study was aimed at investigating the activity and safety of pegylated liposomal doxorubicin (PLD) and gemcitabine (GEM) as front-line therapy in a large series of chemotherapy-naïve recurrent/metastatic breast cancer patients. From June 2003 to December 2006, a total of 71 recurrent/metastatic breast cancer patients were enrolled. Median age was 63 years (range=37-79), and 31 patients (43.7%) were > or =65 years old. Patients received PLD, 25 mg m(-2), day 1, followed by GEM, 800 mg m(-2), days 1 and 8, q21. Response was evaluable in 64 cases. Eight complete (12.5%) and 17 partial responses (26.6%) were registered, with an overall response rate of 39.1%. Thirty patients (46.9%) experienced stable disease, with an overall clinical benefit of 85.9%. Median time to progression (TTP) was 11 months, whereas median overall survival (OS) was not reached. The rate of 1- and 2-year OS was 79 and 61%, respectively. A total of 443 courses were evaluable for toxicity: grade 3 and 4 neutropaenia affected 14 patients (20.3%) and 3 patients (4.3%), respectively. Grade 3 and 4 palmar-plantar erythrodysesthesia syndrome was documented in five cases (7.2%) and one case (1.4%), whereas grade 3 and 4 mucositis occurred in six cases (8.7%) and two cases (2.9%), respectively. Grade 2 cardiac toxicity was observed in only one case. Interestingly enough, there was no difference in the percentage and severity of either haematological or non-haematological toxicity according to the age of the patients (<65 vs > or =65 years). We confirmed in a large, very homogenous study sample of chemotherapy-naïve recurrent/metastatic breast cancer patients the efficacy and safety of PLD/GEM combination, providing response rates, median TTP and OS values comparable with those achieved with more toxic combinations.

  5. A multi-centre phase IIa clinical study of predictive testing for preeclampsia: improved pregnancy outcomes via early detection (IMPROvED)

    PubMed Central

    2013-01-01

    Background 5% of first time pregnancies are complicated by pre-eclampsia, the leading cause of maternal death in Europe. No clinically useful screening test exists; consequentially clinicians are unable to offer targeted surveillance or preventative strategies. IMPROvED Consortium members have pioneered a personalised medicine approach to identifying blood-borne biomarkers through recent technological advancements, involving mapping of the blood metabolome and proteome. The key objective is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for pre-eclampsia. Methods/Design We report the design of a multicentre, phase IIa clinical study aiming to recruit 5000 low risk primiparous women to assess and refine innovative prototype tests based on emerging metabolomic and proteomic technologies. Participation involves maternal phlebotomy at 15 and 20 weeks’ gestation, with optional testing and biobanking at 11 and 34 weeks. Blood samples will be analysed using two innovative, proprietary prototype platforms; one metabolomic based and one proteomic based, both of which outperform current biomarker based screening tests at comparable gestations. Analytical and clinical data will be collated and analysed via the Copenhagen Trials Unit. Discussion The IMPROvED study is expected to refine proteomic and metabolomic panels, combined with clinical parameters, and evaluate clinical applicability as an early pregnancy predictive test for pre-eclampsia. If ‘at risk’ patients can be identified, this will allow stratified care with personalised fetal and maternal surveillance, early diagnosis, timely intervention, and significant health economic savings. The IMPROvED biobank will be accessible to the European scientific community for high quality research into the cause and prevention of adverse pregnancy outcome. Trial registration Trial registration number NCT01891240 The IMPROvED project is funded by the seventh framework

  6. Evaluations of phase-only double random phase encoding based on key-space analysis.

    PubMed

    Nakano, Kazuya; Takeda, Masafumi; Suzuki, Hiroyuki; Yamaguchi, Masahiro

    2013-02-20

    Although initial research shows that double-random phase encoding (DRPE) is vulnerable to known-plaintext attacks that use phase retrieval algorithms, subsequent research has shown that phase-only DRPE, in which the Fourier amplitude component of an image encrypted with classical DRPE remains constant, is resistant to attacks that apply phase retrieval algorithms. Herein, we numerically analyze the key-space of DRPE and investigate the distribution property of decryption keys for classical and phase-only DRPE. We determine the difference in the distribution property of successful decryption keys for these DRPE techniques from the numerical analysis results and then discuss the security offered by them.

  7. Phase Transitions and Equilibrium Measures in Random Matrix Models

    NASA Astrophysics Data System (ADS)

    Martínez-Finkelshtein, A.; Orive, R.; Rakhmanov, E. A.

    2015-02-01

    The paper is devoted to a study of phase transitions in the Hermitian random matrix models with a polynomial potential. In an alternative equivalent language, we study families of equilibrium measures on the real line in a polynomial external field. The total mass of the measure is considered as the main parameter, which may be interpreted also either as temperature or time. Our main tools are differentiation formulas with respect to the parameters of the problem, and a representation of the equilibrium potential in terms of a hyperelliptic integral. Using this combination we introduce and investigate a dynamical system (system of ODEs) describing the evolution of families of equilibrium measures. On this basis we are able to systematically derive a number of new results on phase transitions, such as the local behavior of the system at all kinds of phase transitions, as well as to review a number of known ones.

  8. Cascading dynamics on random networks: crossover in phase transition.

    PubMed

    Liu, Run-Ran; Wang, Wen-Xu; Lai, Ying-Cheng; Wang, Bing-Hong

    2012-02-01

    In a complex network, random initial attacks or failures can trigger subsequent failures in a cascading manner, which is effectively a phase transition. Recent works have demonstrated that in networks with interdependent links so that the failure of one node causes the immediate failures of all nodes connected to it by such links, both first- and second-order phase transitions can arise. Moreover, there is a crossover between the two types of transitions at a critical system-parameter value. We demonstrate that these phenomena can occur in the more general setting where no interdependent links are present. A heuristic theory is derived to estimate the crossover and phase-transition points, and a remarkable agreement with numerics is obtained.

  9. Cascading dynamics on random networks: Crossover in phase transition

    NASA Astrophysics Data System (ADS)

    Liu, Run-Ran; Wang, Wen-Xu; Lai, Ying-Cheng; Wang, Bing-Hong

    2012-02-01

    In a complex network, random initial attacks or failures can trigger subsequent failures in a cascading manner, which is effectively a phase transition. Recent works have demonstrated that in networks with interdependent links so that the failure of one node causes the immediate failures of all nodes connected to it by such links, both first- and second-order phase transitions can arise. Moreover, there is a crossover between the two types of transitions at a critical system-parameter value. We demonstrate that these phenomena can occur in the more general setting where no interdependent links are present. A heuristic theory is derived to estimate the crossover and phase-transition points, and a remarkable agreement with numerics is obtained.

  10. Drugs, Women and Violence in the Americas: U.S. Results of a Multi-Centric Pilot Project (Phase 1)

    PubMed Central

    González-Guarda, Rosa María; Peragallo, Nilda; Lynch, Ami; Nemes, Susanna

    2011-01-01

    Objectives To explore the collective and individual experiences that Latin American females in the U. S. have with substance abuse, violence and risky sexual behaviors. Methods This study was conducted in two phases that were carried out from July 2006 to June 2007 in south Florida. This paper covers Phase 1. In Phase 1, focus groups were conducted among 93 women in English, Spanish and Portuguese. Through content analyses of the focus group transcriptions, major themes were identified. Results Participants identified substance abuse, violence and risky sexual behaviors as closely related problems of great concern in Latina women in the U.S. Three important themes emerged from the focus groups. These included “Living in the US and the Devaluing of Latino Culture,” the “Vicious Cycle of Abuse” and “Breaking the Silence”. Conclusions The results from this study suggest that substance abuse, violence and HIV should be addressed in an integrative and comprehensive manner. Recommendations for the development of policies, programs and services addressing substance abuse, violence and risk for HIV among Latinos are provided. PMID:21593995

  11. Pre-Study protocol MagPEP: a multicentre randomized controlled trial of magnesium sulphate in the prevention of post-ERCP pancreatitis

    PubMed Central

    2013-01-01

    Background Acute pancreatitis is the most common complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). In spite of continuing research, no pharmacologic agent capable of effectively reducing the incidence of ERCP-induced pancreatitis has found its way into clinical practise. A number of experimental studies suggest that intrapancreatic calcium concentrations play an important role in the initiation of intracellular protease activation, an initiating step in the course of acute pancreatitis. Magnesium can act as a calcium-antagonist and counteracts effects in calcium signalling. It can thereby attenuate the intracellular activation of proteolytic digestive enzymes in the pancreas and reduces the severity of experimental pancreatitis when administered either intravenously or as a food supplement. Methods We designed a randomized, double-blind, placebo-controlled phase III study to test whether the administration of intravenous magnesium sulphate before and after ERCP reduces the incidence and the severity of post-ERCP pancreatitis. A total of 502 adult patients with a medical indication for ERCP are to be randomized to receive either 4930 mg magnesium sulphate (= 20 mmol magnesium) or placebo 60 min before and 6 hours after ERCP. The incidence of clinical post-ERCP pancreatitis, hyperlipasemia, pain levels, use of analgetics and length of hospital stay will be evaluated. Conclusions If magnesium sulphate is found to be effective in preventing post-ERCP pancreatitis, this inexpensive agent with limited adverse effects could be used as a routine pharmacological prophylaxis. Trial registration Current Controlled Trials ISRCTN46556454 PMID:23320650

  12. Phase shifting interferometry from two normalized interferograms with random tilt phase-shift.

    PubMed

    Liu, Fengwei; Wu, Yongqian; Wu, Fan

    2015-07-27

    We propose a novel phase shifting interferometry from two normalized interferograms with random tilt phase-shift. The determination of tilt phase-shift is performed by extracting the tilted phase-shift plane from the phase difference of two normalized interferograms, and with the calculated tilt phase-shift value the phase distribution can be retrieved from the two normalized frames. By analyzing the distribution of phase difference and utilizing special points fitting method, the tilted phase-shift plane is extracted in three different cases, which relate to different magnitudes of tilts. Proposed method has been applied to simulations and experiments successfully and the satisfactory results manifest that proposed method is of high accuracy and high speed compared with the three step iterative method. Additionally, both open and closed fringe can be analyzed with proposed method. What's more, it cannot only eliminate the small tilt-shift error caused by slight vibration in phase-shifting interferometry, but also detect the large tilt phase-shift in phase-tilting interferometry. Thus, it will relaxes the requirements on the accuracy of phase shifter, and the costly phase shifter may even be useless by applying proposed method in high amplitude vibrated circumstance to achieve high-precision analysis.

  13. Doorway states in the random-phase approximation

    SciTech Connect

    De Pace, A.; Molinari, A.; Weidenmüller, H.A.

    2014-12-15

    By coupling a doorway state to a sea of random background states, we develop the theory of doorway states in the framework of the random-phase approximation (RPA). Because of the symmetry of the RPA equations, that theory is radically different from the standard description of doorway states in the shell model. We derive the Pastur equation in the limit of large matrix dimension and show that the results agree with those of matrix diagonalization in large spaces. The complexity of the Pastur equation does not allow for an analytical approach that would approximately describe the doorway state. Our numerical results display unexpected features: The coupling of the doorway state with states of opposite energy leads to strong mutual attraction.

  14. Finite amplitude method for the quasiparticle random-phase approximation

    SciTech Connect

    Avogadro, Paolo; Nakatsukasa, Takashi

    2011-07-15

    We present the finite amplitude method (FAM), originally proposed in Ref. [17], for superfluid systems. A Hartree-Fock-Bogoliubov code may be transformed into a code of the quasiparticle-random-phase approximation (QRPA) with simple modifications. This technique has advantages over the conventional QRPA calculations, such as coding feasibility and computational cost. We perform the fully self-consistent linear-response calculation for the spherical neutron-rich nucleus {sup 174}Sn, modifying the hfbrad code, to demonstrate the accuracy, feasibility, and usefulness of the FAM.

  15. Qubit Metrology of Ultralow Phase Noise Using Randomized Benchmarking

    NASA Astrophysics Data System (ADS)

    O'Malley, P. J. J.; Kelly, J.; Barends, R.; Campbell, B.; Chen, Y.; Chen, Z.; Chiaro, B.; Dunsworth, A.; Fowler, A. G.; Hoi, I.-C.; Jeffrey, E.; Megrant, A.; Mutus, J.; Neill, C.; Quintana, C.; Roushan, P.; Sank, D.; Vainsencher, A.; Wenner, J.; White, T. C.; Korotkov, A. N.; Cleland, A. N.; Martinis, John M.

    2015-04-01

    A precise measurement of dephasing over a range of time scales is critical for improving quantum gates beyond the error correction threshold. We present a metrological tool based on randomized benchmarking capable of greatly increasing the precision of Ramsey and spin-echo sequences by the repeated but incoherent addition of phase noise. We find our superconducting-quantum-interference-device-based qubit is not limited by 1 /f flux noise at short time scales but instead observe a telegraph noise mechanism that is not amenable to study with standard measurement techniques.

  16. Fully phase image encryption using double random-structured phase masks in gyrator domain.

    PubMed

    Singh, Hukum; Yadav, A K; Vashisth, Sunanda; Singh, Kehar

    2014-10-01

    We propose a method for fully phase image encryption based on double random-structured phase mask encoding in the gyrator transform (GT) domain. The security of the system is strengthened by parameters used in the construction of a structured phase mask (SPM) based on a devil's vortex Fresnel lens (DVFL). The input image is recovered using the correct parameters of the SPMs, transform orders of the GT, and conjugate of the random phase masks. The use of a DVFL-based SPM enhances security by increasing the key space for encryption, and also overcomes the problem of axis alignment associated with an optical setup. The proposed scheme can also be implemented optically. The computed values of mean squared error between the retrieved and the original image show the efficacy of the proposed scheme. We have also investigated the scheme's sensitivity to the encryption parameters, and robustness against occlusion and multiplicative Gaussian noise attacks.

  17. Range sidelobe reduction for the random binary phase codes

    NASA Astrophysics Data System (ADS)

    Gu, Hong; Liu, Guosui; Sun, Guangmin; Li, Xi; Su, Weimin

    1997-06-01

    Based on the statistics theory and the pulse compression technique, a statistical method of reducing the range sidelobe (RSL) of the random binary phase codes (RBPC) is presented, which is different from those of decreasing the RSL of the pseudorandom binary phase codes. The theoretical analysis and computer simulation show that it is possible to suppress the peak RSL to lower than -30 dB, which can effectively guarantee the RBPC radar with good electronic counter-countermeasures feature applicable. Additionally, owing to the Doppler of the target, the maximum loss of the ratio of the mainlobe and sidelobe (MSR) is also discussed. In the meantime, the approach to realization of the RSL reduction with digital signal processors is given.

  18. Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine tumours: a multicentre, single-group, phase 2 study

    PubMed Central

    Phan, Alexandria T; Halperin, Daniel M; Chan, Jennifer A; Fogelman, David R; Hess, Kenneth R; Malinowski, Paige; Regan, Eileen; Ng, Chaan S; Yao, James C; Kulke, Matthew H

    2015-01-01

    Summary Background Treatment options for advanced, well-differentiated neuroendocrine tumours (NETs) remain scarce. Pazopanib is an orally bioavailable, small molecule, multitargeted kinase inhibitor that inhibits VEGF receptors 1, 2, and 3. We did a study of the efficacy of pazopanib with depot octreotide in patients with advanced NETs. Methods We did a parallel cohort study of patients with metastatic or locally advanced grade 1–2 carcinoid tumours or pancreatic NETs, by use of a single-group, two-stage design. Patients received pazopanib 800 mg orally once per day and octreotide at their preprotocol dosage. The primary endpoint was the proportion of patients achieving an objective response, as assessed by investigators, by intention-to-treat analysis. This study is registered with ClinicalTrials.gov, identifier NCT00454363, and was completed in March, 2014. Findings Between April 12, 2007, and July 2, 2009, we enrolled 52 patients, including 32 individuals with pancreatic NETs and 20 individuals with carcinoid tumours. Seven (21.9%, 95% CI 11.0–38.8) of 32 patients with pancreatic NETs achieved an objective response. We detected no responses in the first stage of the cohort with carcinoid tumours, and we terminated accrual at 20 patients. Toxic effects included one patient with grade 4 hypertriglyceridaemia and one with grade 4 thrombosis, with the most common grade three events being aminotransferase increases and neutropenia, each of which happened in 3 patients. In all 52 patients, the most frequently observed toxic effects were fatigue (39 [75%]), nausea (33 [63%]), diarrhoea (33 [63%]), and hypertension (28 [54%]). Interpretation Treatment with pazopanib is associated with tumour response for patients with pancreatic NETs, but not for carcinoid tumours; a randomised controlled phase 3 study to assess pazopanib in advanced pancreatic NETs is warranted. Funding US National Cancer Institute of the National Institutes of Health. PMID:25956795

  19. Glassy phases and driven response of the phase-field-crystal model with random pinning.

    PubMed

    Granato, E; Ramos, J A P; Achim, C V; Lehikoinen, J; Ying, S C; Ala-Nissila, T; Elder, K R

    2011-09-01

    We study the structural correlations and the nonlinear response to a driving force of a two-dimensional phase-field-crystal model with random pinning. The model provides an effective continuous description of lattice systems in the presence of disordered external pinning centers, allowing for both elastic and plastic deformations. We find that the phase-field crystal with disorder assumes an amorphous glassy ground state, with only short-ranged positional and orientational correlations, even in the limit of weak disorder. Under increasing driving force, the pinned amorphous-glass phase evolves into a moving plastic-flow phase and then, finally, a moving smectic phase. The transverse response of the moving smectic phase shows a vanishing transverse critical force for increasing system sizes.

  20. Nonergodic Phases in Strongly Disordered Random Regular Graphs.

    PubMed

    Altshuler, B L; Cuevas, E; Ioffe, L B; Kravtsov, V E

    2016-10-07

    We combine numerical diagonalization with semianalytical calculations to prove the existence of the intermediate nonergodic but delocalized phase in the Anderson model on disordered hierarchical lattices. We suggest a new generalized population dynamics that is able to detect the violation of ergodicity of the delocalized states within the Abou-Chakra, Anderson, and Thouless recursive scheme. This result is supplemented by statistics of random wave functions extracted from exact diagonalization of the Anderson model on ensemble of disordered random regular graphs (RRG) of N sites with the connectivity K=2. By extrapolation of the results of both approaches to N→∞ we obtain the fractal dimensions D_{1}(W) and D_{2}(W) as well as the population dynamics exponent D(W) with the accuracy sufficient to claim that they are nontrivial in the broad interval of disorder strength W_{E}10^{5} reveals a singularity in D_{1,2}(W) dependencies which provides clear evidence for the first order transition between the two delocalized phases on RRG at W_{E}≈10.0. We discuss the implications of these results for quantum and classical nonintegrable and many-body systems.

  1. Nonergodic Phases in Strongly Disordered Random Regular Graphs

    NASA Astrophysics Data System (ADS)

    Altshuler, B. L.; Cuevas, E.; Ioffe, L. B.; Kravtsov, V. E.

    2016-10-01

    We combine numerical diagonalization with semianalytical calculations to prove the existence of the intermediate nonergodic but delocalized phase in the Anderson model on disordered hierarchical lattices. We suggest a new generalized population dynamics that is able to detect the violation of ergodicity of the delocalized states within the Abou-Chakra, Anderson, and Thouless recursive scheme. This result is supplemented by statistics of random wave functions extracted from exact diagonalization of the Anderson model on ensemble of disordered random regular graphs (RRG) of N sites with the connectivity K =2 . By extrapolation of the results of both approaches to N →∞ we obtain the fractal dimensions D1(W ) and D2(W ) as well as the population dynamics exponent D (W ) with the accuracy sufficient to claim that they are nontrivial in the broad interval of disorder strength WE1 05 reveals a singularity in D1 ,2(W ) dependencies which provides clear evidence for the first order transition between the two delocalized phases on RRG at WE≈10.0 . We discuss the implications of these results for quantum and classical nonintegrable and many-body systems.

  2. The peculiar phase structure of random graph bisection

    SciTech Connect

    Percus, Allon G; Istrate, Gabriel; Goncalves, Bruno T; Sumi, Robert Z

    2008-01-01

    The mincut graph bisection problem involves partitioning the n vertices of a graph into disjoint subsets, each containing exactly n/2 vertices, while minimizing the number of 'cut' edges with an endpoint in each subset. When considered over sparse random graphs, the phase structure of the graph bisection problem displays certain familiar properties, but also some surprises. It is known that when the mean degree is below the critical value of 2 log 2, the cutsize is zero with high probability. We study how the minimum cutsize increases with mean degree above this critical threshold, finding a new analytical upper bound that improves considerably upon previous bounds. Combined with recent results on expander graphs, our bound suggests the unusual scenario that random graph bisection is replica symmetric up to and beyond the critical threshold, with a replica symmetry breaking transition possibly taking place above the threshold. An intriguing algorithmic consequence is that although the problem is NP-hard, we can find near-optimal cutsizes (whose ratio to the optimal value approaches 1 asymptotically) in polynomial time for typical instances near the phase transition.

  3. Safety and efficacy of oral febuxostat for treatment of HLA-B*5801-negative gout: a randomized, open-label, multicentre, allopurinol-controlled study

    PubMed Central

    Yu, K-H; Lai, J-H; Hsu, P-N; Chen, D-Y; Chen, C-J; Lin, H-Y

    2016-01-01

    Objectives: This phase IIIB study compared the efficacy and safety of febuxostat and allopurinol in gout patients with or without tophi who were HLA-B*5801 negative. Method: Eligible patients were randomized to a febuxostat group (80 mg QD) or an allopurinol group (300 mg QD). Following an initial 2-week washout period, over the next 12 weeks we made five measurements of serum urate levels along with assessments of adverse events (AEs). Results: Forty-three out of 152 screened subjects (28.3%) were ineligible either because of the presence of the HLA-B*5801 allele or for various other reasons. The febuxostat group (n = 54) and the allopurinol group (n = 55) had no significant differences in demographic or baseline characteristics. From week 2 to week 12, the febuxostat group had a significantly lower serum urate level than the allopurinol group (p ≤ 0.001 for all comparisons) and significantly more patients with serum urate levels less than 6.0 mg/dL. The serum urate levels of the febuxostat group declined by more than 40% from week 2 to week 12 and this decrease was greater than that in the allopurinol group (~30%). The two groups were similar in terms of AEs. Conclusions: Febuxostat was more effective than allopurinol in reducing the serum urate levels of Han Chinese patients with gout or tophaceous gout who were HLA-B*5801 negative, without causing any serious skin reactions. Febuxostat should be considered for treatment of Han Chinese patients with gout who are HLA-B*5801 negative. PMID:26771445

  4. Safety of intramuscular influenza vaccine in patients receiving oral anticoagulation therapy: a single blinded multi-centre randomized controlled clinical trial

    PubMed Central

    Casajuana, Josep; Iglesias, Begoña; Fàbregas, Mireia; Fina, Francesc; Vallès, Joan-Antoni; Aragonès, Rosa; Benítez, Mència; Zabaleta, Edurne

    2008-01-01

    Background Influenza vaccines are recommended for administration by the intramuscular route. However, many physicians use the subcutaneous route for patients receiving an oral anticoagulant because this route is thought to induce fewer hemorrhagic side effects. Our aim is to assess the safety of intramuscular administration of influenza vaccine in patients on oral anticoagulation therapy. Methods Design: Randomised, controlled, single blinded, multi-centre clinical trial. Setting: 4 primary care practices in Barcelona, Spain. Participants: 229 patients on oral anticoagulation therapy eligible for influenza vaccine during the 2003–2004 season. Interventions: intramuscular administration of influenza vaccine in the experimental group (129 patients) compared to subcutaneous administration in the control group (100 patients). Primary outcome: change in the circumference of the arm at the site of injection at 24 hours. Secondary outcomes: appearance of local reactions and pain at 24 hours and at 10 days; change in INR (International Normalized Ratio) at 24 hours and at 10 days. Analysis was by intention to treat using the 95% confidence intervals of the proportions or mean differences. Results Baseline variables in the two groups were similar. No major side effects or major haemorrhage during the follow-up period were reported. No significant differences were observed in the primary outcome between the two groups. The appearance of local adverse reactions was more frequent in the subcutaneous administration group (37,4% vs. 17,4%, 95% confidence interval of the difference 8,2% to 31,8%). Conclusion This study shows that the intramuscular administration route of influenza vaccine in patients on anticoagulant therapy does not have more side effects than the subcutaneous administration route. Registration number NCT00137579 at clinicaltrials.gov PMID:18507871

  5. Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: A multicentric phase II study

    SciTech Connect

    Valentini, Vincenzo . E-mail: vvalentini@rm.unicatt.it; Morganti, Alessio G.; Gambacorta, M. Antonietta; Mohiuddin, Mohammed; Doglietto, G. Battista; Coco, Claudio; De Paoli, Antonino; Rossi, Carlo; Di Russo, Annamaria; Valvo, Francesca; Bolzicco, Giampaolo; Dalla Palma, Maurizio

    2006-03-15

    Purpose: The combination of irradiation and total mesorectal excision for rectal carcinoma has significantly lowered the incidence of local recurrence. However, a new problem is represented by the patient with locally recurrent cancer who has received previous irradiation to the pelvis. In these patients, local recurrence is very often not easily resectable and reirradiation is expected to be associated with a high risk of late toxicity. The aim of this multicenter phase II study is to evaluate the response rate, resectability rate, local control, and treatment-related toxicity of preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis. Methods and Materials: Patients with histologically proven pelvic recurrence of rectal carcinoma, with the absence of extrapelvic disease or bony involvement and previous pelvic irradiation with doses {<=}55 Gy; age {>=}18 years; performance status (PS) (Karnofsky) {>=}60, and who gave institutional review board-approved written informed consent were treated by preoperative chemoradiation. Radiotherapy was delivered to a planning target volume (PTV2) including the gross tumor volume (GTV) plus a 4-cm margin, with a dose of 30 Gy (1.2 Gy twice daily with a minimum 6-h interval). A boost was delivered, with the same fractionation schedule, to a PTV1 including the GTV plus a 2-cm margin (10.8 Gy). During the radiation treatment, concurrent chemotherapy was delivered (5-fluorouracil, protracted intravenous infusion, 225 mg/m{sup 2}/day, 7 days per week). Four to 6 weeks after the end of chemoradiation, patients were evaluated for tumor resectability, and, when feasible, surgical resection of recurrence was performed between 6-8 weeks from the end of chemoradiation. Adjuvant chemotherapy was prescribed to all patients, using Raltitrexed, 3 mg/square meter (sm), every 3 weeks, for a total of 5 cycles. Patients were staged using the computed tomography (CT)-based F

  6. Testing a random phase approximation for bounded turbulent flow.

    PubMed

    Ulitsky, M; Clark, T; Turner, L

    1999-05-01

    Tractable implementation of a spectral closure requires that the modal representation of the energy satisfy a restricted random phase approximation (RRPA). This condition is exactly satisfied when the statistical system is homogeneous and the basis functions are Fourier modes. In this case, the ensemble average of the spectral covariance diagonalizes, i.e., =delta(k(1)+k(2)), where c(k,t) is a Fourier coefficient in a Galerkin representation of the velocity field. However, for inhomogeneous statistical systems in which the Fourier system is inappropriate, the RRPA requires validation. We use direct numerical simulations (DNSs) of the Navier-Stokes and truncated Euler equations to test the degree to which the RRPA is satisfied when applied to a recent representation due to Turner (LANL Unclassified Report No. LA-UR-96-3257) of a bounded turbulent rectangular channel flow with free slip, stress free walls. It is shown that a complete test of the RRPA for a fully inhomogeneous DNS with N3 grid points actually requires N3+1 members in the ensemble. The "randomness" of the phase can be characterized by a probability density function (PDF) of the modulus of the normalized spectral covariance. Results reveal that for both the Navier-Stokes and Euler systems the PDF does not change in time as the turbulence decays, and that the PDF for the Euler system is virtually identical to the one produced from an ensemble of random fields. This result is consistent with the equipartition of energy for the Euler system, in which the RRPA becomes an exact result rather than an approximation as the number of realizations approaches N3+1. The slight differences observed between the PDF produced from the random fields and the one from the Navier-Stokes system are thus shown to be entirely a result of the presence of a finite viscosity. It is also shown that there is great variation between statistics computed over the ensemble and those for a single

  7. Testing a random phase approximation for bounded turbulent flow

    NASA Astrophysics Data System (ADS)

    Ulitsky, Mark; Clark, Tim; Turner, Leaf

    1999-05-01

    Tractable implementation of a spectral closure requires that the modal representation of the energy satisfy a restricted random phase approximation (RRPA). This condition is exactly satisfied when the statistical system is homogeneous and the basis functions are Fourier modes. In this case, the ensemble average of the spectral covariance diagonalizes, i.e., =δ(k1+k2), where c(k,t) is a Fourier coefficient in a Galerkin representation of the velocity field. However, for inhomogeneous statistical systems in which the Fourier system is inappropriate, the RRPA requires validation. We use direct numerical simulations (DNSs) of the Navier-Stokes and truncated Euler equations to test the degree to which the RRPA is satisfied when applied to a recent representation due to Turner (LANL Unclassified Report No. LA-UR-96-3257) of a bounded turbulent rectangular channel flow with free slip, stress free walls. It is shown that a complete test of the RRPA for a fully inhomogeneous DNS with N3 grid points actually requires N3+1 members in the ensemble. The ``randomness'' of the phase can be characterized by a probability density function (PDF) of the modulus of the normalized spectral covariance. Results reveal that for both the Navier-Stokes and Euler systems the PDF does not change in time as the turbulence decays, and that the PDF for the Euler system is virtually identical to the one produced from an ensemble of random fields. This result is consistent with the equipartition of energy for the Euler system, in which the RRPA becomes an exact result rather than an approximation as the number of realizations approaches N3+1. The slight differences observed between the PDF produced from the random fields and the one from the Navier-Stokes system are thus shown to be entirely a result of the presence of a finite viscosity. It is also shown that there is great variation between statistics computed over the ensemble and those for a single realization.

  8. Analytic Interatomic Forces in the Random Phase Approximation

    NASA Astrophysics Data System (ADS)

    Ramberger, Benjamin; Schäfer, Tobias; Kresse, Georg

    2017-03-01

    We discuss that in the random phase approximation (RPA) the first derivative of the energy with respect to the Green's function is the self-energy in the G W approximation. This relationship allows us to derive compact equations for the RPA interatomic forces. We also show that position dependent overlap operators are elegantly incorporated in the present framework. The RPA force equations have been implemented in the projector augmented wave formalism, and we present illustrative applications, including ab initio molecular dynamics simulations, the calculation of phonon dispersion relations for diamond and graphite, as well as structural relaxations for water on boron nitride. The present derivation establishes a concise framework for forces within perturbative approaches and is also applicable to more involved approximations for the correlation energy.

  9. Surface wake in the random-phase approximation

    SciTech Connect

    Garcia de Abajo, F.J. ); Echenique, P.M. )

    1993-11-01

    The scalar-electric-potential distribution set up by an ion traveling in the vicinity of a plane solid-vacuum interface, that is, the surface-wake potential, is investigated with the specular-reflection model to describe the response of the surface and with the random-phase approximation for the dielectric function of the bulk material. This permits us to address the study of the low-velocity surface wake: the static potential is found to have a dip at the position of the ion; that dip is shifted towards the direction opposite to the velocity vector for velocities smaller than the threshold of creation of plasmons ([approx]1.3[ital v][sub [ital F

  10. Limitations of the number self-consistent random phase approximation

    NASA Astrophysics Data System (ADS)

    Mariano, Alejandro; Hirsch, Jorge G.

    2000-05-01

    The quasiparticle random phase approximation (QRPA) equations are solved taking into account the Pauli principle at the expectation value level, and allowing changes in the mean field occupation numbers to minimize the energy while having the correct number of particles in the correlated vacuum. The study of Fermi pn excitations in 76Ge using a realistic Hilbert space shows that the pairing energy gaps in the modified mean field are diminished up to one half of the experimental value when strong proton-neutron correlations are present. Additionally, the Ikeda sum rule for Fermi transitions is violated due to the lack of scattering terms in the phonon operators. These results call for a critical revision of the double β decay half-lives estimated using the QRPA extensions when standard QRPA calculations collapse.

  11. Exploring the Random Phase Approximately for materials chemistry and physics

    SciTech Connect

    Ruzsinsky, Adrienn

    2015-03-23

    This proposal focuses on improved accuracy for the delicate energy differences of interest in materials chemistry with the fully nonlocal random phase approximation (RPA) in a density functional context. Could RPA or RPA-like approaches become standard methods of first-principles electronic-structure calculation for atoms, molecules, solids, surfaces, and nano-structures? Direct RPA includes the full exact exchange energy and a nonlocal correlation energy from the occupied and unoccupied Kohn-Sham orbitals and orbital energies, with an approximate but universal description of long-range van der Waals attraction. RPA also improves upon simple pair-wise interaction potentials or vdW density functional theory. This improvement is essential to capture accurate energy differences in metals and different phases of semiconductors. The applications in this proposal are challenges for the simpler approximations of Kohn-Sham density functional theory, which are part of the current “standard model” for quantum chemistry and condensed matter physics. Within this project we already applied RPA on different structural phase transitions on semiconductors, metals and molecules. Although RPA predicts accurate structural parameters, RPA has proven not equally accurate in all kinds of structural phase transitions. Therefore a correction to RPA can be necessary in many cases. We are currently implementing and testing a nonempirical, spatially nonlocal, frequency-dependent model for the exchange-correlation kernel in the adiabatic-connection fluctuation-dissipation context. This kernel predicts a nearly-exact correlation energy for the electron gas of uniform density. If RPA or RPA-like approaches prove to be reliably accurate, then expected increases in computer power may make them standard in the electronic-structure calculations of the future.

  12. Coulomb glass in the restricted random phase approximation

    NASA Astrophysics Data System (ADS)

    Basylko, S. A.; Onischouk, V. A.; Rosengren, A.

    2002-06-01

    A three-dimensional model of N/2 electrons localized on N randomly distributed donor sites of density n and with the acceptor charge uniformly smeared on these sites, - e/2 on each, has been considered in the restricted random phase approximation (RRPA) which uses the set of 3 N Fourier components of the local charge density as the independent collective variables. The energy e( T) per site and the density of one-site excitation energy (DOSE) g( ɛ) are shown to be, respectively, in excellent quantitative and in good qualitative agreement with the Monte Carlo simulation data in the whole temperature region 0.1< T<100, where these simulations were performed ( e2n1/3/ kB being the temperature scale). The pair correlator for the one-site energies g( ɛ,± ɛ, r) is found to have the slow decoupling law ˜(±1/ r) for T≲1 and r≫ rd ( rd, Debye screening radius). The status of the commonly accepted asymptotic g( ɛ)˜( ɛ- μ) d-1 ( d and μ being, respectively, the spatial dimension and the Fermi energy) is discussed. The “deduction” of this asymptotic is shown to be based on the strong and questionable conjecture about decoupling of correlations between one-site excitation energies in the vicinity of μ.

  13. Optical double image security using random phase fractional Fourier domain encoding and phase-retrieval algorithm

    NASA Astrophysics Data System (ADS)

    Rajput, Sudheesh K.; Nishchal, Naveen K.

    2017-04-01

    We propose a novel security scheme based on the double random phase fractional domain encoding (DRPE) and modified Gerchberg-Saxton (G-S) phase retrieval algorithm for securing two images simultaneously. Any one of the images to be encrypted is converted into a phase-only image using modified G-S algorithm and this function is used as a key for encrypting another image. The original images are retrieved employing the concept of known-plaintext attack and following the DRPE decryption steps with all correct keys. The proposed scheme is also used for encryption of two color images with the help of convolution theorem and phase-truncated fractional Fourier transform. With some modification, the scheme is extended for simultaneous encryption of gray-scale and color images. As a proof-of-concept, simulation results have been presented for securing two gray-scale images, two color images, and simultaneous gray-scale and color images.

  14. Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (II) Physiological and Symptomatic Responses of Early-Postmenopausal Women to Standardized doses of Maca in Double Blind, Randomized, Placebo-Controlled, Multi-Centre Clinical Study.

    PubMed

    Meissner, H O; Mscisz, A; Reich-Bilinska, H; Kapczynski, W; Mrozikiewicz, P; Bobkiewicz-Kozlowska, T; Kedzia, B; Lowicka, A; Barchia, I

    2006-12-01

    This was a double-blind, randomized, placebo-corrected, outpatient, multi-centre (five sites) clinical study, in which a total of 168 Caucasian early-postmenopausal women volunteers (age>49 years) participated after fulfilling the criteria: follicle stimulating hormone (FSH) >30 IU/ml and estrogen (E2) <40 pg/ml levels at admission. They were randomly allocated to Placebo and Pre-Gelatinized Organic Maca (Maca-GO) treatment, according to different monthly treatment sequences scheduled for each site. Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day) during three (Trial I; n=102) or four (Trial II; n=66) months study periods. At the baseline and follow- up monthly intervals, blood levels of FSH, E2, progesterone (PRG) and lutinizing hormone (LH), as well as serum cholesterol (CHOL), triglycerides (TRG), high- and low density lipoproteins (HDL and LDL) were measured. Menopausal symptoms were assessed according to Greene's Score (GMS) and Kupperman's Index (KMI). Data were analyzed using multivariate technique on blocs of monthly results in one model and Maca versus Placebo contrast in another model. A total of 124 women concluded the study. Maca-GO significantly stimulated production of E2 (P<0.001) with a simultaneous suppression (P<0.05) of blood FSH, increase (P<0.05) in HDL. Maca-GO significantly reduced both frequency and severity of individual menopausal symptoms (hot flushes and night sweating in particular) resulting in significant (P<0.001) alleviation of KMI (from 22 to 10), thus, offering an attractive non-hormonal addition to the choices available to early-postmenopausal women in the form of a natural plant alternative to Hormone Replacement Therapy (HRT) - hence, reducing dependence on hormone therapy programs.

  15. Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: Updated results of a randomized multicentric trial in advanced head-and-neck cancer

    SciTech Connect

    Semrau, Robert . E-mail: Robert.Semrau@uk-koeln.de; Mueller, Rolf-Peter; Stuetzer, Hartmut; Staar, Susanne; Schroeder, Ursula; Guntinas-Lichius, Orlando; Kocher, Martin; Eich, Hans Theodor; Dietz, Andreas; Flentje, Michael; Rudat, Volker; Volling, Peter; Schroeder, Michael; Eckel, Hans Edmund

    2006-04-01

    Purpose: To prove an expected benefit of concurrent radiochemotherapy (RCT), a two-arm randomized multicentric study was performed. In a subgroup analysis the influence of pretherapeutical hemoglobin level (p-Hb) on survival under locoregional control (SLC) was tested. Patients and Methods: The study included primarily untreated Stage III/IV (International Union Against Cancer [UICC]) oropharyngeal and hypopharyngeal carcinomas. Patients were randomized to receive either hyperfractionated (hf) and accelerated (acc) RCT with two cycles 5-fluorouracil (600 mg/m{sup 2}/day) and carboplatin (70 mg/m{sup 2}/day) on Days 1-5 and 29-33 or hf-acc radiotherapy (RT) alone. Total RT dose in both arms was 69.9 Gy in 38 days in concomitant boost technique. Results: After a median follow-up time of 57 months, SLC is significantly better in RCT than in RT (p = 0.01), with median SLC of 17 months and 11 months, respectively. Also overall survival (OS) shows a benefit for RCT (p 0.016), with a median survival of 23 months for RCT and 16 months for RT. However, the benefit in SLC and OS is not seen in hypopharyngeal carcinomas. In a multivariate analysis of oropharyngeal cancer patients, p-Hb levels lower than 12.7 g/dL resulted in lower SLC compared with higher p-Hb levels up to 13.8 g/dL. P-Hb levels >13.8 g/dL did not further improve SLC. Conclusions: Hyperfractionated-accelerated RCT is superior to hf-acc RT in oropharyngeal carcinomas. P-Hb levels >13.8 g/dL do not further improve SLC.

  16. Predictors of haemoglobin levels and resistance to erythropoiesis-stimulating agents in patients treated with low-flux haemodialysis, haemofiltration and haemodiafiltration: results of a multicentre randomized and controlled trial

    PubMed Central

    Locatelli, Francesco; Altieri, Paolo; Andrulli, Simeone; Sau, Giovanna; Bolasco, Piergiorgio; Pedrini, Luciano A.; Basile, Carlo; David, Salvatore; Feriani, Mariano; Nebiolo, Pier Eugenio; Ferrara, Rocco; Casu, Domenica; Logias, Francesco; Tarchini, Renzo; Cadinu, Francesco; Passaghe, Mario; Fundoni, Gianfranco; Villa, Giuseppe; Di Iorio, Biagio Raffaele; Zoccali, Carmine

    2012-01-01

    Background Predictors of haemoglobin (Hb) levels and resistance to erythropoiesis-stimulating agents (ESAs) in dialysis patients have not yet been clearly defined. Some mainly uncontrolled studies suggest that online haemodiafiltration (HDF) may have a beneficial effect on Hb, whereas no data are available concerning online haemofiltration (HF). The objectives of this study were to evaluate the effects of convective treatments (CTs) on Hb levels and ESA resistance in comparison with low-flux haemodialysis (HD) and to evaluate the predictors of these outcomes. Methods Primary multivariate analysis was made of a pre-specified secondary outcome of a multicentre, open-label, randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: online pre-dilution HF (36 patients) or online pre-dilution HDF (40 patients). Results CTs did not affect Hb levels (P = 0.596) or ESA resistance (P = 0.984). Hb correlated with polycystic kidney disease (P = 0.001), C-reactive protein (P = 0.025), ferritin (P = 0.018), ESA dose (P < 0.001) and total cholesterol (P = 0.021). The participating centres were the main source of Hb variability (partial eta2 0.313, P < 0.001). ESA resistance directly correlated with serum ferritin (P = 0.030) and beta2 microglobulin (P = 0.065); participating centres were again a major source of variance (partial eta2 0.367, P < 0.001). Transferrin saturation did not predict either outcome variables (P = 0.277 and P = 0.170). Conclusions In comparison with low-flux HD, CTs did not significantly improve Hb levels or ESA resistance. The main sources of variability were participating centres, ESA dose and the underlying disease. PMID:22622452

  17. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial

    PubMed Central

    Kwon, Eugene D; Drake, Charles G; Scher, Howard I; Fizazi, Karim; Bossi, Alberto; van den Eertwegh, Alfons J M; Krainer, Michael; Houede, Nadine; Santos, Ricardo; Mahammedi, Hakim; Ng, Siobhan; Maio, Michele; Franke, Fabio A; Sundar, Santhanam; Agarwal, Neeraj; Bergman, Andries M; Ciuleanu, Tudor E; Korbenfeld, Ernesto; Sengeløv, Lisa; Hansen, Steinbjorn; Logothetis, Christopher; Beer, Tomasz M; McHenry, M Brent; Gagnier, Paul; Liu, David; Gerritsen, Winald R

    2015-01-01

    Summary Background Ipilimumab is a fully human monoclonal antibody that binds cytotoxic T-lymphocyte antigen 4 to enhance antitumour immunity. Our aim was to assess the use of ipilimumab after radiotherapy in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel chemotherapy. Methods We did a multicentre, randomised, double-blind, phase 3 trial in which men with at least one bone metastasis from castration-resistant prostate cancer that had progressed after docetaxel treatment were randomly assigned in a 1:1 ratio to receive bone-directed radiotherapy (8 Gy in one fraction) followed by either ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Non-progressing patients could continue to receive ipilimumab at 10 mg/kg or placebo as maintenance therapy every 3 months until disease progression, unacceptable toxic effect, or death. Patients were randomly assigned to either treatment group via a minimisation algorithm, and stratified by Eastern Cooperative Oncology Group performance status, alkaline phosphatase concentration, haemoglobin concentration, and investigator site. Patients and investigators were masked to treatment allocation. The primary endpoint was overall survival, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00861614. Findings From May 26, 2009, to Feb 15, 2012, 799 patients were randomly assigned (399 to ipilimumab and 400 to placebo), all of whom were included in the intention-to-treat analysis. Median overall survival was 11·2 months (95% CI 9·5–12·7) with ipilimumab and 10·0 months (8·3–11·0) with placebo (hazard ratio [HR] 0·85, 0·72–1·00; p=0·053). However, the assessment of the proportional hazards assumption showed that it was violated (p=0·0031). A piecewise hazard model showed that the HR changed over time: the HR for 0–5 months was 1·46 (95% CI 1·10–1·95), for 5–12 months was 0·65 (0·50–0·85), and

  18. Statistics of light deflection in a random two-phase medium

    SciTech Connect

    Sviridov, A P

    2007-01-31

    The statistics of the angles of light deflection during its propagation in a random two-phase medium with randomly oriented phase interfaces is considered within the framework of geometrical optics. The probabilities of finding a randomly walking photon in different phases of the inhomogeneous medium are calculated. Analytic expressions are obtained for the scattering phase function and the scattering phase matrix which relates the Stokes vector of the incident light beam with the Stokes vectors of deflected beams. (special issue devoted to multiple radiation scattering in random media)

  19. Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder.

    PubMed

    Moore, Nicholas; Verdoux, Hélène; Fantino, Bruno

    2005-05-01

    Pre-clinical studies, active-control clinical trials and meta-analyses indicate that escitalopram (S-citalopram) might be more effective than citalopram, the racemic mixture of S- and R-citalopram. The present study aimed to confirm the superior efficacy of escitalopram over citalopram. A double-blind, randomized clinical trial was performed in which general practitioners and psychiatrists compared fixed doses of escitalopram (20 mg/day) with citalopram (40 mg/day) over 8 weeks in outpatients with major depressive disorder (MDD) [baseline Montgomery-Asberg Depression Rating Scale (MADRS) score > or =30]. Primary efficacy parameter was change from baseline to last assessment in the MADRS total score. Out of 138 (aged 44.1+/-10.9 years; initial MADRS score 36.3+/-4.8) and 142 (aged 46.2+/-11.1 years; initial MADRS score 35.7+/-4.4) evaluable patients who were randomized to escitalopram and citalopram, respectively, six and 15 withdrew prematurely (P=0.05). The MADRS score decreased more in the escitalopram than in the citalopram arm (-22.4+/-12.9 versus -20.3+/-12.7; P<0.05). There were more treatment responders with escitalopram (76.1%) than with citalopram (61.3%, P<0.01). Adjusted remitter rates were 56.1% and 43.6%, respectively (P<0.05). Tolerability was similar in both groups. This randomized double-blind trial confirms that escitalopram has a superior effect to citalopram in MDD.

  20. Communication: Random phase approximation renormalized many-body perturbation theory

    SciTech Connect

    Bates, Jefferson E.; Furche, Filipp

    2013-11-07

    We derive a renormalized many-body perturbation theory (MBPT) starting from the random phase approximation (RPA). This RPA-renormalized perturbation theory extends the scope of single-reference MBPT methods to small-gap systems without significantly increasing the computational cost. The leading correction to RPA, termed the approximate exchange kernel (AXK), substantially improves upon RPA atomization energies and ionization potentials without affecting other properties such as barrier heights where RPA is already accurate. Thus, AXK is more balanced than second-order screened exchange [A. Grüneis et al., J. Chem. Phys. 131, 154115 (2009)], which tends to overcorrect RPA for systems with stronger static correlation. Similarly, AXK avoids the divergence of second-order Møller-Plesset (MP2) theory for small gap systems and delivers a much more consistent performance than MP2 across the periodic table at comparable cost. RPA+AXK thus is an accurate, non-empirical, and robust tool to assess and improve semi-local density functional theory for a wide range of systems previously inaccessible to first-principles electronic structure calculations.

  1. Communication: Random phase approximation renormalized many-body perturbation theory

    NASA Astrophysics Data System (ADS)

    Bates, Jefferson E.; Furche, Filipp

    2013-11-01

    We derive a renormalized many-body perturbation theory (MBPT) starting from the random phase approximation (RPA). This RPA-renormalized perturbation theory extends the scope of single-reference MBPT methods to small-gap systems without significantly increasing the computational cost. The leading correction to RPA, termed the approximate exchange kernel (AXK), substantially improves upon RPA atomization energies and ionization potentials without affecting other properties such as barrier heights where RPA is already accurate. Thus, AXK is more balanced than second-order screened exchange [A. Grüneis et al., J. Chem. Phys. 131, 154115 (2009)], which tends to overcorrect RPA for systems with stronger static correlation. Similarly, AXK avoids the divergence of second-order Møller-Plesset (MP2) theory for small gap systems and delivers a much more consistent performance than MP2 across the periodic table at comparable cost. RPA+AXK thus is an accurate, non-empirical, and robust tool to assess and improve semi-local density functional theory for a wide range of systems previously inaccessible to first-principles electronic structure calculations.

  2. Expectation values of single-particle operators in the random phase approximation ground state

    NASA Astrophysics Data System (ADS)

    Kosov, D. S.

    2017-02-01

    We developed a method for computing matrix elements of single-particle operators in the correlated random phase approximation ground state. Working with the explicit random phase approximation ground state wavefunction, we derived a practically useful and simple expression for a molecular property in terms of random phase approximation amplitudes. The theory is illustrated by the calculation of molecular dipole moments for a set of representative molecules.

  3. Expectation values of single-particle operators in the random phase approximation ground state.

    PubMed

    Kosov, D S

    2017-02-07

    We developed a method for computing matrix elements of single-particle operators in the correlated random phase approximation ground state. Working with the explicit random phase approximation ground state wavefunction, we derived a practically useful and simple expression for a molecular property in terms of random phase approximation amplitudes. The theory is illustrated by the calculation of molecular dipole moments for a set of representative molecules.

  4. Cyclosporin A is superior to cyclophosphamide in children with steroid-resistant nephrotic syndrome-a randomized controlled multicentre trial by the Arbeitsgemeinschaft für Pädiatrische Nephrologie.

    PubMed

    Plank, Christian; Kalb, Veronica; Hinkes, Bernward; Hildebrandt, Friedhelm; Gefeller, Olaf; Rascher, Wolfgang

    2008-09-01

    First line immunosuppressive treatment in steroid-resistant nephrotic syndrome in children is still open to discussion. We conducted a controlled multicentre randomized open label trial to test the efficacy and safety of cyclosporin A (CSA) versus cyclophosphamide pulses (CPH) in the initial therapy of children with newly diagnosed primary steroid-resistant nephrotic syndrome and histologically proven minimal change disease, focal segmental glomerulosclerosis or mesangial hypercellularity. Patients in the CSA group (n = 15) were initially treated with 150 mg/m(2) CSA orally to achieve trough levels of 120-180 ng/ml, while patients in the CPH group (n = 17) received CPH pulses (500 mg/m(2) per month intravenous). All patients were on alternate prednisone therapy. Patients with proteinuria >40 mg/m(2) per hour at 12 weeks of therapy were allocated to a non-responder protocol with high-dose CSA therapy or methylprednisolone pulses. At week 12, nine of the 15 (60%) CSA patients showed at least partial remission, evidences by a reduction of proteinuria <40 mg/h per m(2). In contrast, three of the 17 (17%) CPH patients responded (p < 0.05, intention-to-treat). Given these results, the study was stopped, in accordance with the protocol. After 24 weeks, complete remission was reached by two of the 15 (13%) CSA and one of the 17 (5%) CPH patients (p = n.s.). Partial remission was achieved by seven of the 15 (46%) CSA and two of the 15 (11%) CPH patients (p <0.05). Five patients in the CSA group and 14 patients in the CPH group were withdrawn from the study, most of them during the non-responder protocol. The number of adverse events was comparable between both groups. We conclude that CSA is more effective than CPH in inducing at least partial remission in steroid-resistant nephrotic syndrome in children.

  5. Web-based screening and brief intervention for poly-drug use among teenagers: study protocol of a multicentre two-arm randomized controlled trial

    PubMed Central

    2012-01-01

    Background Mid to late adolescence is characterised by a vulnerability to problematic substance use since the consumption of alcohol and illicit drugs is frequently initiated and increased in this life period. While the detrimental long- and short-term effects of problematic consumption patterns in adolescence pose a major public health concern, current prevention programs targeting alcohol- and other substance-using adolescents are scarce. The study described in this protocol will test the effectiveness of a web-based brief intervention aimed at reducing problematic alcohol use and promoting abstinence from illegal drugs in adolescents with risky substance use aged 16 to 18 years old in four EU-countries. Methods/design To determine the effectiveness of our web-BI, we apply a two-arm randomized controlled trial (RCT) study design, with baseline assessment at study entry and a three month follow-up assessment. Adolescents aged 16 to 18 years from Belgium, the Czech Republic, Germany, and Sweden will be randomly assigned to either the fully electronically delivered brief intervention group (N = 400) or an assessment only control group (N = 400) depending on their screening for risky substance use (using the CRAFFT). Recruitment, informed consent, randomization, intervention and follow-up will be implemented online. Primary outcomes are reductions in frequency and quantity of use of alcohol and drugs other than alcohol over a 30 day period, as well as consumption per typical occasion. Secondary outcomes concern changes in substance use related cognitions including the constructs of the Theory of Planned Behaviour, implementation intentions, and stages of change. Moreover the study addresses a number of moderator variables, including age of first use, general psychopathology and quality of parent–child relationship. Discussion The trial is expected to contribute to the growing literature on theory- and web-based brief interventions for adolescents. We will

  6. A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroïtin sulphate 2% for painful bladder syndrome/interstitial cystitis

    PubMed Central

    Tutolo, Manuela; Ammirati, Enrico; Castagna, Giulia; Klockaerts, Katrien; Plancke, Hendrik; Ost, Dieter; der Aa, Frank Van; Ridder, Dirk De

    2017-01-01

    ABSTRACT Objective To compare effectiveness of intravesical chondroïtin sulphate (CS) 2% and dimethyl sulphoxide (DMSO) 50% in patients with painful bladder syndrome/interstitial cystitis (PBS/IC). Materials and methods Patients were randomized to receive either 6 weekly instillations of CS 2% or 50% DMSO. Primary endpoint was difference in proportion of patients achieving score 6 (moderately improved) or 7 (markedly improved) in both groups using the Global Response Assessment (GRA) scale. Secondary parameters were mean 24-hours frequency and nocturia on a 3-day micturition dairy, changes from baseline in O’Leary-Sant questionnaire score and visual analog scale (VAS) for suprapubic pain. Results Thirty-six patients were the intention to treat population (22 in CS and 14 in DMSO group). In DMSO group, 57% withdrew consent and only 6 concluded the trial. Major reasons were pain during and after instillation, intolerable garlic odor and lack of efficacy. In CS group, 27% withdrew consent. Compared with DMSO group, more patients in CS group (72.7% vs. 14%) reported moderate or marked improvement (P=0.002, 95% CI 0.05-0.72) and achieved a reduction in VAS scores (20% vs. 8.3%). CS group performed significantly better in pain reduction (-1.2 vs. -0.6) and nocturia (-2.4 vs. -0.7) and better in total O’Leary reduction (-9.8 vs. -7.2). CS was better tolerated. The trial was stopped due to high number of drop-outs with DMSO. Conclusions Intravesical CS 2% is viable treatment for PBS/IC with minimal side effects. DMSO should be used with caution and with active monitoring of side effects. More randomized controlled studies on intravesical treatments are needed. PMID:28124536

  7. Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study.

    PubMed

    Xu, W-M; Cui, Y-T; Wang, L; Yang, H; Liang, Z-Q; Li, X-M; Zhang, S-L; Qiao, F-Y; Campbell, F; Chang, C-N; Gardner, S; Atkins, M

    2009-02-01

    This randomized, double-blind, placebo-controlled study evaluated whether lamivudine given during late pregnancy can reduce hepatitis B virus (HBV) perinatal transmission in highly viraemic mothers. Mothers were randomized to either lamivudine 100 mg or placebo from week 32 of gestation to week 4 postpartum. At birth, infants received recombinant HBV vaccine with or without HBIg and were followed until week 52. One hundred and fifty mothers, with a gestational age of 26-30 weeks and serum HBV DNA >1000 MEq/mL (bDNA assay), were treated. A total of 141 infants received immunoprophylaxis at birth. In lamivudine-treated mothers, 56 infants received vaccine + HBIg (lamivudine + vaccine + HBIg) and 26 infants received vaccine (lamivudine + vaccine). In placebo-treated mothers, 59 infants received vaccine + HBIg (placebo + vaccine + HBIg). At week 52, in the primary analyses where missing data was counted as failures, infants in the lamivudine + vaccine + HBIg group had a significant decrease in incidence of HBsAg seropositivity (10/56, 18%vs 23/59, 39%; P = 0.014) and in detectable HBV DNA (11/56, 20%vs 27/59, 46%; P = 0.003) compared to infants in the placebo + vaccine + HBIg group. Sensitivity analyses to evaluate the impact of missing data at week 52 resulting from a high dropout rate (13% in the lamivudine + vaccine + HBIg group and 31% in the placebo + vaccine + HBIg group) remained consistent with the primary analysis in that lower transmission rates were still observed in the infants of lamivudine-treated mothers, but the differences were not statistically significant. No safety concerns were noted in the lamivudine-treated mothers or their infants. Results of this study suggest that lamivudine reduced HBV transmission from highly viraemic mothers to their infants who received passive/active immunization.

  8. Preventive effect of Malva on urinary toxicity after radiation therapy in prostate cancer patients: A multi-centric, double-blind, randomized clinical trial

    PubMed Central

    Mofid, Bahram; Rezaeizadeh, Hossein; Jaladat, Amir Mohammad; Atarzadeh, Fatemeh; Moeini, Reihane; Motevalian, Abbas; Mosalaie, Ahmad; Farhan, Farshid; Rakhsha, Afshin; Kashi, Amir Shahram Yousefi

    2015-01-01

    Background: For patients receiving external beam radiation therapy (EBRT) after radical prostatectomy as adjuvant treatment or patients receiving EBRT as definitive treatment, partial irradiation of the urinary bladder is common. Many of such patients experience some degree of radiation-induced cystitis during or after EBRT. There is currently no efficient treatment for preventing radiation cystitis. Objective: The aim of this study was to evaluate the effectiveness of one of the safe mucilaginous herbs (Malva) in preventing radiation-induced dysuria in patients who are undergoing EBRT for prostate cancer. Methods: From April 2013 to August 2014, 68 patients were randomized into two groups using four block randomization, 34 to the drug (Malva) group and 34 to the placebo group. Of the 68 patients who began the study, 60 completed it. They were instructed to use the medication, i.e., Malva or the placebo, three times a day for six weeks. They were followed by a physician every two weeks for eight weeks, and urinary function was assessed in each visit by asking questions based on the Visual Prostate Symptom Score (VPSS) and a dysuria severity score. The changes in the VPSS and dysuria severity score between baseline and each follow-up visit were compared between the two groups in the study using repeated measures analysis of variance (ANOVA) and t-tests. Results: The median age of the 68 patients was 66. Twenty-one of 27 patients in the control group (77.7%) suffered from dysuria, while dysuria was detected in 23 of 33 patients (69.6%) who received Malva (odds ratio=2.70 for dysuria). After two weeks, four weeks, and six weeks of treatment with Malva, dysuria due to EBRT was milder in the treatment group than in the control group, and the differences were statistically significant (p = 0.005, p = 0.004, p = 0.001, respectively). Conclusion: To the best of our knowledge, our study is the first study to assess the protective effect of a mucilaginous herb (Malva

  9. Efficacy of Diosmectite (Smecta)® in the Treatment of Acute Watery Diarrhoea in Adults: A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study

    PubMed Central

    Khediri, Faouzi; Mrad, Abdennebi Ilhem; Azzouz, Moussadek; Doughi, Hedi; Najjar, Taoufik; Mathiex-Fortunet, Hélène; Garnier, Philippe; Cortot, Antoine

    2011-01-01

    Background. Although diosmectite has demonstrated efficacy in the treatment of acute watery diarrhoea in children, its efficacy in adults still needs to be assessed. The objective of this study was therefore to assess the efficacy of diosmectite on the time to recovery in adults with acute diarrhoea. Methods. A total of 346 adults with at least three watery stools per day over a period of less than 48 hours were prospectively randomized to diosmectite (6 g tid) or placebo during four days. The primary endpoint was time to diarrhoea recovery. Results. In the intention-to-treat population, median time to recovery was 53.8 hours (range [3.7–167.3]) with diosmectite (n = 166) versus 69.0 hours [2.2–165.2] with placebo, (n = 163; P = .029), which corresponds to a difference of 15.2 hours. Diosmectite was well tolerated. Conclusion. Diosmectite at 6 g tid was well tolerated and reduced the time to recovery of acute watery diarrhoea episode in a clinically relevant manner. PMID:21760777

  10. Betamethasone valerate dressing is non-inferior to calcipotriol–betamethasone dipropionate ointment in the treatment of patients with mild-to-moderate chronic plaque psoriasis: results of a randomized assessor-blinded multicentre trial

    PubMed Central

    Ortonne, J-P; Esposito, M; Chimenti, S; Kapińska-Mrowiecka, M; Grodzińska, A; Naldi, L; Frangione, V

    2014-01-01

    Background A ready-to-use betamethasone valerate 0.1% (BMV) dressing was found to be superior to placebo dressing and a reference 0.1% BMV cream in the treatment of patients with chronic plaque psoriasis (CPP). Methods This multicentre, prospective, randomized, investigator-blinded, controlled, non-inferiority trial compared the efficacy and safety of the BMV dressing to the calcipotriol–betamethasone dipropionate (CBD) ointment during a 4-week treatment of patients with mild to moderate CPP. The primary efficacy endpoint was the 4-item psoriasis total severity score (TSS-4) at week 4, and the associated non-inferiority margin was 1 point. Secondary outcome measures included the psoriasis global assessment (PGA) score and patients’ quality of life (QoL). Safety was assessed through adverse events (AE) reporting in each treatment group. Results Of 325 screened patients, 324 were randomized to BMV (N = 165) or CBD (N = 159), and were considered evaluable for the safety and intention-to-treat (ITT) efficacy analyses. Per protocol (PP) populations included 133 and 131 patients in the BMV and CBD groups respectively. The mean adjusted TSS-4 significantly decreased through the study from baseline in both groups. The PP (primary) analysis of week 4 data revealed a −0.288 (95% CI: −0.610 to 0.034) not significant between-group difference in adjusted means, demonstrating non-inferiority of BMV to CBD. Non-inferiority was also demonstrated in the ITT analysis. The PGA and other secondary outcomes were significantly improved from baseline in both groups at week 4. The QoL score was slightly better in the CBD group at week 4, but no difference was observed at follow-up. No safety or tolerability concerns were observed in either group. Conflicts of interest Centro Studi GISED, the centre led by LN, received a grant from IBSA Institut Biochimique SA. VF is an employee of IBSA Institut Biochimique SA. PMID:24256460

  11. Hydrogen multicentre bonds.

    PubMed

    Janotti, Anderson; Van de Walle, Chris G

    2007-01-01

    The concept of a chemical bond stands out as a major development in the process of understanding how atoms are held together in molecules and solids. Lewis' classical picture of chemical bonds as shared-electron pairs evolved to the quantum-mechanical valence-bond and molecular-orbital theories, and the classification of molecules and solids in terms of their bonding type: covalent, ionic, van der Waals and metallic. Along with the more complex hydrogen bonds and three-centre bonds, they form a paradigm within which the structure of almost all molecules and solids can be understood. Here, we present evidence for hydrogen multicentre bonds-a generalization of three-centre bonds-in which a hydrogen atom equally bonds to four or more other atoms. When substituting for oxygen in metal oxides, hydrogen bonds equally to all the surrounding metal atoms, becoming fourfold coordinated in ZnO, and sixfold coordinated in MgO. These multicentre bonds are remarkably strong despite their large hydrogen-metal distances. The calculated local vibration mode frequency in MgO agrees with infrared spectroscopy measurements. Multicoordinated hydrogen also explains the dependence of electrical conductivity on oxygen partial pressure, resolving a long-standing controversy on the role of point defects in unintentional n-type conductivity of ZnO (refs 8-10).

  12. Multiscale assessment of treatment efficacy in adults with ADHD: A randomized placebo-controlled, multi-centre study with extended-release methylphenidate

    PubMed Central

    Retz, Wolfgang; Rösler, Michael; Ose, Claudia; Scherag, André; Alm, Barbara; Philipsen, Alexandra; Fischer, Roland; Ammer, Richard

    2012-01-01

    Objectives This trial was performed to test the efficacy and safety of an extended-release formulation of methylphenidate (MPH ER). Methods A total of 162 adults with ADHD according to DSM-IV were treated for 8 weeks with either two daily individually body weight-adjusted doses of MPH ER up to 1 mg/kg per day (N = 84) or placebo (N = 78). The primary efficacy outcome was the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) 8 weeks after randomization. Secondary efficacy measures were the ADHD Diagnostic Checklist (ADHD-DC), the Conners Adult Attention Deficit Disorder Scale (CAARS-S:L), the Clinical Global Impression (CGI) and the Sheehan Disability Scale (SDS). Results At week 8 a significantly higher decline of the total WRAADDS score was found in the MPH ER group as compared to the placebo group (P = 0.0003). The rates of responders were 50% in the MPH ER and 18% in the placebo group (P < 0.0001). Furthermore, similar effects were observed for the secondary efficacy variable: ADHD-DC score (P = 0.004), CAARS-S:L score (P = 0.008) and the SDS score (P = 0.017). 50% of the MPH ER group and 24.4% of the placebo group were improved “much” or “very much” according to the CGI rating (P = 0.0001). MPH ER treatment was well tolerated. At week 2 also the mean heart rate was significantly higher in the MPH ER group as compared to the placebo group (P = 0.01). No differences between the study groups were observed regarding mean blood pressure at any visit. Conclusions This clinical trial demonstrated statistically significant and clinical relevant effects of MPH ER in adults with ADHD for several self- and investigator-rated ADHD psychopathology and also functional efficacy measures. PMID:21155632

  13. Deep Learning the Quantum Phase Transitions in Random Two-Dimensional Electron Systems

    NASA Astrophysics Data System (ADS)

    Ohtsuki, Tomoki; Ohtsuki, Tomi

    2016-12-01

    Random electron systems show rich phases such as Anderson insulator, diffusive metal, quantum Hall and quantum anomalous Hall insulators, Weyl semimetal, as well as strong/weak topological insulators. Eigenfunctions of each matter phase have specific features, but owing to the random nature of systems, determining the matter phase from eigenfunctions is difficult. Here, we propose the deep learning algorithm to capture the features of eigenfunctions. Localization-delocalization transition, as well as disordered Chern insulator-Anderson insulator transition, is discussed.

  14. Vulnerability of impulse attack-free four random phase mask cryptosystems to chosen-plaintext attack

    NASA Astrophysics Data System (ADS)

    Li, Tuo; Shi, Yishi

    2016-03-01

    An attack-free four random phase mask cryptosystem is breached in the paper. The decryption key of the system can be easily accessed by the opponent by using a new type of powerful three-dimensional phase retrieval method. Our result, to the best of our knowledge, is the first work to show this security flaw in the attack-free four random phase mask cryptosystem. Meanwhile, a set of numerical simulations is provided to demonstrate the robustness of the presented method.

  15. Anomalously elastic intermediate phase in randomly layered superfluids, superconductors, and planar magnets.

    PubMed

    Mohan, Priyanka; Goldbart, Paul M; Narayanan, Rajesh; Toner, John; Vojta, Thomas

    2010-08-20

    We show that layered quenched randomness in planar magnets leads to an unusual intermediate phase between the conventional ferromagnetic low-temperature and paramagnetic high-temperature phases. In this intermediate phase, which is part of the Griffiths region, the spin-wave stiffness perpendicular to the random layers displays anomalous scaling behavior, with a continuously variable anomalous exponent, while the magnetization and the stiffness parallel to the layers both remain finite. Analogous results hold for superfluids and superconductors. We study the two phase transitions into the anomalous elastic phase, and we discuss the universality of these results, and implications of finite sample size as well as possible experiments.

  16. Partition function for a two dimensional plasma in the random phase approximation

    NASA Technical Reports Server (NTRS)

    Seyler, C. E., Jr.

    1974-01-01

    The partition function for a two-dimensional plasma is evaluated within the random phase approximation. The periodic boundary conditions are fully taken into account by including the periodic image interactions. In the guiding-center limit, the negative temperature threshold energy is evaluated, and a value different from previous calculations results. When an identical random phase evaluated, and a value different from previous calculations results. When an identical random phase evaluation is applied to the finite gyroradius plasma, the Salzberg-Prager-May equation of state is recovered.

  17. Efficacy of degarelix in prostate cancer patients following failure on luteinizing hormone-releasing hormone agonist treatment: results from an open-label, multicentre, uncontrolled, phase II trial (CS27)

    PubMed Central

    Simson, Gabriele; Goble, Sandra; Persson, Bo-Eric

    2015-01-01

    Objective: To evaluate the efficacy of second-line degarelix in patients with prostate cancer (PCa) after treatment failure with a luteinizing hormone-releasing hormone (LHRH) agonist. Methods: This 1-year exploratory, multicentre, open-label phase II trial was performed in 2 patient cohorts (Cohort 1, n = 25; Cohort 2, n = 12) in Germany. Patients with castrate-resistant PCa after primary hormonal treatment received degarelix 240 mg, followed by 11 monthly maintenance doses of 80 mg. The primary endpoint was the proportion of patients with decreasing/stable prostate-specific antigen (PSA) (relative change ⩽+10% of baseline PSA) after 3 months. Results: At Month 3, the response rate (intention-to-treat, last observation carried forward analysis) was 16.7% [95% confidence interval (CI): 4.74–37.38] in Cohort 1 and 33.3% (95% CI: 9.92–65.11) in Cohort 2. The probability of completing 12 months without PSA progression was 8.8% (95% CI: 1.51–24.3) in Cohort 1 and 8.3% (95% CI: 0.5–31.1) in Cohort 2. Degarelix was well tolerated; the most frequently reported adverse events were local injection-site reactions. Conclusions: In PCa patients who failed LHRH therapy, degarelix was well tolerated and achieved a limited PSA response. Phase III trials show that disease control benefits with degarelix versus agonists are more clearly demonstrated as first-line therapy. PMID:26161141

  18. Phase transitions, magnetism and surface adsorptions assessed by meta-GGA functionals and random phase approximation

    NASA Astrophysics Data System (ADS)

    Xiao, Bing

    The meta-GGA functionals and random phase approximation are tested for phase transitions and a strongly correlated transition metal oxide in this dissertation. One of the latest meta-GGA functionals is also employed to study the van der Waals bound system in surface science. Our main purpose is to reveal the performance of new exchange-correlation functionals on various properties and systems. We are also interested in seeking the possible relationship between the performance of a semilocal functional and its exchange enhancement factor. We have studied the structural phase transitions in crystalline Si (insulator to metal), SiO2 (insulator to insulator) and Zr (metal to metal) systems, as a test of exchange energy semilocal functionals on Jacob's ladder. Our results confirm the energy-geometry delimma of GGAs in three systems. The most sophisticated non-empirical meta-generalized gradient approximations (meta-GGAs) such as TPSS (Tao-Perdew-Staroveov-Scuseria) and revTPSS (revised TPSS) give better lattice constants than PBE, but the phase transition parameters (energy difference and transition pressure) are smaller and less realistic than those from the latter GGA. However, the recent functionals of meta-GGA made simple family (MGGA_MS) behave differently to those previous meta-GGAs, predicting larger and more realistic phase transition parameters. Meanwhile, MGGA_MS also delivers the equilibrium geometry of crystalline materials similar to previous non-empirical meta-GGAs. In contrast to semilocal functionals, the nonlocal functionals such as the range-separated hybrid functional HSE06 (Heyd-Scuseria-Ernzerhof) and non-self consistent random phase approximation (RPA) are not only able to give the accurate equilibrium geometry , but also predict the realistic phase transition parameters for Si and SiO2 systems. The ground state of rutile-type vanadium dioxide (R-VO2) represents a great challenge to the current density functional theory. In this dissertation, we

  19. A combination of gefitinib and FOLFOX-4 as first-line treatment in advanced colorectal cancer patients. A GISCAD multicentre phase II study including a biological analysis of EGFR overexpression, amplification and NF-kB activation

    PubMed Central

    Cascinu, S; Berardi, R; Salvagni, S; Beretta, G D; Catalano, V; Pucci, F; Sobrero, A; Tagliaferri, P; Labianca, R; Scartozzi, M; Crocicchio, F; Mari, E; Ardizzoni, A

    2007-01-01

    Interesting activity has been reported by combining chemotherapy with cetuximab. An alternative approach for blocking EGFR function has been the development of small-molecule inhibitors of tyrosine kinase domain such as gefitinib. We designed a multicentre phase II study in advanced colorectal cancer combining gefitinib+FOLFOX in order to determine the activity and to relate EGFR expression and gene amplification and NF-kB activation to therapeutic results. Patients received FOLFOX-4 regimen plus gefitinib as first-line treatment. Tumour samples were analysed for EGFR protein expression by immunohistochemical analysis and for EGFR gene amplification by fluorescence in situ hybridisation (FISH), chromogenic in situ hybridisation (CISH) and NF-kB activation. Forty-three patients were enrolled into this study; 15 patients experienced a partial response (response rate=34.9%), whereas other 12 (27.9%) had a stable disease. Median progression-free survival (PFS) was 7.8 months and median overall survival (OS) was 13.9 months. We did not find any relationship with EGFR overexpression, gene amplification, while NF-kB activation was associated with a resistance to therapy. Gefitinib does not seem to increase the activity of FOLFOX in advanced colorectal cancer even in patients overexpressing EGFR or with EGFR amplification. Furthermore, while NF-kB activation seems to predict resistance to chemotherapy as demonstrated ‘in vitro' models, gefitinib does not overcome this mechanism of resistance, as reported for cetuximab. PMID:18059397

  20. Security enhancement of the phase-shifting interferometry-based cryptosystem by independent random phase modulation in each exposure

    NASA Astrophysics Data System (ADS)

    Liao, Meihua; He, Wenqi; Lu, Dajiang; Wu, Jiachen; Peng, Xiang

    2017-02-01

    The traditional phase-shifting interferometry (PSI)-based cryptosystem is one of the most classical optical cryptosystems. It employs the Mach-Zahnder interferometer to record the intensity distributions to partly overcome the inconvenience while storing the complex-valued ciphertext in some other optical cryptosystems (e.g., double random phase encoding technique). However, it has been proven to be vulnerable to chosen-plaintext attack and known-plaintext attack. In this manuscript, we propose an alternative method to enhance the security strength of the traditional PSI-based cryptosystem. By substituting the fixed random phase mask (RPM) and the phase retarder in the reference arm with four independent and different RPMs (served as secret keys) in four exposures, we can correspondingly capture four intensity-only patterns (regarded as ciphertexts). Theoretical analysis, especially with respect to security characteristics, as well as the numerical simulations are presented to verify the feasibility and reliability of the proposed cryptosystem.

  1. Randomness-driven Quantum Phase Transition in Bond-alternating Haldane Chain

    NASA Astrophysics Data System (ADS)

    Arakawa, Takayuki; Todo, Synge; Takayama, Hajime

    2005-04-01

    The effect of bond randomness on the spin-gapped ground state of the spin-1 bond-alternating antiferromagnetic Heisenberg chain is discussed. By using the loop cluster quantum Monte Carlo method, we investigate the stability of topological order in terms of the recently proposed twist order parameter [M. Nakamura and S. Todo: Phys. Rev. Lett. 89 (2002) 077204]. It is observed that the dimer phases as well as the Haldane phase of the spin-1 Heisenberg chain are robust against a weak randomness, though the valence-bond-solid-like topological order in the latter phase is destroyed by introducing a disorder stronger than the critical value.

  2. Amplitude-phase retrieval attack free image encryption based on two random masks and interference

    NASA Astrophysics Data System (ADS)

    Liansheng, Sui; bei, Zhou; Zhanmin, Wang; qindong, Sun

    2016-11-01

    An amplitude-phase retrieval attack free encryption scheme is proposed by using two random masks, where one is considered as the random image and other as the public key. Initially, the random image is encrypted to two phase-only masks based on interference technique with the help of the public key. These two phase-only masks are real-valued functions and used as the encryption keys. Then, the plain image is encrypted to the ciphertext with the white noise distribution by using the phase-truncated Fourier-transform-based encoding scheme with the previous encryption keys. The encryption process is nonlinear in which no iterative calculation is involved, while the decryption process is linear which can be easily implemented with the 4 f optical system. Moreover, less constraints makes the specific attack unusable. Simulation results are given to verify the feasibility and robustness of the proposed encryption scheme.

  3. Smeared quantum phase transition in the dissipative random quantum Ising model

    NASA Astrophysics Data System (ADS)

    Vojta, Thomas; Hoyos, José A.

    2010-01-01

    We investigate the quantum phase transition in the random transverse-field Ising model under the influence of Ohmic dissipation. To this end, we numerically implement a strong-disorder renormalization-group scheme. We find that Ohmic dissipation destroys the quantum critical point and the associated quantum Griffiths phase by smearing. Our results quantitatively confirm a recent theory [J.A. Hoyos, T. Vojta, Phys. Rev. Lett. 100 (2008) 240601] of smeared quantum phase transitions.

  4. Mathematic model analysis of Gaussian beam propagation through an arbitrary thickness random phase screen.

    PubMed

    Tian, Yuzhen; Guo, Jin; Wang, Rui; Wang, Tingfeng

    2011-09-12

    In order to research the statistical properties of Gaussian beam propagation through an arbitrary thickness random phase screen for adaptive optics and laser communication application in the laboratory, we establish mathematic models of statistical quantities, which are based on the Rytov method and the thin phase screen model, involved in the propagation process. And the analytic results are developed for an arbitrary thickness phase screen based on the Kolmogorov power spectrum. The comparison between the arbitrary thickness phase screen and the thin phase screen shows that it is more suitable for our results to describe the generalized case, especially the scintillation index.

  5. Masking property of quantum random cipher with phase mask encryption

    NASA Astrophysics Data System (ADS)

    Sohma, Masaki; Hirota, Osamu

    2014-10-01

    The security analysis of physical encryption protocol based on coherent pulse position modulation (CPPM) originated by Yuen is one of the most interesting topics in the study of cryptosystem with a security level beyond the Shannon limit. Although the implementation of CPPM scheme has certain difficulty, several methods have been proposed recently. This paper deals with the CPPM encryption in terms of symplectic transformation, which includes a phase mask encryption as a special example, and formulates a unified security analysis for such encryption schemes. Specifically, we give a lower bound of Eve's symbol error probability using reliability function theory to ensure that our proposed system exceeds the Shannon limit. Then we assume the secret key is given to Eve after her heterodyne measurement. Since this assumption means that Eve has a great advantage in the sense of the conventional cryptography, the lower bound of her error indeed ensures the security level beyond the Shannon limit. In addition, we show some numerical examples of the security performance.

  6. Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose–response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)—a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial

    PubMed Central

    Takeuchi, Tsutomu; Tanaka, Yoshiya; Ishiguro, Naoki; Yamanaka, Hisashi; Yoneda, Toshiyuki; Ohira, Takeshi; Okubo, Naoki; Genant, Harry K

    2016-01-01

    Objectives To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA). Methods In this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months. Results Denosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo. Conclusions Addition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction. Trial registration number JapicCTI-101263. PMID:26585988

  7. Phase transitions in optimal search times: How random walkers should combine resetting and flight scales.

    PubMed

    Campos, Daniel; Méndez, Vicenç

    2015-12-01

    Recent works have explored the properties of Lévy flights with resetting in one-dimensional domains and have reported the existence of phase transitions in the phase space of parameters which minimizes the mean first passage time (MFPT) through the origin [L. Kusmierz et al., Phys. Rev. Lett. 113, 220602 (2014)]. Here, we show how actually an interesting dynamics, including also phase transitions for the minimization of the MFPT, can also be obtained without invoking the use of Lévy statistics but for the simpler case of random walks with exponentially distributed flights of constant speed. We explore this dynamics both in the case of finite and infinite domains, and for different implementations of the resetting mechanism to show that different ways to introduce resetting consistently lead to a quite similar dynamics. The use of exponential flights has the strong advantage that exact solutions can be obtained easily for the MFPT through the origin, so a complete analytical characterization of the system dynamics can be provided. Furthermore, we discuss in detail how the phase transitions observed in random walks with resetting are closely related to several ideas recurrently used in the field of random search theory, in particular, to other mechanisms proposed to understand random search in space as mortal random walks or multiscale random walks. As a whole, we corroborate that one of the essential ingredients behind MFPT minimization lies in the combination of multiple movement scales (regardless of their specific origin).

  8. Improvement in holographic storage capacity by use of double-random phase encryption.

    PubMed

    Tan, X; Matoba, O; Shimura, T; Kuroda, K

    2001-09-10

    We show that a double-random encryption technique can improve the storage capacity of an angular-multiplexed holographic memory system. In the holographic memory system, input binary images are encrypted into white-noise-like images by use of two random phase masks located at the input and the Fourier planes. These encrypted images are stored as holograms in a photorefractive medium by use of angular multiplexing. All the images are encrypted by different sets of random phase masks. Even when the angle separation between adjacent images is small enough to cause cross talk between adjacent images, original binary data can be recovered with the correct phase mask; the other reconstructed images remain white-noise-like images because incorrect masks are used. Therefore the capacity of the proposed system can be larger than that of a conventional holographic memory system without the random phase encryption technique. Numerical evaluation and experimental results are presented to confirm that the capacity of the system with random phase masks is larger than that of the conventional memory system.

  9. Color image security system using double random-structured phase encoding in gyrator transform domain.

    PubMed

    Abuturab, Muhammad Rafiq

    2012-05-20

    A novel method for encoding color information based on a double random phase mask and a double structured phase mask in a gyrator transform domain is proposed. The amplitude transmittance of the Fresnel zone plate is used as structured phase-mask encoding. A color image is first segregated into red, green, and blue component images. Each of these component images are then independently encrypted using first a random phase mask placed at the image plane and transmitted through the first structured phase mask. They are then encoded by the first gyrator transform. The resulting information is again encrypted by a second random phase mask placed at the gyrator transform plane and transmitted through the second structured phase mask, and then encoded by the second gyrator transform. The system parameters of the structured phase mask and gyrator transform in each channel serve as additional encryption keys and enlarge the key space. The encryption process can be realized with an electro-optical hybrid system. The proposed system avoids problems arising from misalignment and benefits of a higher space-bandwidth product. Numerical simulations are presented to confirm the security, validity, and possibility of the proposed idea.

  10. Random exchange interaction effects on the phase transitions in frustrated classical Heisenberg model

    SciTech Connect

    Li, W. C.; Song, X.; Feng, J. J.; Zeng, M.; Gao, X. S.; Qin, M. H.; Jia, X. T.

    2015-07-07

    In this work, the effects of the random exchange interaction on the phase transitions and phase diagrams of classical frustrated Heisenberg model are investigated by Monte Carlo simulation in order to simulate the chemical doping effect in real materials. It is observed that the antiferromagnetic transitions shift toward low temperature with the increasing magnitude of the random exchange interaction, which can be qualitatively understood from the competitions among local spin states. This study is related to the magnetic properties in the doped iron-based superconductors.

  11. Quantum image encryption based on generalized Arnold transform and double random-phase encoding

    NASA Astrophysics Data System (ADS)

    Zhou, Nan Run; Hua, Tian Xiang; Gong, Li Hua; Pei, Dong Ju; Liao, Qing Hong

    2015-04-01

    A quantum realization of the generalized Arnold transform is designed. A novel quantum image encryption algorithm based on generalized Arnold transform and double random-phase encoding is proposed. The pixels are scrambled by the generalized Arnold transform, and the gray-level information of images is encoded by the double random-phase operations. The keys of the encryption algorithm include the independent parameters of coefficients matrix, iterative times and classical binary sequences, and thus, the key space is extremely large. Numerical simulations and theoretical analyses demonstrate that the proposed algorithm with good feasibility and effectiveness has lower computational complexity than its classical counterpart.

  12. The generation of 68 Gbps quantum random number by measuring laser phase fluctuations

    SciTech Connect

    Nie, You-Qi; Liu, Yang; Zhang, Jun Pan, Jian-Wei; Huang, Leilei; Payne, Frank

    2015-06-15

    The speed of a quantum random number generator is essential for practical applications, such as high-speed quantum key distribution systems. Here, we push the speed of a quantum random number generator to 68 Gbps by operating a laser around its threshold level. To achieve the rate, not only high-speed photodetector and high sampling rate are needed but also a very stable interferometer is required. A practical interferometer with active feedback instead of common temperature control is developed to meet the requirement of stability. Phase fluctuations of the laser are measured by the interferometer with a photodetector and then digitalized to raw random numbers with a rate of 80 Gbps. The min-entropy of the raw data is evaluated by modeling the system and is used to quantify the quantum randomness of the raw data. The bias of the raw data caused by other signals, such as classical and detection noises, can be removed by Toeplitz-matrix hashing randomness extraction. The final random numbers can pass through the standard randomness tests. Our demonstration shows that high-speed quantum random number generators are ready for practical usage.

  13. The generation of 68 Gbps quantum random number by measuring laser phase fluctuations.

    PubMed

    Nie, You-Qi; Huang, Leilei; Liu, Yang; Payne, Frank; Zhang, Jun; Pan, Jian-Wei

    2015-06-01

    The speed of a quantum random number generator is essential for practical applications, such as high-speed quantum key distribution systems. Here, we push the speed of a quantum random number generator to 68 Gbps by operating a laser around its threshold level. To achieve the rate, not only high-speed photodetector and high sampling rate are needed but also a very stable interferometer is required. A practical interferometer with active feedback instead of common temperature control is developed to meet the requirement of stability. Phase fluctuations of the laser are measured by the interferometer with a photodetector and then digitalized to raw random numbers with a rate of 80 Gbps. The min-entropy of the raw data is evaluated by modeling the system and is used to quantify the quantum randomness of the raw data. The bias of the raw data caused by other signals, such as classical and detection noises, can be removed by Toeplitz-matrix hashing randomness extraction. The final random numbers can pass through the standard randomness tests. Our demonstration shows that high-speed quantum random number generators are ready for practical usage.

  14. The generation of 68 Gbps quantum random number by measuring laser phase fluctuations

    NASA Astrophysics Data System (ADS)

    Nie, You-Qi; Huang, Leilei; Liu, Yang; Payne, Frank; Zhang, Jun; Pan, Jian-Wei

    2015-06-01

    The speed of a quantum random number generator is essential for practical applications, such as high-speed quantum key distribution systems. Here, we push the speed of a quantum random number generator to 68 Gbps by operating a laser around its threshold level. To achieve the rate, not only high-speed photodetector and high sampling rate are needed but also a very stable interferometer is required. A practical interferometer with active feedback instead of common temperature control is developed to meet the requirement of stability. Phase fluctuations of the laser are measured by the interferometer with a photodetector and then digitalized to raw random numbers with a rate of 80 Gbps. The min-entropy of the raw data is evaluated by modeling the system and is used to quantify the quantum randomness of the raw data. The bias of the raw data caused by other signals, such as classical and detection noises, can be removed by Toeplitz-matrix hashing randomness extraction. The final random numbers can pass through the standard randomness tests. Our demonstration shows that high-speed quantum random number generators are ready for practical usage.

  15. The MERITO Study: a multicentre trial of the analgesic effect and tolerability of normal-release oral morphine during 'titration phase' in patients with cancer pain.

    PubMed

    De Conno, F; Ripamonti, C; Fagnoni, E; Brunelli, C; Luzzani, M; Maltoni, M; Arcuri, E; Bertetto, O

    2008-04-01

    Adequate and rapid pain control is one of the main goals of cancer pain treatment. The objective of this study was to assess the effect and tolerability of oral normal-release morphine during the initial phase of treatment in patients with moderate-to-severe cancer pain. Consecutive patients naïve to strong opioids received normal-release morphine 5 or 10 mg every 4 h during the titration phase (first 5 days), depending on previous analgesic therapy. Pain intensity was assessed using an 11-point Numerical Rating Scale (0-10), and data were recorded in a patient-compiled diary. The primary endpoint was the proportion of time with pain control (a reduction of at least 50% with respect to the baseline pain score) during the titration phase. A total of 159 consecutive patients (102 men; mean age 65 years) with cancer-related pain were enrolled. Pain control was observed for 75% (95% CI 70-80) of the follow-up period in the intent-to-treat population. Overall, 50% and 75% of patients achieved pain control within 8 and 24 h after starting normal-release morphine therapy respectively. The mean pain score was 7.63 points at baseline, and decreased to 2.43 and 1.67 points (both P<0.001) at days 3 and 5 respectively. The most commonly reported adverse events were somnolence (24% of patients), constipation (22%), vomiting (13%), nausea (10%) and confusion (7%). Normal-release morphine results in rapid and satisfactory pain control, and is well tolerated, during the strong-opioid titration phase in patients with moderate-to-severe cancer pain.

  16. Phase IA/II, multicentre, open-label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non-Hodgkin or Hodgkin lymphoma.

    PubMed

    Fanale, Michelle; Assouline, Sarit; Kuruvilla, John; Solal-Céligny, Philippe; Heo, Dae S; Verhoef, Gregor; Corradini, Paolo; Abramson, Jeremy S; Offner, Fritz; Engert, Andreas; Dyer, Martin J S; Carreon, Daniel; Ewald, Brett; Baeck, Johan; Younes, Anas; Freedman, Arnold S

    2014-01-01

    Despite advancements in the treatment of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), patients continue to relapse and thus a need for new targeted therapies remains. The CD40 receptor is highly expressed on neoplastic B cells and activation leads to enhanced proliferation and survival. Lucatumumab (HCD122) is a fully human antagonistic CD40 monoclonal antibody. A phase IA/II study was designed to determine the maximum tolerated dose (MTD) and activity of lucatumumab in patients with relapsed/refractory lymphoma. Determination of the MTD was the primary objective of the phase IA dose escalation portion and clinical response was the primary objective of the phase II dose expansion portion. Patients received escalating doses of lucatumumab administered intravenously once weekly for 4 weeks of an 8-week cycle. MTD was determined at 4 mg/kg of lucatumumab. A total of 111 patients with NHL (n = 74) and HL (n = 37) were enrolled. Responses were observed across various lymphoma subtypes. The overall response rate by computed tomography among patients with follicular lymphoma (FL) and marginal zone lymphoma of mucosa-associated lymphatic tissue (MZL/MALT) was 33·3% and 42·9%, respectively. Lucatumumab demonstrates modest activity in relapsed/refractory patients with advanced lymphoma, suggesting that targeting of CD40 warrants further investigation.

  17. Optical information authentication using compressed double-random-phase-encoded images and quick-response codes.

    PubMed

    Wang, Xiaogang; Chen, Wen; Chen, Xudong

    2015-03-09

    In this paper, we develop a new optical information authentication system based on compressed double-random-phase-encoded images and quick-response (QR) codes, where the parameters of optical lightwave are used as keys for optical decryption and the QR code is a key for verification. An input image attached with QR code is first optically encoded in a simplified double random phase encoding (DRPE) scheme without using interferometric setup. From the single encoded intensity pattern recorded by a CCD camera, a compressed double-random-phase-encoded image, i.e., the sparse phase distribution used for optical decryption, is generated by using an iterative phase retrieval technique with QR code. We compare this technique to the other two methods proposed in literature, i.e., Fresnel domain information authentication based on the classical DRPE with holographic technique and information authentication based on DRPE and phase retrieval algorithm. Simulation results show that QR codes are effective on improving the security and data sparsity of optical information encryption and authentication system.

  18. Single-exposure phase-shifting digital holography using a random-complex-amplitude encoded reference wave.

    PubMed

    Imbe, Masatoshi; Nomura, Takanori

    2013-01-01

    The improved single-exposure phase-shifting digital holography using a random-phase reference wave is proposed. The algorithm for obtaining a complex amplitude of an object wave is improved. In the proposed algorithm, the reference wave is treated as not a random-phase but a random-complex amplitude. Therefore, the algorithm uses proper amplitude information of the reference wave. Both numerical simulations and experimental results are given to confirm the effectiveness of the proposed algorithm.

  19. Phase Transitions for the Cavity Approach to the Clique Problem on Random Graphs

    NASA Astrophysics Data System (ADS)

    Gaudillière, Alexandre; Scoppola, Benedetto; Scoppola, Elisabetta; Viale, Massimiliano

    2011-12-01

    We give a rigorous proof of two phase transitions for a disordered statistical mechanics system used to define an algorithm to find large cliques inside Erdös random graphs. Such a system is a conservative probabilistic cellular automaton inspired by the cavity method originally introduced in spin glass theory.

  20. Continuous and discontinuous absorbing-state phase transitions on Voronoi-Delaunay random lattices

    NASA Astrophysics Data System (ADS)

    de Oliveira, Marcelo M.; Alves, Sidiney G.; Ferreira, Silvio C.

    2016-01-01

    We study absorbing-state phase transitions (APTs) in two-dimensional Voronoi-Delaunay (VD) random lattices with quenched coordination disorder. Quenched randomness usually changes the criticality and destroys discontinuous transitions in low-dimensional nonequilibrium systems. We performed extensive simulations of the Ziff-Gulari-Barshad model, and verified that the VD disorder does not change the nature of its discontinuous transition. Our results corroborate recent findings of Barghathi and Vojta [H. Barghathi and T. Vojta, Phys. Rev. Lett. 113, 120602 (2014), 10.1103/PhysRevLett.113.120602], stating the irrelevance of topological disorder in a class of random lattices that includes VD, and raise the interesting possibility that disorder in nonequilibrium APT may, under certain conditions, be irrelevant for the phase coexistence. We also verify that the VD disorder is irrelevant for the critical behavior of models belonging to the directed percolation and Manna universality classes.

  1. Security enhanced optical encryption system by random phase key and permutation key.

    PubMed

    He, Mingzhao; Tan, Qiaofeng; Cao, Liangcai; He, Qingsheng; Jin, Guofan

    2009-12-07

    Conventional double random phase encoding (DRPE) encrypts plaintext to white noise-like ciphertext which may attract attention of eavesdroppers, and recent research reported that DRPE is vulnerable to various attacks. Here we propose a security enhanced optical encryption system that can hide the existence of secret information by watermarking. The plaintext is encrypted using iterative fractional Fourier transform with random phase key, and ciphertext is randomly permuted with permutation key before watermarking. Cryptanalysis shows that linearity of the security system has been broken and the permutation key prevent the attacker from accessing the ciphertext in various attacks. A series of simulations have shown the effectiveness of this system and the security strength is enhanced for invisibility, nonlinearity and resistance against attacks.

  2. Drugs, Women and Violence in the Americas: U.S. Quantitative Results of a Multi-Centric Pilot Project (Phase 2)

    PubMed Central

    González-Guarda, Rosa María; Peragallo, Nilda; Lynch, Ami; Nemes, Susanna

    2011-01-01

    Objectives To explore the collective and individual experiences that Latin American females in the U.S. have with substance abuse, violence and risky sexual behaviors. Methods This study was conducted in two phases from July 2006 to June 2007 in south Florida. This paper covers Phase 2. In Phase 2, questionnaires were provided to women to test whether there is a relationship between demographics, acculturation, depression, self-esteem and substance use/abuse; whether there is a relationship between demographics, acculturation, depression, self-esteem and violence exposure and victimization; whether there is a relationship between demographics, acculturation, depression, self-esteem, HIV knowledge and STD and HIV/AIDS risks among respondents; and whether there is a relationship between substance abuse, violence victimization and HIV/AIDS risks among respondents. Results Participants reported high rates of alcohol and drug abuse among their current or most recent partners. This is a major concern because partner alcohol use and drug use was related to partner physical, sexual and psychological abuse. Only two factors were associated with lifetime drug use: income and acculturation. Over half of the participants reported being victims of at least one form of abuse during childhood and adulthood. A substantial component of abuse reported during adulthood was perpetrated by a currently or recent intimate partner. Conclusions The results from this study suggest that substance abuse, violence and HIV should be addressed in an integrative and comprehensive manner. Recommendations for the development of policies, programs and services addressing substance abuse, violence and risk for HIV among Latinos are provided. PMID:22504304

  3. Depinning and nonequilibrium dynamic phases of particle assemblies driven over random and ordered substrates: a review

    NASA Astrophysics Data System (ADS)

    Reichhardt, C.; Olson Reichhardt, C. J.

    2017-02-01

    We review the depinning and nonequilibrium phases of collectively interacting particle systems driven over random or periodic substrates. This type of system is relevant to vortices in type-II superconductors, sliding charge density waves, electron crystals, colloids, stripe and pattern forming systems, and skyrmions, and could also have connections to jamming, glassy behaviors, and active matter. These systems are also ideal for exploring the broader issues of characterizing transient and steady state nonequilibrium flow phases as well as nonequilibrium phase transitions between distinct dynamical phases, analogous to phase transitions between different equilibrium states. We discuss the differences between elastic and plastic depinning on random substrates and the different types of nonequilibrium phases which are associated with specific features in the velocity-force curves, fluctuation spectra, scaling relations, and local or global particle ordering. We describe how these quantities can change depending on the dimension, anisotropy, disorder strength, and the presence of hysteresis. Within the moving phase we discuss how there can be a transition from a liquid-like state to dynamically ordered moving crystal, smectic, or nematic states. Systems with periodic or quasiperiodic substrates can have multiple nonequilibrium second or first order transitions in the moving state between chaotic and coherent phases, and can exhibit hysteresis. We also discuss systems with competing repulsive and attractive interactions, which undergo dynamical transitions into stripes and other complex morphologies when driven over random substrates. Throughout this work we highlight open issues and future directions such as absorbing phase transitions, nonequilibrium work relations, inertia, the role of non-dissipative dynamics such as Magnus effects, and how these results could be extended to the broader issues of plasticity in crystals, amorphous solids, and jamming phenomena.

  4. Depinning and nonequilibrium dynamic phases of particle assemblies driven over random and ordered substrates: A review

    DOE PAGES

    Reichhardt, Charles; Olson Reichhardt, Cynthia Jane

    2016-12-20

    Here, we review the depinning and nonequilibrium phases of collectively interacting particle systems driven over random or periodic substrates. This type of system is relevant to vortices in type-II superconductors, sliding charge density waves, electron crystals, colloids, stripe and pattern forming systems, and skyrmions, and could also have connections to jamming, glassy behaviors, and active matter. These systems are also ideal for exploring the broader issues of characterizing transient and steady state nonequilibrium flow phases as well as nonequilibrium phase transitions between distinct dynamical phases, analogous to phase transitions between different equilibrium states. We discuss the differences between elastic andmore » plastic depinning on random substrates and the different types of nonequilibrium phases which are associated with specific features in the velocity-force curves, fluctuation spectra, scaling relations, and local or global particle ordering. We describe how these quantities can change depending on the dimension, anisotropy, disorder strength, and the presence of hysteresis. Within the moving phase we discuss how there can be a transition from a liquid-like state to dynamically ordered moving crystal, smectic, or nematic states. Systems with periodic or quasiperiodic substrates can have multiple nonequilibrium second or first order transitions in the moving state between chaotic and coherent phases, and can exhibit hysteresis. We also discuss systems with competing repulsive and attractive interactions, which undergo dynamical transitions into stripes and other complex morphologies when driven over random substrates. Throughout this work we highlight open issues and future directions such as absorbing phase transitions, nonequilibrium work relations, inertia, the role of non-dissipative dynamics such as Magnus effects, and how these results could be extended to the broader issues of plasticity in crystals, amorphous solids, and jamming

  5. Depinning and nonequilibrium dynamic phases of particle assemblies driven over random and ordered substrates: A review

    SciTech Connect

    Reichhardt, Charles; Olson Reichhardt, Cynthia Jane

    2016-12-20

    Here, we review the depinning and nonequilibrium phases of collectively interacting particle systems driven over random or periodic substrates. This type of system is relevant to vortices in type-II superconductors, sliding charge density waves, electron crystals, colloids, stripe and pattern forming systems, and skyrmions, and could also have connections to jamming, glassy behaviors, and active matter. These systems are also ideal for exploring the broader issues of characterizing transient and steady state nonequilibrium flow phases as well as nonequilibrium phase transitions between distinct dynamical phases, analogous to phase transitions between different equilibrium states. We discuss the differences between elastic and plastic depinning on random substrates and the different types of nonequilibrium phases which are associated with specific features in the velocity-force curves, fluctuation spectra, scaling relations, and local or global particle ordering. We describe how these quantities can change depending on the dimension, anisotropy, disorder strength, and the presence of hysteresis. Within the moving phase we discuss how there can be a transition from a liquid-like state to dynamically ordered moving crystal, smectic, or nematic states. Systems with periodic or quasiperiodic substrates can have multiple nonequilibrium second or first order transitions in the moving state between chaotic and coherent phases, and can exhibit hysteresis. We also discuss systems with competing repulsive and attractive interactions, which undergo dynamical transitions into stripes and other complex morphologies when driven over random substrates. Throughout this work we highlight open issues and future directions such as absorbing phase transitions, nonequilibrium work relations, inertia, the role of non-dissipative dynamics such as Magnus effects, and how these results could be extended to the broader issues of plasticity in crystals, amorphous solids, and jamming phenomena.

  6. Fractional Fourier transform-based optical encryption with treble random phase-encoding

    NASA Astrophysics Data System (ADS)

    Xin, Yi; Tao, Ran; Wang, Yue

    2008-03-01

    We propose a new architecture of optical encryption technique using the fractional Fourier transform with three statistically independent random phase masks. Compared with the existing double-phase encoding method in the fractional Fourier-domain, the proposed extra phase mask in the last fractional Fourier domain makes the architecture symmetrical, and additive processing to the encrypted image can be turned into complex stationary white noise after decryption, and enlarge the key space without any degradation of its robustness to blind decryption. This property can be utilized to improve the quality of the recover image. Simulation results have verified the validity.

  7. Parametric down-conversion with nonideal and random quasi-phase-matching

    PubMed Central

    Yang, Chun-Yao; Lin, Chun; Liljestrand, Charlotte; Su, Wei-Min; Canalias, Carlota; Chuu, Chih-Sung

    2016-01-01

    Quasi-phase-matching (QPM) has enriched the capacity of parametric down-conversion (PDC) in generating biphotons for many fundamental tests and advanced applications. However, it is not clear how the nonidealities and randomness in the QPM grating of a parametric down-converter may affect the quantum properties of the biphotons. This paper intends to provide insights into the interplay between PDC and nonideal or random QPM structures. Using a periodically poled nonlinear crystal with short periodicity, we conduct experimental and theoretical studies of PDC subject to nonideal duty cycle and random errors in domain lengths. We report the observation of biphotons emerging through noncritical birefringent-phasematching, which is impossible to occur in PDC with an ideal QPM grating, and a biphoton spectrum determined by the details of nonidealities and randomness. We also observed QPM biphotons with a diminished strength. These features are both confirmed by our theory. Our work provides new perspectives for biphoton engineering with QPM. PMID:27173482

  8. Hacking on decoy-state quantum key distribution system with partial phase randomization

    PubMed Central

    Sun, Shi-Hai; Jiang, Mu-Sheng; Ma, Xiang-Chun; Li, Chun-Yan; Liang, Lin-Mei

    2014-01-01

    Quantum key distribution (QKD) provides means for unconditional secure key transmission between two distant parties. However, in practical implementations, it suffers from quantum hacking due to device imperfections. Here we propose a hybrid measurement attack, with only linear optics, homodyne detection, and single photon detection, to the widely used vacuum + weak decoy state QKD system when the phase of source is partially randomized. Our analysis shows that, in some parameter regimes, the proposed attack would result in an entanglement breaking channel but still be able to trick the legitimate users to believe they have transmitted secure keys. That is, the eavesdropper is able to steal all the key information without discovered by the users. Thus, our proposal reveals that partial phase randomization is not sufficient to guarantee the security of phase-encoding QKD systems with weak coherent states. PMID:24755767

  9. Three random phase encryption technology in the Fresnel diffraction system based on computer-generated hologram

    NASA Astrophysics Data System (ADS)

    Xi, Si-xing; Wang, Xiaolei; Sun, Xin; Chang, Shengjiang; Lin, Lie

    2014-01-01

    We propose a new method of image encryption using Fourier computer-generated hologram (CGH) in the encryption system of multiple Fresnel diffraction transforms with phase masks. The digital image to be encrypted is modulated by a series of three random-phase masks in Fresnel diffraction system and finally is transformed into a complex-amplitude image which is stationary white noise (in which the information is like stationary-white-noise). Because the complex-amplitude information is not easy to be directly saved, the binary real value Fourier CGH is applied to record it. Compared with the traditional double random-phase image encryption technology, this method adds new keys which enhance the image encryption security and the Fourier CGH greatly improves the antinoise performance.

  10. Hacking on decoy-state quantum key distribution system with partial phase randomization

    NASA Astrophysics Data System (ADS)

    Sun, Shi-Hai; Jiang, Mu-Sheng; Ma, Xiang-Chun; Li, Chun-Yan; Liang, Lin-Mei

    2014-04-01

    Quantum key distribution (QKD) provides means for unconditional secure key transmission between two distant parties. However, in practical implementations, it suffers from quantum hacking due to device imperfections. Here we propose a hybrid measurement attack, with only linear optics, homodyne detection, and single photon detection, to the widely used vacuum + weak decoy state QKD system when the phase of source is partially randomized. Our analysis shows that, in some parameter regimes, the proposed attack would result in an entanglement breaking channel but still be able to trick the legitimate users to believe they have transmitted secure keys. That is, the eavesdropper is able to steal all the key information without discovered by the users. Thus, our proposal reveals that partial phase randomization is not sufficient to guarantee the security of phase-encoding QKD systems with weak coherent states.

  11. Hacking on decoy-state quantum key distribution system with partial phase randomization.

    PubMed

    Sun, Shi-Hai; Jiang, Mu-Sheng; Ma, Xiang-Chun; Li, Chun-Yan; Liang, Lin-Mei

    2014-04-23

    Quantum key distribution (QKD) provides means for unconditional secure key transmission between two distant parties. However, in practical implementations, it suffers from quantum hacking due to device imperfections. Here we propose a hybrid measurement attack, with only linear optics, homodyne detection, and single photon detection, to the widely used vacuum + weak decoy state QKD system when the phase of source is partially randomized. Our analysis shows that, in some parameter regimes, the proposed attack would result in an entanglement breaking channel but still be able to trick the legitimate users to believe they have transmitted secure keys. That is, the eavesdropper is able to steal all the key information without discovered by the users. Thus, our proposal reveals that partial phase randomization is not sufficient to guarantee the security of phase-encoding QKD systems with weak coherent states.

  12. Phase transitions of the random-bond Potts chain with long-range interactions

    NASA Astrophysics Data System (ADS)

    Anglès d'Auriac, Jean-Christian; Iglói, Ferenc

    2016-12-01

    We study phase transitions of the ferromagnetic q -state Potts chain with random nearest-neighbor couplings having a variance Δ2 and with homogeneous long-range interactions, which decay with distance as a power r-(1 +σ ), σ >0 . In the large-q limit the free-energy of random samples of length L ≤2048 is calculated exactly by a combinatorial optimization algorithm. The phase transition stays first order for σ <σc(Δ ) ≤0.5 , while the correlation length becomes divergent at the transition point for σc(Δ ) <σ <1 . In the latter regime the average magnetization is continuous for small enough Δ , but for larger Δ —according to the numerical results—it becomes discontinuous at the transition point, thus the phase transition is expected of mixed order.

  13. Deep Learning the Quantum Phase Transitions in Random Electron Systems: Applications to Three Dimensions

    NASA Astrophysics Data System (ADS)

    Ohtsuki, Tomi; Ohtsuki, Tomoki

    2017-04-01

    Three-dimensional random electron systems undergo quantum phase transitions and show rich phase diagrams. Examples of the phases are the band gap insulator, Anderson insulator, strong and weak topological insulators, Weyl semimetal, and diffusive metal. As in the previous paper on two-dimensional quantum phase transitions [J. Phys. Soc. Jpn. 85, 123706 (2016)], we use an image recognition algorithm based on a multilayered convolutional neural network to identify which phase the eigenfunction belongs to. The Anderson model for localization-delocalization transition, the Wilson-Dirac model for topological insulators, and the layered Chern insulator model for Weyl semimetal are studied. The situation where the standard transfer matrix approach is not applicable is also treated by this method.

  14. A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD.

    PubMed

    Socié, Gérard; Vigouroux, Stéphane; Yakoub-Agha, Ibrahim; Bay, Jacques-Olivier; Fürst, Sabine; Bilger, Karin; Suarez, Felipe; Michallet, Mauricette; Bron, Dominique; Gard, Philippe; Medeghri, Zakaria; Lehert, Philippe; Lai, Chinglin; Corn, Tim; Vernant, Jean-Paul

    2017-02-02

    Treatment of steroid-resistant acute graft-versus-host disease (GVHD) remains an unmet clinical need. Inolimomab, a monoclonal antibody to CD25, has shown encouraging results in phase 2 trials. This phase 3 randomized, open-label, multicenter trial compared inolimomab vs usual care in adult patients with steroid-refractory acute GVHD. Patients were randomly selected to receive treatment with inolimomab or usual care (the control group was treated with antithymocyte globulin [ATG]). The primary objective was to evaluate overall survival at 1 year without changing baseline allocated therapy. A total of 100 patients were randomly placed: 49 patients in the inolimomab arm and 51 patients in the ATG arm. The primary criteria were reached by 14 patients (28.5%) in the inolimomab and 11 patients (21.5%) in the ATG arms, with a hazard ratio of 0.874 (P = .28). With a minimum follow-up of 1 year, 26 (53%) and 31 (60%) patients died in the inolimomab and ATG arms, respectively. Adverse events were similar in the 2 arms, with fewer viral infections in the inolimomab arm compared with the ATG arm. The primary end point of this randomized phase 3 trial was not achieved. The lack of a statistically significant effect confirms the need for development of more effective treatments for acute GVHD. This trial is registered to https://www.clinicaltrialsregister.eu/ctr-search/search as EUDRACT 2007-005009-24.

  15. Population growth in random media. I. Variational formula and phase diagram

    NASA Astrophysics Data System (ADS)

    Greven, A.; den Hollander, F.

    1991-12-01

    We consider an infinite system of particles on the integer lattice Z that: (1) migrate to the right with a random delay, (2) branch along the way according to a random law depending on their position (random medium). In Part I, the first part of a two-part presentation, the initial configuration has one particle at each site. The long-time limit exponential growth rate of the expected number of particles at site 0 (local particle density) does not depend on the realization of the random medium, but only on the law. It is computed in the form of a variational formula that can be solved explicitly. The result reveals two phase transitions associated with localization vs. delocalization and survival vs. extinction. In earlier work the exponential growth rate of the Cesaro limit of the number of particles per site (global particle density) was studied and a different variational formula was found, but with similar structure, solution, and phases. Combination of the two results reveals an intermediate phase where the population globally survives but locally becomes extinct (i.e., dies out on any fixed finite set of sites).

  16. Parallel multicentre randomised trial of a clinical trial question prompt list in patients considering participation in phase 3 cancer treatment trials

    PubMed Central

    Tattersall, Martin H N; Jefford, Michael; Martin, Andrew; Olver, Ian; Thompson, John F; Brown, Richard F; Butow, Phyllis N

    2017-01-01

    Objective To evaluate the effect of a clinical trial question prompt list in patients considering enrolment in cancer treatment trials. Setting Tertiary cancer referral hospitals in three state capital cities in Australia. Participants 88 patients with cancer attending three cancer centres in Australia, who were considering enrolment in phase 3 treatment trials, were invited to enrol in an unblinded randomised trial of provision of a clinical trial question prompt list (QPL) before consenting to enrol in the treatment trial. Interventions We developed and pilot tested a targeted QPL for patients with cancer considering clinical trial participation (the clinical trial QPL). Consenting patients were randomised to receive the clinical trial QPL or not before further discussion with their oncologist and/or trial nurse about the treatment trial. Primary and secondary outcomes Questionnaires were completed at baseline and within 3 weeks of deciding on treatment trial participation. Main outcome measure: scores on the Quality of Informed Consent questionnaire (QuIC). Results 88 patients of 130 sought for the study were enrolled (43 males), and 45 received the clinical trial QPL. 49% of trials were chemotherapy interventions for patients with advanced disease, 35% and 16% were surgical adjuvant and radiation adjuvant trials respectively. 70 patients completed all relevant questionnaires. 28 of 43 patients in the control arm compared with 39 of 45 patients receiving the clinical trial QPL completed the QuIC (p=0.0124). There were no significant differences in the QuIC scores between the randomised groups (QuIC part A p=0.08 and QuIC part B p=0.92). There were no differences in patient satisfaction with decisions or in anxiety levels between the randomised groups. Conclusions Use of a question prompt list did not significantly change the QuIC scores in this randomised trial. ANZCTR 12606000214538 prospectively registered 31/5/2006. Trial registration number Results, ACTRN

  17. Efficiency pedestal in quasi-phase-matching devices with random duty-cycle errors.

    PubMed

    Pelc, J S; Phillips, C R; Chang, D; Langrock, C; Fejer, M M

    2011-03-15

    It is shown that random duty-cycle errors in quasi-phase-matching (QPM) nonlinear optical devices enhance the efficiency of processes far from the QPM peak. An analytical theory is shown to agree well with numerical solutions of second-harmonic generation (SHG) in disordered QPM gratings. The measured efficiency of 1550 nm band SHG in a periodically poled lithium niobate (PPLN) waveguide away from the QPM peak agrees with observations of domain disorder in a PPLN wafer by Zygo interferometry. If suppression of parasitic nonlinear interactions is important in a specific application of QPM devices, control of random duty-cycle errors is critical.

  18. Phase Diagram of a Three-Dimensional Antiferromagnet with Random Magnetic Anisotropy

    SciTech Connect

    Perez, Felio A.; Borisov, Pavel; Johnson, Trent A.; Stanescu, Tudor D.; Trappen, Robbyn; Holcomb, Mikel B.; Lederman, David; Fitzsimmons, M. R.; Aczel, Adam A.; Hong, Tao

    2015-03-04

    Three-dimensional (3D) antiferromagnets with random magnetic anisotropy (RMA) that were experimentally studied to date have competing two-dimensional and three-dimensional exchange interactions which can obscure the authentic effects of RMA. The magnetic phase diagram of FexNi1-xF2 epitaxial thin films with true random single-ion anisotropy was deduced from magnetometry and neutron scattering measurements and analyzed using mean field theory. Regions with uniaxial, oblique and easy plane anisotropies were identified. A RMA-induced glass region was discovered where a Griffiths-like breakdown of long-range spin order occurs.

  19. Phase Diagram of a Three-Dimensional Antiferromagnet with Random Magnetic Anisotropy

    DOE PAGES

    Perez, Felio A.; Borisov, Pavel; Johnson, Trent A.; ...

    2015-03-04

    Three-dimensional (3D) antiferromagnets with random magnetic anisotropy (RMA) that were experimentally studied to date have competing two-dimensional and three-dimensional exchange interactions which can obscure the authentic effects of RMA. The magnetic phase diagram of FexNi1-xF2 epitaxial thin films with true random single-ion anisotropy was deduced from magnetometry and neutron scattering measurements and analyzed using mean field theory. Regions with uniaxial, oblique and easy plane anisotropies were identified. A RMA-induced glass region was discovered where a Griffiths-like breakdown of long-range spin order occurs.

  20. Lensless digital holography with diffuse illumination through a pseudo-random phase mask.

    PubMed

    Bernet, Stefan; Harm, Walter; Jesacher, Alexander; Ritsch-Marte, Monika

    2011-12-05

    Microscopic imaging with a setup consisting of a pseudo-random phase mask, and an open CMOS camera, without an imaging objective, is demonstrated. The pseudo random phase mask acts as a diffuser for an incoming laser beam, scattering a speckle pattern to a CMOS chip, which is recorded once as a reference. A sample which is afterwards inserted somewhere in the optical beam path changes the speckle pattern. A single (non-iterative) image processing step, comparing the modified speckle pattern with the previously recorded one, generates a sharp image of the sample. After a first calibration the method works in real-time and allows quantitative imaging of complex (amplitude and phase) samples in an extended three-dimensional volume. Since no lenses are used, the method is free from lens abberations. Compared to standard inline holography the diffuse sample illumination improves the axial sectioning capability by increasing the effective numerical aperture in the illumination path, and it suppresses the undesired so-called twin images. For demonstration, a high resolution spatial light modulator (SLM) is programmed to act as the pseudo-random phase mask. We show experimental results, imaging microscopic biological samples, e.g. insects, within an extended volume at a distance of 15 cm with a transverse and longitudinal resolution of about 60 μm and 400 μm, respectively.

  1. Role of an encapsulating layer for reducing resistance drift in phase change random access memory

    NASA Astrophysics Data System (ADS)

    Jin, Bo; Kim, Jungsik; Pi, Dong-Hai; Kim, Hyoung Seop; Meyyappan, M.; Lee, Jeong-Soo

    2014-12-01

    Phase change random access memory (PCRAM) devices exhibit a steady increase in resistance in the amorphous phase upon aging and this resistance drift phenomenon directly affects the device reliability. A stress relaxation model is used here to study the effect of a device encapsulating layer material in addressing the resistance drift phenomenon in PCRAM. The resistance drift can be increased or decreased depending on the biaxial moduli of the phase change material (YPCM) and the encapsulating layer material (YELM) according to the stress relationship between them in the drift regime. The proposed model suggests that the resistance drift can be effectively reduced by selecting a proper material as an encapsulating layer. Moreover, our model explains that reducing the size of the phase change material (PCM) while fully reset and reducing the amorphous/crystalline ratio in PCM help to improve the resistance drift, and thus opens an avenue for highly reliable multilevel PCRAM applications.

  2. Phase diagram of the classical Heisenberg model in a trimodal random field distribution

    NASA Astrophysics Data System (ADS)

    Santos-Filho, A.; Albuquerque, D. F. de; Santos-Filho, J. B.; Batista, T. S. Araujo

    2016-11-01

    The classical spin 1 / 2 Heisenberg model on a simple cubic lattice, with fluctuating bond interactions between nearest neighbors and in the presence of a random magnetic field, is investigated by effective field theory based on two-spin cluster. The random field is drawn from the asymmetric and anisotropic trimodal probability distribution. The fluctuating bond is extracted from the symmetric and anisotropic bimodal probability. We estimate the transition temperatures, and the phase diagram in the Tc- h, Tc- p and Tc - α planes. We observe that the temperature of the tricritical point decreases with the increase of disorder in exchange interactions until the system ceases to display tricritical behavior. The disorder of the interactions and reentrant phenomena depends on the trimodal distribution of the random field.

  3. Subtraction method in the second random-phase approximation: First applications with a Skyrme energy functional

    NASA Astrophysics Data System (ADS)

    Gambacurta, D.; Grasso, M.; Engel, J.

    2015-09-01

    We make use of a subtraction procedure, introduced to overcome double-counting problems in beyond-mean-field theories, in the second random-phase-approximation (SRPA) for the first time. This procedure guarantees the stability of the SRPA (so that all excitation energies are real). We show that the method fits perfectly into nuclear density-functional theory. We illustrate applications to the monopole and quadrupole response and to low-lying 0+ and 2+ states in the nucleus 16O . We show that the subtraction procedure leads to (i) results that are weakly cutoff dependent and (ii) a considerable reduction of the SRPA downwards shift with respect to the random-phase approximation (RPA) spectra (systematically found in all previous applications). This implementation of the SRPA model will allow a reliable analysis of the effects of two particle-two hole configurations (2p2h) on the excitation spectra of medium-mass and heavy nuclei.

  4. Phase diagram and criticality of the random anisotropy model in the large-N limit

    NASA Astrophysics Data System (ADS)

    Mouhanna, Dominique; Tarjus, Gilles

    2016-12-01

    We revisit the thermodynamic behavior of the random-anisotropy O(N ) model by investigating its large-N limit. We focus on the system at zero temperature where the mean-field-like artifacts of the large-N limit are less severe. We analyze the connection between the description in terms of self-consistent Schwinger-Dyson equations and the functional renormalization group. We provide a unified description of the phase diagram and critical behavior of the model and clarify the nature of the possible "glassy" phases. Finally we discuss the implications of our findings for the finite-N and finite-temperature systems.

  5. Atomic decoration of a random-cluster model for icosahedral-phase AlMnSi

    SciTech Connect

    Robertson, J.L.; Moss, S.C. )

    1991-01-21

    Preliminary results on the atomic decoration of a random-cluster model for icosahedral-phase alloys are presented. The calculated neutron and x-ray intensities compare quite favorably with experimental intensity data on {ital i}-AlMnSi. The origin of the peak at {ital Q}=1.62 A{sup {minus}1}, associated with the prepeak found in amorphous'' AlMnSi, as well as the ubiquitous diffuse'' scattering, seen experimentally under the groups of strong peaks in all icosahedral-phase alloys, are revealed selectively in the calculated partial intensities for Al-Al, Al-Mn, and Mn-Mn correlations.

  6. Photoionization cross sections for atomic chlorine using an open-shell random phase approximation

    NASA Technical Reports Server (NTRS)

    Starace, A. F.; Armstrong, L., Jr.

    1975-01-01

    The use of the Random Phase Approximation with Exchange (RPAE) for calculating partial and total photoionization cross sections and photoelectron angular distributions for open shell atoms is examined for atomic chlorine. Whereas the RPAE corrections in argon (Z=18) are large, it is found that those in chlorine (Z=17) are much smaller due to geometric factors. Hartree-Fock calculations with and without core relaxation are also presented. Sizable deviations from the close coupling results of Conneely are also found.

  7. Extended proton-neutron quasiparticle random-phase approximation in a boson expansion method

    NASA Astrophysics Data System (ADS)

    Civitarese, O.; Montani, F.; Reboiro, M.

    1999-08-01

    The proton-neutron quasiparticle random phase approximation (pn-QRPA) is extended to include next to leading order terms of the QRPA harmonic expansion. The procedure is tested for the case of a separable Hamiltonian in the SO(5) symmetry representation. The pn-QRPA equation of motion is solved by using a boson expansion technique adapted to the treatment of proton-neutron correlations. The resulting wave functions are used to calculate the matrix elements of double-Fermi transitions.

  8. Experimental study on the existence and properties of speckle phase vortices in the diffraction region near random surfaces.

    PubMed

    Chen, Xiaoyi; Li, Zhenhua; Li, Haixia; Zhang, Meina; Cheng, Chuanfu

    2012-07-30

    We design an optical setup to extract phase vortices in which the interference intensity of reference light wave and speckle fields produced by random screens with different roughness values in the diffraction region near random screens is obtained. Random screens with different roughness are used as samples. Fourier transform is used to extract speckle phase vortices from the interference intensity, and the experimental results show that the phase vortices can be produced when the roughness of the screen is large enough, and they even may appear on the surface. The density of phase vortices would become larger with an increase of the distances in the diffraction region near the random screen. When the distance is certain, the density of phase vortices becomes larger with the increase of roughness. These results would be helpful for understanding the formation of phase vortices.

  9. Information security system by iterative multiple-phase retrieval and pixel random permutation.

    PubMed

    Meng, Xiang-Feng; Cai, Lu-Zhong; Yang, Xiu-Lun; Shen, Xiao-Xia; Dong, Guo-Yan

    2006-05-10

    A novel information security system based on multiple-phase retrieval by an iterative Fresnel-transform algorithm and pixel random permutation (PRP) technique is proposed. In this method a series of phase masks cascaded in free space are employed and the phase distributions of all the masks are adjusted simultaneously in each iteration. It can achieve faster convergence and better quality of the recovered image compared with double-phase encoding and a similar approach in the spatial-frequency domain with the same number of phase masks and can provide a higher degree of freedom in key space with more geometric parameters as supplementary keys. Furthermore, the security level of this method is greatly improved by the introduction of the PRP technique. The feasibility of this method and its robustness against occlusion and additional noise attacks are verified by computer simulations. The performance of this technique for different numbers of phase masks and quantized phase levels is investigated systematically with the correlation coefficient and mean square error as convergence criterions.

  10. Vapour-liquid phase diagram for an ionic fluid in a random porous medium.

    PubMed

    Holovko, M F; Patsahan, O; Patsahan, T

    2016-10-19

    We study the vapour-liquid phase behaviour of an ionic fluid confined in a random porous matrix formed by uncharged hard sphere particles. The ionic fluid is modelled as an equimolar binary mixture of oppositely charged equisized hard spheres, the so-called restricted primitive model (RPM). Considering the matrix-fluid system as a partly-quenched model, we develop a theoretical approach which combines the method of collective variables with the extension of the scaled-particle theory (SPT) for a hard-sphere fluid confined in a disordered hard-sphere matrix. The approach allows us to formulate the perturbation theory using the SPT for the description of the thermodynamics of the reference system. The phase diagrams of the RPM in matrices of different porosities and for different size ratios of matrix and fluid particles are calculated in the random-phase approximation and also when the effects of higher-order correlations between ions are taken into account. Both approximations correctly reproduce the basic effects of porous media on the vapour-liquid phase diagram, i.e. with a decrease of porosity the critical point shifts towards lower fluid densities and lower temperatures and the coexistence region gets narrower. For the fixed matrix porosity, both the critical temperature and the critical density increase with an increase of size of matrix particles and tend to the critical values of the bulk RPM.

  11. Vapour-liquid phase diagram for an ionic fluid in a random porous medium

    NASA Astrophysics Data System (ADS)

    Holovko, M. F.; Patsahan, O.; Patsahan, T.

    2016-10-01

    We study the vapour-liquid phase behaviour of an ionic fluid confined in a random porous matrix formed by uncharged hard sphere particles. The ionic fluid is modelled as an equimolar binary mixture of oppositely charged equisized hard spheres, the so-called restricted primitive model (RPM). Considering the matrix-fluid system as a partly-quenched model, we develop a theoretical approach which combines the method of collective variables with the extension of the scaled-particle theory (SPT) for a hard-sphere fluid confined in a disordered hard-sphere matrix. The approach allows us to formulate the perturbation theory using the SPT for the description of the thermodynamics of the reference system. The phase diagrams of the RPM in matrices of different porosities and for different size ratios of matrix and fluid particles are calculated in the random-phase approximation and also when the effects of higher-order correlations between ions are taken into account. Both approximations correctly reproduce the basic effects of porous media on the vapour-liquid phase diagram, i.e. with a decrease of porosity the critical point shifts towards lower fluid densities and lower temperatures and the coexistence region gets narrower. For the fixed matrix porosity, both the critical temperature and the critical density increase with an increase of size of matrix particles and tend to the critical values of the bulk RPM.

  12. Single-phase and two-phase flow properties of mesaverde tight sandstone formation; random-network modeling approach

    NASA Astrophysics Data System (ADS)

    Bashtani, Farzad; Maini, Brij; Kantzas, Apostolos

    2016-08-01

    3D random networks are constructed in order to represent the tight Mesaverde formation which is located in north Wyoming, USA. The porous-space is represented by pore bodies of different shapes and sizes which are connected to each other by pore throats of varying length and diameter. Pore bodies are randomly distributed in space and their connectivity varies based on the connectivity number distribution which is used in order to generate the network. Network representations are then validated using publicly available mercury porosimetry experiments. The network modeling software solves the fundamental equations of two-phase immiscible flow incorporating wettability and contact angle variability. Quasi-static displacement is assumed. Single phase macroscopic properties (porosity, permeability) are calculated and whenever possible are compared to experimental data. Using this information drainage and imbibition capillary pressure, and relative permeability curves are predicted and (whenever possible) compared to experimental data. The calculated information is grouped and compared to available literature information on typical behavior of tight formations. Capillary pressure curve for primary drainage process is predicted and compared to experimental mercury porosimetry in order to validate the virtual porous media by history matching. Relative permeability curves are also calculated and presented.

  13. Many-body localization phase transition: A simplified strong-randomness approximate renormalization group

    NASA Astrophysics Data System (ADS)

    Zhang, Liangsheng; Zhao, Bo; Devakul, Trithep; Huse, David A.

    2016-06-01

    We present a simplified strong-randomness renormalization group (RG) that captures some aspects of the many-body localization (MBL) phase transition in generic disordered one-dimensional systems. This RG can be formulated analytically and is mathematically equivalent to a domain coarsening model that has been previously solved. The critical fixed-point distribution and critical exponents (that satisfy the Chayes inequality) are thus obtained analytically or to numerical precision. This reproduces some, but not all, of the qualitative features of the MBL phase transition that are indicated by previous numerical work and approximate RG studies: our RG might serve as a "zeroth-order" approximation for future RG studies. One interesting feature that we highlight is that the rare Griffiths regions are fractal. For thermal Griffiths regions within the MBL phase, this feature might be qualitatively correctly captured by our RG. If this is correct beyond our approximations, then these Griffiths effects are stronger than has been previously assumed.

  14. Low crosstalk optical hierarchical authentication with a fixed random phase lock based on two beams interference

    NASA Astrophysics Data System (ADS)

    Lu, Dajiang; He, Wenqi; Peng, Xiang

    2015-09-01

    We propose a novel method to achieve the purpose of hierarchical authentication based on two beams interference. In this method, different target images indicating different authentication levels are analytically encoded into corresponding phase-only masks (phase keys) and amplitude-only masks (amplitude keys) with the help of a random phase mask, which is created in advance and acts as the fixed lock of this authentication system. For the authentication process, a legal user can obtain a specified target image at the output plane if his/her phase key, and amplitude key, which should be settled close against the fixed internal phase lock, are respectively illuminated by two coherent beams. By comparing the target image with all the standard certification images in the database, the system can thus verify the user's identity. In simple terms, this system can not only confirm the legality of a user but also distinguish his/her identity level. Moreover, in despite of the internal phase lock of this system being fixed, the crosstalk between different pairs of keys hold by different users is low. Theoretical analysis and numerical simulation are both provided to demonstrate the validity of this method.

  15. Phase Behavior and Percolation Properties of the Patchy Colloidal Fluids in the Random Porous Media.

    PubMed

    Kalyuzhnyi, Y V; Holovko, M; Patsahan, T; Cummings, P T

    2014-12-18

    The lack of a simple analytical description of the hard-sphere fluid in a matrix with hard-core obstacles is limiting progress in the development of thermodynamic perturbation theories for the fluid in random porous media. We propose a simple and highly accurate analytical scheme, which allows us to calculate thermodynamic and percolation properties of a network-forming fluid confined in the random porous media, represented by the hard-sphere fluid and overlapping hard-sphere matrices, respectively. Our scheme is based on the combination of scaled-particle theory, Wertheim's thermodynamic perturbation theory for associating fluids and extension of the Flory-Stockmayer theory for percolation. The liquid-gas phase diagram and percolation threshold line for several versions of the patchy colloidal fluid model confined in a random porous media are calculated and discussed. The method presented enables calculation of the thermodynamic and percolation properties of a large variety of polymerizing and network-forming fluids confined in random porous media.

  16. Chaos Control for Coupling of the Double-Well Duffing System Based on Random Phase Disturbance

    NASA Astrophysics Data System (ADS)

    Wu, Gang; Li, Longsuo; Cong, Xinrong

    2013-06-01

    Non-feedback methods of chaos control are suited for practical applications. For possible practical applications of the control methods, the robustness of the methods in the presence of noise is of special interest. The noise can be in the form of external disturbances to the system or in the form of uncertainties due to inexact model of the system. This paper deals with the effect of random phase disturbance for a class of coupling of the Double-Well Duffing system in the presence of the noise. Lyapunov index is an important indicator to describe chaos. When the sign of the top Lyapunov exponent is positive, the system is chaotic. We compute top Lyapunov exponent by the Khasminskii's transform formula of spherical coordinate and extension of Wedig's algorithm based on linear stochastic system. With the change of the average of top Lyapunov exponent sign, we show that random phase can suppress chaos. Finally Poincaré map and phase portraits analysis are studied to confirm the obtained results.

  17. Phase IV, open-label, randomized study of low-dose recombinant human follicle-stimulating hormone protocols for ovulation induction

    PubMed Central

    2014-01-01

    Background This Phase IV, open-label, multicentre, randomized study (MEnTOR) compared two low-dose recombinant human follicle-stimulating hormone (r-hFSH) protocols for ovulation induction. Methods This study was conducted in six Middle Eastern countries between March 2009 and March 2011. Eligible women (18–37 years), with World Health Organization Group II anovulatory infertility, were randomized to receive r-hFSH (starting daily dose: 75 IU) as a chronic low-dose (CLD) (37.5 IU dose increase on Day 14) or low-dose (LD) (37.5 IU dose increase on Day 7) protocol if no follicles were ≥10 mm. The maximum r-hFSH daily dose permitted was 225 IU/day. The total length of ovarian stimulation could not exceed 35 days, unless ultrasound assessment suggested imminent follicular growth and maturation. Patients underwent only one treatment cycle. Primary endpoint: incidence of mono-follicular development. Secondary endpoints included: stimulation duration and rates of bi-follicular development; human chorionic gonadotrophin administration rate; clinical pregnancy; and cycle cancellation (owing to inadequate response). Adverse events (AEs) were recorded. The primary efficacy analysis was performed using data from all patients who received at least one dose of correct study medication, had at least one efficacy assessment, and no protocol violations at treatment start (CLD group, n = 122; LD group, n = 125). Results Mono-follicular development rates (primary endpoint) were similar in both groups (CLD: 56.6% [69/122] versus LD: 55.2% [69/125], p = 0.93; primary efficacy analysis population). Similarly, there were no significant differences between groups in bi-follicular development, clinical pregnancy or cycle cancellation (inadequate response) rates. In patients who received human chorionic gonadotrophin injections, the mean duration of stimulation was 13.7 days in the CLD group and 12.9 days in the LD group. Clinical pregnancy rates for those

  18. Expeditious Stochastic Calculation of Random-Phase Approximation Energies for Thousands of Electrons in Three Dimensions.

    PubMed

    Neuhauser, Daniel; Rabani, Eran; Baer, Roi

    2013-04-04

    A fast method is developed for calculating the random phase approximation (RPA) correlation energy for density functional theory. The correlation energy is given by a trace over a projected RPA response matrix, and the trace is taken by a stochastic approach using random perturbation vectors. For a fixed statistical error in the total energy per electron, the method scales, at most, quadratically with the system size; however, in practice, due to self-averaging, it requires less statistical sampling as the system grows, and the performance is close to linear scaling. We demonstrate the method by calculating the RPA correlation energy for cadmium selenide and silicon nanocrystals with over 1500 electrons. We find that the RPA correlation energies per electron are largely independent of the nanocrystal size. In addition, we show that a correlated sampling technique enables calculation of the energy difference between two slightly distorted configurations with scaling and a statistical error similar to that of the total energy per electron.

  19. Generalized Hammersley Process and Phase Transition for Activated Random Walk Models

    NASA Astrophysics Data System (ADS)

    Rolla, Leonardo T.

    2008-12-01

    * ACTIVATED RANDOM WALK MODEL * This is a conservative particle system on the lattice, with a Markovian continuous-time evolution. Active particles perform random walks without interaction, and they may as well change their state to passive, then stopping to jump. When particles of both types occupy the same site, they all become active. This model exhibits phase transition in the sense that for low initial densities the system locally fixates and for high densities it keeps active. Though extensively studied in the physics literature, the matter of giving a mathematical proof of such phase transition remained as an open problem for several years. In this work we identify some variables that are sufficient to characterize fixation and at the same time are stochastically monotone in the model's parameters. We employ an explicit graphical representation in order to obtain the monotonicity. With this method we prove that there is a unique phase transition for the one-dimensional finite-range random walk. Joint with V. Sidoravicius. * BROKEN LINE PROCESS * We introduce the broken line process and derive some of its properties. Its discrete version is presented first and a natural generalization to the continuum is then proposed and studied. The broken lines are related to the Young diagram and the Hammersley process and are useful for computing last passage percolation values and finding maximal oriented paths. For a class of passage time distributions there is a family of boundary conditions that make the process stationary and reversible. One application is a simple proof of the explicit law of large numbers for last passage percolation with exponential and geometric distributions. Joint with V. Sidoravicius, D. Surgailis, and M. E. Vares.

  20. QRAP: A numerical code for projected (Q)uasiparticle (RA)ndom (P)hase approximation

    NASA Astrophysics Data System (ADS)

    Samana, A. R.; Krmpotić, F.; Bertulani, C. A.

    2010-06-01

    A computer code for quasiparticle random phase approximation - QRPA and projected quasiparticle random phase approximation - PQRPA models of nuclear structure is explained in details. The residual interaction is approximated by a simple δ-force. An important application of the code consists in evaluating nuclear matrix elements involved in neutrino-nucleus reactions. As an example, cross sections for 56Fe and 12C are calculated and the code output is explained. The application to other nuclei and the description of other nuclear and weak decay processes are also discussed. Program summaryTitle of program: QRAP ( Quasiparticle RAndom Phase approximation) Computers: The code has been created on a PC, but also runs on UNIX or LINUX machines Operating systems: WINDOWS or UNIX Program language used: Fortran-77 Memory required to execute with typical data: 16 Mbytes of RAM memory and 2 MB of hard disk space No. of lines in distributed program, including test data, etc.: ˜ 8000 No. of bytes in distributed program, including test data, etc.: ˜ 256 kB Distribution format: tar.gz Nature of physical problem: The program calculates neutrino- and antineutrino-nucleus cross sections as a function of the incident neutrino energy, and muon capture rates, using the QRPA or PQRPA as nuclear structure models. Method of solution: The QRPA, or PQRPA, equations are solved in a self-consistent way for even-even nuclei. The nuclear matrix elements for the neutrino-nucleus interaction are treated as the beta inverse reaction of odd-odd nuclei as function of the transfer momentum. Typical running time: ≈ 5 min on a 3 GHz processor for Data set 1.

  1. Gyrator transform based double random phase encoding with sparse representation for information authentication

    NASA Astrophysics Data System (ADS)

    Chen, Jun-xin; Zhu, Zhi-liang; Fu, Chong; Yu, Hai; Zhang, Li-bo

    2015-07-01

    Optical information security systems have drawn long-term concerns. In this paper, an optical information authentication approach using gyrator transform based double random phase encoding with sparse representation is proposed. Different from traditional optical encryption schemes, only sparse version of the ciphertext is preserved, and hence the decrypted result is completely unrecognizable and shows no similarity to the plaintext. However, we demonstrate that the noise-like decipher result can be effectively authenticated by means of optical correlation approach. Simulations prove that the proposed method is feasible and effective, and can provide additional protection for optical security systems.

  2. Self-consistent relativistic random-phase approximation with vacuum polarization

    SciTech Connect

    Haga, A.; Toki, H.; Tamenaga, S.; Horikawa, Y.; Yadav, H.L.

    2005-09-01

    We present a theoretical formulation for the description of nuclear excitations within the framework of a relativistic random-phase approximation whereby the vacuum polarization arising from nucleon-antinucleon fields is duly accounted for. The vacuum contribution to the Lagrangian is explicitly described as extra new terms of interacting mesons by means of the derivative expansion of the effective action. It is shown that the self-consistent calculation yields zero eigenvalue for the spurious isoscalar-dipole state and also conserves the vector-current density.

  3. Color image authentication scheme via multispectral photon-counting double random phase encoding

    NASA Astrophysics Data System (ADS)

    Moon, Inkyu

    2015-05-01

    In this paper, we present an overview of a color image authentication scheme via multispectral photon-counting (MPCI) double random phase encoding (DRPE). The MPCI makes image sparse distributed and DRPE lets image be stationary white noise which make intruder attacks difficult. In this method, the original RGB image is down-sampled into Bayer image and then be encrypted with DRPE. The encrypted image is photon-counted and transmitted on internet channel. For image authentication, the decrypted Bayer image is interpolated into RBC image with demosaicing algorithm. Experimental results show that the decrypted image is not visually recognized under low light level but can be verified with nonlinear correlation algorithm.

  4. Simulating of the measurement-device independent quantum key distribution with phase randomized general sources

    PubMed Central

    Wang, Qin; Wang, Xiang-Bin

    2014-01-01

    We present a model on the simulation of the measurement-device independent quantum key distribution (MDI-QKD) with phase randomized general sources. It can be used to predict experimental observations of a MDI-QKD with linear channel loss, simulating corresponding values for the gains, the error rates in different basis, and also the final key rates. Our model can be applicable to the MDI-QKDs with arbitrary probabilistic mixture of different photon states or using any coding schemes. Therefore, it is useful in characterizing and evaluating the performance of the MDI-QKD protocol, making it a valuable tool in studying the quantum key distributions. PMID:24728000

  5. Random quasi-phase-matched conversion of broadband radiation in a nonlinear photonic crystal

    SciTech Connect

    Aleksandrovsky, A. S.; Vyunishev, A. M.; Zaitsev, A. I.; Slabko, V. V.

    2010-11-15

    Radiation in the range 187.5-215 nm was generated via random quasi-phase-matched frequency doubling of femtosecond laser pulses in nonlinear photonic crystals of strontium tetraborate. A broad spectrum of fundamental radiation favors the probing of the nonlinear photonic crystal band structure. The red shift of the band structure upon the fundamental wave-vector rotation was observed. No principal limitations of the tuning range at its shorter wavelength boundary from the nonlinear photonic crystal (NPC) material are found. Calculation shows that the NPC structure enables enhancement of nonlinear generation in the vacuum ultraviolet.

  6. Microstructural Characterization in Reliability Measurement of Phase Change Random Access Memory

    NASA Astrophysics Data System (ADS)

    Bae, Junsoo; Hwang, Kyuman; Park, Kwangho; Jeon, Seongbu; Kang, Dae-hwan; Park, Soonoh; Ahn, Juhyeon; Kim, Seoksik; Jeong, Gitae; Chung, Chilhee

    2011-04-01

    The cell failures after cycling endurance in phase-change random access memory (PRAM) have been classified into three groups, which have been analyzed by transmission electron microscopy (TEM). Both stuck reset of the set state (D0) and stuck set of the reset state (D1) are due to a void created inside GeSbTe (GST) film or thereby lowering density of GST film. The decrease of the both set and reset resistances that leads to the tails from the reset distribution are induced from the Sb increase with cycles.

  7. Equilibrium phase behavior and maximally random jammed state of truncated tetrahedra.

    PubMed

    Chen, Duyu; Jiao, Yang; Torquato, Salvatore

    2014-07-17

    Numerous recent investigations have been devoted to the determination of the equilibrium phase behavior and packing characteristics of hard nonspherical particles, including ellipsoids, superballs, and polyhedra, to name but just a few shapes. Systems of hard nonspherical particles exhibit a variety of stable phases with different degrees of translational and orientational order, including isotropic liquid, solid crystal, rotator and a variety of liquid crystal phases. In this paper, we employ a Monte Carlo implementation of the adaptive-shrinking-cell (ASC) numerical scheme and free-energy calculations to ascertain with high precision the equilibrium phase behavior of systems of congruent Archimedean truncated tetrahedra over the entire range of possible densities up to the maximal nearly space-filling density. In particular, we find that the system undergoes two first-order phase transitions as the density increases: first a liquid-solid transition and then a solid-solid transition. The isotropic liquid phase coexists with the Conway-Torquato (CT) crystal phase at intermediate densities, verifying the result of a previous qualitative study [ J. Chem. Phys. 2011 , 135 , 151101 ]. The freezing- and melting-point packing fractions for this transition are respectively ϕF = 0.496 ± 0.006 and ϕM = 0.591 ± 0.005. At higher densities, we find that the CT phase undergoes another first-order phase transition to one associated with the densest-known crystal, with coexistence densities in the range ϕ ∈ [0.780 ± 0.002, 0.802 ± 0.003]. We find no evidence for stable rotator (or plastic) or nematic phases. We also generate the maximally random jammed (MRJ) packings of truncated tetrahedra, which may be regarded to be the glassy end state of a rapid compression of the liquid. Specifically, we systematically study the structural characteristics of the MRJ packings, including the centroidal pair correlation function, structure factor and orientational pair correlation

  8. High energy X-ray phase and dark-field imaging using a random absorption mask.

    PubMed

    Wang, Hongchang; Kashyap, Yogesh; Cai, Biao; Sawhney, Kawal

    2016-07-28

    High energy X-ray imaging has unique advantage over conventional X-ray imaging, since it enables higher penetration into materials with significantly reduced radiation damage. However, the absorption contrast in high energy region is considerably low due to the reduced X-ray absorption cross section for most materials. Even though the X-ray phase and dark-field imaging techniques can provide substantially increased contrast and complementary information, fabricating dedicated optics for high energies still remain a challenge. To address this issue, we present an alternative X-ray imaging approach to produce transmission, phase and scattering signals at high X-ray energies by using a random absorption mask. Importantly, in addition to the synchrotron radiation source, this approach has been demonstrated for practical imaging application with a laboratory-based microfocus X-ray source. This new imaging method could be potentially useful for studying thick samples or heavy materials for advanced research in materials science.

  9. Dual-channel in-line digital holographic double random phase encryption.

    PubMed

    Das, Bhargab; Yelleswarapu, Chandra S; Rao, D V G L N

    2012-10-01

    We present a robust encryption method for the encoding of 2D/3D objects using digital holography and virtual optics. Using our recently developed dual-plane in-line digital holography technique, two in-line digital holograms are recorded at two different planes and are encrypted using two different double random phase encryption configurations, independently. The process of using two mutually exclusive encryption channels makes the system more robust against attacks since both the channels should be decrypted accurately in order to get a recognizable reconstruction. Results show that the reconstructed object is unrecognizable even when the portion of the correct phase keys used during decryption is close to 75%. The system is verified against blind decryptions by evaluating the SNR and MSE. Validation of the proposed method and sensitivities of the associated parameters are quantitatively analyzed and illustrated.

  10. Numerical evidence of the double-Griffiths phase of the random quantum Ashkin-Teller chain

    NASA Astrophysics Data System (ADS)

    Chatelain, Christophe; Voliotis, Dimitrios

    2016-01-01

    The random quantum Ashkin-Teller chain is studied numerically by means of time-dependent Density-Matrix Renormalization Group. The critical lines are estimated as the location of the peaks of the integrated autocorrelation times, computed from spin-spin and polarization-polarization autocorrelation functions. Disorder fluctuations of magnetization and polarization are observed to be maximum on these critical lines. Entanglement entropy leads to the same phase diagram, though with larger finite-size effects. The decay of spin-spin and polarization-polarization autocorrelation functions provides numerical evidence of the existence of a double Griffiths phase when taking into account finite-size effects. The two associated dynamical exponents z increase rapidly as the critical lines are approached, in agreement with the recent conjecture of a divergence at the two transitions in the thermodynamic limit.

  11. Computer and graphics modeling of heat transfer and phase change in a wall with randomly imbibed PCM

    SciTech Connect

    Solomon, A.D.

    1989-03-01

    We describe the theoretical basis and computer implementation of a simulation code for heat transfer and phase change in a rectangular 2-dimensional region in which PCM has been randomly placed with a preassigned volume fraction.

  12. Twin-image reduction method for in-line digital holography using periphery and random reference phase-shifting techniques

    NASA Astrophysics Data System (ADS)

    Oshima, Teppei; Matsudo, Yusuke; Kakue, Takashi; Arai, Daisuke; Shimobaba, Tomoyoshi; Ito, Tomoyoshi

    2015-09-01

    Digital holography has the twin image problem that unwanted lights (conjugate and direct lights) overlap in the object light in the reconstruction process. As a method for extracting only the object light, phase-shifting digital holography is widely used; however, this method is not applicable for the observation of moving objects, because this method requires the recording of plural holograms. In this study, we propose a twin-image reduction method by combining the "periphery" method with the "random phase-shifting" method. The proposed method succeeded in improving the reconstruction quality, compared to other one-shot recording methods ("parallel phase-shifting digital holography" and "random phase-shifting").

  13. Phase fluctuations of radio waves experiencing total reflection from a randomly inhomogeneous plasma layer

    NASA Astrophysics Data System (ADS)

    Afanasiev, N. T.; Afanasiev, A. N.; Larunin, O. A.; Markov, V. P.

    2010-05-01

    We examine the problem of small-angle scattering of radio waves experiencing total reflection from a randomly inhomogeneous layer of plasma. We consider the waves to be normally incident on the layer. To take into account the scattering peculiarities in the neighborhood of the reflection point, we introduce an analytical transformation for the eikonal equation solution derived by the perturbation method. This transformation permits calculations of radio-wave phase fluctuations for any monotonous profile of the regular dielectric permittivity of the plasma in the layer. Using this approach, we have derived analytical formulas for the variance and two-dimensional spatial spectrum of phase fluctuations, depending on the three-dimensional power spectrum of plasma fluctuations. We have also estimated a contribution of reflection point fluctuations to the phase fluctuations and determined the limits of applicability of the derived formulas. The presented analytical transformation of the eikonal equation solution can be used to calculate other statistical moments of the radio wave phase in many problems of solar-terrestrial physics where scattering and reflection of radio waves by plasma formations are important.

  14. Diagnosis of the phase function of random media from light reflectance

    NASA Astrophysics Data System (ADS)

    Xu, Min

    2016-03-01

    Light reflectance has been widely used to diagnose random media in both in situ and in vivo applications. The quantification of the phase function of the medium from reflectance measurements, however, remains elusive due to the lack of an explicit connection between the light reflectance profile and the phase function. Here we first present an analytical model for reflectance of scattered light at an arbitrary source-detector separation by forward-peaked scattering media such as biological tissue and cells. The model incorporates the improved small-angle scattering approximation (SAA) to radiative transfer for sub-diffusive light reflectance and expresses the dependence of the light reflectance on the phase function of the scattering medium in a closed form. A spreading length scale, lΘ, is found to characterise subdiffusive light reflectance at the high spatial frequency (close separation) limit. After validation by Monte Carlo simulations, we then demonstrate the application of the model in accurate determination of the complete set of optical properties and the phase function of a turbid medium from the profile of subdiffusive and diffusive light reflectance.

  15. Diagnosis of the phase function of random media from light reflectance

    PubMed Central

    Xu, Min

    2016-01-01

    Light reflectance has been widely used to diagnose random media in both in situ and in vivo applications. The quantification of the phase function of the medium from reflectance measurements, however, remains elusive due to the lack of an explicit connection between the light reflectance profile and the phase function. Here we first present an analytical model for reflectance of scattered light at an arbitrary source-detector separation by forward-peaked scattering media such as biological tissue and cells. The model incorporates the improved small-angle scattering approximation (SAA) to radiative transfer for sub-diffusive light reflectance and expresses the dependence of the light reflectance on the phase function of the scattering medium in a closed form. A spreading length scale, lΘ, is found to characterise subdiffusive light reflectance at the high spatial frequency (close separation) limit. After validation by Monte Carlo simulations, we then demonstrate the application of the model in accurate determination of the complete set of optical properties and the phase function of a turbid medium from the profile of subdiffusive and diffusive light reflectance. PMID:26935167

  16. Diagnosis of the phase function of random media from light reflectance.

    PubMed

    Xu, Min

    2016-03-03

    Light reflectance has been widely used to diagnose random media in both in situ and in vivo applications. The quantification of the phase function of the medium from reflectance measurements, however, remains elusive due to the lack of an explicit connection between the light reflectance profile and the phase function. Here we first present an analytical model for reflectance of scattered light at an arbitrary source-detector separation by forward-peaked scattering media such as biological tissue and cells. The model incorporates the improved small-angle scattering approximation (SAA) to radiative transfer for sub-diffusive light reflectance and expresses the dependence of the light reflectance on the phase function of the scattering medium in a closed form. A spreading length scale, lΘ, is found to characterise subdiffusive light reflectance at the high spatial frequency (close separation) limit. After validation by Monte Carlo simulations, we then demonstrate the application of the model in accurate determination of the complete set of optical properties and the phase function of a turbid medium from the profile of subdiffusive and diffusive light reflectance.

  17. Phase Transition for the Large-Dimensional Contact Process with Random Recovery Rates on Open Clusters

    NASA Astrophysics Data System (ADS)

    Xue, Xiaofeng

    2016-12-01

    In this paper we are concerned with the contact process with random recovery rates on open clusters of bond percolation on Z^d. Let ξ be a random variable such that P(ξ ≥ 1)=1, which ensures E1/ξ <+∞, then we assign i. i. d. copies of ξ on the vertices as the random recovery rates. Assuming that each edge is open with probability p and the infection can only spread through the open edges, then we obtain that limsup _{d→ +∞}λ _d≤ λ _c=1/pE{1}/{ξ}, where λ _d is the critical value of the process on Z^d, i.e., the maximum of the infection rates with which the infection dies out with probability one when only the origin is infected at t=0. To prove the above main result, we show that the following phase transition occurs. Assuming that lceil log drceil vertices are infected at t=0, where these vertices can be located anywhere, then when the infection rate λ >λ _c, the process survives with high probability as d→ +∞ while when λ <λ _c, the process dies out at time O(log d) with high probability.

  18. Phase transitions for random states and a semicircle law for the partial transpose

    NASA Astrophysics Data System (ADS)

    Aubrun, Guillaume; Szarek, Stanisław J.; Ye, Deping

    2012-03-01

    For a system of N identical particles in a random pure state, there is a threshold k0=k0(N)˜N/5 such that two subsystems of k particles each typically share entanglement if k>k0, and typically do not share entanglement if kphase transition for the positive partial transpose (PPT) property can be described even more precisely. For example, for N qubits the two subsystems of size k are typically in a PPT state if kk1. Since, for a given state of the entire system, the induced state of a subsystem is given by the partial trace, the above facts can be rephrased as properties of random induced states. An important step in the analysis depends on identifying the asymptotic spectral density of the partial transposes of such random induced states, a result which is interesting in its own right.

  19. Nonequilibrium phase transitions in lattice systems with random-field competing kinetics

    NASA Astrophysics Data System (ADS)

    López-Lacomba, A. I.; Marro, J.

    1992-10-01

    We study a class of lattice interacting-spin systems evolving stochastically under the simultaneous operation of several spin-flip mechanisms, each acting independently and responding to a different applied magnetic field. This induces an extra randomness which may occur in real systems, e.g., a magnetic system under the action of a field varying with a much shorter period than the mean time between successive transitions. Such a situation-in which one may say in some sense that frustration has a dynamical origin- may also be viewed as a nonequilibrium version of the random-field Ising model. By following a method of investigating stationary probability distributions in systems with competing kinetics [P. L. Garrido and J. Marro, Phys. Rev. Lett. 62, 1929 (1989)], we solve one-dimensional lattices supporting different field distributions and transition rates for the elementary kinetical processes, thus revealing a rich variety of phase transitions and critical phenomena. Some exact results for lattices of arbitrary dimension, and comparisons with the standard quenched and annealed random-field models, and with a nonequilibrium diluted antiferromagnetic system, are also reported.

  20. A random phased array device for delivery of high intensity focused ultrasound.

    PubMed

    Hand, J W; Shaw, A; Sadhoo, N; Rajagopal, S; Dickinson, R J; Gavrilov, L R

    2009-10-07

    Randomized phased arrays can offer electronic steering of a single focus and simultaneous multiple foci concomitant with low levels of secondary maxima and are potentially useful as sources of high intensity focused ultrasound (HIFU). This work describes laboratory testing of a 1 MHz random phased array consisting of 254 elements on a spherical shell of radius of curvature 130 mm and diameter 170 mm. Acoustic output power and efficiency are measured for a range of input electrical powers, and field distributions for various single- and multiple-focus conditions are evaluated by a novel technique using an infrared camera to provide rapid imaging of temperature changes on the surface of an absorbing target. Experimental results show that the array can steer a single focus laterally to at least +/-15 mm off axis and axially to more than +/-15 mm from the centre of curvature of the array and patterns of four and five simultaneous foci +/-10 mm laterally and axially whilst maintaining low intensity levels in secondary maxima away from the targeted area in good agreement with linear theoretical predictions. Experiments in which pork meat was thermally ablated indicate that contiguous lesions several cm(3) in volume can be produced using the patterns of multiple foci.

  1. Efficient Text Encryption and Hiding with Double-Random Phase-Encoding

    PubMed Central

    Sang, Jun; Ling, Shenggui; Alam, Mohammad S.

    2012-01-01

    In this paper, a double-random phase-encoding technique-based text encryption and hiding method is proposed. First, the secret text is transformed into a 2-dimensional array and the higher bits of the elements in the transformed array are used to store the bit stream of the secret text, while the lower bits are filled with specific values. Then, the transformed array is encoded with double-random phase-encoding technique. Finally, the encoded array is superimposed on an expanded host image to obtain the image embedded with hidden data. The performance of the proposed technique, including the hiding capacity, the recovery accuracy of the secret text, and the quality of the image embedded with hidden data, is tested via analytical modeling and test data stream. Experimental results show that the secret text can be recovered either accurately or almost accurately, while maintaining the quality of the host image embedded with hidden data by properly selecting the method of transforming the secret text into an array and the superimposition coefficient. By using optical information processing techniques, the proposed method has been found to significantly improve the security of text information transmission, while ensuring hiding capacity at a prescribed level. PMID:23202003

  2. Optical cryptosystem of color images using random phase masks in the fractional wavelet transform domain

    NASA Astrophysics Data System (ADS)

    Singh, Hukum

    2016-05-01

    An optical color image encryption in the Fractional Wavelet Transform (FWT) domain is carried out. The original images are segregated into three colors components: R (red), G (green) and B (blue). After that the components are encrypted separately using double random phase encoding (DRPE) in the FWT domain. Random phase masks (RPMs) are used in the input as well as in Fourier plane. The images to be encrypted are transformed with the discrete wavelet transform (DWT), the resulting coefficients from the DWT are multiplied each one by masks different form RPM. Masks are independent each other and the results are applied an inverse discrete Wavelet Transform (IDWT), obtaining the encrypted images. The input images are recovered from their corresponding encrypted images by using the correct parameters of the FWT, and its digital implementation has been performed using MATLAB 7.6.0 (R2008a). The mother wavelet family and fractional orders associated with the FWT are extra keys that access difficulty an attacker; thereby the scheme is more secure as compared to conventional techniques. The sensitivity of proposed scheme is verified with encryption parameters, occlusions, and noise attacks.

  3. Fixation using alternative implants for the treatment of hip fractures (FAITH): design and rationale for a multi-centre randomized trial comparing sliding hip screws and cancellous screws on revision surgery rates and quality of life in the treatment of femoral neck fractures

    PubMed Central

    2014-01-01

    Background Hip fractures are a common type of fragility fracture that afflict 293,000 Americans (over 5,000 per week) and 35,000 Canadians (over 670 per week) annually. Despite the large population impact the optimal fixation technique for low energy femoral neck fractures remains controversial. The primary objective of the FAITH study is to assess the impact of cancellous screw fixation versus sliding hip screws on rates of revision surgery at 24 months in individuals with femoral neck fractures. The secondary objective is to determine the impact on health-related quality of life, functional outcomes, health state utilities, fracture healing, mortality and fracture-related adverse events. Methods/Design FAITH is a multi-centre, multi-national randomized controlled trial utilizing minimization to determine patient allocation. Surgeons in North America, Europe, Australia, and Asia will recruit a total of at least 1,000 patients with low-energy femoral neck fractures. Using central randomization, patients will be allocated to receive surgical treatment with cancellous screws or a sliding hip screw. Patient outcomes will be assessed at one week (baseline), 10 weeks, 6, 12, 18, and 24 months post initial fixation. We will independently adjudicate revision surgery and complications within 24 months of the initial fixation. Outcome analysis will be performed using a Cox proportional hazards model and likelihood ratio test. Discussion This study represents major international efforts to definitively resolve the treatment of low-energy femoral neck fractures. This trial will not only change current Orthopaedic practice, but will also set a benchmark for the conduct of future Orthopaedic trials. Trial registration The FAITH trial is registered at ClinicalTrials.gov (Identifier NCT00761813). PMID:24965132

  4. 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

  5. Global phase diagram of two-dimensional Dirac fermions in random potentials

    NASA Astrophysics Data System (ADS)

    Ryu, S.; Mudry, C.; Ludwig, A. W. W.; Furusaki, A.

    2012-06-01

    Anderson localization is studied for two flavors of massless Dirac fermions in two-dimensional space perturbed by static disorder that is invariant under a chiral symmetry (chS) and a time-reversal symmetry (TRS) operation which, when squared, is equal either to plus or minus the identity. The former TRS (symmetry class BDI) can, for example, be realized when the Dirac fermions emerge from spinless fermions hopping on a two-dimensional lattice with a linear energy dispersion such as the honeycomb lattice (graphene) or the square lattice with π flux per plaquette. The latter TRS is realized by the surface states of three-dimensional Z2-topological band insulators in symmetry class CII. In the phase diagram parametrized by the disorder strengths, there is an infrared stable line of critical points for both symmetry classes BDI and CII. Here we discuss a “global phase diagram” in which disordered Dirac fermion systems in all three chiral symmetry classes, AIII, CII, and BDI, occur in four quadrants, sharing one corner which represents the clean Dirac fermion limit. This phase diagram also includes symmetry classes AII [e.g., appearing at the surface of a disordered three-dimensional Z2-topological band insulator in the spin-orbit (symplectic) symmetry class] and D (e.g., the random bond Ising model in two dimensions) as boundaries separating regions of the phase diagram belonging to the three chS classes AIII, BDI, and CII. Moreover, we argue that physics of Anderson localization in the CII phase can be presented in terms of a non-linear-σ model (NLσM) with a Z2-topological term. We thereby complete the derivation of topological or Wess-Zumino-Novikov-Witten terms in the NLσM description of disordered fermionic models in all ten symmetry classes relevant to Anderson localization in two spatial dimensions.

  6. Therapeutic Intervention in Multiple Sclerosis with Alpha B-Crystallin: A Randomized Controlled Phase IIa Trial

    PubMed Central

    van Noort, Johannes M.; Bsibsi, Malika; Nacken, Peter J.; Verbeek, Richard; Venneker, Edna H.G.

    2015-01-01

    As a molecular chaperone and activator of Toll-like receptor 2-mediated protective responses by microglia and macrophages, the small heat shock protein alpha B-crystallin (HspB5) exerts therapeutic effects in different animal models for neuroinflammation, including the model for multiple sclerosis (MS). Yet, HspB5 can also stimulate human antigen-specific memory T cells to release IFN-γ, a cytokine with well-documented detrimental effects during MS. In this study, we explored in a Phase IIa randomized clinical trial the therapeutic application of HspB5 in relapsing-remitting MS (RR-MS), using intravenous doses sufficient to support its protective effects, but too low to trigger pathogenic memory T-cell responses. These sub-immunogenic doses were selected based on in vitro analysis of the dose-response profile of human T cells and macrophages to HspB5, and on the immunological effects of HspB5 in healthy humans as established in a preparatory Phase I study. In a 48-week randomized, placebo-controlled, double-blind Phase IIa trial, three bimonthly intravenous injections of 7.5, 12.5 or 17.5 mg HspB5 were found to be safe and well tolerated in RR-MS patients. While predefined clinical endpoints did not differ significantly between the relatively small groups of MS patients treated with either HspB5 or placebo, repeated administration especially of the lower doses of HspB5 led to a progressive decline in MS lesion activity as monitored by magnetic resonance imaging (MRI), which was not seen in the placebo group. Exploratory linear regression analysis revealed this decline to be significant in the combined group receiving either of the two lower doses, and to result in a 76% reduction in both number and total volumes of active MRI lesions at 9 months into the study. These data provide the first indication for clinical benefit resulting from intervention in RR-MS with HspB5. Trial Registration: ClinicalTrials.gov Phase I: NCT02442557; Phase IIa: NCT02442570 PMID

  7. Retrieval of phase distributions from the quadriwave lateral shearing interferogram obtained by randomly encoded hybrid grating

    NASA Astrophysics Data System (ADS)

    Ling, Tong; Yang, Yongying; Liu, Dong; Yue, Xiumei; Jiang, Jiabin

    2015-10-01

    A wavefront retrieval method for the quadriwave lateral shearing interferogram obtained by randomly encoded hybrid grating (REHG) is proposed. The REHG consists of a binary amplitude grating and a phase chessboard, and the Faunhofer diffractions of this grating only contain the +/-1 orders in two orthogonal directions. As a result, no order selection mask is ever needed by the REHG for quadriwave lateral shearing interference. To retrieve the phase distributions from the REHG interferograms, fast Fourier transform (FFT) technique is employed at first to get the frequency spectrum. By performing inverse fast Fourier transform (IFFT) of the +1 order spectrum in the x and y directions, it is possible to extract shearing wavefronts from the interferogram in both two orthogonal directions. Using the translation property of Fourier transform, the relationship between the Fourier spectrum of the shearing wavefronts and the Fourier spectrum of the wavefront under test is deduced. The wavefront under test is retrieved by establishing an evaluation function firstly and finding the minimum value with least-square-solution. Analysis and compensations are made to reduce the errors in the testing results. Simulation experiments have shown that this method can retrieve different phase distributions without losing high-frequency information.

  8. Super-rough glassy phase of the random field XY model in two dimensions.

    PubMed

    Perret, Anthony; Ristivojevic, Zoran; Le Doussal, Pierre; Schehr, Grégory; Wiese, Kay J

    2012-10-12

    We study both analytically, using the renormalization group (RG) to two loop order, and numerically, using an exact polynomial algorithm, the disorder-induced glass phase of the two-dimensional XY model with quenched random symmetry-breaking fields and without vortices. In the super-rough glassy phase, i.e., below the critical temperature T(c), the disorder and thermally averaged correlation function B(r) of the phase field θ(x), B(r)=([θ(x)-θ(x+r)](2)) behaves, for r > a, as B(r) is approximately equal to A(τ)ln(2)(r/a) where r=|r| and a is a microscopic length scale. We derive the RG equations up to cubic order in τ=(T(c)-T)/T(c) and predict the universal amplitude A(τ)=2τ(2)-2τ(3)+O(τ(4)). The universality of A(τ) results from nontrivial cancellations between nonuniversal constants of RG equations. Using an exact polynomial algorithm on an equivalent dimer version of the model we compute A(τ) numerically and obtain a remarkable agreement with our analytical prediction, up to τ≈0.5.

  9. Spatial cross modulation method using a random diffuser and phase-only spatial light modulator for constructing arbitrary complex fields.

    PubMed

    Shibukawa, Atsushi; Okamoto, Atsushi; Takabayashi, Masanori; Tomita, Akihisa

    2014-02-24

    We propose a spatial cross modulation method using a random diffuser and a phase-only spatial light modulator (SLM), by which arbitrary complex-amplitude fields can be generated with higher spatial resolution and diffraction efficiency than off-axis and double-phase computer-generated holograms. Our method encodes the original complex object as a phase-only diffusion image by scattering the complex object using a random diffuser. In addition, all incoming light to the SLM is consumed for a single diffraction order, making a diffraction efficiency of more than 90% possible. This method can be applied for holographic data storage, three-dimensional displays, and other such applications.

  10. Double-random-phase encryption with photon counting for image authentication using only the amplitude of the encrypted image.

    PubMed

    Wang, Yong; Markman, Adam; Quan, Chenggen; Javidi, Bahram

    2016-11-01

    We present a photon-counting double-random-phase encryption technique that only requires the photon-limited amplitude of the encrypted image for decryption. The double-random-phase encryption is used to encrypt an image, generating a complex image. Photon counting is applied to the amplitude of the encrypted image, generating a sparse noise-like image; however, the phase information is not retained. By not using the phase information, the encryption process is simplified, allowing for intensity detection and also less information to be recorded. Using a phase numerically generated from the correct encryption keys together with the photon-limited amplitude of the encrypted image, we are able to decrypt the image. Moreover, nonlinear correlation algorithms can be used to authenticate the decrypted image. Both amplitude-based and full-phase encryption using the proposed method are investigated. Preliminary computational results and performance evaluation are presented.

  11. Concepts for a theoretical and experimental study of lifting rotor random loads and vibrations, Phase 1

    NASA Technical Reports Server (NTRS)

    Hohenemser, K. H.; Gaonkar, G. H.

    1967-01-01

    A number of lifting rotor conditions with random inputs are discussed. The present state of random process theory, applicable to lifting rotor problems is sketched. Possible theories of random blade flapping and random blade flap-bending are outlined and their limitations discussed. A plan for preliminary experiments to study random flapping motions of a see-saw rotor is developed.

  12. Avalanche and bit independence characteristics of double random phase encoding in the Fourier and Fresnel domains.

    PubMed

    Moon, Inkyu; Yi, Faliu; Lee, Yeon H; Javidi, Bahram

    2014-05-01

    In this work, we evaluate the avalanche effect and bit independence properties of the double random phase encoding (DRPE) algorithm in the Fourier and Fresnel domains. Experimental results show that DRPE has excellent bit independence characteristics in both the Fourier and Fresnel domains. However, DRPE achieves better avalanche effect results in the Fresnel domain than in the Fourier domain. DRPE gives especially poor avalanche effect results in the Fourier domain when only one bit is changed in the plaintext or in the encryption key. Despite this, DRPE shows satisfactory avalanche effect results in the Fresnel domain when any other number of bits changes in the plaintext or in the encryption key. To the best of our knowledge, this is the first report on the avalanche effect and bit independence behaviors of optical encryption approaches for bit units.

  13. Insight into organic reactions from the direct random phase approximation and its corrections

    SciTech Connect

    Ruzsinszky, Adrienn; Zhang, Igor Ying; Scheffler, Matthias

    2015-10-14

    The performance of the random phase approximation (RPA) and beyond-RPA approximations for the treatment of electron correlation is benchmarked on three different molecular test sets. The test sets are chosen to represent three typical sources of error which can contribute to the failure of most density functional approximations in chemical reactions. The first test set (atomization and n-homodesmotic reactions) offers a gradually increasing balance of error from the chemical environment. The second test set (Diels-Alder reaction cycloaddition = DARC) reflects more the effect of weak dispersion interactions in chemical reactions. Finally, the third test set (self-interaction error 11 = SIE11) represents reactions which are exposed to noticeable self-interaction errors. This work seeks to answer whether any one of the many-body approximations considered here successfully addresses all these challenges.

  14. Insight into organic reactions from the direct random phase approximation and its corrections

    NASA Astrophysics Data System (ADS)

    Ruzsinszky, Adrienn; Zhang, Igor Ying; Scheffler, Matthias

    2015-10-01

    The performance of the random phase approximation (RPA) and beyond-RPA approximations for the treatment of electron correlation is benchmarked on three different molecular test sets. The test sets are chosen to represent three typical sources of error which can contribute to the failure of most density functional approximations in chemical reactions. The first test set (atomization and n-homodesmotic reactions) offers a gradually increasing balance of error from the chemical environment. The second test set (Diels-Alder reaction cycloaddition = DARC) reflects more the effect of weak dispersion interactions in chemical reactions. Finally, the third test set (self-interaction error 11 = SIE11) represents reactions which are exposed to noticeable self-interaction errors. This work seeks to answer whether any one of the many-body approximations considered here successfully addresses all these challenges.

  15. Double random phase encryption scheme to multiplex and simultaneous encode multiple images.

    PubMed

    Alfalou, Ayman; Mansour, Ali

    2009-11-01

    Here we present a new approach of multiplexing and simultaneous encoding of target images. Our approach can enhance the encryption level of a classical double random phase (DRP) encryption system by adding a supplementary security layer. The new approach can be divided into two security layers. The first layer is called the multiplexing level, which consists in using iterative Fourier transformations along with several encryption key images. These latter can be a set of biometric images. At the second layer, we use a classical DRP system. The two layers enable us to encode several target images (multi-encryption) and to reduce, at the same time, the requested decoded information (transmitted or storage information).

  16. N-block separable random phase approximation: dipole oscillations in sodium clusters and {C}_{60} fullerene

    NASA Astrophysics Data System (ADS)

    Palade, D. I.; Baran, V.

    2016-09-01

    We generalize the schematic model based on the Random Phase Approximation (RPA) with separable interaction, to a collection of subspaces of ph excitations which interact with different coupling constants. This ansatz notably lowers the numerical effort involved, by reducing the RPA eigenvalue problem to a finite small dimensional system of equation. We derive the associated dispersion relation and the normalization condition for the newly defined unknowns of the system. In contrast with the standard separable approach, the present formalism is able to describe more than one collective excitation even in the degenerate limit, giving also access to the nature of the resonance. The theoretical framework is tested investigating the dipolar oscillations in various neutral and singly charged sodium clusters and C 60 fullerene with results in good agreement with full RPA calculations and experimental data. It is proven that the 40 eV resonance present in photoabsorption spectra of C 60 is a localized surface plasmon.

  17. Pseudo-random-bit-sequence phase modulation for reduced errors in a fiber optic gyroscope.

    PubMed

    Chamoun, Jacob; Digonnet, Michel J F

    2016-12-15

    Low noise and drift in a laser-driven fiber optic gyroscope (FOG) are demonstrated by interrogating the sensor with a low-coherence laser. The laser coherence was reduced by broadening its optical spectrum using an external electro-optic phase modulator driven by either a sinusoidal or a pseudo-random bit sequence (PRBS) waveform. The noise reduction measured in a FOG driven by a modulated laser agrees with the calculations based on the broadened laser spectrum. Using PRBS modulation, the linewidth of a laser was broadened from 10 MHz to more than 10 GHz, leading to a measured FOG noise of only 0.00073  deg/√h and a drift of 0.023  deg/h. To the best of our knowledge, these are the lowest noise and drift reported in a laser-driven FOG, and this noise is below the requirement for the inertial navigation of aircraft.

  18. Density-functional correction of random-phase-approximation correlation with results for jellium surface energies

    NASA Astrophysics Data System (ADS)

    Kurth, Stefan; Perdew, John P.

    1999-04-01

    Since long-range electron-electron correlation is treated properly in the random phase approximation (RPA), we define short-range correlation as the correction to the RPA. The effects of short-range correlation are investigated here in the local spin density (LSD) approximation and the generalized gradient approximation (GGA). Results are presented for atoms, molecules, and jellium surfaces. It is found that (1) short-range correlation energies are less sensitive to the inclusion of density gradients than are full correlation energies, and (2) short-range correlation makes a surprisingly small contribution to surface and molecular atomization energies. In order to improve the accuracy of electronic-structure calculations, we therefore combine a GGA treatment of short-range correlation with a full RPA treatment of the exchange-correlation energy. This approach leads to jellium surface energies close to those of the LSD approximation for exchange and correlation together (but not for each separately).

  19. Experimental evaluation of fingerprint verification system based on double random phase encoding

    NASA Astrophysics Data System (ADS)

    Suzuki, Hiroyuki; Yamaguchi, Masahiro; Yachida, Masuyoshi; Ohyama, Nagaaki; Tashima, Hideaki; Obi, Takashi

    2006-03-01

    We proposed a smart card holder authentication system that combines fingerprint verification with PIN verification by applying a double random phase encoding scheme. In this system, the probability of accurate verification of an authorized individual reduces when the fingerprint is shifted significantly. In this paper, a review of the proposed system is presented and preprocessing for improving the false rejection rate is proposed. In the proposed method, the position difference between two fingerprint images is estimated by using an optimized template for core detection. When the estimated difference exceeds the permissible level, the user inputs the fingerprint again. The effectiveness of the proposed method is confirmed by a computational experiment; its results show that the false rejection rate is improved.

  20. Evaluation of ground-state entanglement in spin systems with the random phase approximation

    NASA Astrophysics Data System (ADS)

    Matera, J. M.; Rossignoli, R.; Canosa, N.

    2010-11-01

    We discuss a general treatment based on the mean field plus random-phase approximation (RPA) for the evaluation of subsystem entropies and negativities in ground states of spin systems. The approach leads to a tractable general method that becomes straightforward in translationally invariant arrays. The method is examined in arrays of arbitrary spin with XYZ couplings of general range in a uniform transverse field, where the RPA around both the normal and parity-breaking mean-field state, together with parity-restoration effects, is discussed in detail. In the case of a uniformly connected XYZ array of arbitrary size, the method is shown to provide simple analytic expressions for the entanglement entropy of any global bipartition, as well as for the negativity between any two subsystems, which become exact for large spin. The limit case of a spin s pair is also discussed.

  1. Simulation study on heat conduction of a nanoscale phase-change random access memory cell.

    PubMed

    Kim, Junho; Song, Ki-Bong

    2006-11-01

    We have investigated heat transfer characteristics of a nano-scale phase-change random access memory (PRAM) cell using finite element method (FEM) simulation. Our PRAM cell is based on ternary chalcogenide alloy, Ge2Sb2Te5 (GST), which is used as a recording layer. For contact area of 100 x 100 nm2, simulations of crystallization and amorphization processes were carried out. Physical quantities such as electric conductivity, thermal conductivity, and specific heat were treated as temperature-dependent parameters. Through many simulations, it is concluded that one can reduce set current by decreasing both electric conductivities of amorphous GST and crystalline GST, and in addition to these conditions by decreasing electric conductivity of molten GST one can also reduce reset current significantly.

  2. Quantum Phase Transition in the Two-Dimensional Random Transverse-Field Ising Model

    NASA Astrophysics Data System (ADS)

    Pich, C.; Young, A. P.

    1998-03-01

    We study the quantum phase transition in the random transverse-field Ising model by Monte Carlo simulations. In one-dimension it has been established that this system has the following striking behavior: (i) the dynamical exponent is infinite, and (ii) the exponents for the divergence of the average and typical correlation lengths are different. An important issue is whether this behavior is special to one-dimension or whether similar behavior persists in higher dimensions. Here we attempt to answer this question by studies of the two-dimensional model. Our simulations use the Wolff cluster algorithm and the results are analyzed by anisotropic finite size scaling, paying particular attention to the Binder ratio of moments of the order parameter distribution and the distribution of the spin-spin correlation functions for various distances.

  3. Self-consistent quasiparticle random-phase approximation for a multilevel pairing model

    SciTech Connect

    Hung, N. Quang; Dang, N. Dinh

    2007-11-15

    Particle-number projection within the Lipkin-Nogami (LN) method is applied to the self-consistent quasiparticle random-phase approximation (SCQRPA), which is tested in an exactly solvable multilevel pairing model. The SCQRPA equations are numerically solved to find the energies of the ground and excited states at various numbers {omega} of doubly degenerate equidistant levels. The use of the LN method allows one to avoid the collapse of the BCS (QRPA) to obtain the energies of the ground and excited states as smooth functions of the interaction parameter G. The comparison between results given by different approximations such as the SCRPA, QRPA, LNQRPA, SCQRPA, and LNSCQRPA is carried out. Although the use of the LN method significantly improves the agreement with the exact results in the intermediate coupling region, we found that in the strong coupling region the SCQRPA results are closest to the exact ones.

  4. Rare events statistics of random walks on networks: localisation and other dynamical phase transitions

    NASA Astrophysics Data System (ADS)

    De Bacco, Caterina; Guggiola, Alberto; Kühn, Reimer; Paga, Pierre

    2016-05-01

    Rare event statistics for random walks on complex networks are investigated using the large deviation formalism. Within this formalism, rare events are realised as typical events in a suitably deformed path-ensemble, and their statistics can be studied in terms of spectral properties of a deformed Markov transition matrix. We observe two different types of phase transition in such systems: (i) rare events which are singled out for sufficiently large values of the deformation parameter may correspond to localised modes of the deformed transition matrix; (ii) ‘mode-switching transitions’ may occur as the deformation parameter is varied. Details depend on the nature of the observable for which the rare event statistics is studied, as well as on the underlying graph ensemble. In the present paper we report results on rare events statistics for path averages of random walks in Erdős-Rényi and scale free networks. Large deviation rate functions and localisation properties are studied numerically. For observables of the type considered here, we also derive an analytical approximation for the Legendre transform of the large deviation rate function, which is valid in the large connectivity limit. It is found to agree well with simulations.

  5. Efficient self-consistent treatment of electron correlation within the random phase approximation

    NASA Astrophysics Data System (ADS)

    Bleiziffer, Patrick; Heßelmann, Andreas; Görling, Andreas

    2013-08-01

    A self-consistent Kohn-Sham (KS) method is presented that treats correlation on the basis of the adiabatic-connection dissipation-fluctuation theorem employing the direct random phase approximation (dRPA), i.e., taking into account only the Coulomb kernel while neglecting the exchange-correlation kernel in the calculation of the Kohn-Sham correlation energy and potential. The method, denoted self-consistent dRPA method, furthermore treats exactly the exchange energy and the local multiplicative KS exchange potential. It uses Gaussian basis sets, is reasonably efficient, exhibiting a scaling of the computational effort with the forth power of the system size, and thus is generally applicable to molecules. The resulting dRPA correlation potentials in contrast to common approximate correlation potentials are in good agreement with exact reference potentials. The negatives of the eigenvalues of the highest occupied molecular orbitals are found to be in good agreement with experimental ionization potentials. Total energies from self-consistent dRPA calculations, as expected, are even poorer than non-self-consistent dRPA total energies and dRPA reaction and non-covalent binding energies do not significantly benefit from self-consistency. On the other hand, energies obtained with a recently introduced adiabatic-connection dissipation-fluctuation approach (EXXRPA+, exact-exchange random phase approximation) that takes into account, besides the Coulomb kernel, also the exact frequency-dependent exchange kernel are significantly improved if evaluated with orbitals obtained from a self-consistent dRPA calculation instead of an exact exchange-only calculation. Total energies, reaction energies, and noncovalent binding energies obtained in this way are of the same quality as those of high-level quantum chemistry methods, like the coupled cluster singles doubles method which is computationally more demanding.

  6. Top eigenvalue of a random matrix: large deviations and third order phase transition

    NASA Astrophysics Data System (ADS)

    Majumdar, Satya N.; Schehr, Grégory

    2014-01-01

    We study the fluctuations of the largest eigenvalue λmax of N × N random matrices in the limit of large N. The main focus is on Gaussian β ensembles, including in particular the Gaussian orthogonal (β = 1), unitary (β = 2) and symplectic (β = 4) ensembles. The probability density function (PDF) of λmax consists, for large N, of a central part described by Tracy-Widom distributions flanked, on both sides, by two large deviation tails. While the central part characterizes the typical fluctuations of λmax—of order {O}(N^{-2/3}) —the large deviation tails are instead associated with extremely rare fluctuations—of order {O}(1). Here we review some recent developments in the theory of these extremely rare events using a Coulomb gas approach. We discuss in particular the third order phase transition which separates the left tail from the right tail, a transition akin to the so-called Gross-Witten-Wadia phase transition found in 2-d lattice quantum chromodynamics. We also discuss the occurrence of similar third order transitions in various physical problems, including non-intersecting Brownian motions, conductance fluctuations in mesoscopic physics and entanglement in a bipartite system.

  7. High energy X-ray phase and dark-field imaging using a random absorption mask

    PubMed Central

    Wang, Hongchang; Kashyap, Yogesh; Cai, Biao; Sawhney, Kawal

    2016-01-01

    High energy X-ray imaging has unique advantage over conventional X-ray imaging, since it enables higher penetration into materials with significantly reduced radiation damage. However, the absorption contrast in high energy region is considerably low due to the reduced X-ray absorption cross section for most materials. Even though the X-ray phase and dark-field imaging techniques can provide substantially increased contrast and complementary information, fabricating dedicated optics for high energies still remain a challenge. To address this issue, we present an alternative X-ray imaging approach to produce transmission, phase and scattering signals at high X-ray energies by using a random absorption mask. Importantly, in addition to the synchrotron radiation source, this approach has been demonstrated for practical imaging application with a laboratory-based microfocus X-ray source. This new imaging method could be potentially useful for studying thick samples or heavy materials for advanced research in materials science. PMID:27466217

  8. Probability Distribution, Moments and Phase Transition for Directed Polymers with Random Signs on Hierarchical Lattices.

    NASA Astrophysics Data System (ADS)

    Aponte, Eduardo; Medina, Ernesto

    1998-03-01

    We study sums of directed paths on a hierarchical lattice, where each bond has either a positive or negative sign. We attempt to address the controversy of whether a phase transition occurs as a function of ± sign fraction on the bonds, by computing the path sum distribution exactly. We also use exact moment recursion relations(E. Medina and M. Kardar, Jour. Stat. Phys. 71), 967 (1993) to check whether moments determine a unique probability distribution. We find evidence of a second order phase transition at a critical ± sign fraction in contrast to a first order transition found in the mean field theory. We also find that while moments determine a unique distribution above the second order transition, below the transition they grow faster than exponential. Therefore, in the latter case, there is no, one to one, relation between distribution and moments. The statistical model of random signs is the basis of the Nguyen-Spivak-Shklovskii model for quantum interference effects in insulators.

  9. Influence of limited random-phase of objects on the image quality of 3D holographic display

    NASA Astrophysics Data System (ADS)

    Ma, He; Liu, Juan; Yang, Minqiang; Li, Xin; Xue, Gaolei; Wang, Yongtian

    2017-02-01

    Limited-random-phase time average method is proposed to suppress the speckle noise of three dimensional (3D) holographic display. The initial phase and the range of the random phase are studied, as well as their influence on the optical quality of the reconstructed images, and the appropriate initial phase ranges on object surfaces are obtained. Numerical simulations and optical experiments with 2D and 3D reconstructed images are performed, where the objects with limited phase range can suppress the speckle noise in reconstructed images effectively. It is expected to achieve high-quality reconstructed images in 2D or 3D display in the future because of its effectiveness and simplicity.

  10. A Locust Phase Change Model with Multiple Switching States and Random Perturbation

    NASA Astrophysics Data System (ADS)

    Xiang, Changcheng; Tang, Sanyi; Cheke, Robert A.; Qin, Wenjie

    2016-12-01

    Insects such as locusts and some moths can transform from a solitarious phase when they remain in loose populations and a gregarious phase, when they may swarm. Therefore, the key to effective management of outbreaks of species such as the desert locust Schistocercagregaria is early detection of when they are in the threshold state between the two phases, followed by timely control of their hopper stages before they fledge because the control of flying adult swarms is costly and often ineffective. Definitions of gregarization thresholds should assist preventive control measures and avoid treatment of areas that might not lead to gregarization. In order to better understand the effects of the threshold density which represents the gregarization threshold on the outbreak of a locust population, we developed a model of a discrete switching system. The proposed model allows us to address: (1) How frequently switching occurs from solitarious to gregarious phases and vice versa; (2) When do stable switching transients occur, the existence of which indicate that solutions with larger amplitudes can switch to a stable attractor with a value less than the switching threshold density?; and (3) How does random perturbation influence the switching pattern? Our results show that both subsystems have refuge equilibrium points, outbreak equilibrium points and bistable equilibria. Further, the outbreak equilibrium points and bistable equilibria can coexist for a wide range of parameters and can switch from one to another. This type of switching is sensitive to the intrinsic growth rate and the initial values of the locust population, and may result in locust population outbreaks and phase switching once a small perturbation occurs. Moreover, the simulation results indicate that the switching transient patterns become identical after some generations, suggesting that the evolving process of the perturbation system is not related to the initial value after some fixed number of

  11. Validation of the k-filtering technique for a signal composed of random phase plane waves and non-random coherent structures

    NASA Astrophysics Data System (ADS)

    Roberts, O. W.; Li, X.; Jeska, L.

    2014-08-01

    Recent observations of astrophysical magnetic fields have shown the presence of fluctuations being wave-like (propagating in the plasma frame) and those described as being structure-like (advected by the plasma bulk velocity). Typically with single spacecraft missions it is impossible to differentiate between these two fluctuations, due to the inherent spatio-temporal ambiguity associated with a single point measurement. However missions such as Cluster which contain multiple spacecraft have allowed temporal and spatial changes to be resolved, with techniques such as the k-filtering technique. While this technique does not assume Taylor's hypothesis as is necessary with single spacecraft missions, it does require weak stationarity of the time series, and that the fluctuations can be described by a superposition of plane waves with random phase. In this paper we test whether the method can cope with a synthetic signal which is composed of a combination of non-random phase coherent structures with a mean radius d and a mean separation λ, as well as plane waves with random phase.

  12. Validation of the k-filtering technique for a signal composed of random-phase plane waves and non-random coherent structures

    NASA Astrophysics Data System (ADS)

    Roberts, O. W.; Li, X.; Jeska, L.

    2014-12-01

    Recent observations of astrophysical magnetic fields have shown the presence of fluctuations being wave-like (propagating in the plasma frame) and those described as being structure-like (advected by the plasma bulk velocity). Typically with single-spacecraft missions it is impossible to differentiate between these two fluctuations, due to the inherent spatio-temporal ambiguity associated with a single point measurement. However missions such as Cluster which contain multiple spacecraft have allowed for temporal and spatial changes to be resolved, using techniques such as k filtering. While this technique does not assume Taylor's hypothesis it requires both weak stationarity of the time series and that the fluctuations can be described by a superposition of plane waves with random phases. In this paper we test whether the method can cope with a synthetic signal which is composed of a combination of non-random-phase coherent structures with a mean radius d and a mean separation λ, as well as plane waves with random phase.

  13. Effects of Random Circuit Fabrication Errors on Small Signal Gain and on Output Phase In a Traveling Wave Tube

    NASA Astrophysics Data System (ADS)

    Rittersdorf, I. M.; Antonsen, T. M., Jr.; Chernin, D.; Lau, Y. Y.

    2011-10-01

    Random fabrication errors may have detrimental effects on the performance of traveling-wave tubes (TWTs) of all types. A new scaling law for the modification in the average small signal gain and in the output phase is derived from the third order ordinary differential equation that governs the forward wave interaction in a TWT in the presence of random error that is distributed along the axis of the tube. Analytical results compare favorably with numerical results, in both gain and phase modifications as a result of random error in the phase velocity of the slow wave circuit. Results on the effect of the reverse-propagating circuit mode will be reported. This work supported by AFOSR, ONR, L-3 Communications Electron Devices, and Northrop Grumman Corporation.

  14. A Phase III, randomized, controlled, non-inferiority trial of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in patients with complicated skin and soft tissue infection with systemic inflammatory response or underlying comorbidities

    PubMed Central

    Dryden, Matthew; Zhang, Yingyuan; Wilson, David; Iaconis, Joseph P.; Gonzalez, Jesus

    2016-01-01

    Objectives Increasing the ceftaroline fosamil dose beyond 600 mg every 12 h may provide additional benefit for patients with complicated skin and soft tissue infections (cSSTIs) with severe inflammation and/or reduced pathogen susceptibility. A Phase III multicentre, randomized trial evaluated the safety and efficacy of ceftaroline fosamil 600 mg every 8 h in this setting. Methods Adult patients with cSSTI and systemic inflammation or comorbidities were randomized 2:1 to intravenous ceftaroline fosamil (600 mg every 8 h) or vancomycin (15 mg/kg every 12 h) plus aztreonam (1 g every 8 h) for 5–14 days. Clinical cure was assessed at the test of cure (TOC) visit (8–15 days after the final dose) in the modified ITT (MITT) and clinically evaluable (CE) populations. Non-inferiority was defined as a lower limit of the 95% CI around the treatment difference greater than –10%. An MRSA-focused expansion period was initiated after completion of the main study. Clinicaltrials.gov registration numbers NCT01499277 and NCT02202135. Results Clinical cure rates at TOC demonstrated non-inferiority of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in the MITT and CE populations: 396/506 (78.3%) versus 202/255 (79.2%) patients (difference −1.0%, 95% CI −6.9, 5.4) and 342/395 (86.6%) versus 180/211 (85.3%) patients (difference 1.3%, 95% CI −4.3, 7.5), respectively. In the expansion period, 3/4 (75%) patients treated with ceftaroline fosamil were cured at TOC. The frequency of adverse events was similar between groups. Conclusions Ceftaroline fosamil 600 mg every 8 h was effective for cSSTI patients with evidence of systemic inflammation and/or comorbidities. No new safety signals were identified. PMID:27585969

  15. Multilevel Monte Carlo for Two Phase Flow and Transport in a Subsurface Reservoir with Random Permeability

    NASA Astrophysics Data System (ADS)

    Müller, Florian; Jenny, Patrick; Daniel, Meyer

    2014-05-01

    To a large extent, the flow and transport behaviour within a subsurface reservoir is governed by its permeability. Typically, permeability measurements of a subsurface reservoir are affordable at few spatial locations only. Due to this lack of information, permeability fields are preferably described by stochastic models rather than deterministically. A stochastic method is needed to asses the transition of the input uncertainty in permeability through the system of partial differential equations describing flow and transport to the output quantity of interest. Monte Carlo (MC) is an established method for quantifying uncertainty arising in subsurface flow and transport problems. Although robust and easy to implement, MC suffers from slow statistical convergence. To reduce the computational cost of MC, the multilevel Monte Carlo (MLMC) method was introduced. Instead of sampling a random output quantity of interest on the finest affordable grid as in case of MC, MLMC operates on a hierarchy of grids. If parts of the sampling process are successfully delegated to coarser grids where sampling is inexpensive, MLMC can dramatically outperform MC. MLMC has proven to accelerate MC for several applications including integration problems, stochastic ordinary differential equations in finance as well as stochastic elliptic and hyperbolic partial differential equations. In this study, MLMC is combined with a reservoir simulator to assess uncertain two phase (water/oil) flow and transport within a random permeability field. The performance of MLMC is compared to MC for a two-dimensional reservoir with a multi-point Gaussian logarithmic permeability field. It is found that MLMC yields significant speed-ups with respect to MC while providing results of essentially equal accuracy. This finding holds true not only for one specific Gaussian logarithmic permeability model but for a range of correlation lengths and variances.

  16. Recombinant Bile Salt-Stimulated Lipase in Preterm Infant Feeding: A Randomized Phase 3 Study

    PubMed Central

    Casper, Charlotte; Hascoet, Jean-Michel; Ertl, Tibor; Gadzinowski, Janusz S.; Carnielli, Virgilio; Rigo, Jacques; Lapillonne, Alexandre; Couce, María L.; Vågerö, Mårten; Palmgren, Ingrid; Timdahl, Kristina; Hernell, Olle

    2016-01-01

    Introduction Feeding strategies are critical for healthy growth in preterm infants. Bile salt-stimulated lipase (BSSL), present in human milk, is important for fat digestion and absorption but is inactivated during pasteurization and absent in formula. This study evaluated if recombinant human BSSL (rhBSSL) improves growth in preterm infants when added to formula or pasteurized breast milk. Patients and Methods LAIF (Lipase Added to Infant Feeding) was a randomized, double-blind, placebo-controlled phase 3 study in infants born before 32 weeks of gestation. The primary efficacy variable was growth velocity (g/kg/day) during 4 weeks intervention. Follow-up visits were at 3 and 12 months. The study was performed at 54 centers in 10 European countries. Results In total 415 patients were randomized (rhBSSL n = 207, placebo n = 208), 410 patients were analyzed (rhBSSL n = 206, placebo n = 204) and 365 patients were followed until 12 months. Overall, there was no significantly improved growth velocity during rhBSSL treatment compared to placebo (16.77 vs. 16.56 g/kg/day, estimated difference 0.21 g/kg/day, 95% CI [-0.40; 0.83]), nor were secondary endpoints met. However, in a predefined subgroup, small for gestational age infants, there was a significant effect on growth in favor of rhBSSL during treatment. The incidence of adverse events was higher in the rhBSSL group during treatment. Conclusions Although this study did not meet its primary endpoint, except in a subgroup of infants small for gestational age, and there was an imbalance in short-term safety, these data provide insights in nutrition, growth and development in preterm infants. Trial Registration ClinicalTrials.gov NCT01413581 PMID:27244221

  17. The OptiMUM-study: EMDR therapy in pregnant women with posttraumatic stress disorder after previous childbirth and pregnant women with fear of childbirth: design of a multicentre randomized controlled trial

    PubMed Central

    Baas, M. A. M.; Stramrood, C. A. I.; Dijksman, L. M.; de Jongh, A.; van Pampus, M. G.

    2017-01-01

    ABSTRACT Background: Approximately 3% of women develop posttraumatic stress disorder (PTSD) after giving birth, and 7.5% of pregnant women show a pathological fear of childbirth (FoC). FoC or childbirth-related PTSD during (a subsequent) pregnancy can lead to a request for an elective caesarean section as well as adverse obstetrical and neonatal outcomes. For PTSD in general, and several subtypes of specific phobia, eye movement desensitization and reprocessing (EMDR) therapy has been proven effective, but little is known about the effects of applying EMDR during pregnancy. Objective: To describe the protocol of the OptiMUM-study. The main aim of the study is to determine whether EMDR therapy is an effective and safe treatment for pregnant women with childbirth-related PTSD or FoC. In addition, the cost-effectiveness of this approach will be analysed. Method: The single-blind OptiMUM-study consists of two two-armed randomized controlled trials (RCTs) with overlapping design. In several hospitals and community midwifery practices in Amsterdam, the Netherlands, all eligible pregnant women with a gestational age between eight and 20 weeks will be administered the Wijma delivery expectations questionnaire (WDEQ) to asses FoC. Multiparous women will also receive the PTSD checklist for DSM-5 (PCL-5) to screen for possible PTSD. The clinician administered PTSD scale (CAPS-5) will be used for assessing PTSD according to DSM-5 in women scoring above the PCL-5 cut-off value. Fifty women with childbirth-related PTSD and 120 women with FoC will be randomly allocated to either EMDR therapy carried out by a psychologist or care-as-usual. Women currently undergoing psychological treatment or women younger than 18 years will not be included. Primary outcome measures are severity of childbirth-related PTSD or FoC symptoms. Secondary outcomes are percentage of PTSD diagnoses, percentage caesarean sections, subjective childbirth experience, obstetrical and neonatal complications

  18. Randomized Placebo-Controlled Phase II Trial of Autologous Mesenchymal Stem Cells in Multiple Sclerosis

    PubMed Central

    Blanco, Yolanda; Marín, Pedro; Moreno, Beatriz; Berenguer, Joan; Gabilondo, Iñigo; Martínez-Heras, Eloy; Sola-Valls, Nuria; Arnaiz, Joan-Albert; Andreu, Enrique J.; Fernández, Begoña; Bullich, Santi; Sánchez-Dalmau, Bernardo; Graus, Francesc; Villoslada, Pablo; Saiz, Albert

    2014-01-01

    Objective Uncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL) on magnetic resonance imaging (MRI) at 6 months and at the end of the study. Methods Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS) 3.0–6.5 were randomized to receive IV 1–2×106 bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite), and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects. Results At baseline 9 patients were randomized to receive MSCs (n = 5) or placebo (n = 4). One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1–8.8 vs 12.3, 95% CI = 4.4–34.5, p = 0.064), and at the end of study to reduced mean GEL (−2.8±5.9 vs 3±5.4, p = 0.075). No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+) cells in blood of MSCs treated patients. Conclusion Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266 PMID:25436769

  19. Phase 3 Randomized Trial on Larynx Preservation Comparing Sequential vs Alternating Chemotherapy and Radiotherapy

    PubMed Central

    Rolland, F.; Tesselaar, M.; Bardet, E.; Leemans, C. R.; Geoffrois, L.; Hupperets, P.; Barzan, L.; de Raucourt, D.; Chevalier, D.; Licitra, L.; Lunghi, F.; Stupp, R.; Lacombe, D.; Bogaerts, J.; Horiot, J. C.; Bernier, J.; Vermorken, J. B.

    2009-01-01

    Background Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer. Methods Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3–T4) or hypopharynx (T2–T4), with regional lymph nodes in the neck staged as N0–N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The Kaplan–Meier method was used to obtain time-to-event data. Results The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the

  20. A Phase 2 Randomized Clinical Trial of Intravitreal Bevacizumab for Diabetic Macular Edema

    PubMed Central

    2008-01-01

    Objective To provide data on the short-term effect of intravitreal bevacizumab for diabetic macular edema (DME). Design Randomized phase 2 clinical trial. Participants 121 eyes of 121 subjects (109 eligible for analysis) with DME and Snellen acuity equivalent ranging from 20/32-20/320. Interventions Random assignment to one of five groups: focal photocoagulation at baseline (N=19, Group A), intravitreal injection of 1.25mg bevacizumab at baseline and 6 weeks (N=22, Group B), intravitreal injection of 2.5mg bevacizumab at baseline and 6 weeks (N=24, Group C), intravitreal injection of 1.25mg bevacizumab at baseline and sham injection at 6 weeks (N=22, Group D), or intravitreal injection of 1.25mg bevacizumab at baseline and 6 weeks with photocoagulation at 3 weeks (N=22, Group E). Main Outcome Measures Central subfield thickness (CST) on optical coherence tomography and best-corrected visual acuity (VA) were measured at baseline and after 3, 6, 9, 12, 18, and 24 weeks. Results At baseline, median CST was 411 microns and median Snellen VA equivalent was 20/50. Compared with Group A, Groups B and C had a greater reduction in CST at 3 weeks and about one line better median visual acuity over 12 weeks. There were no meaningful differences between Groups B and C in CST reduction or VA improvement. A CST reduction >11% (the reliability limit) was present at 3 weeks in 36/84 (43%) bevacizumab-treated eyes and in 5/18 (28%) eyes treated with laser alone, and at 6 weeks in 31/84 (37%) and 9/18 (50%) eyes, respectively. Combining focal photocoagulation with bevacizumab resulted in no apparent short-term benefit or adverse outcomes. Endophthalmitis developed in one eye. The following events occurred during the first 24 weeks in subjects treated with bevacizumab without attributing cause to the drug: myocardial infarction (N=2), congestive heart failure (N=1), elevated blood pressure (N=3), and worsened renal function (N=3). Conclusion These results demonstrate that

  1. A simulation of the measurement of electrical conductivity in randomly generated two-phase rocks.

    NASA Astrophysics Data System (ADS)

    Mandolesi, Eric; Moorkamp, Max; Jones, Alan G.

    2014-05-01

    Geological models of the subsurface require detailed data, often unavailable from direct observation or well logs. Hence imaging the subsurface relies on models obtained by interpretation of geophysical data. Several electromagnetic (EM) geophysical methods focus on the EM properties of rocks and sediments to determine a reliable image of the subsurface, while the same electromagnetic properties are directly measured in laboratories. Often these laboratory measurements return equivocal results that are difficult to reconcile with field observations. Recently different numerical approaches have been investigated in order to understand the effects of the geometry and continuity of interconnected pathways of conductors on EM field measurements, often restricting the studies to direct current (DC) sources. Bearing in mind the time-varying nature of the natural electromagnetic sources that play a role in field measurements, we numerically simulate the effects of such EM sources on the conductivity measured on the surface of a randomly generated three-dimensional body embedded in a uniform host by using electromagnetic induction equations, thus simulating a magnetotelluric (MT) survey. A key point in such a simulation is the scalability of the problem: the deeper the target, the longer the period of the EM source is needed. On the other hand, a long period signal ignores small heterogeneous conductors in the target bulk of the material, averaging the different conductivities in a median value. Since most real rocks are poor conductors, we have modeled a two-phase mixture of rock and interconnected conductive elements (representing melts, saline fluids, sulphidic, carbonitic, or metallic sediments, etc.), randomly generated within the background host. We have compared the results from the simulated measurements with the target rock embedded at different depths with electrical conductivity predicted by both Hashin-Shtrikman (HS) bounds and an updated multi-phase Archie

  2. A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization

    PubMed Central

    Baker, Valerie L.; Jones, Christopher A.; Doody, Kevin; Foulk, Russell; Yee, Bill; Adamson, G. David; Cometti, Barbara; DeVane, Gary; Hubert, Gary; Trevisan, Silvia; Hoehler, Fred; Jones, Clarence; Soules, Michael

    2014-01-01

    STUDY QUESTION Is the ongoing pregnancy rate with a new aqueous formulation of subcutaneous progesterone (Prolutex®) non-inferior to vaginal progesterone (Endometrin®) when used for luteal phase support of in vitro fertilization? SUMMARY ANSWER In the per-protocol (PP) population, the ongoing pregnancy rates per oocyte retrieval at 12 weeks of gestation were comparable between Prolutex and Endometrin (41.6 versus 44.4%), with a difference between groups of −2.8% (95% confidence interval (CI) −9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. WHAT IS KNOWN ALREADY Luteal phase support has been clearly demonstrated to improve pregnancy rates in women undergoing in vitro fertilization (IVF). Because of the increased risk of ovarian hyperstimulation syndrome associated with the use of hCG, progesterone has become the treatment of choice for luteal phase support. STUDY DESIGN, SIZE, DURATION This prospective, open-label, randomized, controlled, parallel-group, multicentre, two-arm, non-inferiority study was performed at eight fertility clinics. A total of 800 women, aged 18–42 years, with a BMI of ≤30 kg/m2, with <3 prior completed assisted reproductive technology (ART) cycles, exhibiting baseline (Days 2–3) FSH of ≤15 IU/L and undergoing IVF at 8 centres (seven private, one academic) in the USA, were enrolled from January 2009 through June 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 800 women undergoing IVF were randomized after retrieval of at least three oocytes to an aqueous preparation of progesterone administered subcutaneously (25 mg daily) or vaginal progesterone (100 mg bid daily). Randomization was performed to enrol 100 patients at each site using a randomization list that was generated with Statistical Analysis Software (SAS®). If a viable pregnancy occurred, progesterone treatment was continued up to 12 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE Using a PP analysis

  3. The comparative effects of povidone-iodine and normal saline mouthwashes on oral mucositis in patients after high-dose chemotherapy and APBSCT--results of a randomized multicentre study.

    PubMed

    Vokurka, Samuel; Bystrická, Eva; Koza, Vladimír; Scudlová, Jana; Pavlicová, Vladislava; Valentová, Dana; Bocková, Jana; Misaniová, Lubica

    2005-07-01

    Antimicrobial solutions are widely used in the nursing care of chemotherapy induced oral mucositis (OM). There is little evidence, however, supporting their use for reducing mucosal damage. In our study, 132 patients were randomized to use normal saline (n=65) or povidone-iodine diluted 1:100 (n=67) mouthwashes for OM prophylaxis and treatment after high-dose chemotherapy comprising BEAM or HD-L-PAM followed by autologous peripheral stem cell transplantation. The study groups were well balanced in respect of age, sex, chemotherapy and the number of CD34+ cells in the graft. No significant difference was found between the groups in respect of OM characteristics, fever of unknown origin (FUO) and other infections. The antimicrobial solution was less tolerable for patients. OM occurred significantly more often in females than in males (86% vs 60%, P=0.0016) and was worse and of longer duration. The mechanical effect of mouthwashes might have a certain importance in FUO prevention. When indicating oral rinses, the patient's individual preference and tolerance of solutions offered should be considered.

  4. A 2-Year, Phase IV, Multicentre, Observational Study of Ranibizumab 0.5 mg in Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice: The EPICOHORT Study.

    PubMed

    Pagliarini, Sergio; Beatty, Stephen; Lipkova, Blandina; Perez-Salvador Garcia, Eduardo; Reynders, Stefaan; Gekkieva, Margarita; Si Bouazza, Abdelkader; Pilz, Stefan

    2014-01-01

    Purpose. To assess the safety profile of ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice. Methods. This 2-year, multicentre, observational study was conducted to capture real-world early practice and outcomes across Europe, shortly after European licensing of ranibizumab for nAMD. Being observational in nature, the study did not impose diagnostic/therapeutic interventions/visit schedule. Patients were to be treated as per the EU summary of product characteristics (SmPC) in effect during the study. Key outcome measures were incidence of selected adverse events (AEs), treatment exposure, bilateral treatment, compliance to the EU SmPC, and best-corrected visual acuity (BCVA) over 2 years. Results. 755 of 770 patients received treatment. Ranibizumab was generally well tolerated with low incidence of selected AEs (0%-1.9%). Patients received 6.2 (mean) injections and 133 patients received bilateral treatment over 2 years. Protocol deviation to treatment compliance was reported in majority of patients. The observed decline in mean BCVA (Month 12, +1.5; Month 24, -1.3 letters) may be associated with undertreatment as suggested by BCVA subgroup analysis. Conclusion. The EPICOHORT study conducted in routine clinical practice reinforces the well-established safety profile of ranibizumab in nAMD. In early European practice it appeared that the nAMD patients were undertreated.

  5. Pre-trial quality assurance processes for an intensity-modulated radiation therapy (IMRT) trial: PARSPORT, a UK multicentre Phase III trial comparing conventional radiotherapy and parotid-sparing IMRT for locally advanced head and neck cancer.

    PubMed

    Clark, C H; Miles, E A; Urbano, M T Guerrero; Bhide, S A; Bidmead, A M; Harrington, K J; Nutting, C M

    2009-07-01

    The purpose of this study was to compare conventional radiotherapy with parotid gland-sparing intensity-modulated radiation therapy (IMRT) using the PARSPORT trial. The validity of such a trial depends on the radiotherapy planning and delivery meeting a defined standard across all centres. At the outset, many of the centres had little or no experience of delivering IMRT; therefore, quality assurance processes were devised to ensure consistency and standardisation of all processes for comparison within the trial. The pre-trial quality assurance (QA) programme and results are described. Each centre undertook exercises in target volume definition and treatment planning, completed a resource questionnaire and produced a process document. Additionally, the QA team visited each participating centre. Each exercise had to be accepted before patients could be recruited into the trial. 10 centres successfully completed the quality assurance exercises. A range of treatment planning systems, linear accelerators and delivery methods were used for the planning exercises, and all the plans created reached the standard required for participation in this multicentre trial. All 10 participating centres achieved implementation of a comprehensive and robust IMRT programme for treatment of head and neck cancer.

  6. Amplitude-phase retrieval attack free cryptosystem based on direct attack to phase-truncated Fourier-transform-based encryption using a random amplitude mask.

    PubMed

    Wang, Xiaogang; Zhao, Daomu

    2013-09-15

    We propose a simple amplitude-phase retrieval attack free cryptosystem based on direct attack to phase-truncated Fourier-transform-based encryption using a random amplitude mask (RAM). The RAM that is not saved during the encryption provides extremely high security for the two private keys, and no iterative calculations are involved in the nonlinear encryption process. Lack of enough constraints makes the specific attack based on iterative amplitude-phase retrieval algorithms unusable. Numerical simulation results are given for testing the validity and security of the proposed approach.

  7. Time-reversal acoustic focusing system as a virtual random phased array.

    PubMed

    Sarvazyan, Armen; Fillinger, Laurent; Gavrilov, Leonid

    2010-04-01

    This paper compares the performance of two different systems for dynamic focusing of ultrasonic waves: conventional 2-D phased arrays (PA) and a focusing system based on the principles of time-reversed acoustics (TRA). Focused ultrasound fields obtained in the experiments with the TRA focusing system (TRA FS), which employs a liquid-filled reverberator with 4 piezotransducers attached to its wall, are compared with the focused fields obtained by mathematical simulation of PAs comprised from several tens to several hundreds of elements distributed randomly on the array surface. The experimental and simulated focusing systems had the same aperture and operated at a frequency centered about 600 kHz. Experimental results demonstrated that the TRA FS with a small number of channels can produce complex focused patterns and can steer them with efficiency comparable to that of a PA with hundreds of elements. It is shown that the TRA FS can be realized using an extremely simple means, such as a reverberator made of a water-filled plastic bottle with just a few piezotransducers attached to its walls.

  8. Broadband diffuse terahertz wave scattering by flexible metasurface with randomized phase distribution

    PubMed Central

    Zhang, Yin; Liang, Lanju; Yang, Jing; Feng, Yijun; Zhu, Bo; Zhao, Junming; Jiang, Tian; Jin, Biaobing; Liu, Weiwei

    2016-01-01

    Suppressing specular electromagnetic wave reflection or backward radar cross section is important and of broad interests in practical electromagnetic engineering. Here, we present a scheme to achieve broadband backward scattering reduction through diffuse terahertz wave reflection by a flexible metasurface. The diffuse scattering of terahertz wave is caused by the randomized reflection phase distribution on the metasurface, which consists of meta-particles of differently sized metallic patches arranged on top of a grounded polyimide substrate simply through a certain computer generated pseudorandom sequence. Both numerical simulations and experimental results demonstrate the ultralow specular reflection over a broad frequency band and wide angle of incidence due to the re-distribution of the incident energy into various directions. The diffuse scattering property is also polarization insensitive and can be well preserved when the flexible metasurface is conformably wrapped on a curved reflective object. The proposed design opens up a new route for specular reflection suppression, and may be applicable in stealth and other technology in the terahertz spectrum. PMID:27225031

  9. Steganographic optical image encryption system based on reversible data hiding and double random phase encoding

    NASA Astrophysics Data System (ADS)

    Chuang, Cheng-Hung; Chen, Yen-Lin

    2013-02-01

    This study presents a steganographic optical image encryption system based on reversible data hiding and double random phase encoding (DRPE) techniques. Conventional optical image encryption systems can securely transmit valuable images using an encryption method for possible application in optical transmission systems. The steganographic optical image encryption system based on the DRPE technique has been investigated to hide secret data in encrypted images. However, the DRPE techniques vulnerable to attacks and many of the data hiding methods in the DRPE system can distort the decrypted images. The proposed system, based on reversible data hiding, uses a JBIG2 compression scheme to achieve lossless decrypted image quality and perform a prior encryption process. Thus, the DRPE technique enables a more secured optical encryption process. The proposed method extracts and compresses the bit planes of the original image using the lossless JBIG2 technique. The secret data are embedded in the remaining storage space. The RSA algorithm can cipher the compressed binary bits and secret data for advanced security. Experimental results show that the proposed system achieves a high data embedding capacity and lossless reconstruction of the original images.

  10. Restricted second random phase approximations and Tamm-Dancoff approximations for electronic excitation energy calculations

    NASA Astrophysics Data System (ADS)

    Peng, Degao; Yang, Yang; Zhang, Peng; Yang, Weitao

    2014-12-01

    In this article, we develop systematically second random phase approximations (RPA) and Tamm-Dancoff approximations (TDA) of particle-hole and particle-particle channels for calculating molecular excitation energies. The second particle-hole RPA/TDA can capture double excitations missed by the particle-hole RPA/TDA and time-dependent density-functional theory (TDDFT), while the second particle-particle RPA/TDA recovers non-highest-occupied-molecular-orbital excitations missed by the particle-particle RPA/TDA. With proper orbital restrictions, these restricted second RPAs and TDAs have a formal scaling of only O(N4). The restricted versions of second RPAs and TDAs are tested with various small molecules to show some positive results. Data suggest that the restricted second particle-hole TDA (r2ph-TDA) has the best overall performance with a correlation coefficient similar to TDDFT, but with a larger negative bias. The negative bias of the r2ph-TDA may be induced by the unaccounted ground state correlation energy to be investigated further. Overall, the r2ph-TDA is recommended to study systems with both single and some low-lying double excitations with a moderate accuracy. Some expressions on excited state property evaluations, such as < hat{S}2rangle are also developed and tested.

  11. Restricted second random phase approximations and Tamm-Dancoff approximations for electronic excitation energy calculations

    SciTech Connect

    Peng, Degao; Yang, Yang; Zhang, Peng; Yang, Weitao

    2014-12-07

    In this article, we develop systematically second random phase approximations (RPA) and Tamm-Dancoff approximations (TDA) of particle-hole and particle-particle channels for calculating molecular excitation energies. The second particle-hole RPA/TDA can capture double excitations missed by the particle-hole RPA/TDA and time-dependent density-functional theory (TDDFT), while the second particle-particle RPA/TDA recovers non-highest-occupied-molecular-orbital excitations missed by the particle-particle RPA/TDA. With proper orbital restrictions, these restricted second RPAs and TDAs have a formal scaling of only O(N{sup 4}). The restricted versions of second RPAs and TDAs are tested with various small molecules to show some positive results. Data suggest that the restricted second particle-hole TDA (r2ph-TDA) has the best overall performance with a correlation coefficient similar to TDDFT, but with a larger negative bias. The negative bias of the r2ph-TDA may be induced by the unaccounted ground state correlation energy to be investigated further. Overall, the r2ph-TDA is recommended to study systems with both single and some low-lying double excitations with a moderate accuracy. Some expressions on excited state property evaluations, such as 〈S{sup ^2}〉 are also developed and tested.

  12. Restricted second random phase approximations and Tamm-Dancoff approximations for electronic excitation energy calculations.

    PubMed

    Peng, Degao; Yang, Yang; Zhang, Peng; Yang, Weitao

    2014-12-07

    In this article, we develop systematically second random phase approximations (RPA) and Tamm-Dancoff approximations (TDA) of particle-hole and particle-particle channels for calculating molecular excitation energies. The second particle-hole RPA/TDA can capture double excitations missed by the particle-hole RPA/TDA and time-dependent density-functional theory (TDDFT), while the second particle-particle RPA/TDA recovers non-highest-occupied-molecular-orbital excitations missed by the particle-particle RPA/TDA. With proper orbital restrictions, these restricted second RPAs and TDAs have a formal scaling of only O(N(4)). The restricted versions of second RPAs and TDAs are tested with various small molecules to show some positive results. Data suggest that the restricted second particle-hole TDA (r2ph-TDA) has the best overall performance with a correlation coefficient similar to TDDFT, but with a larger negative bias. The negative bias of the r2ph-TDA may be induced by the unaccounted ground state correlation energy to be investigated further. Overall, the r2ph-TDA is recommended to study systems with both single and some low-lying double excitations with a moderate accuracy. Some expressions on excited state property evaluations, such as ⟨Ŝ(2)⟩ are also developed and tested.

  13. Large-scale continuum random-phase approximation predictions of dipole strength for astrophysical applications

    NASA Astrophysics Data System (ADS)

    Daoutidis, I.; Goriely, S.

    2012-09-01

    Large-scale calculations of the E1 strength are performed within the random phase approximation (RPA) based on the relativistic point-coupling mean field approach in order to derive the radiative neutron capture cross sections for all nuclei of astrophysical interest. While the coupling to the single-particle continuum is taken into account in an explicit and self-consistent way, additional corrections like the coupling to complex configurations and the temperature and deformation effects are included in a phenomenological way to account for a complete description of the nuclear dynamical problem. It is shown that the resulting E1-strength function based on the PCF1 force is in close agreement with photoabsorption data as well as the available experimental E1 strength data at low energies. For neutron-rich nuclei, as well as light neutron-deficient nuclei, a low-lying so-called pygmy resonance is found systematically in the 5-10 MeV region. The corresponding strength can reach 10% of the giant dipole strength in the neutron-rich region and about 5% in the neutron-deficient region, and is found to be reduced in the vicinity of the shell closures. Finally, the neutron capture reaction rates of neutron-rich nuclei is found to be about 2-5 times larger than those predicted on the basis of the nonrelativistic RPA calculation and about a factor 50 larger than obtained with traditional Lorentzian-type approaches.

  14. Low excitations of 16O using generalized density matrix random phase approximation GDRPA

    NASA Astrophysics Data System (ADS)

    Taqi, Ali H.; Radhi, R. A.; Hussein, Adil M.

    2014-07-01

    The random phase approximation (RPA) equations based on the generalized density matrix (GDM), the so-called GDRPA are reformulated in a more compact matrix form, which renders the method especially suitable for realistic nuclear structure calculations. The GDRPA Hamiltonian is expressed in terms of the one-body particle-particle (pp) and hole-hole (hh) density matrices, and the nuclear force contributes not only in the particle-hole (ph) channel, as in normal ph-RPA, but also in the pp and hh channels. The Hamiltonian is diagonalized iteratively starting from initial guess values and the iterating process is carried out until self-consistency is achieved. The calculation in the model space 1p, 1d and 2s using Warburton and Brown interaction WBP is performed for 16O. The GDRPA in the ph shell model calculations is tested, by comparing the energy eigenvalues and the electron scattering form factors with the results of the normal RPA and with the available experimental data.

  15. Particle-particle and quasiparticle random phase approximations: Connections to coupled cluster theory

    NASA Astrophysics Data System (ADS)

    Scuseria, Gustavo E.; Henderson, Thomas M.; Bulik, Ireneusz W.

    2013-09-01

    We establish a formal connection between the particle-particle (pp) random phase approximation (RPA) and the ladder channel of the coupled cluster doubles (CCD) equations. The relationship between RPA and CCD is best understood within a Bogoliubov quasiparticle (qp) RPA formalism. This work is a follow-up to our previous formal proof on the connection between particle-hole (ph) RPA and ring-CCD. Whereas RPA is a quasibosonic approximation, CC theory is a "correct bosonization" in the sense that the wavefunction and Hilbert space are exactly fermionic, yet the amplitude equations can be interpreted as adding different quasibosonic RPA channels together. Coupled cluster theory achieves this goal by interacting the ph (ring) and pp (ladder) diagrams via a third channel that we here call "crossed-ring" whose presence allows for full fermionic antisymmetry. Additionally, coupled cluster incorporates what we call "mosaic" terms which can be absorbed into defining a new effective one-body Hamiltonian. The inclusion of these mosaic terms seems to be quite important. The pp-RPA and qp-RPA equations are textbook material in nuclear structure physics but are largely unknown in quantum chemistry, where particle number fluctuations and Bogoliubov determinants are rarely used. We believe that the ideas and connections discussed in this paper may help design improved ways of incorporating RPA correlation into density functionals based on a CC perspective.

  16. Dielectric Matrix Formulation of Correlation Energies in the Random Phase Approximation: Inclusion of Exchange Effects.

    PubMed

    Mussard, Bastien; Rocca, Dario; Jansen, Georg; Ángyán, János G

    2016-05-10

    Starting from the general expression for the ground state correlation energy in the adiabatic-connection fluctuation-dissipation theorem (ACFDT) framework, it is shown that the dielectric matrix formulation, which is usually applied to calculate the direct random phase approximation (dRPA) correlation energy, can be used for alternative RPA expressions including exchange effects. Within this famework, the ACFDT analog of the second order screened exchange (SOSEX) approximation leads to a logarithmic formula for the correlation energy similar to the direct RPA expression. Alternatively, the contribution of the exchange can be included in the kernel used to evaluate the response functions. In this case, the use of an approximate kernel is crucial to simplify the formalism and to obtain a correlation energy in logarithmic form. Technical details of the implementation of these methods are discussed, and it is shown that one can take advantage of density fitting or Cholesky decomposition techniques to improve the computational efficiency; a discussion on the numerical quadrature made on the frequency variable is also provided. A series of test calculations on atomic correlation energies and molecular reaction energies shows that exchange effects are instrumental for improvement over direct RPA results.

  17. Biometrics based key management of double random phase encoding scheme using error control codes

    NASA Astrophysics Data System (ADS)

    Saini, Nirmala; Sinha, Aloka

    2013-08-01

    In this paper, an optical security system has been proposed in which key of the double random phase encoding technique is linked to the biometrics of the user to make it user specific. The error in recognition due to the biometric variation is corrected by encoding the key using the BCH code. A user specific shuffling key is used to increase the separation between genuine and impostor Hamming distance distribution. This shuffling key is then further secured using the RSA public key encryption to enhance the security of the system. XOR operation is performed between the encoded key and the feature vector obtained from the biometrics. The RSA encoded shuffling key and the data obtained from the XOR operation are stored into a token. The main advantage of the present technique is that the key retrieval is possible only in the simultaneous presence of the token and the biometrics of the user which not only authenticates the presence of the original input but also secures the key of the system. Computational experiments showed the effectiveness of the proposed technique for key retrieval in the decryption process by using the live biometrics of the user.

  18. Ultrafast switching in nanoscale phase-change random access memory with superlattice-like structures.

    PubMed

    Loke, Desmond; Shi, Luping; Wang, Weijie; Zhao, Rong; Yang, Hongxin; Ng, Lung-Tat; Lim, Kian-Guan; Chong, Tow-Chong; Yeo, Yee-Chia

    2011-06-24

    Phase-change random access memory cells with superlattice-like (SLL) GeTe/Sb(2)Te(3) were demonstrated to have excellent scaling performance in terms of switching speed and operating voltage. In this study, the correlations between the cell size, switching speed and operating voltage of the SLL cells were identified and investigated. We found that small SLL cells can achieve faster switching speed and lower operating voltage compared to the large SLL cells. Fast amorphization and crystallization of 300 ps and 1 ns were achieved in the 40 nm SLL cells, respectively, both significantly faster than those observed in the Ge(2)Sb(2)Te(5) (GST) cells of the same cell size. 40 nm SLL cells were found to switch with low amorphization voltage of 0.9 V when pulse-widths of 5 ns were employed, which is much lower than the 1.6 V required by the GST cells of the same cell size. These effects can be attributed to the fast heterogeneous crystallization, low thermal conductivity and high resistivity of the SLL structures. Nanoscale PCRAM with SLL structure promises applications in high speed and low power memory devices.

  19. Particle-particle and quasiparticle random phase approximations: connections to coupled cluster theory.

    PubMed

    Scuseria, Gustavo E; Henderson, Thomas M; Bulik, Ireneusz W

    2013-09-14

    We establish a formal connection between the particle-particle (pp) random phase approximation (RPA) and the ladder channel of the coupled cluster doubles (CCD) equations. The relationship between RPA and CCD is best understood within a Bogoliubov quasiparticle (qp) RPA formalism. This work is a follow-up to our previous formal proof on the connection between particle-hole (ph) RPA and ring-CCD. Whereas RPA is a quasibosonic approximation, CC theory is a "correct bosonization" in the sense that the wavefunction and Hilbert space are exactly fermionic, yet the amplitude equations can be interpreted as adding different quasibosonic RPA channels together. Coupled cluster theory achieves this goal by interacting the ph (ring) and pp (ladder) diagrams via a third channel that we here call "crossed-ring" whose presence allows for full fermionic antisymmetry. Additionally, coupled cluster incorporates what we call "mosaic" terms which can be absorbed into defining a new effective one-body Hamiltonian. The inclusion of these mosaic terms seems to be quite important. The pp-RPA and qp-RPA equations are textbook material in nuclear structure physics but are largely unknown in quantum chemistry, where particle number fluctuations and Bogoliubov determinants are rarely used. We believe that the ideas and connections discussed in this paper may help design improved ways of incorporating RPA correlation into density functionals based on a CC perspective.

  20. Improved description of metal oxide stability: Beyond the random phase approximation with renormalized kernels

    NASA Astrophysics Data System (ADS)

    Jauho, Thomas S.; Olsen, Thomas; Bligaard, Thomas; Thygesen, Kristian S.

    2015-09-01

    The renormalized adiabatic PBE (rAPBE) method has recently been shown to comprise a significant improvement over the random phase approximation (RPA) for total energy calculations of simple solids and molecules. Here we consider the formation energies of 19 group I and II metal oxides and a few transition-metal oxides. The mean absolute error relative to experiments is 0.21 eV and 0.38 eV per oxygen atom for rAPBE and RPA, respectively, and thus the rAPBE method greatly improves the description of metal-oxygen bonds across a wide range of oxides. The failure of the RPA can be partly attributed to the lack of error cancellation between the correlation energy of the oxide on the one hand and the bulk metal and oxygen molecule on the other hand, which are all separately predicted much too negative by the RPA. We ascribe the improved performance of the rAPBE to its significantly better description of absolute correlation energies which reduces the need for error cancellation. The rAPBE is just one out of an entire class of renormalized exchange-correlation kernels which should be further investigated.

  1. Beyond-mean-field corrections within the second random-phase approximation

    NASA Astrophysics Data System (ADS)

    Grasso, M.; Gambacurta, D.; Engel, J.

    2016-06-01

    A subtraction procedure, introduced to overcome double-counting problems in beyond-mean-field theories, is used in the second random-phase approximation (SRPA). Doublecounting problems arise in the energy-density functional framework in all cases where effective interactions tailored at leading order are used for higher-order calculations, such as those done in the SRPA model. It was recently shown that this subtraction procedure also guarantees that the stability condition related to the Thouless theorem is verified in extended RPA models. We discuss applications of the subtraction procedure, introduced within the SRPA model, to the nucleus 16O. The application of the subtraction procedure leads to: (i) stable results that are weakly cutoff dependent; (ii) a considerable upwards correction of the SRPA spectra (which were systematically shifted downwards by several MeV with respect to RPA spectra, in all previous calculations). With this important implementation of the model, many applications may be foreseen to analyze the genuine impact of 2 particle-2 hole configurations (without any cutoff dependences and anomalous shifts) on the excitation spectra of medium-mass and heavy nuclei.

  2. Linear-scaling implementation of the direct random-phase approximation

    SciTech Connect

    Kállay, Mihály

    2015-05-28

    We report the linear-scaling implementation of the direct random-phase approximation (dRPA) for closed-shell molecular systems. As a bonus, linear-scaling algorithms are also presented for the second-order screened exchange extension of dRPA as well as for the second-order Møller–Plesset (MP2) method and its spin-scaled variants. Our approach is based on an incremental scheme which is an extension of our previous local correlation method [Rolik et al., J. Chem. Phys. 139, 094105 (2013)]. The approach extensively uses local natural orbitals to reduce the size of the molecular orbital basis of local correlation domains. In addition, we also demonstrate that using natural auxiliary functions [M. Kállay, J. Chem. Phys. 141, 244113 (2014)], the size of the auxiliary basis of the domains and thus that of the three-center Coulomb integral lists can be reduced by an order of magnitude, which results in significant savings in computation time. The new approach is validated by extensive test calculations for energies and energy differences. Our benchmark calculations also demonstrate that the new method enables dRPA calculations for molecules with more than 1000 atoms and 10 000 basis functions on a single processor.

  3. Random phase approximation with second-order screened exchange for current-carrying atomic states

    NASA Astrophysics Data System (ADS)

    Zhu, Wuming; Zhang, Liang; Trickey, S. B.

    2016-12-01

    The direct random phase approximation (RPA) and RPA with second-order screened exchange (SOSEX) have been implemented with complex orbitals as a basis for treating open-shell atoms. Both RPA and RPA+SOSEX are natural implicit current density functionals because the paramagnetic current density implicitly is included through the use of complex orbitals. We confirm that inclusion of the SOSEX correction improves the total energy accuracy substantially compared to RPA, especially for smaller-Z atoms. Computational complexity makes post self-consistent-field (post-SCF) evaluation of RPA-type expressions commonplace, so orbital basis origins and properties become important. Sizable differences are found in correlation energies, total atomic energies, and ionization energies for RPA-type functionals evaluated in the post-SCF fashion with orbital sets obtained from different schemes. Reference orbitals from Kohn-Sham calculations with semi-local functionals are more suitable for RPA+SOSEX to generate accurate total energies, but reference orbitals from exact exchange (non-local) yield essentially energetically degenerate open-shell atom ground states. RPA+SOSEX correlation combined with exact exchange calculated from a hybrid reference orbital set (half the exchange calculated from exact-exchange orbitals, the other half of the exchange from orbitals optimized for the Perdew-Burke-Ernzerhof (PBE) exchange functional) gives the best overall performance. Numerical results show that the RPA-like functional with SOSEX correction can be used as a practical implicit current density functional when current effects should be included.

  4. Treating KSHV-Associated Multicentric Castleman Disease

    Cancer.gov

    In this study, patients with KSHV-associated multicentric Castleman disease will receive IV tocilizumab every other week for up to 12 weeks. Patients who do not benefit may go on to receive high-dose AZT and valganciclovir as well.

  5. Multicentre evaluation of the Bayer DAX system.

    PubMed

    Morosini, L; Rossetti, M; Berti, P; Pallotti, G; Fabbri, V; Mambelli, M C; Franceschin, A; Dell'Anna, L; Cappelletti, P; Brocco, G

    1993-12-01

    The analytical performance of the DAX, a high-throughput random access analyser, was studied according to ECCLS guidelines (ECCLS Document Vol. 3, No. 2, Beuth Verlag, Berlin, 1986) in a multicentre evaluation involving four laboratories. The trial took about 4 months. Determinations of 12 analytes produced more than 60,000 data. The imprecision study on 3 control sera for all analytes gave a within-run CV (median of 4 laboratories) which never exceeded 3% and was below 2% in 94% of the results. The median between-day CV was less than 3% in 92% of the results, with a highest value of 5.0%. No significant drift was detected during the 5-hour work period. No relevant sample- and cuvette-related carry-over was found. The manufacturer's claims concerning linearity were fulfilled or exceeded. The recovery of the assigned values for the control sera (median of 4 laboratories) ranged from 94 to 106%. In the method comparison on patients' samples, deviations were statistically significant in some cases, due to differences either in the methods used or in the calibration of the systems used for comparison; the regression lines, as inspected visually, and the coefficients of correlation were, however, generally acceptable. Imprecision and inaccuracy were within the acceptability limits as recommended by the Société Française de Biologie Clinique (SFBC) (Biochim. Clin. 12 (1988) 284-327) and the Deutsche Gesellschaft für Klinische Chemie (DGKC) (Dt. Arztebl. 85 (11) (1988) A697-A712). The limits of acceptance, proposed more recently by Fraser et al. (Eur. J. Clin. Chem. Clin. Biochem. 30 (1992) 311-317), were met in thirty-three of thirty-six cases. The alpha-amylase assay was significantly affected by bilirubin and haemolysis; interferences for the remaining analytes were predictable and well-known from the literature. The rate of sample throughput was found to be in agreement with that claimed by the manufacturer. The software did not present problems and was readily

  6. Methadone induction in primary care (ANRS-Methaville): a phase III randomized intervention trial

    PubMed Central

    2012-01-01

    Background In France, the rapid scale-up of buprenorphine, an opioid maintenance treatment (OMT), in primary care for drug users has led to an impressive reduction in HIV prevalence among injecting drug users (IDU) but has had no major effect on Hepatitis C incidence. To date, patients willing to start methadone can only do so in a methadone clinic (a medical centre for drug and alcohol dependence (CSAPA) or a hospital setting) and are referred to primary care physicians after dose stabilization. This study aims to assess the effectiveness of methadone in patients who initiated treatment in primary care compared with those who initiated it in a CSAPA, by measuring abstinence from street opioid use after one year of treatment. Methods/Design The ANRS-Methaville study is a randomized multicenter non-inferiority control trial comparing methadone induction (lasting approximately 2 weeks) in primary care and in CSAPA. The model of care chosen for methadone induction in primary care was based on study-specific pre-training of all physicians, exclusion criteria and daily supervision of methadone during the initiation phase. Between January 2009 and January 2011, 10 sites each having one CSAPA and several primary care physicians, were identified to recruit patients to be randomized into two groups, one starting methadone in primary care (n = 147), the other in CSAPA (n = 48). The primary outcome of the study is the proportion of participants abstinent from street opioids after 1 year of treatment i.e. non-inferiority of primary care model in terms of the proportion of patients not using street opioids compared with the proportion observed in those starting methadone in a CSAPA. Discussion The ANRS-Methaville study is the first in France to use an interventional trial to improve access to OMT for drug users. Once the non-inferiority results become available, the Ministry of Health and agency for the safety of health products may change the the New Drug Application

  7. Focusing of high-intensity ultrasound through the rib cage using a therapeutic random phased array.

    PubMed

    Bobkova, Svetlana; Gavrilov, Leonid; Khokhlova, Vera; Shaw, Adam; Hand, Jeffrey

    2010-06-01

    A method for focusing high-intensity ultrasound (HIFU) through a rib cage that aims to minimize heating of the ribs while maintaining high intensities at the focus (or foci) was proposed and tested theoretically and experimentally. Two approaches, one based on geometric acoustics and the other accounting for diffraction effects associated with propagation through the rib cage, were investigated theoretically for idealized source conditions. It is shown that for an idealized radiator, the diffraction approach provides a 23% gain in peak intensity and results in significantly less power losses on the ribs (1% vs. 7.5% of the irradiated power) compared with the geometric one. A 2-D 1-MHz phased array with 254 randomly distributed elements, tissue-mimicking phantoms and samples of porcine rib cages are used in experiments; the geometric approach is used to configure how the array is driven. Intensity distributions are measured in the plane of the ribs and in the focal plane using an infrared camera. Theoretical and experimental results show that it is possible to provide adequate focusing through the ribs without overheating them for a single focus and several foci, including steering at +/- 10-15 mm off and +/- 20 mm along the array axis. Focus splitting caused by the periodic spatial structure of ribs is demonstrated both in simulations and experiments; the parameters of splitting are quantified. The ability to produce thermal lesions with a split focal pattern in ex vivo porcine tissue placed beyond the rib phantom is also demonstrated. The results suggest that the method is potentially useful for clinical applications of HIFU, for which the rib cage lies between the transducer(s) and the targeted tissue.

  8. Focusing of high intensity ultrasound through the rib cage using a therapeutic random phased array

    PubMed Central

    Bobkova, Svetlana; Gavrilov, Leonid; Khokhlova, Vera; Shaw, Adam; Hand, Jeffrey; #, ||

    2010-01-01

    A method for focusing high intensity ultrasound through a rib cage that aims to minimize heating of the ribs whilst maintaining high intensities at the focus (or foci) is proposed and tested theoretically and experimentally. Two approaches, one based on geometric acoustics and the other accounting for diffraction effects associated with propagation through the rib cage, are investigated theoretically for idealized source conditions. It is shown that for an idealized radiator the diffraction approach provides a 23% gain in peak intensity and results in significantly less power losses on the ribs (1% versus 7.5% of the irradiated power) compared with the geometric one. A 2D 1-MHz phased array with 254 randomly distributed elements, tissue mimicking phantoms, and samples of porcine rib cages are used in experiments; the geometric approach is used to configure how the array is driven. Intensity distributions are measured in the plane of the ribs and in the focal plane using an infra-red camera. Theoretical and experimental results show that it is possible to provide adequate focusing through the ribs without overheating them for a single focus and several foci, including steering at ± 10–15 mm off and ± 20 mm along the array axis. Focus splitting due to the periodic spatial structure of ribs is demonstrated both in simulations and experiments; the parameters of splitting are quantified. The ability to produce thermal lesions with a split focal pattern in ex vivo porcine tissue placed beyond the rib phantom is also demonstrated. The results suggest that the method is potentially useful for clinical applications of HIFU for which the rib cage lies between the transducer(s) and the targeted tissue. PMID:20510186

  9. Thermochemistry and Geometries for Transition-Metal Chemistry from the Random Phase Approximation.

    PubMed

    Waitt, Craig; Ferrara, Nashali M; Eshuis, Henk

    2016-11-08

    Performance of the random phase approximation (RPA) is tested for thermochemistry and geometries of transition-metal chemistry using various benchmarks obtained either computationally or experimentally. Comparison is made to popular (semi)local meta- and hybrid density functionals as well as to the second-order Møller-Plesset perturbation theory (MP2) and its spin-component-scaled derivatives. The benchmark sets include reaction energies, barrier heights, and dissociation energies of prototype bond-activation reactions, dissociation energies for a set of large transition-metal complexes, bond lengths and dissociation energies of metal hydride ions, and bond lengths and angles of a set of closed-shell first-row transition-metal complexes. The emphasis is on first-row transition-metal chemistry, though for energies, elements beyond the first-row are included. Attention is paid to the basis set convergence of RPA. For thermochemistry, RPA performs on par or better than the density functional theory (DFT) functionals presented and is significantly more accurate than MP2. The largest errors are observed in dissociation energies where the electronic environment is altered substantially. For structural parameters, very good results were obtained, and RPA meets the high quality of structures from DFT. In most cases, well-converged structures are obtained with basis sets of triple-zeta quality. MP2 optimized values can often not be obtained and are on average of inferior quality. Though chemical accuracy is not reached, the RPA method is a step forward toward a systematic, parameter-free, all-round method to describe transition-metal chemistry.

  10. Skyrme random-phase-approximation description of lowest Kπ=2γ+ states in axially deformed nuclei

    NASA Astrophysics Data System (ADS)

    Nesterenko, V. O.; Kartavenko, V. G.; Kleinig, W.; Kvasil, J.; Repko, A.; Jolos, R. V.; Reinhard, P.-G.

    2016-03-01

    The lowest quadrupole γ -vibrational Kπ=2+ states in axially deformed rare-earth (Nd, Sm, Gd, Dy, Er, Yb, Hf, W) and actinide (U) nuclei are systematically investigated within the separable random-phase-approximation (SRPA) based on the Skyrme functional. The energies Eγ and reduced transition probabilities B (E 2 ) of 2γ+ states are calculated with the Skyrme forces SV-bas and SkM*. The energies of two-quasiparticle configurations forming the SRPA basis are corrected by using the pairing blocking effect. This results in a systematic downshift of Eγ by 0.3-0.5 MeV and thus in a better agreement with the experiment, especially in Sm, Gd, Dy, Hf, and W regions. For other isotopic chains, a noticeable overestimation of Eγ and too weak collectivity of 2γ+ states still persist. It is shown that domains of nuclei with low and high 2γ+ collectivity are related to the structure of the lowest two-quasiparticle states and conservation of the Nilsson selection rules. The description of 2γ+ states with SV-bas and SkM* is similar in light rare-earth nuclei but deviates in heavier nuclei. However SV-bas much better reproduces the quadrupole deformation and energy of the isoscalar giant quadrupole resonance. The accuracy of SRPA is justified by comparison with exact RPA. The calculations suggest that a further development of the self-consistent calculation schemes is needed for a systematic satisfactory description of the 2γ+ states.

  11. Hindrance Velocity Model for Phase Segregation in Suspensions of Poly-dispersed Randomly Oriented Spheroids

    NASA Astrophysics Data System (ADS)

    Faroughi, S. A.; Huber, C.

    2015-12-01

    Crystal settling and bubbles migration in magmas have significant effects on the physical and chemical evolution of magmas. The rate of phase segregation is controlled by the force balance that governs the migration of particles suspended in the melt. The relative velocity of a single particle or bubble in a quiescent infinite fluid (melt) is well characterized; however, the interplay between particles or bubbles in suspensions and emulsions and its effect on their settling/rising velocity remains poorly quantified. We propose a theoretical model for the hindered velocity of non-Brownian emulsions of nondeformable droplets, and suspensions of spherical solid particles in the creeping flow regime. The model is based on three sets of hydrodynamic corrections: two on the drag coefficient experienced by each particle to account for both return flow and Smoluchowski effects and a correction on the mixture rheology to account for nonlocal interactions between particles. The model is then extended for mono-disperse non-spherical solid particles that are randomly oriented. The non-spherical particles are idealized as spheroids and characterized by their aspect ratio. The poly-disperse nature of natural suspensions is then taken into consideration by introducing an effective volume fraction of particles for each class of mono-disperse particles sizes. Our model is tested against new and published experimental data over a wide range of particle volume fraction and viscosity ratios between the constituents of dispersions. We find an excellent agreement between our model and experiments. We also show two significant applications for our model: (1) We demonstrate that hindered settling can increase mineral residence time by up to an order of magnitude in convecting magma chambers. (2) We provide a model to correct for particle interactions in the conventional hydrometer test to estimate the particle size distribution in soils. Our model offers a greatly improved agreement with

  12. Exchange-correlation energy from pairing matrix fluctuation and the particle-particle random phase approximation.

    PubMed

    van Aggelen, Helen; Yang, Yang; Yang, Weitao

    2014-05-14

    Despite their unmatched success for many applications, commonly used local, semi-local, and hybrid density functionals still face challenges when it comes to describing long-range interactions, static correlation, and electron delocalization. Density functionals of both the occupied and virtual orbitals are able to address these problems. The particle-hole (ph-) Random Phase Approximation (RPA), a functional of occupied and virtual orbitals, has recently known a revival within the density functional theory community. Following up on an idea introduced in our recent communication [H. van Aggelen, Y. Yang, and W. Yang, Phys. Rev. A 88, 030501 (2013)], we formulate more general adiabatic connections for the correlation energy in terms of pairing matrix fluctuations described by the particle-particle (pp-) propagator. With numerical examples of the pp-RPA, the lowest-order approximation to the pp-propagator, we illustrate the potential of density functional approximations based on pairing matrix fluctuations. The pp-RPA is size-extensive, self-interaction free, fully anti-symmetric, describes the strong static correlation limit in H2, and eliminates delocalization errors in H2(+) and other single-bond systems. It gives surprisingly good non-bonded interaction energies--competitive with the ph-RPA--with the correct R(-6) asymptotic decay as a function of the separation R, which we argue is mainly attributable to its correct second-order energy term. While the pp-RPA tends to underestimate absolute correlation energies, it gives good relative energies: much better atomization energies than the ph-RPA, as it has no tendency to underbind, and reaction energies of similar quality. The adiabatic connection in terms of pairing matrix fluctuation paves the way for promising new density functional approximations.

  13. Effective restoration of dipole sum rules within the renormalized random-phase approximation

    NASA Astrophysics Data System (ADS)

    Hung, N. Quang; Dang, N. Dinh; Hao, T. V. Nhan; Phuc, L. Tan

    2016-12-01

    The dipole excitations for calcium and zirconium isotopes are studied within the fully self-consistent Hartree-Fock mean field incorporated with the renormalized random-phase approximation (RRPA) using the Skyrme interaction SLy5. The RRPA takes into account the effect of ground-state correlations beyond RPA owing to the Pauli principle between the particle-hole pairs that form the RPA excitations as well as the correlations due to the particle-particle and hole-hole transitions, whose effects are treated here in an effective way. By comparing the RPA results with the RRPA ones, which are obtained for isoscalar (IS) and isovector (IV) dipole excitations in 48,52,58Ca and 90,96,110Zr, it is shown that ground-state correlations beyond the RPA reduce the IS transition strengths. They also shift up the energy of the lowest IV dipole state and slightly push down the peak energy of the IV giant dipole resonance. As the result, the energy-weighted sums of strengths of both IS and IV modes decrease, causing the violation of the corresponding energy-weighted sum rules (EWSR). It is shown that this sum rule violation can be eliminated by taking into account the contribution of the particle-particle and hole-hole excitations together with the particle-hole ones in a simple and perturbative way. Consequently, the ratio of the energy-weighted sum of strengths of the pygmy dipole resonance to that of the giant dipole resonance increases.

  14. Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia

    PubMed Central

    Flynn, Joseph M.; Kipps, Thomas J.; Boxer, Michael; Kolibaba, Kathryn S.; Carlile, David J.; Fingerle-Rowson, Guenter; Tyson, Nicola; Hirata, Jamie; Sharman, Jeff P.

    2016-01-01

    Obinutuzumab is a glycoengineered, type 2 anti-CD20 humanized antibody with single-agent activity in relapsed chronic lymphocytic leukemia (CLL). With other CD20 antibodies, a dose-response relationship has been shown. We therefore performed a randomized phase 2 study in symptomatic, untreated CLL patients to evaluate if an obinutuzumab dose response exists. Obinutuzumab was given at a dose of 1000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 8 and day 15 of cycle 1; 1000 mg day 1 of cycles 2-8) or 2000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 3, 2000 mg day 8 and day 15 of cycle 1; 2000 mg day 1 of cycles 2-8). The primary end point was overall response rate (ORR). Eighty patients were enrolled with similar demographics: median age 67 years, 41% high-risk Rai disease, and 10% del(17p)(13.1). ORR (67% vs 49%, P = .08) and complete response (CR) or CR with incomplete cytopenia response (20% vs 5%) favored 2000 mg obinutuzumab. Overall, therapy was well tolerated, and infusion events were manageable. This study demonstrates significant efficacy of obinutuzumab monotherapy, for 1000 mg as well as for 2000 mg, in untreated CLL patients with acceptable toxicity. Although exploratory, a dose-response relationship may exist, but its relevance to improving progression-free survival is uncertain and will require further follow-up. This trial was registered at www.clinicaltrials.gov as #NCT01414205. PMID:26472752

  15. Benchmark tests and spin adaptation for the particle-particle random phase approximation.

    PubMed

    Yang, Yang; van Aggelen, Helen; Steinmann, Stephan N; Peng, Degao; Yang, Weitao

    2013-11-07

    The particle-particle random phase approximation (pp-RPA) provides an approximation to the correlation energy in density functional theory via the adiabatic connection [H. van Aggelen, Y. Yang, and W. Yang, Phys. Rev. A 88, 030501 (2013)]. It has virtually no delocalization error nor static correlation error for single-bond systems. However, with its formal O(N(6)) scaling, the pp-RPA is computationally expensive. In this paper, we implement a spin-separated and spin-adapted pp-RPA algorithm, which reduces the computational cost by a substantial factor. We then perform benchmark tests on the G2/97 enthalpies of formation database, DBH24 reaction barrier database, and four test sets for non-bonded interactions (HB6/04, CT7/04, DI6/04, and WI9/04). For the G2/97 database, the pp-RPA gives a significantly smaller mean absolute error (8.3 kcal/mol) than the direct particle-hole RPA (ph-RPA) (22.7 kcal/mol). Furthermore, the error in the pp-RPA is nearly constant with the number of atoms in a molecule, while the error in the ph-RPA increases. For chemical reactions involving typical organic closed-shell molecules, pp- and ph-RPA both give accurate reaction energies. Similarly, both RPAs perform well for reaction barriers and nonbonded interactions. These results suggest that the pp-RPA gives reliable energies in chemical applications. The adiabatic connection formalism based on pairing matrix fluctuation is therefore expected to lead to widely applicable and accurate density functionals.

  16. Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia.

    PubMed

    Byrd, John C; Flynn, Joseph M; Kipps, Thomas J; Boxer, Michael; Kolibaba, Kathryn S; Carlile, David J; Fingerle-Rowson, Guenter; Tyson, Nicola; Hirata, Jamie; Sharman, Jeff P

    2016-01-07

    Obinutuzumab is a glycoengineered, type 2 anti-CD20 humanized antibody with single-agent activity in relapsed chronic lymphocytic leukemia (CLL). With other CD20 antibodies, a dose-response relationship has been shown. We therefore performed a randomized phase 2 study in symptomatic, untreated CLL patients to evaluate if an obinutuzumab dose response exists. Obinutuzumab was given at a dose of 1000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 8 and day 15 of cycle 1; 1000 mg day 1 of cycles 2-8) or 2000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 3, 2000 mg day 8 and day 15 of cycle 1; 2000 mg day 1 of cycles 2-8). The primary end point was overall response rate (ORR). Eighty patients were enrolled with similar demographics: median age 67 years, 41% high-risk Rai disease, and 10% del(17p)(13.1). ORR (67% vs 49%, P = .08) and complete response (CR) or CR with incomplete cytopenia response (20% vs 5%) favored 2000 mg obinutuzumab. Overall, therapy was well tolerated, and infusion events were manageable. This study demonstrates significant efficacy of obinutuzumab monotherapy, for 1000 mg as well as for 2000 mg, in untreated CLL patients with acceptable toxicity. Although exploratory, a dose-response relationship may exist, but its relevance to improving progression-free survival is uncertain and will require further follow-up. This trial was registered at www.clinicaltrials.gov as #NCT01414205.

  17. Simulating dissipative phenomena with a random phase thermal wavefunctions, high temperature application of the Surrogate Hamiltonian approach

    NASA Astrophysics Data System (ADS)

    Gelman, David; Kosloff, Ronnie

    2003-11-01

    A scheme for calculating thermally averaged observables for quantum dissipative systems is presented. The method is based on a wavefunction with equal amplitude and random phase composed of a complete set of states, which is then propagated in imaginary time β/2. Application to a Surrogate Hamiltonian simulation of a molecule subject to an ultrafast pulse coupled to a bath is studied. Compared to Boltzmann thermal averaging the method scales more favorably with an increase in the number of bath modes. A self-averaging phenomenon was identified which reduces the number of random sets required to converge the thermal average.

  18. Accelerated three-dimensional cine phase contrast imaging using randomly undersampled echo planar imaging with compressed sensing reconstruction.

    PubMed

    Basha, Tamer A; Akçakaya, Mehmet; Goddu, Beth; Berg, Sophie; Nezafat, Reza

    2015-01-01

    The aim of this study was to implement and evaluate an accelerated three-dimensional (3D) cine phase contrast MRI sequence by combining a randomly sampled 3D k-space acquisition sequence with an echo planar imaging (EPI) readout. An accelerated 3D cine phase contrast MRI sequence was implemented by combining EPI readout with randomly undersampled 3D k-space data suitable for compressed sensing (CS) reconstruction. The undersampled data were then reconstructed using low-dimensional structural self-learning and thresholding (LOST). 3D phase contrast MRI was acquired in 11 healthy adults using an overall acceleration of 7 (EPI factor of 3 and CS rate of 3). For comparison, a single two-dimensional (2D) cine phase contrast scan was also performed with sensitivity encoding (SENSE) rate 2 and approximately at the level of the pulmonary artery bifurcation. The stroke volume and mean velocity in both the ascending and descending aorta were measured and compared between two sequences using Bland-Altman plots. An average scan time of 3 min and 30 s, corresponding to an acceleration rate of 7, was achieved for 3D cine phase contrast scan with one direction flow encoding, voxel size of 2 × 2 × 3 mm(3) , foot-head coverage of 6 cm and temporal resolution of 30 ms. The mean velocity and stroke volume in both the ascending and descending aorta were statistically equivalent between the proposed 3D sequence and the standard 2D cine phase contrast sequence. The combination of EPI with a randomly undersampled 3D k-space sampling sequence using LOST reconstruction allows a seven-fold reduction in scan time of 3D cine phase contrast MRI without compromising blood flow quantification.

  19. Spin-glass phase transition and behavior of nonlinear susceptibility in the Sherrington-Kirkpatrick model with random fields

    NASA Astrophysics Data System (ADS)

    Morais, C. V.; Zimmer, F. M.; Lazo, M. J.; Magalhães, S. G.; Nobre, F. D.

    2016-06-01

    The behavior of the nonlinear susceptibility χ3 and its relation to the spin-glass transition temperature Tf in the presence of random fields are investigated. To accomplish this task, the Sherrington-Kirkpatrick model is studied through the replica formalism, within a one-step replica-symmetry-breaking procedure. In addition, the dependence of the Almeida-Thouless eigenvalue λAT (replicon) on the random fields is analyzed. Particularly, in the absence of random fields, the temperature Tf can be traced by a divergence in the spin-glass susceptibility χSG, which presents a term inversely proportional to the replicon λAT. As a result of a relation between χSG and χ3, the latter also presents a divergence at Tf, which comes as a direct consequence of λAT=0 at Tf. However, our results show that, in the presence of random fields, χ3 presents a rounded maximum at a temperature T* which does not coincide with the spin-glass transition temperature Tf (i.e., T*>Tf for a given applied random field). Thus, the maximum value of χ3 at T* reflects the effects of the random fields in the paramagnetic phase instead of the nontrivial ergodicity breaking associated with the spin-glass phase transition. It is also shown that χ3 still maintains a dependence on the replicon λAT, although in a more complicated way as compared with the case without random fields. These results are discussed in view of recent observations in the LiHoxY1 -xF4 compound.

  20. Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

    PubMed Central

    Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

    2013-01-01

    Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (p<0.05) among groups in both phases; the 200 mg group received the least amount in Phase 1, and the 600 mg group received the most in both phases. In Phase 1, tramadol 200 mg produced significantly lower peak ratings than placebo on ratings of insomnia, lacrimation, muscular tension, and sneezing. Only tramadol 600 mg produced miosis in Phase 1. In Phase 2, tramadol 600 mg produced higher peak ratings of rhinorrhea, irritable, depressed, heavy/sluggish, and hot/cold flashes than placebo. There were no serious adverse events and no signal of abuse liability for tramadol. Conclusions ER tramadol 200 mg modestly attenuated opioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

  1. Analytical First-Order Molecular Properties and Forces within the Adiabatic Connection Random Phase Approximation.

    PubMed

    Burow, Asbjörn M; Bates, Jefferson E; Furche, Filipp; Eshuis, Henk

    2014-01-14

    The random phase approximation (RPA) is an increasingly popular method for computing molecular ground-state correlation energies within the adiabatic connection fluctuation-dissipation theorem framework of density functional theory. We present an efficient analytical implementation of first-order RPA molecular properties and nuclear forces using the resolution-of-the-identity (RI) approximation and imaginary frequency integration. The centerpiece of our approach is a variational RPA energy Lagrangian invariant under unitary transformations of occupied and virtual reference orbitals, respectively. Its construction requires the solution of a single coupled-perturbed Kohn-Sham equation independent of the number of perturbations. Energy gradients with respect to nuclear displacements and other first-order properties such as one-particle densities or dipole moments are obtained from partial derivatives of the Lagrangian. Our RPA energy gradient implementation exhibits the same [Formula: see text] scaling with system size N as a single-point RPA energy calculation. In typical applications, the cost for computing the entire gradient vector with respect to nuclear displacements is ∼5 times that of a single-point RPA energy calculation. Derivatives of the quadrature nodes and weights used for frequency integration are essential for RPA gradients with an accuracy consistent with RPA energies and can be included in our approach. The quality of RPA equilibrium structures is assessed by comparison to accurate theoretical and experimental data for covalent main group compounds, weakly bonded dimers, and transition metal complexes. RPA outperforms semilocal functionals as well as second-order Møller-Plesset (MP2) theory, which fails badly for the transition metal compounds. Dipole moments of polarizable molecules and weakly bound dimers show a similar trend. RPA harmonic vibrational frequencies are nearly of coupled cluster singles, doubles, and perturbative triples quality

  2. A Randomized Controlled Phase Ib Trial of the Malaria Vaccine Candidate GMZ2 in African Children

    PubMed Central

    Hounkpatin, Aurore B.; Schaumburg, Frieder; Ngoa, Ulysse Ateba; Esen, Meral; Fendel, Rolf; de Salazar, Pablo Martinez; Mürbeth, Raymund E.; Milligan, Paul; Imbault, Nathalie; Imoukhuede, Egeruan Babatunde; Theisen, Michael; Jepsen, Søren; Noor, Ramadhani A.; Okech, Brenda; Kremsner, Peter G.; Mordmüller, Benjamin

    2011-01-01

    Background GMZ2 is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP) that mediates an immune response against the blood stage of the parasite. Two previous phase I clinical trials, one in naïve European adults and one in malaria-exposed Gabonese adults showed that GMZ2 was well tolerated and immunogenic. Here, we present data on safety and immunogenicity of GMZ2 in one to five year old Gabonese children, a target population for future malaria vaccine efficacy trials. Methodology/Principal Findings Thirty children one to five years of age were randomized to receive three doses of either 30 µg or 100 µg of GMZ2, or rabies vaccine. GMZ2, adjuvanted in aluminum hydroxide, was administered on Days 0, 28 and 56. All participants received a full course of their respective vaccination and were followed up for one year. Both 30 µg and 100 µg GMZ2 vaccine doses were well tolerated and induced antibodies and memory B-cells against GMZ2 as well as its antigenic constituents MSP3 and GLURP. After three doses of vaccine, the geometric mean concentration of antibodies to GMZ2 was 19-fold (95%CI: 11,34) higher in the 30 µg GMZ2 group than in the rabies vaccine controls, and 16-fold (7,36) higher in the 100 µg GMZ2 group than the rabies group. Geometric mean concentration of antibodies to MSP3 was 2.7-fold (1.6,4.6) higher in the 30 µg group than in the rabies group and 3.8-fold (1.5,9.6) higher in the 100 µg group. Memory B-cells against GMZ2 developed in both GMZ2 vaccinated groups. Conclusions/Significance Both 30 µg as well as 100 µg intramuscular GMZ2 are immunogenic, well tolerated, and safe in young, malaria-exposed Gabonese children. This result confirms previous findings in naïve and malaria-exposed adults and supports further clinical development of GMZ2. Trial Registration ClinicalTrials.gov NCT00703066 PMID:21829466

  3. Femtosecond two-photon photoassociation of hot magnesium atoms: A quantum dynamical study using thermal random phase wavefunctions

    SciTech Connect

    Amaran, Saieswari; Kosloff, Ronnie; Tomza, Michał; Skomorowski, Wojciech; Pawłowski, Filip; Moszynski, Robert; Rybak, Leonid; Levin, Liat; Amitay, Zohar; Berglund, J. Martin; Reich, Daniel M.; Koch, Christiane P.

    2013-10-28

    Two-photon photoassociation of hot magnesium atoms by femtosecond laser pulses, creating electronically excited magnesium dimer molecules, is studied from first principles, combining ab initio quantum chemistry and molecular quantum dynamics. This theoretical framework allows for rationalizing the generation of molecular rovibrational coherence from thermally hot atoms [L. Rybak, S. Amaran, L. Levin, M. Tomza, R. Moszynski, R. Kosloff, C. P. Koch, and Z. Amitay, Phys. Rev. Lett. 107, 273001 (2011)]. Random phase thermal wavefunctions are employed to model the thermal ensemble of hot colliding atoms. Comparing two different choices of basis functions, random phase wavefunctions built from eigenstates are found to have the fastest convergence for the photoassociation yield. The interaction of the colliding atoms with a femtosecond laser pulse is modeled non-perturbatively to account for strong-field effects.

  4. Experiment on synchronization of semiconductor lasers by common injection of constant-amplitude random-phase light.

    PubMed

    Aida, Hiroki; Arahata, Masaya; Okumura, Haruka; Koizumi, Hayato; Uchida, Atsushi; Yoshimura, Kazuyuki; Muramatsu, Jun; Davis, Peter

    2012-05-21

    We experimentally and numerically observe the synchronization between two semiconductor lasers induced by common optical injection with constant-amplitude and random-phase modulation in configurations with and without optical feedback. Large cross correlation (~0.9) between the intensity oscillations of the two response lasers can be achieved although the correlation between the drive laser and either one of the two response lasers is very small (~0.2). High quality synchronization is achieved in the presence of optical feedback in response lasers with matched feedback phase offset. We investigate the dependence of synchronization on parameter values over wide parameter ranges.

  5. Hybrid random walk-linear discriminant analysis method for unwrapping quantitative phase microscopy images of biological samples

    PubMed Central

    Kim, Diane N. H.; Teitell, Michael A.; Reed, Jason; Zangle, Thomas A.

    2015-01-01

    Abstract. Standard algorithms for phase unwrapping often fail for interferometric quantitative phase imaging (QPI) of biological samples due to the variable morphology of these samples and the requirement to image at low light intensities to avoid phototoxicity. We describe a new algorithm combining random walk-based image segmentation with linear discriminant analysis (LDA)-based feature detection, using assumptions about the morphology of biological samples to account for phase ambiguities when standard methods have failed. We present three versions of our method: first, a method for LDA image segmentation based on a manually compiled training dataset; second, a method using a random walker (RW) algorithm informed by the assumed properties of a biological phase image; and third, an algorithm which combines LDA-based edge detection with an efficient RW algorithm. We show that the combination of LDA plus the RW algorithm gives the best overall performance with little speed penalty compared to LDA alone, and that this algorithm can be further optimized using a genetic algorithm to yield superior performance for phase unwrapping of QPI data from biological samples. PMID:26305212

  6. Giant resonances in {sup 238}U within the quasiparticle random-phase approximation with the Gogny force

    SciTech Connect

    Peru, S.; Gosselin, G.; Martini, M.; Dupuis, M.; Hilaire, S.

    2011-01-15

    Fully consistent axially-symmetric deformed quasiparticle random-phase approximation (QRPA) calculations have been performed, using the same Gogny D1S effective force for both the Hartree-Fock-Bogolyubov mean field and QRPA matrix. New implementation of this approach leads to the applicability of QRPA to heavy deformed nuclei. Giant resonances and low-energy collective states for monopole, dipole, quadrupole, and octupole modes are predicted for the heavy deformed nucleus {sup 238}U and compared with experimental data.

  7. Field-Induced Multiple Reentrant Quantum Phase Transitions in Randomly Dimerized Antiferromagnetic S=1/2 Heisenberg Chains

    NASA Astrophysics Data System (ADS)

    Hida, Kazuo

    2006-07-01

    The multiple reentrant quantum phase transitions in the S=1/2 antiferromagnetic Heisenberg chains with random bond alternation in the magnetic field are investigated by the density matrix renormalization group method combined with interchain mean field approximation. It is assumed that odd numbered bonds are antiferromagnetic with strength J and even numbered bonds can take the values JS and JW (JS > J > JW > 0) randomly with the probabilities p and 1- p, respectively. The pure version ( p=0 and 1) of this model has a spin gap but exhibits a field-induced antiferromagnetism in the presence of interchain coupling if Zeeman energy due to the magnetic field exceeds the spin gap. For 0 < p < 1, antiferromagnetism is induced by randomness at the small field region where the ground state is disordered due to the spin gap in the pure version. At the same time, this model exhibits randomness-induced plateaus at several values of magnetization. The antiferromagnetism is destroyed on the plateaus. As a consequence, we find a series of reentrant quantum phase transitions between transverse antiferromagnetic phases and disordered plateau phases with the increase of magnetic field for a moderate strength of interchain coupling. Above the main plateaus, the magnetization curve consists of a series of small plateaus and jumps between them. It is also found that antiferromagnetism is induced by infinitesimal interchain coupling at the jumps between the small plateaus. We conclude that this antiferromagnetism is supported by the mixing of low-lying excited states by the staggered interchain mean field even though the spin correlation function is short ranged in the ground state of each chain.

  8. Phase fluctuations of a radio wave in the case of total internal reflection from a randomly inhomogeneous ionosphere

    NASA Astrophysics Data System (ADS)

    Afanasiev, N. T.; Laryunin, O. A.; Markov, V. P.

    2009-10-01

    Based on the geometrical-optics approximation, we propose a method for calculation of statistical moments of the radio-wave phase in the case of total internal reflection from a randomly inhomogeneous ionosphere with a monotonic height profile of regular dielectric permittivity. To take into account the radio-wave scattering at the reflection point in a correct way, we perform analytical transformation of the eikonal equation solution derived in a first approximation of the perturbation method.

  9. The topology of large-scale structure. I - Topology and the random phase hypothesis. [galactic formation models

    NASA Technical Reports Server (NTRS)

    Weinberg, David H.; Gott, J. Richard, III; Melott, Adrian L.

    1987-01-01

    Many models for the formation of galaxies and large-scale structure assume a spectrum of random phase (Gaussian), small-amplitude density fluctuations as initial conditions. In such scenarios, the topology of the galaxy distribution on large scales relates directly to the topology of the initial density fluctuations. Here a quantitative measure of topology - the genus of contours in a smoothed density distribution - is described and applied to numerical simulations of galaxy clustering, to a variety of three-dimensional toy models, and to a volume-limited sample of the CfA redshift survey. For random phase distributions the genus of density contours exhibits a universal dependence on threshold density. The clustering simulations show that a smoothing length of 2-3 times the mass correlation length is sufficient to recover the topology of the initial fluctuations from the evolved galaxy distribution. Cold dark matter and white noise models retain a random phase topology at shorter smoothing lengths, but massive neutrino models develop a cellular topology.

  10. A randomized two-stage design for phase II clinical trials based on a Bayesian predictive approach.

    PubMed

    Cellamare, Matteo; Sambucini, Valeria

    2015-03-15

    The rate of failure in phase III oncology trials is surprisingly high, partly owing to inadequate phase II studies. Recently, the use of randomized designs in phase II is being increasingly recommended, to avoid the limits of studies that use a historical control. We propose a two-arm two-stage design based on a Bayesian predictive approach. The idea is to ensure a large probability, expressed in terms of the prior predictive probability of the data, of obtaining a substantial posterior evidence in favour of the experimental treatment, under the assumption that it is actually more effective than the standard agent. This design is a randomized version of the two-stage design that has been proposed for single-arm phase II trials by Sambucini. We examine the main features of our novel design as all the parameters involved vary and compare our approach with Jung's minimax and optimal designs. An illustrative example is also provided online as a supplementary material to this article.

  11. Two-bit multi-level phase change random access memory with a triple phase change material stack structure

    NASA Astrophysics Data System (ADS)

    Gyanathan, Ashvini; Yeo, Yee-Chia

    2012-11-01

    This work demonstrates a novel two-bit multi-level device structure comprising three phase change material (PCM) layers, separated by SiN thermal barrier layers. This triple PCM stack consisted of (from bottom to top), Ge2Sb2Te5 (GST), an ultrathin SiN barrier, nitrogen-doped GST, another ultrathin SiN barrier, and Ag0.5In0.5Sb3Te6. The PCM layers can selectively amorphize to form 4 different resistance levels ("00," "01," "10," and "11") using respective voltage pulses. Electrical characterization was extensively performed on these devices. Thermal analysis was also done to understand the physics behind the phase changing characteristics of the two-bit memory devices. The melting and crystallization temperatures of the PCMs play important roles in the power consumption of the multi-level devices. The electrical resistivities and thermal conductivities of the PCMs and the SiN thermal barrier are also crucial factors contributing to the phase changing behaviour of the PCMs in the two-bit multi-level PCRAM device.

  12. Spectral shifts and switches in random fields upon interaction with negative-phase materials

    SciTech Connect

    Tong Zhisong; Korotkova, Olga

    2010-07-15

    Spectral shifts in stochastic beam-like fields on interaction with layers of positive- and negative-phase materials are examined on the basis of the ABCD-matrix approach and generalized Huygens-Fresnel principle. It is found that boundaries between such materials may cause spectral switches. Effect of absorption of negative-phase materials on the beam spectrum is discussed. Our results may find applications in connection with spectrum-selection optical interconnects, spectrally encoded information transfer, image formation in systems involving negative-phase materials, and geometrically tunable metamaterials.

  13. Continuity of the Phase Transition for Planar Random-Cluster and Potts Models with {1 ≤ q ≤ 4}

    NASA Astrophysics Data System (ADS)

    Duminil-Copin, Hugo; Sidoravicius, Vladas; Tassion, Vincent

    2017-01-01

    This article studies the planar Potts model and its random-cluster representation. We show that the phase transition of the nearest-neighbor ferromagnetic q-state Potts model on Z^2 is continuous for {q in {2,3,4}}, in the sense that there exists a unique Gibbs state, or equivalently that there is no ordering for the critical Gibbs states with monochromatic boundary conditions. The proof uses the random-cluster model with cluster-weight {q ≥ 1} (note that q is not necessarily an integer) and is based on two ingredients: The fact that the two-point function for the free state decays sub-exponentially fast for cluster-weights {1≤ q≤ 4}, which is derived studying parafermionic observables on a discrete Riemann surface.

  14. Design of a Phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine.

    PubMed

    Delrieu, Isabelle; Leboulleux, Didier; Ivinson, Karen; Gessner, Bradford D

    2015-03-24

    Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist.

  15. Active control on high-order coherence and statistic characterization on random phase fluctuation of two classical point sources

    PubMed Central

    Hong, Peilong; Li, Liming; Liu, Jianji; Zhang, Guoquan

    2016-01-01

    Young’s double-slit or two-beam interference is of fundamental importance to understand various interference effects, in which the stationary phase difference between two beams plays the key role in the first-order coherence. Different from the case of first-order coherence, in the high-order optical coherence the statistic behavior of the optical phase will play the key role. In this article, by employing a fundamental interfering configuration with two classical point sources, we showed that the high- order optical coherence between two classical point sources can be actively designed by controlling the statistic behavior of the relative phase difference between two point sources. Synchronous position Nth-order subwavelength interference with an effective wavelength of λ/M was demonstrated, in which λ is the wavelength of point sources and M is an integer not larger than N. Interestingly, we found that the synchronous position Nth-order interference fringe fingerprints the statistic trace of random phase fluctuation of two classical point sources, therefore, it provides an effective way to characterize the statistic properties of phase fluctuation for incoherent light sources. PMID:27021589

  16. Double-image encryption without information disclosure using phase-truncation Fourier transforms and a random amplitude mask.

    PubMed

    Wang, Xiaogang; Zhao, Daomu; Chen, Yixiang

    2014-08-10

    We present a study about information disclosure in phase-truncation-based cryptosystems. The main information of the original image to be encoded can be obtained by using a decryption key in the worst case. The problem cannot be thoroughly solved by imaginary part truncating, keeping the encryption keys as private keys, or applying different phase keys for different plaintexts during each encryption process as well as the phase modulation in the frequency domain. In order to eliminate the risk of unintended information disclosure, we further propose a nonlinear spatial and spectral encoding technique using a random amplitude mask (RAM). The encryption process involving two security layers can be fully controlled by a RAM. The spatial encoding of the plaintext images and the simultaneous encryption of the plaintext images and the encryption key greatly enhance the security of system, avoiding several attacks that have cracked the phase-truncation-based cryptosystems. Besides, the hybrid encryption system retains the advantage of a trap door one-way function of phase truncation. Numerical results have demonstrated the feasibility and effectiveness of the proposed encryption algorithm.

  17. Damage detection using transient trajectories in phase-space with extended random decrement technique under non-stationary excitations

    NASA Astrophysics Data System (ADS)

    Liu, Gang; Mao, Zhu; Todd, Michael

    2016-11-01

    This paper proposes a damage detection method based on the geometrical variation of transient trajectories in phase-space, and the proposed methodology is compatible with non-stationary excitations (e.g., earthquake-induced ground motion). The work presented assumes zero-mean non-stationary excitation, and extends the random decrement technique to convert non-stationary response signals of the structure into free-vibration data. Transient trajectories of the structure are reconstructed via the embedding theorem from the converted free-vibration data, and trajectories are mapped successively into phase-space to enhance statistical analysis. Based upon the characterized system dynamics in terms of phase-space, the time prediction error is adopted as the damage index. To identify the presence and severity of damage in a statistically rigorous way, receiver operating characteristic curves and the Bhattacharyya distance are employed. The results from both numerical simulations and experiments validate the proposed framework, when the test structures are subject to non-stationary excitations. The extension achieved in this paper enables the phase-space damage detection approach to be compatible with non-stationary scenarios, such as traffic, wind, and earthquake loadings. Moreover, the results indicate that this phase-state-based method is able to identify damage-induced nonlinearity in response, which is an intrinsic characteristic associated with most structural damage types.

  18. Active control on high-order coherence and statistic characterization on random phase fluctuation of two classical point sources.

    PubMed

    Hong, Peilong; Li, Liming; Liu, Jianji; Zhang, Guoquan

    2016-03-29

    Young's double-slit or two-beam interference is of fundamental importance to understand various interference effects, in which the stationary phase difference between two beams plays the key role in the first-order coherence. Different from the case of first-order coherence, in the high-order optical coherence the statistic behavior of the optical phase will play the key role. In this article, by employing a fundamental interfering configuration with two classical point sources, we showed that the high- order optical coherence between two classical point sources can be actively designed by controlling the statistic behavior of the relative phase difference between two point sources. Synchronous position Nth-order subwavelength interference with an effective wavelength of λ/M was demonstrated, in which λ is the wavelength of point sources and M is an integer not larger than N. Interestingly, we found that the synchronous position Nth-order interference fringe fingerprints the statistic trace of random phase fluctuation of two classical point sources, therefore, it provides an effective way to characterize the statistic properties of phase fluctuation for incoherent light sources.

  19. Role of deformation on giant resonances within the quasiparticle random-phase approximation and the Gogny force

    SciTech Connect

    Peru, S.; Goutte, H.

    2008-04-15

    Fully consistent axially-symmetric-deformed quasiparticle random phase approximation (QRPA) calculations have been performed, in which the same Gogny D1S effective force has been used for both the Hartree-Fock-Bogolyubov mean field and the QRPA approaches. Giant resonances calculated in deformed {sup 26-28}Si and {sup 22-24}Mg nuclei as well as in the spherical {sup 30}Si and {sup 28}Mg isotopes are presented. Theoretical results for isovector-dipole and isoscalar monopole, quadrupole, and octupole responses are presented and the impact of the intrinsic nuclear deformation is discussed.

  20. Communication: Two-component ring-coupled-cluster computation of the correlation energy in the random-phase approximation

    NASA Astrophysics Data System (ADS)

    Krause, Katharina; Klopper, Wim

    2013-11-01

    Within the framework of density-functional theory, the correlation energy is computed in the random-phase approximation (RPA) using spinors obtained from a two-component relativistic Kohn-Sham calculation accounting for spin-orbit interactions. Ring-coupled-cluster equations are solved to obtain the two-component RPA correlation energy. Results are presented for the hydrides of the halogens Br, I, and At as well as of the coinage metals Cu, Ag, and Au, based on two-component relativistic exact-decoupling Kohn-Sham calculations.

  1. Role of vertex corrections in the matrix formulation of the random phase approximation for the multiorbital Hubbard model

    NASA Astrophysics Data System (ADS)

    Altmeyer, Michaela; Guterding, Daniel; Hirschfeld, P. J.; Maier, Thomas A.; Valentí, Roser; Scalapino, Douglas J.

    2016-12-01

    In the framework of a multiorbital Hubbard model description of superconductivity, a matrix formulation of the superconducting pairing interaction that has been widely used is designed to treat spin, charge, and orbital fluctuations within a random phase approximation (RPA). In terms of Feynman diagrams, this takes into account particle-hole ladder and bubble contributions as expected. It turns out, however, that this matrix formulation also generates additional terms which have the diagrammatic structure of vertex corrections. Here we examine these terms and discuss the relationship between the matrix-RPA superconducting pairing interaction and the Feynman diagrams that it sums.

  2. Communication: Two-component ring-coupled-cluster computation of the correlation energy in the random-phase approximation

    SciTech Connect

    Krause, Katharina; Klopper, Wim

    2013-11-21

    Within the framework of density-functional theory, the correlation energy is computed in the random-phase approximation (RPA) using spinors obtained from a two-component relativistic Kohn–Sham calculation accounting for spin–orbit interactions. Ring-coupled-cluster equations are solved to obtain the two-component RPA correlation energy. Results are presented for the hydrides of the halogens Br, I, and At as well as of the coinage metals Cu, Ag, and Au, based on two-component relativistic exact-decoupling Kohn–Sham calculations.

  3. Analysis on the lateral resolution of optical scanning holography system based on random phase encoding using restricted pupils

    NASA Astrophysics Data System (ADS)

    Wang, Yun; Hu, Jian-Ping; Yuan, Sheng; Xie, Jian; Guo, Xue-Fan; Zhang, Luo-Zhi; Wan, Dao-Ming; Hu, You-Jun; Zhou, Xin

    2014-05-01

    In this paper, we analyze the point spread function of optical scanning holography (OSH) system based on random phase encoding (RPE-OSH) with restricted pupils and compare the lateral resolution of RPE-OSH system with the one of conventional OSH system by the definition of Rayleigh criterion. The results show that the main lobe width of RPE-OSH system is much narrower than that of the conventional OSH system under the same conditions; thus, the reconstructed image in RPE-OSH system has a higher lateral resolution and reserves more detailed information. This conclusion is verified by numerical simulations of the Cymbella cymbiformis image reconstruction.

  4. Core-polarization-corrected random-phase approximation with exact exchange for dipole surface plasmons in silver clusters

    NASA Astrophysics Data System (ADS)

    Xuan, Fengyuan; Guet, Claude

    2016-10-01

    The surface plasmon in silver clusters is red shifted with respect to standard jellium random-phase approximation (RPA) predictions that work well for simple metal clusters. The reason for the deviation arises primarily from the non-negligible polarization interaction between the valence electrons and ionic cores. In order to quantify this effect in the jellium approximation we introduce a modified RPAE (RPA with exact exchange). The jellium background of Ag cores is treated as a polarizable sphere. This model predicts a dipole surface resonance in excellent agreement with published experimental data. Moreover it yields the blue shift (red shift) with decreasing sizes for cationic (anionic) Ag clusters as observed experimentally.

  5. The phase diagram of a directed polymer in random media with p-spin ferromagnetic interactions

    NASA Astrophysics Data System (ADS)

    Wedagedera, J. R.

    2011-01-01

    We consider a directed polymer model with an additive p-spin (p>2) ferromagnetic term in the Hamiltonian. We give a rigorous proof for the specific free energy and derive the phase diagram. This model was proposed previously, and a detailed proof was given in the case p = 2, while the main result was only stated for p > 2. We give a detailed proof of the main result and show the behavior of the model as p → ∞ by constructing the phase diagram also in this case. These results are important in many applications, for instance, in telecommunication and immunology. Our major finding is that in the phase diagram for p > 2, a new transition curve (absent for p = 2) emerges between the paramagnetic region and the so-called mixed region and that the ferromagnetic region diminishes as p → ∞.

  6. The Szilard engine revisited: Entropy, macroscopic randomness, and symmetry breaking phase transitions

    NASA Astrophysics Data System (ADS)

    Parrondo, Juan M. R.

    2001-09-01

    The role of symmetry breaking phase transitions in the Szilard engine is analyzed. It is shown that symmetry breaking is the only necessary ingredient for the engine to work. To support this idea, we show that the Ising model behaves exactly as the Szilard engine. We design a purely macroscopic Maxwell demon from an Ising model, demonstrating that a demon can operate with information about the macrostate of the system. We finally discuss some aspects of the definition of entropy and how thermodynamics should be modified to account for the variations of entropy in second-order phase transitions.

  7. 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.

  8. A randomized controlled trial with bright light and melatonin for delayed sleep phase disorder: effects on subjective and objective sleep.

    PubMed

    Saxvig, Ingvild West; Wilhelmsen-Langeland, Ane; Pallesen, Ståle; Vedaa, Oystein; Nordhus, Inger Hilde; Bjorvatn, Bjørn

    2014-02-01

    Delayed sleep phase disorder (DSPD) is assumed to be common amongst adolescents, with potentially severe consequences in terms of school attendance and daytime functioning. The most common treatment approaches for DSPD are based on the administration of bright light and/or exogenous melatonin with or without adjunct behavioural instructions. Much is generally known about the chronobiological effects of light and melatonin. However, placebo-controlled treatment studies for DSPD are scarce, in particular in adolescents and young adults, and no standardized guidelines exist regarding treatment. The aim of the present study was, therefore, to investigate the short- and long-term effects on sleep of a DSPD treatment protocol involving administration of timed bright light and melatonin alongside gradual advancement of rise time in adolescents and young adults with DSPD in a randomized controlled trial and an open label follow-up study. A total of 40 adolescents and young adults (age range 16-25 years) diagnosed with DSPD were recruited to participate in the study. The participants were randomized to receive treatment for two weeks in one of four treatment conditions: dim light and placebo capsules, bright light and placebo capsules, dim light and melatonin capsules or bright light and melatonin capsules. In a follow-up study, participants were re-randomized to either receive treatment with the combination of bright light and melatonin or no treatment in an open label trial for approximately three months. Light and capsules were administered alongside gradual advancement of rise times. The main end points were sleep as assessed by sleep diaries and actigraphy recordings and circadian phase as assessed by salivary dim light melatonin onset (DLMO). During the two-week intervention, the timing of sleep and DLMO was advanced in all treatment conditions as seen by about 1 h advance of bed time, 2 h advance of rise time and 2 h advance of DLMO in all four groups. Sleep

  9. Shock due to urosepsis: A multicentre study

    PubMed Central

    Yamamichi, Fukashi; Shigemura, Katsumi; Kitagawa, Koichi; Takaba, Kei; Tokimatsu, Issei; Arakawa, Soichi; Fujisawa, Masato

    2017-01-01

    Introduction Urosepsis is a severe infection that can cause shock afterwards. The purpose of this study is to investigate the clinical and bacterial risk factors for shock in those cases with urosepsis caused by urinary tract infection in a multicentre study. Methods Our study included 77 consecutive urosepsis cases from four hospitals. We examined factors such as patient characteristics, underlying disease, serum white blood cell (WBC) count, platelet count, C-reactive protein (CRP) level at the time of diagnosis of urosepsis, urinary tract occlusion, causative bacteria, and bacterial antibiotic susceptibilities. Statistical analyses were performed to assess the potential risk factors for shock during the clinical course of urosepsis by a multivariate analysis. Results We had 38 male and 39 female patients aged 25–104 (median 73). Underlying diseases included cancers (n=22, 28.6 %) and diabetes mellitus (n=17, 22.1 %). Positive blood culture was seen in 74 cases; these involved 88 bacterial strains, of which Escherichia coli was the most common (34 strains, 38.6 %). There were 31 cases with shock (40.3 %) and multivariate analyses demonstrated that serum CRP was the only clinical risk factor for shock due to urosepsis. Conclusions Our study demonstrated that serum CRP was a risk factor for shock during urosepsis in a multicentre analysis. Further prospective studies with a greater number of patients are needed to draw more definitive conclusions. PMID:28360956

  10. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrate Biochemically Relapsed Prostate Cancer

    DTIC Science & Technology

    2015-09-01

    Award Number: W81XWH-09-1-0596 TITLE: A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti- PSMA Monoclonal Antibody J591 in Patients With High...1-0596 A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti- PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrat Biochemically Relapsed...in December 2014 with approval to proceed without modifications. 15. SUBJECT TERMS Prostate cancer, PSA, PSMA , monoclonal antibody

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

    DTIC Science & Technology

    2014-09-01

    Scheinberg DA. Vaccination with Synthetic Analog Peptides Derived from WT1 Oncoprotein Induces T Cell Responses in Patients with Complete Remission ...TITLE:Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of...TITLE:Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality

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

    DTIC Science & Technology

    2012-09-01

    10-1-0699 TITLE: Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after...Prescribed by ANSI Std. Z39.18 W81XWH-10-1-0699 Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant... peptides that are given together with Montanide and GM-CSF as immunologic adjuvants. This WT1 vaccine was previously tested in a small pilot trial

  13. Embolization with larger-caliber coils can increase packing density: Evidence from the pilot phase of a randomized trial.

    PubMed

    Cloutier, Francis; Khoury, Naim; Ghostine, Jimmy; Farzin, Behzad; Kotowski, Marc; Weill, Alain; Roy, Daniel; Raymond, Jean

    2017-02-01

    Background and purpose Endovascular coil embolization of cerebral aneurysms is associated with suboptimal angiographic results in up to 20-30% of patients. Coil packing density has been used as an index of the success of the initial procedure. The trial sought to study the effects of using 15-caliber coils, as compared with 10-caliber coils, on packing density. Methods Does Embolization with Larger coils lead to better Treatment of Aneurysms (DELTA) is an investigator-initiated multicenter prospective, randomized, controlled clinical trial. Patients are randomized 1:1 to embolization with either 10-caliber coils exclusively (control group) or the highest safely achievable proportion of 15-caliber coils and 10-caliber coils if necessary (intervention group) in 4-12-mm aneurysms. The endpoint of the pilot phase of the trial was the capacity to increase packing density of the initial procedure, calculated using a mathematical transformation of the dimensions entered into the case report forms. Secondary outcomes included the total number of coils used per aneurysm, total fluoroscopy time, initial angiographic outcomes and any adverse or undesirable event. Results Seventy patients were recruited between June 2014 and November 2015. Compared with 10-caliber coils, the 15-caliber coil group had a higher median packing density (44% vs 24%, p = 0.017). Results of other outcome measures were similar for the two groups. Conclusion Coiling of small and medium aneurysms randomized to 15-caliber coils achieved higher packing densities compared with coiling using 10-caliber coils.

  14. Phase IV: randomized controlled trial to evaluate lot consistency of trivalent split influenza vaccines in healthy adults.

    PubMed

    Song, Joon Young; Cheong, Hee Jin; Lee, Jacob; Wie, Seong-Heon; Park, Kyung-Hwa; Kee, Sae Yoon; Jeong, Hye Won; Kim, Yeon-Sook; Noh, Ji Yun; Choi, Won Suk; Park, Dae Won; Sohn, Jang Wook; Kim, Woo Joo

    2014-01-01

    Influenza vaccines are the primary method for preventing influenza and its complications. Considering the increasing demand for influenza vaccines, vaccine manufacturers are required to establish large-scale production systems. This phase IV randomized trial was conducted to evaluate the lot consistency of trivalent split influenza vaccines regarding immunogenicity and safety. A total of 1,023 healthy adults aged 18-64 y were enrolled in the study. Subjects were randomly assigned in a 1:1 ratio to receive the GC FLU® Prefilled Syringe or the GC FLU® Injection, and they were further randomized to one of 3 lots of each vaccine in a 1:1:1 ratio. In both GC FLU® Injection and GC FLU® Prefilled Syringe groups, immune responses were equivalent between lots for each of the 3 vaccine strains on day 21. The 2-sided 95% CI of GMT ratios between pairs of lots were between 0.67 and 1.5, meeting the equivalence criteria. After vaccination, all 3 criteria of the European Medicines Agency were met in both GC FLU® Injection and GC FLU® Prefilled Syringe groups. The vaccines showed tolerable safety profiles without serious adverse events. The demonstration of lot consistency, robust immunogenic responses and favorable safety profiles support the reliability of mass-manufacturing systems for the GC FLU® Injection and GC FLU® Prefilled Syringe.

  15. Two Phase II randomized trials on the CRTh2 antagonist AZD1981 in adults with asthma

    PubMed Central

    Kuna, Piotr; Bjermer, Leif; Tornling, Göran

    2016-01-01

    Background Chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cell (CRTh2) receptor antagonists is being investigated for asthma. Objectives The aim of this study was to assess the effects of the CRTh2 receptor antagonist, AZD1981 (with/without inhaled corticosteroids [ICSs]), on lung function and asthma control. Patients and methods Adults aged 18–60 years were enrolled in two randomized, placebo-controlled, parallel-group trials (protocol number: D9830C00003 [study 1, n=209] and protocol number: D9830C00004 [study 2, n=510]). In study 1, patients with stable asthma (forced expiratory volume in 1 second [FEV1]: 65%−110%) were withdrawn from ICS (<400 µg/d) and randomized to AZD1981 1,000 mg twice daily (bid) or placebo. In study 2, patients with uncontrolled asthma (FEV1: 40%−85%) despite ICS therapy (≥500 µg/d) were randomized to 50 mg, 400 mg, or 1,000 mg bid AZD1981 or placebo. The primary efficacy variable for both trials was the change in morning peak expiratory flow after 4 weeks of treatment. Secondary variables included Asthma Control Questionnaire (ACQ-5) scores, FEV1 assessments, safety, and tolerability. In study 2, efficacy was also assessed according to atopic status. Results Following 4 weeks of treatment, there was a nonsignificant increase in morning peak expiratory flow on AZD1981 1,000 mg bid (9.5 L/min vs placebo, P=0.086 [study 1] and 12 L/min vs placebo, P=0.16 [study 2]). In study 2, all doses of AZD1981 provided significant improvements in ACQ-5 scores (0.26–0.3 units vs placebo, P=0.010–0.022); however, there was no dose–response relationship. Improved ACQ-5 scores and FEV1 were observed in the majority of atopic patients treated with AZD1981. AZD1981 was well tolerated across treatment groups. Conclusion Further research may be warranted in atopic patients to fully evaluate the clinical efficacy of AZD1981. PMID:27621597

  16. A randomised multicentre phase II study with cisplatin/docetaxel vs oxaliplatin/docetaxel as first-line therapy in patients with advanced or metastatic non-small cell lung cancer

    PubMed Central

    Atmaca, A; Al-Batran, S-E; Werner, D; Pauligk, C; Güner, T; Koepke, A; Bernhard, H; Wenzel, T; Banat, A-G; Brueck, P; Caca, K; Prasnikar, N; Kullmann, F; Günther Derigs, H; Koenigsmann, M; Dingeldein, G; Neuhaus, T; Jäger, E

    2013-01-01

    Background: This study was designed to compare cisplatin/docetaxel with oxaliplatin/docetaxel in patients with advanced and metastatic non-small lung cancer as a first-line treatment. Methods: Patients were randomly assigned to receive either cisplatin 75 mg m−2 and docetaxel 75 mg m−2 every 3 weeks or oxaliplatin 85 mg m−2 and docetaxel 50 mg m−2 every 2 weeks. The primary end point was response rate, and secondary end points were toxicity, time to progression and overall survival. Results: A total of 88 patients (median age: 65 (39–86) years; stage IV: 93%) were randomly assigned. Response rate (complete and partial response) was 47% (95% CI: 33–61%) in the cisplatin/docetaxel arm and 28% (95% CI: 17–43%) in the oxaliplatin/docetaxel arm (P=0.118). There was no significant difference in time to progression (6.3 vs 4.9 months, P=0.111) and median overall survival (11.6 vs 7.0 months, P=0.102) with cisplatin/docetaxel vs oxaliplatin/docetaxel, although slight trends favouring cisplatin were seen. Oxaliplatin/docetaxel was associated with significantly less (any grade) renal toxicity (56% vs 11%), any grade fatigue (81% vs 59%), complete alopecia (76% vs 27%), any grade leukopenia (84% vs 61%) and grade 3/4 leukopenia (44% vs 14%) and neutropenia (56% vs 27%). Conclusion: Oxaliplatin/docetaxel has activity in metastatic non-small cell lung cancer, but it seems to be inferior to cisplatin/docetaxel. PMID:23329236

  17. Bistable random laser that uses a phase transition of polyethylene glycol

    NASA Astrophysics Data System (ADS)

    Saito, Mitsunori; Nishimura, Yoshihiro

    2016-03-01

    Polyethylene glycol (PEG) is transparent in the liquid phase and turns to a translucent solid through a phase transition at around room temperature. A PEG solution of rhodamine 6G was excited by a laser pulse (527 nm wavelength, 10 ns duration, 190 μJ) to measure fluorescence spectra during the phase transition process. Whereas the fluorescence peak was weak and broad at 60 °C (spontaneous emission), a strong, narrow peak appeared in the temperature range below 50 °C, since a stimulated emission (amplified spontaneous emission) took place due to the scattering in the solid PEG. This laser emission control was repeatable by reversing an electric voltage (-12 or +12 V) that drove a Peltier element. Interestingly, the sample exhibited a strong stimulated emission at 52 °C during the heating process, although no strong emission was visible at the same temperature during the cooling process (bistability). The fluorescence peak wavelength was tunable between 566 and 572 nm by changing the cooling rate.

  18. Beyond the random phase approximation: Stimulated Brillouin backscatter for finite laser coherence times

    SciTech Connect

    Korotkevich, Alexander O.; Lushnikov, Pavel M.; Rose, Harvey A.

    2015-01-15

    We developed a linear theory of backward stimulated Brillouin scatter (BSBS) of a spatially and temporally random laser beam relevant for laser fusion. Our analysis reveals a new collective regime of BSBS (CBSBS). Its intensity threshold is controlled by diffraction, once cT{sub c} exceeds a laser speckle length, with T{sub c} the laser coherence time. The BSBS spatial gain rate is approximately the sum of that due to CBSBS, and a part which is independent of diffraction and varies linearly with T{sub c}. The CBSBS spatial gain rate may be reduced significantly by the temporal bandwidth of KrF-based laser systems compared to the bandwidth currently available to temporally smoothed glass-based laser systems.

  19. Mast Cell Stabilizer (Ketotifen) in Fibromyalgia: Phase 1 Randomized Controlled Clinical Trial

    PubMed Central

    Ang, Dennis C.; Hilligoss, Janna; Stump, Timothy

    2014-01-01

    Objectives Compared to healthy controls, patients with fibromyalgia (FM) have more mast cells in the skin. Whether mast cells are involved in the pathogenesis of FM is unclear. We sought to determine the effects of a mast cell stabilizer (ketotifen) on FM symptoms. Methods Fifty-one FM subjects were randomized to daily oral ketotifen 2 mg BID (n=24) for 8 weeks or placebo (N=27). Mean age of subjects was 51.2 years (standard deviation/SD 8.4); 88% were female and 88% were white; 22% were taking concomitant opiates; and mean pressure pain sensitivity (range 0-20) was 10.0 (0.4). At study entry, the weekly average pain intensity was 6.4 (1.1) and the mean score on the Revised Fibromyalgia Impact Questionnaire (FIQR) was 66.8 (14.0). Results We found no statistically significant treatment group differences from baseline in either group for the two primary measures: weekly average pain intensity [ketotifen −1.3 (1.9) vs. placebo −1.5 (1.9), p=0.7]; and FIQR score [−12.1 (19.5) vs. −12.2 (18.1), p=0.9]. No secondary outcome measures (BPI pain intensity, and pressure pain sensitivity) reached statistical significance; results did not differ in the intent-to-treat and completer analyses. Other than transient sedation [6 (28.6%) vs. 1 (4.0%)], ketotifen was well tolerated. Discussion The study results question whether skin mast cells play a major role in the pathogenesis of FM. However, given the role of mast cells in peripheral and central nociception, and the minimal side effects of ketotifen, a randomized clinical trial using increasing doses of ketotifen may be warranted. PMID:25370135

  20. Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial

    PubMed Central

    Rapp, Stephen R.; Case, L. Doug; Peiffer, Ann; Naughton, Michelle M.; Chan, Michael D.; Stieber, Volker W.; Moore, Dennis F.; Falchuk, Steven C.; Piephoff, James V.; Edenfield, William J.; Giguere, Jeffrey K.; Loghin, Monica E.; Shaw, Edward G.

    2015-01-01

    Purpose Neurotoxic effects of brain irradiation include cognitive impairment in 50% to 90% of patients. Prior studies have suggested that donepezil, a neurotransmitter modulator, may improve cognitive function. Patients and Methods A total of 198 adult brain tumor survivors ≥ 6 months after partial- or whole-brain irradiation were randomly assigned to receive a single daily dose (5 mg for 6 weeks, 10 mg for 18 weeks) of donepezil or placebo. A cognitive test battery assessing memory, attention, language, visuomotor, verbal fluency, and executive functions was administered before random assignment and at 12 and 24 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated. Results Of this mostly middle-age, married, non-Hispanic white sample, 66% had primary brain tumors, 27% had brain metastases, and 8% underwent prophylactic cranial irradiation. After 24 weeks of treatment, the composite scores did not differ significantly between groups (P = .48); however, significant differences favoring donepezil were observed for memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016). Significant interactions between pretreatment cognitive function and treatment were found for cognitive composite (P = .01), immediate recall (P = .05), delayed recall (P = .004), attention (P = .01), visuomotor skills (P = .02), and motor speed and dexterity (P < .001), with the benefits of donepezil greater for those who were more cognitively impaired before study treatment. Conclusion Treatment with donepezil did not significantly improve the overall composite score, but it did result in modest improvements in several cognitive functions, especially among patients with greater pretreatment impairments. PMID:25897156

  1. Rituximab in the Treatment of Refractory Adult and Juvenile Dermatomyositis and Adult Polymyositis: A Randomized, Placebo-phase Trial

    PubMed Central

    Oddis, Chester V.; Reed, Ann M.; Aggarwal, Rohit; Rider, Lisa G.; Ascherman, Dana P.; Levesque, Marc C.; Barohn, Richard J.; Feldman, Brian M.; Harris-Love, Michael O.; Koontz, Diane C.; Fertig, Noreen; Kelley, Stephanie S.; Pryber, Sherrie L.; Miller, Frederick W.; Rockette, Howard E.

    2012-01-01

    Objective To assess the safety and efficacy of rituximab in a randomized, double-blind, placebo-phase, trial of adult and pediatric myositis. Methods Adults with refractory polymyositis and adults and children with refractory dermatomyositis were enrolled. Entry criteria included muscle weakness and ≥2 additional abnormal core set measures (CSM) for adults. JDM patients required ≥ 3 abnormal CSM with or without muscle weakness. Patients were randomized to either ‘rituximab early’ or ‘rituximab late’ and glucocorticoid and immunosuppressive therapy were allowed at entry. The primary endpoint compared the time to achieve the preliminary International Myositis Assessment and Clinical Studies Group definition of improvement (DOI) between the 2 groups. The secondary endpoints were time to achieve ≥20% improvement in muscle strength, and the proportion of early and late rituximab patients achieving DOI at week 8. Results Among 200 randomized patients (76 PM/76 DM/48 JDM), 195 showed no difference in the time to DOI between the rituximab late (n=102) and rituximab early (n=93) groups (p=0.74, log rank) with a median time to DOI of 20.2 weeks and 20.0 weeks respectively. The secondary endpoints also did not significantly differ between the two treatment groups. However, 161 (83%) of randomized patients met the DOI and individual CSM improved in both groups throughout the 44-week trial. Conclusion Although there were no significant differences in the two treatment arms for the primary and secondary endpoints, 83% of refractory adult and juvenile myositis patients met the DOI. The role of B cell depleting therapies in myositis warrants further study with consideration for a different trial design. PMID:23124935

  2. Random quasi-phase-matched nonlinear optical conversion of supercontinuum to the ultraviolet

    SciTech Connect

    Aleksandrovsky, A. S. Vyunishev, A. M.; Zaitsev, A. I.; Slabko, V. V.

    2013-12-16

    Conversion of fs supercontinuum to the ultraviolet (UV) range from 260 to 305 nm in nonlinear photonic crystal of strontium tetraborate is obtained. Spectral shape of generated UV radiation is governed by the shape of supercontinuum spectrum, focusing conditions and phase mismatch in the material of nonlinear photonic crystal. Maximum integral UV power of 2.6 μW was obtained in the case of weaker focusing, and peaks with the spectral width 1–3 nm dominate in the spectrum. Using tight focusing, broadband radiation in the range 265–300 nm was obtained.

  3. Efficacy and safety of single-dose fosaprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving high-dose cisplatin: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial

    PubMed Central

    Saito, H.; Yoshizawa, H.; Yoshimori, K.; Katakami, N.; Katsumata, N.; Kawahara, M.; Eguchi, K.

    2013-01-01

    Background We evaluated the efficacy and safety of single-dose fosaprepitant in combination with intravenous granisetron and dexamethasone. Patients and methods Patients receiving chemotherapy including cisplatin (≥70 mg/m2) were eligible. A total of 347 patients (21% had received cisplatin with vomiting) were enrolled in this trial to receive the fosaprepitant regimen (fosaprepitant 150 mg, intravenous, on day 1 in combination with granisetron, 40 μg/kg, intravenous, on day 1 and dexamethasone, intravenous, on days 1–3) or the control regimen (placebo plus intravenous granisetron and dexamethasone). The primary end point was the percentage of patients who had a complete response (no emesis and no rescue therapy) over the entire treatment course (0–120 h). Results The percentage of patients with a complete response was significantly higher in the fosaprepitant group than in the control group (64% versus 47%, P = 0.0015). The fosaprepitant regimen was more effective than the control regimen in both the acute (0–24 h postchemotherapy) phase (94% versus 81%, P = 0.0006) and the delayed (24–120 h postchemotherapy) phase (65% versus 49%, P = 0.0025). Conclusions Single-dose fosaprepitant used in combination with granisetron and dexamethasone was well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic cancer chemotherapy, including high-dose cisplatin. PMID:23117073

  4. Characteristics of a cluster-randomized phase IV human papillomavirus vaccination effectiveness trial.

    PubMed

    Lehtinen, Matti; Apter, Dan; Baussano, Iacopo; Eriksson, Tiina; Natunen, Kari; Paavonen, Jorma; Vänskä, Simopekka; Bi, Dan; David, Marie-Pierre; Datta, Sanjoy; Struyf, Frank; Jenkins, David; Pukkala, Eero; Garnett, Geoff; Dubin, Gary

    2015-03-03

    High-risk human papillomaviruses (hrHPV) cause anogenital and oropharyngeal cancers. HPV-16/18 virus-like particle vaccine formulated with an AS04 adjuvant is very efficacious against hrHPV associated precancers but the herd effects of different vaccination scenarios are not known. Our cluster randomized trial (NCT00534638) assesses the overall and herd effects of vaccinating girls vs. girls and boys. In two school-years (2007-2008 and 2008-2009) we invited 80,272 1992-1995 born early adolescents to a CRT in 33 communities a priori stratified by low, intermediate and high HPV-16/18 seroprevalence. In 11 Arm A communities 90% of participating girls and boys were assigned to receive HPV-16/18 vaccine, in 11 Arm B communities 90% of girls were assigned to receive HPV-16/18 vaccine - boys were assigned to receive hepatitis B-virus (HBV) vaccine, and in 11 Arm C communities all were assigned to receive HBV-vaccine. Prevalence of HPV in vaccinated and unvaccinated girls is studied at age 18.5 years. Recruitment resulted in equal enrolment of four birth cohorts (born 1992-1995) comprising altogether 32,175 (40% response) early adolescents: 20,514 girls (50.5-53.0% response by arm) and 11,661 boys (21.9-31.6%% response by arm). At the age of 15 years, 79.3% of the vaccinees completed a questionnaire. Among them >98% were living at, and during the week-ends 1.3-1.6% stayed outside, the study site communities. Smoking habit and alcohol consumption were similar in the different trial arms, also mean-age of menarche (12.4 years) and 1st ejaculation (12.6 years), and sexual behaviour (among those <25%, who had had sexual debut) did not differ by arm: mean-age at the sexual debut 14.3 and 14.4 in girls and boys, and proportions of those with multiple (≥5) life-time sexual partners (6.5-7.5%) at the age of 15 years. Uniform residential, life-style and sexual behaviour characteristics indicate successful randomization/enrolment of the CRT. Our CRT will verify modelled

  5. Suvorexant in Patients with Insomnia: Pooled Analyses of Three-Month Data from Phase-3 Randomized Controlled Clinical Trials

    PubMed Central

    Herring, W. Joseph; Connor, Kathleen M.; Snyder, Ellen; Snavely, Duane B.; Zhang, Ying; Hutzelmann, Jill; Matzura-Wolfe, Deborah; Benca, Ruth M.; Krystal, Andrew D.; Walsh, James K.; Lines, Christopher; Roth, Thomas; Michelson, David

    2016-01-01

    Study Objectives: Suvorexant is an orexin receptor antagonist approved for treating insomnia at a maximum dose of 20 mg. Phase-3 trials evaluated two age-adjusted (non-elderly/elderly) dose-regimes of 40/30 mg and 20/15 mg with the primary focus on 40/30 mg. We report here results from pooled analyses of the 20/15 mg dose-regime, which was evaluated as a secondary objective in the trials. Methods: Prespecified analysis of pooled data from two identical randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in non-elderly (18–64 years) and elderly (≥ 65 years) patients with insomnia. Patients were randomized to suvorexant 20/15 mg (non-elderly/elderly), suvorexant 40/30 mg (non-elderly/elderly), or placebo; by design, fewer patients were randomized to 20/15 mg. Efficacy was assessed by self-reported and polysomnography (PSG; subset of patients) sleep maintenance and onset endpoints. Results: Suvorexant 20/15 mg (N = 493 treated) was effective compared to placebo (N = 767 treated) on patient-reported and PSG sleep maintenance and onset endpoints at Night-1 (PSG endpoints) / Week-1 (subjective endpoints), Month-1 and Month-3, except for effects on PSG sleep onset at Month-3. Suvorexant 20/15 mg was generally well tolerated, with 3% of patients discontinuing due to adverse events over 3 months vs. 5.2% on placebo. Somnolence was the most common adverse event (6.7% vs. 3.3% for placebo). There was no systematic evidence of rebound or withdrawal signs or symptoms when suvorexant was discontinued after 3 months of nightly use. Conclusions: Suvorexant 20/15 mg improved sleep onset and maintenance over 3 months of nightly treatment and was generally safe and well tolerated. Clinical Trial Registration: ClinicalTrials.gov trial registration numbers: NCT01097616, NCT01097629. Citation: Herring WJ, Connor KM, Snyder E, Snavely DB, Zhang Y, Hutzelmann J, Matzura-Wolfe D, Benca RM, Krystal AD, Walsh JK, Lines C, Roth T, Michelson D. Suvorexant in

  6. Randomized Phase II Trial of Erlotinib Beyond Progression in Advanced Erlotinib-Responsive Non-Small Cell Lung Cancer

    PubMed Central

    Pennell, Nathan A.; Fu, Pingfu; Saad, Shumaila; Gadgeel, Shirish; Otterson, Gregory A.; Mekhail, Tarek; Snell, Michael; Kuebler, J. Philip; Sharma, Neelesh

    2015-01-01

    Background. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is clearly beneficial in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, acquired resistance develops uniformly and the benefit of continuation of EGFR TKI therapy beyond progression remains unclear. Materials and Methods. This was a randomized phase II study of chemotherapy (arm A: pemetrexed or docetaxel) versus chemotherapy plus erlotinib (ERL) (arm B) in patients with progressive NSCLC following clinical benefit from erlotinib. In arm B, chemotherapy was given with erlotinib at an oral daily dose of 150 mg on days 2–19 of each cycle to minimize negative pharmacodynamic interactions. The primary endpoint was that continuation of erlotinib in this patient population could extend progression-free survival (PFS) by 50%. Results. A total of 46 patients were randomized (arm A: 24; arm B: 22). Patient characteristics were well balanced except there were more female patients in arm A (p = .075). The median PFS of patients in arm A was 5.5 months and for those in arm B, 4.4 months (p = .699). The response rates were 13% and 16% in arms A and B, respectively (p = .79). EGFR status data were available for 39 of the 46 patients and no significant difference in PFS was seen for continuing ERL beyond progression in mutation-positive patients. Substantially more toxicity was seen in arm B than arm A. Conclusion. There was added toxicity but no benefit with the continuation of ERL beyond progression along with chemotherapy as compared with chemotherapy alone. Implications for Practice: The benefits of continuing erlotinib upon progression alongside conventional chemotherapy are unclear. This randomized phase II study, initiated prior to the establishment of routine epidermal growth factor receptor (EGFR) mutation testing, addressed this clinically relevant issue through randomizing patients with prior clinical benefit from erlotinib (thereby enriching

  7. Using a short-pulse diffraction-limited laser beam to probe filamentation of a random phase plate smoothed beam.

    PubMed

    Kline, J L; Montgomery, D S; Flippo, K A; Johnson, R P; Rose, H A; Shimada, T; Williams, E A

    2008-10-01

    A short pulse (few picoseconds) laser probe provides high temporal resolution measurements to elucidate details of fast dynamic phenomena not observable with typical longer laser pulse probes and gated diagnostics. Such a short pulse laser probe (SPLP) has been used to measure filamentation of a random phase plate (RPP) smoothed laser beam in a gas-jet plasma. The plasma index of refraction due to driven density and temperature fluctuations by the RPP beam perturbs the phase front of a SPLP propagating at a 90 degree angle with respect to the RPP interaction beam. The density and temperature fluctuations are quasistatic on the time scale of the SPLP (approximately 2 ps). The transmitted near-field intensity distribution from the SPLP provides a measure of the phase front perturbation. At low plasma densities, the transmitted intensity pattern is asymmetric with striations across the entire probe beam in the direction of the RPP smoothed beam. As the plasma density increases, the striations break up into smaller sizes along the direction of the RPP beam propagation. The breakup of the intensity pattern is consistent with self-focusing of the RPP smoothed interaction beam. Simulations of the experiment using the wave propagation code, PF3D, are in qualitative agreement demonstrating that the asymmetric striations can be attributed to the RPP driven density fluctuations. Quantification of the beam breakup measured by the transmitted SPLP could lead to a new method for measuring self-focusing of lasers in underdense plasmas.

  8. Stationary point analysis of the one-dimensional lattice Landau gauge fixing functional, aka random phase XY Hamiltonian

    SciTech Connect

    Mehta, Dhagash; Kastner, Michael

    2011-06-15

    Research Highlights: > Exact results for all stationary points of some high-dimensional function are given. > They are interpreted as Gribov copies of a lattice Landau gauge fixing functional. > The Gribov ambiguity and the Neuberger problem in compact U(1) are illustrated. > Stationary points are used to discuss a criterion on the absence of phase transitions. - Abstract: We study the stationary points of what is known as the lattice Landau gauge fixing functional in one-dimensional compact U(1) lattice gauge theory, or as the Hamiltonian of the one-dimensional random phase XY model in statistical physics. An analytic solution of all stationary points is derived for lattices with an odd number of lattice sites and periodic boundary conditions. In the context of lattice gauge theory, these stationary points and their indices are used to compute the gauge fixing partition function, making reference in particular to the Neuberger problem. Interpreted as stationary points of the one-dimensional XY Hamiltonian, the solutions and their Hessian determinants allow us to evaluate a criterion which makes predictions on the existence of phase transitions and the corresponding critical energies in the thermodynamic limit.

  9. Once-daily USL255 as adjunctive treatment of partial-onset seizures: Randomized phase III study

    PubMed Central

    Chung, Steve S; Fakhoury, Toufic A; Hogan, R Edward; Nagaraddi, Venkatesh N; Blatt, Ilan; Lawson, Balduin; Arnold, Stephan; Anders, Bob; Clark, Annie M; Laine, Dawn; Meadows, R Shawn; Halvorsen, Mark B

    2014-01-01

    Objective To evaluate the efficacy and safety of USL255, Qudexy™ XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs. Methods In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated. Results Across the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life. Significance The PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects. PMID:24902983

  10. First-principles study of relative stability of rutile and anatase TiO2 using the random phase approximation.

    PubMed

    Cui, Zhi-Hao; Wu, Feng; Jiang, Hong

    2016-11-02

    The relative stability of TiO2 in the rutile and anatase structure is wrongly described by density functional theory in various local, semilocal, or even hybrid functional approximations. In this work, we have found that by considering high-order correlations in the adiabatic connection fluctuation-dissipation theory with the random phase approximation (ACFDT-RPA), rutile is correctly predicted to be more stable than anatase, which can be physically attributed to different characters in the electronic band structure of rutile and anatase, including, in particular, that rutile has a smaller band gap than anatase. We further consider the zero-point energy and finite-temperature effects based on the harmonic approximation, and we found that the inclusion of the zero-point energy correction can further increase the relative stability of rutile, and leads to a better quantitative agreement with available experimental measurements. Our study indicates the importance of considering high-order dynamical correlation effects to correctly predict the relative phase stability of polymorphic materials, especially for those systems in which the less stable phase as predicted by conventional local, semilocal or even hybrid density functional approximations has a smaller band gap than the more stable one.

  11. Multicentric Castleman's Disease in a Child Revealed by Chronic Diarrhea

    PubMed Central

    Benmiloud, Sarra; Chaouki, Sana; Atmani, Samir; Hida, Moustapha

    2015-01-01

    Multicentric Castleman's disease is a rare benign and unexplained lymphoproliferative disorder that is extremely uncommon in children. It presents with fever, systemic symptoms, generalized lymphadenopathy, and laboratory markers of inflammation. Its treatment is not standardized and its prognosis is poor. We report a novel case of multicentric Castleman's disease in a 13-year-old girl who had presented with chronic diarrhea as the only initial presenting symptom. The diagnosis of celiac or inflammatory bowel diseases was suspected, but two and a half years later, the diagnosis of multicentric Castleman's disease was brought following the appearance of abdominal mass whose biopsy revealed Castleman's disease in the plasma cell form. The outcome was favorable after treatment by corticosteroid, chemotherapy, and surgery. The occurrence of diarrhea as the initial symptom of multicentric Castleman's disease without lymph node involvement is very rare. This case report underlines the diagnostic difficulties and the long interval between onset and diagnosis when diarrhea occurs first. PMID:25737793

  12. Distribution of nanoscale nuclei in the amorphous dome of a phase change random access memory

    SciTech Connect

    Lee, Bong-Sub Darmawikarta, Kristof; Abelson, John R.; Raoux, Simone; Shih, Yen-Hao; Zhu, Yu

    2014-02-17

    The nanoscale crystal nuclei in an amorphous Ge{sub 2}Sb{sub 2}Te{sub 5} bit in a phase change memory device were evaluated by fluctuation transmission electron microscopy. The quench time in the device (∼10 ns) afforded more and larger nuclei in the melt-quenched state than in the as-deposited state. However, nuclei were even more numerous and larger in a test structure with a longer quench time (∼100 ns), verifying the prediction of nucleation theory that slower cooling produces more nuclei. It also demonstrates that the thermal design of devices will strongly influence the population of nuclei, and thus the speed and data retention characteristics.

  13. A Phase III Randomized Trial of the Timing of Meloxicam With Iodine-125 Prostate Brachytherapy

    SciTech Connect

    Crook, Juanita; Patil, Nikhilesh; Wallace, Kris; Borg, Jette; Zhou, David; Ma, Clement; Pond, Greg

    2010-06-01

    Purpose: Nonsteroidal anti-inflammatory medication is used to reduce prostate edema and urinary symptoms following prostate brachytherapy. We hypothesized that a cyclooxygenase-2 (COX-2) inhibitor regimen started 1 week prior to seed implant might diminish the inflammatory response, thus reducing edema, retention rates, and symptom severity. Methods and Materials: From March 2004 to February 2008, 316 men consented to an institutional review board-approved randomized study of a 4-week course of meloxicam, 7.5 mg orally twice per day, starting either on the day of implant or 1 week prior to implant. Brachytherapy was performed using iodine-125 seeds and was preplanned and performed under transrectal ultrasound (TRUS) and fluoroscopic guidance. Prostate volume obtained by MR imaging at 1 month was compared to baseline prostate volume obtained by TRUS planimetry and expressed as an edema factor. The trial endpoints were prostate edema at 1 month, International Prostate Symptom Score (IPSS) questionnaire results at 1 and 3 months, and any need for catheterization. Results: Results for 300 men were analyzed. Median age was 61 (range, 45-79 years), and median TRUS prostate volume was 35.7 cc (range, 18.1-69.5 cc). Median IPSS at baseline was 5 (range, 0-24) and was 15 at 1 month, 16 at 3 months, and 10 at 6 months. Catheterization was required for 7% of patients (6.2% day 0 arm vs. 7.9% day -7 arm; p = 0.65). The median edema factor at 1 month was 1.02 (range, 0.73-1.7). 1.01 day 0 arm vs. 1.05 day -7 arm. Baseline prostate volume remained the primary predictor of postimplant urinary retention. Conclusions: Starting meloxicam 1 week prior to brachytherapy compared to starting immediately after the procedure did not reduce 1-month edema, improve IPSSs at 1 or 3 months, or reduce the need for catheterization.

  14. Order and randomness in Kolmogorov-Johnson-Mehl-Avrami-type phase transitions

    NASA Astrophysics Data System (ADS)

    Fanfoni, M.; Persichetti, L.; Tomellini, M.

    2012-09-01

    The distribution of points on a 2D domain influences the kinetics of its coverage when a growth law is attached at each point. This implies that the kinetics of space filling can be adopted as a descriptor of the degree of order of the initial point distribution. In this paper, the degree of order of an initial array of points has been changed following two paths: (i) from a regular square lattice, through increasing displacement assigned to each point, towards Poissonian disorder; (ii) from a Poissonian distribution, by introducing a hard core potential with increasing correlation lengths, towards a more ordered lattice. A linear growth law has been attached to the points of the initial array and the kinetics X(Xe), where Xe is the extended coverage as defined in the Kolmogorov-Johnson-Mehl-Avrami model, has been monitored. The quantitative analysis has been performed by fitting the kinetics to an equation which we propose for the first time and which has proved to be, in fact, highly suitable for the purpose. The results demonstrate that the gross of variation from order to disorder is obtained for point displacements, u, of the order of a, the latter being the constant of a square lattice. Vice versa, the introduction of a correlation distance in a random distribution provokes at most an order limited to the first neighbors and no real order can ever be reached. Others descriptors have been investigated, all confirming our results. We also developed an analytical description based on the use of the f-functions, as have been defined by Van Kampen, up to the second order terms. Such a description has been shown to work well for u/a < 1 within an interval ΔXe which depends on the ɛ value.

  15. Information verification cryptosystem using one-time keys based on double random phase encoding and public-key cryptography

    NASA Astrophysics Data System (ADS)

    Zhao, Tieyu; Ran, Qiwen; Yuan, Lin; Chi, Yingying; Ma, Jing

    2016-08-01

    A novel image encryption system based on double random phase encoding (DRPE) and RSA public-key algorithm is proposed. The main characteristic of the system is that each encryption process produces a new decryption key (even for the same plaintext), thus the encryption system conforms to the feature of the one-time pad (OTP) cryptography. The other characteristic of the system is the use of fingerprint key. Only with the rightful authorization will the true decryption be obtained, otherwise the decryption will result in noisy images. So the proposed system can be used to determine whether the ciphertext is falsified by attackers. In addition, the system conforms to the basic agreement of asymmetric cryptosystem (ACS) due to the combination with the RSA public-key algorithm. The simulation results show that the encryption scheme has high robustness against the existing attacks.

  16. Multilevel Monte Carlo for two phase flow and Buckley–Leverett transport in random heterogeneous porous media

    SciTech Connect

    Müller, Florian Jenny, Patrick Meyer, Daniel W.

    2013-10-01

    Monte Carlo (MC) is a well known method for quantifying uncertainty arising for example in subsurface flow problems. Although robust and easy to implement, MC suffers from slow convergence. Extending MC by means of multigrid techniques yields the multilevel Monte Carlo (MLMC) method. MLMC has proven to greatly accelerate MC for several applications including stochastic ordinary differential equations in finance, elliptic stochastic partial differential equations and also hyperbolic problems. In this study, MLMC is combined with a streamline-based solver to assess uncertain two phase flow and Buckley–Leverett transport in random heterogeneous porous media. The performance of MLMC is compared to MC for a two dimensional reservoir with a multi-point Gaussian logarithmic permeability field. The influence of the variance and the correlation length of the logarithmic permeability on the MLMC performance is studied.

  17. Efficient asymmetric image authentication schemes based on photon counting-double random phase encoding and RSA algorithms.

    PubMed

    Moon, Inkyu; Yi, Faliu; Han, Mingu; Lee, Jieun

    2016-06-01

    Recently, double random phase encoding (DRPE) has been integrated with the photon counting (PC) imaging technique for the purpose of secure image authentication. In this scheme, the same key should be securely distributed and shared between the sender and receiver, but this is one of the most vexing problems of symmetric cryptosystems. In this study, we propose an efficient asymmetric image authentication scheme by combining the PC-DRPE and RSA algorithms, which solves key management and distribution problems. The retrieved image from the proposed authentication method contains photon-limited encrypted data obtained by means of PC-DRPE. Therefore, the original image can be protected while the retrieved image can be efficiently verified using a statistical nonlinear correlation approach. Experimental results demonstrate the feasibility of our proposed asymmetric image authentication method.

  18. Continuum quasiparticle random-phase approximation for astrophysical direct neutron capture reactions on neutron-rich nuclei

    NASA Astrophysics Data System (ADS)

    Matsuo, Masayuki

    2015-03-01

    I formulate a many-body theory to calculate the cross section of direct radiative neutron capture reaction by means of the Hartree-Fock-Bogoliubov mean-field model and the continuum quasiparticle random-phase approximation (QRPA). A focus is put on very-neutron-rich nuclei and low-energy neutron kinetic energy in the range from 1 keV to several MeV, which is relevant to the rapid neutron capture process of nucleosynthesis. I begin with the photoabsorption cross section and the E 1 strength function. Next, in order to apply the reciprocity theorem, I decompose the cross section into partial cross sections corresponding to different channels of one- and two-neutron emission decays of photo-excited states. A numerical example is shown for the photo-absorption of 142Sn and the neutron capture of 141Sn .

  19. Double, Rydberg and charge transfer excitations from pairing matrix fluctuation and particle-particle random phase approximation

    SciTech Connect

    Yang, Yang; Aggelen, Helen van; Yang, Weitao

    2013-12-14

    Double, Rydberg, and charge transfer (CT) excitations have been great challenges for time-dependent density functional theory (TDDFT). Starting from an (N ± 2)-electron single-determinant reference, we investigate excitations for the N-electron system through the pairing matrix fluctuation, which contains information on two-electron addition/removal processes. We adopt the particle-particle random phase approximation (pp-RPA) and the particle-particle Tamm-Dancoff approximation (pp-TDA) to approximate the pairing matrix fluctuation and then determine excitation energies by the differences of two-electron addition/removal energies. This approach captures all types of interesting excitations: single and double excitations are described accurately, Rydberg excitations are in good agreement with experimental data and CT excitations display correct 1/R dependence. Furthermore, the pp-RPA and the pp-TDA have a computational cost similar to TDDFT and consequently are promising for practical calculations.

  20. Double, Rydberg and charge transfer excitations from pairing matrix fluctuation and particle-particle random phase approximation

    NASA Astrophysics Data System (ADS)

    Yang, Yang; van Aggelen, Helen; Yang, Weitao

    2013-12-01

    Double, Rydberg, and charge transfer (CT) excitations have been great challenges for time-dependent density functional theory (TDDFT). Starting from an (N ± 2)-electron single-determinant reference, we investigate excitations for the N-electron system through the pairing matrix fluctuation, which contains information on two-electron addition/removal processes. We adopt the particle-particle random phase approximation (pp-RPA) and the particle-particle Tamm-Dancoff approximation (pp-TDA) to approximate the pairing matrix fluctuation and then determine excitation energies by the differences of two-electron addition/removal energies. This approach captures all types of interesting excitations: single and double excitations are described accurately, Rydberg excitations are in good agreement with experimental data and CT excitations display correct 1/R dependence. Furthermore, the pp-RPA and the pp-TDA have a computational cost similar to TDDFT and consequently are promising for practical calculations.

  1. Double, Rydberg and Charge Transfer Excitations from Pairing Matrix Fluctuation and Particle-Particle Random Phase Approximation

    NASA Astrophysics Data System (ADS)

    Yang, Yang; van Aggelen, Helen; Yang, Weitao

    2014-03-01

    Double, Rydberg and charge transfer (CT) excitations have been great challenges for time-dependent density functional theory (TDDFT). Starting from an (N +/- 2) -electron single-determinant reference, we investigate excitations for the N-electron system through the pairing matrix fluctuation, which contains information on two-electron addition/removal processes. We adopt the particle-particle random phase approximation (pp-RPA) and the particle-particle Tamm-Dancoff approximation (pp-TDA) to approximate the pairing matrix fluctuation and then determine excitation energies by the differences of two-electron addition/removal energies. This approach captures all types of interesting excitations: single and double excitations are described accurately, Rydberg excitations are in good agreement with experimental data and CT excitations display correct 1/R dependence. Furthermore, the pp-RPA and the pp-TDA have a computational cost similar to TDDFT and consequently are promising for practical calculations.

  2. Low-lying dipole modes in 26,28Ne in the quasiparticle relativistic random phase approximation

    NASA Astrophysics Data System (ADS)

    Cao, Li-Gang; Ma, Zhong-Yu

    2005-03-01

    The low-lying isovector dipole strengths in the neutron-rich nuclei 26Ne and 28Ne are investigated in the quasiparticle relativistic random phase approximation. Nuclear ground-state properties are calculated in an extended relativistic mean field theory plus Bardeen-Cooper-Schrieffer (BCS) method where the contribution of the resonant continuum to pairing correlations is properly treated. Numerical calculations are tested in the case of isovector dipole and isoscalar quadrupole modes in the neutron-rich nucleus 22O. It is found that in the present calculation, low-lying isovector dipole strengths at Ex<10MeV in nuclei 26Ne and 26Ne exhaust about 4.9% and 5.8% of the Thomas-Reiche-Kuhn dipole sum rule, respectively. The centroid energy of the low-lying dipole excitation is located at 8.3 MeV in 26Ne and 7.9 MeV in 28Ne.

  3. Density functional formulation of the random-phase approximation for inhomogeneous fluids: Application to the Gaussian core and Coulomb particles

    NASA Astrophysics Data System (ADS)

    Frydel, Derek; Ma, Manman

    2016-06-01

    Using the adiabatic connection, we formulate the free energy in terms of the correlation function of a fictitious system, hλ(r ,r') , in which interactions λ u (r ,r') are gradually switched on as λ changes from 0 to 1. The function hλ(r ,r') is then obtained from the inhomogeneous Ornstein-Zernike equation and the two equations constitute a general liquid-state framework for treating inhomogeneous fluids. The two equations do not yet constitute a closed set. In the present work we use the closure cλ(r ,r') ≈-λ β u (r ,r') , known as the random-phase approximation (RPA). We demonstrate that the RPA is identical with the variational Gaussian approximation derived within the field-theoretical framework, originally derived and used for charged particles. We apply our generalized RPA approximation to the Gaussian core model and Coulomb charges.

  4. Double, Rydberg and charge transfer excitations from pairing matrix fluctuation and particle-particle random phase approximation.

    PubMed

    Yang, Yang; van Aggelen, Helen; Yang, Weitao

    2013-12-14

    Double, Rydberg, and charge transfer (CT) excitations have been great challenges for time-dependent density functional theory (TDDFT). Starting from an (N ± 2)-electron single-determinant reference, we investigate excitations for the N-electron system through the pairing matrix fluctuation, which contains information on two-electron addition/removal processes. We adopt the particle-particle random phase approximation (pp-RPA) and the particle-particle Tamm-Dancoff approximation (pp-TDA) to approximate the pairing matrix fluctuation and then determine excitation energies by the differences of two-electron addition/removal energies. This approach captures all types of interesting excitations: single and double excitations are described accurately, Rydberg excitations are in good agreement with experimental data and CT excitations display correct 1/R dependence. Furthermore, the pp-RPA and the pp-TDA have a computational cost similar to TDDFT and consequently are promising for practical calculations.

  5. Multiple-image encryption by space multiplexing based on compressive sensing and the double-random phase-encoding technique.

    PubMed

    Deepan, B; Quan, C; Wang, Y; Tay, C J

    2014-07-10

    In this paper, a new multiple-image encryption and decryption technique that utilizes the compressive sensing (CS) concept along with a double-random phase encryption (DRPE) has been proposed. The space multiplexing method is employed for integrating multiple-image data. The method, which results in a nonlinear encryption system, is able to overcome the vulnerability of classical DRPE. The CS technique and space multiplexing are able to provide additional key space in the proposed method. A numerical experiment of the proposed method is implemented and the results show that the proposed method has good accuracy and is more robust than classical DRPE. The proposed system is also employed against chosen-plaintext attacks and it is found that the inclusion of compressive sensing enhances robustness against the attacks.

  6. Pygmy dipole response of proton-rich argon nuclei in random-phase approximation and no-core shell model

    SciTech Connect

    Barbieri, C.; Martinez-Pinedo, G.; Caurier, E.; Langanke, K.

    2008-02-15

    The occurrence of a pygmy dipole resonance in proton rich {sup 32,34}Ar is studied using the unitary correlator operator method interaction V{sub UCOM}, based on Argonne V18. Predictions from the random-phase approximation (RPA) and the shell model in a no-core basis are compared. It is found that the inclusion of configuration mixing up to two-particles-two-holes broadens the pygmy strength slightly and reduces sensibly its strength, as compared to the RPA predictions. For {sup 32}Ar, a clear peak associated with a pygmy resonance is found. For {sup 34}Ar, the pygmy states are obtained close to the giant dipole resonance and mix with it.

  7. Phase I Randomized Safety Study of Twice Daily Dosing of Acidform Vaginal Gel: Candidate Antimicrobial Contraceptive

    PubMed Central

    Keller, Marla J.; Carpenter, Colleen A.; Lo, Yungtai; Einstein, Mark H.; Liu, Congzhou; Fredricks, David N.; Herold, Betsy C.

    2012-01-01

    Background Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. Methods Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL) at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. Results The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002). While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08). Conclusions Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than placebo and lower levels

  8. Application of a Dual-Hybrid Direct Random Phase Approximation to Water Clusters.

    PubMed

    Mezei, Pál D; Ruzsinszky, Adrienn; Csonka, Gábor I

    2016-09-13

    In water clusters, there is a delicate balance of van der Waals interactions and hydrogen bonds. Although semilocal and nonlocal density functional approximations have been recently routinely applied to water in various phases, the accurate description of hydrogen bonds remains a challenge. The most popular density functional approaches fail to predict the correct ordering of the energies of water clusters. To illustrate the required accuracy, the CCSD(T) complete basis set extrapolated dissociation energy difference between the two lowest energy hexamer structures is 0.06 kcal mol(-1) per monomer. In this work, we assessed interaction energies in neutral and ionic water clusters with various density functionals with or without van der Waals correction. Generally, van der Waals approximations play a significant role in clusters with increasing size, while hybrid functionals improve the description of hydrogen bonds. Despite these general trends, none of the tested density functional approximations with or without van der Waals correction and exact exchange mixing can lead to a uniform performance for neutral and ionic water clusters. The recently constructed dual-hybrid dRPA75 approximation is a successful combination of exact and semilocal exchange, and nonlocal correlation in its energy, while utilizing a high fraction of exact exchange. We have shown that the dRPA75 method has a systematic error, which can be efficiently compensated for by the aug-cc-pVTZ basis set for small- and medium-sized water clusters.

  9. A randomized Phase 2 trial of telavancin versus standard therapy in patients with uncomplicated Staphylococcus aureus bacteremia: the ASSURE study

    PubMed Central

    2014-01-01

    Background Staphylococcus aureus bacteremia is a common infection associated with significant morbidity and mortality. Telavancin is a bactericidal lipoglycopeptide active against Gram-positive pathogens, including methicillin-resistant S. aureus (MRSA). We conducted a randomized, double-blind, Phase 2 trial in patients with uncomplicated S. aureus bacteremia. Methods Patients were randomized to either telavancin or standard therapy (vancomycin or anti-staphylococcal penicillin) for 14 days. Continuation criteria were set to avoid complicated S. aureus bacteremia. The primary end point was clinical cure at 84 days. Results In total, 60 patients were randomized and 58 received ≥1 study medication dose (all-treated), 31 patients fulfilled inclusion/exclusion and continuation criteria (all-treated target [ATT]) (telavancin 15, standard therapy 16), and 17 patients were clinically evaluable (CE) (telavancin 8, standard therapy 9). Mean age (ATT) was 60 years. Intravenous catheters were the most common source of S. aureus bacteremia and ~50% of patients had MRSA. A similar proportion of CE patients were cured in the telavancin (88%) and standard therapy (89%) groups. All patients with MRSA bacteremia were cured and one patient with MSSA bacteremia failed study treatment in each group. Although adverse events (AEs) were more common in the telavancin ATT group (90% vs. 72%), AEs leading to drug discontinuation were similar (7%) in both treatment arms. Potentially clinically significant increases in serum creatinine (≥1.5 mg/dl and at least 50% greater than baseline) were more common in the telavancin group (20% vs. 7%). Conclusions This study suggests that telavancin may have utility for treatment of uncomplicated S. aureus bacteremia; additional studies are warranted. (Telavancin for Treatment of Uncomplicated Staphylococcus Aureus Bacteremia (ASSURE); NCT00062647). PMID:24884578

  10. Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase II trial

    PubMed Central

    Ikeda, M.; Shimizu, S.; Sato, T.; Morimoto, M.; Kojima, Y.; Inaba, Y.; Hagihara, A.; Kudo, M.; Nakamori, S.; Kaneko, S.; Sugimoto, R.; Tahara, T.; Ohmura, T.; Yasui, K.; Sato, K.; Ishii, H.; Furuse, J.; Okusaka, T.

    2016-01-01

    Background Sorafenib (Sor) is acknowledged as a standard therapy for advanced hepatocellular carcinoma (HCC). This trial was conducted to evaluate the effect of addition of hepatic arterial infusion chemotherapy with cisplatin (SorCDDP) to Sor for the treatment of advanced HCC. Patients and methods We conducted a multicenter open-labeled randomized phase II trial in chemo-naïve patients with advanced HCC with Child-Pugh scores of 5–7. Eligible patients were randomly assigned 2:1 to receive SorCDDP (sorafenib: 400 mg bid; cisplatin: 65 mg/m2, day 1, every 4–6 weeks) or Sor (400 mg bid). The primary end point was overall survival. Results A total of 108 patients were randomized (Sor, n = 42; SorCDDP, n = 66). The median survival in the Sor and SorCDDP arms were 8.7 and 10.6 months, respectively [stratified hazard ratio (95% confidence interval), 0.60 (0.38–0.96), P = 0.031]. The median time to progression and the response rate were, respectively, 2.8 months and 7.3% in the Sor arm and 3.1 months and 21.7% in the SorCDDP arm. The adverse events were more frequent in the SorCDDP arm than in the Sor arm, but well-tolerated. Conclusion SorCDDP yielded favorable overall survival when compared with Sor in patients with advanced HCC. Clinical Trial registration UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703. PMID:27573564

  11. Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer

    PubMed Central

    Liu, Mei-Ching; Lee, Soo Chin; Vanlemmens, Laurence; Ferrero, Jean-Marc; Tabei, Toshio; Pivot, Xavier; Iwata, Hiroji; Aogi, Kenjiro; Lugo-Quintana, Roberto; Harbeck, Nadia; Brickman, Marla J.; Zhang, Ke; Kern, Kenneth A.; Martin, Miguel

    2010-01-01

    This multicenter, randomized, open-label phase III trial (planned enrollment: 700 patients) was conducted to test the hypothesis that single-agent sunitinib improves progression-free survival (PFS) compared with capecitabine as treatment for advanced breast cancer (ABC). Patients with HER2-negative ABC that recurred after anthracycline and taxane therapy were randomized (1:1) to sunitinib 37.5 mg/day or capecitabine 1,250 mg/m2 (1,000 mg/m2 in patients >65 years) BID on days 1–14 q3w. The independent data-monitoring committee (DMC) determined during the first interim analysis (238 patients randomized to sunitinib, 244 to capecitabine) that the trial be terminated due to futility in reaching the primary endpoint. No statistical evidence supported the hypothesis that sunitinib improved PFS compared with capecitabine (one-sided P = 0.999). The data indicated that PFS was shorter with sunitinib than capecitabine (median 2.8 vs. 4.2 months, respectively; HR, 1.47; 95% CI, 1.16–1.87; two-sided P = 0.002). Median overall survival (15.3 vs. 24.6 months; HR, 1.17; two-sided P = 0.350) and objective response rates (11 vs. 16%; odds ratio, 0.65; P = 0.109) were numerically inferior with sunitinib versus capecitabine. While no new or unexpected safety findings were reported, sunitinib treatment was associated with higher frequencies and greater severities of many common adverse events (AEs) compared with capecitabine, resulting in more temporary discontinuations due to AEs with sunitinib (66 vs. 51%). The relative dose intensity was lower with sunitinib than capecitabine (73 vs. 95%). Based on these efficacy and safety results, sunitinib should not be used as monotherapy for patients with ABC. PMID:20339913

  12. Phase II Prospective Randomized Trial of a Low-Fat Diet with Fish Oil Supplementation in Men Undergoing Radical Prostatectomy

    PubMed Central

    Aronson, William J.; Kobayashi, Naoko; Barnard, R. James; Henning, Susanne; Jardack, Patricia M.; Liu, Bingrong; Gray, Ashley; Wan, Junxiang; Konijeti, Ramdev; Freedland, Stephen J.; Castor, Brandon; Heber, David; Elashoff, David; Said, Jonathan; Cohen, Pinchas; Galet, Colette

    2011-01-01

    Preclinical studies suggest lowering dietary fat and decreasing the ratio of omega-6 to omega-3 polyunsaturated fatty acids decreases the risk of prostate cancer development and progression. We conducted a phase II randomized trial to test the effect of decreasing dietary fat combined with decreasing the dietary omega-6:omega-3 ratio on biomarkers related to prostate cancer development and progression. Patients undergoing radical prostatectomy were randomly assigned to receive a low-fat diet with 5 grams of fish oil daily (dietary omega-6:omega-3 ratio of 2:1) or a control western diet (omega-6:omega-3 ratio of 15:1) for 4–6 weeks prior to surgery. The primary endpoint was change in serum IGF-1 between arms. Secondary endpoints were serum IGFBP-1, prostate prostaglandin E-2 levels, omega-6:omega-3 fatty acid ratios, COX-2 and markers of proliferation and apoptosis. Fifty-five patients were randomized and 48 completed the trial. There was no treatment difference in the primary outcome. Positive secondary outcomes in the low-fat fish oil vs. western group were reduced benign and malignant prostate tissue omega-6:omega-3 ratios, reduced proliferation (Ki67 index), and reduced proliferation in an ex-vivo bioassay when patient sera was applied to prostate cancer cells in vitro. In summary, 4–6 weeks of a low-fat diet and fish oil capsules to achieve an omega-6:omega-3 fatty acid ratio of 2:1 had no effect on serum IGF-1 levels, though in secondary analyses the intervention resulted in decreased prostate cancer proliferation and decreased prostate tissue omega-6:omega-3 ratios. These results support further studies evaluating reduction of dietary fat with fish oil supplementation on modulating prostate cancer biology. PMID:22027686

  13. Recombinant human interleukin-1 receptor antagonist in severe traumatic brain injury: a phase II randomized control trial

    PubMed Central

    Helmy, Adel; Guilfoyle, Mathew R; Carpenter, Keri LH; Pickard, John D; Menon, David K; Hutchinson, Peter J

    2014-01-01

    Traumatic brain injury (TBI) is the commonest cause of death and disability in those aged under 40 years. Interleukin-1 receptor antagonist (IL1ra) is an endogenous competitive antagonist at the interleukin-1 type-1 receptor (IL-1R). Antagonism at the IL-1R confers neuroprotection in several rodent models of neuronal injury (i.e., trauma, stroke and excitotoxicity). We describe a single center, phase II, open label, randomized-control study of recombinant human IL1ra (rhIL1ra, anakinra) in severe TBI, at a dose of 100 mg subcutaneously once a day for 5 days in 20 patients randomized 1:1. We provide safety data (primary outcome) in this pathology, utilize cerebral microdialysis to directly determine brain extracellular concentrations of IL1ra and 41 cytokines and chemokines, and use principal component analysis (PCA) to explore the resultant cerebral cytokine profile. Interleukin-1 receptor antagonist was safe, penetrated into plasma and the brain extracellular fluid. The PCA showed a separation in cytokine profiles after IL1ra administration. A candidate cytokine from this analysis, macrophage-derived chemoattractant, was significantly lower in the rhIL1ra-treated group. Our results provide promising data for rhIL1ra as a therapeutic candidate by showing safety, brain penetration and a modification of the neuroinflammatory response to TBI by a putative neuroprotective agent in humans for the first time. PMID:24569690

  14. Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib

    PubMed Central

    Rimassa, Lorenza; Abbadessa, Giovanni; Personeni, Nicola; Porta, Camillo; Borbath, Ivan; Daniele, Bruno; Salvagni, Stefania; Van Laethem, Jean-Luc; Van Vlierberghe, Hans; Trojan, Jörg; De Toni, Enrico N.; Weiss, Alan; Miles, Steven; Gasbarrini, Antonio; Lencioni, Monica; Lamar, Maria E.; Wang, Yunxia; Shuster, Dale; Schwartz, Brian E.; Santoro, Armando

    2016-01-01

    ARQ 197-215 was a randomized placebo-controlled phase II study testing the MET inhibitor tivantinib in second-line hepatocellular carcinoma (HCC) patients. It identified tumor MET as a key biomarker in HCC. Aim of this research was to study the prognostic and predictive value of tumor (MET, the receptor tyrosine kinase encoded by the homonymous MNNG-HOS transforming gene) and circulating (MET, hepatocyte growth factor [HGF], alpha-fetoprotein [AFP], vascular endothelial growth factor [VEGF]) biomarkers in second-line HCC. Tumor MET-High status was centrally assessed by immunohistochemistry. Circulating biomarkers were centrally analyzed on serum samples collected at baseline and every 4-8 weeks, using medians as cut-off to determine High/Low status. Tumor MET, tested in 77 patients, was more frequently High after (82%) versus before (40%) sorafenib. A significant interaction (p = 0.04) between tivantinib and baseline tumor MET in terms of survival was observed. Baseline circulating MET and HGF (102 patients) High status correlated with shorter survival (HR 0.61, p = 0.03, and HR 0.60, p = 0.02, respectively), while the association between AFP (104 patients) or VEGF (103 patients) status and survival was non-significant. Conclusions: Tumor MET levels were higher in patients treated with sorafenib. Circulating biomarkers such as MET and HGF may be prognostic in second-line HCC. These results need to be confirmed in larger randomized clinical trials. PMID:27579536

  15. Recombinant human interleukin-1 receptor antagonist in severe traumatic brain injury: a phase II randomized control trial.

    PubMed

    Helmy, Adel; Guilfoyle, Mathew R; Carpenter, Keri L H; Pickard, John D; Menon, David K; Hutchinson, Peter J

    2014-05-01

    Traumatic brain injury (TBI) is the commonest cause of death and disability in those aged under 40 years. Interleukin-1 receptor antagonist (IL1ra) is an endogenous competitive antagonist at the interleukin-1 type-1 receptor (IL-1R). Antagonism at the IL-1R confers neuroprotection in several rodent models of neuronal injury (i.e., trauma, stroke and excitotoxicity). We describe a single center, phase II, open label, randomized-control study of recombinant human IL1ra (rhIL1ra, anakinra) in severe TBI, at a dose of 100 mg subcutaneously once a day for 5 days in 20 patients randomized 1:1. We provide safety data (primary outcome) in this pathology, utilize cerebral microdialysis to directly determine brain extracellular concentrations of IL1ra and 41 cytokines and chemokines, and use principal component analysis (PCA) to explore the resultant cerebral cytokine profile. Interleukin-1 receptor antagonist was safe, penetrated into plasma and the brain extracellular fluid. The PCA showed a separation in cytokine profiles after IL1ra administration. A candidate cytokine from this analysis, macrophage-derived chemoattractant, was significantly lower in the rhIL1ra-treated group. Our results provide promising data for rhIL1ra as a therapeutic candidate by showing safety, brain penetration and a modification of the neuroinflammatory response to TBI by a putative neuroprotective agent in humans for the first time.

  16. Frozen phases with re-entrant transition for random heteropolymers with composition specific and annealed cross-links

    NASA Astrophysics Data System (ADS)

    Gutman, Lorin; Shakhnovich, Eugene

    1997-07-01

    A field theoretic formalism of random heteropolymers (RHPs) with composition specific cross-links that are annealed, is developed in this work. This system can serve as a simple meaningful model of proteins with disulfide bonds. The agent that cross-links the macromolecules, as in real proteins, is assumed to maintain an equilibrium cross-linking density within the heteropolymer globule; this situation is reminiscent to in vivo reagent induced cross-linking, and protrudes the experimental desired control on formation and dissolution of cross-links. The starting point of our analysis, i.e. the random heteropolymer Hamiltonian, captures both the chain connectivity and the essentially quenched nature of amino-acids distribution reminiscent of linear uncross-linked polypeptides. The conformational statistics of the RHP is determined within the replica approach. For experimentally realizable values of the RHP interaction parameters, we predict the appearance of two frozen phases of RHPs wherein a small number of chain conformations of order O(1) are being sampled. At the interim between the two phases our calculation predicts the appearance of a re-entrant transition wherein the number of chain conformations sampled is of order O(N). The occurrence of the re-entrant transition is due to a tight competition between the intersegment interactions (measured by χF), and the propensity of composition specific and annealed cross-links to form (determined by the chemical potential of the cross-linking agent). We suggest how to traverse the re-entrant transition line, by chemically manipulating the competition of dissimilar interactions of the disparate segments, and the specific propensity of the peptides to cross-link, and also, we provide an explanation for the observation that in nature cross-linking between alike rather than dissimilar segments is observed.

  17. Phase II double-blind placebo-controlled randomized study of armodafinil for brain radiation-induced fatigue

    PubMed Central

    Page, Brandi R.; Shaw, Edward G.; Lu, Lingyi; Bryant, David; Grisell, David; Lesser, Glenn J.; Monitto, Drew C.; Naughton, Michelle J.; Rapp, Stephen R.; Savona, Steven R.; Shah, Sunjay; Case, Doug; Chan, Michael D.

    2015-01-01

    Background Common acute-term side effects of brain radiotherapy (RT) include fatigue, drowsiness, decreased physical functioning, and decreased quality of life (QOL). We hypothesized that armodafinil (a wakefulness-promoting drug known to reduce fatigue and increase cognitive function in breast cancer patients receiving chemotherapy) would result in reduced fatigue and sleepiness for patients receiving brain RT. Methods A phase II, multi-institutional, placebo-controlled randomized trial assessed feasibility of armodafinil 150 mg/day in participants receiving brain RT, from whom we obtained estimates of variability for fatigue, sleepiness, QOL, cognitive function, and treatment effect. Results From September 20, 2010, to October 20, 2012, 54 participants enrolled with 80% retention and 94% self-reported compliance. There were no grade 4–5 toxicities, and the incidence of grade 2–3 toxicities was similar between treatment arms, the most common of which were anxiety and nausea (15%), headaches (19%), and insomnia (20%). There were no statistically significant differences in end-RT or 4 week post-RT outcomes between armodafinil and placebo in any outcomes (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, Brief Fatigue Inventory, Epworth Sleepiness Scale, FACT-Brain, and FACIT-cognitive function). However, in participants with more baseline fatigue, those treated with armodafinil did better than those who received the placebo on the end-RT assessments for several outcomes. Conclusion Armodafinil 150 mg/day was well tolerated in primary brain tumor patients undergoing RT with good compliance. While there was no overall significant effect on fatigue, those with greater baseline fatigue experienced improved QOL and reduced fatigue when using armodafinil. These data suggest that a prospective, phase III randomized trial is warranted for patients with greater baseline fatigue. PMID:25972454

  18. Conservative treatment of retinoblastoma: a prospective phase II randomized trial of neoadjuvant chemotherapy followed by local treatments and chemothermotherapy

    PubMed Central

    Lumbroso-Le Rouic, L; Aerts, I; Hajage, D; Lévy-Gabriel, C; Savignoni, A; Algret, N; Cassoux, N; Bertozzi, A-I; Esteve, M; Doz, F; Desjardins, L

    2016-01-01

    Purpose Intraocular retinoblastoma treatments often combine chemotherapy and focal treatments. A first prospective protocol of conservative treatments in our institution showed the efficacy of the use of two courses of chemoreduction with etoposide and carboplatin, followed by chemothermotherapy using carboplatin as a single agent and diode laser. In order to decrease the possible long-term toxicity of chemotherapy due to etoposide, a randomized neoadjuvant phase II protocol was conducted using vincristine–carboplatin vs etoposide–carboplatin. Patients and methods The study was proposed when initial tumor characteristics did not allow front-line local treatments. Patients included in this phase II noncomparative randomized study of neoadjuvant chemotherapy received vincristin–carboplatin (new arm) vs etoposide–carboplatin (our reference arm). They were subsequently treated by local treatments and chemothermotherapy. Primary end point was the need for secondary enucleation or external beam radiotherapy (EBRT) not exceeding 40% at 2 years. Results A total of 65 eyes in 55 children were included in the study (May 2004 to August 2009). Of these, 32 eyes (27 children) were treated in the arm etoposide–carboplatin and 33 eyes (28 children) in the arm vincristin–carboplatin. At 2 years after treatment, 23/33 (69.7%) eyes were treated and salvaged without EBRT or enucleation in the arm vincristin–carboplatin and 26/32 (81.2%) in the arm etoposide–carboplatin. Conclusion Even if the two treatment arms could be considered as sufficiently active according to the study decision rules, neoadjuvant chemotherapy by two cycles of vincristine–carboplatin followed by chemothermotherapy appear to offer less optimal local control than the etoposide–carboplatin combination. PMID:26427984

  19. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer

    PubMed Central

    Paller, CJ; Ye, X; Wozniak, PJ; Gillespie, BK; Sieber, PR; Greengold, RH; Stockton, BR; Hertzman, BL; Efros, MD; Roper, RP; Liker, HR; Carducci, MA

    2012-01-01

    BACKGROUND Pomegranate juice has been associated with PSA doubling time (PSADT) elongation in a single-arm phase II trial. This study assesses biological activity of two doses of pomegranate extract (POMx) in men with recurrent prostate cancer, using changes in PSADT as the primary outcome. METHODS This randomized, multi-center, double-blind phase II, dose-exploring trial randomized men with a rising PSA and without metastases to receive 1 or 3 g of POMx, stratified by baseline PSADT and Gleason score. Patients (104) were enrolled and treated for up to 18 months. The intent-to-treat (ITT) population was 96% white, with median age 74.5 years and median Gleason score 7. This study was designed to detect a 6-month on-study increase in PSADT from baseline in each arm. RESULTS: Overall, median PSADT in the ITT population lengthened from 11.9 months at baseline to 18.5 months after treatment (P<0.001). PSADT lengthened in the low-dose group from 11.9 to 18.8 months and 12.2 to 17.5 months in the high-dose group, with no significant difference between dose groups (P =0.554). PSADT increases >100% of baseline were observed in 43% of patients. Declining PSA levels were observed in 13 patients (13%). In all, 42% of patients discontinued treatment before meeting the protocol-definition of PSA progression, or 18 months, primarily due to a rising PSA. No significant changes occurred in testosterone. Although no clinically significant toxicities were seen, diarrhea was seen in 1.9% and 13.5% of patients in the 1- and 3-g dose groups, respectively. CONCLUSIONS POMx treatment was associated with ≥6 month increases in PSADT in both treatment arms without adverse effects. The significance of this on-study slowing of PSADT remains unclear, reinforcing the need for placebo-controlled studies in this patient population. PMID:22689129

  20. Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study

    PubMed Central

    2009-01-01

    Background This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR) inhibitor cetuximab combined with irinotecan, folinic acid (FA) and two different doses of infusional 5-fluorouracil (5-FU) in the first-line treatment of EGFR-detectable metastatic colorectal cancer. Methods The 5-FU dose was selected on the basis of dose-limiting toxicities (DLTs) during part I of the study. Patients received cetuximab (400 mg/m2 initial dose and 250 mg/m2/week thereafter) and every 2 weeks irinotecan (180 mg/m2), FA (400 mg/m2) and 5-FU (either low dose [LD], 300 mg/m2 bolus plus 2,000 mg/m2 46-hour infusion, n = 7; or, high-dose [HD], 400 mg/m2 bolus plus 2,400 mg/m2; n = 45). Results Only two DLTs occurred in the HD group, and HD 5-FU was selected for use in part II. Apart from rash, commonly observed grade 3/4 adverse events such as leucopenia, diarrhoea, vomiting and asthenia occurred within the expected range for FOLFIRI. Among 52 patients, the overall response rate was 48%. Median progression-free survival (PFS) was 8.6 months (counting all reported progressions) and the median overall survival was 22.4 months. Treatment facilitated the resection of initially unresectable metastases in fourteen patients (27%): of these, 10 patients (71%) had no residual tumour after surgery, and these resections hindered the estimation of PFS. Conclusion The combination of cetuximab and FOLFIRI was active and well tolerated in this setting. Initially unresectable metastases became resectable in one-quarter of patients, with a high number of complete resections, and these promising results formed the basis for the investigation of FOLFIRI with and without cetuximab in the phase III CRYSTAL trial. PMID:19366444

  1. Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial

    PubMed Central

    Hoy, Anna M.; Semple, Scott I.; Mungall, Will; Lennen, Ross J.; Moran, Carmel M.; Pellicoro, Antonella; Aucott, Rebecca L.; Severin, Thomas; Saini, Rajnish; Yates, Denise; Dongre, Neelesh; Duffield, Jeremy S.; Webb, David J.; Iredale, John P.; Hayes, Peter C.

    2017-01-01

    Background Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2) is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1) and has been shown to increase renal perfusion in healthy human volunteers. We hypothesized that serelaxin could ameliorate renal vasoconstriction and renal dysfunction in patients with cirrhosis and portal hypertension. Methods and findings To establish preclinical proof of concept, we developed two independent rat models of cirrhosis that were characterized by progressive reduction in renal blood flow and glomerular filtration rate and showed evidence of renal endothelial dysfunction. We then set out to further explore and validate our hypothesis in a phase 2 randomized open-label parallel-group study in male and female patients with alcohol-related cirrhosis and portal hypertension. Forty patients were randomized 1:1 to treatment with serelaxin intravenous (i.v.) infusion (for 60 min at 80 μg/kg/d and then 60 min at 30 μg/kg/d) or terlipressin (single 2-mg i.v. bolus), and the regional hemodynamic effects were quantified by phase contrast magnetic resonance angiography at baseline and after 120 min. The primary endpoint was the change from baseline in total renal artery blood flow. Therapeutic targeting of renal vasoconstriction with serelaxin in the rat models increased kidney perfusion, oxygenation, and function through reduction in renal vascular resistance, reversal of endothelial dysfunction, and increased activation of the

  2. GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study

    PubMed Central

    2014-01-01

    Background In Europe, gastric cancer remains diagnosed at advanced stage (serosal and/or lymph node involvement). Despite curative management combining perioperative systemic chemotherapy and gastrectomy with D1-D2 lymph node dissection, 5-year survival rates of T3 and/or N + patients remain under 30%. More than 50% of recurrences are peritoneal and/or locoregional. The use of adjuvant hyperthermic intraperitoneal chemotherapy that eliminates free cancer cells that can be released into peritoneal cavity during the gastrectomy and prevents peritoneal carcinomatosis recurrences, was extensively evaluated by several randomized trials conducted in Asia. Two meta-analysis reported that adjuvant hyperthermic intraperitoneal chemotherapy significantly reduces the peritoneal recurrences and significantly improves the overall survival. As it was previously done for the evaluation of the extension of lymph node dissection, it seems very important to validate on European or caucasian patients the results observed in trials performed in Asia. Methods/design GASTRICHIP is a prospective, open, randomized multicenter phase III clinical study with two arms that aims to evaluate the effects of hyperthermic intraperitoneal chemotherapy with oxaliplatin on patients with gastric cancer involving the serosa and/or lymph node involvement and/or with positive cytology at peritoneal washing, treated with perioperative systemic chemotherapy and D1-D2 curative gastrectomy. Peroperatively, at the end of curative surgery, patients will be randomized after preoperatively written consent has been given for participation. Primary endpoint will be overall survival from the date of surgery to the date of death or to the end of follow-up (5 years). Secondary endpoint will be 3- and 5-year recurrence-free survival, site of recurrence, morbidity, and quality of life. An ancillary study will compare the incidence of positive peritoneal cytology pre- and post-gastrectomy in two arms of the study

  3. Antiangiogenic Therapy in Advanced Non-small-cell Lung Cancer: A Meta-analysis of Phase III Randomized Trials.

    PubMed

    Raphael, Jacques; Chan, Kelvin; Karim, Safiya; Kerbel, Robert; Lam, Henry; Santos, Keemo Delos; Saluja, Ronak; Verma, Sunil

    2017-01-12

    We conducted a meta-analysis to evaluate the efficacy of adding any antiangiogenic therapy (AT) to the standard of care in advanced non-small-cell lung cancer (NSCLC). The electronic databases Ovid PubMed, Cochrane Central Register of Controlled Trials, and Embase were searched to identify eligible trials. We included all phase III randomized trials with any line and type of treatment, histology. and AT dose. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and pooled odds ratio (OR) for overall response rates (RR) were calculated. We divided the population into 2 subgroups based on the bevacizumab dose. Data of 19,098 patients from 25 phase III trials were analyzed. Compared with the standard of care, the addition of AT did not prolong OS (HR 0.98; 95% confidence interval [CI], 0.96-1.00; P = .1 and HR 0.97; 95% CI, 0.94-1.00; P = .06 for groups 1 and 2, respectively). However, there was a significant improvement in PFS with the addition of AT (HR 0.85; 95% CI, 0.79-0.91; P < .00001 and HR 0.81; 95% CI, 0.75-0.88; P < .00001 for groups 1 and 2, respectively) and overall RR (OR 1.61; 95% CI, 1.30-2.01; P < .0001 and OR 1.72; 95% CI, 1.39-2.14; P < .00001 for groups 1 and 2, respectively). This is the first meta-analysis including only all phase III trials with AT in NSCLC showing no significant effect on OS and an improvement in PFS and RR only. The role of AT in advanced NSCLC is still questionable; strong validated biomarkers are eagerly needed to predict which subgroup might benefit the most from such therapy.

  4. Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer: PEGASUS-PC Study.

    PubMed

    Yamaue, Hiroki; Tsunoda, Takuya; Tani, Masaji; Miyazawa, Motoki; Yamao, Kenji; Mizuno, Nobumasa; Okusaka, Takuji; Ueno, Hideki; Boku, Narikazu; Fukutomi, Akira; Ishii, Hiroshi; Ohkawa, Shinichi; Furukawa, Masayuki; Maguchi, Hiroyuki; Ikeda, Masafumi; Togashi, Yosuke; Nishio, Kazuto; Ohashi, Yasuo

    2015-07-01

    Gemcitabine is a key drug for the treatment of pancreatic cancer; however, with its limitation in clinical benefits, the development of another potent therapeutic is necessary. Vascular endothelial growth factor receptor 2 is an essential target for tumor angiogenesis, and we have conducted a phase I clinical trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide (elpamotide). Based on the promising results of this phase I trial, a multicenter, randomized, placebo-controlled, double-blind phase II/III clinical trial has been carried out for pancreatic cancer. The eligibility criteria included locally advanced or metastatic pancreatic cancer. Patients were assigned to either the Active group (elpamotide + gemcitabine) or Placebo group (placebo + gemcitabine) in a 2:1 ratio by the dynamic allocation method. The primary endpoint was overall survival. The Harrington-Fleming test was applied to the statistical analysis in this study to evaluate the time-lagged effect of immunotherapy appropriately. A total of 153 patients (Active group, n = 100; Placebo group, n = 53) were included in the analysis. No statistically significant differences were found between the two groups in the prolongation of overall survival (Harrington-Fleming P-value, 0.918; log-rank P-value, 0.897; hazard ratio, 0.87, 95% confidence interval [CI], 0.486-1.557). Median survival time was 8.36 months (95% CI, 7.46-10.18) for the Active group and 8.54 months (95% CI, 7.33-10.84) for the Placebo group. The toxicity observed in both groups was manageable. Combination therapy of elpamotide with gemcitabine was well tolerated. Despite the lack of benefit in overall survival, subgroup analysis suggested that the patients who experienced severe injection site reaction, such as ulceration and erosion, might have better survival.

  5. Phase III randomized trial of autologous cytokine-induced killer cell immunotherapy for newly diagnosed glioblastoma in korea

    PubMed Central

    Kang, Shin-Hyuk; Lee, Jae Won; Chang, Jong-Hee; Kim, Jeong-Hoon; Lim, Young-Jin; Koh, Young-Cho; Chung, Yong-Gu; Kim, Jae-Min; Kim, Choong-Hyun

    2017-01-01

    Purpose Adoptive cell immunotherapy involves an ex vivo expansion of autologous cytokine-induced killer (CIK) cells before their reinfusion into the host. We evaluated the efficacy and safety of CIK cell immunotherapy with radiotherapy-temozolomide (TMZ) for the treatment of newly diagnosed glioblastomas. Experimental design In this multi-center, open-label, phase 3 study, we randomly assigned patients with newly diagnosed glioblastoma to receive CIK cell immunotherapy combined with standard TMZ chemoradiotherapy (CIK immunotherapy group) or standard TMZ chemoradiotherapy alone (control group). The efficacy endpoints were analyzed in the intention-to-treat set and in the per protocol set. Results Between December 2008 and October 2012, a total of 180 patients were randomly assigned to the CIK immunotherapy (n = 91) or control group (n = 89. In the intention-to-treat analysis set, median PFS was 8.1 months (95% confidence interval (CI), 5.8 to 8.5 months) in the CIK immunotherapy group, as compared to 5.4 months (95% CI, 3.3 to 7.9 months) in the control group (one-sided log-rank, p = 0.0401). Overall survival did not differ significantly between two groups. Grade 3 or higher adverse events, health-related quality of life and performance status between two groups did not show a significant difference. Conclusions The addition of CIK cells immunotherapy to standard chemoradiotherapy with TMZ improved PFS. However, the CIK immunotherapy group did not show evidence of a beneficial effect on overall survival. PMID:27690294

  6. S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial)

    PubMed Central

    Yoshida, M.; Ishiguro, M.; Ikejiri, K.; Mochizuki, I.; Nakamoto, Y.; Kinugasa, Y.; Takagane, A.; Endo, T.; Shinozaki, H.; Takii, Y.; Mochizuki, H.; Kotake, K.; Kameoka, S.; Takahashi, K.; Watanabe, T.; Watanabe, M.; Boku, N.; Tomita, N.; Nakatani, E.; Sugihara, K.

    2014-01-01

    Background S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur–uracil plus leucovorin (UFT/LV). Patients and methods Patients aged 20–80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80–120 mg/day on days 1–28 every 42 days; four courses) or UFT/LV (UFT: 300–600 mg/day and LV: 75 mg/day on days 1–28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years. Results A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70–1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups. Conclusion Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer. ClinicalTrials.gov NCT00660894. PMID:24942277

  7. Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM

    PubMed Central

    Offidani, Massimo; Pégourie, Brigitte; De La Rubia, Javier; Garderet, Laurent; Laribi, Kamel; Bosi, Alberto; Marasca, Roberto; Laubach, Jacob; Mohrbacher, Ann; Carella, Angelo Michele; Singhal, Anil K.; Tsao, L. Claire; Lynch, Mark; Bleickardt, Eric; Jou, Ying-Ming; Robbins, Michael; Palumbo, Antonio

    2016-01-01

    In this proof-of-concept, open-label, phase 2 study, patients with relapsed/refractory multiple myeloma (RRMM) received elotuzumab with bortezomib and dexamethasone (EBd) or bortezomib and dexamethasone (Bd) until disease progression/unacceptable toxicity. Primary endpoint was progression-free survival (PFS); secondary/exploratory endpoints included overall response rate (ORR) and overall survival (OS). Two-sided 0.30 significance level was specified (80% power, 103 events) to detect hazard ratio (HR) of 0.69. Efficacy and safety analyses were performed on all randomized patients and all treated patients, respectively. Of 152 randomized patients (77 EBd, 75 Bd), 150 were treated (75 EBd, 75 Bd). PFS was greater with EBd vs Bd (HR, 0.72; 70% confidence interval [CI], 0.59-0.88; stratified log-rank P = .09); median PFS was longer with EBd (9.7 months) vs Bd (6.9 months). In an updated analysis, EBd-treated patients homozygous for the high-affinity FcγRIIIa allele had median PFS of 22.3 months vs 9.8 months in EBd-treated patients homozygous for the low-affinity allele. ORR was 66% (EBd) vs 63% (Bd). Very good partial response or better occurred in 36% of patients (EBd) vs 27% (Bd). Early OS results, based on 40 deaths, revealed an HR of 0.61 (70% CI, 0.43-0.85). To date, 60 deaths have occurred (28 EBd, 32 Bd). No additional clinically significant adverse events occurred with EBd vs Bd. Grade 1/2 infusion reaction rate was low (5% EBd) and mitigated with premedication. In patients with RRMM, elotuzumab, an immunostimulatory antibody, appears to provide clinical benefit without added clinically significant toxicity when combined with Bd vs Bd alone. Registered to ClinicalTrials.gov as NCT01478048. PMID:27091875

  8. A randomized phase II trial of personalized peptide vaccine with low dose cyclophosphamide in biliary tract cancer.

    PubMed

    Shirahama, Takahisa; Muroya, Daisuke; Matsueda, Satoko; Yamada, Akira; Shichijo, Shigeki; Naito, Masayasu; Yamashita, Takuto; Sakamoto, Shinjiro; Okuda, Koji; Itoh, Kyogo; Sasada, Tetsuro; Yutani, Shigeru

    2017-02-11

    Since the prognosis of advanced biliary tract cancer (aBTC) still remains very poor, new therapeutic approaches, including immunotherapies, need to be developed. In the current study, we conducted an open-label randomized phase II study to test whether low dose cyclophosphamide (CPA) could improve antigen-specific immune responses and clinical efficacy of personalized peptide vaccination (PPV) in 49 previously treated aBTC patients. Patients with aBTC refractory to at least one regimen of chemotherapies were randomly assigned to receive PPV with low dose CPA (100 mg/ day for 7 days before vaccination) (PPV/CPA, n=24) or PPV alone (n=25). A maximum of four HLA-matched peptides were selected based on the pre-existing peptide-specific IgG responses, followed by subcutaneous administration. T cell responses to the vaccinated peptides in the PPV/CPA arm tended to be greater than those in the PPV alone arm. The PPV/CPA arm showed significantly better progression-free survival (median time: 6.1 vs 2.9 months; hazard ratio (HR): 0.427; P = 0.008) and overall survival (median time: 12.1 vs 5.9 months; HR: 0.376; P = 0.004), compared to the PPV alone arm. The PPV alone arm, but not the PPV/CPA arm, showed significant increase in plasma IL-6 after vaccinations, which might be associated with inhibition of antigen-specific T cell responses. These results suggested that combined treatment with low dose CPA could provide clinical benefits in aBTC patients under PPV, possibly through prevention of IL-6-mediated immune suppression. Further clinical studies would be recommended to clarify the clinical efficacy of PPV/CPA in aBTC patients. This article is protected by copyright. All rights reserved.

  9. 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

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

    SciTech Connect

    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

    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), or 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.

  11. A Randomized Placebo-Controlled Phase IIb Trial of A3309, A Bile Acid Transporter Inhibitor, for Chronic Idiopathic Constipation

    PubMed Central

    Chey, William D; Camilleri, Michael; Chang, Lin; Rikner, Leif; Graffner, Hans

    2011-01-01

    OBJECTIVES: A3309 is a minimally absorbed ileal bile acid (BA) transporter (IBAT) inhibitor. We conducted an 8-week, multicenter, randomized, double-blind, placebo-controlled, parallel group, phase IIb study, which evaluated A3309 in patients with chronic idiopathic constipation (CIC). METHODS: Patients with CIC (modified Rome III criteria and <3 complete (CSBM) spontaneous bowel movements (SBMs)/week during the 2-week baseline) were randomized to 5, 10, or 15 mg A3309 or placebo once daily. The primary end point was change in SBM number during week 1 compared with baseline. Other bowel and abdominal symptoms were assessed as secondary end points. Serum 7αC4 and lipids were evaluated as biomarkers of BA synthesis/loss. RESULTS: In all, 190 patients (mean 48 years, 90% female) were randomized. Mean increase (95% confidence interval) in SBM for week 1 were 1.7 (0.7–2.8) for placebo vs. 2.5 (1.5–3.5), 4.0 (2.9–5.0), and 5.4 (4.4–6.4) for 5 mg, 10 mg (P<0.002), and 15 mg (P<0.001) A3309, respectively. Increased stool frequency was maintained over 8 weeks. Time to first SBM and CSBM were significantly reduced in the 10- and 15-mg A3309 groups compared with placebo. Straining and bloating decreased with A3309 compared with placebo (P<0.05). Increased 7αC4 and reduced low-density lipoprotein cholesterol with A3309 suggested increased BA synthesis and BA loss. The most common adverse events (AEs) were abdominal pain and diarrhea, which occurred most commonly in the 15-mg A3309 group. No drug-related serious AEs were observed. CONCLUSIONS: A3309 increased stool frequency and improved constipation-related symptoms in CIC; effects were maintained over 8 weeks of treatment. PMID:21606974

  12. Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer

    PubMed Central

    Borad, Mitesh J.; Reddy, Shantan G.; Bahary, Nathan; Uronis, Hope E.; Sigal, Darren; Cohn, Allen L.; Schelman, William R.; Stephenson, Joe; Chiorean, E. Gabriela; Rosen, Peter J.; Ulrich, Brian; Dragovich, Tomislav; Del Prete, Salvatore A.; Rarick, Mark; Eng, Clarence; Kroll, Stew; Ryan, David P.

    2015-01-01

    Purpose TH-302 is an investigational hypoxia-activated prodrug that releases the DNA alkylator bromo-isophosphoramide mustard in hypoxic settings. This phase II study (NCT01144455) evaluated gemcitabine plus TH-302 in patients with previously untreated, locally advanced or metastatic pancreatic cancer. Patients and Methods Patients were randomly assigned 1:1:1 to gemcitabine (1,000 mg/m2), gemcitabine plus TH-302 240 mg/m2 (G+T240), or gemcitabine plus TH-302 340 mg/m2 (G+T340). Randomized crossover after progression on gemcitabine was allowed. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, CA 19-9 response, and safety. Results Two hundred fourteen patients (77% with metastatic disease) were enrolled between June 2010 and July 2011. PFS was significantly longer with gemcitabine plus TH-302 (pooled combination arms) compared with gemcitabine alone (median PFS, 5.6 v 3.6 months, respectively; hazard ratio, 0.61; 95% CI, 0.43 to 0.87; P = .005; median PFS for metastatic disease, 5.1 v 3.4 months, respectively). Median PFS times for G+T240 and G+T340 were 5.6 and 6.0 months, respectively. Tumor response was 12%, 17%, and 26% in the gemcitabine, G+T240, and G+T340 arms, respectively (G+T340 v gemcitabine, P = .04). CA 19-9 decrease was greater with G+T340 versus gemcitabine (−5,398 v −549 U/mL, respectively; P = .008). Median OS times for gemcitabine, G+T240, and G+T340 were 6.9, 8.7, and 9.2 months, respectively (P = not significant). The most common adverse events (AEs) were fatigue, nausea, and peripheral edema (frequencies similar across arms). Skin and mucosal toxicities (2% grade 3) and myelosuppression (55% grade 3 or 4) were the most common TH-302–related AEs but were not associated with treatment discontinuation. Conclusion PFS, tumor response, and CA 19-9 response were significantly improved with G+TH-302. G+T340 is being investigated further in the phase III MAESTRO study

  13. Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection

    PubMed Central

    Nord, Carl Erik; Talbot, George H.; Wilcox, Mark; Gerding, Dale N.; Buitrago, Martha; Kracker, Hilke; Charef, Pascal; Cornely, Oliver A.

    2015-01-01

    Cadazolid, a novel fluoroquinolone-oxazolidinone antibiotic, exhibits potent in vitro activity against Clostridium difficile, including the epidemic BI/NAP1/027 strain. This multicenter, randomized, double-blind, active reference group, phase 2 study evaluated the efficacy and safety of oral cadazolid in treatment of adult patients with C. difficile infection (CDI). Eligible patients with first occurrence/first recurrence of CDI were randomized 1:1:1:1 to 250, 500, or 1,000 mg cadazolid twice daily (BID) or oral 125 mg vancomycin four times daily (QID) for 10 days. The primary endpoint was clinical cure at test of cure (48 ± 24 h after the end of treatment; modified intent-to-treat population), defined as resolution of diarrhea with no further CDI treatment required. Secondary endpoints included recurrence rate, sustained clinical response (clinical cure without recurrence), and time to diarrhea resolution. Of 84 patients enrolled, 20, 22, 20, and 22 received 250, 500, or 1,000 mg cadazolid BID or 125 mg vancomycin QID, respectively. The primary endpoint was achieved in 76.5% (80% confidence interval [CI], 58.4, 89.3), 80.0% (63.9, 91.0), 68.4% (51.1, 82.5), and 68.2% (52.3, 81.3) of patients, respectively. There was no evidence of a cadazolid dosage-dependent response. Each dosage of cadazolid resulted in a lower recurrence rate than with vancomycin (18.2 to 25.0% versus 50%). Consequently, higher sustained clinical response rates were observed with cadazolid (46.7 to 60.0%) than with vancomycin (33.3%). The times to diarrhea resolution were similar for cadazolid and vancomycin. Cadazolid was well tolerated, with no safety signal observed. The results of this phase 2 study support further clinical development of cadazolid. (This study has been registered in the United States at ClinicalTrials.gov under registration no. NCT01222702 and in Europe with the European Medicines Agency under registration no. EUDRA-CT 2010-020941-29.) PMID:26248357

  14. Two- and three-phase equilibria of polydisperse Yukawa hard-sphere fluids confined in random porous media: high temperature approximation and scaled particle theory.

    PubMed

    Hvozd, Taras V; Kalyuzhnyi, Yurij V

    2017-02-15

    We have studied the phase behavior of polydisperse Yukawa hard-sphere fluid confined in random porous media using extension and combination of high temperature approximation and scaled particle theory. The porous media are represented by the matrix of randomly placed hard-sphere obstacles. Due to the confinement, polydispersity effects are substantially enhanced. At an intermediate degree of fluid polydispersity and low density of the matrix, we observe two-phase coexistence with two critical points, and cloud and shadow curves forming closed loops of ellipsoidal shape. With the increase of the matrix density and the constant degree of polydispersity, these two critical points merge and disappear, and at lower temperatures the system fractionates into three coexisting phases. A similar phase behavior was observed in the absence of the porous media caused, however, by the increase of the polydispersity.

  15. Genitourinary brucellosis: results of a multicentric study.

    PubMed

    Erdem, H; Elaldi, N; Ak, O; Gulsun, S; Tekin, R; Ulug, M; Duygu, F; Sunnetcioglu, M; Tulek, N; Guler, S; Cag, Y; Kaya, S; Turker, N; Parlak, E; Demirdal, T; Ataman Hatipoglu, C; Avci, A; Bulut, C; Avci, M; Pekok, A; Savasci, U; Kaya, S; Sozen, H; Tasbakan, M; Guven, T; Bolukcu, S; Cesur, S; Sahin-Horasan, E; Kazak, E; Denk, A; Gonen, I; Karagoz, G; Haykir Solay, A; Alici, O; Kader, C; Senturk, G; Tosun, S; Turan, H; Baran, A I; Ozturk-Engin, D; Bozkurt, F; Deveci, O; Inan, A; Kadanali, A; Sayar, M S; Cetin, B; Yemisen, M; Naz, H; Gorenek, L; Agalar, C

    2014-11-01

    This study reviewed the clinical, laboratory, therapeutic and prognostic data on genitourinary involvement of brucellosis in this largest case series reported. This multicentre study pooled adult patients with genitourinary brucellar involvement from 34 centres treated between 2000 and 2013. Diagnosis of the disease was established by conventional methods. Overall 390 patients with genitourinary brucellosis (352 male, 90.2%) were pooled. In male patients, the most frequent involved site was the scrotal area (n=327, 83.8%), as epididymo-orchitis (n=204, 58%), orchitis (n=112, 31.8%) and epididymitis (n=11, 3.1%). In female patients, pyelonephritis (n=33/38, 86.8%) was significantly higher than in male patients (n=11/352, 3.1%; p<0.0001). The mean blood leukocyte count was 7530±3115/mm3. Routine laboratory analysis revealed mild to moderate increases for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The mean treatment duration and length of hospital stay were significantly higher when there were additional brucellar foci (p<0.05). Surgical operations including orchiectomy and abscess drainage were performed in nine (2.3%) patients. Therapeutic failure was detected in six (1.5%), relapse occurred in four (1%), and persistent infertility related to brucellosis occurred in one patient. A localized scrotal infection in men or pyelonephritis in women in the absence of leucocytosis and with mild to moderate increases in inflammatory markers should signal the possibility of brucellar genitourinary disease.

  16. Critical points of quadratic renormalizations of random variables and phase transitions of disordered polymer models on diamond lattices.

    PubMed

    Monthus, Cécile; Garel, Thomas

    2008-02-01

    We study the wetting transition and the directed polymer delocalization transition on diamond hierarchical lattices. These two phase transitions with frozen disorder correspond to the critical points of quadratic renormalizations of the partition function. (These exact renormalizations on diamond lattices can also be considered as approximate Migdal-Kadanoff renormalizations for hypercubic lattices.) In terms of the rescaled partition function z=Z/Z(typ) , we find that the critical point corresponds to a fixed point distribution with a power-law tail P(c)(z) ~ Phi(ln z)/z(1+mu) as z-->+infinity [up to some subleading logarithmic correction Phi(ln z)], so that all moments z(n) with n>mu diverge. For the wetting transition, the first moment diverges z=+infinity (case 0random weights determined by the fixed point distribution P(c)(z) are broadly distributed. This induces some changes in the traveling wave solutions with respect to the usual case of more narrow distributions.

  17. A randomized phase II trial comparing chemoimmunotherapy with or without bevacizumab in previously untreated patients with chronic lymphocytic leukemia

    PubMed Central

    Kay, Neil E.; Strati, Paolo; LaPlant, Betsy R.; Leis, Jose F.; Nikcevich, Daniel; Call, Timothy G.; Pettinger, Adam M.; Lesnick, Connie E.; Hanson, Curtis A.; Shanafelt, Tait D.

    2016-01-01

    Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF) with in vitro pro-apoptotic and antiangiogenic effects on chronic lymphocytic leukemia (CLL) cells. As monotherapy in patients with CLL, it has no clinical activity. Here we report the results of an open-label, randomized phase II trial comparing the combination of pentostatin, cyclophosphamide and rituximab (PCR) either without or with bevacizumab (PCR-B) in previously untreated CLL patients. A total of 65 evaluable patients were enrolled, 32 receiving PCR and 33 PCR-B. A higher rate of grade 3-4 cardiovascular toxicity was observed with PCR-B (33% vs. 3%, p < 0.003). Patients treated with PCR-B had a trend for a higher complete remission (CR) rate (54.5% vs 31.3%; p = 0.08), longer progression-free survival (PFS)(p = 0.06) and treatment-free survival (TFS)(p = 0.09). No differences in PFS and TFS by IGHV mutational status were observed with the addition of bevacizumab. A significant post-treatment increase in VEGF levels was observed in the PCR-B arm (29.77 to 57.05 pg/mL); in the PCR-B arm, lower baseline CCL-3 levels were significantly associated with achievement of CR (p = 0.01). In conclusion, the addition of bevacizumab to chemoimmunotherapy in CLL is generally well-tolerated and appears to prolong PFS and TFS. PMID:27861157

  18. Detection and measurement of fetal abdominal contour in ultrasound images via local phase information and iterative randomized Hough transform.

    PubMed

    Wang, Weiming; Qin, Jing; Zhu, Lei; Ni, Dong; Chui, Yim-Pan; Heng, Pheng-Ann

    2014-01-01

    Due to the characteristic artifacts of ultrasound images, e.g., speckle noise, shadows and intensity inhomogeneity, traditional intensity-based methods usually have limited success on the segmentation of fetal abdominal contour. This paper presents a novel approach to detect and measure the abdominal contour from fetal ultrasound images in two steps. First, a local phase-based measure called multiscale feature asymmetry (MSFA) is de ned from the monogenic signal to detect the boundaries of fetal abdomen. The MSFA measure is intensity invariant and provides an absolute measurement for the signi cance of features in the image. Second, in order to detect the ellipse that ts to the abdominal contour, the iterative randomized Hough transform is employed to exclude the interferences of the inner boundaries, after which the detected ellipse gradually converges to the outer boundaries of the abdomen. Experimental results in clinical ultrasound images demonstrate the high agreement between our approach and manual approach on the measurement of abdominal circumference (mean sign difference is 0.42% and correlation coef cient is 0.9973), which indicates that the proposed approach can be used as a reliable and accurate tool for obstetrical care and diagnosis.

  19. Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: A randomized placebo-controlled phase III study

    SciTech Connect

    Buentzel, Jens . E-mail: jens.buentzel@shk-ndh.de; Micke, Oliver; Adamietz, Irenaus A.; Monnier, Alain; Glatzel, Michael; Vries, Alexander de

    2006-03-01

    Purpose: Clinical trials demonstrated the efficacy and safety of intravenous (i.v.) or subcutaneous (s.c.) amifostine for reducing xerostomia and mucositis after radiotherapy or radiochemotherapy for head-and-neck cancer. This randomized, double-blinded, placebo-controlled, phase III study evaluated the efficacy and safety of i.v. amifostine during radiochemotherapy for head-and-neck cancer. Methods and Materials: Patients from European and American study centers received i.v. amifostine 300 mg/m{sup 2} (n = 67) or placebo (n = 65) before carboplatin 70 mg/m{sup 2} and radiotherapy on Days 1 to 5 and 21 to 25, and i.v. amifostine 200 mg/m{sup 2} or placebo before radiotherapy on other days. Results: Toxicity incidences were (amifostine, placebo, p value): Grade 2 or higher acute xerostomia (39%, 34%, 0.715), Grade 3 or higher acute mucositis (39%, 22%, 0.055), Grade 2 or higher late xerostomia (37%, 24%, 0.235), and Grade 3 or higher treatment-related adverse events (42%, 20%, 0.008). One-year rates of locoregional failure, progression-free survival, and overall survival were not significantly different between treatments. Conclusions: The used amifostine doses were not able to reduce the toxicity of simultaneous radiochemotherapy for head-and-neck cancer. The safety of amifostine and the lack of tumor protection were consistent with previous studies.

  20. Excitation energies from extended random phase approximation employed with approximate one- and two-electron reduced density matrices

    NASA Astrophysics Data System (ADS)

    Chatterjee, Koushik; Pernal, Katarzyna

    2012-11-01

    Starting from Rowe's equation of motion we derive extended random phase approximation (ERPA) equations for excitation energies. The ERPA matrix elements are expressed in terms of the correlated ground state one- and two-electron reduced density matrices, 1- and 2-RDM, respectively. Three ways of obtaining approximate 2-RDM are considered: linearization of the ERPA equations, obtaining 2-RDM from density matrix functionals, and employing 2-RDM corresponding to an antisymmetrized product of strongly orthogonal geminals (APSG) ansatz. Applying the ERPA equations with the exact 2-RDM to a hydrogen molecule reveals that the resulting ^1Σ _g^+ excitation energies are not exact. A correction to the ERPA excitation operator involving some double excitations is proposed leading to the ERPA2 approach, which employs the APSG one- and two-electron reduced density matrices. For two-electron systems ERPA2 satisfies a consistency condition and yields exact singlet excitations. It is shown that 2-RDM corresponding to the APSG theory employed in the ERPA2 equations yields excellent singlet excitation energies for Be and LiH systems, and for the N2 molecule the quality of the potential energy curves is at the coupled cluster singles and doubles level. ERPA2 nearly satisfies the consistency condition for small molecules that partially explains its good performance.

  1. Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine candidate in healthy children: a randomized phase I clinical trial.

    PubMed

    Dotres, Carlos P; Puga, Rinaldo; Ricardo, Yariset; Broño, Carmen R; Paredes, Beatriz; Echemendía, Vladimir; Rosell, Sandra; González, Nadezhda; García-Rivera, Dagmar; Valdés, Yury; Goldblatt, David; Vérez-Bencomo, Vicente

    2014-09-15

    A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 μg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 μg of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173.

  2. Spin-unrestricted random-phase approximation with range separation: Benchmark on atomization energies and reaction barrier heights

    SciTech Connect

    Mussard, Bastien; Reinhardt, Peter; Toulouse, Julien; Ángyán, János G.

    2015-04-21

    We consider several spin-unrestricted random-phase approximation (RPA) variants for calculating correlation energies, with and without range separation, and test them on datasets of atomization energies and reaction barrier heights. We show that range separation greatly improves the accuracy of all RPA variants for these properties. Moreover, we show that a RPA variant with exchange, hereafter referred to as RPAx-SO2, first proposed by Szabo and Ostlund [J. Chem. Phys. 67, 4351 (1977)] in a spin-restricted closed-shell formalism, and extended here to a spin-unrestricted formalism, provides on average the most accurate range-separated RPA variant for atomization energies and reaction barrier heights. Since this range-separated RPAx-SO2 method had already been shown to be among the most accurate range-separated RPA variants for weak intermolecular interactions [J. Toulouse et al., J. Chem. Phys. 135, 084119 (2011)], this works confirms range-separated RPAx-SO2 as a promising method for general chemical applications.

  3. Conversion From Twice-Daily Tacrolimus to Once-Daily Extended Release Tacrolimus (LCPT): The Phase III Randomized MELT Trial

    PubMed Central

    Bunnapradist, S; Ciechanowski, K; West-Thielke, P; Mulgaonkar, S; Rostaing, L; Vasudev, B; Budde, K

    2013-01-01

    Phase III noninferiority trial examining efficacy and safety of converting stable renal transplant recipients from twice-daily tacrolimus to a novel extended-release once-daily tacrolimus formulation (LCPT) with a controlled agglomeration technology. Controls maintained tacrolimus twice daily. The primary efficacy endpoint was proportion of patients with efficacy failures (death, graft failure, locally read biopsy-proven acute rejection [BPAR], or loss to follow-up) within 12 months. Starting LCPT dose was 30% lower (15% for blacks) than preconversion tacrolimus dose; target trough levels were 4–15 ng/mL. A total of 326 patients were randomized; the mITT population (n = 162 each group) was similar demographically in the two groups. Mean daily dose of LCPT was significantly (p < 0.0001) lower than preconversion tacrolimus dose at each visit; mean trough levels between groups were similar. There were four efficacy failures in each group; safety outcomes were similar between groups. Frequency of premature study drug discontinuation was LCPT: 12% versus tacrolimus twice daily: 5% (p = 0.028). LCPT demonstrated noninferiority to tacrolimus twice daily in efficacy failure rates. LCPT may offer a safe and effective alternative for converting patients to a once-daily formulation. Compared to currently available tacrolimus formulation, LCPT requires lower doses to achieve target trough levels. PMID:23279614

  4. Bichromatic coherent random lasing from dye-doped polymer stabilized blue phase liquid crystals controlled by pump light polarization

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Wang, Meng; Yang, Mingchao; Shi, Li-Jie; Deng, Luogen; Yang, Huai

    2016-09-01

    In this paper, we investigate the bichromatic coherent random lasing actions from the dye-doped polymer stabilized blue phase liquid crystals. Two groups of lasing peaks, of which the full widith at half maximum is about 0.3 nm, are clearly observed. The shorter- and longer-wavelength modes are associated with the excitation of the single laser dye (DCM) monomers and dimers respectively. The experimental results show that the competition between the two groups of the lasing peaks can be controlled by varying the polarization of the pump light. When the polarization of the pump light is rotated from 0° to 90°, the intensity of the shorter-wavelength lasing peak group reduces while the intensity of the longer-wavelength lasing peak group increases. In addition, a red shift of the longer-wavelength modes is also observed and the physical mechanisms behind the red-shift phenomenon are discussed. Project supported by the National Natural Science Foundation of China (Grant Nos. 11474021 and 51333001), the Key Program for International S&T Cooperation Projects of China (Grant No. 2013DFB50340), the Issues of Priority Development Areas of the Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20120001130005), and the Key (Key Grant) Project of Chinese Ministry of Education (Grant No. 313002).

  5. Translation of TRO40303 from myocardial infarction models to demonstration of safety and tolerance in a randomized Phase I trial

    PubMed Central

    2014-01-01

    Background Although reperfusion injury has been shown to be responsible for cardiomyocytes death after an acute myocardial infarction, there is currently no drug on the market that reduces this type of injury. TRO40303 is a new cardioprotective compound that was shown to inhibit the opening of the mitochondrial permeability transition pore and reduce infarct size after ischemia-reperfusion in a rat model of cardiac ischemia-reperfusion injury. Methods In the rat model, the therapeutic window and the dose effect relationship were investigated in order to select the proper dose and design for clinical investigations. To evaluate post-ischemic functional recovery, TRO40303 was tested in a model of isolated rat heart. Additionally, TRO40303 was investigated in a Phase I randomized, double-blind, placebo controlled study to assess the safety, tolerability and pharmacokinetics of single intravenous ascending doses of the compound (0.5 to 13 mg/kg) in 72 healthy male, post-menopausal and hysterectomized female subjects at flow rates from 0.04 to 35 mL/min (EudraCT number: 2010-021453-39). This work was supported in part by the French Agence Nationale de la Recherche. Results In the vivo model, TRO40303 reduced infarct size by 40% at 1 mg/kg and by 50% at 3 and 10 mg/kg given by intravenous bolus and was only active when administered before reperfusion. Additionally, TRO40303 provided functional recovery and reduced oxidative stress in the isolated rat heart model. These results, together with pharmacokinetic based allometry to human and non-clinical toxicology data, were used to design the Phase I trial. All the tested doses and flow rates were well tolerated clinically. There were no serious adverse events reported. No relevant changes in vital signs, electrocardiogram parameters, laboratory tests or physical examinations were observed at any time in any dose group. Pharmacokinetics was linear up to 6 mg/kg and slightly ~1.5-fold, hyper-proportional from 6 to 13

  6. Multicentric spinal cord and brain glioblastoma without previous craniotomy

    PubMed Central

    de Eulate-Beramendi, Sayoa A.; Piña-Batista, Kelvin M.; Rodrigo, Victor; Torres-Rivas, Hector E.; Rial-Basalo, Juan C.

    2016-01-01

    Background: Glioblastoma multiforme (GBS) is a highly malignant glioma that rarely presents as an infratentorial tumor. Multicentric gliomas lesions are widely separated in site and/or time and its incidence has been reported between 0.15 and 10%. Multicentric gliomas involving supratentorial and infratentorial region are even more rare. In most cases, infratentorial disease is seen after surgical manipulation or radiation therapy and is usually located in the cerebellum or cervical region. Case Report: We present a rare case of symptomatic multicentric glioma in the brain, fourth ventricle, cervical as well as lumbar glioblastoma in an adult without previous therapeutic intervention. We also review the literature of this rare presentation. Conclusions: This report suggests that GBM is a diffuse disease; the more extended the disease, the worse prognosis it has. The management still remains controversial and further studies are required to understand the prognosis factors of dissemination. PMID:27512613

  7. Integrative radiogenomic analysis for multicentric radiophenotype in glioblastoma

    PubMed Central

    Kong, Doo-Sik; Kim, Jinkuk; Lee, In-Hee; Kim, Sung Tae; Seol, Ho Jun; Lee, Jung-Il; Park, Woong-Yang; Ryu, Gyuha; Wang, Zichen; Ma'ayan, Avi; Nam, Do-Hyun

    2016-01-01

    We postulated that multicentric glioblastoma (GBM) represents more invasiveness form than solitary GBM and has their own genomic characteristics. From May 2004 to June 2010 we retrospectively identified 51 treatment-naïve GBM patients with available clinical information from the Samsung Medical Center data registry. Multicentricity of the tumor was defined as the presence of multiple foci on the T1 contrast enhancement of MR images or having high signal for multiple lesions without contiguity of each other on the FLAIR image. Kaplan-Meier survival analysis demonstrated that multicentric GBM had worse prognosis than solitary GBM (median, 16.03 vs. 20.57 months, p < 0.05). Copy number variation (CNV) analysis revealed there was an increase in 11 regions, and a decrease in 17 regions, in the multicentric GBM. Gene expression profiling identified 738 genes to be increased and 623 genes to be decreased in the multicentric radiophenotype (p < 0.001). Integration of the CNV and expression datasets identified twelve representative genes: CPM, LANCL2, LAMP1, GAS6, DCUN1D2, CDK4, AGAP2, TSPAN33, PDLIM1, CLDN12, and GTPBP10 having high correlation across CNV, gene expression and patient outcome. Network and enrichment analyses showed that the multicentric tumor had elevated fibrotic signaling pathways compared with a more proliferative and mitogenic signal in the solitary tumors. Noninvasive radiological imaging together with integrative radiogenomic analysis can provide an important tool in helping to advance personalized therapy for the more clinically aggressive subset of GBM. PMID:26863628

  8. Dasatinib first-line: Multicentric Italian experience outside clinical trials.

    PubMed

    Breccia, Massimo; Stagno, Fabio; Luciano, Luigiana; Abruzzese, Elisabetta; Annunziata, Mario; D'Adda, Mariella; Maggi, Alessandro; Sgherza, Nicola; Russo-Rossi, Antonella; Pregno, Patrizia; Castagnetti, Fausto; Iurlo, Alessandra; Latagliata, Roberto; Cedrone, Michele; Di Renzo, Nicola; Sorà, Federica; Rege-Cambrin, Giovanna; La Nasa, Giorgio; Scortechini, Anna Rita; Greco, Giovanna; Franceschini, Luca; Sica, Simona; Bocchia, Monica; Crugnola, Monica; Orlandi, Esther; Guarini, Attilio; Specchia, Giorgina; Rosti, Gianantonio; Saglio, Giuseppe; Alimena, Giuliana

    2016-01-01

    Dasatinib was approved for the treatment of chronic phase (CP) chronic myeloid leukemia (CML) patients in first line therapy based on the demonstration of efficacy and safety reported in patients enrolled in clinical trials. We describe a multicentric Italian "real-life" experience of dasatinib used as frontline treatment outside clinical trials. One hundred and nine patients (median age 54 years) were treated from January 2012 to December 2013. Increased incidence of high risk patients were detected according to stratification (26% according to Sokal score, 19% according to Euro score and 16% according to EUTOS) when compared to company sponsored studies. Median time from diagnosis to start of dasatinib was 18 days. Ten patients received unscheduled starting dose (6 patients 50mg and 4 patients 80 mg QD), whereas 99 patients started with 100mg QD. At 3 months, 92% of patients achieved a BCR-ABL ratio less than 10%. At 6 months, the rate of CCyR was 91% and the rate of MR3 was 40%, with 8% of the patients reaching MR4.5. Ninety-three patients were evaluable at 12 months: the rate of MR3 was 62%, with MR4.5 being achieved by 19% of the patients. At a median follow-up of 12 months, 27 patients (24.7%) were receiving the drug at reduced dose. Two patients (1.8%) experienced a lymphoid blast crisis and the overall incidence of resistance was 8%. As regards safety, the major side effects recorded were thrombocytopenia, neutropenia and pleural effusions, which occurred in 22%, 10% and 8% of patients, respectively. Present results, achieved in a large cohort of patients treated outside clinical trials, further confirm the efficacy and safety of dasatinib as firstline treatment in CML.

  9. Dose-dependent change in biomarkers during neoadjuvant endocrine therapy with fulvestrant: results from NEWEST, a randomized Phase II study.

    PubMed

    Kuter, Irene; Gee, Julia M W; Hegg, Roberto; Singer, Christian F; Badwe, Rajendra A; Lowe, Elizabeth S; Emeribe, Ugochi A; Anderson, Elizabeth; Sapunar, Francisco; Finlay, Pauline; Nicholson, Robert I; Bines, José; Harbeck, Nadia

    2012-05-01

    NEWEST (Neoadjuvant Endocrine Therapy for Women with Estrogen-Sensitive Tumors) is the first study to compare biological and clinical activity of fulvestrant 500 versus 250 mg in the neoadjuvant breast cancer setting. We hypothesized that fulvestrant 500 mg may be superior to 250 mg in blocking estrogen receptor (ER) signaling and growth. A multicenter, randomized, open-label, Phase II study was performed to compare fulvestrant 500 mg (500 mg/month plus 500 mg on day 14 of month 1) versus fulvestrant 250 mg/month for 16 weeks prior to surgery in postmenopausal women with ER+ locally advanced breast cancer. Core biopsies at baseline, week 4, and surgery were assessed for biomarker changes. Primary endpoint: change in Ki67 labeling index (LI) from baseline to week 4 determined by automated computer imaging system (ACIS). Secondary endpoints: ER protein expression and function; progesterone receptor (PgR) expression; tumor response; tolerability. ER and PgR were examined retrospectively using the H score method. A total of 211 patients were randomized (fulvestrant 500 mg: n = 109; 250 mg: n = 102). At week 4, fulvestrant 500 mg resulted in greater reduction of Ki67 LI and ER expression versus 250 mg (-78.8 vs. -47.4% [p < 0.0001] and -25.0 vs. -13.5% [p = 0.0002], respectively [ACIS]); PgR suppression was not significantly different (-22.7 vs. -17.6; p = 0.5677). However, H score detected even greater suppression of ER (-50.3 vs. -13.7%; p < 0.0001) and greater PgR suppression (-80.5 vs. -46.3%; p = 0.0018) for fulvestrant 500 versus 250 mg. At week 16, tumor response rates were 22.9 and 20.6% for fulvestrant 500 and 250 mg, respectively, with considerable decline in all markers by both ACIS and H score. No detrimental effects on endometrial thickness or bone markers and no new safety concerns were identified. This provides the first evidence of greater biological activity for fulvestrant 500 versus 250 mg in depleting ER expression, function, and growth.

  10. A Phase 2 Randomized Trial of a Rifapentine plus Moxifloxacin-Based Regimen for Treatment of Pulmonary Tuberculosis

    PubMed Central

    Conde, Marcus B.; Mello, Fernanda C. Q.; Duarte, Rafael Silva; Cavalcante, Solange C.; Rolla, Valeria; Dalcolmo, Margareth; Loredo, Carla; Durovni, Betina; Armstrong, Derek T.; Efron, Anne; Barnes, Grace L.; Marzinke, Mark A.; Savic, Radojka M.; Dooley, Kelly E.; Cohn, Silvia; Moulton, Lawrence H.; Chaisson, Richard E.; Dorman, Susan E.

    2016-01-01

    Background The combination of rifapentine and moxifloxacin administered daily with other anti-tuberculosis drugs is highly active in mouse models of tuberculosis chemotherapy. The objective of this phase 2 clinical trial was to determine the bactericidal activity, safety, and tolerability of a regimen comprised of rifapentine, moxifloxacin, isoniazid, and pyrazinamide administered daily during the first 8 weeks of pulmonary tuberculosis treatment. Methods Adults with sputum smear-positive pulmonary tuberculosis were randomized to receive either rifapentine (approximately 7.5 mg/kg) plus moxifloxacin (investigational arm), or rifampin (approximately 10 mg/kg) plus ethambutol (control) daily for 8 weeks, along with isoniazid and pyrazinamide. The primary endpoint was sputum culture status at completion of 8 weeks of treatment. Results 121 participants (56% of accrual target) were enrolled. At completion of 8 weeks of treatment, negative cultures using Löwenstein-Jensen (LJ) medium occurred in 47/60 (78%) participants in the investigational arm vs. 43/51 (84%, p = 0.47) in the control arm; negative cultures using liquid medium occurred in 37/47 (79%) in the investigational arm vs. 27/41 (66%, p = 0.23) in the control arm. Time to stable culture conversion was shorter for the investigational arm vs. the control arm using liquid culture medium (p = 0.03), but there was no difference using LJ medium. Median rifapentine area under the concentration-time curve (AUC0-24) was 313 mcg*h/mL, similar to recent studies of rifapentine dosed at 450–600 mg daily. Median moxifloxacin AUC0-24 was 28.0 mcg*h/mL, much lower than in trials where rifapentine was given only intermittently with moxifloxacin. The proportion of participants discontinuing assigned treatment for reasons other than microbiological ineligibility was higher in the investigational arm vs. the control arm (11/62 [18%] vs. 3/59 [5%], p = 0.04) although the proportions of grade 3 or higher adverse events were

  11. Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial.

    PubMed

    Lu, Charles; Lee, J Jack; Komaki, Ritsuko; Herbst, Roy S; Feng, Lei; Evans, William K; Choy, Hak; Desjardins, Pierre; Esparaz, Benjamin T; Truong, Mylene T; Saxman, Scott; Kelaghan, Joseph; Bleyer, Archie; Fisch, Michael J

    2010-06-16

    BACKGROUND AE-941 is a standardized aqueous shark cartilage extract with antiangiogenic properties that has previously been evaluated in phase I and II clinical trials. Our objective was to determine the effect of adding AE-941 to chemoradiotherapy on overall survival of patients with unresectable stage III non-small cell lung cancer (NSCLC). METHODS A randomized, double-blinded, placebo-controlled, phase III clinical trial was designed to test the efficacy of AE-941 in unresectable stage III NSCLC patients who were treated with chemoradiotherapy. Between June 5, 2000, and February 6, 2006, 379 eligible patients were enrolled in community and academic oncology centers across the United States and Canada. In February 2006, the trial was closed to new patient entry before meeting the target sample size because of insufficient accrual. All subjects received induction chemotherapy followed by concurrent chemotherapy with chest radiotherapy. Each participating center administered one of the two chemotherapy regimens, either carboplatin and paclitaxel, or cisplatin and vinorelbine. The primary endpoint was overall survival, and secondary endpoints were time to progression, progression-free survival, tumor response rate, and toxic effects. Event-time distributions were estimated by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS There was no statistically significant difference in overall survival between the chemoradiotherapy plus AE-941 group (n = 188; median survival = 14.4 months, 95% confidence interval = 12.6 to 17.9 months) and the chemoradiotherapy plus placebo group (n = 191; median survival = 15.6 months, 95% confidence interval = 13.8 to 18.1 months) (P = .73). Time to progression, progression-free survival, and tumor response rates were not statistically significantly different between the AE-941 and the placebo groups. No differences between the two groups were observed in common grade 3 or higher toxic effects attributable to

  12. A Randomized Phase II Study of Linsitinib (OSI-906) Versus Topotecan in Patients With Relapsed Small-Cell Lung Cancer

    PubMed Central

    Otterson, Gregory A.; Dowlati, Afshin; Traynor, Anne M.; Horn, Leora; Owonikoko, Taofeek K.; Ross, Helen J.; Hann, Christine L.; Abu Hejleh, Taher; Nieva, Jorge; Zhao, Xiuhua; Schell, Michael; Sullivan, Daniel M.

    2016-01-01

    Lessons Learned Targeted therapy options for SCLC patients are limited; no agent, thus far, has resulted in a strategy promising enough to progress to phase III trials. Linsitinib, a potent insulin growth factor-1-receptor tyrosine kinase inhibitor, may be one agent with activity against SCLC. Despite lack of a reliable predictive biomarker in this disease, which may have partly contributed to the negative outcome reported here, linsitinib, although safe, showed no clinical activity in unselected, relapsed SCLC patients. Background. Treatment of relapsed small-cell lung cancer (SCLC) remains suboptimal. Insulin growth factor-1 receptor (IGF-1R) signaling plays a role in growth, survival, and chemoresistance in SCLC. Linsitinib is a potent IGF-1R tyrosine kinase inhibitor that potentially may be active against SCLC. Methods. In this phase II study, 8 eligible patients were randomly assigned in a 1:2 ratio to topotecan (1.5 mg/m2 intravenously or 2.3 mg/m2 orally, daily for 5 days for 4 cycles) or linsitinib (150 mg orally twice daily until progression). The primary endpoint was progression-free survival. Patients with relapsed SCLC, platinum sensitive or resistant, performance status (PS) 0–2, and adequate hematologic, renal, and hepatic function were enrolled. Patients with diabetes, cirrhosis, and those taking insulinotropic agents were excluded. Crossover to linsitinib was allowed at progression. Results. Fifteen patients received topotecan (8 resistant, 3 with PS 2) and 29 received linsitinib (16 resistant, 5 with PS 2). Two partial responses were observed with topotecan. Only 4 of 15 patients with topotecan and 1 of 29 with linsitinib achieved stable disease. Median progression-free survival was 3.0 (95% confidence interval [CI], 1.5–3.6) and 1.2 (95% CI, 1.1–1.4) months for topotecan and linsitinib, respectively (p = .0001). Median survival was 5.3 (95% CI, 2.2–7.6) and 3.4 (95% CI, 1.8–5.6) months for topotecan and linsitinib, respectively (p = .71

  13. Accurate and efficient calculation of excitation energies with the active-space particle-particle random phase approximation

    DOE PAGES

    Zhang, Du; Yang, Weitao

    2016-10-13

    An efficient method for calculating excitation energies based on the particle-particle random phase approximation (ppRPA) is presented. Neglecting the contributions from the high-lying virtual states and the low-lying core states leads to the significantly smaller active-space ppRPA matrix while keeping the error to within 0.05 eV from the corresponding full ppRPA excitation energies. The resulting computational cost is significantly reduced and becomes less than the construction of the non-local Fock exchange potential matrix in the self-consistent-field (SCF) procedure. With only a modest number of active orbitals, the original ppRPA singlet-triplet (ST) gaps as well as the low-lying single and doublemore » excitation energies can be accurately reproduced at much reduced computational costs, up to 100 times faster than the iterative Davidson diagonalization of the original full ppRPA matrix. For high-lying Rydberg excitations where the Davidson algorithm fails, the computational savings of active-space ppRPA with respect to the direct diagonalization is even more dramatic. The virtues of the underlying full ppRPA combined with the significantly lower computational cost of the active-space approach will significantly expand the applicability of the ppRPA method to calculate excitation energies at a cost of O(K^{4}), with a prefactor much smaller than a single SCF Hartree-Fock (HF)/hybrid functional calculation, thus opening up new possibilities for the quantum mechanical study of excited state electronic structure of large systems.« less

  14. Difluprednate 0.05% Versus Prednisolone Acetate 1% for Endogenous Anterior Uveitis: A Phase III, Multicenter, Randomized Study

    PubMed Central

    Sheppard, John D.; Toyos, Melissa M.; Kempen, John H.; Kaur, Paramjit; Foster, C. Stephen

    2014-01-01

    Purpose. Endogenous anterior uveitis (AU), when untreated, may lead to vision loss. This study compared the safety and efficacy of difluprednate versus prednisolone acetate for the treatment of this condition. Methods. This phase III, double-masked, noninferiority study randomized patients with mild to moderate endogenous AU to receive difluprednate 0.05% (n = 56) four times daily, alternating with vehicle four times daily, or prednisolone acetate 1% (n = 54) eight times daily. The 14-day treatment period was followed by a 14-day dose-tapering period and a 14-day observation period. The primary efficacy end point was change in anterior chamber cell grade (range, 0 for ≤1 cell to 4 for >50 cells) from baseline to day 14. Results. At day 14, the mean change in anterior chamber cell grade with difluprednate was noninferior to that with prednisolone acetate (−2.2 vs. −2.0, P = 0.16). The proportions of difluprednate-treated patients versus prednisolone acetate–treated patients demonstrating complete clearing of anterior chamber cells at day 3 were 13.0% vs. 2.1% (P = 0.046) and at day 21 were 73.9% vs. 63.8% (P = 0.013). A significant between-group difference in the mean IOP increase was seen at day 3 (2.5 mm Hg for difluprednate-treated patients and 0.1 mm Hg for prednisolone acetate–treated patients, P = 0.0013) but not at other time points. The mean IOP values in both groups remained less than 21 mm Hg throughout the study. Conclusions. Difluprednate 0.05% four times daily is well tolerated and is noninferior to prednisolone acetate 1% eight times daily for the treatment of endogenous AU. (ClinicalTrials.gov number, NCT01201798.) PMID:24677110

  15. Large-scale deformed quasiparticle random-phase approximation calculations of the γ -ray strength function using the Gogny force

    NASA Astrophysics Data System (ADS)

    Martini, M.; Péru, S.; Hilaire, S.; Goriely, S.; Lechaftois, F.

    2016-07-01

    Valuable theoretical predictions of nuclear dipole excitations in the whole chart are of great interest for different nuclear applications, including in particular nuclear astrophysics. Here we present large-scale calculations of the E 1 γ -ray strength function obtained in the framework of the axially symmetric deformed quasiparticle random-phase approximation based on the finite-range Gogny force. This approach is applied to even-even nuclei, the strength function for odd nuclei being derived by interpolation. The convergence with respect to the adopted number of harmonic oscillator shells and the cutoff energy introduced in the 2-quasiparticle (2 -q p ) excitation space is analyzed. The calculations performed with two different Gogny interactions, namely D1S and D1M, are compared. A systematic energy shift of the E 1 strength is found for D1M relative to D1S, leading to a lower energy centroid and a smaller energy-weighted sum rule for D1M. When comparing with experimental photoabsorption data, the Gogny-QRPA predictions are found to overestimate the giant dipole energy by typically ˜2 MeV. Despite the microscopic nature of our self-consistent Hartree-Fock-Bogoliubov plus QRPA calculation, some phenomenological corrections need to be included to take into account the effects beyond the standard 2 -q p QRPA excitations and the coupling between the single-particle and low-lying collective phonon degrees of freedom. For this purpose, three prescriptions of folding procedure are considered and adjusted to reproduce experimental photoabsorption data at best. All of them are shown to lead to somewhat similar predictions of the E 1 strength, both at low energies and for exotic neutron-rich nuclei. Predictions of γ -ray strength functions and Maxwellian-averaged neutron capture rates for the whole Sn isotopic chain are also discussed and compared with previous theoretical calculations.

  16. Accurate and efficient calculation of excitation energies with the active-space particle-particle random phase approximation

    SciTech Connect

    Zhang, Du; Yang, Weitao

    2016-10-13

    An efficient method for calculating excitation energies based on the particle-particle random phase approximation (ppRPA) is presented. Neglecting the contributions from the high-lying virtual states and the low-lying core states leads to the significantly smaller active-space ppRPA matrix while keeping the error to within 0.05 eV from the corresponding full ppRPA excitation energies. The resulting computational cost is significantly reduced and becomes less than the construction of the non-local Fock exchange potential matrix in the self-consistent-field (SCF) procedure. With only a modest number of active orbitals, the original ppRPA singlet-triplet (ST) gaps as well as the low-lying single and double excitation energies can be accurately reproduced at much reduced computational costs, up to 100 times faster than the iterative Davidson diagonalization of the original full ppRPA matrix. For high-lying Rydberg excitations where the Davidson algorithm fails, the computational savings of active-space ppRPA with respect to the direct diagonalization is even more dramatic. The virtues of the underlying full ppRPA combined with the significantly lower computational cost of the active-space approach will significantly expand the applicability of the ppRPA method to calculate excitation energies at a cost of O(K^{4}), with a prefactor much smaller than a single SCF Hartree-Fock (HF)/hybrid functional calculation, thus opening up new possibilities for the quantum mechanical study of excited state electronic structure of large systems.

  17. Localization transition in random Lévy matrices: multifractality of eigenvectors in the localized phase and at criticality

    NASA Astrophysics Data System (ADS)

    Monthus, Cécile

    2016-09-01

    For random Lévy matrices of size N× N , where matrix elements are drawn with some heavy-tailed distribution P≤ft({{H}ij}\\right)\\propto {{N} -1}|{{H}ij}{{|}-1-μ} with 0<μ <2 (infinite variance), there exists an extensive number of finite eigenvalues E  =  O(1), while the maximal eigenvalue grows as {{E}\\text{max}}∼ {{N}\\frac{1μ}} . Here we study the localization properties of the corresponding eigenvectors via some strong disorder perturbative expansion that remains consistent within the localized phase and that yields their inverse participation ratios (IPR) Y q as a function of the continuous parameter 0. In the region 0<μ <1 , we find that all eigenvectors are localized but display some multifractality: the IPR are finite above some threshold q  >  q c but diverge in the region 0  <  q  <  q c near the origin. In the region 1<μ <2 , only the sub-extensive fraction {{N}\\frac{3{2+μ}}} of the biggest eigenvalues corresponding to the region |E|≥slant {{N}\\frac{(μ -1)μ (2+μ )}}} remains localized, while the extensive number of other states of smaller energy are delocalized. For the extensive number of finite eigenvalues E  =  O(1), the localization/delocalization transition thus takes place at the critical value {{μ\\text{c}}=1 corresponding to Cauchy matrices: the IPR Y q of the corresponding critical eigenstates follow the strong-multifractality spectrum characterized by the generalized fractal dimensions {{D}\\text{criti}}(q)=\\frac{1-2q}{1-q}θ ≤ft(0≤slant q≤slant \\frac{1}{2}\\right) , which has been found previously in various other Localization problems in spaces of effective infinite dimensionality.

  18. PREVENTION OF CONVERSION TO ABNORMAL TCD WITH HYDROXYUREA IN SICKLE CELL ANEMIA: A PHASE III INTERNATIONAL RANDOMIZED CLINICAL TRIAL

    PubMed Central

    Hankins, Jane S.; McCarville, M. Beth; Rankine-Mullings, Angela; Reid, Marvin E.; Lobo, Clarisse L.C.; Moura, Patricia G.; Ali, Susanna; Soares, Deanne; Aldred, Karen; Jay, Dennis W.; Aygun, Banu; Bennett, John; Kang, Guolian; Goldsmith, Jonathan C.; Smeltzer, Matthew P.; Boyett, James M.; Ware, Russell E.

    2015-01-01

    Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was an NHLBI-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ0-thalassemia (1), and HbSD (1), median age 5.4 years (range, 2.7-9.8)]. Due to slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI 0 to 35%) in the hydroxyurea arm and 47% (95% CI 6 to 81%) in observation arm at 15 months (p=0.16). In post-hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities, compared to observation (0% versus 50%, p=0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (−15.5 versus +10.2 cm/sec, p=0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities. PMID:26414435

  19. Effect of rosuvastatin on diabetic polyneuropathy: a randomized, double-blind, placebo-controlled Phase IIa study

    PubMed Central

    Hernández-Ojeda, Jaime; Román-Pintos, Luis Miguel; Rodríguez-Carrízalez, Adolfo Daniel; Troyo-Sanromán, Rogelio; Cardona-Muñoz, Ernesto Germán; Alatorre-Carranza, María del Pilar; Miranda-Díaz, Alejandra Guillermina

    2014-01-01

    Background Diabetic neuropathy affects 50%–66% of patients with diabetes mellitus. Oxidative stress generates nerve dysfunction by causing segmental demyelinization and axonal degeneration. Antioxidants are considered to be the only etiologic management for diabetic polyneuropathy, and statins such as rosuvastatin increase nitric oxide bioavailability and reduce lipid peroxidation. The aim of this study was to evaluate the antioxidant effect of rosuvastatin in diabetic polyneuropathy. Methods We conducted a randomized, double-blind, placebo-controlled Phase IIa clinical trial in patients with type 2 diabetes and diabetic polyneuropathy (DPN) stage ≥1b. We allocated subjects to two parallel groups (1:1) that received rosuvastatin 20 mg or placebo for 12 weeks. Primary outcomes were neuropathic symptom score, disability score, and nerve conduction studies, and secondary outcomes were glycemic control, lipid and hepatic profile, lipid peroxidation, and nerve growth factor beta (NGF-β) levels. Results Both groups were of similar age and duration since diagnosis of diabetes and DPN. We observed improvement of DPN in the rosuvastatin group from stage 2a (88.2%) to stage 1b (41.2%), improvement of neuropathic symptom score from 4.5±2 to 2.4±1.8, and significant (P=0.001) reductions of peroneal nerve conduction velocity (from 40.8±2.2 to 42.1±1.6 seconds) and lipid peroxidation (from 25.4±2 to 12.2±4.0 nmol/mL), with no significant change in glycemic control or β-NGF. Conclusion The severity, symptoms, and nerve conduction parameters of DPN improved after 12 weeks of treatment with rosuvastatin. These beneficial effects appear to be attributable to reductions in lipid peroxidation and oxidative stress. PMID:25214797

  20. Cediranib in combination with fulvestrant in hormone-sensitive metastatic breast cancer: a randomized Phase II study.

    PubMed

    Hyams, David M; Chan, Arlene; de Oliveira, Celia; Snyder, Raymond; Vinholes, Jeferson; Audeh, M William; Alencar, Victor M; Lombard, Janine; Mookerjee, Bijoyesh; Xu, John; Brown, Kathryn; Klein, Paula

    2013-10-01

    Hormone receptor-positive breast cancer is treated with estrogen inhibitors. Fulvestrant (FASLODEX™), an estrogen receptor (ER) antagonist with no known agonist effects, competitively binds, blocks and degrades the ER. Vascular endothelial growth factor (VEGF) may mediate resistance to ER antagonists. Cediranib is a highly potent VEGF signaling inhibitor with activity against all three VEGF receptors. This randomized Phase II study evaluated cediranib plus fulvestrant. Postmenopausal women with hormone-sensitive metastatic breast cancer were eligible. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), duration of response, clinical benefit rate (CBR), safety/tolerability and pharmacokinetics (PK). Patients received cediranib 45 mg/day (n=31) or placebo (n=31) both plus fulvestrant. Demographic/baseline characteristics were well balanced. Patients treated with cediranib had a numerical advantage in PFS (hazard ratio=0.867, P=0.669; median 223 vs. 112 days, respectively) and ORR (22 vs. 8 %, respectively) vs. placebo, although not statistically significant. CBR was 42 % in both arms. The most common adverse events (AEs) in the cediranib arm were diarrhea (68 %), fatigue (61 %) and hypertension (55 %). The incidence of grade ≥ 3 AEs (68 % vs. 32 %), serious AEs (48 % vs. 13 %), discontinuation AEs (39 % vs. 10 %), and cediranib dose reductions/interruptions (74 % vs. 32 %) were higher in the cediranib arm. There was no evidence of a clinically relevant effect of cediranib on fulvestrant PK. Cediranib plus fulvestrant may demonstrate clinical activity in this population, but cediranib 45 mg was not sufficiently well tolerated. Investigation of lower doses of cediranib plus hormonal/chemotherapy could be considered.

  1. The effectiveness of integrated health information technologies across the phases of medication management: a systematic review of randomized controlled trials

    PubMed Central

    Lokker, Cynthia; Handler, Steven M; Dolovich, Lisa R; Holbrook, Anne M; O'Reilly, Daria; Tamblyn, Robyn; Hemens, Brian J; Basu, Runki; Troyan, Sue; Roshanov, Pavel S

    2011-01-01

    Objective The US Agency for Healthcare Research and Quality funded an evidence report to address seven questions on multiple aspects of the effectiveness of medication management information technology (MMIT) and its components (prescribing, order communication, dispensing, administering, and monitoring). Materials and Methods Medline and 11 other databases without language or date limitations to mid-2010. Randomized controlled trials (RCTs) assessing integrated MMIT were selected by two independent reviewers. Reviewers assessed study quality and extracted data. Senior staff checked accuracy. Results Most of the 87 RCTs focused on clinical decision support and computerized provider order entry systems, were performed in hospitals and clinics, included primarily physicians and sometimes nurses but not other health professionals, and studied process changes related to prescribing and monitoring medication. Processes of care improved for prescribing and monitoring mostly in hospital settings, but the few studies measuring clinical outcomes showed small or no improvements. Studies were performed most frequently in the USA (n=63), Europe (n=16), and Canada (n=6). Discussion Many studies had limited description of systems, installations, institutions, and targets of the intervention. Problems with methods and analyses were also found. Few studies addressed order communication, dispensing, or administering, non-physician prescribers or pharmacists and their MMIT tools, or patients and caregivers. Other study methods are also needed to completely understand the effects of MMIT. Conclusions Almost half of MMIT interventions improved the process of care, but few studies measured clinical outcomes. This large body of literature, although instructive, is not uniformly distributed across settings, people, medication phases, or outcomes. PMID:21852412

  2. Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial.

    PubMed

    Hankins, Jane S; McCarville, Mary Beth; Rankine-Mullings, Angela; Reid, Marvin E; Lobo, Clarisse L C; Moura, Patricia G; Ali, Susanna; Soares, Deanne P; Aldred, Karen; Jay, Dennis W; Aygun, Banu; Bennett, John; Kang, Guolian; Goldsmith, Jonathan C; Smeltzer, Matthew P; Boyett, James M; Ware, Russell E

    2015-12-01

    Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart, Lung, and Blood Institute-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ(0) -thalassemia (1), and HbSD (1), median age = 5.4 years (range, 2.7-9.8)]. Because of the slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI = 0-35%) in the hydroxyurea arm and 47% (95% CI = 6-81%) in observation arm at 15 months (P = 0.16). In post hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities when compared with observation (0% vs. 50%, P = 0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (-15.5 vs. +10.2 cm/sec, P = 0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities.

  3. Accurate and efficient calculation of excitation energies with the active-space particle-particle random phase approximation

    NASA Astrophysics Data System (ADS)

    Zhang, Du; Yang, Weitao

    2016-10-01

    An efficient method for calculating excitation energies based on the particle-particle random phase approximation (ppRPA) is presented. Neglecting the contributions from the high-lying virtual states and the low-lying core states leads to the significantly smaller active-space ppRPA matrix while keeping the error to within 0.05 eV from the corresponding full ppRPA excitation energies. The resulting computational cost is significantly reduced and becomes less than the construction of the non-local Fock exchange potential matrix in the self-consistent-field (SCF) procedure. With only a modest number of active orbitals, the original ppRPA singlet-triplet (ST) gaps as well as the low-lying single and double excitation energies can be accurately reproduced at much reduced computational costs, up to 100 times faster than the iterative Davidson diagonalization of the original full ppRPA matrix. For high-lying Rydberg excitations where the Davidson algorithm fails, the computational savings of active-space ppRPA with respect to the direct diagonalization is even more dramatic. The virtues of the underlying full ppRPA combined with the significantly lower computational cost of the active-space approach will significantly expand the applicability of the ppRPA method to calculate excitation energies at a cost of O(K4), with a prefactor much smaller than a single SCF Hartree-Fock (HF)/hybrid functional calculation, thus opening up new possibilities for the quantum mechanical study of excited state electronic structure of large systems.

  4. An interesterified palm olein test meal decreases early-phase postprandial lipemia compared to palm olein: a randomized controlled trial.

    PubMed

    Hall, Wendy L; Brito, Marcela Fiuza; Huang, Junlan; Wood, Lucy V; Filippou, Androulla; Sanders, Thomas A B; Berry, Sarah E E

    2014-09-01

    Palm oil that has been interesterified to produce a higher proportion of palmitic acid (16:0) in the sn-2 position reduces postprandial lipemia in young, normolipidemic men and women, but effects in older subjects with higher fasting triacylglycerol (TAG) concentrations are unknown. We tested the hypothesis that high-fat meals rich in interesterified palm olein (IPO) decrease lipemia and alter plasma lipoprotein fraction composition compared to native palm olein (NPO) in men aged 40-70 years with fasting TAG concentrations ≥1.2 mmol/L. Postprandial changes in plasma lipids following meals containing 75 g fat (NPO and IPO) were compared using a randomized, double-blind crossover design (n = 11). Although there were no significant differences in plasma TAG concentrations between meals over the total 6-h postprandial measurement period, IPO resulted in a decreased plasma TAG response during the first 4 h of the postprandial period (iAUC 1.65 mmol/L h, 95% CI 1.01-2.29) compared to NPO (iAUC 2.33 mmol/L h, 95% CI 1.58-3.07); meal effect P = 0.024. Chylomicron fraction TAG concentrations at 4-6 h were slightly reduced following IPO compared to NPO [NPO-IPO mean difference 0.29 mmol/L (95% CI -0.01-0.59), P = 0.055]. There were no differences in IDL fraction TAG, cholesterol or apolipoprotein B48 concentrations following IPO compared with NPO. In conclusion, consuming a meal containing palm olein with a higher proportion of 16:0 in the sn-2 position decreases postprandial lipemia compared to native palm olein during the early phase of the postprandial period in men with higher than optimal fasting triacylglycerol concentrations.

  5. Preventing Depressive Relapse and Recurrence in Higher Risk Cognitive Therapy Responders: A Randomized Trial of Continuation Phase Cognitive Therapy, Fluoxetine, or Matched Pill Placebo

    PubMed Central

    Jarrett, Robin B.; Minhajuddin, Abu; Gershenfeld, Howard; Friedman, Edward S.; Thase, Michael E.

    2014-01-01

    Context Strategies to improve the course of recurrent major depressive disorder (MDD) have great public health relevance. To reduce the risk of relapse/recurrence after acute phase Cognitive Therapy (CT), a continuation phase model of therapy (C-CT) may improve outcomes. Objectives To test the efficacy of C-CT and fluoxetine (FLX) for relapse prevention in a placebo (PBO) controlled randomized trial and compare the durability of prophylaxis after discontinuation of treatments. Design A sequential, three stage design with: acute phase (all patients received 12 weeks of CT), 8 month experimental phase (responders at higher risk were randomized to C-CT, FLX, or PBO), and 24 months of longitudinal, post-treatment follow-up. Setting Two university-based specialty clinics. Patients 523 adults with recurrent MDD began acute phase CT, of which 241 “higher risk” responders were randomized and 181 subsequently entered the follow-up. Interventions CT responders at higher risk for relapse were randomized to receive 8 months of C-CT (n = 86), FLX (n = 86) or PBO (n = 69). Main Outcome Measures Survival analyses of relapse/recurrence rates, as determined by “blinded” evaluators using DSM-IV criteria and the LIFE interview. Results As predicted, the C-CT or FLX groups were significantly less likely to relapse than the PBO group across 8 months. Relapse/recurrence rates for C-CT and FLX were nearly identical during the 8 months of treatment, although C-CT patients were more likely to accept randomization, stayed in treatment longer, and attended more sessions than those in FLX/PBO. Contrary to prediction, relapse/recurrence rates following the discontinuation of C-CT and FLX did not differ. Conclusions Relapse risk was reduced by both C-CT and FLX in an “enriched” randomization sampling only CT responders. The preventive effects of C-CT were not significantly more ‘durable’ than those of FLX after treatment was stopped, suggesting that some higher risk patients may

  6. Two-dimensional pseudo-random optical phased array based on tandem optical injection locking of vertical cavity surface emitting lasers.

    PubMed

    Sayyah, Keyvan; Efimov, Oleg; Patterson, Pamela; Schaffner, James; White, Carson; Seurin, Jean-Francois; Xu, Guoyang; Miglo, Alexander

    2015-07-27

    We demonstrate, both theoretically and experimentally, a pseudo-random, two-dimensional optical phased array (OPA) concept based on tandem injection locking of 64-element vertical cavity surface emitting laser (VCSEL) arrays. A low cavity-Q VCSEL design resulted in an injection locking optical power of less than 1 μW per VCSEL, providing large OPA scaling potential. Tandem injection locking of two VCSEL arrays resulted in measured controllable optical phase change of 0-1.6π. A high quality beam formed with suppressed grating lobes due to the pseudo-random array design was demonstrated with performance close to simulated results. A preliminary 2.2° x 1.2° beam steering example using the tandem arrays was also demonstrated.

  7. Defect-mediated relaxation in the random tiling phase of a binary mixture: Birth, death and mobility of an atomic zipper

    SciTech Connect

    Tondl, Elisabeth; Ramsay, Malcolm; Harrowell, Peter; Widmer-Cooper, Asaph

    2014-03-14

    This paper describes the mechanism of defect-mediated relaxation in a dodecagonal square-triangle random tiling phase exhibited by a simulated binary mixture of soft discs in 2D. We examine the internal transitions within the elementary mobile defect (christened the “zipper”) that allow it to move, as well as the mechanisms by which the zipper is created and annihilated. The structural relaxation of the random tiling phase is quantified and we show that this relaxation is well described by a model based on the distribution of waiting times for each atom to be visited by the diffusing zipper. This system, representing one of the few instances where a well defined mobile defect is capable of structural relaxation, can provide a valuable test case for general theories of relaxation in complex and disordered materials.

  8. Tensor hypercontracted ppRPA: Reducing the cost of the particle-particle random phase approximation from O(r 6) to O(r 4)

    NASA Astrophysics Data System (ADS)

    Shenvi, Neil; van Aggelen, Helen; Yang, Yang; Yang, Weitao

    2014-07-01

    In recent years, interest in the random-phase approximation (RPA) has grown rapidly. At the same time, tensor hypercontraction has emerged as an intriguing method to reduce the computational cost of electronic structure algorithms. In this paper, we combine the particle-particle random phase approximation with tensor hypercontraction to produce the tensor-hypercontracted particle-particle RPA (THC-ppRPA) algorithm. Unlike previous implementations of ppRPA which scale as O(r6), the THC-ppRPA algorithm scales asymptotically as only O(r4), albeit with a much larger prefactor than the traditional algorithm. We apply THC-ppRPA to several model systems and show that it yields the same results as traditional ppRPA to within mH accuracy. Our method opens the door to the development of post-Kohn Sham functionals based on ppRPA without the excessive asymptotic cost of traditional ppRPA implementations.

  9. Defect-mediated relaxation in the random tiling phase of a binary mixture: Birth, death and mobility of an atomic zipper

    NASA Astrophysics Data System (ADS)

    Tondl, Elisabeth; Ramsay, Malcolm; Harrowell, Peter; Widmer-Cooper, Asaph

    2014-03-01

    This paper describes the mechanism of defect-mediated relaxation in a dodecagonal square-triangle random tiling phase exhibited by a simulated binary mixture of soft discs in 2D. We examine the internal transitions within the elementary mobile defect (christened the "zipper") that allow it to move, as well as the mechanisms by which the zipper is created and annihilated. The structural relaxation of the random tiling phase is quantified and we show that this relaxation is well described by a model based on the distribution of waiting times for each atom to be visited by the diffusing zipper. This system, representing one of the few instances where a well defined mobile defect is capable of structural relaxation, can provide a valuable test case for general theories of relaxation in complex and disordered materials.

  10. Multicenter Randomized Controlled Trial on Duration of Therapy for Thrombosis in Children and Young Adults (Kids-DOTT): Pilot/Feasibility Phase Findings

    PubMed Central

    Goldenberg, N.A.; Abshire, T.; Blatchford, P.J.; Fenton, L.Z.; Halperin, J.L.; Hiatt, W.R.; Kessler, C.M.; Kittelson, J.M.; Manco-Johnson, M.J.; Spyropoulos, A.C.; Steg, P.G.; Stence, N.V.; Turpie, A.G.G.; Schulman, S.

    2015-01-01

    BACKGROUND Randomized controlled trials (RCTs) in pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. METHODS Kids-DOTT is a multicenter RCT investigating non-inferiority of a 6-week (shortened) vs. 3-month (conventional) duration of anticoagulation in patients <21 years old with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically-relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded endpoint, parallel-cohort RCT design. RESULTS No eligibility violations or randomization errors occurred. Of enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in pre-specified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Inter-observer agreement between local vs. blinded central determination of venous occlusion by imaging at 6 weeks post-diagnosis was strong (κ-statistic=0.75; 95% confidence interval [CI] 0.48–1.0). Primary efficacy and safety event rates were 3.3% (95% CI 0.3–11.5%) and 1.4% (0.03–7.4%). CONCLUSIONS The P/F phase of Kids-DOTT has demonstrated validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention, and endpoint rates to inform the fully-powered RCT. PMID:26118944

  11. Blinded sample size recalculation in multicentre trials with normally distributed outcome.

    PubMed

    Jensen, Katrin; Kieser, Meinhard

    2010-06-01

    The internal pilot study design enables to estimate nuisance parameters required for sample size calculation on the basis of data accumulated in an ongoing trial. By this, misspecifications made when determining the sample size in the planning phase can be corrected employing updated knowledge. According to regulatory guidelines, blindness of all personnel involved in the trial has to be preserved and the specified type I error rate has to be controlled when the internal pilot study design is applied. Especially in the late phase of drug development, most clinical studies are run in more than one centre. In these multicentre trials, one may have to deal with an unequal distribution of the patient numbers among the centres. Depending on the type of the analysis (weighted or unweighted), unequal centre sample sizes may lead to a substantial loss of power. Like the variance, the magnitude of imbalance is difficult to predict in the planning phase. We propose a blinded sample size recalculation procedure for the internal pilot study design in multicentre trials with normally distributed outcome and two balanced treatment groups that are analysed applying the weighted or the unweighted approach. The method addresses both uncertainty with respect to the variance of the endpoint and the extent of disparity of the centre sample sizes. The actual type I error rate as well as the expected power and sample size of the procedure is investigated in simulation studies. For the weighted analysis as well as for the unweighted analysis, the maximal type I error rate was not or only minimally exceeded. Furthermore, application of the proposed procedure led to an expected power that achieves the specified value in many cases and is throughout very close to it.

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

    DTIC Science & Technology

    2015-09-01

    1 Award Number: W81XWH-10-1-0699 TITLE: Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural...WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy 5a. CONTRACT NUMBER 5b...malignant pleural mesothelioma (MPM), and is a rational target for immunotherapy. We have developed a vaccine comprised of four WT1 heteroclitic

  13. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    DTIC Science & Technology

    2012-09-01

    DATES COVERED (From - To) 4. TITLE AND SUBTITLE A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti- PSMA Monoclonal Antibody J591 5a. CONTRACT...to proceed with enrollment. 15. SUBJECT TERMS Prostate cancer, PSA, PSMA , monoclonal antibody, radioimmunotherapy 16. SECURITY CLASSIFICATION OF...micrometastases that may be targeted with radioimmunotherapy. Prostate specific membrane antigen ( PSMA ) is the single, most well-established, highly restricted

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

    DTIC Science & Technology

    2013-09-01

    Analog Peptides Derived from WT1 Oncoprotein Induces T Cell Responses in Patients with Complete Remission from Acute Myeloid Leukemia (AML), Blood 2010...10-1-0699 TITLE: Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after...vaccine comprised of four WT1 heteroclitic peptides that are given together with Montanide and GM- CSF as immunologic adjuvants. This WT1 vaccine was

  15. Properties of the random-singlet phase: From the disordered Heisenberg chain to an amorphous valence-bond solid

    NASA Astrophysics Data System (ADS)

    Shu, Yu-Rong; Yao, Dao-Xin; Ke, Chih-Wei; Lin, Yu-Cheng; Sandvik, Anders W.

    2016-11-01

    We use a strong-disorder renormalization group (SDRG) method and ground-state quantum Monte Carlo (QMC) simulations to study S =1 /2 spin chains with random couplings, calculating disorder-averaged spin and dimer correlations. The QMC simulations demonstrate logarithmic corrections to the power-law decaying correlations obtained with the SDRG scheme. The same asymptotic forms apply both for systems with standard Heisenberg exchange and for certain multispin couplings leading to spontaneous dimerization in the clean system. We show that the logarithmic corrections arise in the valence-bond (singlet pair) basis from a contribution that cannot be generated by the SDRG scheme. In the model with multispin couplings, where the clean system dimerizes spontaneously, random singlets form between spinons localized at domain walls in the presence of disorder. This amorphous valence-bond solid is asymptotically a random-singlet state and only differs from the random-exchange Heisenberg chain in its short-distance properties.

  16. Raising the bar for enthusiasm when looking at results of randomized phase II trials—the case of sunitinib in small-cell lung cancer

    PubMed Central

    Di Maio, Massimo; Bironzo, Paolo

    2016-01-01

    With the advent of targeted agents, randomized phase II trials designed with explicit comparative intent, to allow a better interpretation of the results obtained with experimental treatment, have become a common approach for anti-cancer drug development. In the Cancer and Leukemia Group B (CALGB) 30504 randomized phase II trial, patients with extensive-stage small-cell lung cancer (SCLC), without progression after four to six cycles of standard chemotherapy with cisplatin or carboplatin plus etoposide, were randomized to sunitinib or placebo, until disease progression. Primary endpoint of the study was progression-free survival (PFS), and the results were formally positive [hazard ratio (HR) 0.62; one-sided P=0.02]. However, the prognosis of patients with extensive-stage SCLC is particularly bad, and even a relevant relative benefit (i.e., an encouraging HR) will likely correspond to a debatable absolute benefit: the difference in median PFS between patients treated with sunitinib and patients assigned to control arm was slightly higher than 1.5 months. Is this difference in median PFS big enough to predict a clinically relevant benefit in overall survival? Unfortunately, we do not know. From a “clinical” point of view, is this small absolute improvement in PFS relevant enough to further invest in the strategy? Probably not, also considering the absence of known predictive factors. If the results of the phase II trial had been really promising, the subsequent phase III study should have been promptly conducted, but this was not the case. It seems that, this time, the bar for enthusiasm was already raised in the phase II setting. PMID:26958498

  17. Effect of intravenous β-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial

    PubMed Central

    Smith, Fang Gao; Perkins, Gavin D; Gates, Simon; Young, Duncan; McAuley, Daniel F; Tunnicliffe, William; Khan, Zahid; Lamb, Sarah E

    2012-01-01

    Summary Background In a previous randomised controlled phase 2 trial, intravenous infusion of salbutamol for up to 7 days in patients with acute respiratory distress syndrome (ARDS) reduced extravascular lung water and plateau airway pressure. We assessed the effects of this intervention on mortality in patients with ARDS. Methods We did a multicentre, placebo-controlled, parallel-group, randomised trial at 46 UK intensive-care units between December, 2006, and March, 2010. Intubated and mechanically ventilated patients (aged ≥16 years) within 72 h of ARDS onset were randomly assigned to receive either salbutamol (15 μg/kg ideal bodyweight per h) or placebo for up to 7 days. Randomisation was done by a central telephone or web-based randomisation service with minmisation by centre, pressure of arterial oxygen to fractional inspired oxygen concentration (PaO2/FIO2) ratio, and age. All participants, caregivers, and investigators were masked to group allocation. The primary outcome was death within 28 days of randomisation. Analysis was by intention-to-treat. This trial is registered, ISRCTN38366450 and EudraCT number 2006-002647-86. Findings We randomly assigned 162 patients to the salbutamol group and 164 to the placebo group. One patient in each group withdrew consent. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality (55 [34%] of 161 patients died in the salbutamol group vs 38 (23%) of 163 in the placebo group; risk ratio [RR] 1·47, 95% CI 1·03–2·08). Interpretation Treatment with intravenous salbutamol early in the course of ARDS was poorly tolerated. Treatment is unlikely to be beneficial, and could worsen outcomes. Routine use of β-2 agonist treatment in ventilated patients with this disorder cannot be recommended. Funding UK Medical Research Council, UK Department of Health, UK Intensive Care Foundation. PMID:22166903

  18. Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre, Single-Blind Randomised Control Pilot Trial

    PubMed Central

    Hollands, Kristen L.; Pelton, Trudy A.; Wimperis, Andrew; Whitham, Diane; Tan, Wei; Jowett, Sue; Sackley, Catherine M.; Wing, Alan M.; Tyson, Sarah F.; Mathias, Jonathan; Hensman, Marianne; van Vliet, Paulette M.

    2015-01-01

    Objectives Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. Design This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services Participants Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments Intervention Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks. Main outcome measures: Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up. Results Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms. Conclusions Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Trial Registration Clinicaltrials.gov NCT01600391 PMID:26445137

  19. Phase Transitions in Disordered Systems: The Example of the Random-Field Ising Model in Four Dimensions.

    PubMed

    Fytas, Nikolaos G; Martín-Mayor, Víctor; Picco, Marco; Sourlas, Nicolas

    2016-06-03

    By performing a high-statistics simulation of the D=4 random-field Ising model at zero temperature for different shapes of the random-field distribution, we show that the model is ruled by a single universality class. We compute to a high accuracy the complete set of critical exponents for this class, including the correction-to-scaling exponent. Our results indicate that in four dimensions (i) dimensional reduction as predicted by the perturbative renormalization group does not hold and (ii) three independent critical exponents are needed to describe the transition.

  20. Phase Transitions in Disordered Systems: The Example of the Random-Field Ising Model in Four Dimensions

    NASA Astrophysics Data System (ADS)

    Fytas, Nikolaos G.; Martín-Mayor, Víctor; Picco, Marco; Sourlas, Nicolas

    2016-06-01

    By performing a high-statistics simulation of the D =4 random-field Ising model at zero temperature for different shapes of the random-field distribution, we show that the model is ruled by a single universality class. We compute to a high accuracy the complete set of critical exponents for this class, including the correction-to-scaling exponent. Our results indicate that in four dimensions (i) dimensional reduction as predicted by the perturbative renormalization group does not hold and (ii) three independent critical exponents are needed to describe the transition.

  1. A developmental hypothesis to explain the multicentricity of breast cancer

    PubMed Central

    Sharpe, C R

    1998-01-01

    In this article the author proposes that the multicentricity of breast cancer might be explained by a developmental hypothesis. Genetic alterations ("hits") occurring in epithelial stem cells during the development of the breast may be transmitted to populations of daughter cells during growth. As a result, areas of the breast may be predisposed to malignant transformation with the occurrence of further genetic hits. Areas with the same predisposition should be anatomically connected, and earlier hits during breast development should result in larger areas of predisposition. The multicentricity of breast cancer would be explained if multiple lesions--monoclonal for the predisposing genetic hit and polyclonal for subsequent hits--developed within a predisposed area. Multiple lesions arising from the spread of disease by extension would be expected to share many genetic hits. The author discusses the implications that further evidence supporting the developmental hypothesis would have for the prevention and treatment of breast cancer. PMID:9679488

  2. Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies

    PubMed Central

    Burri, Christian; Yeramian, Patrick D.; Merolle, Ada; Serge, Kazadi Kyanza; Mpanya, Alain; Lutumba, Pascal; Mesu, Victor Kande Betu Ku; Lubaki, Jean-Pierre Fina; Mpoto, Alfred Mpoo; Thompson, Mark; Munungu, Blaise Fungula; Josenando, Théophilo; Bernhard, Sonja C.; Olson, Carol A.; Blum, Johannes; Tidwell, Richard R.; Pohlig, Gabriele

    2016-01-01

    Background Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT. Methods The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent. Findings/Conclusion Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3. PMID:26881924

  3. The Effect of Disorder on the Free-Energy for the Random Walk Pinning Model: Smoothing of the Phase Transition and Low Temperature Asymptotics

    NASA Astrophysics Data System (ADS)

    Berger, Quentin; Lacoin, Hubert

    2011-01-01

    We consider the continuous time version of the Random Walk Pinning Model (RWPM), studied in (Berger and Toninelli (Electron. J. Probab., to appear) and Birkner and Sun (Ann. Inst. Henri Poincaré Probab. Stat. 46:414-441, 2010; arXiv:0912.1663). Given a fixed realization of a random walk Y on ℤ d with jump rate ρ (that plays the role of the random medium), we modify the law of a random walk X on ℤ d with jump rate 1 by reweighting the paths, giving an energy reward proportional to the intersection time Lt(X,Y)=int0t {1}_{Xs=Ys} {d}s: the weight of the path under the new measure is exp ( βL t ( X, Y)), β∈ℝ. As β increases, the system exhibits a delocalization/localization transition: there is a critical value β c , such that if β> β c the two walks stick together for almost-all Y realizations. A natural question is that of disorder relevance, that is whether the quenched and annealed systems have the same behavior. In this paper we investigate how the disorder modifies the shape of the free energy curve: (1) We prove that, in dimension d≥3, the presence of disorder makes the phase transition at least of second order. This, in dimension d≥4, contrasts with the fact that the phase transition of the annealed system is of first order. (2) In any dimension, we prove that disorder modifies the low temperature asymptotic of the free energy.

  4. Phase-coherent elastic scattering of electromagnetic waves from a random array of resonant dielectric ridges on a dielectric substrate: Weak roughness limit

    NASA Astrophysics Data System (ADS)

    Danila, B.; McGurn, A. R.

    2005-03-01

    A theoretical discussion is given of the diffuse scattering of p -polarized electromagnetic waves from a vacuum-dielectric interface characterized by a one-dimensional disorder in the form of parallel, Gaussian shaped, dielectric ridges positioned at random on a planar semi-infinite dielectric substrate. The parameters of the surface roughness are chosen so that the surface is characterized as weakly rough with a low ridge concentration. The emphasis is on phase coherent features in the speckle pattern of light scattered from the surface. These features are determined from the intensity-intensity correlation function of the speckle pattern and are studied as functions of the frequency of light for frequencies near the dielectric frequency resonances of the ridge material. In the first part of the study, the ridges on the substrate are taken to be identical, made from either GaAs, NaF, or ZnS. The substrate for all cases is CdS. In a second set of studies, the heights and widths of the ridges are statistically distributed. The effects of these different types of randomness on the scattering from the random array of dielectric ridges is determined near the dielectric resonance frequency of the ridge material. The work presented is an extension of studies [A. B. McGurn and R. M. Fitzgerald, Phys. Rev. B 65, 155414 (2002)] that originally treated only the differential reflection coefficient of the diffuse scattering of light (not speckle correlation functions) from a system of identical ridges. The object of the present work is to demonstrate the effects of the dielectric frequency resonances of the ridge materials on the phase coherent features found in the speckle patterns of the diffusely scattered light. The dielectric frequency resonances are shown to enhance the observation of the weak localization of electromagnetic surface waves at the random interface. The frequencies treated in this work are in the infrared. Previous weak localization studies have

  5. Promoting state health department evidence-based cancer and chronic disease prevention: a multi-phase dissemination study with a cluster randomized trial component

    PubMed Central

    2013-01-01

    Background Cancer and other chronic diseases reduce quality and length of life and productivity, and represent a significant financial burden to society. Evidence-based public health approaches to prevent cancer and other chronic diseases have been identified in recent decades and have the potential for high impact. Yet, barriers to implement prevention approaches persist as a result of multiple factors including lack of organizational support, limited resources, competing emerging priorities and crises, and limited skill among the public health workforce. The purpose of this study is to learn how best to promote the adoption of evidence based public health practice related to chronic disease prevention. Methods/design This paper describes the methods for a multi-phase dissemination study with a cluster randomized trial component that will evaluate the dissemination of public health knowledge about evidence-based prevention of cancer and other chronic diseases. Phase one involves development of measures of practitioner views on and organizational supports for evidence-based public health and data collection using a national online survey involving state health department chronic disease practitioners. In phase two, a cluster randomized trial design will be conducted to test receptivity and usefulness of dissemination strategies directed toward state health department chronic disease practitioners to enhance capacity and organizational support for evidence-based chronic disease prevention. Twelve state health department chronic disease units will be randomly selected and assigned to intervention or control. State health department staff and the university-based study team will jointly identify, refine, and select dissemination strategies within intervention units. Intervention (dissemination) strategies may include multi-day in-person training workshops, electronic information exchange modalities, and remote technical assistance. Evaluation methods include pre

  6. Communication: An effective linear-scaling atomic-orbital reformulation of the random-phase approximation using a contracted double-Laplace transformation

    SciTech Connect

    Schurkus, Henry F.; Ochsenfeld, Christian

    2016-01-21

    An atomic-orbital (AO) reformulation of the random-phase approximation (RPA) correlation energy is presented allowing to reduce the steep computational scaling to linear, so that large systems can be studied on simple desktop computers with fully numerically controlled accuracy. Our AO-RPA formulation introduces a contracted double-Laplace transform and employs the overlap-metric resolution-of-the-identity. First timings of our pilot code illustrate the reduced scaling with systems comprising up to 1262 atoms and 10 090 basis functions. .

  7. Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia.

    PubMed

    Roboz, Gail J; Montesinos, Pau; Selleslag, Dominik; Wei, Andrew; Jang, Jun-Ho; Falantes, Jose; Voso, Maria T; Sayar, Hamid; Porkka, Kimmo; Marlton, Paula; Almeida, Antonio; Mohan, Sanjay; Ravandi, Farhad; Garcia-Manero, Guillermo; Skikne, Barry; Kantarjian, Hagop

    2016-02-01

    Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML.

  8. Investigation of thermal resistance and power consumption in Ga-doped indium oxide (In{sub 2}O{sub 3}) nanowire phase change random access memory

    SciTech Connect

    Jin, Bo; Lee, Jeong-Soo E-mail: ljs6951@postech.ac.kr; Lim, Taekyung; Ju, Sanghyun; Latypov, Marat I.; Pi, Dong-Hai; Seop Kim, Hyoung; Meyyappan, M. E-mail: ljs6951@postech.ac.kr

    2014-03-10

    The resistance stability and thermal resistance of phase change memory devices using ∼40 nm diameter Ga-doped In{sub 2}O{sub 3} nanowires (Ga:In{sub 2}O{sub 3} NW) with different Ga-doping concentrations have been investigated. The estimated resistance stability (R(t)/R{sub 0} ratio) improves with higher Ga concentration and is dependent on annealing temperature. The extracted thermal resistance (R{sub th}) increases with higher Ga-concentration and thus the power consumption can be reduced by ∼90% for the 11.5% Ga:In{sub 2}O{sub 3} NW, compared to the 2.1% Ga:In{sub 2}O{sub 3} NW. The excellent characteristics of Ga-doped In{sub 2}O{sub 3} nanowire devices offer an avenue to develop low power and reliable phase change random access memory applications.

  9. Enhanced light out-coupling of OLEDs with low haze by inserting randomly dispersed nanopillar arrays formed by lateral phase separation of polymer blends.

    PubMed

    Lee, Cholho; Kim, Jang-Joo

    2013-11-25

    A simple and efficient method to fabricate light extraction layers is demonstrated by utilizing the phase separation of two polymer blends to enhance the light out-coupling efficiency of OLEDs with low haze. Polystyrene and poly(methyl methacrylate) dissolved in tetrahydrofuran are mixed and spin-coated over ITO-coated glass substrates. Nanopores and nanopillar arrays are formed through lateral phase separation of the polymer blend. The shape, size, and distribution of the patterns can be controlled through changes in the composition and thickness of the coated polymer blends. Phosphorescent OLEDs are fabricated using randomly dispersed nanopillar arrays as light extraction layers and they show a 24% enhancement in external quantum efficiency with a Lambertian emission pattern, no spectrum dependence on viewing angles, and only a small increment in the haze. With these advantages, this newly developed method can be adapted to be used for large-area, flexible substrates for lighting and display applications.

  10. Phase IIB Randomized Study of Topical Difluoromethylornithine and Topical Diclofenac on Sun-Damaged Skin of the Forearm.

    PubMed

    Jeter, Joanne M; Curiel-Lewandrowski, Clara; Stratton, Steven P; Myrdal, Paul B; Warneke, James A; Einspahr, Janine G; Bartels, Hubert G; Yozwiak, Michael; Bermudez, Yira; Hu, Chengcheng; Bartels, Peter; Alberts, David S

    2016-02-01

    Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventive efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin. Individuals with visible cutaneous sun damage were eligible. Subjects were randomized to one of the three groups: topical DFMO applied twice daily, topical diclofenac applied daily, or DFMO plus diclofenac. The treatment was limited to an area on the left forearm, and the duration of use was 90 days. We hypothesized that combination therapy would have increased efficacy compared with single-agent therapy. The primary outcome was change in karyometric average nuclear abnormality (ANA) in the treated skin. Individuals assessing the biomarkers were blinded regarding the treatment for each subject. A total of 156 subjects were randomized; 144 had baseline and end-of-study biopsies, and 136 subjects completed the study. The ANA unexpectedly increased for all groups, with higher values correlating with clinical cutaneous inflammation. Nearly all of the adverse events were local cutaneous effects. One subject had cutaneous toxicity that required treatment discontinuation. Significantly more adverse events were seen in the groups taking diclofenac. Overall, the study indicated that the addition of topical DFMO to topical diclofenac did not enhance its activity. Both agents caused inflammation on a cellular and clinical level, which may have confounded the measurement of chemopreventive effects. More significant effects may be observed in subjects with greater baseline cutaneous damage.

  11. Relationship between clustering and algorithmic phase transitions in the random k-XORSAT model and its NP-complete extensions

    NASA Astrophysics Data System (ADS)

    Altarelli, F.; Monasson, R.; Zamponi, F.

    2008-01-01

    We study the performances of stochastic heuristic search algorithms on Uniquely Extendible Constraint Satisfaction Problems with random inputs. We show that, for any heuristic preserving the Poissonian nature of the underlying instance, the (heuristic-dependent) largest ratio αa of constraints per variables for which a search algorithm is likely to find solutions is smaller than the critical ratio αd above which solutions are clustered and highly correlated. In addition we show that the clustering ratio can be reached when the number k of variables per constraints goes to infinity by the so-called Generalized Unit Clause heuristic.

  12. Ising spins on randomly multi-branched Husimi square lattice: Thermodynamics and phase transition in cross-dimensional range

    NASA Astrophysics Data System (ADS)

    Huang, Ran

    2016-10-01

    An inhomogeneous random recursive lattice is constructed from the multi-branched Husimi square lattice. The number of repeating units connected on one vertex is randomly set to be 2 or 3 with a fixed ratio P2 or P3 with P2 +P3 = 1. The lattice is designed to describe complex thermodynamic systems with variable coordinating neighbors, e.g. the asymmetric range around the surface of a bulk system. Classical ferromagnetic spin-1 Ising model is solved on the lattice to achieve an annealed solution via the local exact calculation technique. The model exhibits distinct spontaneous magnetization similar to the deterministic system, with however rigorous thermal fluctuations and significant singularities on the entropy behavior around the critical temperature, indicating a complex superheating frustration in the cross-dimensional range induced by the stochasticity. The critical temperature was found to be exponentially correlated to the structural ratio P with the coefficient fitted as 0.53187, while the ground state energy presents linear correlation to P, implying a well-defined average property according to the structural ratio.

  13. Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

    SciTech Connect

    Berk, Lawrence . E-mail: Berklb@moffitt.usf.edu; Berkey, Brian; Rich, Tyvin; Hrushesky, William; Gallagher, Michael; Kudrimoti, Mahesh; McGarry, Ronald C.; Suh, John; Mehta, Minesh

    2007-07-01

    Purpose: To determine if high-dose melatonin for Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Class 2 patients with brain metastases improved survival over historical controls, and to determine if the time of day melatonin was given affected its toxicity or efficacy. RTOG 0119 was a phase II randomized trial for this group of patients. Methods and Materials: RTOG RPA Class 2 patients with brain metastases were randomized to 20 mg of melatonin, given either in the morning (8-9 AM) or in the evening (8-9 PM). All patients received radiation therapy (30 Gy in 10 fractions) in the afternoon. Melatonin was continued until neurologic deterioration or death. The primary endpoint was overall survival time. Neurologic deterioration, as reflected by the Mini-Mental Status Examination, was also measured. Results: Neither of the randomized groups had survival distributions that differed significantly from the historic controls of patients treated with whole-brain radiotherapy. The median survivals of the morning and evening melatonin treatments were 3.4 and 2.8 months, while the RTOG historical control survival was 4.1 months. Conclusions: High-dose melatonin did not show any beneficial effect in this group of patients.

  14. Bioengineered Temporomandibular Joint Disk Implants: Study Protocol for a Two-Phase Exploratory Randomized Preclinical Pilot Trial in 18 Black Merino Sheep (TEMPOJIMS)

    PubMed Central

    Monje, Florencio Gil; González-García, Raúl; Little, Christopher B; Mónico, Lisete; Pinho, Mário; Santos, Fábio Abade; Carrapiço, Belmira; Gonçalves, Sandra Cavaco; Morouço, Pedro; Alves, Nuno; Moura, Carla; Wang, Yadong; Jeffries, Eric; Gao, Jin; Sousa, Rita; Neto, Lia Lucas; Caldeira, Daniel; Salvado, Francisco

    2017-01-01

    Background Preclinical trials are essential to test efficacious options to substitute the temporomandibular joint (TMJ) disk. The contemporary absence of an ideal treatment for patients with severe TMJ disorders can be related to difficulties concerning the appropriate study design to conduct preclinical trials in the TMJ field. These difficulties can be associated with the use of heterogeneous animal models, the use of the contralateral TMJ as control, the absence of rigorous randomized controlled preclinical trials with blinded outcomes assessors, and difficulties involving multidisciplinary teams. Objective This study aims to develop a new, reproducible, and effective study design for preclinical research in the TMJ domain, obtaining rigorous data related to (1) identify the impact of bilateral discectomy in black Merino sheep, (2) identify the impact of bilateral discopexy in black Merino sheep, and (3) identify the impact of three different bioengineering TMJ discs in black Merino sheep. Methods A two-phase exploratory randomized controlled preclinical trial with blinded outcomes is proposed. In the first phase, nine sheep are randomized into three different surgical bilateral procedures: bilateral discectomy, bilateral discopexy, and sham surgery. In the second phase, nine sheep are randomized to bilaterally test three different TMJ bioengineering disk implants. The primary outcome is the histological gradation of TMJ. Secondary outcomes are imaging changes, absolute masticatory time, ruminant time per cycle, ruminant kinetics, ruminant area, and sheep weight. Results Previous preclinical studies in this field have used the contralateral unoperated side as a control, different animal models ranging from mice to a canine model, with nonrandomized, nonblinded and uncontrolled study designs and limited outcomes measures. The main goal of this exploratory preclinical protocol is to set a new standard for future preclinical trials in oromaxillofacial surgery

  15. Tensor hypercontracted ppRPA: Reducing the cost of the particle-particle random phase approximation from O(r {sup 6}) to O(r {sup 4})

    SciTech Connect

    Shenvi, Neil; Yang, Yang; Yang, Weitao; Aggelen, Helen van

    2014-07-14

    In recent years, interest in the random-phase approximation (RPA) has grown rapidly. At the same time, tensor hypercontraction has emerged as an intriguing method to reduce the computational cost of electronic structure algorithms. In this paper, we combine the particle-particle random phase approximation with tensor hypercontraction to produce the tensor-hypercontracted particle-particle RPA (THC-ppRPA) algorithm. Unlike previous implementations of ppRPA which scale as O(r{sup 6}), the THC-ppRPA algorithm scales asymptotically as only O(r{sup 4}), albeit with a much larger prefactor than the traditional algorithm. We apply THC-ppRPA to several model systems and show that it yields the same results as traditional ppRPA to within mH accuracy. Our method opens the door to the development of post-Kohn Sham functionals based on ppRPA without the excessive asymptotic cost of traditional ppRPA implementations.

  16. Zoledronic Acid for Prevention of Bone Loss in Patients Receiving Primary Therapy for Lymphomas: A Prospective, Randomized Controlled Phase III Trial

    PubMed Central

    Westin, Jason R.; Thompson, Michael A.; Cataldo, Vince D.; Fayad, Luis E.; Fowler, Nathan; Fanale, Michelle A.; Neelapu, Saatva; Samaniego, Felipe; Romaguera, Jorge; Shah, Jatin; McLaughlin, Peter; Pro, Barbara; Kwak, Larry W.; Sanjorjo, Perpetua; Murphy, William A.; Jimenez, Camillo; Toth, Bela; Dong, Wenli; Hagemeister, Fredrick B.

    2013-01-01

    In patients with newly diagnosed lymphoma, low bone mineral density (BMD) is common at diagnosis and worsens with therapy. Our randomized phase III trial demonstrates that 2 doses of zoledronic acid (ZA) and supplementation with calcium and vitamin D effectively prevent further bone loss. Background Patients with lymphoma are at risk of development of bone mineral density (BMD) loss from therapy with high-dose corticosteroids and alkylating agents. Zoledronic acid (ZA), a bisphosphonate, may prevent this complication of therapy. We evaluated the effect of ZA on the change in BMD and surrogate biomarkers in patients with lymphoma receiving initial chemotherapy. Patients and Methods Our phase III trial randomized 74 patients with newly diagnosed lymphoma and a baseline BMD of ≥ −2.0 to receive oral calcium and vitamin D daily with or without ZA at enrollment and at 6 months after enrollment. BMD was evaluated at baseline and 1 year after enrollment. Secondary biomarker endpoints were collected at baseline and at 3, 6, 9, and 12 months after enrollment. Results Forty-three percent of patients had baseline osteopenia. Fifty-three patients were evaluable for response: 24 received ZA and had stable BMD during the observation period, whereas 29 patients in the control group had decreased BMD (P < .05 at lumbar spine and bilateral femoral neck). Twenty-one randomized patients were not evaluable for response because of lymphoma progression or death, withdrawn consent/incomplete testing, or ineligibility. Bone biomarkers were higher in the control group at all intervals after treatment (P < .001). No fractures or intervention-related toxicities were observed during this trial. Conclusions Newly diagnosed patients with lymphoma are at risk of low BMD, which may worsen with therapy. Treatment with ZA effectively stabilizes BMD and prevents bone loss. Our data suggest that BMD testing and prophylaxis should be considered as an early intervention for a preventable problem

  17. The Public Repository of Xenografts (ProXe) enables discovery and randomized phase II-like trials in mice

    PubMed Central

    Townsend, Elizabeth C.; Murakami, Mark A.; Christodoulou, Alexandra; Christie, Amanda L.; Köster, Johannes; DeSouza, Tiffany A.; Morgan, Elizabeth A.; Kallgren, Scott P.; Liu, Huiyun; Wu, Shuo-Chieh; Plana, Olivia; Montero, Joan; Stevenson, Kristen E.; Rao, Prakash; Vadhi, Raga; Andreeff, Michael; Armand, Philippe; Ballen, Karen K.; Barzaghi-Rinaudo, Patrizia; Cahill, Sarah; Clark, Rachael A.; Cooke, Vesselina G.; Davids, Matthew S.; DeAngelo, Daniel J.; Dorfman, David M.; Eaton, Hilary; Ebert, Benjamin L.; Etchin, Julia; Firestone, Brant; Fisher, David C.; Freedman, Arnold S.; Galinsky, Ilene A.; Gao, Hui; Garcia, Jacqueline S.; Garnache-Ottou, Francine; Graubert, Timothy A.; Gutierrez, Alejandro; Halilovic, Ensar; Harris, Marian H.; Herbert, Zachary T.; Horwitz, Steven M.; Inghirami, Giorgio; Intlekoffer, Andrew M.; Ito, Moriko; Izraeli, Shai; Jacobsen, Eric D.; Jacobson, Caron A.; Jeay, Sébastien; Jeremias, Irmela; Kelliher, Michelle A.; Koch, Raphael; Konopleva, Marina; Kopp, Nadja; Kornblau, Steven M.; Kung, Andrew L.; Kupper, Thomas S.; LaBoeuf, Nicole; LaCasce, Ann S.; Lees, Emma; Li, Loretta S.; Look, A. Thomas; Murakami, Masato; Muschen, Markus; Neuberg, Donna; Ng, Samuel Y.; Odejide, Oreofe O.; Orkin, Stuart H.; Paquette, Rachel R.; Place, Andrew E.; Roderick, Justine E.; Ryan, Jeremy A.; Sallan, Stephen E.; Shoji, Brent; Silverman, Lewis B.; Soiffer, Robert J.; Steensma, David P.; Stegmaier, Kimberly; Stone, Richard M.; Tamburini, Jerome; Thorner, Aaron R.; van Hummelen, Paul; Wadleigh, Martha; Wiesmann, Marion; Weng, Andrew P.; Wuerthner, Jens U.; Williams, David A.; Wollison, Bruce M.; Lane, Andrew A.; Letai, Anthony; Bertagnolli, Monica M.; Ritz, Jerome; Brown, Myles; Long, Henry; Aster, Jon C.; Shipp, Margaret A.; Griffin, James D.; Weinstock, David M.

    2016-01-01

    Summary Over 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publically available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment called the Public Repository of Xenografts (PRoXe; www.proxe.org). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional and proteomic biomarkers in both treatment-naïve and relapsed/refractory disease. PMID:27070704

  18. Effect of Borago Officinalis Extract on Moderate Persistent Asthma: A Phase two Randomized, Double Blind, Placebo-Controlled Clinical Trial

    PubMed Central

    Khashkhashi Moghaddam, Sara; Saeedi, Parisa; Ghaffari, Sakineh

    2016-01-01

    Background: Borago officinalis and its derivatives are used in folk medicine to treat asthma because of its special effect on allergic disorders. It suppresses the tumor necrosis factor-alpha (TNF-alpha) and delivers gamma-linolenic acid. The objective of this clinical trial was to determine the effect of Borago officinalis on clinical and physiological findings in moderate persistent asthma. Materials and Methods: This prospective, randomized, double blind, placebo-controlled, clinical trial was conducted on patients aged 15–90 years with moderate asthma and forced expiratory volume in one second (FEV1) of 60–79% of predicted who presented to a sub-specialty clinic of pulmonary medicine. We randomly allocated subjects to receive either Borago extract (5 mL three times a day) or a matched placebo for one month. The primary outcome was the asthma control test (ACT) score and fractional exhaled nitric oxide (FENO) test. Secondary outcomes included clinical findings, spirometry, and sputum cytology including inflammatory cells. Results: Thirty-eight subjects with a mean age of 46.8±15.3 years and mean duration of asthma of 71±103 months were enrolled in our study. Cough, dyspnea, wheezing, nocturnal symptoms, and airway hyper-responsiveness reduced significantly in the Borago group after the treatment and ACT scores improved significantly (10.8±5.26 before and 15.4±5.12 after the trial). Flare up of asthma and emergency department visits in the Borago group also decreased significantly (3.6±2.33 to 2±1.86 flare ups per month and 0.62±0.9 to 0.05±0.23 for emergency department visits per month). Physiological parameters including spirometry, FENO, and sputum cytology including eosinophil and neutrophil did not change significantly. Conclusion: Borago improved the clinical findings of asthma, but it was not able to suppress the inflammation involved in asthma. PMID:28210282

  19. European, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder.

    PubMed

    Coghill, David; Banaschewski, Tobias; Lecendreux, Michel; Soutullo, Cesar; Johnson, Mats; Zuddas, Alessandro; Anderson, Colleen; Civil, Richard; Higgins, Nicholas; Lyne, Andrew; Squires, Liza

    2013-10-01

    This study evaluated the efficacy and safety of lisdexamfetamine dimesylate (LDX) compared with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in Europe. Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference arm. Patients (6-17 years old) with a baseline ADHD Rating Scale version IV (ADHD-RS-IV) total score ≥ 28 were randomized (1:1:1) to dose-optimized LDX (30, 50, or 70 mg/day), OROS-MPH (18, 36, or 54 mg/day) or placebo for 7 weeks. Primary and key secondary efficacy measures were the investigator-rated ADHD-RS-IV and the Clinical Global Impressions-Improvement (CGI-I) rating, respectively. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs. Of 336 patients randomized, 196 completed the study. The difference between LDX and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -18.6 (95% confidence interval [CI]: -21.5 to -15.7) (p<0.001; effect size, 1.80). The difference between OROS-MPH and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -13.0 (95% CI: -15.9 to -10.2) (p<0.001; effect size, 1.26). The proportions (95% CI) of patients showing improvement (CGI-I of 1 or 2) at endpoint were 78% (70-86), 14% (8-21), and 61% (51-70) for LDX, placebo, and OROS-MPH. The most common TEAEs for LDX were decreased appetite, headache, and insomnia. Mean changes in vital signs were modest and consistent with the known profile of LDX. LDX was effective and generally well tolerated in children and adolescents with ADHD.

  20. Multicentric intradural extramedullary ependymoma: Report of a rare case

    PubMed Central

    Vats, Atul; Ramdasi, Raghvendra; Zaveri, Gautam; Pandya, Sunil

    2015-01-01

    Spinal ependymoma commonly presents as an intramedullary tumor. We present a rare case of multicentric intradural extramedullary spinal ependymoma. A 59 years old female presented to us with spastic quadriparesis for 10 months. Magnetic resonance imaging of the spinal cord showed discretely located enhancing tumor masses from at C1-C2, C6-C7, and D4 to L3 level. Subtotal resection of the symptomatic tumor at C6-C7 and D7-D9 was done. The patient underwent radiotherapy with 50.4 Gy. At follow-up of 11 months, patient is doing well. The relevant literature is reviewed. PMID:26288550

  1. Efficacy and safety of high-dose baclofen for the treatment of alcohol dependence: A multicentre, randomised, double-blind controlled trial.

    PubMed

    Beraha, Esther M; Salemink, Elske; Goudriaan, Anna E; Bakker, Abraham; de Jong, David; Smits, Natasha; Zwart, Jan Willem; Geest, Dick van; Bodewits, Pieter; Schiphof, Tom; Defourny, Harma; van Tricht, Mirjam; van den Brink, Wim; Wiers, Reinout W

    2016-12-01

    Previous randomised placebo-controlled trials with low-to-medium doses of baclofen (30-60mg) showed inconsistent results, but case studies suggested a dose-response effect and positive outcomes in patients on high doses of baclofen (up to 270mg). Its prescription was temporary permitted for the treatment of alcohol dependence (AD) in France, and baclofen is now widely prescribed. Recently, a small RCT found a strong effect of a mean dose of 180mg baclofen. In the present study the efficacy and safety of high doses of baclofen was examined in a multicentre, double-blind, placebo-controlled trial. 151 patients were randomly assigned to either six weeks titration and ten weeks high-dose baclofen (N=58; up to 150mg), low-dose baclofen (N=31; 30mg), or placebo (N=62). The primary outcome measure was time to first relapse. Nine of the 58 patients (15.5%) in the high-dose group reached 150mg and the mean baclofen dose in this group was 93.6mg (SD=40.3). No differences between the survival distributions for the three groups were found in the time to first relapse during the ten-weeks high-dose phase (χ(2)=0.41; p=0.813) or the 16-weeks complete medication period (χ(2)=0.04; p=0.982). There were frequent dose-related adverse events in terms of fatigue, sleepiness, and dry mouth. One medication related serious adverse event occurred in the high-dose baclofen group. Neither low nor high doses of baclofen were effective in the treatment of AD. Adverse events were frequent, although generally mild and transient. Therefore, large-scale prescription of baclofen for the treatment of AD seems premature and should be reconsidered.

  2. Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials

    PubMed Central

    2012-01-01

    Background Schizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect. Objectives This meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD). Only the randomized controlled trials (RCTs) comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012. Data sources MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression. Study eligible criteria, participants and interventions Eligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i) depression severity, ii) response rate, iii) overall discontinuation rate, or iv) discontinuation rate due to adverse events. No language restriction was applied. Study appraisal and synthesis methods All abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were computed by using a random effect model. Results A total of 1,497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR). The pooled mean change scores of the Montgomery-Asberg Depression Rating Scale

  3. A comparison of DC and time-varying measurement of electrical conductivity in randomly generated two-phase networks.

    NASA Astrophysics Data System (ADS)

    Mandolesi, Eric; Moorkamp, Max; Jones, Alan G.

    2015-04-01

    Most electromagnetic (EM) geophysical methods focus on the electrical properties of rocks and sediments to determine reliable images of the subsurface, images routinely used in a broad range of applications. Often laboratory measurements of the same EM properties return equivocal results that are difficult to reconcile with observations obtained by EM imaging techniques. These inconsistencies lead to major interpretation problems. Different numerical approaches have been investigated in order to understand the consequences of the presence or absence of interconnected networks of fractures and pores on EM field measurements. These networks have a crucial effect on the EM field measurements, given that they can be permeated by conductive fluids that enhance the conductivity measurements of the whole environment. Most of the above-mentioned studies restrict their examination to direct current (DC) sources only. Bearing in mind that the time-varying nature of the natural electromagnetic sources play a major role in field measurements, we numerically model the effects of such EM sources on the conductivity measured on the surface of a randomly generated three-dimensional body buried in a uniform conductivity host by simulating a magnetotelluric (MT) station measurements on the top of the target random host itself. As a second experiment we simulated a DC measurement of the target bulk conductivity. The spatial distribution and shape of the conductor network allows in fact the propagation of time-varying EM fields by induction, leading the two different methods to measure a different numerical value for the bulk of the same physical property. We have compared the results from the simulated measurements obtained considering time-varying and DC sources with electrical conductivity predicted by both Hashin-Shtrikman (HS) bounds and Archie's Law, and we have compared these results with statistical properties of the model themselves. Our results suggest that for time

  4. A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer

    PubMed Central

    Deplanque, G.; Demarchi, M.; Hebbar, M.; Flynn, P.; Melichar, B.; Atkins, J.; Nowara, E.; Moyé, L.; Piquemal, D.; Ritter, D.; Dubreuil, P.; Mansfield, C. D.; Acin, Y.; Moussy, A.; Hermine, O.; Hammel, P.

    2015-01-01

    Background Masitinib is a selective oral tyrosine–kinase inhibitor. The efficacy and safety of masitinib combined with gemcitabine was compared against single-agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC). Patients and methods Patients with inoperable, chemotherapy-naïve, PDAC were randomized (1 : 1) to receive gemcitabine (1000 mg/m2) in combination with either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall survival (OS) in the modified intent-to-treat population. Secondary OS analyses aimed to characterize subgroups with poor survival while receiving single-agent gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These prospectively declared subgroups were based on pharmacogenomic data or a baseline characteristic. Results Three hundred and fifty-three patients were randomly assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus gemcitabine (N = 178). Median OS was similar between treatment-arms for the overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR) of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having a significantly poor survival rate when receiving single-agent gemcitabine; one defined by an overexpression of acyl–CoA oxidase-1 (ACOX1) in blood, and another via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent a critical unmet medical need as evidenced from median OS of 5.5 months in patients receiving single-agent gemcitabine, and comprise an estimated 63% of patients. A significant treatment effect was observed in these subgroups for masitinib with median OS of 11.7 months in the ‘ACOX1’ subgroup [HR = 0.23 (0.10; 0.51), P = 0.001], and 8.0 months in the ‘pain’ subgroup [HR = 0.62 (0.43; 0.89), P = 0.012]. Despite an increased toxicity of the combination as compared with single-agent gemcitabine, side-effects remained manageable. Conclusions The

  5. A Randomized Phase 1 Dose Escalation Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Trabodenoson in Healthy Adult Volunteers

    PubMed Central

    Laties, Alan; Rich, Cadmus C.; Stoltz, Randall; Humbert, Vernon; Brickman, Chaim; McVicar, William

    2016-01-01

    Abstract Purpose: To investigate the safety, tolerability, and pharmacokinetics of trabodenoson, a highly selective adenosine mimetic targeting the adenosine A1 receptor. Methods: In Part 1, 60 healthy adult volunteers were randomized to 14 days of twice-daily topical monocular application of placebo or trabodenoson (200, 400, 800, 1,600, 2,400, or 3,200 μg). In Part 2, 10 subjects were randomized to placebo or 8 escalating doses of bilateral trabodenoson (total daily doses: 1,800–6,400 μg). Results: The incidence of treatment-related adverse events in Part 1 was similar in the trabodenoson (27.8%) and placebo (25.0%) groups. Most were mild in intensity. The most common adverse events (AEs) for trabodenoson and placebo were headache (25.0% vs. 33%, respectively) and eye pain (11.1% vs. 4.2%, respectively). Ocular AEs were infrequent (16.7% and 17.9%, respectively), were self-limited, lasted <24 h, and were typically mild in intensity. The most common ocular AE was eye pain (9.5% and 3.6%, respectively), with a single observation of ocular hyperemia (200 μg trabodenoson). Trabodenoson was rapidly absorbed [median time to maximum concentration (tmax): ∼0.08 to 0.27 h] and eliminated (t½: 0.48–2.0 h), with no evidence of drug accumulation. Systemic exposure to topical trabodenoson was dose related but not dose proportional, with a plateau effect at doses ≥2,400 mg per eye. No clinically significant treatment-related systemic AEs were observed, and increasing systemic exposure had no effect on heart rate or blood pressure. Conclusions: Ocular doses of trabodenoson up to 3,200 μg per eye were safe and well tolerated in the eye and resulted in no detectable systemic effects in healthy adult volunteers. PMID:27046445

  6. Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial

    PubMed Central

    Geissler, Edward K.; Schnitzbauer, Andreas A.; Zülke, Carl; Lamby, Philipp E.; Proneth, Andrea; Duvoux, Christophe; Burra, Patrizia; Jauch, Karl-Walter; Rentsch, Markus; Ganten, Tom M.; Schmidt, Jan; Settmacher, Utz; Heise, Michael; Rossi, Giorgio; Cillo, Umberto; Kneteman, Norman; Adam, René; van Hoek, Bart; Bachellier, Philippe; Wolf, Philippe; Rostaing, Lionel; Bechstein, Wolf O.; Rizell, Magnus; Powell, James; Hidalgo, Ernest; Gugenheim, Jean; Wolters, Heiner; Brockmann, Jens; Roy, André; Mutzbauer, Ingrid; Schlitt, Angela; Beckebaum, Susanne; Graeb, Christian; Nadalin, Silvio; Valente, Umberto; Turrión, Victor Sánchez; Jamieson, Neville; Scholz, Tim; Colledan, Michele; Fändrich, Fred; Becker, Thomas; Söderdahl, Gunnar; Chazouillères, Olivier; Mäkisalo, Heikki; Pageaux, Georges-Philippe; Steininger, Rudolf; Soliman, Thomas; de Jong, Koert P.; Pirenne, Jacques; Margreiter, Raimund; Pratschke, Johann; Pinna, Antonio D.; Hauss, Johann; Schreiber, Stefan; Strasser, Simone; Klempnauer, Jürgen; Troisi, Roberto I.; Bhoori, Sherrie; Lerut, Jan; Bilbao, Itxarone; Klein, Christian G.; Königsrainer, Alfred; Mirza, Darius F.; Otto, Gerd; Mazzaferro, Vincenzo; Neuhaus, Peter; Schlitt, Hans J.

    2016-01-01

    Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor–free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor–free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC. PMID:26555945

  7. Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial.

    PubMed

    Raje, N; Vadhan-Raj, S; Willenbacher, W; Terpos, E; Hungria, V; Spencer, A; Alexeeva, Y; Facon, T; Stewart, A K; Feng, A; Braun, A; Balakumaran, A; Roodman, G D

    2016-01-08

    In a phase 3 trial of denosumab vs zoledronic acid in patients (n=1776) with bone metastases and solid tumors or multiple myeloma, denosumab was superior to zoledronic acid for the primary end point of prevention of skeletal-related events. There was no difference in overall survival between the two groups; however, an ad hoc overall survival analysis in the multiple myeloma subset of patients (n=180) favored zoledronic acid (hazard ratio (HR) 2.26; 95% confidence interval (CI) 1.13-4.50; P=0.014). In the present analysis, we found imbalances between the groups with respect to baseline risk characteristics. HRs with two-sided 95% CIs were estimated using the Cox model. After adjustment in a covariate analysis, the CI crossed unity (HR 1.86; 95% CI 0.90-3.84; P=0.0954). Furthermore, we found a higher rate of early withdrawals for the reasons of lost to follow-up and withdrawal of consent in the zoledronic acid group; after accounting for these, the HR was 1.31 (95% CI 0.80-2.15; P=0.278). In conclusion, the survival results in multiple myeloma patients in this trial were confounded and will eventually be resolved by an ongoing phase 3 trial.

  8. A Phase II Randomized Trial Of Lycopene-Rich Tomato Extract Among Men With High-Grade Prostatic Intraepithelial Neoplasia

    PubMed Central

    Gann, Peter H.; Deaton, Ryan J.; Rueter, Erika Enk; van Breemen, Richard B.; Nonn, Larisa; Macias, Virgilia; Han, Misop; Ananthanarayanan, Viju

    2015-01-01

    Background A diverse body of evidence suggests that lycopene might inhibit prostate cancer development. We conducted a 6-month repeat biopsy randomized trial among men with HGPIN. Here we report results for serum lycopene, PSA and IGF proteins, histopathological review, and tissue markers for proliferation (MCM-2) and cell cycle inhibition (p27). Methods Participants consumed placebo or tomato extract capsules containing 30 mg/day lycopene. Pre- and post-treatment biopsies were immunostained and digitally scored. Serum lycopene was determined by LC-MS-MS. In secondary analyses, pathologists blindly reviewed each biopsy to score histological features. Results 58 men completed the trial. Serum lycopene increased 0.55 μmol/L with treatment and declined 0.29 μmol/L with placebo. We observed no meaningful differences in PSA, IGF-1 or IGFBP3 concentrations between groups, nor any differences in expression of MCM-2 or p27 in epithelial nuclei. Prevalences of cancer, HGPIN, atrophy or inflammation post-treatment were similar; however, more extensive atrophy and less extensive HGPIN was more common in the lycopene group. Conclusions Despite large differences in serum lycopene following intervention, no treatment effects were apparent on either the serum or benign tissue endpoints. Larger studies are warranted to determine whether changes observed in extent of HGPIN and focal atrophy can be replicated. PMID:26422197

  9. A randomized, evaluator-blind, phase 2 study comparing the safety and efficacy of omadacycline to those of linezolid for treatment of complicated skin and skin structure infections.

    PubMed

    Noel, Gary J; Draper, Michael P; Hait, Howard; Tanaka, S Ken; Arbeit, Robert D

    2012-11-01

    A randomized, investigator-blind, multicenter phase 2 trial involving patients with complicated skin and skin structure infections (cSSSI) compared the safety and efficacy of omadacycline, a broad-spectrum agent with activity against methicillin-resistant Staphylococcus aureus (MRSA), to those of linezolid (with or without aztreonam). Patients were randomized 1:1 to omadacycline (100 mg intravenously [i.v.] once a day [QD] with an option to transition to 200 mg orally QD) or linezolid (600 mg i.v. twice daily [BID] with an option to transition to 600 mg orally BID) at 11 U.S. sites. Patients suspected or documented to have infections caused by Gram-negative bacteria were given aztreonam (2 g i.v. every 12 h [q12h]) if randomized to linezolid or matching placebo infusions if randomized to omadacycline. Adverse events were reported in 46 (41.4%) omadacycline-treated and 55 (50.9%) linezolid-treated patients. Adverse events related to treatment were assessed by investigators in 24 (21.6%) omadacycline-treated and 33 (30.6%) linezolid-treated patients. The gastrointestinal tract was most commonly involved, with adverse events reported in 21 (18.9%) patients exposed to omadacycline and 20 (18.5%) exposed to linezolid. Rates of successful clinical response in the intent-to-treat (ITT) and clinical evaluable (CE) populations favored omadacycline (ITT, 88.3% versus 75.9%; 95% confidence interval [CI], 1.9 to 22.9; CE, 98.0% versus 93.2%; 95% CI, -1.7 to 11.3). For microbiologically evaluable (ME) patients with S. aureus infections, the clinical success rates were 97.2% (70/72) in omadacycline-treated and 92.7% (51/55) in linezolid-treated patients. This phase 2 experience supports conclusions that omadacycline is well tolerated in cSSSI patients and that this aminomethylcycline has potential to be an effective treatment for serious skin infections.

  10. Early-stage squamous cell carcinoma of the oropharynx: Radiotherapy vs. Trans-Oral Robotic Surgery (ORATOR) – study protocol for a randomized phase II trial

    PubMed Central

    2013-01-01

    Background The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has markedly increased over the last three decades due to newly found associations with human papillomavirus (HPV) infection. Primary radiotherapy (RT) is the treatment of choice for OPSCC at most centers, and over the last decade, the addition of concurrent chemotherapy has led to a significant improvement in survival, but at the cost of increased acute and late toxicity. Transoral robotic surgery (TORS) has emerged as a promising alternative treatment, with preliminary case series demonstrating encouraging oncologic, functional, and quality of life (QOL) outcomes. However, comparisons of TORS and RT in a non-randomized fashion are susceptible to bias. The goal of this randomized phase II study is to compare QOL, functional outcomes, toxicity profiles, and survival following primary RT (± chemotherapy) vs. TORS (± adjuvant [chemo] RT) in patients with OPSCC. Methods/Design The target patient population comprises OPSCC patients who would be unlikely to require chemotherapy post-resection: Tumor stage T1-T2 with likely negative margins at surgery; Nodal stage N0-2, ≤3 cm in size, with no evidence of extranodal extension on imaging. Participants will be randomized in a 1:1 ratio between Arm 1 (RT ± chemotherapy) and Arm 2 (TORS ± adjuvant [chemo] RT). In Arm 1, patients with N0 disease will receive RT alone, whereas N1-2 patients will receive concurrent chemoradiation. In Arm 2, patients will undergo TORS along with selective neck dissections, which may be staged. Pathologic high-risk features will be used to determine the requirement for adjuvant radiotherapy +/- chemotherapy. The primary endpoint is QOL score using the M.D. Anderson Dysphagia Inventory (MDADI), with secondary endpoints including survival, toxicity, other QOL outcomes, and swallowing function. A sample of 68 patients is required. Discussion This study, if successful, will provide a much-needed randomized

  11. A prospective, randomized, double-blind study of the tolerability of rifapentine 600, 900, and 1,200 mg plus isoniazid in the continuation phase of tuberculosis treatment.

    PubMed

    Bock, Naomi N; Sterling, Timothy R; Hamilton, Carol D; Pachucki, Connie; Wang, Yong-Cheng; Conwell, Donna S; Mosher, Ann; Samuels, Mary; Vernon, Andrew

    2002-06-01

    Once-weekly rifapentine 600 mg plus isoniazid (INH) during the continuation phase treatment of tuberculosis is associated with a relapse rate higher than that of twice-weekly rifampin plus INH. The safety and tolerability of higher rifapentine doses need to be determined. We conducted a prospective, randomized, double-blind trial of rifapentine at three doses (600, 900, and 1,200 mg) plus INH 15 mg/kg once weekly in the continuation phase treatment of culture-positive tuberculosis in 150 human immunodeficiency virus-seronegative adults. Outcome measures were discontinuation of therapy for any reason and adverse events on therapy. Treatment was discontinued in 3 of 52 (6%), 2 of 51 (4%), and 3 of 47 (6%) in the rifapentine 600-, 900-, and 1,200-mg treatment arms, respectively. Only one discontinuation, in the rifapentine 1,200-mg arm, was due to an adverse event possibly associated with study therapy. There was a trend toward more adverse events, possibly associated with study therapy, in the highest-dose arms (p = 0.051). Rifapentine 900-mg, once-weekly dosing appears to be safe and well tolerated and is being evaluated in Phase III efficacy trials of treatment of latent tuberculosis. Further evaluation of the safety and tolerability of rifapentine 1,200 mg is warranted.

  12. Phase transitions in a three-dimensional kinetic spin-1/2 Ising model with random field: effective-field-theory study.

    PubMed

    Costabile, Emanuel; de Sousa, J Ricardo

    2012-01-01

    The dynamical phase transitions of the kinetic Ising model in the presence of a random magnetic field with a bimodal probability distribution is studied by using effective-field theory (EFT) with correlations. We have used a Glauber-type stochastic dynamic to describe the time evolution of the system, where the system strongly depends on the H≡√(c) root mean square deviation of the magnetic field. The EFT dynamic equation is given for the simple cubic lattice (z=6), and the dynamic order parameter is calculated. The system presents ferromagnetic and paramagnetic states for low and high temperatures, respectively. Our results predict first-order transitions at low temperatures and large disorder strengths, which corresponds to the existence of a nonequilibrium tricritical point (TCP) in a phase diagram in the T-H plane. We compare the results with the equilibrium phase diagram, where only the first-order line is different. Our qualitative results are compatible with recent Monte Carlo simulations.

  13. Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study)

    PubMed Central

    2011-01-01

    Background Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neo)adjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC) has been designed to explore the efficacy of neoadjuvant chemotherapy. Methods/Design This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m2) for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m2, oxaliplatin 100 mg/m2) followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked intraoperatively, and

  14. Bevacizumab and temozolomide versus temozolomide alone as neoadjuvant treatment in unresected glioblastoma: the GENOM 009 randomized phase II trial.

    PubMed

    Balana, Carmen; De Las Penas, Ramon; Sepúlveda, Juan Manuel; Gil-Gil, Miguel J; Luque, Raquel; Gallego, Oscar; Carrato, Cristina; Sanz, Carolina; Reynes, Gaspar; Herrero, Ana; Ramirez, Jose Luis; Pérez-Segura, Pedro; Berrocal, Alfonso; Vieitez, Jose Maria; Garcia, Almudena; Vazquez-Estevez, Sergio; Peralta, Sergi; Fernandez, Isaura; Henriquez, Ivan; Martinez-Garcia, Maria; De la Cruz, Juan Jose; Capellades, Jaume; Giner, Pilar; Villà, Salvador

    2016-05-01

    We sought to determine the impact of bevacizumab on reduction of tumor size prior to chemoradiotherapy in unresected glioblastoma patients. Patients were randomized 1:1 to receive temozolomide (TMZ arm) or temozolomide plus bevacizumab (TMZ + BEV arm). In both arms, neoadjuvant treatment was temozolomide (85 mg/m(2), days 1-21, two 28-day cycles), concurrent radiation plus temozolomide, and six cycles of adjuvant temozolomide. In the TMZ + BEV arm, bevacizumab (10 mg/kg) was added on days 1 and 15 of each neoadjuvant cycle and on days 1, 15 and 30 of concurrent treatment. The primary endpoint was investigator-assessed response to neoadjuvant treatment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the impact on outcome of MGMT methylation in tumor and serum. One hundred and two patients were included; 43 in the TMZ arm and 44 in the TMZ + BEV arm were evaluable for response. Results favored the TMZ + BEV arm in terms of objective response (3 [6.7 %] vs. 11 [22.9 %]; odds ratio 4.2; P = 0.04). PFS and OS were longer in the TMZ + BEV arm, though the difference did not reach statistical significance. MGMT methylation in tumor, but not in serum, was associated with outcome. More patients experienced toxicities in the TMZ + BEV than in the TMZ arm (P = 0.06). The combination of bevacizumab plus temozolomide is more active than temozolomide alone and may well confer benefit in terms of tumor shrinkage in unresected patients albeit at the expense of greater toxicity.

  15. Lisdexamfetamine Dimesylate for Adults with Moderate to Severe Binge Eating Disorder: Results of Two Pivotal Phase 3 Randomized Controlled Trials

    PubMed Central

    McElroy, Susan L; Hudson, James; Ferreira-Cornwell, M Celeste; Radewonuk, Jana; Whitaker, Timothy; Gasior, Maria

    2016-01-01

    The efficacy and safety of lisdexamfetamine dimesylate (LDX) vs placebo in binge eating disorder (BED) was evaluated in two multicenter, double-blind, placebo-controlled trials. Adults (study 1, n=383; study 2, n=390) meeting DSM-IV-TR BED criteria were randomized (1:1) to placebo or LDX (50 or 70 mg/day) dose titration; optimized doses were maintained to the end of double-blind treatment (week 12/early termination). Change from baseline in binge eating days/week at weeks 11−12 (primary efficacy endpoint) was assessed with mixed-effects models for repeated measures. Secondary endpoints related to binge eating and medical parameters, safety, and treatment compliance were also assessed. Least squares mean (95% CI) treatment differences for change from baseline binge eating days/week at weeks 11–12 significantly favored LDX (study 1: –1.35 [–1.70, –1.01] study 2: –1.66 [–2.04, –1.28] both P<0.001). In both studies, treatment-emergent adverse events (TEAEs) reported by ⩾10% of LDX participants were dry mouth, insomnia, and headache. Serious TEAEs occurred in two (1.1%) placebo participants in each study and in three (1.6%) and one (0.6%) LDX participants in study 1 and study 2, respectively. Across studies, mean increases from baseline at week 12/early termination with LDX for pulse and systolic and diastolic blood pressure ranged from 4.41–6.31 b.p.m. and 0.2–1.45 and 1.06–1.83 mm Hg, respectively. LDX (50 and 70 mg/day) was superior to placebo in decreasing binge eating days/week from baseline and improving binge eating–related key secondary endpoints. Safety results appear consistent with the known safety profile of LDX. PMID:26346638

  16. Efficacy profile of a bivalent Staphylococcus aureus glycoconjugated vaccine in adults on hemodialysis: Phase III randomized study.

    PubMed

    Fattom, Ali; Matalon, Albert; Buerkert, John; Taylor, Kimberly; Damaso, Silvia; Boutriau, Dominique

    2015-01-01

    In a previous study in end-stage renal disease (ESRD) hemodialysis patients, a single dose of Staphylococcus aureus type 5 and 8 capsular polysaccharides (T5/T8) conjugated to nontoxic recombinant Pseudomonas aeruginosa exotoxin A investigational vaccine showed no efficacy against S. aureus bacteremia 1 year post-vaccination, but a trend for efficacy was observed over the first 40 weeks post-vaccination. Vaccine efficacy (VE) of 2 vaccine doses was therefore evaluated. In a double-blind trial 3359 ESRD patients were randomized (1:1) to receive vaccine or placebo at week 0 and 35. VE in preventing S. aureus bacteremia was assessed between 3-35 weeks and 3-60 weeks post-dose-1. Anti-T5 and anti-T8 antibodies were measured. Serious adverse events (SAEs) were recorded for 42 days post-vaccination and deaths until study end. No significant difference in the incidence of S. aureus bacteremia was observed between vaccine and placebo groups between weeks 3-35 weeks post-dose 1 (VE -23%, 95%CI: -98;23, p = 0.39) or at 3-60 weeks post-dose-1 (VE -8%, 95%CI: -57;26, p = 0.70). Day 42 geometric mean antibody concentrations were 272.4 μg/ml and 242.0 μg/ml (T5 and T8, respectively) in vaccinees. SAEs were reported by 24%/25.3% of vaccinees/placebo recipients. These data do not show a protective effect of either 1 or 2 vaccine doses against S. aureus bacteremia in ESRD patients. The vaccine induced a robust immune response and had an acceptable safety profile. Further investigation suggested possible suboptimal vaccine quality (manufacturing) and a need to expand the antigen composition of the vaccine. This study is registered at www.clinicaltrials.gov NCT00071214.

  17. A Phase 1 Randomized Plac