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
Boer, R H de; Smith, I E; Pastorino, U; O'Brien, M E R; Ramage, F; Ashley, S; Goldstraw, P
1999-01-01
Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m−2, vinblastine 6 mg m−2 and cisplatin 50 mg m−2 (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III–IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial. © 1999 Cancer Research Campaign PMID:10188899
Ridolfi, Laura; Bertetto, Oscar; Santo, Antonio; Naglieri, Emanuele; Lopez, Massimo; Recchia, Francesco; Lissoni, Paolo; Galliano, Marco; Testore, Franco; Porta, Camillo; Maglie, Monica; Dall'agata, Monia; Fumagalli, Luca; Ridolfi, Ruggero
2011-10-01
Non-small cell lung cancer (NSCLC) is associated with IL-2-dependent cell-mediated immunodeficiency. As IL-2 is the main lymphocyte growth factor, a phase III randomized multicenter trial was conducted to evaluate the impact of subcutaneous low-dose IL-2 added to standard chemotherapy (CT) on overall survival (OS) in advanced NSCLC patients. Patients (n=241) with histologically confirmed stage IIIb or IV non-operable NSCLC underwent stratified randomization on the basis of center, ECOG PS, stage of disease and percentage of weight loss. Patients received gemcitabine (1000 mg/m2) on days 1 and 8 + cisplatin (100 mg/m2) on day 2 every 21 days for a maximum of 6 cycles [chemotherapy (CT) arm]. In the CT+IL-2 arm, patients also received low-dose subcutaneous IL-2 3,000,000 IU/die on days 3-5, 9-11, 15-17. The study had 90% power to detect a 20% absolute increase in 1-year OS with 118 patients/arm. An overall response (OR) rate of 12.8% (14% in the CT+IL-2 arm and 11.4% in CT arm) was observed. Stable disease was 70 and 66.7%, and progressive disease 16 and 21.8% in the CT+IL-2 and CT arms, respectively. No differences in response were found in any subgroup analysis. At a median follow-up of 32 months, 1-year OS was 45% for the CT+IL-2 arm vs. 51% for the CT arm (p=0.456 log-rank). Median progression-free survival was 6.6 months in the CT+IL-2 arm vs. 6.9 months in the CT arm (p=0.573, log-rank). A higher number of grade 4 toxicities were reported with CT+IL-2. The most common grade ≥3 adverse events were gastrointestinal toxicity (mainly nausea and diarrhea) and myelosuppression. No relevant differences in clinical outcome were observed from the addition of IL-2 to CT. Future studies investigating the role of T-regulators in chemoimmunotherapeutic regimens could be performed. PMID:21720704
Kokki, Hannu; Kokki, Merja
2010-01-01
Fever is a common symptom in children and one of the major concerns of parents of younger and preschool-age children. To compare the efficacy and safety of ketoprofen with that of paracetamol (acetaminophen) and ibuprofen in the treatment of febrile conditions in children. Two prospective, randomized, double-blind, double-dummy, repeated-dose, multicentre, phase III studies with two parallel groups in each study were conducted in primary-care outpatient clinics. Children aged 6 months to 6 years presenting with a febrile condition and an oral body temperature of > or =38.8 degrees C or rectal temperature of > or =39 degrees C were eligible for inclusion. Patients were randomized to receive either ketoprofen syrup 0.5 mg/kg, ibuprofen suspension 5 mg/kg or paracetamol suspension 15 mg/kg every 6 hours by the oral route. The primary outcome measure was the change in temperature at 3 hours (H3), compared with baseline (H0). All three treatments provided similar mean maximum decreases of 1.4-1.5 degrees C in body temperature at H3 compared with H0. Use of ketoprofen was not associated with any increased risk of adverse events compared with the two reference compounds. Ketoprofen 0.5 mg/kg appeared to be equivalent to the standard antipyretic doses of the reference products ibuprofen 5 mg/kg and paracetamol 15 mg/kg. Ketoprofen at the 0.5 mg/kg dose should be an effective and safe option for symptomatic management of fever in children. PMID:20380479
Correale, Pierpaolo; Botta, Cirino; Rotundo, Maria S; Guglielmo, Annamaria; Conca, Raffaele; Licchetta, Antonella; Pastina, Pierpaolo; Bestoso, Elena; Ciliberto, Domenico; Cusi, Maria G; Fioravanti, Antonella; Guidelli, Giacomo M; Bianco, Maria T; Misso, Gabriella; Martino, Elodia; Caraglia, Michele; Tassone, Pierfrancesco; Mini, Enrico; Mantovani, Giovanni; Ridolfi, Ruggero; Pirtoli, Luigi; Tagliaferri, Pierosandro
2014-01-01
The GOLFIG-2 phase III trial was designed to compare the immunobiological activity and antitumor efficacy of GOLFIG chemoimmunotherapy regimen with standard FOLFOX-4 chemotherapy in frontline treatment of metastatic colorectal cancer (mCRC) patients. This trial was conceived on the basis of previous evidence of antitumor and immunomodulating activity of the GOLFIG regimen in mCRC. GOLFIG-2 is a multicentric open/label phase III trial (EUDRACT: 2005-003458-81). Chemo-naive mCRC patients were randomized in a 1:1 ratio to receive biweekly standard FOLFOX-4 or GOLFIG [gemcitabine (1000 mg/m(2), day 1); oxaliplatin (85 mg/m(2), day 2); levofolinate (100 mg/m(2), days 1-2), 5-fluorouracil (5-FU) (400 mg/m(2) in bolus followed by 24 h infusion at 800 mg/m(2),days 1-2), sc. GM-CSF (100 μg, days 3-7); sc. aldesleukin (0·5 MIU bi-daily, days 8-14 and 17-30)] treatments. The study underwent early termination because of poor recruitment in the control arm. After a median follow-up of 43.83 months, GOLFIG regimen showed superiority over FOLFOX in terms of progression-free survival [median 9·23 (95% confidence interval (CI), 6·9-11.5) vs. median 5.70 (95% CI, 3.38-8.02) months; hazard ratio (HR): 0.52 (95% CI, 0.35-0.77), P=0·002] and response rate [66.1% (95% CI, 0.41-0.73) vs. 37·0% (95% CI, 0.28-0.59), P=0.002], with a trend to longer survival [median 21.63 (95% CI, 18.09-25.18) vs. 14.57 mo (95% CI, 9.07-20.07); HR: 0·79 (95% CI, 0.52-1.21); P=0.28]. Patients in the experimental arm showed higher incidence of non-neutropenic fever (18.5%), autoimmunity signs (18.5%), an increase in the number of monocytes, eosinophils, CD4(+) T lymphocytes, natural killer cells, and a decrease in immunoregulatory (CD3(+)CD4(+)CD25(+)FoxP3(+)) T cells. Taken together, these findings provide proof-of-principle that GOLFIG chemoimmunotherapy may represent a novel reliable option for first-line treatment of mCRC. PMID:24316553
Zhang, H; Shan, C; Hua, Z; Zhao, P; Zhang, H
2009-01-01
The objective of this study was to evaluate the efficacy of treating chronic idiopathic urticaria (CIU) with levamisole in combination with levocetirizine. This was a multicentre, randomized, double-blind, controlled trial that included 132 patients with active CIU who were treated for 6 weeks with either levocetirizine alone (control group; n = 65) or levamisole plus levocetirizine (treatment group; n = 67). Response to therapy was evaluated by measuring the efficacy rate. After 2 weeks of treatment, there was no significant difference in the efficacy rate between the treatment and control groups (54.84% and 42.37%, respectively). After 6 weeks of treatment, a statistically significant difference in the efficacy rate was observed between the groups (76.27% and 54.39% for the treatment and control groups, respectively). This study demonstrated that a combination of levamisole plus levocetirizine is more effective than levocetirizine alone and potentially provides a new, promising approach to the treatment of CIU. PMID:19761700
Liu, Rong; Luo, Chaozhi; Liu, Jin; Zhang, Wensheng; Li, Yan; Xu, Jing
2016-07-01
The present phase II study aimed to compare the efficacy and safety of fospropofol disodium for injection (FospropofolFD ) and propofol when given during the induction of general anaesthesia in patients scheduled for elective surgery. FospropofolFD is a water-soluble prodrug of propofol. Approved by the Ethical Committee, 240 participants aged 18-65 years were equally randomly allocated to receive an intravenous bolus of FospropofolFD 20 mg/kg or propofol 2 mg/kg without any anaesthetic pre-treatment. The primary efficacy end-point was the sedation success rate within 5 min. after administering investigational drugs (the sedation success is defined as obtaining Modified Observer's Assessment of Alertness/Sedation scale score of 1). All the participants completed the induction and intubation within 25 min. after administration. The sedation success rates within 5 min. after administration of FospropofolFD 20 mg/kg and propofol 2 mg/kg were 94.50% versus 100% in the intention-to-treat population and 95.10% versus 100% in the per-protocol population, respectively. The non-inferiority test obtained a p-value less than 0.025, and the lower limits of the one-sided 97.5% confidence interval were more than -0.09. This meant that FospropofolFD 20 mg/kg was considered non-inferior to propofol 2 mg/kg for the primary efficacy end-point. Compared with propofol 2 mg/kg, FospropofolFD 20 mg/kg had a slower sedation efficacy. No serious adverse events were observed in the two groups. The sedation success rate within 5 min. after administration of FospropofolFD 20 mg/kg was non-inferior to propofol 2 mg/kg, and FospropofolFD 20 mg/kg can be used for the induction of general anaesthesia safely. PMID:26781338
Passalacqua, Rodolfo; Caminiti, Caterina; Buti, Sebastiano; Porta, Camillo; Camisa, Roberta; Braglia, Luca; Tomasello, Gianluca; Vaglio, Augusto; Labianca, Roberto; Rondini, Ermanno; Sabbatini, Roberto; Nastasi, Giuseppe; Artioli, Fabrizio; Prati, Andrea; Potenzoni, Michele; Pezzuolo, Debora; Oliva, Elena; Alberici, Federico; Buzio, Carlo
2014-01-01
There is currently no standard therapy to reduce the recurrence rate after surgery for renal cell carcinoma (RCC). The aim of this study was to assess efficacy and safety of adjuvant treatment with low doses of interleukin-2 (IL-2)+interferon-α (IFN-α) in operable RCC. The patients were randomized 1:1 to receive a 4-week cycle of low-dose IL-2+IFN-α or observation after primary surgery for RCC. Treatment cycles were repeated every 4 months for the first 2 years and every 6 months for the subsequent 3 years. The primary endpoint was recurrence-free survival (RFS); safety; and overall survival (OS) were secondary endpoints. ClinicalTrials.gov registration number was NCT00502034. 303/310 randomized patients (156 in the immunotherapy arm and 154 in the observation group) were evaluable at the intention-to-treat analyses. The 2 arms were well balanced. At a median follow-up of 52 months (range, 12-151 mo), RFS, and OS were similar, with an estimated hazard ratio (HR) of 0.84 [95% confidence interval (CI), 0.54-1.31; P=0.44] and of 1.07 (95% CI, 0.64-1.79; P=0.79), respectively in the 2 groups. Unplanned, subgroup analysis showed a positive effect of the treatment for patients with age 60 years and younger, pN0, tumor grades 1-2, and pT3a stage. Among patients with the combined presence of ≥ 2 of these factors, immunotherapy had a positive effect on RFS (HR=0.44; 95% CI, 0.24-0.82; P ≤ 0.01), whereas patients with <2 factors in the treatment arm exhibited a significant poorer OS (HR=2.27; 95% CI, 1.03-5.03 P=0.037). Toxicity of immunotherapy was mild and limited to World Health Organization grade 1-2 in most cases. Adjuvant immunotherapy with IL-2+IFN-α showed no RFS or OS improvement in RCC patients who underwent radical surgery. The results of subset analysis here presented are only hypothesis generating. PMID:25304727
L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN) - a randomized multicentre trial
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
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
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. PMID:25180016
Gorlitzer, Michael; Wagner, Florian; Pfeiffer, Steffen; Folkmann, Sandra; Meinhart, Johann; Fischlein, Theodor; Reichenspurner, Hermann; Grabenwoeger, Martin
2013-01-01
OBJECTIVES A prospective randomized multicentre trial was performed to analyse the efficacy of a vest (Posthorax support vest®) to prevent sternal wound infection after cardiac surgery, and to identify risk factors. METHODS From September 2007 to March 2010, 2539 patients undergoing cardiac surgery via median sternotomy were prospectively randomized into those who received a Posthorax® vest and those who did not. Patients were instructed to wear the vest postoperatively for 24 h a day for at least 6 weeks; the duration of follow-up was 90 days. Patients who did not use the vest within a period of 72 h postoperatively were regarded as study dropouts. Statistical calculations were based on an intention-to-treat (ITT) analysis. Further evaluations comprised all subgroups of patients. RESULTS Complete data were available for 2539 patients (age 67 ± 11years, 45% female). Of these, 1351 were randomized to receive a vest, while 1188 received no vest. No significant differences were observed between groups regarding age, gender, diabetes, body mass index, chronic obstructive pulmonary disease (COPD), renal failure, the logistic EuroSCORE and the indication for surgery. The frequency of deep wound complications (dWC: mediastinitis and sternal dehiscence) was significantly lower in vest (n = 14; 1.04%) vs non-vest (n = 27; 2.27%) patients (ITT, P < 0.01), but superficial complications did not differ between groups. Subanalysis of vest patients revealed that only 933 (Group A) wore the vest according to the protocol, while 202 (Group BR) refused to wear the vest (non-compliance) and 216 (Group BN) did not use the vest for other reasons. All dWC occurred in Groups BR (n = 7) and BN (n = 7), although these groups had the same preoperative risk profile as Group A. Postoperatively, Group BN had a prolonged intubation time, a longer stay in the intensive care unit, greater use of intra-aortic balloon pump, higher frequency of COPD and a larger percentage of patients who
A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma
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
2012-01-01
Background Neck pain is one of the chief symptoms of cervical spondylosis (CS). Acupuncture is a well-accepted and widely used complementary therapy for the management of neck pain caused by CS. In this paper, we present a randomized controlled trial protocol evaluating the use of acupuncture for CS neck pain, comparing the effects of the optimized acupuncture therapy in real practice compared with sham and shallow acupuncture. Methods/Design This trial uses a multicentre, parallel-group, randomized, sham acupuncture and shallow acupuncture, controlled single-blind design. Nine hospitals are involved as trial centres. 945 patients who meet inclusion criteria are randomly assigned to receive optimized acupuncture therapy, sham acupuncture or shallow acupuncture by a computerized central randomization system. The interventions past for 4 weeks with eight to ten treatments in total. The group allocations and interventions are concealed to patients and statisticians. The Northwick Park Neck Pain Questionnaire (NPQ) is used as the primary outcome measure, and the McGill Pain Questionnaire (MPQ) and The Short Form (36) Health Survey (SF-36) are applied as secondary outcome measures. The evaluation is performed at baseline, at the end of the intervention, and at the end of the first month and the third month during follow-up. The statistical analyses will include baseline data comparison and repeated measures of analysis of variance (ANOVA) for primary and secondary outcomes of group and time differences. Adverse events (AEs) will be reported if they occur. Discussion This trial is a multicentre randomized control trial (RCT) on the efficacy of acupuncture for CS neck pain and has a large sample size and central randomization in China. It will strictly follow the CONSORT statement and STRICTA extension guideline to report high-quality study results. By setting the control groups as sham and shallow acupuncture, this study attempts to reveal the effects of real acupuncture
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
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.
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
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. PMID:10997497
Phase transitions on random lattices: how random is topological disorder?
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. PMID:25279615
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
Short-course eflornithine in Gambian trypanosomiasis: a multicentre randomized controlled trial.
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
Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial
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
Towfigh, S; Pasternak, J; Poirier, A; Leister, H; Babinchak, T
2010-08-01
Tigecycline (TGC) has demonstrated clinical efficacy and safety, in comparison with imipenem/cilastatin in phase 3 clinical trials, for complicated intra-abdominal infection (cIAI). The present study comprised a multicentre, open-label, randomized study of TGC vs. ceftriaxone plus metronidazole (CTX/MET) for the treatment of patients with cIAI. Eligible subjects were randomized (1:1) to receive either an initial dose of TGC (100 mg) followed by 50 mg every 12 h or CTX (2 g once daily) plus MET (1-2 g daily), for 4-14 days. The primary endpoint was the clinical response in the clinically evaluable (CE) population at the test of cure (TOC) assessment. Of 473 randomized subjects, 376 were CE. Among these, clinical cure rates were 70.4% (133/189) with TGC vs. 74.3% (139/187) with CTX/MET (95% CI -13.1 to 5.1; p 0.009 for non-inferiority). Clinical cure rates for subjects with Acute Physiological and Chronic Health Evaluation II scores > or =10 were 56.8% (21/37) with TGC vs. 58.3% (21/36) with CTX/MET. The microbiologic response was similar between the two treatment arms, with microbiological eradication at TOC achieved in 68.1% (94/138) of TGC-treated subjects and 71.5% (98/137) of CTX/MET-treated subjects. (The most frequently reported adverse events (AEs) for both treatment arms were nausea (TGC, 38.6% vs CTX/MET, 27.7%) and vomiting (TGC, 23.3% vs CTX/MET, 17.7%). Overall discontinuation rates as a result of an AE were 8.9% and 4.8% in TGC- and comparator-treated subjects, respectively. The results obtained in the present study demonstrate that TGC monotherapy is non-inferior to a combination regimen of CTX/MET with respect to treating subjects with cIAI. PMID:20670293
Entanglement of phase-random states
NASA Astrophysics Data System (ADS)
Nakata, Yoshifumi; Turner, Peter; Murao, Mio
2014-12-01
In order to study generic properties of time-evolving states by time-independent Hamiltonian dynamics, we introduce phase-random states, an ensemble of pure states with fixed amplitudes and uniformly distributed phases in a fixed basis. We compute the average amount of entanglement of phase-random states analytically, and show that the average can be extremely large when the amplitudes are equal and the basis is separable. We also study implications on Hamiltonian dynamics, in particular the realization of the canonical state in a subsystem.
Phase Transitions on Random Lattices: How Random is Topological Disorder?
NASA Astrophysics Data System (ADS)
Barghathi, Hatem; Vojta, Thomas
2015-03-01
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) / (2 d) 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. This work was supported by the NSF under Grant Nos. DMR-1205803 and PHYS-1066293. We acknowledge the hospitality of the Aspen Center for Physics.
Patris, M; Bouchard, J M; Bougerol, T; Charbonnier, J F; Chevalier, J F; Clerc, G; Cyran, C; Van Amerongen, P; Lemming, O; Høpfner Petersen, H E
1996-06-01
Two selective serotonin reuptake inhibitors (SSRIs), citalopram and fluoxetine, both at a daily dose of 20 mg, were compared in patients with unipolar major depression treated in general practice. This was a multicentre, double-blind, randomized trial carried out in France. The duration of treatment was 8 weeks. Patients were assessed by means of the Montgomery-Asberg Depression Rating Scale (MADRS), the 17 items Hamilton Depression Rating Scale (HAMD) and the investigator's Clinical Global Impressions (CGI), Observed and spontaneously reported adverse events were also recorded. A total of 357 patients of both sexes, aged between 21 and 73 years, entered the double-blind phase of the trial. A clear reduction of both the MADRS and the HAMD mean total scores was observed in both treatment groups with no statistically significant differences between treatments. Apart from back pain recorded more frequently in the citalopram group, no significant difference was found between the two treatment groups with regard to adverse events, and both citalopram and fluoxetine were considered to be well tolerated. It was concluded that citalopram was as effective as fluoxetine in the treatment of unipolar major depression. Citalopram showed an earlier onset of recovery than fluoxetine. PMID:8803650
Random-phase metasurfaces at optical wavelengths
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
Random-phase metasurfaces at optical wavelengths.
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
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.
Random fields at a nonequilibrium phase transition.
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. PMID:23215170
Fast phase randomization via two-folds
Jeffrey, M. R.
2016-01-01
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. PMID:27118901
Schiele, F; Lindgaerde, F; Eriksson, H; Bassand, J P; Wallmark, A; Hansson, P O; Grollier, G; Sjo, M; Moia, M; Camez, A; Smyth, V; Walker, M
1997-05-01
The aim of this multicentre, prospective, randomised, dose-ranging study was to compare the safety and efficacy of subcutaneous recombinant hirudin (HBW 023) against intravenous sodium heparin in acute lower limb deep venous thrombosis (DVT). Patients were randomized to treatment with either HBW 023 or heparin for 5 +/- 1 days. HBW 023 was given according to body-weight in three dose groups. Thromboembolic disease was assessed by phlebography and ventilation/perfusion (V/Q) scanning on Day 1 and Day 5 +/- 1. One hundred and fifty-five patients were enrolled, of these 121 were evaluable for efficacy analysis. Significantly fewer patients on HBW 023 developed new V/Q abnormalities during the treatment period, (p = 0.006). There was no difference between the groups in thrombus extension or regression, major bleeding complications or serious adverse events. There were significantly fewer findings of new V/Q mismatch after treatment with HBW 023, and anticoagulant control was superior in these patients. PMID:9184388
Evolutionary Phase Transitions in Random Environments.
Skanata, Antun; Kussell, Edo
2016-07-15
We present analytical results for long-term growth rates of structured populations in randomly fluctuating environments, which we apply to predict how cellular response networks evolve. We show that networks which respond rapidly to a stimulus will evolve phenotypic memory exclusively under random (i.e., nonperiodic) environments. We identify the evolutionary phase diagram for simple response networks, which we show can exhibit both continuous and discontinuous transitions. Our approach enables exact analysis of diverse evolutionary systems, from viral epidemics to emergence of drug resistance. PMID:27472146
Evolutionary Phase Transitions in Random Environments
NASA Astrophysics Data System (ADS)
Skanata, Antun; Kussell, Edo
2016-07-01
We present analytical results for long-term growth rates of structured populations in randomly fluctuating environments, which we apply to predict how cellular response networks evolve. We show that networks which respond rapidly to a stimulus will evolve phenotypic memory exclusively under random (i.e., nonperiodic) environments. We identify the evolutionary phase diagram for simple response networks, which we show can exhibit both continuous and discontinuous transitions. Our approach enables exact analysis of diverse evolutionary systems, from viral epidemics to emergence of drug resistance.
Riccio, M; Battiston, B; Pajardi, G; Corradi, M; Passaretti, U; Atzei, A; Altissimi, M; Vaienti, L; Catalano, F; Del Bene, M; Fasolo, P; Ceruso, M; Luchetti, R; Landi, A
2010-02-01
Hyaloglide is a hyaluronan-based gel based on a novel auto-crosslinked technology designed to reduce postsurgical adhesions. Its efficacy was assessed in a multicentred randomized controlled trial comparing the results of flexor tenolysis in zone 2 following failed flexor tendon repairs. In the control group a standard release was performed. In the treated group, Hyaloglide was applied into the flexor sheath and around the site of tenolysis. Forty-five patients, 19 controls and 26 treated with Hyaloglide, were enrolled in 13 centres. All the patients were evaluated at 30, 60, 90 and 180 days after surgery by testing Total Active Motion, Quick-DASH questionnaire and number of working days lost after surgery. Patients in the Hyaloglide group had a statistically better recovery of finger motion at all time intervals and returned earlier to work and daily activities. The use of Hyaloglide did not appear to increase the complication rate. PMID:19710086
Random phase textures: theory and synthesis.
Galerne, Bruno; Gousseau, Yann; Morel, Jean-Michel
2011-01-01
This paper explores the mathematical and algorithmic properties of two sample-based texture models: random phase noise (RPN) and asymptotic discrete spot noise (ADSN). These models permit to synthesize random phase textures. They arguably derive from linearized versions of two early Julesz texture discrimination theories. The ensuing mathematical analysis shows that, contrarily to some statements in the literature, RPN and ADSN are different stochastic processes. Nevertheless, numerous experiments also suggest that the textures obtained by these algorithms from identical samples are perceptually similar. The relevance of this study is enhanced by three technical contributions providing solutions to obstacles that prevented the use of RPN or ADSN to emulate textures. First, RPN and ADSN algorithms are extended to color images. Second, a preprocessing is proposed to avoid artifacts due to the nonperiodicity of real-world texture samples. Finally, the method is extended to synthesize textures with arbitrary size from a given sample. PMID:20550995
Faddeev random-phase approximation for molecules
Degroote, Matthias; Van Neck, Dimitri; Barbieri, Carlo
2011-04-15
The Faddeev random-phase approximation is a Green's function technique that makes use of Faddeev equations to couple the motion of a single electron to the two-particle-one-hole and two-hole-one-particle excitations. This method goes beyond the frequently used third-order algebraic diagrammatic construction method: all diagrams involving the exchange of phonons in the particle-hole and particle-particle channel are retained, but the phonons are now described at the level of the random-phase approximation, which includes ground-state correlations, rather than at the Tamm-Dancoff approximation level, where ground-state correlations are excluded. Previously applied to atoms, this paper presents results for small molecules at equilibrium geometry.
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.
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). PMID:26729448
Nabholtz, J M; Chalabi, N; Radosevic-Robin, N; Dauplat, M M; Mouret-Reynier, M A; Van Praagh, I; Servent, V; Jacquin, J P; Benmammar, K E; Kullab, S; Bahadoor, M R K; Kwiatkowski, F; Cayre, A; Abrial, C; Durando, X; Bignon, Y J; Chollet, P; Penault-Llorca, F
2016-05-01
Systemic therapy for triple negative breast cancer (TNBC) is mostly based upon chemotherapy. Epithelial Growth Factor Receptor (EGFR) is overexpressed in around 50% of TNBC and may play a role in its pathogenesis. Consequently, we performed a multicentric pilot Phase II neoadjuvant trial of cetuximab (anti-EGFR antibody) combined with docetaxel for patients with operable, Stage II-III TNBC. Therapy consisted of weekly cetuximab (first infusion: 400 mg/m(2), then 250 mg/m(2)) combined with six cycles of docetaxel (T: 100 mg/m(2)) q.3 weeks. Subsequently, all patients underwent surgery. The primary endpoint was pathological complete response (pCR) while clinical response, toxicity and ancillary studies were secondary endpoints. Paraffin-embedded and frozen tumor samples were systematically collected in order to identify predictive biomarkers of efficacy and resistance. From a total of 35 accrued patients, 25 were assessable for pathologic response. The pCR rate was 24% [95% CI: 7.3-40.7]. Complete clinical response rate (cCR) was observed in 22% of cases. Conservative surgery was performed in 75% of patients. Toxicity, mostly cutaneous and hematologic, was manageable. The pre-therapy ratio between CD8+ and FOXP3+ tumor-infiltrating lymphocytes equal or higher than 2.75 was predictive of pCR: 43% versus 0%, p = 0.047. Cetuximab in combination with docetaxel displays a modest activity, but acceptable toxicity as neoadjuvant therapy of operable TNBC. Similarly to previous observations using panitumumab, another anti-EGFR antibody, the immune component of the tumor microenvironment may play an important role in predicting TNBC response to the neoadjuvant therapy. PMID:26649807
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
Four-phase rhinomanometry: a multicentric retrospective analysis of 36,563 clinical measurements.
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. PMID:26198284
Tembe, D. V.; Dhavale, A.; Desai, H.; Mane, D. N.; Raut, S. K.; Dhingra, G.; Sardesai, U.; Saoji, S.; Rohra, M.; Shinde, V. G.; Padsalge, M.; Paliwal, A.; Abbasi, K.; Devnani, P.; Papinwar, S.; Phadke, S.; Mehta, H.; Bhailume, V.
2011-01-01
Aim. To compare the efficacy and safety of armodafinil, the R-enantiomer of modafinil, with modafinil in patients of shift work sleep disorder (SWSD). Material and Methods. This was a 12-week, randomized, comparative, double-blind, multicentric, parallel-group study in 211 patients of SWSD, receiving armodafinil (150 mg) or modafinil (200 mg) one hour prior to the night shift. Outcome Measures. Efficacy was assessed by change in stanford sleepiness score (SSS) by at least 2 grades (responder) and global assessment for efficacy. Safety was assessed by incidence of adverse events, change in laboratory parameters, ECG, and global assessment of tolerability. Results. Both modafinil and armodafinil significantly improved sleepiness mean grades as compared to baseline (P < .0001). Responder rates with armodafinil (72.12%) and modafinil (74.29%) were comparable (P = .76). Adverse event incidences were comparable. Conclusion. Armodafinil was found to be safe and effective in the treatment of SWSD in Indian patients. The study did not demonstrate any difference in efficacy and safety of armodafinil 150 mg and modafinil 200 mg. PMID:21766023
2010-01-01
Background Acute pharyngitis is one of the most frequent consultations to the general practitioner and in most of the cases an antibiotic is prescribed in primary care in Spain. Bacterial etiology, mainly by group A beta-hemolytic streptococcus (GABHS), accounts for 10-20% of all these infections in adults. The purpose of this study is to assess the impact of rapid antigen detection testing (RADT) to identify GABHS in acute pharyngitis on the utilization of antibiotics in primary care. Methods/design Multicentric randomized controlled trial in which antibiotic prescription between two groups of patients with acute pharyngitis will be compared. The trial will include two arms, a control and an intervention group in which RADT will be performed. The primary outcome measure will be the proportion of inappropriate antibiotic prescription in each group. Two hundred seventy-six patients are required to detect a reduction in antibiotic prescription from 85% in the control group to 75% in the intervention group with a power of 90% and a level of significance of 5%. Secondary outcome measures will be specific antibiotic treatment, antibiotic resistance rates, secondary effects, days without working, medical visits during the first month and patient satisfaction. Discussion The implementation of RADT would allow a more rational use of antibiotics and would prevent adverse effects of antibiotics, emergence of antibiotic resistance and the growth of inefficient health expenses. Trial registration ISRCTN23587778 PMID:20331895
Armstrong, Matthew J; Barton, Darren; Gaunt, Piers; Hull, Diana; Guo, Kathy; Stocken, Deborah; Gough, Stephen C L; Tomlinson, Jeremy W; Brown, Rachel M; Hübscher, Stefan G; Newsome, Philip N
2013-01-01
Introduction Non-alcoholic steatohepatitis (NASH) is now the commonest cause of chronic liver disease. Despite this, there are no universally accepted pharmacological therapies for NASH. Liraglutide (Victoza), a human glucagon-like peptide-1 (GLP-1) analogue, has been shown to improve weight loss, glycaemic control and liver enzymes in type 2 diabetes. There is currently a lack of prospective-controlled studies investigating the efficacy of GLP-1 analogues in patients with NASH. Methods and analysis Liraglutide efficacy and action in NASH (LEAN) is a phase II, multicentre, double-blinded, placebo-controlled, randomised clinical trial designed to investigate whether a 48-week treatment with 1.8 mg liraglutide will result in improvements in liver histology in patients with NASH. Adult, overweight (body mass index ≥25 kg/m2) patients with biopsy-confirmed NASH were assessed for eligibility at five recruitment centres in the UK. Patients who satisfied the eligibility criteria were randomly assigned (1:1) to receive once-daily subcutaneous injections of either 1.8 mg liraglutide or liraglutide-placebo (control). Using A'Hern's single stage phase II methodology (significance level 0.05; power 0.90) and accounting for an estimated 20% withdrawal rate, a minimum of 25 patients were randomised to each treatment group. The primary outcome measure will be centrally assessed using an intention-to-treat analysis of the proportion of evaluable patients achieving an improvement in liver histology between liver biopsies at baseline and after 48 weeks of treatment. Histological improvement will be defined as a combination of the disappearance of active NASH and no worsening in fibrosis. Ethics and dissemination The protocol was approved by the National Research Ethics Service (East Midlands—Northampton committee; 10/H0402/32) and the Medicines and Healthcare products Regulatory Agency. Recruitment into the LEAN started in August 2010 and ended in May 2013, with 52
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
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
Random phase-shifting interferometry based on independent component analysis
NASA Astrophysics Data System (ADS)
Xu, Xiaofei; Lu, Xiaoxu; Tian, Jindong; Shou, Junwei; Zheng, Dejin; Zhong, Liyun
2016-07-01
In random phase-shifting interferometry, a novel phase retrieval algorithm is proposed based on the independent component analysis (ICA). By performing the recombination of pixel position, a sequence of phase-shifting interferograms with random phase shifts are decomposed into a group of mutual independent components, and then the background and the measured phase of interferogram can obtained with a simple arctangent operation. Compared with the conventional advanced iterative algorithm (AIA) with high accuracy, both the simulation and the experimental results demonstrate that the proposed ICA algorithm reveals high accuracy, rapid convergence, and good noise-tolerance in random phase-shifting interferometry.
Phase Structure of the Random Zq Models in 2D
NASA Astrophysics Data System (ADS)
Sasamoto, T.; Nishimori, H.
We discuss the phase diagram of the random Zq models in two dimensions. It is argued that, when q is large enough, there exist three phases in the phase diagram with two axes being the temperature and the strength of randomness. Our conlusions are derived based on the application of the duality arguments for random systems, which have been formulated recently by Maillard et al.
Self-Consistent Random Phase Approximation
NASA Astrophysics Data System (ADS)
Rohr, Daniel; Hellgren, Maria; Gross, E. K. U.
2012-02-01
We report self-consistent Random Phase Approximation (RPA) calculations within the Density Functional Theory. The calculations are performed by the direct minimization scheme for the optimized effective potential method developed by Yang et al. [1]. We show results for the dissociation curve of H2^+, H2 and LiH with the RPA, where the exchange correlation kernel has been set to zero. For H2^+ and H2 we also show results for RPAX, where the exact exchange kernel has been included. The RPA, in general, over-correlates. At intermediate distances a maximum is obtained that lies above the exact energy. This is known from non-self-consistent calculations and is still present in the self-consistent results. The RPAX energies are higher than the RPA energies. At equilibrium distance they accurately reproduce the exact total energy. In the dissociation limit they improve upon RPA, but are still too low. For H2^+ the RPAX correlation energy is zero. Consequently, RPAX gives the exact dissociation curve. We also present the local potentials. They indicate that a peak at the bond midpoint builds up with increasing bond distance. This is expected for the exact KS potential.[4pt] [1] W. Yang, and Q. Wu, Phys. Rev. Lett., 89, 143002 (2002)
Ndiaye, Jean Louis; Randrianarivelojosia, Milijaona; Sagara, Issaka; Brasseur, Philippe; Ndiaye, Ibrahima; Faye, Babacar; Randrianasolo, Laurence; Ratsimbasoa, Arsène; Forlemu, Doris; Moor, Vicky Ama; Traore, Aminata; Dicko, Yahia; Dara, Niawanlou; Lameyre, Valérie; Diallo, Mouctar; Djimde, Abdoulaye; Same-Ekobo, Albert; Gaye, Oumar
2009-01-01
Background The use of artemisinin derivative-based combination therapy (ACT) such as artesunate plus amodiaquine is currently recommended for the treatment of uncomplicated Plasmodium falciparum malaria. Fixed-dose combinations are more adapted to patients than regimens involving multiple tablets and improve treatment compliance. A fixed-dose combination of artesunate + amodiaquine (ASAQ) was recently developed. To assess the efficacy and safety of this new combination and to define its optimum dosage regimen (once or twice daily) in the treatment of uncomplicated P. falciparum malaria, a multicentre clinical study was conducted. Methods A multicentre, randomized, controlled, investigator-blinded, parallel-group study was conducted in five African centers in Cameroon, Madagascar, Mali and Senegal from March to December 2006. Efficacy and safety of ASAQ were assessed compared to those of artemether + lumefantrine (AL). The WHO protocol with a 28-day follow-up for assessing the drug therapeutic efficacy was used. Patients suffering from uncomplicated P. falciparum malaria were randomized to receive ASAQ orally once daily (ASAQ1), ASAQ twice daily (ASAQ2) or AL twice daily (AL) for three days. The primary outcome was PCR-corrected parasitological cure rate and clinical response. Results Of 941 patients initially randomized and stratified into two age groups (<5 years, and ≥5 years), 936 (99.5%) were retained for the intent to treat (ITT) analysis, and 859 (91.3%) patients for the per protocol (PP) analysis. Among ITT population, up to D28, PCR-corrected adequate parasitological and clinical response rates were 95.2% in the ASAQ1 group, 94.9% in the ASAQ2 group and 95.5% in the AL group. Moreover, the cure rate evaluated among PP population was ≥98.5% in both ASAQ therapeutic arms. Therapeutic response rates did not display any significant differences between age groups or between one geographical site and another. Altogether, this demonstrates the non
Ponikowski, Piotr; Mitrovic, Veselin; Ruda, Mikhail; Fernandez, Alberto; Voors, Adriaan A.; Vishnevsky, Alexander; Cotter, Gad; Milo, Olga; Laessing, Ute; Zhang, Yiming; Dahlke, Marion; Zymlinski, Robert; Metra, Marco
2014-01-01
Aims The aim of this study was to evaluate the haemodynamic effects of serelaxin (30 µg/kg/day 20-h infusion and 4-h post-infusion period) in patients with acute heart failure (AHF). Methods and results This double-blind, multicentre study randomized 71 AHF patients with pulmonary capillary wedge pressure (PCWP) ≥18 mmHg, systolic blood pressure (BP) ≥115 mmHg, and estimated glomerular filtration rate ≥30 mL/min/1.73 m2 to serelaxin (n = 34) or placebo (n = 37) within 48 h of hospitalization. Co-primary endpoints were peak change from baseline in PCWP and cardiac index (CI) during the first 8 h of infusion. Among 63 patients eligible for haemodynamic analysis (serelaxin, n = 32; placebo, n = 31), those treated with serelaxin had a significantly higher decrease in peak PCWP during the first 8 h of infusion (difference vs. placebo: −2.44 mmHg, P = 0.004). Serelaxin showed no significant effect on the peak change in CI vs. placebo. Among secondary haemodynamic endpoints, a highly significant reduction in pulmonary artery pressure (PAP) was observed throughout the serelaxin infusion (largest difference in mean PAP vs. placebo: −5.17 mmHg at 4 h, P < 0.0001). Right atrial pressure, systemic/pulmonary vascular resistance, and systolic/diastolic BP decreased from baseline with serelaxin vs. placebo and treatment differences reached statistical significance at some time points. Serelaxin administration improved renal function and decreased N-terminal pro-brain natriuretic peptide levels vs. placebo. Treatment with serelaxin was well tolerated with no apparent safety concerns. Conclusion The haemodynamic effects of serelaxin observed in the present study provide plausible mechanistic support for improvement in signs and symptoms of congestion observed with this agent in AHF patients. ClinicalTrials.gov identifier NCT01543854. PMID:24255129
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
Júnior, Lúcio Honório de Carvalho; Soares, Luiz Fernando Machado; Gonçalves, Matheus Braga Jacques; Gomes, Tiago Pinto de Oliveira; Oliveira, Juraci Rosa de; Coelho, Mauro Gualberto; Santos, Rogério Luciano dos; Andrade, Marco Antônio Percope de; Silva, Guilherme de Lima e; Novais, Eduardo Nilo Vasconcelos
2015-01-01
To evaluate whether, by using an arthropump (irrigation equipment with pressure sensor), pneumatic tourniquet use could interfere with the duration of surgery, recovery of movement and joint volume in patients who underwent knee videoarthroscopy for partial meniscectomy. Methods: 103 patients divided randomly into two groups regarding use or nonuse of a pneumatic tourniquet were evaluated in five different centers by seven different surgeons. The variables were evaluated during the surgery and seven days after the operation. Results: No statistically significant differences were found among any of the variables studied. Conclusion: There are no reasons that would either justify or discredit tourniquet use in this specific situation. PMID:27022588
Zech, C J; Korpraphong, P; Huppertz, A; Denecke, T; Kim, M-J; Tanomkiat, W; Jonas, E; Ba-Ssalamah, A
2014-01-01
Background This multicentre international randomized trial compared the impact of gadoxetic acid-enhanced magnetic resonance imaging (MRI), MRI with extracellular contrast medium (ECCM-MRI) and contrast-enhanced computed tomography (CE-CT) as a first-line imaging method in patients with suspected colorectal cancer liver metastases (CRCLM). Methods Between October 2008 and September 2010, patients with suspected CRCLM were randomized to one of the three imaging modalities. The primary endpoint was the proportion of patients for whom further imaging after initial imaging was required for a confident diagnosis. Secondary variables included confidence in the therapeutic decision, intraoperative deviations from the initial imaging-based surgical plan as a result of additional operative findings, and diagnostic efficacy of the imaging modalities versus intraoperative and pathological extent of the disease. Results A total of 360 patients were enrolled. Efficacy was analysed in 342 patients (118, 112 and 112 with gadoxetic acid-enhanced MRI, ECCM-MRI and CE-CT respectively as the initial imaging procedure). Further imaging was required in 0 of 118, 19 (17·0 per cent) of 112 and 44 (39·3 per cent) of 112 patients respectively (P < 0·001). Diagnostic confidence was high or very high in 98·3 per cent of patients for gadoxetic acid-enhanced MRI, 85·7 per cent for ECCM-MRI and 65·2 per cent for CE-CT. Surgical plans were changed during surgery in 28, 32 and 47 per cent of patients in the respective groups. Conclusion The diagnostic performance of gadoxetic acid-enhanced MRI was better than that of CE-CT and ECCM-MRI as the initial imaging modality. No further imaging was needed in the gadoxetic acid-enhanced MRI group and comparison of diagnostic efficacy parameters demonstrated the diagnostic superiority of gadoxetic acid-enhanced MRI. Registration number: NCT00764621( http://clinicaltrials.gov ); EudraCT number: 2008-000583-16 ( https://eudract.ema.europa.eu/ ). PMID
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
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. PMID:24329913
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
Double random-phase encoding in the Fresnel domain.
Situ, Guohai; Zhang, Jingjuan
2004-07-15
A lensless optical security system based on double random-phase encoding in the Fresnel domain is proposed. This technique can encrypt a primary image to random noise by use of two statistically independent random-phase masks in the input and transform planes, respectively. In this system the positions of the significant planes and the operation wavelength, as well as the phase codes, are used as keys to encrypt and recover the primary image. Therefore higher security is achieved. The sensitivity of the decrypted image to shifting along the propagation direction and to the wavelength are also investigated. PMID:15309826
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).
Lower Bounds for Phase Estimation of PSK Packets with Random Phase
NASA Technical Reports Server (NTRS)
Drake, Jeffrey
1999-01-01
In this paper, we derive new Cramer-Rao bounds (CRBs) for the estimation of phase from a block of random M-PSK (M=2,4,8) symbols where the phase to be estimated is a random variable. Existing bounds for 2 and 4-PSK which model the phase as non-random are extended to obtain a new 8-PSK CRB. The new random phase bounds are compared to the new 8-PSK and existing 2,4-PSK bounds which model the phase as non-random. We see that the random phase CRBs more accurately model the behavior if the phase, as normally happens, is suppose to be constrained to the interval [-pi/M,pi/M).
Phase randomization of three-wave interactions in capillary waves.
Punzmann, H; Shats, M G; Xia, H
2009-08-01
We present new experimental results on the transition from coherent-phase to random-phase three-wave interactions in capillary waves under parametric excitation. Above the excitation threshold, coherent wave harmonics spectrally broaden. An increase in the pumping amplitude increases spectral widths of wave harmonics and eventually causes a strong decrease in the degree of the three-wave phase coupling. The results point to the modulation instability of capillary waves, which leads to breaking of continuous waves into ensembles of short-lived wavelets or envelope solitons, as the reason for the phase randomization of three-wave interactions. PMID:19792572
NASA Astrophysics Data System (ADS)
Avena, L.; Thomann, P.
2012-07-01
We perform simulations for one dimensional continuous-time random walks in two dynamic random environments with fast (independent spin-flips) and slow (simple symmetric exclusion) decay of space-time correlations, respectively. We focus on the asymptotic speeds and the scaling limits of such random walks. We observe different behaviors depending on the dynamics of the underlying random environment and the ratio between the jump rate of the random walk and the one of the environment. We compare our data with well known results for static random environment. We observe that the non-diffusive regime known so far only for the static case can occur in the dynamical setup too. Such anomalous fluctuations give rise to a new phase diagram. Further we discuss possible consequences for more general static and dynamic random environments.
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.
Spatial Distribution of Phase Singularities in Optical Random Vector Waves.
De Angelis, L; Alpeggiani, F; Di Falco, A; Kuipers, L
2016-08-26
Phase singularities are dislocations widely studied in optical fields as well as in other areas of physics. With experiment and theory we show that the vectorial nature of light affects the spatial distribution of phase singularities in random light fields. While in scalar random waves phase singularities exhibit spatial distributions reminiscent of particles in isotropic liquids, in vector fields their distribution for the different vector components becomes anisotropic due to the direct relation between propagation and field direction. By incorporating this relation in the theory for scalar fields by Berry and Dennis [Proc. R. Soc. A 456, 2059 (2000)], we quantitatively describe our experiments. PMID:27610854
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.
Ultrafast quantum random number generation based on quantum phase fluctuations.
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. PMID:22714224
van Rhee, Frits; Casper, Corey; Voorhees, Peter M.; Fayad, Luis E.; van de Velde, Helgi; Vermeulen, Jessica; Qin, Xiang; Qi, Ming; Tromp, Brenda; Kurzrock, Razelle
2015-01-01
Background Multicentric Castleman disease (MCD) is a rare, systemic lymphoproliferative disorder driven by interleukin (IL)-6 overproduction. Siltuximab, an anti-IL-6 monoclonal antibody, has demonstrated durable tumor and symptomatic responses in a multinational, randomized, placebo-controlled study of MCD. Methods This preplanned safety analysis was conducted to evaluate the long-term safety of siltuximab treatment among 19 patients with MCD who had stable disease or better and were enrolled in a phase-1 study and subsequent ongoing, open-label, phase-2 extension study. Dosing was 11 mg/kg administered intravenously every 3 weeks, per protocol, or every 6 weeks at the investigator's discretion. Safety monitoring focused on potential risks associated with the anti-IL-6 mechanism of action. Investigator-assessed disease control status was also documented. Results Median treatment duration for the 19 patients was 5.1 (range 3.4, 7.2) years, with 14 (74%) patients treated for >4 years. Grade-≥3 adverse events (AEs) reported in >1 patient included hypertension (n = 3) and nausea, cellulitis, and fatigue (n = 2 each). Grade-≥3 AEs at least possibly attributed to siltuximab were leukopenia, lymphopenia, and a serious AE of polycythemia (n = 1 each). Hypertriglyceridemia and hypercholesterolemia (total cholesterol) were reported in 8 and 9 patients, respectively. No disease relapses were observed, and 8 of 19 patients were able to switch to an every-6-week dosing schedule. Conclusions All MCD patients in this extension study have received siltuximab for a prolonged duration (up to 7 years) without evidence of cumulative toxicity or treatment discontinuations and with few serious infections. All patients are alive, demonstrate sustained disease control, and continue to receive siltuximab. PMID:26327301
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.
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
2014-01-01
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. PMID:24617454
Absolute uniqueness of phase retrieval with random illumination
NASA Astrophysics Data System (ADS)
Fannjiang, Albert
2012-07-01
Random illumination is proposed to enforce absolute uniqueness and resolve all types of ambiguity, trivial or nontrivial, in phase retrieval. Almost sure irreducibility is proved for any complex-valued object whose support set has rank ⩾ 2. While the new irreducibility result can be viewed as a probabilistic version of the classical result by Bruck, Sodin and Hayes, it provides a novel perspective and an effective method for phase retrieval. In particular, almost sure uniqueness, up to a global phase, is proved for complex-valued objects under general two-point conditions. Under a tight sector constraint absolute uniqueness is proved to hold with probability exponentially close to unity as the object sparsity increases. Under a magnitude constraint with random amplitude illumination, uniqueness modulo global phase is proved to hold with probability exponentially close to unity as object sparsity increases. For general complex-valued objects without any constraint, almost sure uniqueness up to global phase is established with two sets of Fourier magnitude data under two independent illuminations. Numerical experiments suggest that random illumination essentially alleviates most, if not all, numerical problems commonly associated with the standard phasing algorithms.
Phase conjugation with random fields and with deterministic and random scatterers
Gbur, G.; Wolf, E.
1999-01-01
The theory of distortion correction by phase conjugation, developed since the discovery of this phenomenon many years ago, applies to situations when the field that is conjugated is monochromatic and the medium with which it interacts is deterministic. In this Letter a generalization of the theory is presented that applies to phase conjugation of partially coherent waves interacting with either deterministic or random weakly scattering nonabsorbing media. {copyright} {ital 1999} {ital Optical Society of America}
Transformation of phase transitions driven by an anisotropic random field
NASA Astrophysics Data System (ADS)
Popa-Nita, V.; Kralj, Samo
2005-04-01
We carry out a comparative study of the influence of a random anisotropy field on continuous and discontinuous phase transitions. The ordered phase, which is reached via a continuous symmetry breaking phase transition, is characterized by an order parameter and by a corresponding hydrodynamic continuum field. We assume that the response of the hydrodynamic field to the imposed disorder results in a domainlike pattern of the system. For a strong enough disorder both transitions become gradual. For weaker disorder strengths the disorder converts a second order transition into a discontinuous one.
Neutron diffusion in a randomly inhomogeneous multiplying medium with random phase approximation
NASA Astrophysics Data System (ADS)
Imre, Kaya; Akcasu, A. Ziya
2012-06-01
Neutron diffusion in a randomly inhomogeneous multiplying medium is studied. By making use of a random phase assumption we show that the average neutron density approximately satisfies an integral equation in Fourier space, which is solved using Kummer functions. We used multi-dimensional formulation. In the case of one dimension, we obtain the result of Rosenbluth and Tao for the mean total density for large t. In the three-dimensional case, a closed form of solution is derived for the mean total neutron density. Its asymptotic behavior is also investigated for large t.
Neutron diffusion in a randomly inhomogeneous multiplying medium with random phase approximation
Imre, Kaya; Akcasu, A. Ziya
2012-06-15
Neutron diffusion in a randomly inhomogeneous multiplying medium is studied. By making use of a random phase assumption we show that the average neutron density approximately satisfies an integral equation in Fourier space, which is solved using Kummer functions. We used multi-dimensional formulation. In the case of one dimension, we obtain the result of Rosenbluth and Tao for the mean total density for large t. In the three-dimensional case, a closed form of solution is derived for the mean total neutron density. Its asymptotic behavior is also investigated for large t.
Three-dimensional photon counting double-random-phase encryption.
Cho, Myungjin; Javidi, Bahram
2013-09-01
In this Letter, we present a three-dimensional (3D) photon counting double-random-phase encryption (DRPE) technique using passive integral imaging. A 3D photon counting DRPE can encrypt a 3D scene and provides more security and authentications due to photon counting Poisson nonlinear transformation on the encrypted image. In addition, 3D imaging allows verification of the 3D object at different depths. Preliminary results and performance evaluation have been presented. PMID:23988912
2013-01-01
Background Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. Methods This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. Results Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. Conclusion Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. Trial registration ClinicalTrials.gov Identifier NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18. PMID:24053191
Katayama, Kanako; Misawa, Sonoko; Sato, Yasunori; Sobue, Gen; Yabe, Ichiro; Watanabe, Osamu; Nishizawa, Masatoyo; Kusunoki, Susumu; Kikuchi, Seiji; Nakashima, Ichiro; Ikeda, Shu-ichi; Kohara, Nobuo; Kanda, Takashi; Kira, Jun-ichi; Hanaoka, Hideki; Kuwabara, Satoshi
2015-01-01
Introduction Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome is a fatal systemic disorder associated with plasma cell dyscrasia and the overproduction of the vascular endothelial growth factor (VEGF). Recently, the prognosis of POEMS was substantially improved by introduction of therapeutic intervention for myeloma. However, no randomised clinical trial has been performed because of the rarity and severity of the disease. Methods and analysis The Japanese POEMS syndrome with Thalidomide (J-POST) Trial is a phase II/III multicentre, double-blinded, randomised, controlled trial that aims to evaluate the efficacy and safety of a 24-week treatment with thalidomide in POEMS syndrome, with an additional 48-week open-label safety study. Adults with POEMS syndrome who have no indication for transplantation are assessed for eligibility at 12 tertiary neurology centres in Japan. Patients who satisfy the eligibility criteria are randomised (1:1) to receive thalidomide (100–300 mg daily) plus dexamethasone (12 mg/m2 on days 1–4 of a 28-day cycle) or placebo plus dexamethasone. Both treatments were administered for 24 weeks (six cycles; randomised comparative study period). Patients who complete the randomised study period or show subacute deterioration during the randomised period participate in the subsequent 48-week open-label safety study (long-term safety period). The primary end point of the study is the reduction rate of serum VEGF levels at 24 weeks. Ethics and dissemination The protocol was approved by the Institutional Review Board of each hospital. The trial was notified and registered at the Pharmaceutical and Medical Devices Agency, Japan (No. 22-1716). The J-POST Trial is currently ongoing and is due to finish in August 2015. The findings of this trial will be disseminated through peer-reviewed publications and conference presentations and will also be disseminated to participants. Trial registration number
Camporese, Giuseppe; Bernardi, Enrico; Noventa, Franco; Bosco, Mario; Monteleone, Giuseppe; Santoro, Luca; Bortoluzzi, Cristiano; Freguja, Stefano; Nardin, Michela; Marullo, Matteo; Zanon, Giacomo; Mazzola, Claudio; Damiani, Guido; Maniscalco, Pietro; Imberti, Davide; Lodigiani, Corrado; Becattini, Cecilia; Tonello, Chiara; Agnelli, Giancarlo
2016-08-01
Without thromboprophylaxis, knee arthroscopy (KA) carries a low to moderate risk of venous thromboembolism. Over 5 million arthroscopies are performed worldwide yearly. It was our study objective to assess the efficacy and safety of rivaroxaban for thromboprophylaxis after therapeutic KA. Patients undergoing KA in nine Italian teaching or community hospitals were allocated to once-daily rivaroxaban (10 mg) or placebo for seven days in a phase II, multicentre, double-blind, placebo-controlled randomised trial. The primary efficacy outcome was a composite of all-cause death, symptomatic thromboembolism and asymptomatic proximal DVT at three months; major bleeding represented the primary safety outcome. All patients underwent whole-leg ultrasonography at day 7(+1), or earlier if symptomatic. A total of 241 patients were randomised (122 rivaroxaban, 119 placebo), and 234 completed the study. The primary efficacy outcome occurred in 1/120 of the rivaroxaban group and in 7/114 of the placebo group (0.8 % vs 6.1 %, respectively, p=0.03; absolute risk difference, -5.3 %, 95 % CI, -11.4 to -0.8; crude relative risk 0.14, 95 % CI, 0.02 to 0.83; number-needed-to-treat=19). No major bleedings were observed. We found no association between different arthroscopic procedures and thrombotic events. Small sample size, high exclusion rate, and low number of anterior cruciate ligament reconstruction procedures are the main limitations of our study. In conclusion, a seven-day course of 10-mg rivaroxaban may be safely employed for thromboprophylaxis after KA. Whether prophylaxis after KA should be given to all patients, or to selected "high-risk" subjects, remains to be determined. A larger trial to verify our preliminary results is warranted. PMID:27075710
Coiffier, Bertrand; Thieblemont, Catherine; de Guibert, Sophie; Dupuis, Jehan; Ribrag, Vincent; Bouabdallah, Réda; Morschhauser, Franck; Navarro, Robert; Le Gouill, Steven; Haioun, Corinne; Houot, Roch; Casasnovas, Olivier; Holte, Harald; Lamy, Thierry; Broussais, Florence; Payrard, Sandrine; Hatteville, Laurence; Tilly, Hervé
2016-06-01
In this phase II, multicentre, single-arm study, 52 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) received the anti-CD19 antibody-drug conjugate coltuximab ravtansine (55 mg/m(2) ) and rituximab (375 mg/m(2) ) weekly for 4 weeks, then every 2 weeks for 8 weeks. The primary endpoint was objective response rate (ORR) by International Working Group Criteria. The primary objective was to reject the null hypothesis of an ORR of ≤40%. Among 45 evaluable patients, the ORR was 31·1% (80% confidence interval [CI]: 22·0-41·6%) and the primary objective was not met. The ORR appeared higher in patients with relapsed disease (58·3% [80% CI: 36·2-78·1%]) versus those refractory to their last (42·9% [80% CI: 17·0-72·1%]) or first-line therapy (15·4% [80% CI: 6·9-28·4%]). Median progression-free survival, overall survival and duration of response were 3·9 [80% CI: 3·22-3·98], 9·0 [80% CI: 6·47-13·67] and 8·6 (range: 0-18) months, respectively. The pharmacokinetics of both drugs were unaffected by co-administration. Common adverse events included gastrointestinal disorders (52%) and asthenia (25%). No patients discontinued due to adverse events. In conclusion, coltuximab ravtansine with rituximab was well tolerated and yielded clinical responses in a subset of patients with relapsed/refractory DLBCL. PMID:27010483
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
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
Drugs, Women and Violence in the Americas: U.S. Results of a Multi-Centric Pilot Project (Phase 1).
González-Guarda, Rosa María; Peragallo, Nilda; Lynch, Ami; Nemes, Susanna
2010-09-01
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
Random and ordered phases of off-lattice rhombus tiles.
Whitelam, Stephen; Tamblyn, Isaac; Beton, Peter H; Garrahan, Juan P
2012-01-20
We study the covering of the plane by nonoverlapping rhombus tiles, a problem well studied only in the limiting case of dimer coverings of regular lattices. We go beyond this limit by allowing tiles to take any position and orientation on the plane, to be of irregular shape, and to possess different types of attractive interactions. Using extensive numerical simulations, we show that at large tile densities there is a phase transition from a fluid of rhombus tiles to a solid packing with broken rotational symmetry. We observe self-assembly of broken-symmetry phases, even at low densities, in the presence of attractive tile-tile interactions. Depending on the tile shape and interactions, the solid phase can be random, possessing critical orientational fluctuations, or crystalline. Our results suggest strategies for controlling tiling order in experiments involving "molecular rhombi." PMID:22400760
Random and ordered phases of off-lattice rhombus tiles
NASA Astrophysics Data System (ADS)
Whitelam, Stephen; Tamblyn, Isaac; Beton, Peter; Garrahan, Juan
2012-02-01
We study the covering of the plane by non-overlapping rhombus tiles, a problem well-studied only in the limiting case of dimer coverings of regular lattices. We go beyond this limit by allowing tiles to take any position and orientation on the plane, to be of irregular shape, and to possess different types of attractive interactions. Using extensive numerical simulations we show that at large tile densities there is a phase transition from a fluid of rhombus tiles to a solid packing with broken rotational symmetry. We observe self-assembly of broken-symmetry phases, even at low densities, in the presence of attractive tile-tile interactions. Depending on tile shape and interactions the solid phase can be random, possessing critical orientational fluctuations, or crystalline. Our results suggest strategies for controlling tiling order in experiments involving ``molecular rhombi.''
Random and Ordered Phases of Off-Lattice Rhombus Tiles
NASA Astrophysics Data System (ADS)
Whitelam, Stephen; Tamblyn, Isaac; Beton, Peter H.; Garrahan, Juan P.
2012-01-01
We study the covering of the plane by nonoverlapping rhombus tiles, a problem well studied only in the limiting case of dimer coverings of regular lattices. We go beyond this limit by allowing tiles to take any position and orientation on the plane, to be of irregular shape, and to possess different types of attractive interactions. Using extensive numerical simulations, we show that at large tile densities there is a phase transition from a fluid of rhombus tiles to a solid packing with broken rotational symmetry. We observe self-assembly of broken-symmetry phases, even at low densities, in the presence of attractive tile-tile interactions. Depending on the tile shape and interactions, the solid phase can be random, possessing critical orientational fluctuations, or crystalline. Our results suggest strategies for controlling tiling order in experiments involving “molecular rhombi.”
Phase diffusion and random walk interpretation of electromagnetic scattering
NASA Astrophysics Data System (ADS)
Bahcivan, Hasan; Hysell, David L.; Kelley, Michael C.
2003-08-01
The relaxation behavior of phase observables for different particle diffusion models is found to establish a ground for radioscience interpretations of coherent backscatter spectra. The characteristic function for a random walk process at twice the incident radiation wave number is associated with the complex amplitude of the scattered field from a medium containing refractive index fluctuations. The phase relaxation function can be connected to the evolution of the characteristic function and may describe the average regression of the scattered field from a spontaneous fluctuation undergoing turbulent mixing. This connection holds when we assume that the stochastic description of particle movements based on a diffusion model is valid. The phase relaxation function, when identified as the generalized susceptibility function of the fluctuation dissipation theorem, is related to the spectral density of the scattered field from steady-state fluctuations.
2014-01-01
Background Aviscumine, a recombinant plant protein, is an immune modulator that induces ribotoxic stress at the 28S ribosomal RNA subunit. In this way cytokine release and T-cell responses are enhanced. This phase II trial was conducted to test the efficacy and safety of aviscumine in patients with systemically pre-treated metastatic melanoma stage IV. Methods A total of 32 patients with progressive stage IV melanoma after failure of standard therapy were enrolled onto a single-arm, multi-centre, open-label, phase II trial. All patients had an ECOG performance status of 0 or 1. Patients received 350 ng aviscumine twice weekly by subcutaneous injection until progression. The primary end points were progression-free survival (PFS) and overall survival (OS). Safety was assessed as adverse events (AEs). Tumor response was assessed every eight weeks and survival of patients was followed up to one year after the end of therapy. Thirty one patients (intent-to-treat population (ITT)) were assessed for efficacy; safety was assessed in the whole population. Results One patient achieved a partial response (PR) and 10 patients showed stable disease/no change (SD). The median progression-free survival (mPFS) was 63 days (95% CI 57–85) and median overall survival (mOS) was 335 days (95% CI 210–604). In total 210 treatment-emergent adverse events were recorded. Grade 1 or 2 AEs occurred in 72% of patients and were mostly application-site effects such as pruritus Grade 3–4 treatment-emergent drug-related adverse events occurred in 9% of patients. Conclusion These results suggest that aviscumine may have a clinical impact in patients with previously treated metastatic melanoma and provide rationale for further clinical evaluation of this agent. In the light of effective new immune checkpoint blockers it might be a candidate for combinations with these agents. Trial registration ClinicalTrials.gov: NCT00658437 PMID:25324973
Tebib, Jacques; Mariette, Xavier; Bourgeois, Pierre; Flipo, René-Marc; Gaudin, Philippe; Le Loët, Xavier; Gineste, Paul; Guy, Laurent; Mansfield, Colin D; Moussy, Alain; Dubreuil, Patrice; Hermine, Olivier; Sibilia, Jean
2009-01-01
Introduction Since current treatment options for patients suffering from active rheumatoid arthritis (RA) remain inadequate, especially for those unresponsive to disease-modifying antirheumatic drugs (DMARDs), new and improved medication is needed. This study evaluates the safety and efficacy of masitinib (AB1010), a potent and selective protein tyrosine kinase inhibitor of c-KIT, in the monotherapy treatment of DMARD-refractory RA. Methods This was a multicentre, uncontrolled, open-label, randomised, dose-ranging, phase 2a trial. Masitinib was administered orally to 43 patients who had inadequate response to DMARDs, at initial randomised dosing levels of 3 and 6 mg/kg per day over a 12-week period. Dose adjustment was permitted based upon tolerability and response criteria. Efficacy was assessed via American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) responses, disease activity score using 28 joint counts (DAS28), index of improvement in RA (ACRn) and C-reactive protein (CRP) improvement, relative to baseline at week 12. Results Improvement was observed in all efficacy endpoints, including ACR20/50/70 scores of 54%, 26% and 8%, respectively, and a reduction in CRP level by greater than 50% for approximately half the population. This improvement was sustainable throughout an extension phase (> 84 weeks) and was also independent of initial DMARD resistance (anti-tumour necrosis factor-alpha and/or methotrexate). A relatively high patient withdrawal rate (37%) required the use of last observation carried forward (LOCF) data imputation. Incidence of adverse events was high (95%), although the majority were of mild or moderate severity with a considerable decline in frequency observed after 12 weeks of treatment. Two nonfatal serious adverse events were reported. Dose-response analyses tentatively indicate that an initial dosing level of 6.0 mg/kg per day administered orally in two daily intakes is the most appropriate, based upon potency
NASA Astrophysics Data System (ADS)
Carpio, Justine Patricia L.; Almoro, Percival F.
2014-10-01
A technique for digital watermarking of smooth object wavefronts using digital random phase modulation and multiple-plane iterative phase retrieval is demonstrated experimentally. A complex-valued watermark is first encrypted using two random phase masks of known distributions before being superposed onto a set of host wavefront intensity patterns. Encryption scaling factor and depth of randomization of the masks are optimized such that the amplitude and phase watermarks are decrypted successfully and are not distorting the host wavefront. Given that the watermarked intensity patterns and the numerous decryption keys are available (i.e. distances between recording planes, light source wavelength, pixel size, random phase masks and their distances to the planes are all known), increasing the number of watermarked patterns used results in enhanced quality of decrypted watermarks. The main advantage of wavefront watermarking via the phase retrieval approach compared to the holographic approach is the avoidance of reference wave-induced aberration. Watermarking of wavefronts from lenses and unstained human cheek cells demonstrate the effectiveness of the technique.
Doorway states in the random-phase approximation
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.
Laser-beam apodization with a graded random phase window.
Haas, R A; Summers, M A; Linford, G J
1986-10-01
Experiments and analysis indicate that graded random phase modulation can be used to apodize a laser beam. In the case of an obscuration or a hard edge it can prevent the formation of Fresnel-diffraction ripples. For example, here the interaction of a 1-microm-wavelength laser beam with a central obscuration of half-width a = 100 microm is studied theoretically. It is found that if the exit surface of a window, placed immediately downstream of the obstacle, is randomly modulated with a Gaussian amplitude transverse correlation length l = 50 microm and a mean-square amplitude that decreases exponentially from a peak height of ~1 microm(2) away from the center of the obscuration with transverse scale length L = 500 microm, then the Fresnel-diffraction ripples normally produced by the obscuration are eliminated. The scaling of these results is also discussed. The calculations are in general agreement with experimental results. PMID:19738707
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
Finite amplitude method for the quasiparticle random-phase approximation
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.
Modified random phase approximation for multipole excitations at finite temperature
Dang, N.D. )
1992-03-01
The modified finite-temperature random phase approximation (FT-RPA) has been constructed by taking the influence of thermostat on the structure of quasiparticles into account. The modified FT-RPA linear response for electric quadrupole ({lambda}{sup {pi}}=2{sup +}) and octupole ({lambda}{sup {pi}}=3{sup {minus}}) excitations in {sup 58}Ni has been calculated as a function of the nuclear temperature. As compared to the conventional FT-RPA, the modified FT-RPA has given a stronger spreading for the strength distribution of quadrupole excitations at finite temperature {ital T}{le}3 MeV.
Garcia-Aguilar, Julio; Chow, Oliver S; Smith, David D; Marcet, Jorge E; Cataldo, Peter A; Varma, Madhulika G; Kumar, Anjali S; Oommen, Samuel; Coutsoftides, Theodore; Hunt, Steven R; Stamos, Michael J; Ternent, Charles A; Herzig, Daniel O; Fichera, Alessandro; Polite, Blase N; Dietz, David W; Patil, Sujata; Avila, Karin
2015-01-01
Summary Background Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response. Methods We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II–III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m2 per day by continuous infusion throughout radiotherapy, and 45.0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5.4 Gy). Patients in group 1 had total mesorectal excision 6–8 weeks after chemoradiation. Patients in groups 2–4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m2 or 400 mg/m2, according to the discretion of the treating investigator, oxaliplatin 85 mg/m2 in a 2-h infusion, bolus fluorouracil 400 mg/m2 on day 1, and a 46-h infusion of fluorouracil 2400 mg/m2. The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816. Findings Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10–30) of 60 patients in group 1, 17 (25%, 16–37) of 67 in group 2, 20 (30%, 19–42) of 67 in group 3, and 25 (38%, 27–51) of 65 in group 4 achieved a pathological complete response (p=0.0036). Study group was
Schoemaker, N E; Kuppens, I E L M; Moiseyenko, V; Glimelius, B; Kjaer, M; Starkhammer, H; Richel, D J; Smaaland, R; Bertelsen, K; Poulsen, J P; Voznyi, E; Norum, J; Fennelly, D; Tveit, K M; Garin, A; Gruia, G; Mourier, A; Sibaud, D; Lefebvre, P; Beijnen, J H; Schellens, J H M; ten Bokkel Huinink, W W
2004-10-18
The purpose of this phase II trial was to compare the efficacy, safety and pharmacokinetics of four irinotecan schedules for the treatment of metastatic colorectal cancer. In total, 174 5-fluorouracil pretreated patients were randomised to: arm A (n=41), 350 mg m(-2) irinotecan as a 90-min i.v. infusion q3 weeks; arm B (n=38), 125 mg m(-2) irinotecan as a 90-min i.v. infusion weekly x 4 weeks q6 weeks; arm C (n=46), 250 mg m(-2) irinotecan as a 90-min i.v. infusion q2 weeks; or arm D (n=49), 10 mg m(-2) day(-1) irinotecan as a 14-day continuous infusion q3 weeks. No significant differences in efficacy across the four arms were observed, although a shorter time to treatment failure was noted for arm D (1.7 months; P=0.02). Overall response rates were in the range 5-11%. Secondary end points included median survival (6.4-9.4 months), and time to progression (2.7-3.8 months) and treatment failure (1.7-3.2 months). Similarly, there were no significant differences in the incidence of grade 3-4 toxicities, although the toxicity profile between arms A, B, and C and D did differ. Generally, significantly less haematologic toxicity, alopecia and cholinergic syndrome were observed in arm D; however, there was a trend for increased gastrointestinal toxicity. Irinotecan is an effective and safe second-line treatment for colorectal cancer. The schedules examined yielded equivalent results, indicating that there is no advantage of the prolonged vs short infusion schedules. PMID:15381932
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
A new phase of disordered phonons modelled by random matrices
NASA Astrophysics Data System (ADS)
Schmittner, Sebastian; Zirnbauer, Martin
2015-03-01
Starting from the clean harmonic crystal and not invoking two-level systems, we propose a model for phonons in a disordered solid. In this model the strength of mass and spring constant disorder can be increased separately. Both types of disorder are modelled by random matrices that couple the degrees of freedom locally. Treated in coherent potential approximation (CPA), the speed of sound decreases with increasing disorder until it reaches zero at finite disorder strength. There, a critical transition to a strong disorder phase occurs. In this novel phase, we find the density of states at zero energy in three dimensions to be finite, leading to a linear temperature dependence of the heat capacity, as observed experimentally for vitreous systems. For any disorder strength, our model is stable, i.e. masses and spring constants are positive, and there are no runaway dynamics. This is ensured by using appropriate probability distributions, inspired by Wishart ensembles, for the random matrices. The CPA self-consistency equations are derived in a very accessible way using planar diagrams. The talk focuses on the model and the results. The first author acknowledges financial support by the Deutsche Telekom Stiftung.
The peculiar phase structure of random graph bisection
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.
Ständer, Sonja; Metz, Martin; Ramos F, Mac H; Maurer, Marcus; Schoepke, Nicole; Tsianakas, Athanasios; Zeidler, Claudia; Luger, Thomas A
2016-08-23
This study was a prospective, parallel-group, randomized, double-blind, vehicle-controlled, multi-centre clinical trial to compare the efficacy of topical sertaconazole 2% cream with vehicle in reducing chronic pruritus in subjects with atopic dermatitis, and to assess its safety and local tolerability. A total of 70 subjects applied either of the 2 treatments twice daily for a period of 4 weeks on affected, itchy skin areas. Treatment efficacy was evaluated primarily considering the item itch intensity on a 5-point verbal rating scale. Insomnia, state of atopic dermatitis (Scoring Atopic Dermatitis; SCORAD), quality of life and therapy benefit were also assessed. No significant difference between active treatment and vehicle was found at any of the time-points for any of the investigated parameters. Under the experimental conditions of the study, sertaconazole 2% cream did not exert anti-pruritic effects that were better than vehicle in subjects with atopic dermatitis who had chronic pruritus. Trial registration ClinicalTrials.gov #NCT01792713. PMID:26527564
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
Glassy phases and driven response of the phase-field-crystal model with random pinning.
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. PMID:22060323
NASA Astrophysics Data System (ADS)
Almaev, R. Kh; Suvorov, A. A.
1993-09-01
We investigate the statistical characteristics of the phase of a wave propagating along a ranging path that includes a phase-conjugate mirror through a medium whose complex permittivity ɛ varies randomly. We obtain expressions for the mean change and variance of fluctuations in the phase of a plane wave. We show that phase fluctuations caused by the random changes of the imaginary part of ɛ are not canceled by the phase-conjugate mirror. We obtain conditions for the appearance of enhanced backward scattering in comparison with the mean phase and variance of phase fluctuations for the reflected wave in this absorbing, randomly inhomogeneous medium.
Meissner, H. O.; Mscisz, A.; Reich-Bilinska, H.; Kapczynski, W.; Mrozikiewicz, P.; Bobkiewicz-Kozlowska, T.; Kedzia, B.; Lowicka, A.; Barchia, I.
2006-01-01
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. PMID:23675005
A mathematical formulation of the random phase approximation for crystals
NASA Astrophysics Data System (ADS)
Cancès, Eric; Stoltz, Gabriel
2012-11-01
This works extends the recent study on the dielectric permittivity of crystals within the Hartree model [E. Cances and M. Lewin, Arch. Rational Mech. Anal., 197 (2010) 139--177] to the time-dependent setting. In particular, we prove the existence and uniqueness of the nonlinear Hartree dynamics (also called the random phase approximation in the physics literature), in a suitable functional space allowing to describe a local defect embedded in a perfect crystal. We also give a rigorous mathematical definition of the microscopic frequency-dependent polarization matrix, and derive the macroscopic Maxwell-Gauss equation for insulating and semiconducting crystals, from a first order approximation of the nonlinear Hartree model, by means of homogenization arguments.
Continuum random-phase approximation for relativistic point coupling models
Daoutidis, J.; Ring, P.
2009-08-15
Continuum relativistic random-phase approximation (CRPA) is used to investigate collective excitation phenomena in several spherical nuclei along the periodic table. We start from relativistic mean-field calculations based on a covariant density functional with density-dependent zero-range forces. From the same functional an effective interaction is obtained as the second derivative with respect to the density. This interaction is used in relativistic CRPA calculations for the investigation of isoscalar monopole, isovector dipole, and isoscalar quadrupole resonances of spherical nuclei. In particular we study the low-lying E1 strength in the vicinity of the neutron evaporation threshold. The properties of the resonances, such as centroid energies and strengths distributions are compared with results of discrete RPA calculations for the same model as well as with experimental data.
Phase transitions in the coloring of random graphs.
Zdeborová, Lenka; Krzakała, Florent
2007-09-01
We consider the problem of coloring the vertices of a large sparse random graph with a given number of colors so that no adjacent vertices have the same color. Using the cavity method, we present a detailed and systematic analytical study of the space of proper colorings (solutions). We show that for a fixed number of colors and as the average vertex degree (number of constraints) increases, the set of solutions undergoes several phase transitions similar to those observed in the mean field theory of glasses. First, at the clustering transition, the entropically dominant part of the phase space decomposes into an exponential number of pure states so that beyond this transition a uniform sampling of solutions becomes hard. Afterward, the space of solutions condenses over a finite number of the largest states and consequently the total entropy of solutions becomes smaller than the annealed one. Another transition takes place when in all the entropically dominant states a finite fraction of nodes freezes so that each of these nodes is allowed a single color in all the solutions inside the state. Eventually, above the coloring threshold, no more solutions are available. We compute all the critical connectivities for Erdos-Rényi and regular random graphs and determine their asymptotic values for a large number of colors. Finally, we discuss the algorithmic consequences of our findings. We argue that the onset of computational hardness is not associated with the clustering transition and we suggest instead that the freezing transition might be the relevant phenomenon. We also discuss the performance of a simple local Walk-COL algorithm and of the belief propagation algorithm in the light of our results. PMID:17930223
Exploring the Random Phase Approximately for materials chemistry and physics
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.
Dewan, Bhupesh; Philipose, Nisha
2011-01-01
Background. Empirical therapy with antisecretory agents like PPIs and H2RAs has long been the traditional approach in the initial management of uninvestigated dyspepsia. Aim. The objective of the study was to examine relief of dyspepsia with lafutidine, a second-generation H2-RA, and rabeprazole and to compare their efficacy. Methods. This was a randomized, open, comparative trial in adult uninvestigated dyspeptic patients, who had at least moderate severity of symptoms, defined as a score of ≥4 on a 7-point global overall symptom (GOS) scale, and were randomized to receive once daily either lafutidine 10 mg or rabeprazole 20 mg for 4 weeks. Results. A total of 236 patients were enrolled, out of which 194 patients were included in the analysis. At the end of week 4, a significant difference was observed for symptom relief (lafutidine 89.90% versus rabeprazole 65.26%, P < .01) and symptom resolution (lafutidine 70.71% versus rabeprazole 25.26%, P < .01). Both the drugs were well tolerated. Conclusion. Both lafutidine and rabeprazole provide symptom relief in patients with heartburn-dominant uninvestigated dyspepsia. The present study confirms the appropriateness of lafutidine as an empiric treatment and superior efficacy for primary care practice patients with dyspepsia. PMID:21687618
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
Postradiation multicentric osteosarcoma
Tillotson, C.; Rosenberg, A.; Gebhardt, M.; Rosenthal, D.I.
1988-07-01
The oncogenic effects of radiation are well-established. Osteosarcomas and fibrosarcomas are the two most common histologic types of secondary sarcoma. In this article a case of postradiation osteosarcoma is presented in which four discrete foci of sarcomatous transformation have occurred in the tibia and fibula after irradiation for a rhabdomyosarcoma of the calf 8 years earlier. A review of the literature reveals no similar case. Although synchronous, multifocal osteosarcoma without prior radiation has been described, this case differs in clinical, radiographic, and pathologic features; it best fits the description of postradiation multicentric osteosarcoma.
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. PMID:19175878
Random Phase Approximation in Surface Chemistry: Water Splitting on Iron.
Karlický, František; Lazar, Petr; Dubecký, Matúš; Otyepka, Michal
2013-08-13
The reaction of water with zero-valent iron (anaerobic corrosion) is a complex chemical process involving physisorption and chemisorption events. We employ random phase approximation (RPA) along with gradient-corrected and hybrid density functional theory (DFT) functionals to study the reaction of water with the Fe atom and Fe(100) surface. We show that the involvement of the exact electron exchange and nonlocal correlation effects in RPA improves the description of all steps of the reaction on the Fe surface with respect to standard [meaning local density approximation (LDA) or generalized gradient approximation (GGA)] DFT methods. The reaction profile calculated by range-separated hybrid functional HSE06 agrees reasonably well with the RPA profile, which makes HSE06 a computationally less demanding alternative to RPA. We also investigate the reaction of the Fe atom with water using DFT, RPA, and coupled-cluster through the perturbative triples complete basis set [CCSD(T)-3s3p-DKH/CBS] method. Local DFT methods significantly underestimate reaction barriers, while the reaction kinetics and thermodynamics from RPA agree with the reference CCSD(T) data. Both systems, i.e., the Fe atom and Fe(100), provide the same reaction mechanism, indicating that anaerobic corrosion is a stepwise process involving one-electron steps, with the first reaction step (formation of the HFeOH intermediate) representing the rate-limiting step. PMID:26584120
Predicting the Catalytic Reactions using Random Phase Approximation
NASA Astrophysics Data System (ADS)
Yan, J.; Olsen, T.; Mortensen, J. J.; Jacobsen, K. W.; Thygesen, K. S.; Abild-Pedersen, F.; Norskov, J. K.
2012-02-01
Density functional theory has became the workhorse for simulations of catalytic reactions and computational design of novel catalysis. The generally applied semi-local exchange-correlation functionals have successfully predicted catalytic reaction trends over a variety of surfaces. However, in order to achieve quantitative predictions of reaction rates for molecule-surface systems, in particular where there is weak Van der Waals interactions or strong correlation, it is of vital importance to include non-local correlation effects. The use of random phase approximation (RPA) to construct the correlation energy, combined with the exact, self-interaction free exchange energy, offers a non-empirical way for accurately describe the adsorption energies [1] and dispersion forces [2]. We have recently implemented RPA in the GPAW code [3-4], an electronic structure package using projector augmented wave method and real space grids. In this talk I will present our initial results comparing RPA and generalized gradient functionals for the activation energies and reaction energies for transition metal or metal oxide surfaces. [4pt] [1] L. Schimka, et.al, Nature Mat. 9, 741 (2010) [2] T. Olsen, et.al, Phys. Rev. Lett. 107, 156401 (2011) [3] J. Yan, et.al, Phys. Rev. B 83, 245122 (2011). [4] J. Yan, et.al, Phys. Rev. Lett. 106, 146803 (2011)
Separable pairing force for relativistic quasiparticle random-phase approximation
Tian Yuan; Ma Zhongyu; Ring, Peter
2009-06-15
We have introduced a separable pairing force, which was adjusted to reproduce the pairing properties of the Gogny force in nuclear matter. This separable pairing force is able to describe in relativistic Hartree-Bogoliubov (RHB) calculations the pairing properties in the ground state of finite nuclei on almost the same footing as the original Gogny interaction. In this work we investigate excited states using the Relativistic Quasiparticle Random-Phase Approximation (RQRPA) with the same separable pairing force. For consistency the Goldstone modes and the convergence with various cutoff parameters in this version of RQRPA are studied. The first excited 2{sup +} states for the chain of Sn isotopes with Z=50 and the chain of isotones with N=82 isotones are calculated in RQRPA together with the 3{sup -} states of Sn isotopes. By comparing our results with experimental data and with the results of the original Gogny force we find that this simple separable pairing interaction is very successful in depicting the pairing properties of vibrational excitations.
Communication: Random phase approximation renormalized many-body perturbation theory
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.
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
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
McCready, J.; Chow, A. W.; Lowe, M. D.; Segal, O. R.; Ahsan, S.; de Bono, J.; Dhaliwal, M.; Mfuko, C.; Ng, A.; Rowland, E. R.; Bradley, R. J. W.; Paisey, J.; Roberts, P.; Morgan, J. M.; Sandilands, A.; Yue, A.; Lambiase, P. D.
2014-01-01
Aims The current challenge in atrial fibrillation (AF) treatment is to develop effective, efficient, and safe ablation strategies. This randomized controlled trial assesses the medium-term efficacy of duty-cycled radiofrequency ablation via the circular pulmonary vein ablation catheter (PVAC) vs. conventional electro-anatomically guided wide-area circumferential ablation (WACA). Methods and results One hundred and eighty-eight patients (mean age 62 ± 12 years, 116 M : 72 F) with paroxysmal AF were prospectively randomized to PVAC or WACA strategies and sequentially followed for 12 months. The primary endpoint was freedom from symptomatic or documented >30 s AF off medications for 7 days at 12 months post-procedure. One hundred and eighty-three patients completed 12 m follow-up. Ninety-four patients underwent PVAC PV isolation with 372 of 376 pulmonary veins (PVs) successfully isolated and all PVs isolated in 92 WACA patients. Three WACA and no PVAC patients developed tamponade. Fifty-six percent of WACA and 60% of PVAC patients were free of AF at 12 months post-procedure (P = ns) with a significant attrition rate from 77 to 78%, respectively, at 6 months. The mean procedure (140 ± 43 vs. 167 ± 42 min, P<0.0001), fluoroscopy (35 ± 16 vs. 42 ± 20 min, P<0.05) times were significantly shorter for PVAC than for WACA. Two patients developed strokes within 72 h of the procedure in the PVAC group, one possibly related directly to PVAC ablation in a high-risk patient and none in the WACA group (P = ns). Two of the 47 patients in the PVAC group who underwent repeat ablation had sub-clinical mild PV stenoses of 25–50% and 1 WACA patient developed delayed severe PV stenosis requiring venoplasty. Conclusion The pulmonary vein ablation catheter is equivalent in efficacy to WACA with reduced procedural and fluoroscopy times. However, there is a risk of thrombo-embolic and pulmonary stenosis complications which needs to be addressed and prospectively monitored. Clinical
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
Lacour, J; Laplanche, A; Malafosse, M; Gallot, D; Julien, M; Rotman, N; Guivarc'h, M; Roullet-Audy, J C; Lasser, P; Hautefeuille, P
1992-12-01
In a double blind study, patients with operable carcinoma of the colon and the upper rectum, who have undergone a macroscopically complete resection of their tumor, were randomized to receive either (i) polyadenylic-polyuridylic acid (AU), one i.v. injection of 60 mg (in 50 ml of solution) once a week for 6 weeks, or (ii) a placebo (P) one i.v. injection of 50 ml of a saline solution with the same schedule. From January 1983 to December 1986, 288 patients were enrolled: 145 in AU group and 143 in P group. The main clinical and pathological characteristics were equally distributed throughout the two groups. There was a significant difference (P < 0.02) in the overall survival (OS) between the two groups, in favor of the P group. The 5-year OS rate was 68% (SD = 4%) in the AU group versus 81% (SD = 3%) in the P group. Thus, AU as a single adjuvant, appears to be ineffective and therefore has no indication in the treatment of colorectal carcinoma. PMID:1478293
Zuckermann, Andreas; Wang, Shoei-Shen; Ross, Heather; Frigerio, Maria; Eisen, Howard J.; Bara, Christoph; Hoefer, Daniel; Cotrufo, Maurizio; Dong, Gaohong; Junge, Guido; Keogh, Anne M.
2011-01-01
A six-month, multicenter, randomized, open-label study was undertaken to determine whether renal function is improved using reduced-exposure cyclosporine (CsA) versus standard-exposure CsA in 199 de novo heart transplant patients receiving everolimus and steroids ± induction therapy. Mean C2 levels were at the low end of the target range in standard-exposure patients (n = 100) and exceeded target range in reduced-exposure patients (n = 99) throughout the study. Mean serum creatinine at Month 6 (the primary endpoint) was 141.0 ± 53.1 μmol/L in standard-exposure patients versus 130.1 ± 53.7 μmol/L in reduced-exposure patients (P = 0.093). The incidence of biopsy-proven acute rejection ≥3A at Month 6 was 21.0% (21/100) in the standard-exposure group and 16.2% (16/99) in the reduced-exposure group (n.s.). Adverse events and infections were similar between treatment groups. Thus, everolimus with reduced-exposure CsA resulted in comparable efficacy compared to standard-exposure CsA. No renal function benefits were demonstrated; that is possibly related to poor adherence to reduced CsA exposure. PMID:22295178
Inelmen, E M; D'Alessio, M; Gatto, M R; Baggio, M B; Jimenez, G; Bizzotto, M G; Enzi, G
1994-04-01
We studied hematological indexes (RBC, HB, HT, MCV), serum iron and serum ferritin values in 1784 randomly selected subjects aged 65 and over (725 males and 1059 females) divided into five age groups (65-69, 70-74, 75-79, 80-84, > or = 85 years). The subjects were classified as anemic and normochromic according to the criteria for a "geriatric" level of anemia (HB < or = 12 g/dL in both sexes) as well as "W.H.O." levels for anemia (HB < 13 g/dL in males and < 12 g/dL in females). Macrocytosis (MCV > 100 fl) and low serum ferritin level (< or = 12 ng/dL) were classified according to MCV and serum ferritin values. Mean HB values in males were 14.85 +/- 1.33; 14.82 +/- 1.40; 14.77 +/- 1.43; 14.59 +/- 1.47 and 13.83 +/- 1.13 in the five age groups (65-69, 70-74, 75-79, 80-84 and > or = 85 years) respectively; in females, they were 13.77 +/- 1.15; 13.75 +/- 1.27; 13.44 +/- 1.39; 13.44 +/- 1.52 and 13.34 +/- 1.61, respectively. There was a low frequency of anemia in the entire sample: 2.9% in males and 9.9% in females according to the "geriatric" level, and 9.4% in males and 8.8% in females according to the "W.H.O." level. There was a higher prevalence of macrocytosis in males (6.3%) than in females (3.3%). We conclude that red cell parameters tend to decrease in aging, and further investigations are needed that exclude persons with existing chronic conditions, and incorporate data on nutritional status. PMID:7918735
2013-01-01
Background Annually approximately 100.000 patients undergo a laparotomy in the Netherlands. About 15,000 of these patients will develop an incisional hernia. Both open and laparoscopic surgical repair have been proven to be safe. However, the most effective treatment of incisional hernias remains unclear. This study, the ‘INCH-trial’, comparing cost-effectiveness of open and laparoscopic incisional hernia repair, is therefore needed. Methods/Design A randomized multi-center clinical trial comparing cost-effectiveness of open and laparoscopic repair of incisional hernias. Patients with a symptomatic incisional hernia, eligible for laparoscopic and open incisional hernia repair. Only surgeons, experienced in both open and laparoscopic incisional hernia repair, will participate in the INCH trial. During incisional hernia repair, a mesh is placed under or on top of the fascia, with a minimal overlap of 5 cm. Primary endpoint is length of hospital stay after an incisional hernia repair. Secondary endpoints are time to full recovery within three months after index surgery, post-operative complications, recurrences, mortality and quality of life. Our hypothesis is that laparoscopic incisional hernia repair comes with a significant shorter hospital stay compared to open incisional hernia repair. A difference of two days is considered significant. One-hunderd-and-thirty-five patients are enrolled in each treatment arm. The economic evaluation will be performed from a societal perspective. Primary outcomes are costs per patient related to time-to-recovery and quality of life. The main goal of the trial is to establish whether laparoscopic incisional hernia repair is superior to conventional open incisional hernia repair in terms of cost-effectiveness. This is measured through length of hospital stay and quality of life. Secondary endpoints are re-operation rate due to post-operative complications or recurrences, mortality and quality of life. Discussion The difference
Heyderman, Robert S; Madhi, Shabir A; French, Neil; Cutland, Clare; Ngwira, Bagrey; Kayambo, Doris; Mboizi, Robert; Koen, Anthonet; Jose, Lisa; Olugbosi, Morounfolu; Wittke, Frederik; Slobod, Karen; Dull, Peter M
2016-01-01
Summary Background Neonates born to women infected with HIV are at increased risk for invasive group B streptococcus (GBS) disease. We aimed to compare safety and immunogenicity of trivalent glycoconjugate GBS vaccine in pregnant women with and without HIV in Malawi and South Africa. Methods In our non-randomised phase 2, open-label, multicentre study, we recruited pregnant women attending two antenatal clinics, one in Blantyre, Malawi, and one in Soweto, Johannesburg, South Africa. Participants were divided into three groups on the basis of their HIV infection status (no infection, infection and high CD4 cell count [>350 cells per μL], and infection and low CD4 cell count [>50 to ≤350 cells per μL]) and received a 5 μg dose of glycoconjugate GBS vaccine (serotypes Ia, Ib, and III, with CRM197 [Novartis Vaccines, Siena, Italy]) intramuscularly at 24–35 weeks' gestation. GBS serotype-specific antibody concentrations were measured before vaccination (day 1), day 15, day 31, and at delivery, and in infants at birth and day 42 of life. The primary outcomes were safety in mothers and infants and the amount of placental transfer of GBS serotype-specific antibodies from mothers to their infants. All immunogenicity and safety analyses were done on the full analysis set, including participants who, or whose mother, correctly received the vaccine and who provided at least one valid assessable serum sample. This study is registered with ClinicalTrials.gov, number NCT01412801. Findings 270 women and 266 infants were enrolled between Sept 26, 2011, and Dec 4, 2012 (90 women and 87 infants without HIV, 89 and 88 with HIV and high CD4 cell counts, and 91 and 91 with HIV and low CD4 cell counts, respectively). Seven women were lost to follow-up, six withdrew consent, one died, and two relocated. Eight infants died or were stillborn and two were lost to follow-up. Across serotypes, fold change in antibody concentrations were higher for the HIV-uninfected group than the HIV
Electron correlation effects beyond the random phase approximation
NASA Astrophysics Data System (ADS)
Fan, J. D.; Malozovsky, Y. M.
2016-04-01
The methods that have been used to deal with a many-particle system can be basically sorted into three types: Hamiltonian, field theory and phenomenological method. The first two methods are more popular. Traditionally, the Hamiltonian method has been widely adopted in the conventional electronic theory for metals, alloys and semiconductors. Basically, the mean-field approximation (MFA) that has been working well for a weakly coupled system like a metal is employed to simplify a Hamiltonian corresponding to a particular electron system. However, for a strongly coupled many-particle system like a cuprate superconductor MFA should in principle not apply. Therefore, the field theory on the basis of Green’s function and the Feynman diagrams must be invoked. In this method, one is however more familiar with the random phase approximation (RPA) that gives rise to the same results as MFA because of being short of the information for higher-order terms of interaction. For a strongly coupled electron system, it is obvious that one has to deal with higher-order terms of a pair interaction to get a correct solution. Any ignorance of the higher-order terms implies that the more sophisticated information contained in those terms is discarded. However, to date one has not reached a consensus on how to deal with the higher-order terms beyond RPA. We preset here a method that is termed the diagrammatic iteration approach (DIA) and able to derive higher-order terms of the interaction from the information of lower-order ones on the basis of Feynman diagram, with which one is able to go beyond RPA step by step. It is in principle possible that all of higher-order terms can be obtained, and then sorted to groups of diagrams. It turns out that each of the groups can be replaced by an equivalent one, forming a diagrammatic Dyson-equation-like relation. The diagrammatic solution is eventually “translated” to a four-dimensional integral equation. The method can be applied to a
Truly random number generation based on measurement of phase noise of a laser.
Guo, Hong; Tang, Wenzhuo; Liu, Yu; Wei, Wei
2010-05-01
We present a simple approach to realize truly random number generator based on measuring the phase noise of a single-mode vertical cavity surface emitting laser. The true randomness of the quantum phase noise originates from the spontaneous emission of photons and the random bit generation rate is ultimately limited only by the laser linewidth. With the final bit generation rate of 20 Mbit/s, the truly random bit sequence guaranteed by the uncertainty principle of quantum mechanics passes the three standard randomness tests (ENT, Diehard, and NIST Statistical Test Suites). Moreover, a continuously generated random bit sequence, with length up to 14 Gbit, is verified by two additional criteria for its true randomness. PMID:20866215
Phase transition in the assignment problem for random matrices
NASA Astrophysics Data System (ADS)
Esteve, J. G.; Falceto, F.
2005-12-01
We report an analytic and numerical study of a phase transition in a P problem (the assignment problem) that separates two phases whose representatives are the simple matching problem (an easy P problem) and the traveling-salesman problem (a NP-complete problem). Like other phase transitions found in combinatoric problems (K-satisfiability, number partitioning) this can help to understand the nature of the difficulties in solving NP problems an to find more accurate algorithms for them.
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. PMID:20868107
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.
Ultra-fast quantum randomness generation by accelerated phase diffusion in a pulsed laser diode.
Abellán, C; Amaya, W; Jofre, M; Curty, M; Acín, A; Capmany, J; Pruneri, V; Mitchell, M W
2014-01-27
We demonstrate a high bit-rate quantum random number generator by interferometric detection of phase diffusion in a gain-switched DFB laser diode. Gain switching at few-GHz frequencies produces a train of bright pulses with nearly equal amplitudes and random phases. An unbalanced Mach-Zehnder interferometer is used to interfere subsequent pulses and thereby generate strong random-amplitude pulses, which are detected and digitized to produce a high-rate random bit string. Using established models of semiconductor laser field dynamics, we predict a regime of high visibility interference and nearly complete vacuum-fluctuation-induced phase diffusion between pulses. These are confirmed by measurement of pulse power statistics at the output of the interferometer. Using a 5.825 GHz excitation rate and 14-bit digitization, we observe 43 Gbps quantum randomness generation. PMID:24515170
Chiral random grain boundary phase of achiral hockey-stick liquid crystals.
Chen, Dong; Wang, Haitao; Li, Min; Glaser, Matthew A; Maclennan, Joseph E; Clark, Noel A
2014-12-01
A disordered chiral conglomerate, the random grain boundary (RGB) phase, has been observed below the smectic A liquid crystal phase of an achiral, hockey-stick molecule. In cells, the RGB phase appears dark between crossed polarizers but decrossing the polarizers reveals large left- and right-handed chiral domains with opposite optical rotation. Freeze-fracture transmission electron microscopy reveals that the RGB phase is an assembly of randomly oriented blocks of smectic layers, an arrangement that distinguishes the RGB from the dark, chiral conglomerate phases of bent-core mesogens. X-ray diffraction indicates that there is significant layer shrinkage at the SmA-RGB phase transition, which is marked by the collapse of layers with long-range order into small, randomly oriented smectic blocks. PMID:25310113
Variance of phase fluctuations of waves propagating through a random medium
NASA Technical Reports Server (NTRS)
Chu, Nelson C.; Kong, Jin AU; Yueh, Simon H.; Nghiem, Son V.; Fleischman, Jack G.; Ayasli, Serpil; Shin, Robert T.
1992-01-01
As an electromagnetic wave propagates through a random scattering medium, such as a forest, its energy is attenuated and random phase fluctuations are induced. The magnitude of the random phase fluctuations induced is important in estimating how well a Synthetic Aperture Radar (SAR) can image objects within the scattering medium. The two-layer random medium model, consisting of a scattering layer between free space and ground, is used to calculate the variance of the phase fluctuations induced between a transmitter located above the random medium and a receiver located below the random medium. The scattering properties of the random medium are characterized by a correlation function of the random permittivity fluctuations. The effective permittivity of the random medium is first calculated using the strong fluctuation theory, which accounts for large permittivity fluctuations of the scatterers. The distorted Born approximation is used to calculate the first-order scattered field. A perturbation series for the phase of the received field in the Rytov approximation is then introduced and the variance of the phase fluctuations is also calculated assuming that the transmitter and receiver are in the paraxial limit of the random medium, which allows an analytic solution to be obtained. Results are compared using the paraxial approximation, scalar Green's function formulation, and dyadic Green's function formulation. The effects studied are the dependence of the variance of the phase fluctuations on receiver location in lossy and lossless regions, medium thickness, correlation length and fractional volume of scatterers, depolarization of the incident wave, ground layer permittivity, angle of incidence, and polarization.
Self-consistent continuum random-phase approximation calculations with finite-range interactions
De Donno, V.; Co', G.; Anguiano, M.; Lallena, A. M.
2011-04-15
We present a technique that treats, without approximations, the continuum part of the excitation spectrum in random phase approximation calculations with finite-range interactions. The interaction used in Hartree-Fock calculations to generate the single-particle basis is also used in continuum random phase approximation calculations. We show results for electric dipole and quadrupole excitations in {sup 16}O, {sup 22}O, {sup 24}O, {sup 40}Ca, {sup 48}Ca, and {sup 52}Ca nuclei. We compare our results with those of the traditional discrete random phase approximation, with continuum independent-particle model results, and with results obtained by a phenomenological random phase approximation approach. We study the relevance of the continuum, of the residual interaction, and of the self-consistency. We also compare our results with the available total photoabsorption cross-section data.
Phase-change Random Access Memory: A Scalable Technology
Raoux, S.; Burr, G; Breitwisch, M; Rettner, C; Chen, Y; Shelby, R; Salinga, M; Krebs, D; Chen, S; Lung, H
2008-01-01
Nonvolatile RAM using resistance contrast in phase-change materials [or phase-change RAM (PCRAM)] is a promising technology for future storage-class memory. However, such a technology can succeed only if it can scale smaller in size, given the increasingly tiny memory cells that are projected for future technology nodes (i.e., generations). We first discuss the critical aspects that may affect the scaling of PCRAM, including materials properties, power consumption during programming and read operations, thermal cross-talk between memory cells, and failure mechanisms. We then discuss experiments that directly address the scaling properties of the phase-change materials themselves, including studies of phase transitions in both nanoparticles and ultrathin films as a function of particle size and film thickness. This work in materials directly motivated the successful creation of a series of prototype PCRAM devices, which have been fabricated and tested at phase-change material cross-sections with extremely small dimensions as low as 3 nm x 20 nm. These device measurements provide a clear demonstration of the excellent scaling potential offered by this technology, and they are also consistent with the scaling behavior predicted by extensive device simulations. Finally, we discuss issues of device integration and cell design, manufacturability, and reliability.
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
Non-equilibrium Phase Transitions: Activated Random Walks at Criticality
NASA Astrophysics Data System (ADS)
Cabezas, M.; Rolla, L. T.; Sidoravicius, V.
2014-06-01
In this paper we present rigorous results on the critical behavior of the Activated Random Walk model. We conjecture that on a general class of graphs, including , and under general initial conditions, the system at the critical point does not reach an absorbing state. We prove this for the case where the sleep rate is infinite. Moreover, for the one-dimensional asymmetric system, we identify the scaling limit of the flow through the origin at criticality. The case remains largely open, with the exception of the one-dimensional totally-asymmetric case, for which it is known that there is no fixation at criticality.
Optical Security Card by Three-dimensional Random Phase Distribution
NASA Astrophysics Data System (ADS)
Matoba, Osamu; Nitta, Kouichi
2007-10-01
An optical security card based on a three-dimensional (3D) phase object is presented. This card enables us to develop a personal authentification system and secure data storage in a highly scattering medium. The authentification is implemented by the correlation between a speckle pattern of the 3D phase object and stored speckle patterns. For secure data storage, absorption distribution is involved in a scattering volume medium. Appropriate user can only reconstruct the absorption distribution by solving inverse problem. Experimental and numerical results are presented to show the effectiveness of the proposed system.
2010-01-01
Aims Cardiovascular magnetic resonance (CMR) allows non-invasive phase contrast measurements of flow through planes transecting large vessels. However, some clinically valuable applications are highly sensitive to errors caused by small offsets of measured velocities if these are not adequately corrected, for example by the use of static tissue or static phantom correction of the offset error. We studied the severity of uncorrected velocity offset errors across sites and CMR systems. Methods and Results In a multi-centre, multi-vendor study, breath-hold through-plane retrospectively ECG-gated phase contrast acquisitions, as are used clinically for aortic and pulmonary flow measurement, were applied to static gelatin phantoms in twelve 1.5 T CMR systems, using a velocity encoding range of 150 cm/s. No post-processing corrections of offsets were implemented. The greatest uncorrected velocity offset, taken as an average over a 'great vessel' region (30 mm diameter) located up to 70 mm in-plane distance from the magnet isocenter, ranged from 0.4 cm/s to 4.9 cm/s. It averaged 2.7 cm/s over all the planes and systems. By theoretical calculation, a velocity offset error of 0.6 cm/s (representing just 0.4% of a 150 cm/s velocity encoding range) is barely acceptable, potentially causing about 5% miscalculation of cardiac output and up to 10% error in shunt measurement. Conclusion In the absence of hardware or software upgrades able to reduce phase offset errors, all the systems tested appeared to require post-acquisition correction to achieve consistently reliable breath-hold measurements of flow. The effectiveness of offset correction software will still need testing with respect to clinical flow acquisitions. PMID:20074359
NASA Astrophysics Data System (ADS)
Sun, Shi-Hai; Liang, Lin-Mei
2012-08-01
Phase randomization is a very important assumption in the BB84 quantum key distribution (QKD) system with weak coherent source; otherwise, eavesdropper may spy the final key. In this Letter, a stable and monitored active phase randomization scheme for the one-way and two-way QKD system is proposed and demonstrated in experiments. Furthermore, our scheme gives an easy way for Alice to monitor the degree of randomization in experiments. Therefore, we expect our scheme to become a standard part in future QKD systems due to its secure significance and feasibility.
Coherent-phase or random-phase acceleration of electron beams in solar flares
NASA Technical Reports Server (NTRS)
Aschwanden, Markus J.; Benz, Arnold O.; Montello, Maria L.
1994-01-01
Time structures of electron beam signatures at radio wavelengths are investigated to probe correlated versus random behavior in solar flares. In particular we address the issue whether acceleration and injection of electron beams is coherently modulated by a single source, or whether the injection is driven by a stochastic (possibly spatially fragmented) process. We analyze a total of approximately = 6000 type III bursts observed by Ikarus (Zurich) in the frequency range of 100-500 MHz, during 359 solar flares with simultaneous greater than or = 25 keV hard X-ray emission, in the years 1890-1983. In 155 flares we find a total of 260 continuous type III groups, with an average number of 13 +/- 9 bursts per group, a mean duration of D = 12 +/- 14 s, a mean period of P = 2.0 +/- 1.2 s, with the highest burst rate at a frequency of nu = 310 +/- 120 MHz. Pulse periods have been measured between 0.5 and 10 s, and can be described by an exponential distribution, i.e., N(P) varies as e (exp -P/1.0s). The period shows a frequency dependence of P(nu)=46(exp-0.6)(sub MHz)s for different flares, but is invariant during a particular flare. We measure the mean period P and its standard deviation sigma (sub p) in each type III group, and quantify the degree of periodicity (or phase-coherence) by the dimensionless parameter sigma (sub p)P. The representative sample of 260 type III burst groups shows a mean periodicity of sigma (sub p/P) = 0.37 +/- 0.12, while Monte Carlo simulations of an equivalent set of truly random time series show a distinctly different value of sigma (sub p)P = 0.93 +/- 0.26. This result indicates that the injection of electron beams is coherently modulated by a particle acceleration source which is either compact or has a global organization on a timescale of seconds, in contrast to an incoherent acceleration source, which is stochastic either in time or space. We discuss the constraints on the size of the acceleration region resulting from electron beam
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
2014-01-01
Background Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications. Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation. This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones. Methods/design The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo. Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The
Wallace, Daniel J; Kalunian, Kenneth; Petri, Michelle A; Strand, Vibeke; Houssiau, Frederic A; Pike, Marilyn; Kilgallen, Brian; Bongardt, Sabine; Barry, Anna; Kelley, Lexy; Gordon, Caroline
2014-01-01
Objective To identify a suitable dosing regimen of the CD22-targeted monoclonal antibody epratuzumab in adults with moderately to severely active systemic lupus erythematosus (SLE). Methods A phase IIb, multicentre, randomised controlled study (NCT00624351) was conducted with 227 patients (37–39 per arm) receiving either: placebo, epratuzumab 200 mg cumulative dose (cd) (100 mg every other week (EOW)), 800 mg cd (400 mg EOW), 2400 mg cd (600 mg weekly), 2400 mg cd (1200 mg EOW), or 3600 mg cd (1800 mg EOW). The primary endpoint (not powered for significance) was the week 12 responder rate measured using a novel composite endpoint, the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA). Results Proportion of responders was higher in all epratuzumab groups than with placebo (overall treatment effect test p=0.148). Exploratory pairwise analysis demonstrated clinical improvement in patients receiving a cd of 2400 mg epratuzumab (OR for 600 mg weekly vs placebo: 3.2 (95% CI 1.1 to 8.8), nominal p=0.03; OR for 1200 mg EOW vs placebo: 2.6 (0.9 to 7.1), nominal p=0.07). Post-hoc comparison of all 2400 mg cd patients versus placebo found an overall treatment effect (OR=2.9 (1.2 to 7.1), nominal p=0.02). Incidence of adverse events (AEs), serious AEs and infusion reactions was similar between epratuzumab and placebo groups, without decreases in immunoglobulin levels and only partial reduction in B-cell levels. Conclusions Treatment with epratuzumab 2400 mg cd was well tolerated in patients with moderately to severely active SLE, and associated with improvements in disease activity. Phase III studies are ongoing. PMID:23313811
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.
NASA Astrophysics Data System (ADS)
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), 10.1103/PhysRevLett.113.220602]. 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).
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.
All-optical quantum random bit generation from intrinsically binary phase of parametric oscillators.
Marandi, Alireza; Leindecker, Nick C; Vodopyanov, Konstantin L; Byer, Robert L
2012-08-13
We demonstrate a novel all-optical quantum random number generator (RNG) based on above-threshold binary phase state selection in a degenerate optical parametric oscillator (OPO). Photodetection is not a part of the random process, and no post processing is required for the generated bit sequence. We show that the outcome is statistically random with 99% confidence, and verify that the randomness is due to the phase of initiating photons generated through spontaneous parametric down conversion of the pump, with negligible contribution of classical noise sources. With the use of micro- and nanoscale OPO resonators, this technique offers a promise for simple, robust, and high-speed on-chip all-optical quantum RNGs. PMID:23038574
Security authentication with a three-dimensional optical phase code using random forest classifier.
Markman, Adam; Carnicer, Artur; Javidi, Bahram
2016-06-01
An object with a unique three-dimensional (3D) optical phase mask attached is analyzed for security and authentication. These 3D optical phase masks are more difficult to duplicate or to have a mathematical formulation compared with 2D masks and thus have improved security capabilities. A quick response code was modulated using a random 3D optical phase mask generating a 3D optical phase code (OPC). Due to the scattering of light through the 3D OPC, a unique speckle pattern based on the materials and structure in the 3D optical phase mask is generated and recorded on a CCD device. Feature extraction is performed by calculating the mean, variance, skewness, kurtosis, and entropy for each recorded speckle pattern. The random forest classifier is used for authentication. Optical experiments demonstrate the feasibility of the authentication scheme. PMID:27409445
Chen, Wen
2015-12-20
A novel method is proposed by using multiple-wavelength double random phase encoding (MW-DRPE) with CCD-plane sparse-phase multiplexing for optical information verification. Two different strategies are applied to conduct sparse-phase multiplexing in the CCD plane. The results demonstrate that large capacity can be achieved for optical multiple-image verification. The proposed optical verification strategy is implemented based on optical encoding, and the keys generated by optical encryption can further guarantee the safety of the designed optical multiple-image verification system. The proposed method provides a novel alternative for DRPE-based optical information verification. PMID:26837040
Simultaneous transmission for an encrypted image and a double random-phase encryption key
NASA Astrophysics Data System (ADS)
Yuan, Sheng; Zhou, Xin; Li, Da-Hai; Zhou, Ding-Fu
2007-06-01
We propose a method to simultaneously transmit double random-phase encryption key and an encrypted image by making use of the fact that an acceptable decryption result can be obtained when only partial data of the encrypted image have been taken in the decryption process. First, the original image data are encoded as an encrypted image by a double random-phase encryption technique. Second, a double random-phase encryption key is encoded as an encoded key by the Rivest-Shamir-Adelman (RSA) public-key encryption algorithm. Then the amplitude of the encrypted image is modulated by the encoded key to form what we call an encoded image. Finally, the encoded image that carries both the encrypted image and the encoded key is delivered to the receiver. Based on such a method, the receiver can have an acceptable result and secure transmission can be guaranteed by the RSA cipher system.
Aoyagi, Reiko; Hamada, Hiromichi; Sato, Yasunori; Suzuki, Hiroyuki; Onouchi, Yoshihiro; Ebata, Ryota; Terauchi, Moe; Terai, Masaru; Hanaoka, Hideki; Hata, Akira
2015-01-01
Introduction Kawasaki disease (KD) is an acute, self-limited vasculitis of unknown aetiology that predominantly affects infants and young children. We hypothesise that cyclosporin A (CsA) may be effective in treating KD by regulating the Ca2+/NFAT signalling pathway. This trial compares the current standard therapy of intravenous immunoglobulin (IVIG) and the combined IVIG+CsA therapy in paediatric patients with severe KD. Methods and analysis This trial is a phase III, multicentre, randomised, open-label, blinded-end point trial that evaluates the efficacy and safety of IVIG+CsA therapy. Patients with severe KD who satisfy the eligibility criteria are randomised (1:1) to receive either CsA (5 mg/kg/day for 5 days; Neoral) plus high-dose IVIG (2 g/kg for 24 h and aspirin 30 mg/kg/day), or high-dose IVIG alone (2 g/kg for 24 h and aspirin 30 mg/kg/day). The primary end point is the frequency of occurrence of coronary artery abnormalities during the trial period. An independent end point review committee will be in charge of the trial assessment. Ethics and dissemination The protocol was approved by the Institutional Review Board of each institution. The trial was notified and registered at the Pharmaceutical and Medical Devices Agency, in Japan. The trial is currently on-going and is scheduled to finish in April 2017. The findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number JMA-IIA00174; Pre-results. PMID:26628527
Sasaki, Tomoyuki; Noda, Kohei; Kawatsuki, Nobuhiro; Ono, Hiroshi
2015-04-01
We present a universal polarization terahertz (THz) phase controller using a randomly aligned liquid crystal (LC) cell with graphene electrodes. The LC cell was fabricated using a nematic LC and two quartz substrates that were coated with a monolayer of graphene as the transparent electrode. The LC in the cell was prepared without any alignment treatments and was randomly aligned. The size of the random domains and the width of the disclination lines in the LC layer were several tens of microns. These textures disappeared when an alternating voltage was applied to the LC through the graphene layers. Using a THz time domain spectroscopic technique, we investigated the complex transmittance of the LC cell. The LC cell was highly transparent in the THz frequency range, and there was little change in the transmittance with the applied voltage. This indicated that the scattering loss originating in the randomly aligned LC molecules was small for the THz waves. We also demonstrated that the THz phase shift could be controlled by the applied voltage. The amplitude of the phase shift was explained by the ordinary and extraordinary refractive indices of the LC. These LC cells with graphene electrodes can be used to realize universal polarization THz phase controllers because of the random alignment. PMID:25831380
Single-shot phase imaging with randomized light (SPIRaL).
Horisaki, Ryoichi; Egami, Riki; Tanida, Jun
2016-02-22
We present a method for single-shot phase imaging with randomized light (SPIRaL). In SPIRaL, the complex (amplitude and phase) field of an object illuminated with a randomized coherent beam is captured with an image sensor, without the need for any reference light. The object field is retrieved from the single captured intensity image by a compressive sensing-based algorithm with a sparsity constraint. SPIRaL has higher observation speed, light efficiency, and flexibility of the implementation compared with previous methods. We demonstrate SPIRaL numerically and experimentally. PMID:26907032
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.
The generation of 68 Gbps quantum random number by measuring laser phase fluctuations.
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. PMID:26133826
The generation of 68 Gbps quantum random number by measuring laser phase fluctuations
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.
2013-01-01
Summary Background Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival. We aimed to assess whether lithium improves survival in patients with ALS. Methods The lithium carbonate in amyotrophic lateral sclerosis (LiCALS) trial is a randomised, double-blind, placebo-controlled trial of oral lithium taken daily for 18 months in patients with ALS. Patients aged at least 18 years who had ALS according to the revised El Escorial criteria, had disease duration between 6 and 36 months, and were taking riluzole were recruited from ten centres in the UK. Patients were randomly assigned (1:1) to receive either lithium or matched placebo tablets. Randomisation was via an online system done at the level of the individual by block randomisation with randomly varying block sizes, stratified by study centre and site of disease onset (limb or bulbar). All patients and assessing study personnel were masked to treatment assignment. The primary endpoint was the rate of survival at 18 months and was analysed by intention to treat. This study is registered with Eudract, number 2008-006891-31. Findings Between May 26, 2009, and Nov 10, 2011, 243 patients were screened, 214 of whom were randomly assigned to receive lithium (107 patients) or placebo (107 patients). Two patients discontinued treatment and one died before the target therapeutic lithium concentration could be achieved. 63 (59%) of 107 patients in the placebo group and 54 (50%) of 107 patients in the lithium group were alive at 18 months. The survival functions did not differ significantly between groups (Mantel-Cox log-rank χ2 on 1 df=1·64; p=0·20). After adjusting for study centre and site of onset using logistic regression, the relative odds of survival at 18 months (lithium vs placebo) was 0·71 (95% CI 0·40–1·24). 56 patients in the placebo group and 61 in the lithium
Phase Separation Kinetics of a Binary Polymer Blend with Added Random Copolymer
NASA Astrophysics Data System (ADS)
Waldow, Dean; Barham, Bethany; Halasa, Adel
1998-03-01
The phase separation kinetics of a polymer blend with increasing amounts of random copolymer was studied using wide angle light scattering. The system is a blend of polystyrene and polybutadiene, and the copolymer is an asymmetric random styrene-butadiene copolymer (80/20). The composition of the blend is near critical and the weight percentages of the added copolymer vary from 0.0 to 2.5 percent. The temperature of the cloud point increases with increasing copolymer amount indicating a destabilizing effect. Light scattering data was collected while temperature was jumped from the one-phase region into the two-phase region near the phase boundary. Early stage and intermediate stage kinetics were analyzed using Cahn-Hillard-Cook theory and scaling theory. The early stage kinetics indicate a slowing of the diffusion constants with added copolymer, and the intermediate stage kinetics suggest that the scaling theory doesn't accurately describe the data.
Deterministic matrices matching the compressed sensing phase transitions of Gaussian random matrices
Monajemi, Hatef; Jafarpour, Sina; Gavish, Matan; Donoho, David L.; Ambikasaran, Sivaram; Bacallado, Sergio; Bharadia, Dinesh; Chen, Yuxin; Choi, Young; Chowdhury, Mainak; Chowdhury, Soham; Damle, Anil; Fithian, Will; Goetz, Georges; Grosenick, Logan; Gross, Sam; Hills, Gage; Hornstein, Michael; Lakkam, Milinda; Lee, Jason; Li, Jian; Liu, Linxi; Sing-Long, Carlos; Marx, Mike; Mittal, Akshay; Monajemi, Hatef; No, Albert; Omrani, Reza; Pekelis, Leonid; Qin, Junjie; Raines, Kevin; Ryu, Ernest; Saxe, Andrew; Shi, Dai; Siilats, Keith; Strauss, David; Tang, Gary; Wang, Chaojun; Zhou, Zoey; Zhu, Zhen
2013-01-01
In compressed sensing, one takes samples of an N-dimensional vector using an matrix A, obtaining undersampled measurements . For random matrices with independent standard Gaussian entries, it is known that, when is k-sparse, there is a precisely determined phase transition: for a certain region in the (,)-phase diagram, convex optimization typically finds the sparsest solution, whereas outside that region, it typically fails. It has been shown empirically that the same property—with the same phase transition location—holds for a wide range of non-Gaussian random matrix ensembles. We report extensive experiments showing that the Gaussian phase transition also describes numerous deterministic matrices, including Spikes and Sines, Spikes and Noiselets, Paley Frames, Delsarte-Goethals Frames, Chirp Sensing Matrices, and Grassmannian Frames. Namely, for each of these deterministic matrices in turn, for a typical k-sparse object, we observe that convex optimization is successful over a region of the phase diagram that coincides with the region known for Gaussian random matrices. Our experiments considered coefficients constrained to for four different sets , and the results establish our finding for each of the four associated phase transitions. PMID:23277588
Wang, Xiaogang; Chen, Wen; Chen, Xudong
2015-03-01
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. PMID:25836845
Single-random phase encoding architecture using a focus tunable lens
NASA Astrophysics Data System (ADS)
Mosso, E. F.; Bolognini, N.; Pérez, D. G.
2016-02-01
We propose a new nonlinear optical architecture based on a focus tunable lens and an iterative phase retrieval algorithm. It constitutes a compact encryption system that uses a single-random phase key to simultaneously encrypt (decrypt) amplitude and phase data. Summarily, the information encoded in a transmittance object (phase and amplitude) is randomly modulated by a diffuser when a laser beam illuminates it; once the beam reaches a focus tunable lens, different subjective speckle distributions are registered at some image plane as the focal length is tuned to different values. This set of speckle patterns constitutes a delocalized ciphertext, which is used in an iterative phase retrieval algorithm to reconstruct a complex ciphertext. The original data are decrypted propagating this ciphertext through a virtual optical system. In this system, amplitude data are straightforwardly decrypted while phase data can only be restored if the random modulation produced in the encryption process is compensated. Thus, an encryption-decryption process and authentication protocol can simultaneously be performed. We validate the feasibility of our proposal with simulated and experimental results.
Security enhanced optical encryption system by random phase key and permutation key.
He, Mingzhao; Tan, Qiaofeng; Cao, Liangcai; He, Qingsheng; Jin, Guofan
2009-12-01
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. PMID:20052170
Continuous and discontinuous absorbing-state phase transitions on Voronoi-Delaunay random lattices.
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)PRLTAO0031-900710.1103/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. PMID:26871027
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.
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.
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
Parametric down-conversion with nonideal and random quasi-phase-matching
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
Parametric down-conversion with nonideal and random quasi-phase-matching.
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
Parametric down-conversion with nonideal and random quasi-phase-matching
NASA Astrophysics Data System (ADS)
Yang, Chun-Yao; Lin, Chun; Liljestrand, Charlotte; Su, Wei-Min; Canalias, Carlota; Chuu, Chih-Sung
2016-05-01
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.
Drew, Yvette; Ledermann, Jonathan; Hall, Geoff; Rea, Daniel; Glasspool, Ros; Highley, Martin; Jayson, Gordon; Sludden, Julieann; Murray, James; Jamieson, David; Halford, Sarah; Acton, Gary; Backholer, Zoe; Mangano, Raffaella; Boddy, Alan; Curtin, Nicola; Plummer, Ruth
2016-01-01
Background: Rucaparib is an orally available potent selective small-molecule inhibitor of poly(ADP-ribose) polymerase (PARP) 1 and 2. Rucaparib induces synthetic lethality in cancer cells defective in the homologous recombination repair pathway including BRCA-1/2. We investigated the efficacy and safety of single-agent rucaparib in germline (g) BRCA mutation carriers with advanced breast and ovarian cancers. Methods: Phase II, open-label, multicentre trial of rucaparib in proven BRCA-1/2 mutation carriers with advanced breast and or ovarian cancer, WHO PS 0–1 and normal organ function. Intravenous (i.v.) and subsequently oral rucaparib were assessed, using a range of dosing schedules, to determine the safety, tolerability, dose-limiting toxic effects and pharmacodynamic (PD) and pharmacokinetic (PK) profiles. Results: Rucaparib was well tolerated in patients up to doses of 480 mg per day and is a potent inhibitor of PARP, with sustained inhibition ⩾24 h after single doses. The i.v. rucaparib (intermittent dosing schedule) resulted in an objective response rate (ORR) of only 2% but with 41% (18 out of 44) patients achieved stable disease for ⩾12 weeks and 3 patients maintaining disease stabilisation for >52 weeks. The ORR for oral rucaparib (across all six dose levels) was 15%. In the oral cohorts, 81% (22 out of 27) of the patients had ovarian cancer and 12 out of 13, who were dosed continuously, achieved RECIST complete response/partial response (CR/PR) or stable disease (SD) ⩾12 weeks, with a median duration of response of 179 days (range 84–567 days). Conclusions: Rucaparib is well tolerated and results in high levels of PARP inhibition in surrogate tissues even at the lowest dose levels. Rucaparib is active in gBRCA-mutant ovarian cancer and this activity correlates with platinum-free interval. The key lessons learned from this study is that continuous rucaparib dosing is required for optimal response, the recommended phase 2 dose (RP2D) for
Toledo Junior, Antonio; Daher, André Bastos; Amaral, Thaís Alves; Carvalho, Sílvio Fernando Guimarães; Romero, Gustavo Adolfo Sierra; Rabello, Ana
2014-01-01
Introduction Parenteral antimony-based compounds are still the standard of care for cutaneous leishmaniasis (CL) treatment in many countries, despite their high toxicity. Previous studies showed that oral azithromycin could be an option for CL treatment. The aim of this study was to evaluate efficacy and safety of oral azithromycin (AZ) for CL treatment compared with injectable meglumine antimoniate (MA). Methods This was a randomized, open-label, 2-arm, non-inferiority clinical trial. Treatment-naïve patients with localized CL were treated with MA (15mg/kg/day up to 1,215mg) or AZ (500mg/day) during 20 consecutive days. The primary efficacy end point was a CL cure 90 days after treatment completion. The analysis was performed with intention-to-treat (ITT) and per protocol (PP) analyses. After an anticipated interim analysis, the study was interrupted due to the high failure rate in the azithromycin group. Results Twenty-four volunteers were included in each group. The MA group had a higher cure rate than the AZ group with the ITT and PP analyses, which were 54.2% versus 20.8% [relative risk (RR) 1.97; 95% confidence intervals (95%CI) 1.13-3.42] and 72.2% versus 23.8% (RR 3.03; 95%CI 1.34-6.87), respectively. No unexpected adverse events were observed. Conclusions Azithromycin is ineffective for CL treatment and does not seem to have a role in the therapeutic arsenal for CL. PMID:25626655
Liu, Xiaoli; Wu, Jiachen; He, Wenqi; Liao, Meihua; Zhang, Chenggong; Peng, Xiang
2015-07-27
We demonstrate in this paper that the traditional double random phase encoding (DRPE) technique is vulnerable to ciphertext-only attack (COA). In this method, an unauthorized user (or say attacker) is assumed to be able to retrieve the corresponding plaintext from the only ciphertext under some certain condition. The proposed scheme mainly relies on a hybrid iterative phase retrieval (HIPR) algorithm, which combines various phase retrieval algorithms. With an estimation of the number of nonzero pixels (NNP) in the original plaintext, an attacker could recover the plaintext in a large extent. The simulation results show that this method is feasible and validate. PMID:26367558
Investigating the Sliding Phase in Strongly and Randomly Coupled Quasi-2D Bose Gasses
NASA Astrophysics Data System (ADS)
Reed, Matthew; Smith, Zack; Dewan, Aftaab; Rolston, Steve
2014-05-01
Asymptotic analytical [Mohan et al. 2010] functional RNG [Pekker et al. 2010] and Monte Carlo [Laflorencie 2012] methods identified an anomalous Griffiths phase in the 3D XY model in the presence of disorder. A stack of cold 2D Bose gasses with random nearest neighbor inter-planar couplings should pass through two phase transitions as one increases temperature, first from a 3D superfluid to a stack of 2D superfluids, and then to a thermal state. We discuss our investigation of this intermediate phase in a stack of strongly coupled quasi-2D Rb 87 pancakes generated by a truly disordered 1D optical potential.
2011-01-01
Background There has been much debate about the appropriate statistical methodology for the evaluation of malaria field studies and the challenges in interpreting data arising from these trials. Methods The present paper describes, for a pivotal phase III efficacy of the RTS, S/AS01 malaria vaccine, the methods of the statistical analysis and the rationale for their selection. The methods used to estimate efficacy of the primary course of vaccination, and of a booster dose, in preventing clinical episodes of uncomplicated and severe malaria, and to determine the duration of protection, are described. The interpretation of various measures of efficacy in terms of the potential public health impact of the vaccine is discussed. Conclusions The methodology selected to analyse the clinical trial must be scientifically sound, acceptable to regulatory authorities and meaningful to those responsible for malaria control and public health policy. Trial registration Clinicaltrials.gov NCT00866619 PMID:21816030
NASA Astrophysics Data System (ADS)
Cao, Chao; Chen, Ru-jun
2009-10-01
In this paper, we present a new copyright information hide method for digital images in Moiré fringe formats. The copyright information is embedded into the protected image and the detecting image based on Fresnel phase matrix. Firstly, using Fresnel diffraction transform, the random phase matrix of copyright information is generated. Then, according to Moiré fringe principle, the protected image and the detecting image are modulated respectively based on the random phase matrix, and the copyright information is embedded into them. When the protected image and the detecting image are overlapped, the copyright information can reappear. Experiment results show that our method has good concealment performance, and is a new way for copyright protection.
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.
Double image encryption based on random phase encoding in the fractional Fourier domain.
Tao, Ran; Xin, Yi; Wang, Yue
2007-11-26
A novel image encryption method is proposed by utilizing random phase encoding in the fractional Fourier domain to encrypt two images into one encrypted image with stationary white distribution. By applying the correct keys which consist of the fractional orders, the random phase masks and the pixel scrambling operator, the two primary images can be recovered without cross-talk. The decryption process is robust against the loss of data. The phase-based image with a larger key space is more sensitive to keys and disturbances than the amplitude-based image. The pixel scrambling operation improves the quality of the decrypted image when noise perturbation occurs. The novel approach is verified by simulations. PMID:19550895
Hacking on decoy-state quantum key distribution system with partial phase randomization.
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
Hacking on decoy-state quantum key distribution system with partial phase randomization
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
NASA Astrophysics Data System (ADS)
Franz, Silvio; Gradenigo, Giacomo; Spigler, Stefano
2016-03-01
We study how the thermodynamic properties of the triangular plaquette model (TPM) are influenced by the addition of extra interactions. The thermodynamics of the original TPM is trivial, while its dynamics is glassy, as usual in kinetically constrained models. As soon as we generalize the model to include additional interactions, a thermodynamic phase transition appears in the system. The additional interactions we consider are either short ranged, forming a regular lattice in the plane, or long ranged of the small-world kind. In the case of long-range interactions we call the new model the random-diluted TPM. We provide arguments that the model so modified should undergo a thermodynamic phase transition, and that in the long-range case this is a glass transition of the "random first-order" kind. Finally, we give support to our conjectures studying the finite-temperature phase diagram of the random-diluted TPM in the Bethe approximation. This corresponds to the exact calculation on the random regular graph, where free energy and configurational entropy can be computed by means of the cavity equations.
Franz, Silvio; Gradenigo, Giacomo; Spigler, Stefano
2016-03-01
We study how the thermodynamic properties of the triangular plaquette model (TPM) are influenced by the addition of extra interactions. The thermodynamics of the original TPM is trivial, while its dynamics is glassy, as usual in kinetically constrained models. As soon as we generalize the model to include additional interactions, a thermodynamic phase transition appears in the system. The additional interactions we consider are either short ranged, forming a regular lattice in the plane, or long ranged of the small-world kind. In the case of long-range interactions we call the new model the random-diluted TPM. We provide arguments that the model so modified should undergo a thermodynamic phase transition, and that in the long-range case this is a glass transition of the "random first-order" kind. Finally, we give support to our conjectures studying the finite-temperature phase diagram of the random-diluted TPM in the Bethe approximation. This corresponds to the exact calculation on the random regular graph, where free energy and configurational entropy can be computed by means of the cavity equations. PMID:27078408
Spin-glass phase transitions and minimum energy of the random feedback vertex set problem.
Qin, Shao-Meng; Zeng, Ying; Zhou, Hai-Jun
2016-08-01
A feedback vertex set (FVS) of an undirected graph contains vertices from every cycle of this graph. Constructing a FVS of sufficiently small cardinality is very difficult in the worst cases, but for random graphs this problem can be efficiently solved by converting it into an appropriate spin-glass model [H.-J. Zhou, Eur. Phys. J. B 86, 455 (2013)EPJBFY1434-602810.1140/epjb/e2013-40690-1]. In the present work we study the spin-glass phase transitions and the minimum energy density of the random FVS problem by the first-step replica-symmetry-breaking (1RSB) mean-field theory. For both regular random graphs and Erdös-Rényi graphs, we determine the inverse temperature β_{l} at which the replica-symmetric mean-field theory loses its local stability, the inverse temperature β_{d} of the dynamical (clustering) phase transition, and the inverse temperature β_{s} of the static (condensation) phase transition. These critical inverse temperatures all change with the mean vertex degree in a nonmonotonic way, and β_{d} is distinct from β_{s} for regular random graphs of vertex degrees K>60, while β_{d} are identical to β_{s} for Erdös-Rényi graphs at least up to mean vertex degree c=512. We then derive the zero-temperature limit of the 1RSB theory and use it to compute the minimum FVS cardinality. PMID:27627285
NASA Astrophysics Data System (ADS)
Genzer, Jan; Kuk Jhon, Young; Krishnamoorti, Ramanan
2010-03-01
We report on the effect of chemical composition, co-monomer distribution and ^1H/^2D isotopic substitution on the phase behavior in random copolymers of poly(styrene-co-4-bromostyrene) (PBrxS), where x denotes the mole fraction of 4-bromostyrene (4-BrS), in cyclohexane. By adjusting the solvent quality during bromination of parent polystyrene, either random or random blocky PBrxS, (r-PBrxS or b-PBrxS, respectively), were synthesized. We study the temperature dependence of phase behavior of PBrxS with various x in cyclohexane as a function of the polymer concentration using cloud point measurements and small-angle neutron scattering. Our results reveal that for a given 4-BrS content, the cloud points of b-PBrxS solutions are consistently higher and broader than those observed in r-PBrxS solutions. The transition temperature has also been found to depend on the isotope substitution of ^1H or ^2D in either the polymer or the solvent. Small angle neutron scattering measurements indicate significant differences in the temperature dependence of the thermodynamic behavior for the random and blocky samples and the nature of the fluctuations upon approaching the phase boundaries.
Ishida, Takashi; Jo, Tatsuro; Takemoto, Shigeki; Suzushima, Hitoshi; Uozumi, Kimiharu; Yamamoto, Kazuhito; Uike, Naokuni; Saburi, Yoshio; Nosaka, Kisato; Utsunomiya, Atae; Tobinai, Kensei; Fujiwara, Hiroshi; Ishitsuka, Kenji; Yoshida, Shinichiro; Taira, Naoya; Moriuchi, Yukiyoshi; Imada, Kazunori; Miyamoto, Toshihiro; Akinaga, Shiro; Tomonaga, Masao; Ueda, Ryuzo
2015-06-01
This multicentre, randomized, phase II study was conducted to examine whether the addition of mogamulizumab, a humanized anti-CC chemokine receptor 4 antibody, to mLSG15, a dose-intensified chemotherapy, further increases efficacy without compromising safety of patients with newly diagnosed aggressive adult T-cell leukaemia-lymphoma (ATL). Patients were assigned 1:1 to receive mLSG15 plus mogamulizumab or mLSG15 alone. The primary endpoint was the complete response rate (%CR); secondary endpoints included the overall response rate (ORR) and safety. The %CR and ORR in the mLSG15-plus-mogamulizumab arm (n = 29) were 52% [95% confidence interval (CI), 33-71%] and 86%, respectively; the corresponding values in the mLSG15 arm (n = 24) were 33% (95% CI, 16-55%) and 75%, respectively. Grade ≥ 3 treatment-emergent adverse events, including anaemia, thrombocytopenia, lymphopenia, leucopenia and decreased appetite, were observed more frequently (≥10% difference) in the mLSG15-plus-mogamulizumab arm. Several adverse events, including skin disorders, cytomegalovirus infection, pyrexia, hyperglycaemia and interstitial lung disease, were observed only in the mLSG15-plus-mogamulizumab arm. Although the combination strategy showed a potentially less favourable safety profile, a higher %CR was achieved, providing the basis for further investigation of this novel treatment for newly diagnosed aggressive ATL. This study was registered at ClinicalTrials.gov, identifier: NCT01173887. PMID:25733162
Ports, WC; Khan, S; Lan, S; Lamba, M; Bolduc, C; Bissonnette, R; Papp, K
2013-01-01
Background Tofacitinib (CP-690,550) is a novel Janus kinase inhibitor in development as an oral formulation for the treatment of several inflammatory diseases including psoriasis. Objectives This phase 2a study aimed to assess the efficacy, systemic safety, local tolerability and systemic pharmacokinetics of topical tofacitinib in mild-to-moderate plaque psoriasis. Methods Two tofacitinib ointment formulations were evaluated in this multicentre, double-blind, vehicle-controlled trial (NCT01246583). Seventy-one patients were randomized 2 : 1 : 2 : 1 to 2% tofacitinib ointment 1, vehicle 1, 2% tofacitinib ointment 2 and vehicle 2, each administered twice daily for 4 weeks to a single fixed 300 cm2 treatment area containing a target plaque with or without one or more nontarget plaques and normal skin. Results The primary endpoint of percentage change from baseline in the Target Plaque Severity Score at week 4 demonstrated statistically significant improvement for ointment 1 [least squares mean (LSM) –54·4%] vs. vehicle 1 (LSM –41·5%), but not ointment 2 (LSM –24·2%) vs. vehicle 2 (LSM –17·2%). Secondary endpoints (target plaque area and Itch Severity Item) improved similarly for tofacitinib ointment vs. corresponding vehicle. Adverse event (AE) occurrence was similar across treatment groups. All AEs were mild or moderate and none were serious or led to subject discontinuation. One application-site AE (erythema) was reported. Tofacitinib mean systemic exposure was minimal and was greater for ointment 1 than for ointment 2. Conclusions Tofacitinib ointment 1 was well tolerated and efficacious compared with vehicle for the treatment of plaque psoriasis. Further study of topical tofacitinib for psoriasis treatment is warranted. PMID:23387374
Phase diagram of a three-dimensional antiferromagnet with random magnetic anisotropy.
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
2015-03-01
Three-dimensional antiferromagnets with random magnetic anisotropy (RMA) that have been 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 Fe_{x}Ni_{1-x}F_{2} 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. PMID:25793845
Mokhtarpour, Laleh; Ponomarenko, Sergey A
2015-11-16
We numerically investigate partially coherent short pulse propagation in nonlinear media near optical resonance. We examine how the pulse state of coherence at the source affects the evolution of the ensemble averaged intensity, mutual coherence function, and temporal degree of coherence of the pulse ensemble. We report evidence of self-induced transparency random phase soliton formation for the relatively coherent incident pulses with sufficiently large average areas. We also show that random pulses lose their coherence on propagation in resonant media and we explain this phenomenon in qualitative terms. PMID:26698507
Phase Diagram of a Three-Dimensional Antiferromagnet with Random Magnetic Anisotropy
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 Fe_{x}Ni_{1-x}F_{2} 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.
Phase Diagram of a Three-Dimensional Antiferromagnet with Random Magnetic Anisotropy
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.
Horne, Andrew W; Skubisz, Monika M; Doust, Ann; Duncan, W Colin; Wallace, Euan; Critchley, Hilary O D; Johns, Terrance G; Norman, Jane E; Bhattacharya, Siladitya; Mollison, Jill; Rassmusen, Michael; Tong, Stephen
2013-01-01
Introduction Tubal ectopic pregnancy (tEP) is the most common life-threatening condition in gynaecology. tEPs with pretreatment serum human chorionic gonadotrophin (hCG) levels <1000 IU/L respond well to outpatient medical treatment with intramuscular methotrexate (MTX). TEPs with hCG >1000 IU/L take a significant time to resolve with MTX and require multiple outpatient monitoring visits. Gefitinib is an orally active epidermal growth factor receptor (EGFR) antagonist. In preclinical studies, we found that EP implantation sites express high levels of EGFR and that gefitinib augments MTX-induced regression of pregnancy-like tissue. We performed a phase I toxicity study administering oral gefitinib and intramuscular MTX to 12 women with tEPs. The combination therapy did not cause significant toxicities and was well tolerated. We noted that combination therapy resolved the tEPs faster than MTX alone. We now describe the protocol of a larger single arm trial to estimate the efficacy and side effects of combination gefitinib and MTX to treat stable tEPs with hCG 1000–10 000 IU/L Methods and analysis We propose to undertake a single-arm multicentre open label trial (in Edinburgh and Melbourne) and recruit 28 women with tEPs (pretreatment serum hCG 1000–10 000 IU/L). We intend to give a single dose of intramuscular MTX (50 mg/m2) and oral gefitinib (250 mg) daily for 7 days. Our primary outcome is the resolution of EP to non-pregnant hCG levels <15 IU/L without requirement of surgery. Our secondary outcomes are comparison of time to resolution against historical controls given MTX only, and safety and tolerability as determined by clinical/biochemical assessment. Ethics and dissemination Ethical approval has been obtained from Scotland A Research Ethics Committee (MREC 11/AL/0350), Southern Health Human Research Ethics Committee B (HREC 11180B) and the Mercy Health Human Research Ethics Committee (R12/25). Data will be presented at international
Demetri, George D; Reichardt, Peter; Kang, Yoon-Koo; Blay, Jean-Yves; Rutkowski, Piotr; Gelderblom, Hans; Hohenberger, Peter; Leahy, Michael; von Mehren, Margaret; Joensuu, Heikki; Badalamenti, Giuseppe; Blackstein, Martin; Cesne, Axel Le; Schöffski, Patrick; Maki, Robert G; Bauer, Sebastian; Nguyen, Binh Bui; Xu, Jianming; Nishida, Toshirou; Chung, John; Kappeler, Christian; Kuss, Iris; Laurent, Dirk; Casali, Paolo
2013-01-01
Summary Background To date, only two agents, imatinib and sunitinib, have shown clinical benefit in patients with gastrointestinal stromal tumours (GISTs), but almost all metastatic GISTs eventually develop resistance to these agents, resulting in fatal disease progression. This phase 3 trial assessed efficacy and safety of regorafenib in patients with metastatic and/or unresectable GIST progressing after failure of at least imatinib and sunitinib. Methods Patients were randomised 2:1 to receive either regorafenib 160 mg orally daily or placebo, plus best supportive care in both arms, for the first 3 weeks of each 4-week cycle. The primary endpoint was progression-free survival (PFS). Upon disease progression, patients on placebo could cross over to regorafenib. Secondary endpoints included overall survival (OS), objective response rate, disease control rate (DCR: rate of durable stable disease lasting for ≥12 weeks plus complete or partial responses), and safety. This trial is registered at ClinicalTrials.gov (NCT01271712). Results From January to August 2011, 240 patients were screened at 57 centres in 17 countries, and 199 patients were randomised to receive regorafenib (n=133) or matching placebo (n=66). Median PFS per independent blinded central review was 4·8 months and 0·9 months, respectively (hazard ratio [HR] 0·27, 95% confidence interval [CI] 0·19–0·39; p<0·0001). Following progression, 56/66 patients (84·8%) on placebo crossed over to regorafenib, resulting in no significant difference in OS between study arms (HR 0·77, 95% CI 0·42–1·41; p=0·199). A best response of partial response or stable disease was observed in 101/133 patients (75·9%) on regorafenib and 23/66 patients (34·8%) on placebo. DCR was 52·6% (70/133 patients) and 9·1% (6/66 patients), respectively. Drug-related adverse events were reported in 130 (98·5%) of 132 regorafenib patients and 45 (68·2%) of 66 placebo patients. The most common grade ≥3 regorafenib
Pearson's random walk in the space of the CMB phases: Evidence for parity asymmetry
Hansen, M.; Frejsel, A. M.; Kim, J.; Naselsky, P.; Nesti, F.
2011-05-15
The temperature fluctuations of the cosmic microwave background (CMB) are supposed to be distributed randomly in both magnitude and phase, following to the simplest model of inflation. In this paper, we look at the odd and even multipoles of the spherical harmonic decomposition of the CMB, and the different characteristics of these, giving rise to a parity asymmetry. We compare the even and odd multipoles in the CMB power spectrum, and also the even and odd mean angles. We find for the multipoles of the power spectrum that there is power excess in odd multipoles, compared to even ones, meaning that we have a parity asymmetry. Further, for the phases, we present a random walk for the mean angles, and find a significant separation for even/odd mean angles, especially so for galactic coordinates. This is further tested and confirmed with a directional parity test, comparing the parity asymmetry in galactic and ecliptic coordinates.
Research on text encryption and hiding method with double-random phase-encoding
NASA Astrophysics Data System (ADS)
Xu, Hongsheng; Sang, Nong
2013-10-01
By using optical image processing techniques, a novel text encryption and hiding method applied by double-random phase-encoding technique is proposed in the paper. The first step is that the secret message is transformed into a 2- dimension array. The higher bits of the elements in the array are used to fill with the bit stream of the secret text, while the lower bits are stored specific values. Then, the transformed array is encoded by double random phase encoding technique. Last, the encoded array is embedded on a public host image to obtain the image embedded with hidden text. The performance of the proposed technique 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.
Chosen-plaintext attack on double-random-phase-encoding-based image hiding method
NASA Astrophysics Data System (ADS)
Xu, Hongsheng; Li, Guirong; Zhu, Xianchen
2015-12-01
By using optical image processing techniques, a novel text encryption and hiding method applied by double-random phase-encoding technique is proposed in the paper. The first step is that the secret message is transformed into a 2- dimension array. The higher bits of the elements in the array are used to fill with the bit stream of the secret text, while the lower bits are stored specific values. Then, the transformed array is encoded by double random phase encoding technique. Last, the encoded array is embedded on a public host image to obtain the image embedded with hidden text. The performance of the proposed technique 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.
Key management of the double random-phase-encoding method using public-key encryption
NASA Astrophysics Data System (ADS)
Saini, Nirmala; Sinha, Aloka
2010-03-01
Public-key encryption has been used to encode the key of the encryption process. In the proposed technique, an input image has been encrypted by using the double random-phase-encoding method using extended fractional Fourier transform. The key of the encryption process have been encoded by using the Rivest-Shamir-Adelman (RSA) public-key encryption algorithm. The encoded key has then been transmitted to the receiver side along with the encrypted image. In the decryption process, first the encoded key has been decrypted using the secret key and then the encrypted image has been decrypted by using the retrieved key parameters. The proposed technique has advantage over double random-phase-encoding method because the problem associated with the transmission of the key has been eliminated by using public-key encryption. Computer simulation has been carried out to validate the proposed technique.
Phase-space representation and polarization domains of random electromagnetic fields.
Castaneda, Roman; Betancur, Rafael; Herrera, Jorge; Carrasquilla, Juan
2008-08-01
The phase-space representation of stationary random electromagnetic fields is developed by using electromagnetic spatial coherence wavelets. The propagation of the field's power and states of spatial coherence and polarization results from correlations between the components of the field vectors at pairs of points in space. Polarization domains are theoretically predicted as the structure of the field polarization at the observation plane. In addition, the phase-space representation provides a generalization of the Poynting theorem. Theoretical predictions are examined by numerically simulating the Young experiment with electromagnetic waves. The experimental implementation of these results is a current subject of research. PMID:18670539
Inada, Yasuhisa Nishiwaki, Seiji; Hirasawa, Taku; Nakamura, Yoshitaka; Hashiya, Akira; Wakabayashi, Shin-ichi; Suzuki, Masa-aki; Matsuzaki, Jumpei
2014-02-10
We have developed a binary random phase array (BRPA) to improve the light extraction performance of white organic light-emitting devices (WOLEDs). We demonstrated that the scattering of incoming light can be controlled by employing diffraction optics to modify the structural parameters of the BRPA. Applying a BRPA to the substrate of the WOLED leads to enhanced extraction efficiency and suppression of angle-dependent color changes. Our systematic study clarifies the effect of scattering on the light extraction of WOLEDs.
Test of finite temperature random-phase approximation on a Lipkin model
Hagino, K.; Minato, F.
2009-10-15
We investigate the applicability of the finite temperature random phase approximation (RPA) using a solvable Lipkin model. We show that the finite temperature RPA reproduces reasonably well the temperature dependence of total strength, both for the positive energy (i.e., the excitation) and the negative energy (i.e., the de-excitation) parts. This is the case even at very low temperatures, which may be relevant to astrophysical purposes.
Hung, N. Quang; Dang, N. Dinh
2010-10-15
The thermodynamic properties of hot nuclei are described within the canonical and microcanonical ensemble approaches. These approaches are derived based on the solutions of the BCS and self-consistent quasiparticle random-phase approximation at zero temperature embedded into the canonical and microcanonical ensembles. The results obtained agree well with the recent data extracted from experimental level densities by the Oslo group for {sup 94}Mo, {sup 98}Mo, {sup 162}Dy, and {sup 172}Yb nuclei.
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.
NASA Astrophysics Data System (ADS)
Carnicer, Arturo; Montes-Usategui, Mario; Arcos, Sergio; Juvells, Ignacio
2005-07-01
We show how optical encryption methods based on double random phase keys are vulnerable to an organized attack of the chosen-ciphertext type. The decryption key can be easily obtained by an opponent who has repeated access to either the encryption or decryption machines. However, we have also devised a solution that prevents the attack. Our results cast doubts on the present security of these techniques.
NASA Astrophysics Data System (ADS)
Kuk Jhon, Young; Krishnamoorti, Ramanan; Genzer, Jan
2008-03-01
We report on the effect of chemical composition, co-monomer distribution and H/D isotopic substitution on the phase behavior in copolymers of poly(styrene-co-4-bromostyrene) (PBrxS), where x denotes the mole fraction of 4-bromostyrene (4-BrS), in cyclohexane. By adjusting the solvent quality during bromination of parent polystyrene, either random or random blocky PBrxS, (r-PBrxS or b-PBrxS, respectively), were synthesized. We studied the temperature dependence of phase behavior of PBrxS with various x in cyclohexane as a function of the polymer concentration using light scattering. Our results reveal that for a given 4-BrS content, the cloud points of b-PBrxS solutions are consistently higher and broader than those observed in r-PBrxS solutions. The transition temperature has also been found to depend on the isotope substitutions of H or D in either the polymer or the solvent. Small angle neutron scattering measurements indicate significant differences in the temperature dependence of the thermodynamic behavior for the random and blocky samples and the nature of the fluctuations upon approaching the phase boundaries.
Molecular phase space transport in water: Non-stationary random walk model
NASA Astrophysics Data System (ADS)
Nerukh, Dmitry; Ryabov, Vladimir; Taiji, Makoto
2009-11-01
Molecular transport in phase space is crucial for chemical reactions because it defines how pre-reactive molecular configurations are found during the time evolution of the system. Using Molecular Dynamics (MD) simulated atomistic trajectories we test the assumption of the normal diffusion in the phase space for bulk water at ambient conditions by checking the equivalence of the transport to the random walk model. Contrary to common expectations we have found that some statistical features of the transport in the phase space differ from those of the normal diffusion models. This implies a non-random character of the path search process by the reacting complexes in water solutions. Our further numerical experiments show that a significant long period of non-stationarity in the transition probabilities of the segments of molecular trajectories can account for the observed non-uniform filling of the phase space. Surprisingly, the characteristic periods in the model non-stationarity constitute hundreds of nanoseconds, that is much longer time scales compared to typical lifetime of known liquid water molecular structures (several picoseconds).
Vapour-liquid phase diagram for an ionic fluid in a random porous medium.
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. PMID:27548356
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.
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.
Brose, Marcia S; Nutting, Christopher M; Jarzab, Barbara; Elisei, Rossella; Siena, Salvatore; Bastholt, Lars; de la Fouchardiere, Christelle; Pacini, Furio; Paschke, Ralf; KeeShong, Young; Sherman, Steven I; Smit, Johannes WA; Chung, John; Kappeler, Christian; Pena, Carol; Molnár, István; Schlumberger, Martin J
2015-01-01
Background Patients with radioactive iodine (131I, RAI)-refractory locally advanced or metastatic differentiated thyroid cancer (DTC) have a poor prognosis due to the lack of effective treatment options. Methods This multicentre, randomized (1:1), double-blind, placebo-controlled, phase 3 study (DECISION; NCT00984282) investigated sorafenib (400 mg orally twice-daily) in patients with RAI-refractory locally advanced or metastatic DTC progressing within the past 14 months. The primary endpoint was progression-free survival (PFS) by central independent review. Patients receiving placebo could crossover to open-label sorafenib upon progression. Archival tumour tissue was examined for BRAF and RAS mutations. Serum thyroglobulin was measured at baseline and each visit. Findings A total of 417 patients were randomized to sorafenib (n=207) or placebo (n=210). Sorafenib treatment significantly improved PFS compared with placebo (hazard ratio, 0·59; 95% confidence interval, 0·45–0·76; P<0·0001; median 10·8 vs. 5·8 months, respectively). PFS improvement was seen in all pre-specified clinical and genetic biomarker subgroups irrespective of mutation status. There was no statistically significant difference in overall survival (hazard ratio, 0·80; 95% confidence interval, 0·54–1·19; P=0·14); median overall survival had not been reached and 150 (71%) patients receiving placebo crossed over to sorafenib upon progression. Response rates (all partial responses) were 12·2% (24/196; sorafenib) and 0·5% (1/201; placebo; p<0·0001). Median thyroglobulin levels increased in the placebo group, and decreased, then paralleled treatment responses in the sorafenib group. Most adverse events were grade 1 or 2. The most common treatment-emergent adverse events in the sorafenib arm were hand–foot skin reaction (76·3%), diarrhoea (68·6%), alopecia (67·1%), and rash/desquamation (50·2%). Interpretation Sorafenib significantly improved PFS compared with placebo in patients
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.
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
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.
Self-consistent relativistic random-phase approximation with vacuum polarization
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.
Broadband diffuse reflections of sound by metasurface with random phase response
NASA Astrophysics Data System (ADS)
Gu, Zhong-ming; Liang, Bin; Zou, Xin-ye; Cheng, Jian-chun
2015-09-01
We have designed an ultrathin planar structure capable of generating diffuse reflections within a broadband. By introducing randomly distributed gradients along the interface, the proposed structure can scatter the incident acoustic waves into all directions and virtually suppress the scattered lobes that will otherwise be remarkable for a planar surface. A practical implementation by labryinthine-like metamaterial with designed phase shift profile is demontrated. The numerical results show that our designed planar surface could be used to mimic a rugged surface as expected. We envision our designed structure to exhibit potentials in applications such as room acoustics and acoustic stealth.
Random fields and the weakly first-order phase transition in superconductors
Busiello, G.; De Cesare, L.; Uzunov, D.I.
1986-10-01
We study the influence of random fields with short-range and long-range correlations on the weakly first-order phase transition in superconductors. Renormalization-group (RG) analysis near the upper critical dimensionality d/sub u/ = 6 (short-range correlations) reveals a new critical behavior which holds if the number of the order-parameter components is n>10. In the long-range case, the RG transformation is self-consistent only if the parameter theta of the long-range correlations is assumed of order epsilon, epsilon = 6-d.
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.
Reconstruction of photon number conditioned states using phase randomized homodyne measurements
NASA Astrophysics Data System (ADS)
Chrzanowski, H. M.; Assad, S. M.; Bernu, J.; Hage, B.; Lund, A. P.; Ralph, T. C.; Lam, P. K.; Symul, T.
2013-05-01
We experimentally demonstrate the reconstruction of a photon number conditioned state without using a photon number discriminating detector. By using only phase randomized homodyne measurements, we reconstruct up to the three photon subtracted squeezed vacuum state. The reconstructed Wigner functions of these states show regions of pronounced negativity, signifying the non-classical nature of the reconstructed states. The techniques presented allow for complete characterization of the role of a conditional measurement on an ensemble of states, and might prove useful in systems where photon counting still proves technically challenging.
NASA Astrophysics Data System (ADS)
Nikšić, T.; Kralj, N.; Tutiš, T.; Vretenar, D.; Ring, P.
2013-10-01
A new implementation of the finite amplitude method (FAM) for the solution of the relativistic quasiparticle random-phase approximation (RQRPA) is presented, based on the relativistic Hartree-Bogoliubov (RHB) model for deformed nuclei. The numerical accuracy and stability of the FAM-RQRPA is tested in a calculation of the monopole response of 22O. As an illustrative example, the model is applied to a study of the evolution of monopole strength in the chain of Sm isotopes, including the splitting of the giant monopole resonance in axially deformed systems.
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.
De Donno, V.; Co', G.; Anguiano, M.; Lallena, A. M.
2011-09-15
We study the electromagnetic responses of {sup 4}He within the framework of the self-consistent continuum random-phase approximation theory. In this approach, the ground-state properties are described by a Hartree-Fock calculation. The single-particle basis constructed in this manner is used in the calculations of the continuum responses of the system. Finite-range interactions are considered in the calculations. We compare our results with photon-absorption cross sections and electron-scattering quasielastic data. From this comparison, and also from the comparison with the results of microscopic calculations, we deduce that our approach describes well the continuum excitation.
Speckle suppression in digital holographic imaging with random phases and different wavelengths
NASA Astrophysics Data System (ADS)
Leng, Junmin; Sang, Xinzhu; Yan, Binbin
2014-03-01
An effective speckle suppression method in digital holography is experimentally demonstrated with a wavelength-tunable coherent light source and a moving diffuser. Multiple off-axis digital holograms with different wavelengths and random phases are obtained. The Fresnel transformation algorithm is used to calculate the diffraction integral in the reconstruction. The speckle noise in the reconstructed images is suppressed by superposing and averaging the intensity of multiple reconstruction images. Experiment results and the parameter evaluation show that the presented method is effective and feasible.
Quantum Monte Carlo method using phase-free random walks with slater determinants.
Zhang, Shiwei; Krakauer, Henry
2003-04-01
We develop a quantum Monte Carlo method for many fermions using random walks in the space of Slater determinants. An approximate approach is formulated with a trial wave function |Psi(T)> to control the phase problem. Using a plane-wave basis and nonlocal pseudopotentials, we apply the method to Be, Si, and P atoms and dimers, and to bulk Si supercells. Single-determinant wave functions from density functional theory calculations were used as |Psi(T)> with no additional optimization. The calculated binding energies of dimers and cohesive energy of bulk Si are in excellent agreement with experiments and are comparable to the best existing theoretical results. PMID:12689312
Computer and graphics modeling of heat transfer and phase change in a wall with randomly imbibed PCM
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.
del Moral, A.; Arnaudas, J.I. ); Gehring, P.M. ); Salamon, M.B. ); Ritter, C. ); Joven, E. ); Cullen, J. (Magnetics Group, Naval Surface Warfare Center, 10901 New Hampshire Avenue, White Oak, Silver Spring, Maryland 20903-5000 (United State
1993-04-01
The low-temperature ([ital T]=0 K) first-order phase transition, predicted to drive systems with both weak random and uniform cubic anisotropy from a correlated spin glass to a ferromagnet, has been observed. At higher temperatures the transition is to a quasi- or random ferromagnet. The transition occurs at a concentration [ital x][sub [ital t
Information hiding based on double random-phase encoding and public-key cryptography.
Sheng, Yuan; Xin, Zhou; Alam, Mohammed S; Xi, Lu; Xiao-Feng, Li
2009-03-01
A novel information hiding method based on double random-phase encoding (DRPE) and Rivest-Shamir-Adleman (RSA) public-key cryptosystem is proposed. In the proposed technique, the inherent diffusion property of DRPE is cleverly utilized to make up the diffusion insufficiency of RSA public-key cryptography, while the RSA cryptosystem is utilized for simultaneous transmission of the cipher text and the two phase-masks, which is not possible under the DRPE technique. This technique combines the complementary advantages of the DPRE and RSA encryption techniques and brings security and convenience for efficient information transmission. Extensive numerical simulation results are presented to verify the performance of the proposed technique. PMID:19259163
Low-noise multiple watermarks technology based on complex double random phase encoding method
NASA Astrophysics Data System (ADS)
Zheng, Jihong; Lu, Rongwen; Sun, Liujie; Zhuang, Songlin
2010-11-01
Based on double random phase encoding method (DRPE), watermarking technology may provide a stable and robust method to protect the copyright of the printing. However, due to its linear character, DRPE exist the serious safety risk when it is attacked. In this paper, a complex coding method, which means adding the chaotic encryption based on logistic mapping before the DRPE coding, is provided and simulated. The results testify the complex method will provide better security protection for the watermarking. Furthermore, a low-noise multiple watermarking is studied, which means embedding multiple watermarks into one host printing and decrypt them with corresponding phase keys individually. The Digital simulation and mathematic analysis show that with the same total embedding weight factor, multiply watermarking will improve signal noise ratio (SNR) of the output printing image significantly. The complex multiply watermark method may provide a robust, stability, reliability copyright protection with higher quality printing image.
Flores, Angel; Robin, Craig; Lanari, Ann; Dajani, Iyad
2014-07-28
We report on pseudo random binary sequence (PRBS) phase modulation for narrow-linewidth, kilowatt-class, monolithic (all-fiber) amplifiers. Stimulated Brillouin scattering (SBS) threshold enhancement factors for different patterns of PRBS modulated fiber amplifiers were experimentally analyzed and agreed well with the theoretical predictions. We also examined seeding of the SBS process by phase modulated signals when the effective linewidth is on the same order as the Brillouin shift frequency. Here ~30% variations in SBS power thresholds were observed from small tunings of the modulation frequency. In addition, a 3 GHz PRBS modulated, 1.17 kW fiber amplifier was demonstrated. Near diffraction-limited beam quality was achieved (M2 = 1.2) with an optical pump efficiency of 83%. Overall, the improved SBS suppression and narrow linewidth achieved through PRBS modulation can have a significant impact on the beam combining of kilowatt class fiber lasers. PMID:25089393
Pseudo-random binary sequency phase modulation in high power Yb-doped fiber amplifiers
NASA Astrophysics Data System (ADS)
Robin, Craig; Dajani, Iyad; Zernigue, Clint; Flores, Angel; Pulford, Ben; Lanari, Ann; Naderi, Shadi
2013-03-01
We present experimental and theoretical studies on the stimulated Brillouin scattering (SBS) threshold in fiber amplifiers seeded with a spectrally broadened single-frequency laser source. An electro-optic phase modulator is driven with various pseudo-random binary sequence (PRBS) patterns to highlight the unique characteristics of this linewidth broadening technique and its facility in SBS mitigation. Theoretical predictions show a variation in SBS suppression based on PRBS pattern and modulation frequency. These predictions are experimentally investigated in a kilowatt level monolithic fiber amplifier operating with near diffraction-limited beam quality. We also show Rayleigh scattering and other sources of back reflected light in phase modulated signals can seed the SBS process and significantly reduce the nonlinear threshold.
High energy X-ray phase and dark-field imaging using a random absorption mask
NASA Astrophysics Data System (ADS)
Wang, Hongchang; Kashyap, Yogesh; Cai, Biao; Sawhney, Kawal
2016-07-01
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.
Dual-channel in-line digital holographic double random phase encryption
Das, Bhargab; Yelleswarapu, Chandra S; Rao, D V G L N
2012-01-01
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. PMID:23471012
Deviations from the mean-field predictions for the phase behaviour of random copolymers melts
NASA Astrophysics Data System (ADS)
Houdayer, J.; Müller, M.
2002-06-01
We investigate the phase behaviour of random copolymers melts via large-scale Monte Carlo simulations. We observe macrophase separation into A- and B-rich phases as predicted by the mean-field theory only for systems with a very large correlation λ of blocks along the polymer chains, far away from the Lifshitz point. For smaller values of λ, we find that a locally segregated, disordered microemulsion-like structure gradually forms as the temperature decreases. As we increase the number of blocks in the polymers, the region of macrophase separation further shrinks. The results of our Monte Carlo simulation are in agreement with a Ginzburg criterium, which suggests that the mean-field theory becomes worse as the number of blocks in polymers increases.
Shimobaba, Tomoyoshi; Makowski, Michał; Nagahama, Yuki; Endo, Yutaka; Hirayama, Ryuji; Hiyama, Daisuke; Hasegawa, Satoki; Sano, Marie; Kakue, Takashi; Oikawa, Minoru; Sugie, Takashige; Takada, Naoki; Ito, Tomoyoshi
2016-05-20
We propose two calculation methods of generating color computer-generated holograms (CGHs) with the random phase-free method and color space conversion in order to improve the image quality and accelerate the calculation. The random phase-free method improves the image quality in monochrome CGH, but it is not performed in color CGH. We first aimed to improve the image quality of color CGH using the random phase-free method and then to accelerate the color CGH generation with a combination of the random phase-free method and color space conversion method, which accelerates the color CGH calculation due to down-sampling of the color components converted by color space conversion. To overcome the problem of image quality degradation that occurs due to the down-sampling of random phases, the combination of the random phase-free method and color space conversion method improves the quality of reconstructed images and accelerates the color CGH calculation. We demonstrated the effectiveness of the proposed method in simulation, and in this paper discuss its application to lensless zoomable holographic projection. PMID:27411145
Peng, Degao; Steinmann, Stephan N; van Aggelen, Helen; Yang, Weitao
2013-09-14
The recent proposal to determine the (exact) correlation energy based on pairing matrix fluctuations by van Aggelen et al. ["Exchange-correlation energy from pairing matrix fluctuation and the particle-particle random phase approximation," preprint arXiv:1306.4957 (2013)] revived the interest in the simplest approximation along this path: the particle-particle random phase approximation (pp-RPA). In this paper, we present an analytical connection and numerical demonstrations of the equivalence of the correlation energy from pp-RPA and ladder-coupled-cluster doubles. These two theories reduce to identical algebraic matrix equations and correlation energy expressions. The numerical examples illustrate that the correlation energy missed by pp-RPA in comparison with coupled-cluster singles and doubles is largely canceled out when considering reaction energies. This theoretical connection will be beneficial to design density functionals with strong ties to coupled-cluster theories and to study molecular properties at the pp-RPA level relying on well established coupled cluster techniques. PMID:24050333
Efficient Text Encryption and Hiding with Double-Random Phase-Encoding
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
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.
Nuclear excitations as coupled one and two random-phase-approximation modes
NASA Astrophysics Data System (ADS)
Gambacurta, D.; Catara, F.; Grasso, M.; Sambataro, M.; Andrés, M. V.; Lanza, E. G.
2016-02-01
We present an extension of the random-phase approximation (RPA) where the RPA phonons are used as building blocks to construct the excited states. In our model, that we call double RPA (DRPA), we include up to two RPA phonons. This is an approximate and simplified way, with respect to the full second random-phase approximation (SRPA), to extend the RPA by including two-particle-two-hole configurations. Some limitations of the standard SRPA model, related to the violation of the stability condition, are not encountered in the DRPA. We also verify in this work that the energy-weighted sum rules are satisfied. The DRPA is applied to low-energy modes and giant resonances in the nucleus 16O. We show that the model (i) produces a global downwards shift of the energies with respect to the RPA spectra and (ii) provides a shift that is, however, strongly reduced compared to that generated by the standard SRPA. This model represents an alternative way of correcting for the SRPA anomalous energy shift, compared to a recently developed extension of the SRPA, where a subtraction procedure is applied. The DRPA provides results in good agreement with the experimental energies, with the exception of those low-lying states that have a dominant two-particle-two-hole nature. For describing such states, higher-order calculations are needed.
Self-consistent extension of random-phase approximation enlarged beyond particle-hole configurations
Gambacurta, Danilo; Catara, Francesco; Grasso, Marcella
2009-07-15
We present a new extension of the random-phase approximation method: the quasiboson approximation is avoided and correlations are included in the ground state without resorting to renormalized operators or renormalized matrix elements; the configuration space is enlarged by considering also elementary excitations corresponding to the annihilation of a particle (hole) and the creation of another particle (hole) on the correlated ground state, together with the particle-hole ones. Two new and relevant advantages of this method with respect to the existing extensions of random-phase approximation are highlighted: (i) the energy weighted sum rules are completely satisfied; (ii) the problem of the existence of nonphysical states in the spectrum, related to the inclusion of particle-particle and hole-hole configurations, is solved: a way to unambiguously disentangle physical from nonphysical states in the excitation spectrum is presented. The method is applied here to a three-level Lipkin model where its quality can be judged by comparing with the exact results. Both advantages (i) and (ii) shall lead to feasible future applications of this extended RPA to several realistic cases.
Jamaluddin, M.B.
1986-01-01
The Boson Expansion Theory of Kishimoto and Tamura has proved to be very successful in describing quadrupole collective motions in even-even nuclei. This theory, however, involves a complicated transformation from the Tamm-Dancoff phonons to the phonons of the random Phase Approximation. In this thesis a Boson Expansion formalism, derived directly from the Random Phase Approximation and set forth by Pedracchi and Tamura, is used to derive the boson forms of the nuclear Hamiltonian and the electromagnetic transition operator. Detailed discussions of the formalism of Pedrocchi and Tamura and its extension needed to perform realistic calculations are presented. The technique used to deriving the boson forms and the formulae used in the calculations are also given a thorough treatment to demonstrate the simplicity of this approach. Finally, the theory is tested by applying it to calculate the energy levels and some electromagnetic properties of the Samarium isotopes. The results show that the present theory is capable of describing the range of behavior from a vibrational to a rotational character of the Samarium isotopes as well as the previous theory.
Diagnosis of the phase function of random media from light reflectance
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
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.
NASA Astrophysics Data System (ADS)
Buckley, Edward; Cable, Adrian; Lawrence, Nic; Wilkinson, Tim
2006-10-01
Holographic displays employing binary phase modulation have been demonstrated to be attractive on the grounds of efficiency and miniaturization, and they offer a plausible approach to two-dimensional (2D) and three-dimensional (3D) image projection and display. A novel algorithm--one-step phase retrieval--and corresponding hardware architecture have recently been proposed, providing the performance required for real-time holographic display. However, since viewing angle varies inversely with pixel size, very small display pixels are required to achieve a wide field of view. This is particularly problematic for 3D displays, as the requirement for a large display with small pixels has hitherto necessitated an unachievably large electrical bandwidth. We present a novel approach, utilizing fixed random pixelated quaternary phase masks of greater resolution than the displayed hologram, to dramatically increase the viewing angle for 2D and 3D holographic displays without incurring a bandwidth penalty or significantly degrading image quality. Furthermore, an algorithm is presented to generate holograms accounting for the presence of such a phase mask, so that only one mask is required.
Multicentric malignant gastrointestinal stromal tumor.
Shukla, Shailaja; Singh, Sanjeet K; Pujani, Mukta
2009-01-01
Malignant gastrointestinal stromal tumor (GIST) is a rare type of sarcoma that is found in the digestive system, most often in the wall of the stomach. Multiple GISTs are extremely rare and usually associated with type 1 neurofibromatosis and familial GIST.We report here a case of a 70-year-old woman who reported pain in the abdomen, loss of appetite, and weight loss for six months. Ultrasound examination showed a small bowel mass along with multiple peritoneal deposits and a mass within the liver. Barium studies were suggestive of a neoplastic pathology of the distal ileum. A differential diagnosis of adenocarcinoma/lymphoma with metastases was entertained. Perioperative findings showed two large growths arising from the jejunum and the distal ileum, along with multiple smaller nodules on the serosal surface and adjoining mesentery of the involved bowel segments. Segmental resection of the involved portions of the intestine was performed. Histopathological features were consistent with those of multicentric malignant GIST-not otherwise specified (GIST-NOS). Follow-up examination three months after surgery showed no evidence of recurrence. PMID:19568556
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
Multi-kW coherent combining of fiber lasers seeded with pseudo random phase modulated light
NASA Astrophysics Data System (ADS)
Flores, Angel; Ehrehreich, Thomas; Holten, Roger; Anderson, Brian; Dajani, Iyad
2016-03-01
We report efficient coherent beam combining of five kilowatt-class fiber amplifiers with a diffractive optical element (DOE). Based on a master oscillator power amplifier (MOPA) configuration, the amplifiers were seeded with pseudo random phase modulated light. Each non-polarization maintaining fiber amplifier was optically path length matched and provides approximately 1.2 kW of near diffraction-limited output power (measured M2<1.1). Consequently, a low power sample of each laser was utilized for active linear polarization control. A low power sample of the combined beam after the DOE provided an error signal for active phase locking which was performed via Locking of Optical Coherence by Single-Detector Electronic-Frequency Tagging (LOCSET). After phase stabilization, the beams were coherently combined via the 1x5 DOE. A total combined output power of 4.9 kW was achieved with 82% combining efficiency and excellent beam quality (M2<1.1). The intrinsic DOE splitter loss was 5%. Similarly, losses due in part to non-ideal polarization, ASE content, uncorrelated wavefront errors, and misalignment errors contributed to the efficiency reduction.
2011-01-01
Background Identification of predictive markers of response to treatment is a major objective in breast cancer. A major problem in clinical sampling is the variability of RNA templates, requiring accurate management of tumour material and subsequent analyses for future translation in clinical practice. Our aim was to establish the feasibility and reliability of high throughput RNA analysis in a prospective trial. Methods This study was conducted on RNA from initial biopsies, in a prospective trial of neoadjuvant chemotherapy in 327 patients with inoperable breast cancer. Four independent centres included patients and samples. Human U133 GeneChips plus 2.0 arrays for transcriptome analysis and quantitative RT-qPCR of 45 target genes and 6 reference genes were analysed on total RNA. Results Thirty seven samples were excluded because i) they contained less than 30% malignant cells, or ii) they provided RNA Integrity Number (RIN) of poor quality. Among the 290 remaining cases, taking into account strict quality control criteria initially defined to ensure good quality of sampling, 78% and 82% samples were eligible for transcriptome and RT-qPCR analyses, respectively. For RT-qPCR, efficiency was corrected by using standard curves for each gene and each plate. It was greater than 90% for all genes. Clustering analysis highlighted relevant breast cancer phenotypes for both techniques (ER+, PR+, HER2+, triple negative). Interestingly, clustering on trancriptome data also demonstrated a "centre effect", probably due to the sampling or extraction methods used in on of the centres. Conversely, the calibration of RT-qPCR analysis led to the centre effect withdrawing, allowing multicentre analysis of gene transcripts with high accuracy. Conclusions Our data showed that strict quality criteria for RNA integrity assessment and well calibrated and standardized RT-qPCR allows multicentre analysis of genes transcripts with high accuracy in the clinical context. More stringent
Telemedicine techniques can be used to facilitate the conduct of multicentre trials.
Kennedy, C; Kirwan, J; Cook, C; Roux, P; Stulting, A; Murdoch, I
2000-01-01
A multicentre randomized controlled trial was established in Pretoria, Bloemfontein and Edendale in South Africa, and coordinated from London. The purpose of the trial was to determine the efficacy of low-dose beta irradiation of glaucoma. Five communication modalities (telephone, fax, e-mail, videoconferencing and face-to-face meetings) were examined in terms of their benefits in a multicentre trial. The eight stages of the multicentre trial examined were: set-up and training, recruitment, standardization, patient management, data transmission, update and data dissemination, clinical follow-up and monitoring, and publication. On four-point Likert scales for rating the usefulness of the communication modalities at each of the eight stages of the trial (from 0 = not useful to 3 = very useful; maximum score 24) the telephone was given a total score of 10, fax 9, e-mail 13, videoconferencing 15 and face-to-face meetings 9. Telemedicine techniques offer considerable benefits in the coordination of multicentre trials by improving data collection, maintaining the efficacy and monitoring of trials, while potentially offering reduced costs in terms of travel and time. The realtime scrutiny of patient records helps to ensure data uniformity and completeness of data collection. Videoconferencing was most useful when considered as one of several communication tools that can be used to improve the effectiveness of a service or process. PMID:11265104
[Multicentric and localized tineas in immunocompromised patients].
García de Acevedo, Beatriz; Villa, Antonio; Hernández-Hernández, Francisca; López-Martínez, Rubén; Llorente, Luis; Orozco-Topete, Rocío
2008-03-01
From the dermatological point of view, multifocal or multicentric tineas are widespread dermatophytic infections affecting two or more anatomical areas. In the immunosuppressed patient, these lesions are frequently atypical and the risk factors are not well established. The aims of this study were: to determine the risk factors associated to multicentric tinea in immunocompromised patients; to evaluate the immune response by trichophytin and candidin skin test, to determine the etiological agent and to quantify some serum interleukines. Thirty-six multicentric tinea and 37 localized tinea patients, both with immunocompromised factors, were included. By means of a questionnaire several risk factors were identified; the trichophytin and candidin skin test was evaluated after 48 hours. Mycological direct examination and culture were performed. The interleukins IL-2, IL-4, IL-10 and interferon gamma were quantified by ELISA. Statistical analysis was made by Chi-square, U Mann Whitney and logistic regression. In disseminated tinea patients a predominance of females (69%) versus localized tinea patients (30%) was observed. Prednisone, azathioprine and cyclophosphamide treatment was associated to multicentric tinea. Trichophytin was negative in all disseminated tinea patients and positive in only three localized tinea cases, candidin was positive in six and eight cases of multicentric and localized tinea respectively. Trichophyton rubrum was the most frequent etiological agent. No differences in interleukin concentrations were found. Female gender and some immunosuppressor treatments were associated with a high probability to develop multicentric tinea. In this study a defect in the cellular immune response was the possible explanation for the extensive reactions. PMID:18338925
Avalanche effect and bit independence behaviors of double random phase encoding schemes
NASA Astrophysics Data System (ADS)
Sultana, Nishat; Moon, Inkyu
2016-06-01
In this paper, we present an overview of the avalanche and bit independence characteristics of double random phase encoding (DRPE) scheme in the virtual optical domains. DRPE apparently demonstrates outstanding bit independence property in both the Fourier and Fresnel domains. Experimental results validate that the DRPE performance in Fresnel domain surpasses the DRPE in Fourier domain by showing better avalanche effect characteristics. The avalanche effect result is remarkably poor for the DRPE in Fourier domain when only one bit of the plaintext or encryption key is altered. In contrast, DRPE in Fresnel domain shows adequate avalanche effect results regardless of how many numbers of bits are altered in the plaintext or in the encryption key.
A study of key features of random atmospheric disturbance models for the approach flight phase
NASA Technical Reports Server (NTRS)
Heffley, R. K.
1977-01-01
An analysis and brief simulator experiment were performed to identify and classify important features of random turbulence for the landing approach flight phase. The analysis of various wind models was carried out within the context of the longitudinal closed-loop pilot/vehicle system. The analysis demonstrated the relative importance of atmospheric disturbance scale lengths, horizontal versus vertical gust components, decreasing altitude, and spectral forms of disturbances versus the pilot/vehicle system. Among certain competing wind models, the analysis predicted no significant difference in pilot performance. This was confirmed by a moving base simulator experiment which evaluated the two most extreme models. A number of conclusions were reached: attitude constrained equations do provide a simple but effective approach to describing the closed-loop pilot/vehicle. At low altitudes the horizontal gust component dominates pilot/vehicle performance.
Lattice energies of molecular solids from the random phase approximation with singles corrections.
Klimeš, Jiří
2016-09-01
We use the random phase approximation (RPA) method with the singles correlation energy contributions to calculate lattice energies of ten molecular solids. While RPA gives too weak binding, underestimating the reference data by 13.7% on average, much improved results are obtained when the singles are included at the GW singles excitations (GWSE) level, with average absolute difference to the reference data of only 3.7%. Consistently with previous results, we find a very good agreement with the reference data for hydrogen bonded systems, while the binding is too weak for systems where dispersion forces dominate. In fact, the overall accuracy of the RPA+GWSE method is similar to an estimated accuracy of the reference data. PMID:27609003
Importance of self-consistency in relativistic continuum random-phase approximation calculations
Yang Ding; Cao Ligang; Tian Yuan; Ma Zhongyu
2010-11-15
A fully consistent relativistic continuum random phase approximation (RCRPA) is constructed, where the contribution of the continuum spectrum to nuclear excitations is treated exactly by the single-particle Green's function technique. The full consistency of the calculations is achieved that the same effective Lagrangian is adopted for the ground state and the excited states. The negative energy states in the Dirac sea are also included in the single-particle Green's function in the no-sea approximation. The currents from the vector meson and photon exchanges and the Coulomb interaction in RCRPA are treated exactly. The spin-orbit interaction is included naturally in the relativistic frame. Numerical results of the RCRPA are checked with the constrained relativistic mean-field theory. We study the effects of the inconsistency, particularly the currents and Coulomb interaction in various collective multipole excitations.
Extended random-phase approximation in a boson formalism with Pauli principle
Sambataro, M.; Catara, F.
1995-06-01
The random-phase approximation (RPA) is examined in a boson formalism and special attention is focused on the problem of the violation of the Pauli principle affecting this theory. A mapping technique is discussed and the boson image of a two-body fermion Hamiltonian is constructed. Within the boson space so defined, an extension of RPA is proposed where structure and energy of the ground state, as well as those of the one-phonon states, are analyzed with regard to the role of the spurious components associated with a violation of the Pauli principle. A multistep minimization procedure for the determination of a better ground state is also examined. Numerical tests are performed within the Lipkin-Meshkov-Glick model.
Simulation study on heat conduction of a nanoscale phase-change random access memory cell.
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. PMID:17252792
Losa, C.; Doessing, T.; Pastore, A.; Vigezzi, E.; Broglia, R. A.
2010-06-15
We present a calculation of the properties of vibrational states in deformed, axially-symmetric even-even nuclei, within the framework of a fully self-consistent quasiparticle random phase approximation (QRPA). The same Skyrme energy density and density-dependent pairing functionals are used to calculate the mean field and the residual interaction in the particle-hole and particle-particle channels. We have tested our software in the case of spherical nuclei against fully self-consistent calculations published in the literature, finding excellent agreement. We investigate the consequences of neglecting the spin-orbit and Coulomb residual interactions in QRPA. Furthermore we discuss the improvement obtained in the QRPA result associated with the removal of spurious modes. Isoscalar and isovector responses in the deformed {sup 24-26}Mg, {sup 34}Mg isotopes are presented and compared to experimental findings.
Niu, Y. F.; Paar, N.; Vretenar, D.; Meng, J.
2011-04-15
We introduce a self-consistent microscopic theoretical framework for modeling the process of electron capture on nuclei in stellar environment, based on relativistic energy density functionals. The finite-temperature relativistic mean-field model is used to calculate the single-nucleon basis and the occupation factors in a target nucleus, and J{sup {pi}}=0{sup {+-}}, 1{sup {+-}}, and 2{sup {+-}} charge-exchange transitions are described by the self-consistent finite-temperature relativistic random-phase approximation. Cross sections and rates are calculated for electron capture on {sup 54,56}Fe and {sup 76,78}Ge in stellar environment, and results compared with predictions of similar and complementary model calculations.
Hung, N. Quang; Dang, N. Dinh
2010-05-15
We propose a description of pairing properties in finite systems within the canonical and microcanonical ensembles. The approach is derived by solving the BCS and self-consistent quasiparticle random-phase approximation with the Lipkin-Nogami particle-number projection at zero temperature. The obtained eigenvalues are embedded into the canonical and microcanonical ensembles. The results obtained are found in quite good agreement with the exact solutions of the doubly-folded equidistant multilevel pairing model as well as the experimental data for {sup 56}Fe nucleus. The merit of the present approach resides in its simplicity and its application to a wider range of particle number, where the exact solution is impracticable.
Encrypted imaging based on algebraic implementation of double random phase encoding.
Nakano, Kazuya; Takeda, Masafumi; Suzuki, Hiroyuki; Yamaguchi, Masahiro
2014-05-10
The security of important information captured by sensors and cameras is currently a growing concern as information theft via techniques such as side-channel attacks become increasingly more prevalent. Double random phase encoding (DRPE) is an optical encryption method based on optical Fourier transform that is currently being used to implement secure coherent optical systems. In this paper, we propose a new DRPE implementation for incoherent optical systems based on integral photography that can be applied to "encrypted imaging (EI)" to optically encrypt an image before it is captured by an image sensor. Because the proposed incoherent DRPE is constituted from conventional DRPE by rewriting the optical encryption via discretization and Euler's formula, its security level is the same as that of conventional DRPE. The results of an experiment in which we encrypted a plaintext image optically and then decrypted it numerically demonstrate that our proposed incoherent optical security system is feasible. PMID:24922013
Particle-particle random-phase approximation applied to beryllium isotopes
Blanchon, G.; Dupuis, M.; Pillet, N.; Mau, N. Vinh; Bonaccorso, A.
2010-09-15
This paper is dedicated to the study of even-even {sup 8-14}Be isotopes, which uses the particle-particle random-phase approximation that accounts for two-body correlations in the core nucleus. A better description of energies and two-particle amplitudes is obtained in comparison with models that assume a neutron closed-shell (or subshell) core. A Woods-Saxon potential corrected by a phenomenological particle-vibration coupling term has been used for the neutron-core interaction and the D1S Gogny force for the neutron-neutron interaction. Calculated ground-state properties as well as excited-state ones are discussed and are compared to experimental data. In particular, results suggest the same 2s{sub 1/2}-1p{sub 1/2} shell inversion in {sup 13}Be as in {sup 11}Be.
Insight into organic reactions from the direct random phase approximation and its corrections
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.
Graphics processing unit-accelerated double random phase encoding for fast image encryption
NASA Astrophysics Data System (ADS)
Lee, Jieun; Yi, Faliu; Saifullah, Rao; Moon, Inkyu
2014-11-01
We propose a fast double random phase encoding (DRPE) algorithm using a graphics processing unit (GPU)-based stream-processing model. A performance analysis of the accelerated DRPE implementation that employs the Compute Unified Device Architecture programming environment is presented. We show that the proposed methodology executed on a GPU can dramatically increase encryption speed compared with central processing unit sequential computing. Our experimental results demonstrate that in encryption data of an image with a pixel size of 1000×1000, where one pixel has a 32-bit depth, our GPU version of the DRPE scheme can be approximately two times faster than the advanced encryption standard algorithm implemented on a GPU. In addition, the quality of parallel processing on the presented DRPE acceleration method is evaluated with performance parameters, such as speedup, efficiency, and redundancy.
Self-consistent quasiparticle random-phase approximation for a multilevel pairing model
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.
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.
Conical Intersections from Particle-Particle Random Phase and Tamm-Dancoff Approximations.
Yang, Yang; Shen, Lin; Zhang, Du; Yang, Weitao
2016-07-01
The particle-particle random phase approximation (pp-RPA) and the particle-particle Tamm-Dancoff approximation (pp-TDA) are applied to the challenging conical intersection problem. Because they describe the ground and excited states on the same footing and naturally take into account the interstate interaction, these particle-particle methods, especially the pp-TDA, can correctly predict the dimensionality of the conical intersection seam as well as describe the potential energy surface in the vicinity of conical intersections. Though the bond length of conical intersections is slightly underestimated compared with the complete-active-space self-consistent field (CASSCF) theory, the efficient particle-particle methods are promising for conical intersections and nonadiabatic dynamics. PMID:27293013
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.
A blind image detection method for information hiding with double random-phase encoding
NASA Astrophysics Data System (ADS)
Sheng, Yuan; Xin, Zhou; Jian-guo, Chen; Yong-liang, Xiao; Qiang, Liu
2009-07-01
In this paper, a blind image detection method based on a statistical hypothesis test for information hiding with double random-phase encoding (DRPE) is proposed. This method aims to establish a quantitative criterion which is used to judge whether there is secret information embedded in the detected image. The main process can be described as follows: at the beginning, we decompose the detected gray-scale image into 8 bit planes considering it has 256 gray levels, and suppose that a secret image has been hidden in the detected image after it was encrypted by DRPE, thus the lower bit planes of the detected image exhibit strong randomness. Then, we divide the bit plane to be tested into many windows, and establish a statistical variable to measure the relativity between pixels in every window. Finally, judge whether the secret image exists in the detected image by operating the t test on all statistical variables. Numerical simulation shows that the accuracy is quite satisfactory, when we need to distinguish the images carrying secret information from a large amount of images.
Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial
Motzer, Robert J.; Rini, Brian I.; McDermott, David F.; Redman, Bruce G.; Kuzel, Timothy M.; Harrison, Michael R.; Vaishampayan, Ulka N.; Drabkin, Harry A.; George, Saby; Logan, Theodore F.; Margolin, Kim A.; Plimack, Elizabeth R.; Lambert, Alexandre M.; Waxman, Ian M.; Hammers, Hans J.
2015-01-01
Purpose Nivolumab is a fully human immunoglobulin G4 programmed death–1 immune checkpoint inhibitor antibody that restores T-cell immune activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned (blinded ratio of 1:1:1) to nivolumab 0.3, 2, or 10 mg/kg intravenously once every 3 weeks. The primary objective was to evaluate the dose-response relationship as measured by progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), and safety. Results A total of 168 patients were randomly assigned to the nivolumab 0.3- (n = 60), 2- (n = 54), and 10-mg/kg (n = 54) cohorts. One hundred eighteen patients (70%) had received more than one prior systemic regimen. Median PFS was 2.7, 4.0, and 4.2 months, respectively (P = .9). Respective ORRs were 20%, 22%, and 20%. Median OS was 18.2 months (80% CI, 16.2 to 24.0 months), 25.5 months (80% CI, 19.8 to 28.8 months), and 24.7 months (80% CI, 15.3 to 26.0 months), respectively. The most common treatment-related adverse event (AE) was fatigue (24%, 22%, and 35%, respectively). Nineteen patients (11%) experienced grade 3 to 4 treatment-related AEs. Conclusion Nivolumab demonstrated antitumor activity with a manageable safety profile across the three doses studied in mRCC. No dose-response relationship was detected as measured by PFS. These efficacy and safety results in mRCC support study in the phase III setting. PMID:25452452
Limburg, Paul J; Mahoney, Michelle R; Ziegler, Katie L Allen; Sontag, Stephen J; Schoen, Robert E; Benya, Richard; Lawson, Michael J; Weinberg, David S; Stoffel, Elena; Chiorean, Michael; Heigh, Russell; Levine, Joel; Della'Zanna, Gary; Rodriguez, Luz; Richmond, Ellen; Gostout, Christopher; Mandrekar, Sumithra J; Smyrk, Thomas C
2011-02-01
Sulindac, atorvastatin, or prebiotic dietary fiber may reduce colorectal cancer (CRC) risk. However, clinical trial data are currently limited. We conducted a randomized, phase II chemoprevention trial involving subjects 40 years or older, with previously resected colon cancer or multiple/advanced colorectal adenomas. Magnification chromoendoscopy (MCE) was performed to identify and characterize rectal aberrant crypt foci (ACF); eligibility criteria required five or more rectal ACFs at baseline. Intervention assignments were as follows: (a) atorvastatin 20 mg qd; (b) sulindac 150 mg bid; (c) oligofructose-enriched inulin (as ORAFTI®Synergy1) 6 gm bid; or (d) control (maltodextrin) 6 gm bid, for 6 months. Percent change in rectal ACF number (%ΔACF) within arm was the primary endpoint. Secondary endpoints included changes in proliferation (Ki67) and apoptosis (caspase-3), as measured from normal mucosa biopsy samples. Among 85 eligible randomized subjects, 76 (86%) completed the trial per protocol. The median (range) of rectal ACF was 9 (5-34) and 8 (0-37) at baseline and postintervention, respectively. The median (SD) for %ΔACF was 5.6 (-69% to 143%), -18.6 (-83% to 160%), -3.6 (-88% to 83%), and -10.0 (-100% to 117%) in the atorvastatin, sulindac, ORAFTI®Synergy1 and control arms, respectively. Neither within-arm (P = 0.12-0.59) nor between-arm (P = 0.30-0.92) comparisons of %ΔACF were statistically significant. The active and control interventions also seemed to have similar effects on mucosal proliferation and apoptosis (P > 0.05 for each comparison). Data from this multicenter, phase II trial do not provide convincing evidence of CRC risk reduction from 6-month interventions with atorvastatin, sulindac, or ORAFTI®Synergy1, although statistical power was limited by the relatively small sample size. PMID:21209397
2013-01-01
Background Neoadjuvant radiochemotherapy (RCT) is now part of the armamentarium of cancer of the lower and middle rectum. It is recommended in current clinical practice prior to surgical excision if the lesion is classified T3/T4 or N+. Histological complete response, defined by the absence of persistent tumor cell invasion and lymph node (ypT0N0) after pathological examination of surgical specimen has been shown to be an independent prognostic factor of overall survival and disease-free survival. Surgical excision is usually performed between 6 and 8 weeks after completion of CRT and pathological complete response rate ranges around 12%. In retrospective studies, a lengthening of the interval after RCT beyond 10 weeks was found as an independent factor increasing the rate of pathological complete response (between 26% and 31%), with a longer disease-free survival and without increasing the operative morbidity. The aim of the present study is to evaluate in 264 patients the rate of pathological complete response rate of rectal cancer after RCT by lengthening the time between RCT and surgery. Methods/design The current study is a multicenter randomized trial in two parallel groups comparing 7 and 11 weeks of delay between the end of RCT and cancer surgery of rectal tumors. At the end of the RCT, surgery is planified and randomization is performed after patient’s written consent for participation. The histological complete response (ypT0N0) will be determined with analysis of the complete residual tumor and double reading by two pathologists blinded of the group of inclusion. Patients will be followed in clinics for 5 years after surgery. Participation in this trial does not change patient’s management in terms of treatment, investigations or visits. Secondary endpoints will include overall and disease free survival, rate of sphincter conservation and quality of mesorectal excision. The number of patients needed is 264. Trial registration Clinical
Tian, Chao; Liu, Shengchun
2016-02-22
We propose a simple and robust phase demodulation algorithm for two-shot fringe patterns with random phase shifts. Based on a smoothness assumption, the phase to be recovered is decomposed into a linear combination of finite terms of orthogonal polynomials, and the expansion coefficients and the phase shift are exhaustively searched through global optimization. The technique is insensitive to noise or defects, and is capable of retrieving phase from low fringe-number (less than one) or low-frequency interferograms. It can also cope with interferograms with very small phase shifts. The retrieved phase is continuous and no further phase unwrapping process is required. The method is expected to be promising to process interferograms with regular fringes, which are common in optical shop testing. Computer simulation and experimental results are presented to demonstrate the performance of the algorithm. PMID:26906984
High energy X-ray phase and dark-field imaging using a random absorption mask
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
High energy X-ray phase and dark-field imaging using a random absorption mask.
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
Schuyler, Adam D; Maciejewski, Mark W; Stern, Alan S; Hoch, Jeffrey C
2015-01-01
Nonuniform sampling (NUS) in multidimensional NMR permits the exploration of higher dimensional experiments and longer evolution times than the Nyquist Theorem practically allows for uniformly sampled experiments. However, the spectra of NUS data include sampling-induced artifacts and may be subject to distortions imposed by sparse data reconstruction techniques, issues not encountered with the discrete Fourier transform (DFT) applied to uniformly sampled data. The characterization of these NUS-induced artifacts allows for more informed sample schedule design and improved spectral quality. The DFT–Convolution Theorem, via the point-spread function (PSF) for a given sampling scheme, provides a useful framework for exploring the nature of NUS sampling artifacts. In this work, we analyze the PSFs for a set of specially constructed NUS schemes to quantify the interplay between randomization and dimensionality for reducing artifacts relative to uniformly undersampled controls. In particular, we find a synergistic relationship between the indirect time dimensions and the “quadrature phase dimension” (i.e. the hypercomplex components collected for quadrature detection). The quadrature phase dimension provides additional degrees of freedom that enable partial-component NUS (collecting a subset of quadrature components) to further reduce sampling-induced aliases relative to traditional full-component NUS (collecting all quadrature components). The efficacy of artifact reduction is exponentially related to the dimensionality of the sample space. Our results quantify the utility of partial-component NUS as an additional means for introducing decoherence into sampling schemes and reducing sampling artifacts in high dimensional experiments. PMID:25899289
Pairing within the self-consistent quasiparticle random-phase approximation at finite temperature
Dang, N. Dinh; Hung, N. Quang
2008-06-15
An approach to pairing in finite nuclei at nonzero temperature is proposed, which incorporates the effects due to the quasiparticle-number fluctuation (QNF) around Bardeen-Cooper-Schrieffer (BCS) mean field and dynamic coupling to quasiparticle-pair vibrations within the self-consistent quasiparticle random-phase approximation (SCQRPA). The numerical calculations of pairing gap, total energy, and heat capacity were carried out within a doubly folded multilevel model as well as realistic nuclei {sup 56}Fe and {sup 120}Sn. The results obtained show that, under the effect of QNF, in the region of moderate and strong couplings, the sharp transition between the superconducting and normal phases is smoothed out, resulting in a thermal pairing gap, which does not collapse at the BCS critical temperature, but has a tail, which extends to high temperature. The dynamic coupling of quasiparticles to SCQRPA vibrations significantly improves the agreement with the results of exact calculations and those obtained within the finite-temperature quantal Monte Carlo method for the total energy and heat capacity. It also causes a deviation of the quasiparticle occupation numbers from the Fermi-Dirac distributions for free fermions.
A Multispectral Photon-Counting Double Random Phase Encoding Scheme for Image Authentication
Yi, Faliu; Moon, Inkyu; Lee, Yeon H.
2014-01-01
In this paper, we propose a new method for color image-based authentication that combines multispectral photon-counting imaging (MPCI) and double random phase encoding (DRPE) schemes. The sparsely distributed information from MPCI and the stationary white noise signal from DRPE make intruder attacks difficult. In this authentication method, the original multispectral RGB color image is down-sampled into a Bayer image. The three types of color samples (red, green and blue color) in the Bayer image are encrypted with DRPE and the amplitude part of the resulting image is photon counted. The corresponding phase information that has nonzero amplitude after photon counting is then kept for decryption. Experimental results show that the retrieved images from the proposed method do not visually resemble their original counterparts. Nevertheless, the original color image can be efficiently verified with statistical nonlinear correlations. Our experimental results also show that different interpolation algorithms applied to Bayer images result in different verification effects for multispectral RGB color images. PMID:24854208
Rojas-Rivera, Jorge; Fernández-Juárez, Gema; Ortiz, Alberto; Hofstra, Julia; Gesualdo, Loreto; Tesar, Vladimir; Wetzels, Jack; Segarra, Alfons; Egido, Jesus; Praga, Manuel
2015-01-01
Background Patients with primary membranous nephropathy (MN) and persistent nephrotic syndrome have a high risk of progression to end-stage renal disease. The Ponticelli protocol (steroids with alkylating agents) is the most effective immunosuppressive therapy for this condition, but it has severe adverse effects. Tacrolimus and rituximab have demonstrated efficacy for remission of nephrotic syndrome in MN with a safer profile. However, the published evidence is largely based on small or short-term observational studies, historical cohorts, comparisons with conservative therapy or clinical trials without appropriate control groups, and there is no head-to-head comparison with the Ponticelli protocol. Methods The STARMEN randomized clinical trial will compare the efficacy of sequential tacrolimus–rituximab therapy with a modified Ponticelli protocol (steroids plus cyclophosphamide). The trial will also evaluate the role of antibodies against the M-type phospholipase A2 receptor (anti-PLA2R) and other antibodies as markers of response to treatment and long-term prognosis. Results The trial has already started with 23 patients having been enrolled as of 1 April 2015, an estimated 21.7% of the estimated sample. PMID:26413273
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.
Multicentric Castleman disease presenting with fever.
Smith, Christiana; Lee-Miller, Cathy; Dishop, Megan K; Cost, Carrye; Wang, Michael; Asturias, Edwin J
2014-12-01
Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder that usually manifests with nonspecific symptoms, including fever and lymphadenopathy. Treatment of pediatric MCD varies greatly. A 21-month-old child was diagnosed with MCD after presenting with fever. He had incomplete response to initial therapy directed at interleukin-6, but improved with subsequent chemotherapy. PMID:25282064
Treating KSHV-Associated Multicentric Castleman Disease
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.
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
Guo, H Y; Cai, Y; Yang, X M; Wang, Z H; Wang, J L; Zhao, X M; Li, J; Hu, X C
2008-01-01
A randomized phase II study using mitomycin (MMC)/cisplatin (DDP) regimen with or without Kanglaite (KLT, a traditional Chinese medicine) as salvage treatment was conducted to exploit KLT's potential effects on patients with advanced breast cancer (ABC). Triweekly regimen consisted of mitomycin (8 mg/m(2)) administered intravenously on day 1, and cisplatin (25 mg/m(2)) intravenously on days 1 to 3. KLT (100 ml) was given intravenously per day on days 1 to 14 every 3 weeks. Between April 2006 and July 2007, 60 patients with a median age of 48 years were randomized into MMC/DDP with or without KLT treatment. In all, the objective response rate (ORR) was 17.5%. There were no significant differences between experimental and control treatments in terms of ORR (14.3% vs. 20.7%, p = 0.730), clinical benefit rates (24.1% vs. 28.6%, p = 0.468), median time to progression (TTP; 3.63 vs. 4.0, p = 0.872), and overall survival (OS; 7.17 vs. not reached, p = 0.120). The median TTP for patients with complete or partial responses was 6.0 months, but only 2.1 months for patients with stable or progressive disease (SD or PD; p = 0.028). While the median OS for patients who obtained clinical benefit from chemotherapy was not reached, that of patients with SD of no more than 6 months or PD was only 7.17 months (p = 0.004). There is no additional benefit when KLT is added to the MMC/DDP doublet in the management of ABC. Patients who obtained clinical benefit from chemotherapy had a longer TTP and OS. PMID:18711764
Theory of laser beam apodization with a graded random phase window.
Haas, R A
1988-07-01
Analysis indicates that graded random phase modulation can be used to apodize a laser beam. In the case of an obscuration or hard edge, it can prevent the formation of Fresnel diffraction ripples. For example, suppose laser radiation of wavelength lambda interacts with a central obscuration of halfwidth a followed immediately by a window. If the exit surface of the window is randomly modulated with a Gaussian amplitude transverse correlation length l and a mean square amplitude t 2(r) that decreases smoothly from a peak height at the obstacle of ~(2) with a transverse scale length L > a > l, then the Fresnel diffraction ripples normally produced by the obscuration are eliminated. Following the apodizer the laser beam consists of two components. One is widely scattered with mean intensity I (s). The other is essentially tunscattered and apodized with mean intensity I (a). The scattered light has an angular divergence proportional to lambda/l. The apodizer intensity transmission is T(a) = exp[-alpha(2)t (2)(r)], where alpha = 2pir(n - 1)/lambda and n is the window refractive index. Tayloring t (2)(r) can produce desired apodization profiles for hard edges and obscurations. Interference between the scattered and unscattered radiation produces intensity fluctuations on the laser beam that have the characteristics of laser speckle. The magnitude of these fluctuations is greatest near the apodizer and at the edge of the apodized beam. The local intensity probability density of the fluctuations is approximately the modified Rician density. Using this distribution the probability of intensity fluctuations exceeding a given value I/I (a) is calculated for several values of r = I (a)/I (s). It is found that for high power applications minimization of optical damage requires r greater, similar 100. This may be achieved by minimizing the correlation length l of the apodizer surface modulation, spatial filtering the beam, and/or placing optical components a sufficient distance
Recombinant Bile Salt-Stimulated Lipase in Preterm Infant Feeding: A Randomized Phase 3 Study
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
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.
NASA Astrophysics Data System (ADS)
Kobayashi, Toshiya; Tomita, Akihisa; Okamoto, Atsushi
2014-09-01
Phase-randomized light is one of the key assumptions in the security proof of the Bennett-Brassard 1984 (BB84) quantum-key-distribution (QKD) protocol using an attenuated laser. Though the assumption has been believed to be satisfied for conventional systems, it should be reexamined for current high-speed QKD systems. The phase correlation may be induced by the overlap of the optical pulses, the interval of which decreases as the clock frequency increases. The phase randomness was investigated experimentally by measuring the visibility of interference. An asymmetric Mach-Zehnder interferometer was used to observe the interference between adjacent pulses from a gain-switched distributed feedback laser diode driven at 10 GHz. Low visibility was observed when the minimum drive current was set far below the threshold, while interference emerged when the minimum drive current was close to the threshold. The theoretical evaluation on the impact of the imperfect phase randomization provides target values for the visibility to guarantee the phase randomness. The experimental and theoretical results show that secure implementation of decoy BB84 protocol is achievable even for the 10-GHz clock frequency by using the laser diode under proper operating conditions.
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
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
A Phase 2 Randomized Clinical Trial of Intravitreal Bevacizumab for Diabetic Macular Edema
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
Tabuchi, Hisaaki; Borucki, Ewa; Berg, Bruce G
2012-08-01
This study investigated the bandwidth of phase sensitivity. Subjects discriminated amplitude-modulated tones (AM), and quasi-frequency-modulated tones (QFM) in a two-interval, forced-choice task. An adaptive threshold procedure was used to estimate the modulation depth needed to discriminate the stimuli as a function of carrier and modulation frequency. Non-monotonicities in threshold-bandwidth functions were often observed at higher modulation frequencies. The results are discussed in terms of two potential cues: (1) waveform envelope, (2) cubic distortion products. In order to degrade the information obtained from auditory distortions, the phase for the carrier frequency was randomly sampled from a uniform distribution, which diminished the non-monotonicities with minimal effect at lower modulation frequencies. Model simulations demonstrated that phase randomization degrades distortion product cues with only a modest effect on temporal cues. Final results show that maximum bandwidths for phase sensitivity (BW(max)) were not proportional to carrier frequencies. PMID:22609773
Beatty, Stephen; Perez-Salvador Garcia, Eduardo; Reynders, Stefaan; 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. PMID:24868458
NASA Astrophysics Data System (ADS)
Sabashvili, Andro; Östlund, Stellan; Granath, Mats
2013-08-01
We calculate the single-particle spectral function for doped bilayer graphene in the low energy limit, described by two parabolic bands with zero band gap and long range Coulomb interaction. Calculations are done using thermal Green's functions in both the random phase approximation (RPA) and the fully self-consistent GW approximation. Consistent with previous studies RPA yields a spectral function which, apart from the Landau quasiparticle peaks, shows additional coherent features interpreted as plasmarons, i.e., composite electron-plasmon excitations. In the GW approximation the plasmaron becomes incoherent and peaks are replaced by much broader features. The deviation of the quasiparticle weight and mass renormalization from their noninteracting values is small which indicates that bilayer graphene is a weakly interacting system. The electron energy loss function, Im[-ɛq-1(ω)] shows a sharp plasmon mode in RPA which in the GW approximation becomes less coherent and thus consistent with the weaker plasmaron features in the corresponding single-particle spectral function.
Time-reversal acoustic focusing system as a virtual random phased array.
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. PMID:20378444
Quasiparticle-random-phase approximation treatment of the transverse wobbling mode reconsidered
NASA Astrophysics Data System (ADS)
Frauendorf, S.; Dönau, F.
2015-12-01
The quasiparticle-random-phase approximation is used to study the properties of the wobbling bands in 163Lu. Assuming that the wobbling mode represents pure isoscalar orientation oscillations results in too low wobbling frequencies and transition probabilities between the one- and zero-phonon wobbling bands that are strongly collective but yet too weak for B (E2 ) out and too strong for B (M1 ) out . The inclusion of an LL interaction, which couples the wobbling mode to the scissors mode, generates the right upshift of the wobbling frequencies and the right suppression of the B (M1 ) out values toward the experimental values, but does not change the B (E2 ) out values. In analogy to the quenching of low-energy E 1 transition by coupling to the isovector giant dipole resonance, a general reduction of the M 1 transitions between quasiparticle configurations caused by coupling to the scissors mode is suggested. The small B (E2 ) out values are related to small triaxiality of the density distribution, which is found by all mean field calculations for the triaxial strongly deformed nuclei in the mass 160 region.
Combining double random phase encoding for color image watermarking in quaternion gyrator domain
NASA Astrophysics Data System (ADS)
Shao, Zhuhong; Duan, Yuping; Coatrieux, Gouenou; Wu, Jiasong; Meng, Jinyu; Shu, Huazhong
2015-05-01
Quaternion representation of color image has attracted great attention due to its capability to treat holistically the three color channels. In a more general way, it has successfully been used in multi-channel signal processing applications over the past few decades. In this study, a joint encryption/watermarking system with more security based on double random phase encoding (DRPE) in quaternion gyrator transform domain is addressed. In the proposed scheme, an RGB-scale watermark image together with a grayscale watermark image or not is encoded into a quaternion matrix and encrypted through the DRPE, the encrypted data is then fused into the middle coefficients of the quaternion gyrator-transformed host image. In the process of extracting watermarks, it is impossible to retrieve them without authorized keys. Compared with the three channels independently processing approach implemented in fractional Fourier domain, the proposed algorithm achieves lower complexity by reason of avoiding repetitive operations. Experimental results have demonstrated the feasibility of the proposed algorithm and its superior performance in terms of noise robustness.
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. PMID:21572204
Consistency of the particle-particle random-phase approximation and renormalization
Dang, Nguyen Dinh
2006-08-15
The consistency condition is tested within the particle-particle random-phase approximation (RPA), renormalized RPA (RRPA), and the self-consistent RPA (SCRPA) making use of the Richardson model of pairing. The two-particle separation energy is calculated in two ways, namely, as the energy of the first addition mode, which adds two particles to a core with N particles, and as the energy of the first removal mode, which removes two particles from the N+2 particle system to get back to the same N-particle core. The corresponding transitions generated by the pairing operators are also calculated. It is found that the results obtained in these two ways of calculations are close to each other only at large values of particle number N and/or small interaction strength. At N{<=}10 for a given value of the interaction strength, the discrepancy between the results obtained in two ways of calculations within the SCRPA is much smaller than those given by the RPA and RRPA.
Linear-scaling implementation of the direct random-phase approximation
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.
Application of the resonating Hartree-Fock random phase approximation to the Lipkin model
NASA Astrophysics Data System (ADS)
Nishiyama, Seiya; Ishida, Kazuhiro; Ido, Moriyoshi
1996-02-01
We have applied the resonating Hartree-Fock (Res-HF) approximation to the exactly solvable Lipkin model by utilizing a newly developed orbital-optimization algorithm. The Res-HF wave function was superposed by two Slater determinants (S-dets) which give two corresponding local energy minima of monopole "deformations". The self-consistent Res-HF calculation gives an excellent ground-state correlation energy. There exist excitations due to small vibrational fluctuations of the orbitals and mixing coefficients around their stationary values. They are described by a new approximation called the resonating Hartree-Fock random phase approximation (Res-HF RPA). Matrices of the second-order variation of the Res-HF energy have the same structures as those of the Res-HF RPA's matrices. The quadratic steepest descent of the Res-HF energy in the orbital optimization is considered to include certainly both effects of RPA-type fluctuations up to higher orders and their mode-mode couplings. It is a very important and interesting task to apply the Res-HF RPA to the Lipkin model with the use of the stationary values and to prove the above argument. It turms out that the Res-HF RPA works far better than the usual HF-RPA and the renormalized one. We also show some important features of the Res-HF RPA.
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.
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
NASA Astrophysics Data System (ADS)
Zhang, Yin; Liang, Lanju; Yang, Jing; Feng, Yijun; Zhu, Bo; Zhao, Junming; Jiang, Tian; Jin, Biaobing; Liu, Weiwei
2016-05-01
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.
Collective nuclear excitations with Skyrme-second random-phase approximation
Gambacurta, D.; Catara, F.; Grasso, M.
2010-05-15
Second random-phase approximation (RPA) calculations with a Skyrme force are performed to describe both high- and low-lying excited states in {sup 16}O. The coupling between one particle-one hole and two particle-two hole as well as that between two particle-two hole configurations among themselves are fully taken into account, and the residual interaction is never neglected; we do not resort therefore to a generally used approximate scheme where only the first kind of coupling is considered. The issue of the rearrangement terms in the matrix elements beyond the standard RPA will be considered in detail in a forthcoming paper. Two approximations are employed here for these rearrangement terms: they are either neglected or evaluated with the RPA procedure. As a general feature of second RPA results, a several-MeV shift of the strength distribution to lower energies is systematically found with respect to RPA distributions. A much more important fragmentation of the strength is also naturally provided by the second RPA owing to the huge number of two particle-two hole configurations. A better description of the excitation energies of the low-lying 0{sup +} and 2{sup +} states is obtained with the second RPA than with the RPA.
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(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. PMID:25481124
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.
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
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.
Molecular tests of the random phase approximation to the exchange-correlation energy functional
NASA Astrophysics Data System (ADS)
Furche, Filipp
2001-11-01
The exchange-correlation energy functional within the random phase approximation (RPA) is recast into an explicitly orbital-dependent form. A method to evaluate the functional in finite basis sets is introduced. The basis set dependence of the RPA correlation energy is analyzed. Extrapolation using large, correlation-consistent basis sets is essential for accurate estimates of RPA correlation energies. The potential energy curve of N2 is discussed. The RPA is found to recover most of the strong static correlation at large bond distance. Atomization energies of main-group molecules are rather uniformly underestimated by the RPA. The method performs better than generalized-gradient-type approximations (GGA's) only for some electron-rich systems. However, the RPA functional is free of error cancellation between exchange and correlation, and behaves qualitatively correct in the high-density limit, as is demonstrated by the coupling strength decomposition of the atomization energy of F2. The GGA short-range correlation correction to the RPA by Yan, Perdew, and Kurth [Phys. Rev. B 61, 16 430 (2000)] does not seem to improve atomization energies consistently.
Quasiparticle random-phase approximation with interactions from the Similarity Renormalization Group
Hergert, H.; Papakonstantinou, P.; Roth, R.
2011-06-15
We have developed a fully consistent framework for calculations in the quasiparticle random-phase approximation (QRPA) with NN interactions from the Similarity Renormalization Group (SRG) and other unitary transformations of realistic interactions. The consistency of our calculations, which use the same Hamiltonian to determine the Hartree-Fock-Bogoliubov ground states and the residual interaction for QRPA, guarantees an excellent decoupling of spurious strength, without the need for empirical corrections. While work is under way to include SRG-evolved 3N interactions, we presently account for some 3N effects by means of a linearly density-dependent interaction, whose strength is adjusted to reproduce the charge radii of closed-shell nuclei across the whole nuclear chart. As a first application, we perform a survey of the monopole, dipole, and quadrupole response of the calcium isotopic chain and of the underlying single-particle spectra, focusing on how their properties depend on the SRG parameter {lambda}. Unrealistic spin-orbit splittings suggest that spin-orbit terms from the 3N interaction are called for. Nevertheless, our general findings are comparable to results from phenomenological QRPA calculations using Skyrme or Gogny energy density functionals. Potentially interesting phenomena related to low-lying strength warrant more systematic investigations in the future.
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.
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.
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. PMID:26986444
Ge2Sb2Te5 Confined Structures and Integration of 64 Mb Phase-Change Random Access Memory
NASA Astrophysics Data System (ADS)
Yeung, Fai; Ahn, Su-Jin; Hwang, Young-Nam; Jeong, Chang-Wook; Song, Yoon-Jong; Lee, Su-Youn; Lee, Se-Ho; Ryoo, Kyung-Chang; Park, Jae-Hyun; Shin, Jae-Min; Jeong, Won-Cheol; Kim, Young-Tae; Koh, Gwan-Hyeob; Jeong, Gi-Tae; Jeong, Hong-Sik; Kim, Kinam
2005-04-01
Phase-change random access memory is considered a potential challenger for conventional memories, such as dynamic random access memory and flash memory due to its numerous advantages. Nevertheless, high reset current is the ultimate problem in developing high-density phase-change random access memory (PRAM). We focus on the adoption of Ge2Sb2Te5 confined structures to achieve lower reset currents. By changing from a normal to a GST confined structure, the reset current drops to as low as 0.8 mA. Eventually, our integrated 64 Mb PRAM based on 0.18 μm CMOS technology offers a large sensing margin: Rreset ˜200 kΩ and Rset ˜2 kΩ, as well as reasonable reliability: an endurance of 1.0× 109 cycles and a retention time of 2 years at 85°C.
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. PMID:24663718
Sharma, Manish R.; Gray, Elizabeth; Goldberg, Richard M.; Sargent, Daniel J.; Karrison, Theodore G.
2015-01-01
Purpose The optimal end point for randomized phase II trials of anticancer therapies remains controversial. We simulated phase II trials by resampling patients from N9741, a randomized phase III trial of chemotherapy regimens for metastatic colorectal cancer, and compared the power of various end points to detect the superior therapy (FOLFOX [infusional fluorouracil, leucovorin, and oxaliplatin] had longer overall survival than both IROX [irinotecan plus oxaliplatin] and IFL [irinotecan and bolus fluorouracil plus leucovorin]). Methods Tumor measurements and progression-free survival (PFS) data were obtained for 1,471 patients; 1,002 had consistently measured tumors and were resampled (5,000 replicates) to simulate two-arm, randomized phase II trials with α = 0.10 (one sided) and 20 to 80 patients per arm. End points included log ratio of tumor size at 6, 12, and 18 weeks relative to baseline; time to tumor growth (TTG), estimated using a nonlinear mixed-effects model; and PFS. Arms were compared using rank sum tests for log ratio and TTG and a log-rank test for PFS. Results For FOLFOX versus IFL, TTG and PFS had similar power, with both exceeding the power of log ratio at 18 weeks; for FOLFOX versus IROX, TTG and log ratio at 18 weeks had similar power, with both exceeding the power of PFS. The best end points exhibited > 80% power with 60 to 80 patients per arm. Conclusion TTG is a powerful end point for randomized phase II trials of cytotoxic therapies in metastatic colorectal cancer; it was either comparable or superior to PFS and log ratio at 18 weeks. Additional studies will be needed to clarify the potential of TTG as a phase II end point. PMID:25349295
NASA Astrophysics Data System (ADS)
Fukuda, Hiroshi; Hotta, Shoji
2000-07-01
The effectiveness of node-connection phase-shifting mask (PSM) was investigated experimentally. In this method, the original design patterns are decomposed into several alternating PSM sub-patterns bas don geometrical rules, and multiple-exposure of these masks reconstructs the original design patterns. This is suitable for random logic interconnects, where wire features are on the 'DA-grid'. We applied this method to patterning a 0.3-micrometers pitch random interconnect with a conventional DUV exposure tool Random interconnect patterns with 0.3-micrometers pitch random interconnect with a conventional DUV exposure tool. Random interconnect patterns with 0.3-micrometers pitch were decomposed using in-house geometrical Boolean operators into three PSMs and were multiply exposed onto the same region of wafer using a KrF exposure tool. Though this is preliminary experiment without mask/process optimization, it shows a possibility of below 0.3-micrometers pitch logic interconnect with KrF tools. Thus, combining this with the phase-edge PSMs or some 'slimming' technologies for shrinking gate-length, the 0.1-micrometers generation logic LSIs are expected to be achieved with conventional DUV exposure tools.
Porosity and specific surface for interpenetrable-sphere models of two-phase random media
NASA Astrophysics Data System (ADS)
Rikvold, Per Arne; Stell, George
1985-01-01
We derive and numerically evaluate expressions for the porosity (matrix volume fraction) φ and the specific surface (interface area per unit volume) s for two specific models of a random two-phase medium in which the medium is considered as a suspension of interpenetrable spheres of radius R, embedded in a uniform matrix. The models and quantities considered have applications to a wide range of problems concerning transport, mechanical, and chemical properties of composite media. Both models contain a continuously variable hardness parameter ɛ, such that for ɛ=1 they reduce to mutually impenetrable spheres, and for ɛ=0 they reduce to fully penetrable spheres. The first of these models, the permeable-sphere model, has been defined only in the context of the Percus-Yevick approximation, which yields for it a unique pair distribution function g2(r1, r2). To find the associated gn(r1,...,rn) for n≳2, which are needed to evaluate φ and s we use the generalized superposition approximation. The second model, the concentric-shell model, can be fully defined without recourse to any particular approximation and proves to be isomorphic to the picture described by the scaled-particle theory of Reiss, Frisch, and Lebowitz. In this case we evaluate φ and s in the scaled-particle approximation introduced by those authors to implement the scaled-particle theory. For both models, we present numerical plots of φ vs dimensionless density, and of s vs φ. We also briefly discuss the relations between the results obtained in the two cases. Finally, we consider generalizations of φ and s that define the volume and surface available to a particle of finite size, rather than a point.
Focusing of high-intensity ultrasound through the rib cage using a therapeutic random phased array.
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. PMID:20510186
Accurate Complete Basis Set Extrapolation of Direct Random Phase Correlation Energies.
Mezei, Pál D; Csonka, Gábor I; Ruzsinszky, Adrienn
2015-08-11
The direct random phase approximation (dRPA) is a promising way to obtain improvements upon the standard semilocal density functional results in many aspects of computational chemistry. In this paper, we address the slow convergence of the calculated dRPA correlation energy with the increase of the quality and size of the popular Gaussian-type Dunning's correlation consistent aug-cc-pVXZ split valence atomic basis set family. The cardinal number X controls the size of the basis set, and we use X = 3-6 in this study. It is known that even the very expensive X = 6 basis sets lead to large errors for the dRPA correlation energy, and thus complete basis set extrapolation is necessary. We study the basis set convergence of the dRPA correlation energies on a set of 65 hydrocarbon isomers from CH4 to C6H6. We calculate the iterative density fitted dRPA correlation energies using an efficient algorithm based on the CC-like form of the equations using the self-consistent HF orbitals. We test the popular inverse cubic, the optimized exponential, and inverse power formulas for complete basis set extrapolation. We have found that the optimized inverse power based extrapolation delivers the best energies. Further analysis showed that the optimal exponent depends on the molecular structure, and the most efficient two-point energy extrapolations that use X = 3 and 4 can be improved considerably by considering the atomic composition and hybridization states of the atoms in the molecules. Our results also show that the optimized exponents that yield accurate X = 3 and 4 extrapolated dRPA energies for atoms or small molecules might be inaccurate for larger molecules. PMID:26574475
Benchmark tests and spin adaptation for the particle-particle random phase approximation
Yang, Yang; Steinmann, Stephan N.; Peng, Degao; Aggelen, Helen van; 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{sup 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.
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
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
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
2016-01-01
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
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.
Focusing of high intensity ultrasound through the rib cage using a therapeutic random phased array
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
Yang, Yang; Peng, Degao; Lu, Jianfeng; Yang, Weitao
2014-09-28
The particle-particle random phase approximation (pp-RPA) has been used to investigate excitation problems in our recent paper [Y. Yang, H. van Aggelen, and W. Yang, J. Chem. Phys. 139, 224105 (2013)]. It has been shown to be capable of describing double, Rydberg, and charge transfer excitations, which are challenging for conventional time-dependent density functional theory (TDDFT). However, its performance on larger molecules is unknown as a result of its expensive O(N(6)) scaling. In this article, we derive and implement a Davidson iterative algorithm for the pp-RPA to calculate the lowest few excitations for large systems. The formal scaling is reduced to O(N(4)), which is comparable with the commonly used configuration interaction singles (CIS) and TDDFT methods. With this iterative algorithm, we carried out benchmark tests on molecules that are significantly larger than the molecules in our previous paper with a reasonably large basis set. Despite some self-consistent field convergence problems with ground state calculations of (N - 2)-electron systems, we are able to accurately capture lowest few excitations for systems with converged calculations. Compared to CIS and TDDFT, there is no systematic bias for the pp-RPA with the mean signed error close to zero. The mean absolute error of pp-RPA with B3LYP or PBE references is similar to that of TDDFT, which suggests that the pp-RPA is a comparable method to TDDFT for large molecules. Moreover, excitations with relatively large non-HOMO excitation contributions are also well described in terms of excitation energies, as long as there is also a relatively large HOMO excitation contribution. These findings, in conjunction with the capability of pp-RPA for describing challenging excitations shown earlier, further demonstrate the potential of pp-RPA as a reliable and general method to describe excitations, and to be a good alternative to TDDFT methods. PMID:25273409
Singlet-triplet energy gaps for diradicals from particle-particle random phase approximation.
Yang, Yang; Peng, Degao; Davidson, Ernest R; Yang, Weitao
2015-05-21
The particle-particle random phase approximation (pp-RPA) for calculating excitation energies has been applied to diradical systems. With pp-RPA, the two nonbonding electrons are treated in a subspace configuration interaction fashion while the remaining part is described by density functional theory (DFT). The vertical or adiabatic singlet-triplet energy gaps for a variety of categories of diradicals, including diatomic diradicals, carbene-like diradicals, disjoint diradicals, four-π-electron diradicals, and benzynes are calculated. Except for some excitations in four-π-electron diradicals, where four-electron correlation may play an important role, the singlet-triplet gaps are generally well predicted by pp-RPA. With a relatively low O(r(4)) scaling, the pp-RPA with DFT references outperforms spin-flip configuration interaction singles. It is similar to or better than the (variational) fractional-spin method. For small diradicals such as diatomic and carbene-like ones, the error of pp-RPA is slightly larger than noncollinear spin-flip time-dependent density functional theory (NC-SF-TDDFT) with LDA or PBE functional. However, for disjoint diradicals and benzynes, the pp-RPA performs much better and is comparable to NC-SF-TDDFT with long-range corrected ωPBEh functional and spin-flip configuration interaction singles with perturbative doubles (SF-CIS(D)). In particular, with a correct asymptotic behavior and being almost free from static correlation error, the pp-RPA with DFT references can well describe the challenging ground state and charge transfer excitations of disjoint diradicals in which almost all other DFT-based methods fail. Therefore, the pp-RPA could be a promising theoretical method for general diradical problems. PMID:25891638
Aggelen, Helen van; Department of Chemistry, Duke University, Durham, North Carolina 27708 ; 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 H{sub 2}, and eliminates delocalization errors in H{sub 2}{sup +} and other single-bond systems. It gives surprisingly good non-bonded interaction energies – competitive with the ph-RPA – with the correct R{sup −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.
Management of multifocal and multicentric gliomas.
Patil, Chirag G; Eboli, Paula; Hu, Jethro
2012-04-01
The diffuse nature of gliomas has long confounded attempts at achieving a definitive cure. The advent of computed tomography and magnetic resonance imaging made it increasingly apparent that gliomas could have a multifocal or multicentric appearance. Treating these tumors is the summit of an already daunting challenge, because the obstacles that must be surmounted to treat gliomas in general, namely, their heterogeneity, diffuse nature, and ability to insidiously invade normal brain, are more conspicuous in this subset of tumors. PMID:22440877
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.
Danzl, Per; Hespanha, João; Moehlis, Jeff
2009-12-01
We present an event-based feedback control method for randomizing the asymptotic phase of oscillatory neurons. Phase randomization is achieved by driving the neuron's state to its phaseless set, a point at which its phase is undefined and is extremely sensitive to background noise. We consider the biologically relevant case of a fixed magnitude constraint on the stimulus signal, and show how the control objective can be accomplished in minimum time. The control synthesis problem is addressed using the minimum-time-optimal Hamilton-Jacobi-Bellman framework, which is quite general and can be applied to any spiking neuron model in the conductance-based Hodgkin-Huxley formalism. We also use this methodology to compute a feedback control protocol for optimal spike rate increase. This framework provides a straightforward means of visualizing isochrons, without actually calculating them in the traditional way. Finally, we present an extension of the phase randomizing control scheme that is applied at the population level, to a network of globally coupled neurons that are firing in synchrony. The applied control signal desynchronizes the population in a demand-controlled way. PMID:19911192
NASA Astrophysics Data System (ADS)
Xi, Lu; Xin, Zhou; Sheng, Yuan; Xiao-feng, Li; Pei, Lu; Yao-yao, Chen
2009-09-01
A new method based on statistical hypothesis detection for information hidden using the double random-phase encoding technique is introduced. According to this method, a series of windows are opened on the lowest bit-plane of image, and an exclusive OR (XOR) operation is performed between different pixels in every window. The results of XOR operation are then analyzed. Using this method, we can judge whether an image contains secret information encrypted by the double random-phase encoding technique. The result of the judgment may be influenced by two parameters, namely the size of the window and the threshold value. A further study is also made to determine the optimal parameters.
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.
NASA Astrophysics Data System (ADS)
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.
2013-10-01
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.
NASA Astrophysics Data System (ADS)
De Donno, V.; Co', G.; Anguiano, M.; Lallena, A. M.
2016-03-01
The formalism of the continuum random-phase approximation theory which treats, without approximations, the continuum part of the single-particle spectrum, is extended to describe charge-exchange excitations. Our approach is self-consistent, meaning that we use a unique, finite-range interaction in the Hartree-Fock calculations which generate the single-particle basis and in the continuum-random phase approximation which describes the excitation. We study excitations induced by the Fermi, Gamow-Teller and spin-dipole operators in doubly magic nuclei by using four Gogny-like finite-range interactions, two of them containing tensor forces. We focus our attention on the importance of the correct treatment of the continuum configuration space and on the effects of the tensor terms of the force.
2013-01-01
The effectiveness of different breast cancer follow-up procedures to decrease breast cancer mortality are still an object of debate, even if intensive follow-up by imaging modalities is not recommended by international guidelines since 1997. We conducted a systematic review of surveillance procedures utilized, in the last ten years, in phase III randomized trials (RCTs) of adjuvant treatments in early stage breast cancer with disease free survival as primary endpoint of the study, in order to verify if a similar variance exists in the scientific world. Follow-up modalities were reported in 66 RCTs, and among them, minimal and intensive approaches were equally represented, each being followed by 33 (50%) trials. The minimal surveillance regimen is preferred by international and North American RCTs (P = 0.001) and by trials involving more than one country (P = 0.004), with no relationship with the number of participating centers (P = 0.173), with pharmaceutical industry sponsorship (P = 0.80) and with trials enrolling > 1000 patients (P = 0.14). At multivariate regression analysis, only geographic location of the trial was predictive for a distinct follow-up methodology (P = 0.008): Western European (P = 0.004) and East Asian studies (P = 0.010) use intensive follow-up procedures with a significantly higher frequency than international RCTs, while no differences have been detected between North American and international RCTs. Stratifying the studies according to the date of beginning of patients enrollment, before or after 1998, in more recent RCTs the minimal approach is more frequently followed by international and North American RCTs (P = 0.01), by trials involving more than one country (P = 0.01) and with more than 50 participating centers (P = 0.02). It would be highly desirable that in the near future breast cancer follow-up procedures will be homogeneous in RCTs and everyday clinical settings. PMID:24438135
Grimme, Stefan; Steinmetz, Marc
2016-08-01
We present a revised form of a double hybrid density functional (DHDF) dubbed PWRB95. It contains semi-local Perdew-Wang exchange and Becke95 correlation with a fixed amount of 50% non-local Fock exchange. New features are that the robust random phase approximation (RPA) is used to calculate the non-local correlation part instead of a second-order perturbative treatment as in standard DHDF, and the non-self-consistent evaluation of the Fock exchange with KS-orbitals at the GGA level which leads to a significant reduction of the computational effort. To account for London dispersion effects we include the non-local VV10 dispersion functional. Only three empirical scaling parameters were adjusted. The PWRB95 results for extensive standard thermochemical benchmarks (GMTKN30 data base) are compared to those of well-known functionals from the classes of (meta-)GGAs, (meta-)hybrid functionals, and DHDFs, as well as to standard (direct) RPA. The new method is furthermore tested on prototype bond activations with (Ni/Pd)-based transition metal catalysts, and two difficult cases for DHDF, namely the isomerization reaction of the [Cu2(en)2O2](2+) complex and the singlet-triplet energy difference in highly unsaturated cyclacenes. The results show that PWRB95 is almost as accurate as standard DHDF for main-group thermochemistry but has a similar or better performance for non-covalent interactions, more difficult transition metal containing molecules and other electronically problematic cases. Because of its relatively weak basis set dependence, PWRB95 can be applied even in combination with AO basis sets of only triple-zeta quality which yields huge overall computational savings by a factor of about 40 compared to standard DHDF/'quadruple-zeta' calculations. Structure optimizations of small molecules with PWRB95 indicate an accurate description of bond distances superior to that provided by TPSS-D3, PBE0-D3, or other RPA type methods. PMID:26695184
Tashima, Hideaki; Takeda, Masafumi; Suzuki, Hiroyuki; Obi, Takashi; Yamaguchi, Masahiro; Ohyama, Nagaaki
2010-06-21
We have shown that the application of double random phase encoding (DRPE) to biometrics enables the use of biometrics as cipher keys for binary data encryption. However, DRPE is reported to be vulnerable to known-plaintext attacks (KPAs) using a phase recovery algorithm. In this study, we investigated the vulnerability of DRPE using fingerprints as cipher keys to the KPAs. By means of computational experiments, we estimated the encryption key and restored the fingerprint image using the estimated key. Further, we propose a method for avoiding the KPA on the DRPE that employs the phase retrieval algorithm. The proposed method makes the amplitude component of the encrypted image constant in order to prevent the amplitude component of the encrypted image from being used as a clue for phase retrieval. Computational experiments showed that the proposed method not only avoids revealing the cipher key and the fingerprint but also serves as a sufficiently accurate verification system. PMID:20588510
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.
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
Kim, Diane N H; Teitell, Michael A; Reed, Jason; Zangle, Thomas A
2015-01-01
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
NASA Astrophysics Data System (ADS)
Kim, Diane N. H.; Teitell, Michael A.; Reed, Jason; Zangle, Thomas A.
2015-11-01
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.
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.
NASA Astrophysics Data System (ADS)
Monthus, Cécile; Garel, Thomas
2010-08-01
We study the dynamical response to an external force F for a particle performing a random walk in a two-dimensional quenched random potential of Hurst exponent H=1/2 . We present numerical results on the statistics of first-passage times that satisfy closed backward master equations. We find that there exists a zero-velocity phase in a finite region of the external force 0
NASA Astrophysics Data System (ADS)
Ryu, Seung Wook; Oh, Jin Ho; Lee, Jong Ho; Choi, Byung Joon; Kim, Won; Hong, Suk Kyoung; Hwang, Cheol Seong; Kim, Hyeong Joon
2008-04-01
The improvement in the phase change characteristics of Ge2Sb2Te5 (GST) films for phase change random access memory applications was investigated by doping the GST films with SiO2 using cosputtering at room temperature. As the sputtering power of SiO2 increased from 0to150W, the activation energy for crystallization increased from 2.1±0.2to3.1±0.15eV. SiO2 inhibited the crystallization of the amorphous GST films, which improved the long term stability of the metastable amorphous phase. The melting point decreased with increasing concentration of SiO2, which reduced the power consumption as well as the reset current.
A flat lens with tunable phase gradient by using random access reconfigurable metamaterial.
Zhu, Weiming; Song, Qinghua; Yan, Libin; Zhang, Wu; Wu, Pin-Chieh; Chin, Lip Ket; Cai, Hong; Tsai, Din Ping; Shen, Zhong Xiang; Deng, Tian Wei; Ting, Sing Kwong; Gu, Yuandong; Lo, Guo Qiang; Kwong, Dim Lee; Yang, Zhen Chuan; Huang, Ru; Liu, Ai-Qun; Zheludev, Nikolay
2015-08-26
The first demonstration of an optofluidic metamaterial is reported where resonant properties of every individual metamolecule can be continuously tuned at will using a microfluidic system. This is called a random-access reconfigurable metamaterial, which is used to provide the first demonstration of a tunable flat lens with wavefront-reshaping capabilities. PMID:26184076
Stankevich, Dmitriy; Istomina, Larissa; Shkuratov, Yuriy; Videen, Gorden
2007-03-20
Phase curves of intensity are calculated for light scattering in media randomly packed with large nontransparent spheres (x=125), the surfaces of which reflect according to the Fresnel equations. We consider three values of refractive index: m = 0.73 + i5.93 (metal Al), 1.6 + i1.72 (metal Fe), and 1.5 + i0.1 (black glass). We use a Monte Carlo ray-tracing approach. Different kinds of electromagnetic phase differences of reciprocal trajectories are investigated for the second and third orders of scattering; the highest orders give comparatively small contributions due to the backward-scattering indicatrix of large nontransparent spheres. We find that the main electromagnetic phase difference between the direct and time-reversal (reciprocal) trajectories is the outer phase difference that depends only on the relative positions of the first and last points of the ray reflections and the phase angle. The inner phase difference is connected with the changing path length of the ray inside the medium. This depends on the particle size and the phase angle that is the angle between the source and receiver from the scatterer, i.e., 180 degrees minus the scattering angle. The inner phase difference can give oscillations in the phase curve consisting of second-order components if the medium consists of strictly monodisperse spheres. Usually the coherent backscattering enhancement is calculated ignoring the shadow-hiding effect. We show that accounting for the shadowing of the reciprocal trajectory is important for the formation of the backscattering effect. The third-order scattering surge is a superposition of wide and narrow opposition spikes that correspond to two different types of scattering trajectories, closed and opened ones. The first type is due to scattering by two particles; the second one corresponds to scattering by three particles. PMID:17334449
Spectral shifts and switches in random fields upon interaction with negative-phase materials
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.
Siltuximab: a targeted therapy for idiopathic multicentric Castleman disease.
Fajgenbaum, David C; Kurzrock, Razelle
2016-01-01
Human herpes virus-8 (HHV-8)-negative or idiopathic multicentric Castleman disease (iMCD) is a rare and deadly disorder that sits at the nexus of hematology/oncology, virology and immunology. Management of iMCD has been challenging due to limited understanding of etiology and pathogenesis and few treatment options. The recent approvals in North America, Europe and Brazil of siltuximab, a monoclonal antibody against IL-6, for iMCD now provide a safe and effective therapy that targets a key aspect of pathogenesis. In the first ever randomized, placebo-controlled trial in iMCD, siltuximab significantly reduced disease burden and symptoms in a large portion (34%) of patients. The optimal dose is 11 mg/kg intravenously every 3 weeks. At this time, duration of treatment is often life-long or until treatment failure. Additional research is needed to identify biomarkers that may assist with predicting treatment effectiveness in iMCD and to investigate the role of siltuximab in HHV-8-positive MCD and pediatric iMCD patients. PMID:26634298
Jain, Sumeet; Dyrdahl, Mitchell H.E.; Gong, Xiaobo; Scriven, L.E.; Bates, Frank S.
2008-10-24
The phase behavior of poly(ethylene oxide)-poly(butadiene) (PEO-PB) diblock copolymers mixed with water was studied using small-angle X-ray scattering (SAXS), cryogenic scanning electron microscopy (cryo-SEM), cryogenic transmission electron microscopy (cryo-TEM), and dynamic mechanical spectroscopy. Two sets of diblocks were synthesized by adding different lengths of PEO to hydroxy terminated PB with degrees of polymerization N{sub PB} = 46 and 170. Two-component mixtures were investigated as a function of block composition and copolymer molecular weight, between 1 and 100 wt % polymer content. Melt phase behavior is consistent with established theory and known experimental behavior for diblock copolymers. Various lyotropic liquid crystalline structures, notably lamellae (L), hexagonally packed cylinders (H), and spheres (S) arranged on cubic (body-centered cubic, face-centered cubic) lattices, were documented as a function of water content. At the higher molecular weights (N{sub PB} = 170), a random network phase (N) was identified over a sizable portion of the phase portrait, located between hexagonally ordered cylinders and ordered lamellae. This new structure, along with branching of cylindrical micelles in the dilute limit, bear a striking similarity to experimentally observed and theoretically predicted phase behavior in certain ternary water/oil/surfactant systems. These findings demonstrate that block copolymer surfactants are characterized by at least four structural building blocks -- spheres, cylinders, bilayers, and branched cylinders -- above a threshold molecular weight.
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
NASA Astrophysics Data System (ADS)
Hong, Peilong; Li, Liming; Liu, Jianji; Zhang, Guoquan
2016-03-01
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.
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
Kawano, T.; Moeller, P.; Wilson, W. B.
2008-11-15
Theoretical {beta}-delayed-neutron spectra are calculated based on the Quasiparticle Random-Phase Approximation (QRPA) and the Hauser-Feshbach statistical model. Neutron emissions from an excited daughter nucleus after {beta} decay to the granddaughter residual are more accurately calculated than in previous evaluations, including all the microscopic nuclear structure information, such as a Gamow-Teller strength distribution and discrete states in the granddaughter. The calculated delayed-neutron spectra agree reasonably well with those evaluations in the ENDF decay library, which are based on experimental data. The model was adopted to generate the delayed-neutron spectra for all 271 precursors.
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.
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.
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.
Agrawal, Y C; Mikkelsen, Ole A
2009-05-25
We present in-water forward scattering phase functions covering the angle range 0.08 to 16 degrees for 19 narrow-sized dispersions of randomly shaped sediment grains. These dispersions cover particle size range from 1 to 20 microns. These phase functions offer a realistic alternative to Mie theory. Qualitatively, (i) the magnitude of phase functions at the smallest angles for equal size spheres and randomly shaped particles are nearly equal; (ii) the oscillations predicted by Mie theory for spheres disappear for random shaped grains, and (iii) the tendency of phase functions of large spheres to merge at large angles is also seen with randomly shaped grains. The data are also provided in tabulated form. PMID:19466130
Bates, F.S.; Koehler, W.C.; Wignall, G.D.; Fetters, L.J.
1986-12-01
A well characterized binary mixture of normal (protonated) and perdeuterated monodisperse 1,2 polybutenes has been studied by small-angle neutron scattering (SANS). For scattering wavevectors q greater than the inverse radius-of-gyration R/sub g//sup -1/, the SANS intensity is quantitatively predicted by the random phase approximation (RPA) theory of deGennes over all measured values of the segment-segment interaction parameter Chi. In the region (Chi s-Chi)Chi s/sup -1/ > 0.5 the interaction parameter determined using the RPA theory for q > R/sub g//sup -1/ is greater than that calculated from the zero-angle intensity based on an Ornstein-Zernike plot, where Chi s represents the limit of single phase stability. These findings indicate a correlation between the critical fluctuation length xi and R/sub g/ which is not accounted for by the RPA theory.
Infinite randomness fixed point of the superconductor-metal quantum phase transition.
Del Maestro, Adrian; Rosenow, Bernd; Müller, Markus; Sachdev, Subir
2008-07-18
We examine the influence of quenched disorder on the superconductor-metal transition, as described by a theory of overdamped Cooper pairs which repel each other. The self-consistent pairing eigenmodes of a quasi-one-dimensional wire are determined numerically. Our results support the recent proposal by Hoyos et al. [Phys. Rev. Lett. 99, 230601 (2007)10.1103/PhysRevLett.99.230601] that the transition is characterized by the same strong-disorder fixed point describing the onset of ferromagnetism in the random quantum Ising chain in a transverse field. PMID:18764263
Infinite Randomness Fixed Point of the Superconductor-Metal Quantum Phase Transition
NASA Astrophysics Data System (ADS)
Del Maestro, Adrian; Rosenow, Bernd; Müller, Markus; Sachdev, Subir
2008-07-01
We examine the influence of quenched disorder on the superconductor-metal transition, as described by a theory of overdamped Cooper pairs which repel each other. The self-consistent pairing eigenmodes of a quasi-one-dimensional wire are determined numerically. Our results support the recent proposal by Hoyos et al. [Phys. Rev. Lett. 99, 230601 (2007)PRLTAO0031-900710.1103/PhysRevLett.99.230601] that the transition is characterized by the same strong-disorder fixed point describing the onset of ferromagnetism in the random quantum Ising chain in a transverse field.
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 → ∞.
Superlattice-like film for high data retention and high speed phase change random access memory
NASA Astrophysics Data System (ADS)
Li, Le; Song, Sannian; Zhang, Zhonghua; Chen, Liangliang; Song, Zhitang; Lv, Shilong; Liu, Bo; Guo, Tianqi
2016-06-01
Superlattice-like film (SLF) was formed alternately by Ti0.43Sb2Te3 (TST) and TiN, and TST is employed as phase change layers and TiN is employed as isolation layers of TST film. Comparing with single TST film with the same thickness, SLF owns higher data retention, higher phase change speed (5 ns) and endurance up to 1 × 105 cycles, and its power consumption of reset operation is significantly decreased by 65.2%. Two-dimensional thermal transient simulation of reset operation indicates that SLF-based device owns higher heating efficiency than 30-nm-thick TST-based device.
Cell identification using single beam lensless imaging with pseudo-random phase encoding.
Javidi, Bahram; Rawat, Siddharth; Komatsu, Satoru; Markman, Adam
2016-08-01
In this Letter, we propose a novel compact optical system for automated cell identification. Our system employs pseudo-random encoding of the light modulated by the cells under inspection to capture the unique opto-biological signature of the micro-organisms by an image sensor and without using a microscope objective lens to magnify the object beam. The proposed instrument can be fabricated using a compact light source, a thin diffuser, and an image sensor connected to computational hardware; thus, it can be compact and cost effective. Experiments are presented using the proposed system to identify and classify various micro-objects and demonstrate proof of concept. The captured opto-biological signature pattern can be attributed to the micro-object's morphology, size, sub-cellular complex structure, index of refraction, internal material composition, etc. Using the captured signature of the micro-object, we extract statistical features such as mean, variance, skewness, kurtosis, entropy, and correlation coefficients for cell identification using the random forest classifier. For comparison, similar identification experiments were repeated with a digital shearing interferometer. To the best of our knowledge, this is the first report on automated cell identification using the proposed approach. PMID:27472644
NASA Astrophysics Data System (ADS)
Zhang, Leihong; Pan, Zilan; Liang, Dong; Ma, Xiuhua; Zhang, Dawei
2015-12-01
An optical encryption method based on compressive ghost imaging (CGI) with double random-phase encoding (DRPE), named DRPE-CGI, is proposed. The information is first encrypted by the sender with DRPE, the DRPE-coded image is encrypted by the system of computational ghost imaging with a secret key. The key of N random-phase vectors is generated by the sender and will be shared with the receiver who is the authorized user. The receiver decrypts the DRPE-coded image with the key, with the aid of CGI and a compressive sensing technique, and then reconstructs the original information by the technique of DRPE-decoding. The experiments suggest that cryptanalysts cannot get any useful information about the original image even if they eavesdrop 60% of the key at a given time, so the security of DRPE-CGI is higher than that of the security of conventional ghost imaging. Furthermore, this method can reduce 40% of the information quantity compared with ghost imaging while the qualities of reconstructing the information are the same. It can also improve the quality of the reconstructed plaintext information compared with DRPE-GI with the same sampling times. This technique can be immediately applied to encryption and data storage with the advantages of high security, fast transmission, and high quality of reconstructed information.
NASA Astrophysics Data System (ADS)
Osorio, Ivan; Lai, Ying-Cheng
2011-09-01
We present a general method to analyze multichannel time series that are becoming increasingly common in many areas of science and engineering. Of particular interest is the degree of synchrony among various channels, motivated by the recognition that characterization of synchrony in a system consisting of many interacting components can provide insights into its fundamental dynamics. Often such a system is complex, high-dimensional, nonlinear, nonstationary, and noisy, rendering unlikely complete synchronization in which the dynamical variables from individual components approach each other asymptotically. Nonetheless, a weaker type of synchrony that lasts for a finite amount of time, namely, phase synchronization, can be expected. Our idea is to calculate the average phase-synchronization times from all available pairs of channels and then to construct a matrix. Due to nonlinearity and stochasticity, the matrix is effectively random. Moreover, since the diagonal elements of the matrix can be arbitrarily large, the matrix can be singular. To overcome this difficulty, we develop a random-matrix based criterion for proper choosing of the diagonal matrix elements. Monitoring of the eigenvalues and the determinant provides a powerful way to assess changes in synchrony. The method is tested using a prototype nonstationary noisy dynamical system, electroencephalogram (scalp) data from absence seizures for which enhanced cortico-thalamic synchrony is presumed, and electrocorticogram (intracranial) data from subjects having partial seizures with secondary generalization for which enhanced local synchrony is similarly presumed.
NASA Astrophysics Data System (ADS)
Zhang, Ningyu; Cheng, Chuanfu; Teng, Shuyun; Chen, Xiaoyi; Xu, Zhizhan
2007-09-01
A new approach based on the gated integration technique is proposed for the accurate measurement of the autocorrelation function of speckle intensities scattered from a random phase screen. The Boxcar used for this technique in the acquisition of the speckle intensity data integrates the photoelectric signal during its sampling gate open, and it repeats the sampling by a preset number, m. The average analog of the m samplings output by the Boxcar enhances the signal-to-noise ratio by √{m}, because the repeated sampling and the average make the useful speckle signals stable, while the randomly varied photoelectric noise is suppressed by 1/√{m}. In the experiment, we use an analog-to-digital converter module to synchronize all the actions such as the stepped movement of the phase screen, the repeated sampling, the readout of the averaged output of the Boxcar, etc. The experimental results show that speckle signals are better recovered from contaminated signals, and the autocorrelation function with the secondary maximum is obtained, indicating that the accuracy of the measurement of the autocorrelation function is greatly improved by the gated integration technique.
Multicentric Castleman's Disease in a Child Revealed by Chronic Diarrhea
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
Ribas, Antoni; Kefford, Richard; Marshall, Margaret A.; Punt, Cornelis J.A.; Haanen, John B.; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L.; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A.; Dreno, Brigitte; Nathan, Paul D.; Mackiewicz, Jacek; Kirkwood, John M.; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel
2013-01-01
Purpose In phase I/II trials, the cytotoxic T lymphocyte–associated antigen-4–blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients and Methods Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). Results In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. Conclusion This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma. PMID:23295794
Mark, Karen E; Spruance, Spotswood; Kinghorn, George R; Sacks, Stephen L; Slade, Herbert B; Meng, Tze-Chiang; Selke, Stacy; Magaret, Amalia; Wald, Anna
2014-09-01
Resiquimod, a Toll-like receptor 7 and 8 agonist, stimulates production of cytokines that promote an antigen-specific T helper type 1 acquired immune response. Animal and phase II human trials showed posttreatment efficacy in reducing recurrent herpes lesion days and/or time to first recurrence. Three phase III randomized, double-blind, vehicle-controlled trials of topical resiquimod to reduce anogenital herpes recurrences were conducted in healthy adults with ≥4 recurrences within the prior year. Participants applied resiquimod 0.01% gel or vehicle gel 2 times per week for 3 weeks to each recurrence for 12 months. Trials 1 and 2 had 2:1 resiquimod-vehicle randomization. Trial 3 had 1:1:1 randomization for resiquimod and 500 mg valacyclovir orally twice daily for 5 days (RESI-VAL), resiquimod and oral placebo (RESI-PLA), and vehicle and oral placebo (VEH-PLA). The median time to first recurrence was similar for resiquimod and vehicle (trial 1, 60 and 56 days, P=0.7; trial 2, 54 and 48 days, P=0.47; trial 3, 51 [RESI-VAL], 55 [RESI-PLA], and 44 [VEH-PLA] days, P=not significant [NS]). The median time to healing of initial treated recurrence was longer for resiquimod (trial 1, 18 compared to 10 days, P<0.001; trial 2, 19 compared to 13 days, P=0.16; trial 3, 14 [RESI-VAL], 16 [RESI-PLA], and 8 [VEH-PLA] days, P<0.001). In trials 1 and 2, moderate to severe erythema and erosion/ulceration at the application site were more common in resiquimod recipients. In conclusion, no posttreatment efficacy of resiquimod 0.01% gel was observed. Increased application site reactions and initial recurrence healing time are consistent with resiquimod-induced cytokine effects. PMID:24709264
Two Phase II randomized trials on the CRTh2 antagonist AZD1981 in adults with asthma
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
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
Genetic investigation of multicentric glioblastoma multiforme: case report.
Schroeder, Brett; Shah, Nameeta; Rostad, Steve; McCullough, Brendan; Aguedan, Brian; Foltz, Greg; Cobbs, Charles
2016-05-01
The authors report a case of multicentric glioblastoma multiforme (GBM) in which all 4 tumor foci were resected and evaluated using both comparative genomic hybridization array and RNA sequencing. Genetic analysis showed that the tumors shared a common origin, although each had its own unique set of genetic aberrations. The authors note that the genetic heterogeneity of multicentric GBM likely contributes to the failures of current treatments. The case underscores the necessity of increased genetic investigation. PMID:26473785
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.
The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice.
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
2016-04-11
More than 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, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). 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-naive and relapsed/refractory disease. PMID:27070704
NASA Astrophysics Data System (ADS)
Korotkevich, Alexander O.; Lushnikov, Pavel M.; Rose, Harvey A.
2015-01-01
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 cTc exceeds a laser speckle length, with Tc 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 Tc. 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.
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
Mast Cell Stabilizer (Ketotifen) in Fibromyalgia: Phase 1 Randomized Controlled Clinical Trial
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
Power Spectrum of Uplink Array Signals with Random Phase and Delay Errors
NASA Technical Reports Server (NTRS)
Vilnrotter, Victor A.
2011-01-01
Link Array signals emanating from different antennas must be compensated for Doppler and delay in order to achieve the N(sup 2) array gain predicted by theory. However compensation is never perfect, leaving residual errors that cause losses in array gain and degradation in signal quality. Here we develop a mathematical model for Uplink Array signals in the presence of phase and delay errors, similar to well-known multipath analyses but with features unique to this problem. The resulting losses and distortions are described, and the power spectral density of the array signal derived first conditioned on a given error vector, then averaged over distributions deemed suitable for Uplink Array applications. The impact of phase and delay errors on array gain and signal distortion are addressed, and the maximum data throughput is quantified in terms of the assumed error statistics.
Observed phase changes and the random sequential packing model for elections in Japan
NASA Astrophysics Data System (ADS)
Itoh, Yoshiaki; Ueda, Sumie
2000-08-01
In Japan the nomination of candidates by some political parties in each constituency seems to have been often performed like car-parking in a street, which explains the territory making behaviour for each candidate. The car-parking model is a one-dimensional sequential packing model. We apply this model to the election data for the House of Councillors and the House of Representatives. We observe phase changes for the election data of the House of Councillors.
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.
Mayxay, Mayfong; Keomany, Sommay; Khanthavong, Maniphone; Souvannasing, Phoutthalavanh; Stepniewska, Kasia; Khomthilath, Tiengthong; Keola, Siamphay; Pongvongsa, Tiengkham; Phompida, Samlane; Ubben, David; Valecha, Neena; White, Nicholas J.; Newton, Paul N.
2010-01-01
We conducted an open, randomized clinical trial of oral dihydroartemisinin-piperaquine (DP) versus artesunate-mefloquine (AM) in 300 patients in Laos with uncomplicated Plasmodium falciparum malaria as part of a multicentre study in Asia. Survival analysis and adjustment for re-infection showed that the 63-day cure rates (95% confidence interval [CI]) were 100% for AM and 99.5% (96.4–99.8%) for DP. The 63-day cure rates per protocol were 99% (97 of 98) for AM and 99.5% (196 of 197) for DP (P = 0.55). The difference (AM minus DP) in cure rates (95% CI) was −0.5% (−5.1 to 2.0%), which is within the 5% non-inferiority margin. The median fever and parasite clearance times were also similar for AM and DP. The proportion of patients with at least one recorded potential adverse event was significantly higher in the AM group (38 of 87, 44%) than in the DP group (57 of 182, 31%) (relative risk = 0.6, 95% CI = 0.4–0.9; P = 0.04). Dihydroartemisinin-piperaquine is not inferior to AM in the treatment of uncomplicated P. falciparum malaria in Laos and is associated with fewer adverse effects. The results of this study were similar to those of the larger multicentre study. PMID:21118925
Kantarjian, Hagop M; Shah, Neil P; Cortes, Jorge E; Baccarani, Michele; Agarwal, Mohan B; Undurraga, María Soledad; Wang, Jianxiang; Ipiña, Juan Julio Kassack; Kim, Dong-Wook; Ogura, Michinori; Pavlovsky, Carolina; Junghanss, Christian; Milone, Jorge H; Nicolini, Franck E; Robak, Tadeusz; Van Droogenbroeck, Jan; Vellenga, Edo; Bradley-Garelik, M Brigid; Zhu, Chao; Hochhaus, Andreas
2012-02-01
Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and safety in imatinib-resistant/-intolerant patients with chronic myeloid leukemia (CML). In the phase 3 DASISION trial, patients with newly diagnosed chronic-phase (CP) CML were randomized to receive dasatinib 100 mg (n = 259) or imatinib 400 mg (n = 260) once daily. Primary data showed superior efficacy for dasatinib compared with imatinib after 12 months, including significantly higher rates of complete cytogenetic response (CCyR), confirmed CCyR (primary end point), and major molecular response (MMR). Here, 24-month data are presented. Cumulative response rates by 24 months in dasatinib and imatinib arms were: CCyR in 86% versus 82%, MMR in 64% versus 46%, and BCR-ABL reduction to ≤ 0.0032% (4.5-log reduction) in 17% versus 8%. Transformation to accelerated-/ blast-phase CML on study occurred in 2.3% with dasatinib versus 5.0% with imatinib. BCR-ABL mutations, assessed after discontinuation, were detected in 10 patients in each arm. In safety analyses, fluid retention, superficial edema, myalgia, vomiting, and rash were less frequent with dasatinib compared with imatinib, whereas pleural effusion and grade 3/4 thrombocytopenia were more frequent with dasatinib. Overall, dasatinib continues to show faster and deeper responses compared with imatinib, supporting first-line use of dasatinib in patients with newly diagnosed CML-CP. This study was registered at ClinicalTrials.gov: NCT00481247. PMID:22160483
Shah, Neil P.; Cortes, Jorge E.; Baccarani, Michele; Agarwal, Mohan B.; Undurraga, María Soledad; Wang, Jianxiang; Kassack Ipiña, Juan Julio; Kim, Dong-Wook; Ogura, Michinori; Pavlovsky, Carolina; Junghanss, Christian; Milone, Jorge H.; Nicolini, Franck E.; Robak, Tadeusz; Van Droogenbroeck, Jan; Vellenga, Edo; Bradley-Garelik, M. Brigid; Zhu, Chao; Hochhaus, Andreas
2012-01-01
Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and safety in imatinib-resistant/-intolerant patients with chronic myeloid leukemia (CML). In the phase 3 DASISION trial, patients with newly diagnosed chronic-phase (CP) CML were randomized to receive dasatinib 100 mg (n = 259) or imatinib 400 mg (n = 260) once daily. Primary data showed superior efficacy for dasatinib compared with imatinib after 12 months, including significantly higher rates of complete cytogenetic response (CCyR), confirmed CCyR (primary end point), and major molecular response (MMR). Here, 24-month data are presented. Cumulative response rates by 24 months in dasatinib and imatinib arms were: CCyR in 86% versus 82%, MMR in 64% versus 46%, and BCR-ABL reduction to ≤ 0.0032% (4.5-log reduction) in 17% versus 8%. Transformation to accelerated-/ blast-phase CML on study occurred in 2.3% with dasatinib versus 5.0% with imatinib. BCR-ABL mutations, assessed after discontinuation, were detected in 10 patients in each arm. In safety analyses, fluid retention, superficial edema, myalgia, vomiting, and rash were less frequent with dasatinib compared with imatinib, whereas pleural effusion and grade 3/4 thrombocytopenia were more frequent with dasatinib. Overall, dasatinib continues to show faster and deeper responses compared with imatinib, supporting first-line use of dasatinib in patients with newly diagnosed CML-CP. This study was registered at ClinicalTrials.gov: NCT00481247. PMID:22160483
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
2015-03-01
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
Kitamura, Masahiro; Nakashima, Keisuke; Kowashi, Yusuke; Fujii, Takeo; Shimauchi, Hidetoshi; Sasano, Takashi; Furuuchi, Toshi; Fukuda, Mitsuo; Noguchi, Toshihide; Shibutani, Toshiaki; Iwayama, Yukio; Takashiba, Shogo; Kurihara, Hidemi; Ninomiya, Masami; Kido, Jun-ichi; Nagata, Toshihiko; Hamachi, Takafumi; Maeda, Katsumasa; Hara, Yoshitaka; Izumi, Yuichi; Hirofuji, Takao; Imai, Enyu; Omae, Masatoshi; Watanuki, Mitsuru; Murakami, Shinya
2008-01-01
Background The options for medical use of signaling molecules as stimulators of tissue regeneration are currently limited. Preclinical evidence suggests that fibroblast growth factor (FGF)-2 can promote periodontal regeneration. This study aimed to clarify the activity of FGF-2 in stimulating regeneration of periodontal tissue lost by periodontitis and to evaluate the safety of such stimulation. Methodology/Principal Findings We used recombinant human FGF-2 with 3% hydroxypropylcellulose (HPC) as vehicle and conducted a randomized double-blinded controlled trial involving 13 facilities. Subjects comprised 74 patients displaying a 2- or 3-walled vertical bone defect as measured ≥3 mm apical to the bone crest. Patients were randomly assigned to 4 groups: Group P, given HPC with no FGF-2; Group L, given HPC containing 0.03% FGF-2; Group M, given HPC containing 0.1% FGF-2; and Group H, given HPC containing 0.3% FGF-2. Each patient underwent flap operation during which we administered 200 µL of the appropriate investigational drug to the bone defect. Before and for 36 weeks following administration, patients underwent periodontal tissue inspections and standardized radiography of the region under investigation. As a result, a significant difference (p = 0.021) in rate of increase in alveolar bone height was identified between Group P (23.92%) and Group H (58.62%) at 36 weeks. The linear increase in alveolar bone height at 36 weeks in Group P and H was 0.95 mm and 1.85 mm, respectively (p = 0.132). No serious adverse events attributable to the investigational drug were identified. Conclusions Although no statistically significant differences were noted for gains in clinical attachment level and alveolar bone gain for FGF-2 groups versus Group P, the significant difference in rate of increase in alveolar bone height (p = 0.021) between Groups P and H at 36 weeks suggests that some efficacy could be expected from FGF-2 in stimulating regeneration of
Haley, E. Clarke; Thompson, John L.P.; Grotta, James C.; Lyden, Patrick D.; Hemmen, Thomas G.; Brown, Devin L.; Fanale, Christopher; Libman, Richard; Kwiatkowski, Thomas G.; Llinas, Rafael H.; Levine, Steven R.; Johnston, Karen C.; Buchsbaum, Richard; Levy, Gilberto; Levin, Bruce
2010-01-01
Background: Intravenous alteplase (rt-PA) remains the only approved treatment for acute ischemic stroke, but its use remains limited. In a previous pilot dose-escalation study, intravenous tenecteplase showed promise as a potentially safer alternative. Therefore, a Phase IIB clinical trial was begun to a) choose a best dose of tenecteplase to carry forward, and b) to provide evidence for either promise or futility of further testing of tenecteplase versus rt-PA. If promise was established, then the trial would continue as a Phase III efficacy trial comparing the selected tenecteplase dose to standard rt-PA. Methods: The trial began as a small, multi-center, randomized, double-blind, controlled clinical trial comparing 0.1, 0.25, and 0.4 mg/kg tenecteplase with standard 0.9 mg/kg rt-PA in patients with acute stroke within 3 hours of onset. An adaptive sequential design used an early (24 hour) assessment of major neurological improvement balanced against occurrence of symptomatic intracranial hemorrhage (ICH) to choose a “best” dose of tenecteplase to carry forward. Once a “best” dose was established, the trial was to continue until at least 100 pairs of the selected tenecteplase dose versus standard rt-PA could be compared by 3 month outcome using the modified Rankin Scale in an interim analysis. Decision rules were devised to yield a clear recommendation to either stop for futility or to continue into Phase III. Results: The trial was prematurely terminated for slow enrollment after only 112 patients had been randomized at 8 clinical centers between 2006 and 2008. The 0.4 mg/kg dose was discarded as inferior after only 73 patients were randomized, but the selection procedure was still unable to distinguish between 0.1 mg/kg and 0.25 mg/kg as a propitious dose at the time the trial was stopped. There were no statistically persuasive differences in 3 month outcomes between the remaining tenecteplase groups and rt-PA. Symptomatic ICH rates were highest in the
Jayson, G. C.; Middleton, M.; Lee, S. M.; Ashcroft, L.; Thatcher, N.
1998-01-01
A randomized phase II trial was performed to compare the efficacy and toxicity of interleukin 2 (IL-2) with an IL-2 and interferon alpha (IFN-alpha) regimen for the treatment of metastatic renal carcinoma. Sixty patients with recurrent renal cell carcinoma (RCC) who had previously undergone a nephrectomy were randomized to receive three cycles of IL-2 or IL-2 with IFN-alpha2b. Eighteen MU of IL-2 were administered subcutaneously on Mondays-Fridays for 3 weeks out of 4. Those patients randomized to receive the combination received the same regimen of IL-2 with 9 MU of IFN-alpha2b subcutaneously on Mondays, Wednesdays and Fridays for 3 weeks out of 4. Thirty patients were randomized to receive each arm. Twenty-nine were evaluable in each arm. Twenty-two patients received three cycles of IL-2 but only 14 patients received three cycles of IL-2/IFN-alpha because of the greater toxicity of the combination. The principal toxicities included nausea, fatigue and fever. There were no complete responses in either arm and only two patients who were treated with IL-2 attained a partial response. Twelve patients in each arm had stable disease and 15 patients in the IL-2 arm and 16 patients in the IL-2/IFN-alpha arm progressed through treatment. There were no significant differences in survival. Ten patients who received IL-2 are alive with a median follow-up of 266 days, whereas six patients who received IL-2/IFN-alpha are alive after a median of 278 days. The median survival from the time of identification of metastatic disease is 444 days in the IL-2 arm and 381 days in the IL-2/IFN-alpha arm. The IL-2/IFN-alpha combination is more toxic than IL-2 alone and this resulted in a reduced number of cycles of treatment. However, the median survival of the two groups was the same, suggesting that further evaluation of the IL-2/IFN-alpha combination should be confined to large prospective randomized clinical trials. PMID:9703284
Once-daily USL255 as adjunctive treatment of partial-onset seizures: Randomized phase III study
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
DNA Priming for Seasonal Influenza Vaccine: A Phase 1b Double-Blind Randomized Clinical Trial
Ledgerwood, Julie E.; Bellamy, Abbie R.; Belshe, Robert; Bernstein, David I.; Edupuganti, Srilatha; Patel, Shital M.; Renehan, Phyllis; Zajdowicz, Thad; Schwartz, Richard; Koup, Richard; Bailer, Robert T.; Yamshchikov, Galina V.; Enama, Mary E.; Sarwar, Uzma; Larkin, Brenda; Graham, Barney S.
2015-01-01
Background The efficacy of current influenza vaccines is limited in vulnerable populations. DNA vaccines can be produced rapidly, and may offer a potential strategy to improve vaccine immunogenicity, indicated by studies with H5 influenza DNA vaccine prime followed by inactivated vaccine boost. Methods Four sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza DNA vaccine prime (n=65) or phosphate buffered saline (PBS) (n=66) administered intramuscularly with Biojector. All subjects received the 2012/13 seasonal inactivated influenza vaccine, trivalent (IIV3) 36 weeks after the priming injection. Vaccine safety and tolerability was the primary objective and measurement of antibody response by hemagglutination inhibition (HAI) was the secondary objective. Results The DNA vaccine prime-IIV3 boost regimen was safe and well tolerated. Significant differences in HAI responses between the DNA vaccine prime and the PBS prime groups were not detected in this study. Conclusion While DNA priming significantly improved the response to a conventional monovalent H5 vaccine in a previous study, it was not effective in adults using seasonal influenza strains, possibly due to pre-existing immunity to the prime, unmatched prime and boost antigens, or the lengthy 36 week boost interval. Careful optimization of the DNA prime-IIV3 boost regimen as related to antigen matching, interval between vaccinations, and pre-existing immune responses to influenza is likely to be needed in further evaluations of this vaccine strategy. In particular, testing this concept in younger age groups with less prior exposure to seasonal influenza strains may be informative. Trial Registration ClinicalTrials.gov NCT01498718 PMID:25950433
A Phase III Randomized Trial of the Timing of Meloxicam With Iodine-125 Prostate Brachytherapy
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.
A Phase 2 Randomized Dose-Finding Study With Esmirtazapine in Patients With Primary Insomnia.
Ruwe, Frank; IJzerman-Boon, Pieta; Roth, Thomas; Zammit, Gary; Ivgy-May, Neely
2016-10-01
The antidepressant mirtazapine is an alternative to classical hypnotics, and this study investigated the efficacy and safety of esmirtazapine (Org 50081, the maleic acid salt of S-mirtazapine) in patients given a diagnosis of primary insomnia after acute (2-day) treatment. Patients aged 18 to 65 years with primary insomnia were randomized to receive placebo or 1.5-, 3.0-, or 4.5-mg esmirtazapine in a balanced 4-way crossover study; 2 sleep laboratory nights with polysomnography were separated by 5-day, single-blind placebo washout periods. Polysomnography-determined total sleep time (primary end point) and patient-reported total sleep time improved by at least 25 minutes with all 3 doses of esmirtazapine (P ≤ 0.001 vs placebo). Polysomnography-measured wake time after sleep onset (P ≤ 0.0001) and latency to persistent sleep also improved vs placebo (P ≤ 0.01, 3.0 and 4.5 mg). Patient-reported sleep quality improved with 3.0- and 4.5-mg esmirtazapine (P ≤ 0.01 and P ≤ 0.05, respectively, vs placebo). Morning alertness and contentment were not altered after esmirtazapine, and calmness increased with 4.5-mg esmirtazapine vs placebo. Evening questionnaires showed no difference in duration of daytime naps but reduced energy and ability to work/function after esmirtazapine treatment periods vs placebo (P < 0.05), although this effect was limited to the first night of each 2-night period. There were few adverse events, no serious adverse events, or clinically relevant treatment differences in vital signs, laboratory values, or electrocardiogram. Esmirtazapine doses of 1.5 to 4.5 mg/day significantly improved quantity and quality of sleep and were generally well tolerated, with no evidence of safety concerns or consistent pattern of residual effects. PMID:27482970
A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia.
Kuriakose, Moni Abraham; Ramdas, Kunnambath; Dey, Bindu; Iyer, Subramanya; Rajan, Gunaseelan; Elango, Kalavathy K; Suresh, Amritha; Ravindran, Divya; Kumar, Rajneesh R; R, Prathiba; Ramachandran, Surya; Kumar, Nisha Asok; Thomas, Gigi; Somanathan, Thara; Ravindran, Hiran K; Ranganathan, Kannan; Katakam, Sudhakar Babu; Parashuram, Shivashankar; Jayaprakash, Vijayvel; Pillai, M Radhakrishna
2016-08-01
Oral leukoplakia is a potentially malignant lesion of the oral cavity, for which no effective treatment is available. We investigated the effectiveness of curcumin, a potent inhibitor of NF-κB/COX-2, molecules perturbed in oral carcinogenesis, to treat leukoplakia. Subjects with oral leukoplakia (n = 223) were randomized (1:1 ratio) to receive orally, either 3.6 g/day of curcumin (n = 111) or placebo (n = 112), for 6 months. The primary endpoint was clinical response obtained by bi-dimensional measurement of leukoplakia size at recruitment and 6 months. Histologic response, combined clinical and histologic response, durability and effect of long-term therapy for an additional six months in partial responders, safety and compliance were the secondary endpoints. Clinical response was observed in 75 (67.5%) subjects [95% confidence interval (CI), 58.4-75.6] in the curcumin and 62 (55.3%; 95% CI, 46.1-64.2) in placebo arm (P = 0.03). This response was durable, with 16 of the 18 (88.9%; 95% CI, 67.2-96.9) subjects with complete response in curcumin and 7 of 8 subjects (87.5%) in placebo arm, demonstrating no relapse after 6 months follow-up. Difference in histologic response between curcumin and placebo was not significant (HR, 0.88, 95% CI, 0.45-1.71; P = 0.71). Combined clinical and histologic response assessment indicated a significantly better response with curcumin (HR, 0.50; 95% CI, 0.27-0.92; P = 0.02). Continued therapy, in subjects with partial response at 6 months, did not yield additional benefit. The treatment did not raise any safety concerns. Treatment of oral leukoplakia with curcumin (3.6 g for six months), thus was well tolerated and demonstrated significant and durable clinical response for 6 months. Cancer Prev Res; 9(8); 683-91. ©2016 AACR. PMID:27267893
Yeoh, Eric E.; Botten, Rochelle J.; Butters, Julie; Di Matteo, Addolorata C.; Holloway, Richard H.; Fowler, Jack
2011-12-01
Purpose: To evaluate the long-term efficacy and toxicity of a hypofractionated (55 Gy in 20 fractions within 4 weeks) vs. a conventionally fractionated (64 Gy in 32 fractions within 6.5 weeks) dose schedule for radiotherapy (RT) for localized carcinoma of the prostate. Methods and Materials: A total of 217 patients were randomized to either the hypofractionated (n = 108) or the conventional (n = 109) dose schedule. Most patients (n = 156) underwent RT planning and RT using a two-dimensional computed tomography method. Efficacy using the clinical, radiologic, and prostate-specific antigen data in each patient was evaluated before RT and at predetermined intervals after RT until death. Gastrointestinal and genitourinary toxicity using the modified Late Effect in Normal Tissue - Subjective Objective Management Analytic (LENT-SOMA) scales was also evaluated before and at intervals after RT to 60 months. Results: The whole group has now been followed for a median of 90 months (range, 3-138). Of the 217 patients, 85 developed biochemical relapse (nadir prostate-specific antigen level + 2 {mu}g/L), 36 in the hypofractionated and 49 in the conventional group. The biochemical relapse-free, but not overall, survival at 90 months was significantly better with the hypofractionated (53%) than with the conventional (34%) schedule. Gastrointestinal and genitourinary toxicity persisted 60 months after RT and did not differ between the two dose schedules. Multivariate analyses revealed that the conventional schedule was of independent prognostic significance, not only for biochemical failure, but also for an increased risk of worse genitourinary symptoms at 4 years. Conclusions: A therapeutic advantage of the hypofractionated compared with the conventional dose schedule for RT of prostate cancer was evident at 90 months in the present study.
Distribution of nanoscale nuclei in the amorphous dome of a phase change random access memory
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.
Bodin, E; Brévart, B; Wagstaff, P; Borello, G
2002-07-01
Numerous pyrotechnic devices are used on satellites to separate structural subsystems, deploy appendages, and activate on-board operating subsystems. The firing of these pyrotechnic mechanisms leads to severe impulsive loads which could sometimes lead to failures in electronic systems. The objective of the present investigation is to assess the relevance of a method combining deterministic calculations and statistical energy analysis to predict the time overall shock environment of electronic equipment components. The methods are applied to the low- and high-frequency ranges, respectively, which may be defined using a modal parameter based on the effective transmissibility. Initially, in order to address the problem of the low-frequency content of the mechanical shock pulse, the linear dynamic response of the equipment was calculated using direct time integration of a finite element model of the structure. The inputs in the form of the accelerations measured in all three directions at each of the four bolted interfaces were injected into the model. The high-frequency content of the shock response is taken into account by considering the intrinsic dynamic filtering of the equipment. This frequency filter magnitude is extrapolated from the transfer function given by statistical energy analysis between the different imposed accelerations and the response accelerations. Their associated phases are synthesized by considering pseudo-modal phase variations around the group velocity of the structural flexural waves. Combining the effects of the high-frequency filter outputs and the low-frequency finite element calculations yields good predictions of the equipment shock time response over the whole frequency range of interest. PMID:12141340
NASA Astrophysics Data System (ADS)
Bodin, E.; Brevart, B.; Wagstaff, P.; Borello, G.
2002-07-01
Numerous pyrotechnic devices are used on satellites to separate structural subsystems, deploy appendages, and activate on-board operating subsystems. The firing of these pyrotechnic mechanisms leads to severe impulsive loads which could sometimes lead to failures in electronic systems. The objective of the present investigation is to assess the relevance of a method combining deterministic calculations and statistical energy analysis to predict the time overall shock environment of electronic equipment components. The methods are applied to the low- and high-frequency ranges, respectively, which may be defined using a modal parameter based on the effective transmissibility. Initially, in order to address the problem of the low-frequency content of the mechanical shock pulse, the linear dynamic response of the equipment was calculated using direct time integration of a finite element model of the structure. The inputs in the form of the accelerations measured in all three directions at each of the four bolted interfaces were injected into the model. The high-frequency content of the shock response is taken into account by considering the intrinsic dynamic filtering of the equipment. This frequency filter magnitude is extrapolated from the transfer function given by statistical energy analysis between the different imposed accelerations and the response accelerations. Their associated phases are synthesized by considering pseudo-modal phase variations around the group velocity of the structural flexural waves. Combining the effects of the high-frequency filter outputs and the low-frequency finite element calculations yields good predictions of the equipment shock time response over the whole frequency range of interest. copyright 2002 Acoustical Society of America.
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
Phase III randomized trial of CED of IL13-PE38QQR vs Gliadel wafers for recurrent glioblastoma†
Kunwar, Sandeep; Chang, Susan; Westphal, Manfred; Vogelbaum, Michael; Sampson, John; Barnett, Gene; Shaffrey, Mark; Ram, Zvi; Piepmeier, Joseph; Prados, Michael; Croteau, David; Pedain, Christoph; Leland, Pamela; Husain, Syed R.; Joshi, Bharat H.; Puri, Raj K.
2010-01-01
Convection-enhanced delivery (CED) of cintredekin besudotox (CB) was compared with Gliadel wafers (GW) in adult patients with glioblastoma multiforme (GBM) at first recurrence. Patients were randomized 2:1 to receive CB or GW. CB (0.5 µg/mL; total flow rate 0.75 mL/h) was administered over 96 hours via 2–4 intraparenchymal catheters placed after tumor resection. GW (3.85%/7.7 mg carmustine per wafer; maximum 8 wafers) were placed immediately after tumor resection. The primary endpoint was overall survival from the time of randomization. Prestated interim analyses were built into the study design. Secondary and tertiary endpoints were safety and health-related quality-of-life assessments. From March 2004 to December 2005, 296 patients were enrolled at 52 centers. Demographic and baseline characteristics were balanced between the 2 treatment arms. Median survival was 36.4 weeks (9.1 months) for CB and 35.3 weeks (8.8 months) for GW (P = .476). For the efficacy evaluable population, the median survival was 45.3 weeks (11.3 months) for CB and 39.8 weeks (10 months) for GW (P = .310). The adverse-events profile was similar in both arms, except that pulmonary embolism was higher in the CB arm (8% vs 1%, P = .014). This is the first randomized phase III evaluation of an agent administered via CED and the first with an active comparator in GBM patients. There was no survival difference between CB administered via CED and GW. Drug distribution was not assessed and may be crucial for evaluating future CED-based therapeutics. PMID:20511192
Arai, Sally; Pidala, Joseph; Pusic, Iskra; Chai, Xiaoyu; Jaglowski, Samantha; Khera, Nandita; Palmer, Jeanne; Chen, George L; Jagasia, Madan H; Mayer, Sebastian A; Wood, William A; Green, Michael; Hyun, Teresa S.; Inamoto, Yoshihiro; Storer, Barry E; Miklos, David B; Shulman, Howard M.; Martin, Paul J; Sarantopoulos, Stefanie; Lee, Stephanie J; Flowers, Mary E D
2015-01-01
Purpose Cutaneous sclerosis (CS) occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life. Experimental design We conducted a prospective, multi-center, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m2 intravenously weekly × 4 doses, repeatable after 3 months) for treatment of CS diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrent malignancy or death. Secondary end points included changes of B cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and non-responders with each therapy. Results SCR was observed in 9 of 35 (26%, 95% CI 13-43%) participants randomized to imatinib and 10 of 37 (27%, 95% CI 14-44%) randomized to rituximab. Six (17%, 95% CI 7-34%) patients in the imatinib arm and 5 (14%, 95% CI 5-29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27+) were seen at enrollment in rituximab-treated patients who had treatment success (p = 0.01), but not in imatinib-treated patients. Conclusion These results support the need for more effective therapies for CS and suggest that activated B cells define a subgroup of patients with CS who are more likely to respond to rituximab. PMID:26378033
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
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.
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.
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. PMID:27411183
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, h_{λ}(r,r^{'}), in which interactions λu(r,r^{'}) are gradually switched on as λ changes from 0 to 1. The function h_{λ}(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 c_{λ}(r,r^{'})≈-λβu(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. PMID:27415213
Sambataro, M.; Suhonen, J.
1997-08-01
The quasiparticle random-phase approximation (QRPA) is reviewed and higher-order approximations are discussed with reference to {beta}-decay physics. The approach is fully developed in a boson formalism. Working within a schematic model, we first illustrate a fermion-boson mapping procedure and apply it to construct boson images of the fermion Hamiltonian at different levels of approximation. The quality of these images is tested through a comparison between approximate and exact spectra. Standard QRPA equations are derived in correspondence with the quasi-boson limit of the first-order boson Hamiltonian. The use of higher-order Hamiltonians is seen to improve considerably the stability of the approximate solutions. The mapping procedure is also applied to Fermi {beta} operators: exact and approximate transition amplitudes are discussed together with the Ikeda sum rule. The range of applicabilty of the QRPA formalism is analyzed. {copyright} {ital 1997} {ital The American Physical Society}
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.
NASA Astrophysics Data System (ADS)
Cheng, Jun; VandeVondele, Joost
2016-02-01
Understanding charge transfer at electrochemical interfaces requires consistent treatment of electronic energy levels in solids and in water at the same level of the electronic structure theory. Using density-functional-theory-based molecular dynamics and thermodynamic integration, the free energy levels of six redox couples in water are calculated at the level of the random phase approximation and a double hybrid density functional. The redox levels, together with the water band positions, are aligned against a computational standard hydrogen electrode, allowing for critical analysis of errors compared to the experiment. It is encouraging that both methods offer a good description of the electronic structures of the solutes and water, showing promise for a full treatment of electrochemical interfaces.
Cheng, Jun; VandeVondele, Joost
2016-02-26
Understanding charge transfer at electrochemical interfaces requires consistent treatment of electronic energy levels in solids and in water at the same level of the electronic structure theory. Using density-functional-theory-based molecular dynamics and thermodynamic integration, the free energy levels of six redox couples in water are calculated at the level of the random phase approximation and a double hybrid density functional. The redox levels, together with the water band positions, are aligned against a computational standard hydrogen electrode, allowing for critical analysis of errors compared to the experiment. It is encouraging that both methods offer a good description of the electronic structures of the solutes and water, showing promise for a full treatment of electrochemical interfaces. PMID:26967430
Hanson, Steen G; Wang, Wei; Jakobsen, Michael L; Takeda, Mitsuo
2008-09-01
The change of coherence and polarization of an electromagnetic beam modulated by a random anisotropic phase screen passing through any optical system is found within the framework of complex ABCD-matrix theory This means that the formalism can treat imaging and Fourier transform and free-space optical systems, as well as fractional Fourier transform systems, with finite-size limiting apertures of Gaussian transmission shape. Thus, the current paper shall be considered as a continuation, extension, and generalization of a previous work by Shirai and Wolf [J. Opt. Soc. Am. A21, 1907 (2004)]. It will be shown that the inclusion of apertures in the optical system strongly influences not only the propagation of spatial coherence but also the degree of polarization of a propagating field. Analytical expressions of coherence and polarization propagation will be given in terms of the matrix elements for any complex optical system. PMID:18758562
NASA Astrophysics Data System (ADS)
Kallush, Shimshon; Fleischer, Sharly; Ultrafast terahertz molecular dynamics Collaboration
2015-05-01
Quantum simulation of large open systems is a hard task that demands huge computation and memory costs. The rotational dynamics of non-linear molecules at high-temperature under external fields is such an example. At room temperature, the initial density matrix populates ~ 104 rotational states, and the whole coupled Hilbert space can reach ~ 106 states. Simulation by neither the direct density matrix nor the full basis set of populated wavefunctions is impossible. We employ the random phase wave function method to represent the initial state and compute several time dependent and independent observables such as the orientation and the alignment of the molecules. The error of the method was found to scale as N- 1 / 2, where N is the number of wave function realizations employed. Scaling vs. the temperature was computed for weak and strong fields. As expected, the convergence of the method increase rapidly with the temperature and the field intensity.
Terasaki, J.; Engel, J.; Bertsch, G. F.
2008-10-15
We use the quasiparticle random-phase approximation (QRPA) and the Skyrme interactions SLy4 and SkM* to systematically calculate energies and transition strengths for the lowest 2{sup +} state in spherical even-even nuclei. The SkM* functional, applied to 178 spherical nuclei between Z=10 and 90, produces excitation energies that are on average 11% higher than experimental values, with residuals that fluctuate about the average by -35% to +55%. The predictions of SkM* and SLy4 have significant differences, in part because of differences in the calculated ground state deformations; SkM* performs better in both the average and dispersion of energies. Comparing the QRPA results with those of generator-coordinate-method (GCM) calculations, we find that the QRPA reproduces trends near closed shells better than the GCM, and that it overpredicts the energies less severely in general.
Batistic, I.; Bishop, A.R. )
1992-03-01
We have developed a method based on a real-space random-phase approximation (RPA) to study the phonon spectra of doped and undoped halogen-bridged transition-metal-chain complexes. The method is very convenient in cases of spatially inhomogeneous mean-field structures. Thus, we are able to find the usual extended phonon modes as well as local modes associated with polaron, bipolaron, kink, exciton, or impurity structures in intrinsically or extrinsically doped systems. The corresponding infrared absorption spectra and Raman spectra (as a function of the excitation energy) are calculated. We demonstrate the method for a homogeneous charge-density-wave system, and for electron and hole polarons. We find that each type of defect has specific signatures in both infrared and Raman spectra, which can help to identify different types of defects experimentally.
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.
Wilson, D.J.; Clarke, A.N.; Kaminski, K.M.; Chang, E.Y.
1997-12-01
A mathematical model is developed to simulate the sparging of dissolved volatile organic compounds (VOCs) and nonaqueous phase liquid (NAPL) from contaminated aquifers. The sparging air moves through the aquifer in persistent, random channels, to which VOC must move by diffusion/dispersion to be removed. The dependence of the rate of remediation on the various model parameters is investigated and some practical conclusions are reached regarding the operation of air sparging wells for aquifer remediation. VOCs of low water solubility (such as alkanes) and present as NAPL are found to be removed by air sparging much more slowly than VOCs of higher water solubility (such as benzene, toluene, ethylbenzene and xylenes) and present as NAPL, due to the very small maximum concentration gradients which can be maintained around droplets of the former. These small concentration gradients result in very slow rates of NAPL solution.
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 .
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.
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.
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.
Chen, Yu-Pei; Chen, Yong; Zhang, Wen-Na; Liang, Shao-Bo; Zong, Jing-Feng; Chen, Lei; Mao, Yan-Ping; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Guo, Ying; Lin, Ai-Hua; Liu, Meng-Zhong; Sun, Ying; Ma, Jun
2015-01-01
The gold standard endpoint in trials of locoregionally advanced nasopharyngeal carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized trial, we evaluated whether progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) or locoregional failure-free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July 2002 and September 2005, 316 eligible patients with stage III-IVB NPC were randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2- and 3-year PFS, FFS, D-FFS, and LR-FFS were tested as surrogate endpoints for 5-year OS using Prentice’s four criteria. The Spearman’s rank correlation coefficient was calculated to assess the strength of the associations. After a median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not significantly different between treatment arms, in rejection of Prentice’s second criterion. Being consistent with all Prentice’s criteria, 2- and 3-year PFS and FFS were valid surrogate endpoints for 5-year OS; the rank correlation coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion, PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5 years; 3-year PFS may be more appropriate for early assessment of long-term survival. PMID:26219568
A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease
Sperling, R.; Keren, R.; Porsteinsson, A.P.; van Dyck, C.H.; Tariot, P.N.; Gilman, S.; Arnold, D.; Abushakra, S.; Hernandez, C.; Crans, G.; Liang, E.; Quinn, G.; Bairu, M.; Pastrak, A.; Cedarbaum, J.M.
2011-01-01
Objective: This randomized, double-blind, placebo-controlled, dose-ranging phase 2 study explored safety, efficacy, and biomarker effects of ELND005 (an oral amyloid anti-aggregation agent) in mild to moderate Alzheimer disease (AD). Methods: A total of 353 patients were randomized to ELND005 (250, 1,000, or 2,000 mg) or placebo twice daily for 78 weeks. Coprimary endpoints were the Neuropsychological Test Battery (NTB) and Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scale. The primary analysis compared 250 mg (n =84) to placebo (n =82) after an imbalance of infections and deaths led to early discontinuation of the 2 higher dose groups. Results: The 250 mg dose demonstrated acceptable safety. The primary efficacy analysis at 78 weeks revealed no significant differences between the treatment groups on the NTB or ADCS-ADL. Brain ventricular volume showed a small but significant increase in the overall 250 mg group (p =0.049). At the 250 mg dose, scyllo-inositol concentrations increased in CSF and brain and CSF Aβx-42 was decreased significantly compared to placebo (p =0.009). Conclusions: Primary clinical efficacy outcomes were not significant. The safety and CSF biomarker results will guide selection of the optimal dose for future studies, which will target earlier stages of AD. Classification of evidence: Due to the small sample sizes, this Class II trial provides insufficient evidence to support or refute a benefit of ELND005. PMID:21917766
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
2014-01-01
Background The prevalence of severe and complex obesity is increasing worldwide and surgery may offer an effective and lasting treatment. Laparoscopic adjustable gastric band and Roux-en-Y gastric bypass surgery are the two main surgical procedures performed. Design This open parallel-group randomised controlled trial will compare the effectiveness, cost-effectiveness and acceptability of gastric band (Band) versus gastric bypass (Bypass) in adults with severe and complex obesity. It has an internal pilot phase (in two centres) with integrated qualitative research to establish effective and optimal methods for recruitment. Adults with a body mass index (BMI) of 40 kg/m2 or more, or a BMI of 35 kg/m2 or more and other co-morbidities will be recruited. At the end of the internal pilot the study will expand into more centres if the pre-set progression criteria of numbers and rates of eligible patients screened and randomised are met and if the expected rates of retention and adherence to treatment allocation are achieved. The trial will test the joint hypotheses that Bypass is non-inferior to Band with respect to more than 50% excess weight loss and that Bypass is superior to Band with respect to health related quality of life (HRQOL, EQ-5D) at three years. Secondary outcomes include other weight loss measures, waist circumference and remission/resolution of co-morbidities; generic and symptom-specific HRQOL; nutritional blood test results; resource use; eating behaviours and adverse events. A core outcome set for reporting the results of obesity surgery will be developed and a systematic review of the evidence for sleeve gastrectomy undertaken to inform the main study design. Discussion By-Band is the first pragmatic study to compare the two most commonly performed bariatric surgical procedures for severe and complex obesity. The design will enable and empower surgeons to learn to recruit and participate in a randomised study. Early evidence shows that timely
Application of a Dual-Hybrid Direct Random Phase Approximation to Water Clusters.
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. PMID:27500940
A random six-phase switch regulates pneumococcal virulence via global epigenetic changes
Manso, Ana Sousa; Chai, Melissa H.; Atack, John M.; Furi, Leonardo; De Ste Croix, Megan; Haigh, Richard; Trappetti, Claudia; Ogunniyi, Abiodun D.; Shewell, Lucy K.; Boitano, Matthew; Clark, Tyson A.; Korlach, Jonas; Blades, Matthew; Mirkes, Evgeny; Gorban, Alexander N.; Paton, James C.; Jennings, Michael P.; Oggioni, Marco R.
2014-01-01
Streptococcus pneumoniae (the pneumococcus) is the world’s foremost bacterial pathogen in both morbidity and mortality. Switching between phenotypic forms (or ‘phases’) that favour asymptomatic carriage or invasive disease was first reported in 1933. Here, we show that the underlying mechanism for such phase variation consists of genetic rearrangements in a Type I restriction-modification system (SpnD39III). The rearrangements generate six alternative specificities with distinct methylation patterns, as defined by single-molecule, real-time (SMRT) methylomics. The SpnD39III variants have distinct gene expression profiles. We demonstrate distinct virulence in experimental infection and in vivo selection for switching between SpnD39III variants. SpnD39III is ubiquitous in pneumococci, indicating an essential role in its biology. Future studies must recognize the potential for switching between these heretofore undetectable, differentiated pneumococcal subpopulations in vitro and in vivo. Similar systems exist in other bacterial genera, indicating the potential for broad exploitation of epigenetic gene regulation. PMID:25268848
A phase I randomized, multicenter trial of CPX in adult subjects with mild cystic fibrosis.
McCarty, Nael A; Standaert, Thomas A; Teresi, Mary; Tuthill, Cynthia; Launspach, Janice; Kelley, Thomas J; Milgram, Laura J H; Hilliard, Kathleen A; Regelmann, Warren E; Weatherly, Mark R; Aitken, Moira L; Konstan, Michael W; Ahrens, Richard C
2002-02-01
CPX (8-cyclopentyl-1,3-dipropylxanthine) is a novel compound currently under development as a potential treatment for cystic fibrosis (CF). The drug has been shown to increase chloride efflux and CFTR trafficking in vitro in CF airway cells. This phase I multicenter, single-dose, placebo-controlled trial was performed at four institutions. Thirty-seven subjects homozygous for the Delta F(508) allele were studied in an escalating dose protocol of seven single-dose cohorts (1, 3, 10, 30, 100, 300, and 1,000 mg) to evaluate the safety, pharmacokinetics, and efficacy of CPX. Efficacy was determined using nasal transepithelial potential difference and sweat chloride measurements prior to dosing and at 1, 2, and 4 hr postdose. The incidence of adverse events in the treatment group was similar to that with placebo, indicating safety of the single doses studied. One serious adverse event (an acute pulmonary exacerbation) occurred 13 days after dosing, and was not considered related to the study drug. The maximal plasma CPX concentration and total amount of CPX absorbed appeared to be linearly related to dose, but was highly variable throughout the dose range studied, suggesting inconsistent absorption. There was no apparent effect of single-dose administration on either nasal transepithelial potential difference or sweat chloride measurements. The positive safety and pharmacokinetic findings of this study support continued development of CPX as a potential therapeutic for CF. PMID:11802244
Scheller, Christian; Wienke, Andreas; Tatagiba, Marcos; Gharabaghi, Alireza; Ramina, Kristofer F; Ganslandt, Oliver; Bischoff, Barbara; Zenk, Johannes; Engelhorn, Tobias; Matthies, Cordula; Westermaier, Thomas; Antoniadis, Gregor; Pedro, Maria Teresa; Rohde, Veit; von Eckardstein, Kajetan; Kretschmer, Thomas; Kornhuber, Malte; Steighardt, Jörg; Richter, Michael; Barker, Fred G; Strauss, Christian
2016-03-01
OBJECT A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results. METHODS An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1-2 mg/hr) and hydroxyethyl starch (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically. RESULTS Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34-3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18-1.30], p = 0.15). Apart from dose-dependent hypotension (p < 0.001), no clinically relevant adverse reactions were observed. CONCLUSIONS There were no statistically significant effects of the treatment. Despite the width of the confidence intervals, the
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. PMID:25867139
Biard, L; Porcher, R; Resche-Rigon, M
2014-07-30
When analysing multicentre data, it may be of interest to test whether the distribution of the endpoint varies among centres. In a mixed-effect model, testing for such a centre effect consists in testing to zero a random centre effect variance component. It has been shown that the usual asymptotic χ(2) distribution of the likelihood ratio and score statistics under the null does not necessarily hold. In the case of censored data, mixed-effects Cox models have been used to account for random effects, but few works have concentrated on testing to zero the variance component of the random effects. We propose a permutation test, using random permutation of the cluster indices, to test for a centre effect in multilevel censored data. Results from a simulation study indicate that the permutation tests have correct type I error rates, contrary to standard likelihood ratio tests, and are more powerful. The proposed tests are illustrated using data of a multicentre clinical trial of induction therapy in acute myeloid leukaemia patients. PMID:24676752
Park, Eun-Ah; Kang, Doo Kyoung; Kim, Sung Jin; Kim, Young-Ju; Kim, Yookyung; Sung, Yon Mi; Song, Soon-Young; Oh, Yu-Whan; Yong, Hwan Seok; Lee, Heon; Jeon, Eui-Yong; Jin, Gong-Yong; Choi, Byoung Wook; Choi, Sang-Il
2016-01-01
Objective This multi-center, randomized, double-blind, phase 3 trial was conducted to compare the safety and efficacy of contrast agents iohexol-380 and iohexol-350 for coronary CT angiography in healthy subjects. Materials and Methods Volunteers were randomized to receive 420 mgI/kg of either iohexol-350 or iohexol-380 using a flow rate of 4 mL/sec. All adverse events were recorded. Two blinded readers independently reviewed the CT images and conflicting results were resolved by a third reader. Luminal attenuations (ascending aorta, left main coronary artery, and left ventricle) in Hounsfield units (HUs) and image quality on a 4-point scale were calculated. Results A total of 225 subjects were given contrast media (115 with iohexol-380 and 110 with iohexol-350). There was no difference in number of adverse drug reactions between groups: 75 events in 56 (48.7%) of 115 subjects in the iohexol-380 group vs. 74 events in 51 (46.4%) of 110 subjects in the iohexol-350 group (p = 0.690). No severe adverse drug reactions were recorded. Neither group showed an increase in serum creatinine. Significant differences in mean density between the groups was found in the ascending aorta: 375.8 ± 71.4 HU with iohexol-380 vs. 356.3 ± 61.5 HU with iohexol-350 (p = 0.030). No significant differences in image quality scores between both groups were observed for all three anatomic evaluations (all, p > 0.05). Conclusion Iohexol-380 provides improved enhancement of the ascending aorta and similar attenuation of the coronary arteries without any increase in adverse drug reactions, as compared with iohexol-350 using an identical amount of total iodine. PMID:27134522
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
Jakubowiak, Andrzej; 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
2016-06-01
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
Noonan, Anne M; Farren, Matthew R; Geyer, Susan M; Huang, Ying; Tahiri, Sanaa; Ahn, Daniel; Mikhail, Sameh; Ciombor, Kristen K; Pant, Shubham; Aparo, Santiago; Sexton, Jennifer; Marshall, John L; Mace, Thomas A; Wu, Christina S; El-Rayes, Bassel; Timmers, Cynthia D; Zwiebel, James; Lesinski, Gregory B; Villalona-Calero, Miguel A; Bekaii-Saab, Tanios S
2016-06-01
Pelareorep causes oncolysis in tumor cells with activated Ras. We hypothesized that pelareorep would have efficacy and immunomodulatory activity in metastatic pancreatic adenocarcinoma (MPA) when combined with carboplatin and paclitaxel. A randomized phase 2 study (NCT01280058) was conducted in treatment-naive patients with MPA randomized to two treatment arms: paclitaxel/carboplatin + pelareorep (Arm A, n = 36 evaluable patients) versus paclitaxel/carboplatin (Arm B, n = 37 evaluable patients). There was no difference in progression-free survival (PFS) between the arms (Arm A PFS = 4.9 months, Arm B PFS = 5.2 months, P = 0.6), and Kirsten rat sarcoma viral oncogene (KRAS) status did not impact outcome. Quality-adjusted Time without Symptoms or Toxicity analysis revealed that the majority of PFS time was without toxicity or progression (4.3 months). Patient immunophenotype appeared important, as soluble immune biomarkers were associated with treatment outcome (fractalkine, interleukin (IL)-6, IL-8, regulated on activation, normal T cell expressed and secreted (RANTES), and vascular endothelial growth factor (VEGF)). Increased circulating T and natural killer (NK)-cell subsets were also significantly associated with treatment outcome. Addition of pelareorep was associated with higher levels of 14 proinflammatory plasma cytokines/chemokines and cells with an immunosuppressive phenotype (Tregs, cytotoxic T lymphocyte associated protein 4 (CTLA4)(+) T cells). Overall, pelareorep was safe but does not improve PFS when administered with carboplatin/paclitaxel, regardless of KRAS mutational status. Immunologic studies suggest that chemotherapy backbone improves immune reconstitution and that targeting remaining immunosuppressive mediators may improve oncolytic virotherapy. PMID:27039845
Kim, Dae Won; Kim-Schulze, Seunghee; DeRaffele, Gail; Jagoda, Michael C.; Broucek, Joseph R.; Zloza, Andrew
2014-01-01
Abstract Oncolytic viruses have shown promise as gene delivery vehicles in the treatment of cancer; however, their efficacy may be inhibited by the induction of anti-viral antibody titers. Fowlpox virus is a nonreplicating and nononcolytic vector that has been associated with lesser humoral but greater cell-mediated immunity in animal tumor models. To test whether fowlpox virus gene therapy is safe and can elicit immune responses in patients with cancer, we conducted a randomized phase I clinical trial of two recombinant fowlpox viruses encoding human B7.1 or a triad of costimulatory molecules (B7.1, ICAM-1, and LFA-3; TRICOM). Twelve patients (10 with melanoma and 2 with colon adenocarcinoma) enrolled in the trial and were randomized to rF-B7.1 or rF-TRICOM administered in a dose escalation manner (∼3.7×107 or ∼3.7×108 plaque-forming units) by intralesional injection every 4 weeks. The therapy was well tolerated, with only four patients experiencing grade 1 fever or injection site pain, and there were no serious adverse events. All patients developed anti-viral antibody titers after vector delivery, and posttreatment anti-carcinoembryonic antigen antibody titers were detected in the two patients with colon cancer. All patients developed CD8+ T cell responses against fowlpox virus, but few responses against defined tumor-associated antigens were observed. This is the first clinical trial of direct (intratumoral) gene therapy with a nononcolytic fowlpox virus. Treatment was well tolerated in patients with metastatic cancer; all subjects exhibited anti-viral antibody responses, but limited tumor-specific T cell responses were detected. Nononcolytic fowlpox viruses are safe and induce limited T cell responses in patients with cancer. Further development may include prime–boost strategies using oncolytic viruses for initial priming. PMID:24484178
Multicentric spinal cord and brain glioblastoma without previous craniotomy
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
Kim, Min Jung; Hong, Chang Won; Kim, Byung Chang; Park, Sung Chan; Han, Kyung Su; Joo, Jungnam; Oh, Jae Hwan; Sohn, Dae Kyung
2016-02-01
The combination of different laxatives at reduced volumes may benefit patients by enhancing efficacy for bowel cleansing and increasing tolerability. However, evidence regarding combined preparations is scarce. This study evaluated whether the combined preparations are associated with enhanced efficacy and tolerability. This randomized phase II study had a single-blind, parallel-arm design. Between December 2013 and September 2014, consecutive patients aged between 20 and 65 years and who required diagnostic colonoscopies were considered for inclusion. Patients were randomly allocated into 4 arms: sodium picosulfate and magnesium citrate (PMC) and polyethylene glycol (PEG) with ascorbic acid in a day-prior (PMC-PEG-DP), PMC and oral sodium phosphate (NaP) in a day-prior (PMC-NaP-DP), PMC and PEG with ascorbic acid in a split-dose (PMC-PEG-SD), and PMC and oral NaP in a split-dose (PMC-NaP-SD). Primary endpoint was the Aronchick scale, and Ottawa scale results by colon segment, patients' adverse gastrointestinal symptoms, and willingness to reuse the same agents were also recorded. Successful bowel preparation was defined as an "excellent" or "good" score on the Aronchick scale. A total of 236 patients were randomized and 229 patients received the planned colonoscopy. The rates of successful bowel preparation in the PMC-PEG-DP, PMC-NaP-DP, PMC-PEG-SD, and PMC-NaP-SD were 82.5%, 64.4%, 100%, and 100%, respectively. Excluding the failed PMC-NaP-DP group, all groups showed satisfactory rates of successful bowel preparation, and the mean Ottawa scores were significantly better in the PMC-PEG-SD and PMC-NaP-SD groups than in the PMC-PEG-DP group (P < 0.0001). The PMC-PEG-DP, PMC-NaP-DP, PMC-PEG-SD, and PMC-NaP-SD groups were similar in terms of rates of adverse gastrointestinal symptoms reported on a 5-point scale (P = 0.40) and willingness to reuse the same combined preparations (P = 0.55). PMC-PEG in a day-prior or split-dose and PMC-NaP in a split
Komatsu, Yoshito; Okita, Kenji; Yuki, Satoshi; Furuhata, Tomohisa; Fukushima, Hiraku; Masuko, Hiroyuki; Kawamoto, Yasuyuki; Isobe, Hiroshi; Miyagishima, Takuto; Sasaki, Kazuaki; Nakamura, Michio; Ohsaki, Yoshinobu; Nakajima, Junta; Tateyama, Miki; Eto, Kazunori; Minami, Shinya; Yokoyama, Ryoji; Iwanaga, Ichiro; Shibuya, Hitoshi; Kudo, Mineo; Oba, Koji; Takahashi, Yasuo
2015-07-01
The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1-3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2-3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at -15% (study treatment group - control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1-3 (difference, 2.5%; 95% confidence interval [CI]: -7.8%-12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2-3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC. PMID:25872578
Komatsu, Yoshito; Okita, Kenji; Yuki, Satoshi; Furuhata, Tomohisa; Fukushima, Hiraku; Masuko, Hiroyuki; Kawamoto, Yasuyuki; Isobe, Hiroshi; Miyagishima, Takuto; Sasaki, Kazuaki; Nakamura, Michio; Ohsaki, Yoshinobu; Nakajima, Junta; Tateyama, Miki; Eto, Kazunori; Minami, Shinya; Yokoyama, Ryoji; Iwanaga, Ichiro; Shibuya, Hitoshi; Kudo, Mineo; Oba, Koji; Takahashi, Yasuo
2015-01-01
The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1–3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2–3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at −15% (study treatment group − control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1–3 (difference, 2.5%; 95% confidence interval [CI]: −7.8%–12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2–3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC. PMID:25872578
Kim, Min Jung; Hong, Chang Won; Kim, Byung Chang; Park, Sung Chan; Han, Kyung Su; Joo, Jungnam; Oh, Jae Hwan; Sohn, Dae Kyung
2016-01-01
Abstract The combination of different laxatives at reduced volumes may benefit patients by enhancing efficacy for bowel cleansing and increasing tolerability. However, evidence regarding combined preparations is scarce. This study evaluated whether the combined preparations are associated with enhanced efficacy and tolerability. This randomized phase II study had a single-blind, parallel-arm design. Between December 2013 and September 2014, consecutive patients aged between 20 and 65 years and who required diagnostic colonoscopies were considered for inclusion. Patients were randomly allocated into 4 arms: sodium picosulfate and magnesium citrate (PMC) and polyethylene glycol (PEG) with ascorbic acid in a day-prior (PMC-PEG-DP), PMC and oral sodium phosphate (NaP) in a day-prior (PMC-NaP-DP), PMC and PEG with ascorbic acid in a split-dose (PMC-PEG-SD), and PMC and oral NaP in a split-dose (PMC-NaP-SD). Primary endpoint was the Aronchick scale, and Ottawa scale results by colon segment, patients’ adverse gastrointestinal symptoms, and willingness to reuse the same agents were also recorded. Successful bowel preparation was defined as an “excellent” or “good” score on the Aronchick scale. A total of 236 patients were randomized and 229 patients received the planned colonoscopy. The rates of successful bowel preparation in the PMC-PEG-DP, PMC-NaP-DP, PMC-PEG-SD, and PMC-NaP-SD were 82.5%, 64.4%, 100%, and 100%, respectively. Excluding the failed PMC-NaP-DP group, all groups showed satisfactory rates of successful bowel preparation, and the mean Ottawa scores were significantly better in the PMC-PEG-SD and PMC-NaP-SD groups than in the PMC-PEG-DP group (P < 0.0001). The PMC-PEG-DP, PMC-NaP-DP, PMC-PEG-SD, and PMC-NaP-SD groups were similar in terms of rates of adverse gastrointestinal symptoms reported on a 5-point scale (P = 0.40) and willingness to reuse the same combined preparations (P = 0.55). PMC-PEG in a day-prior or split-dose and PMC
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.
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
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
Integrative radiogenomic analysis for multicentric radiophenotype in glioblastoma
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
Co-Existence of Multicentric Castleman's Disease and Kaposi's Sarcoma.
Yaghoobi, Reza; Pazyar, Nader; Tavakoli, Sadigheh
2015-01-01
Castleman's disease (CD) or giant lymph node hyperplasia is a rare disorder that can be unicentric or multicentric. Multicentric Castleman's disease (MCD) is manifested by generalized lymphadenopathy, hepatosplenomegaly, polyclonal hypergammaglobulinemia, hematological abnormality, and constitutional symptoms. Human herpesvirus 8 (HHV-8) infection is present in nearly 100% MCD associated with HIV-1 infection, but in about 50% of cases of HIV negative. Herein, we report a 77-year-old man with systemic involvement and skin lesions on the anterior aspect of both legs in the previous site of saphenous vein angioplasty. Co-existence of MCD with Kaposi's sarcoma (KS) led us to present this rare case. PMID:26120185
Dasatinib first-line: Multicentric Italian experience outside clinical trials.
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. PMID:26643920
Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis
Asher, Aliya; Fryze, Waldemar; Kozubski, Wojciech; Wagner, Frank; Aram, Jehan; Tanasescu, Radu; Korolkiewicz, Roman P.; Dirnberger-Hertweck, Maren; Steidl, Stefan; Libretto, Susan E.; Sprenger, Till; Radue, Ernst W.
2015-01-01
Objectives: To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity. Methods: In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infusion of placebo (n = 6) or MOR103 0.5 (n = 8), 1.0 (n = 8), or 2.0 (n = 9) mg/kg every 2 weeks for 10 weeks. Patients had to have ≤10 gadolinium (Gd)-enhancing brain lesions on T1-weighted MRI at baseline. The primary objective was safety. Results: Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The most frequent was nasopharyngitis. Between-group differences in TEAE numbers were small. There were no TEAE-related trial discontinuations, infusion-related reactions, or deaths. Nine patients experienced MS exacerbations: 3, 5, 1, and 0 patient(s) in the placebo, 0.5, 1.0, and 2.0 mg/kg groups, respectively. A few T1 Gd-enhancing lesions and/or new or enlarging T2 lesions indicative of inflammation were observed in all treatment groups. No clinically significant changes were observed in other clinical assessments or laboratory safety assessments. No anti-MOR103 antibodies were detected. PK evaluations indicated dose linearity with low/no drug accumulation over time. Conclusions: MOR103 was generally well-tolerated in patients with RRMS or SPMS. No evidence of immunogenicity was found. Classification of evidence: This phase 1b study provides Class I evidence that MOR103 has acceptable tolerability in patients with MS. PMID:26185773
Garcia-Manero, Guillermo; Jabbour, Elias; Borthakur, Gautam; Faderl, Stefan; Estrov, Zeev; Yang, Hui; Maddipoti, Sirisha; Godley, Lucy A.; Gabrail, Nashat; Berdeja, Jesus G.; Nadeem, Ahmed; Kassalow, Laurent; Kantarjian, Hagop
2013-01-01
Purpose This open-label, randomized phase II trial assessed efficacy and tolerability of two low-dose regimens of subcutaneous (SC) decitabine in patients with low- or intermediate-1–risk myelodysplastic syndrome (MDS). Patients and Methods Patients received decitabine 20 mg/m2 SC per day for 3 consecutive days on days 1, 2, and 3 every 28 days (schedule A) or 20 mg/m2 SC per day once every 7 days on days 1, 8, and 15 every 28 days (schedule B) for up to 1 year. Primary efficacy end point was overall improvement rate (OIR: complete remission [CR], partial remission [PR], marrow CR [mCR], or hematologic improvement [HI]). Secondary end points were HI, transfusion independence, cytogenetic response, overall survival (OS), and time to acute myeloid leukemia or death. Results Efficacy and safety populations were identical: schedule A, n = 43; schedule B, n = 22. Median time from MDS diagnosis to treatment was 3.6 months; 89% had de novo MDS. The trial was terminated early on achievement of protocol-defined OIR superiority of schedule A over schedule B; OIR was 23% for schedule A (seven CRs, three HIs) and 23% for schedule B (one mCR, one PR, three HIs). No differences were observed in secondary end points. Median OS was not reached; approximately 70% of patients were alive at 500 days. Patients in schedule A (67%) and schedule B (59%) were RBC/platelet independent on study. The most frequent drug-related adverse events overall were neutropenia (28% v 36%), anemia (23% v 18%), and thrombocytopenia (16% v 32%). Conclusion In this phase II study, low-dose decitabine showed promising results in patients with low- or intermediate-1–risk MDS. PMID:23733767
Cavity wounds management: a multicentre pilot study.
Meaume, Sylvie; Facy, Olivier; Munoz-Bongrand, Nicolas; Ribemont, Annie-Claude; Sigal, Michele-Lea; Couffinhal, Jean-Claude; Trial, Chloe; Tacca, Olivier; Bohbot, Serge
The objective of this study was to assess acceptability (based on pain at removal), efficacy and tolerance of an absorbent and cohesive rope(UrgoClean Rope, Laboratoires Urgo) in the local management of deep cavity wounds. This study was a prospective, multicentre (13), non comparative clinical study. Patients presenting with an acute or chronic non-infected cavity wound were followed up for four weeks and assessed weekly with a physical examination, in addition to volumetric,planimetric and photographic evaluations. Pain at removal was the primary criterion, assessed on a Visual Analogic Scale. The percentage of the wound surface area reduction and volumetric reduction were considered as secondary efficacy criteria. Forty three patients were included in this study. After one week of treatment dressing removal was painless and continued to be so throughout the period of the trial(four weeks). Median surface area at baseline was 7.74 cm2 and was reduced by 54.5% at week 4 (relative area reduction). Median wound volumetric value was noted 12 ml at baseline and was reduced by 72.7% by the end of treatment. The cohesiveness of the new rope was considered very good by health professionals. No residue was observed on the wound bed during the dressing change with the new rope. There were no adverse events related to the tested rope, during this trial.Pain-free removal associated with good efficacy and tolerance were observed with this new cohesive rope in the healing process of deep cavity wounds and could represent a therapeutic alternative to the usual ropes used in such indications. PMID:24180023
Bone marrow manifestations in multicentric Castleman disease.
Ibrahim, Hazem A H; Balachandran, Kirsty; Bower, Mark; Naresh, Kikkeri N
2016-03-01
This study aimed to document the morphological and immunophenotypic features, and describe the diagnostic features of bone marrow (BM) involvement in human herpes virus 8 Multicentric Castleman disease (HHV8-MCD). BM trephine biopsy (BMTB) specimens from 28 patients were revisited. Samples were evaluated for expression of CD3, CD20, CD138, CD68R, glycophorin C, CD42b, HHV8-latency-associated nuclear antigen (LANA1), Epstein-Barr virus-encoded small RNA and light chains. Presence of significant numbers of HHV8-LANA1(+) lymphoid/plasmacytic cells, noted in 10/28 cases, was indicative of BM involvement and was associated with low CD4 and CD8 counts in peripheral blood. The characteristic morphological appearance of MCD seen in lymph nodes is a rare finding in BMTB. 4/5 cases with lymphoid aggregates were involved by MCD, whereas 6/23 cases without lymphoid aggregates were involved by MCD (P = 0·023). 9/18 cases with hypercellular marrow were involved by MCD, whilst only 1/8 cases with normo/hypocellular marrow showed involvement by MCD (P = 0·070). While 9/21 cases with increased marrow reticulin were involved by MCD, none of the cases with no increase in reticulin were involved by MCD (P = 0·080). Reactive plasmacytosis is a frequent finding. We conclude that bone marrow is involved in a significant proportion of patients with MCD (36%), and involvement can be identified by HHV8-LANA1 immunohistochemistry. PMID:26817834
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. PMID:24212021
NASA Astrophysics Data System (ADS)
Cheoun, Myung-Ki; Ha, Eunja; Hayakawa, T.; Kajino, Toshitaka; Chiba, Satoshi
2010-09-01
The cosmological origins of the two heaviest odd-odd nuclei La138 and Ta180 are believed to be closely related to the neutrino process. We investigate in detail neutrino-induced reactions on the nuclei. Charged current (CC) reactions Ba138(νe,e-)La138 and Hf180(νe,e-)Ta180 are calculated using the standard quasi-particle random phase approximation (QRPA) with neutron-proton pairing as well as neutron-neutron and proton-proton pairing correlations. For the neutral current (NC) reactions La139(ν,ν')La139* and Ta181(ν,ν')Ta181*, we generate ground and excited states of the odd-even target nuclei La139 and Ta181 by operating one quasiparticle to even-even nuclei Ba138 and Hf180, which are assumed as the BCS ground state. Numerical results for CC reactions are shown to be consistent with recent semiempirical data deduced from the Gamow-Teller strength distributions measured in the (He3,t) reaction. Results for NC reactions are estimated to be about 4 to 5 times smaller than the results for CC reactions. Finally, cross sections weighted by the incident neutrino flux in the core-collapse supernova are presented for further applications to the network calculations for relevant nuclear abundances.
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.
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.
Kleinig, W.; Nesterenko, V. O.; Kvasil, J.; Vesely, P.; Reinhard, P.-G.
2008-10-15
The E1(T=1) isovector dipole giant resonance (GDR) in heavy and superheavy deformed nuclei is analyzed over a sample of 18 rare-earth nuclei, four actinides, and three chains of superheavy elements (Z=102, 114, and 120). The basis of the description is the self-consistent separable random-phase approximation (SRPA) using the Skyrme force SLy6. The model well reproduces the experimental data in the rare-earth and actinide regions. The trend of the resonance peak energies follows the estimates from collective models, showing a bias to the volume mode for the rare-earth isotopes and a mix of volume and surface modes for actinides and superheavy elements. The widths of the GDR are mainly determined by the Landau fragmentation, which in turn is found to be strongly influenced by deformation. A deformation splitting of the GDR can contribute to about one-third of the width, and about 1 MeV further broadening can be associated with mechanisms beyond the SRPA description (e.g., escape widths and coupling with complex configurations)
Heßelmann, Andreas
2015-04-14
Molecular excitation energies have been calculated with time-dependent density-functional theory (TDDFT) using random-phase approximation Hessians augmented with exact exchange contributions in various orders. It has been observed that this approach yields fairly accurate local valence excitations if combined with accurate asymptotically corrected exchange-correlation potentials used in the ground-state Kohn-Sham calculations. The inclusion of long-range particle-particle with hole-hole interactions in the kernel leads to errors of 0.14 eV only for the lowest excitations of a selection of three alkene, three carbonyl, and five azabenzene molecules, thus surpassing the accuracy of a number of common TDDFT and even some wave function correlation methods. In the case of long-range charge-transfer excitations, the method typically underestimates accurate reference excitation energies by 8% on average, which is better than with standard hybrid-GGA functionals but worse compared to range-separated functional approximations. PMID:26574370
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.
Technology Transfer Automated Retrieval System (TEKTRAN)
Background: BMS-275291 is a selective matrix metalloproteinase inhibitor (MMPI) that does not inhibit sheddases implicated in the dose-limiting arthritis of older MMPIs. We conducted a randomized phase II trail of two doses of BMS-275291 (1,200 versus 2,400 mg) in hormone-refractory prostate cancer ...
Phase diagram of the random-field Ising system Fe{sub 0.60}Zn{sub 0.40}F{sub 2} at intense fields
Montenegro, F.C.; Lima, K.A.; Torikachvili, M.S.; Lacerda, A.H.
1997-10-01
The critical and irreversibility phase boundaries of the d = 3 diluted uniaxial antiferromagnet Fe{sub 0.60}Zn{sub 0.40}F{sub 2} have been determined under strong external magnetic fields by means of magnetization measurements. The data reveal that the random-field-induced glassy phase, previously observed in the upper part of the (H,T) phase diagram for highly diluted samples (x {approx_equal} 0.3), is extended to higher values of x.
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
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
Berry, James D.; Shefner, Jeremy M.; Conwit, Robin; Schoenfeld, David; Keroack, Myles; Felsenstein, Donna; Krivickas, Lisa; David, William S.; Vriesendorp, Francine; Pestronk, Alan; Caress, James B.; Katz, Jonathan; Simpson, Ericka; Rosenfeld, Jeffrey; Pascuzzi, Robert; Glass, Jonathan; Rezania, Kourosh; Rothstein, Jeffrey D.; Greenblatt, David J.; Cudkowicz, Merit E.
2013-01-01
Objectives Ceftriaxone increases expression of the astrocytic glutamate transporter, EAAT2, which might protect from glutamate-mediated excitotoxicity. A trial using a novel three stage nonstop design, incorporating Phases I-III, tested ceftriaxone in ALS. Stage 1 determined the cerebrospinal fluid pharmacokinetics of ceftriaxone in subjects with ALS. Stage 2 evaluated safety and tolerability for 20-weeks. Analysis of the pharmacokinetics, tolerability, and safety was used to determine the ceftriaxone dosage for Stage 3 efficacy testing. Methods In Stage 1, 66 subjects at ten clinical sites were enrolled and randomized equally into three study groups receiving intravenous placebo, ceftriaxone 2 grams daily or ceftriaxone 4 grams daily divided BID. Participants provided serum and cerebrospinal fluid for pharmacokinetic analysis on study day 7. Participants continued their assigned treatment in Stage 2. The Data and Safety Monitoring Board (DSMB) reviewed the data after the last participants completed 20 weeks on study drug. Results Stage 1 analysis revealed linear pharmacokinetics, and CSF trough levels for both dosage levels exceeding the pre-specified target trough level of 1 µM (0.55 µg/mL). Tolerability (Stages 1 and 2) results showed that ceftriaxone at dosages up to 4 grams/day was well tolerated at 20 weeks. Biliary adverse events were more common with ceftriaxone but not dose-dependent and improved with ursodeoxycholic (ursodiol) therapy. Conclusions The goals of Stages 1 and 2 of the ceftriaxone trial were successfully achieved. Based on the pre-specified decision rules, the DSMB recommended the use of ceftriaxone 4 g/d (divided BID) for Stage 3, which recently closed. Trial Registration ClinicalTrials.gov NCT00349622. PMID:23613806
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
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
Joe, Andrew K; Schnoll-Sussman, Felice; Bresalier, Robert S; Abrams, Julian A; Hibshoosh, Hanina; Cheung, Ken; Friedman, Richard A; Yang, Chung S; Milne, Ginger L; Liu, Diane D; Lee, J Jack; Abdul, Kazeem; Bigg, Michelle; Foreman, Jessica; Su, Tao; Wang, Xiaomei; Ahmed, Aqeel; Neugut, Alfred I; Akpa, Esther; Lippman, Scott M; Perloff, Marjorie; Brown, Powel H; Lightdale, Charles J
2015-12-01
This study was conducted to determine the safety and efficacy of the green tea-derived Polyphenon E (Poly E) in patients with Barrett's Esophagus (BE). Subjects were randomized to a 6-month, twice daily (BID) oral treatment of placebo or Poly E (200, 400, or 600 mg). Endoscopic evaluation, including biopsies, was performed before and after treatment. The primary objective was to demonstrate safety; secondary objectives investigated catechin accumulation and effects in clinical specimens. Of the 44 enrolled subjects, 11 received placebo, and 33 received Poly E. No dose-limiting toxicities were encountered, and a maximum tolerated dose (MTD) was not reached. The recommended phase II dose was 600 mg twice daily. The most common treatment-related adverse events (AE) in Poly E-treated subjects were grade I and II nausea, grade I belching, and grade I lactate dehydrogenase (LDH) elevation. No treatment-related AEs were reported in placebo-treated subjects, aside from grade I laboratory abnormalities. Pill counts and subject diaries were not consistently collected, and compliance was difficult to determine. However, on the basis of an intention-to-treat analysis, there was a significant relationship between Poly E dose and esophageal EGCG level--mean changes (pmol/g) of 0.79 (placebo), 6.06 (200 mg), 35.67 (400 mg), and 34.95 (600 mg); P = 0.005. There was a possible relationship between Poly E dose and urine PGE-M concentration. In conclusion, Poly E was well-tolerated, and treatment with Poly E (400 and 600 mg) but not Poly E (200 mg) or placebo resulted in clinically relevant and detectable EGCG accumulation in the target organ, esophageal mucosa. PMID:26471236
Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033
Tran, Jonathan Q.; Rana, Jitesh; Barkhof, Frederik; Melamed, Isaac; Gevorkyan, Hakop; Wattjes, Mike P.; de Jong, Remko; Brosofsky, Kristin; Ray, Soma; Xu, Lei; Zhao, Jim; Parr, Edward
2014-01-01
Objective: To evaluate the safety, tolerability, and pharmacokinetics (PK) of BIIB033 (anti-LINGO-1 monoclonal antibody) in healthy volunteers and participants with multiple sclerosis (MS). Methods: In 2 separate randomized, placebo-controlled studies, single ascending doses (SAD; 0.1–100 mg/kg) of BIIB033 or placebo were administered via IV infusion or subcutaneous injection to 72 healthy volunteers, and multiple ascending doses (MAD; 0.3–100 mg/kg; 2 doses separated by 14 days) of BIIB033 or placebo were administered via IV infusion to 47 participants with relapsing-remitting or secondary progressive MS. Safety assessments included adverse event (AE) monitoring, neurologic examinations, conventional and nonconventional MRI, EEG, optical coherence tomography, retinal examinations, and evoked potentials. Serum and CSF PK as well as the immunogenicity of BIIB033 were also evaluated. Results: All 72 healthy volunteers and 47 participants with MS were included in the safety analyses. BIIB033 infusions were well tolerated. The frequency of AEs was similar between BIIB033 and placebo. There were no serious AEs or deaths. No clinically significant changes in any of the safety measures were observed. BIIB033 PK was similar between healthy volunteers and participants with MS. Doses of ≥10 mg/kg resulted in BIIB033 concentrations similar to or higher than the concentration associated with 90% of the maximum remyelination effect in rat remyelination studies. The incidence of anti-drug antibody production was low. Conclusions: The emerging safety, tolerability, and PK of BIIB033 support advancing BIIB033 into phase II clinical development as a potential treatment for CNS demyelination disorders. Classification of evidence: This study provides Class I evidence that BIIB033 is well tolerated and safe (serious adverse event rate 0%, 95% confidence interval 0–7.6%). PMID:25340070
Sperk, Elena; Welzel, Grit; Keller, Anke; Kraus-Tiefenbacher, Uta; Gerhardt, Axel; Sütterlin, Marc; Wenz, Frederik
2012-08-01
The randomized phase III trial TARGIT A showed non-inferiority regarding local control after intraoperative radiotherapy (IORT 20 Gy which was followed by whole breast radiotherapy (WBRT) in patients with risk factors only) in comparison to standard WBRT (50-56 Gy) after breast-conserving surgery in selected patients. This is the first analysis of long-term toxicities in the setting of TARGIT. Between 02/2002 and 12/2008, 305 patients were treated within TARGIT A (Arm A: n = 34 IORT, n = 20 IORT + WBRT for risk factors; Arm B WBRT: n = 55) or received IORT as a planned boost (control group: n = 196) at a single center. Toxicity was assessed according to the LENT SOMA scales. No significant differences were seen between Arm A and Arm B regarding fibrosis, breast edema, retraction, ulceration, lymphedema, hyperpigmentation, and pain. Arm A had significantly less telangiectases compared to Arm B (p = 0.049). In the subanalysis (Arm A IORT vs. Arm A IORT + WBRT vs. Arm B), fibrosis had a cumulative rate of 5.9 versus 37.5 versus 18.4 %, respectively (38.2 % IORT boost control group), at 3 years. No telangiectases were seen after IORT alone (0 % Arm A IORT vs. 17.5 % Arm A IORT + WBRT vs. 17.7 % Arm B). The hazard ratio of higher grade toxicity as first event was 0.46 (95 % CI, 0.26-0.83) for Arm A IORT as compared to Arm B (p = 0.010). No recurrences were seen after a median follow-up of 40 months (Arm A) and 42 months (Arm B). With its very low chronic skin toxicity rates and outstanding long-term results regarding toxicity and local control, IORT with 50 kV X-rays is a safe and effective method for treatment of selected breast cancer patients. PMID:22842984
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.
Mcgowan, Ian; Hoesley, Craig; Cranston, Ross D.; Andrew, Philip; Janocko, Laura; Dai, James Y.; Carballo-Dieguez, Alex; Ayudhya, Ratiya Kunjara Na; Piper, Jeanna; Hladik, Florian; Mayer, Ken
2013-01-01
Objective Rectal microbicides are needed to reduce the risk of HIV acquisition associated with unprotected receptive anal intercourse. The MTN-007 study was designed to assess the safety (general and mucosal), adherence, and acceptability of a new reduced glycerin formulation of tenofovir 1% gel. Methods Participants were randomized 1∶1:1∶1 to receive the reduced glycerin formulation of tenofovir 1% gel, a hydroxyethyl cellulose placebo gel, a 2% nonoxynol-9 gel, or no treatment. Each gel was administered as a single dose followed by 7 daily doses. Mucosal safety evaluation included histology, fecal calprotectin, epithelial sloughing, cytokine expression (mRNA and protein), microarrays, flow cytometry of mucosal T cell phenotype, and rectal microflora. Acceptability and adherence were determined by computer-administered questionnaires and interactive telephone response, respectively. Results Sixty-five participants (45 men and 20 women) were recruited into the study. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability) was 87% (reduced glycerin formulation of tenofovir 1% gel), 93% (hydroxyethyl cellulose placebo gel), and 63% (nonoxynol-9 gel). Fecal calprotectin, rectal microflora, and epithelial sloughing did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the nonoxynol-9 gel and other study arms. Conclusions The reduced glycerin formulation of tenofovir 1% gel was safe and well tolerated rectally and should be advanced to Phase 2 development. Trial Registration ClinicalTrials.gov NCT01232803. PMID:23573238
Gambacurta, D.; Catara, F.
2011-09-15
Low-energy dipole excitations are analyzed for the stable isotopes {sup 40}Ca and {sup 48}Ca in the framework of the Skyrme-second random-phase approximation. The corresponding random-phase approximation calculations provide a negligible strength distribution for both nuclei in the energy region from 5 to 10 MeV. The inclusion and the coupling of 2 particle-2 hole configurations in the second random-phase approximation lead to an appreciable dipole response at low energies for the neutron-rich nucleus {sup 48}Ca. The presence of a neutron skin in the nucleus {sup 48}Ca would suggest the interpretation of the low-lying response in terms of a pygmy excitation. The composition of the excitation modes (content of 1 particle-1 hole and 2 particle-2 hole configurations), their transition densities and their collectivity (number and coherence of the different contributions) are analyzed. This analysis indicates that, in general, these excitations cannot be clearly interpreted in terms of oscillations of the neutron skin against the core with the exception of the peak with the largest B(E1) value, which is located at 9.09 MeV. For this peak the neutron transition density dominates and the neutron and proton transition densities oscillate out of phase in the internal part of the nucleus leading to a strong mixing of isoscalar and isovector components. Therefore, this state shows some features usually associated to pygmy resonances.
Ye, Yanrui; Xu, Hang; Quan, Lei; Zhu, Long; Zeng, Jing; Zhou, Ting; Zou, ChengJuan; Cheng, Qing; Bu, Shujie; Tan, Wen
2015-01-01
Background Existing treatments are inadequate for patients at high risk of coronary heart disease caused by elevated levels of plasma low-density lipoprotein cholesterol (LDL-C). Bambuterol is a prodrug of β2-agonist commonly used for the treatment of asthma and chronic obstructive pulmonary disease (COPD) with the advantage of once daily dosing and favorable side effect profile. The potential lipid-lowering effects of bambuterol were unclear, possibly due to the racemic bambuterol (rac-bambuterol) that was used in previous studies. Methods The lipid-lowering effects of R-bambuterol were examined in a randomized phase I trial in 48 healthy Chinese volunteers aged 18–45 years. Participants were randomly assigned to five groups to receive a single dose (2.5 mg, 5 mg or 10 mg) or multiple doses (5 mg) of oral medications of R-bambuterol, or a single dose of rac-bambuterol (10 mg). Plasma lipid levels were measured at baseline, time to peak concentration (Tmax) and 24 h after the treatment. Findings Administration of a single-dose of R-bambuterol resulted in dose-dependent reductions in the levels of plasma LDL-C, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) at Tmax. Levels of LDL-C exhibited the most reductions, which were statistically significant in all three single-dose R-bambuterol groups (all P values < 0.05). R-bambuterol was more potent in LDL-C lowering compared to rac-bambuterol at Tmax (P = 0.08). At 24 h after dosing, the significant lipid lowering effects of R-bambuterol sustained for LDL-C (P = 0.01), ApoB (P = 0.001) and ApoA1 (P = 0.03), but not for HDL-C. The ratio of ApoA1/ApoB was marginally increased (P = 0.06). In the multiple-dose group, LDL-C levels again were significantly reduced (all P values < 0.05), whereas the ratios of ApoA1/ApoB were marginally increased. Interpretation R-bambuterol can lower the plasma levels of LDL-C, and marginally
2013-01-01
Background Clinical trials in traumatic brain injury (TBI) are challenging. Previous trials of complex interventions were conducted in high-income countries, reported long lead times for site setup and low screened-to-recruitment rates. In this report we evaluate the internal pilot phase of an international, multicentre TBI trial of a complex intervention to assess: design and implementation of an online case report form; feasibility of recruitment (sites and patients); feasibility and effectiveness of delivery of the protocol. Methods All aspects of the pilot phase of the trial were conducted as for the main trial. The pilot phase had oversight by independent Steering and Data Monitoring committees. Results Forty sites across 12 countries gained ethical approval. Thirty seven of 40 sites were initiated for recruitment. Of these, 29 had screened patients and 21 randomized at least one patient. Lead times to ethics approval (6.8 weeks), hospital approval (18 weeks), interest to set up (61 weeks), set up to screening (11 weeks), and set up to randomization (31.6 weeks) are comparable with other international trials. Sixteen per cent of screened patients were eligible. We found 88% compliance rate with trial protocol. Conclusion The pilot data demonstrated good feasibility for this large international multicentre randomized controlled trial of hypothermia to control intracranial pressure. The sample size was reduced to 600 patients because of homogeneity of the patient group and we showed an optimized cooling intervention could be delivered. Trial registration Current Controlled Trials: ISRCTN34555414. PMID:24004918
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
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
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.
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.
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.
Randomized phase 2 trial of NP001–a novel immune regulator: Safety and early efficacy in ALS
Block, Gilbert; Katz, Jonathan S.; Barohn, Richard J.; Gopalakrishnan, Vidhya; Cudkowicz, Merit; Zhang, Jane R.; McGrath, Michael S.; Ludington, Elizabeth; Appel, Stan H.; Azhir, Ari
2015-01-01
Objective: To assess the safety, tolerability, and preliminary efficacy of NP001, a novel immune regulator of inflammatory monocytes/macrophages, for slowing progression of amyotrophic lateral sclerosis (ALS). Methods: This was a phase 2 randomized, double-blind, placebo-controlled trial of NP001 in 136 patients with ALS of <3 years' duration and forced vital capacity ≥70%. Participants received NP001 2 mg/kg, NP001 1 mg/kg, or placebo for 6 months. Safety, tolerability, and inflammatory biomarkers were assessed throughout the study. Preliminary efficacy was evaluated using the ALS Functional Rating Scale-Revised (ALSFRS-R) slope and change from baseline, with and without matched historical placebo controls, after 6 months of treatment. A post hoc analysis of the percentage of patients (“responders”) whose ALSFRS-R did not change from baseline was also conducted. Results: NP001 was generally safe and well-tolerated, except for infusion site pain and dizziness. No significant slowing of decline in the primary or secondary measures was observed. However, slowing of progression was observed in the high-dose group in patients with greater inflammation (wide range C-reactive protein). Moreover, NP001 may have dose dependently halted symptom progression in a subset of patients. More than 2 times as many patients on high-dose NP001 (25%) did not progress during 6 months of treatment compared with those on placebo (11%). Most “responders” had an elevated biomarker of inflammation, interleukin-18, and were positive for lipopolysaccharide at baseline, which decreased after treatment with NP001. Conclusion: The arresting of progression of ALS symptoms by NP001 in a subset of patients with marked neuroinflammation, as observed here, will represent a novel therapeutic approach for patients with ALS, if confirmed. Classification of evidence: This study provides Class I evidence that for patients with ALS, NP001 is safe and did not significantly slow progression of the
Winer, Eric S; Safran, Howard; Karaszewska, Boguslawa; Richards, Donald A; Hartner, Lee; Forget, Frederic; Ramlau, Rodryg; Kumar, Kirushna; Mayer, Bhabita; Johnson, Brendan M; Messam, Conrad A; Mostafa Kamel, Yasser
2015-01-01
Preventing chemotherapy-induced thrombocytopenia could avoid chemotherapy dose reductions and delays. The safety and maximum tolerated dose of eltrombopag, an oral thrombopoietin receptor agonist, with gemcitabine-based therapy was evaluated. Patients with advanced solid tumors and platelets ≤300 × 10(9) /L receiving gemcitabine plus cisplatin or carboplatin (Group A) or gemcitabine monotherapy (Group B) were randomized 3:1 to receive eltrombopag or placebo at a starting dose of 100 mg daily administered on days -5 to -1 and days 2-6 starting from cycle 2 of treatment. Nineteen patients (Group A, n = 9; Group B, n = 10) received eltrombopag 100 mg and seven (Group A, n = 3; Group B, n = 4) received matching placebo. Nine eltrombopag patients in Group A and eight in Group B had 38 and 54 occurrences of platelet counts ≥400 × 10(9) /L, respectively. Mean platelet nadirs across cycles 2-6 were 115 × 10(9) /L and 143 × 10(9) /L for eltrombopag-treated patients versus 53 × 10(9) /L and 103 × 10(9) /L for placebo-treated patients in Groups A and B, respectively. No dose-limiting toxicities were reported for eltrombopag; however, due to several occurrences of thrombocytosis, a decision was made not to dose-escalate eltrombopag to >100 mg daily. In Groups A and B, 14% of eltrombopag versus 50% of placebo patients required chemotherapy dose reductions and/or delays for any reason across cycles 3-6. Eltrombopag 100 mg once daily administered 5 days before and after day 1 of chemotherapy was well tolerated with an acceptable safety profile, and will be further tested in a phase II trial. Fewer patients receiving eltrombopag required chemotherapy dose delays and/or reductions compared with those receiving placebo. PMID:25165041
A developmental hypothesis to explain the multicentricity of breast cancer.
Sharpe, C R
1998-07-14
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
A developmental hypothesis to explain the multicentricity of breast cancer
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
Multicentric osteosarcoma presenting as retrobulbar mass: a diagnostic enigma.
Wong, K F; Shu, S J; Luk, I S C; Yuen, H L; Leung, J N S; Chan, J K C
2006-06-01
Osteosarcoma is the most common primary malignant bone tumor of children and adolescents. It often presents as a solitary lesion; multicentric osteosarcoma with synchronous lesions occurring at multiple skeletal sites is very rare. We report a 9-year-old boy with multicentric osteosarcoma who presented with a left retrobulbar non-sclerotic mass. The multiple lesions in bone were mostly non-sclerotic on radiological examination except for a single lesion in the left tibia. Biopsy of the retrobulbar mass showed an unclassifiable poorly differentiated malignant tumor. Marrow aspiration smears showed many large, often segregated, round cells that expressed NB84a. However, trephine biopsy showed the formation of tumoral osteoid by the malignant cells, finally permitting the definitive diagnosis of osteosarcoma to be made. A hypertetraploid clone with complex structural abnormalities was demonstrated by cytogenetic study. PMID:15926165
Di Maio, Massimo; Bironzo, Paolo; Scagliotti, Giorgio Vittorio
2016-02-01
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
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.
NASA Astrophysics Data System (ADS)
Piri, Mohammad; Blunt, Martin J.
2005-02-01
We use the model described in Piri and Blunt [Phys. Rev. E 71, 026301 (2005)] to predict two- and three-phase relative permeabilities of Berea sandstone using a random network to represent the pore space. We predict measured relative permeabilities for two-phase flow in a water-wet system. We then successfully predict the steady-state oil, water, and gas three-phase relative permeabilities measured by Oak (Proceedings of the SPE/DOE Seventh Symposium on Enhanced Oil Recovery, Tulsa, OK, 1990). We also study secondary and tertiary gas injection into media of different wettability and initial oil saturation and interpret the results in terms of pore-scale displacement processes.
Piri, Mohammad; Blunt, Martin J
2005-02-01
We use the model described in Piri and Blunt [Phys. Rev. E 71, 026301 (2005)] to predict two- and three-phase relative permeabilities of Berea sandstone using a random network to represent the pore space. We predict measured relative permeabilities for two-phase flow in a water-wet system. We then successfully predict the steady-state oil, water, and gas three-phase relative permeabilities measured by Oak (Proceedings of the SPE/DOE Seventh Symposium on Enhanced Oil Recovery, Tulsa, OK, 1990). We also study secondary and tertiary gas injection into media of different wettability and initial oil saturation and interpret the results in terms of pore-scale displacement processes. PMID:15783414
Yura, H T; Thrane, L; Andersen, P E
2000-12-01
Within the paraxial approximation, a closed-form solution for the Wigner phase-space distribution function is derived for diffuse reflection and small-angle scattering in a random medium. This solution is based on the extended Huygens-Fresnel principle for the optical field, which is widely used in studies of wave propagation through random media. The results are general in that they apply to both an arbitrary small-angle volume scattering function, and arbitrary (real) ABCD optical systems. Furthermore, they are valid in both the single- and multiple-scattering regimes. Some general features of the Wigner phase-space distribution function are discussed, and analytic results are obtained for various types of scattering functions in the asymptotic limit s > 1, where s is the optical depth. In particular, explicit results are presented for optical coherence tomography (OCT) systems. On this basis, a novel way of creating OCT images based on measurements of the momentum width of the Wigner phase-space distribution is suggested, and the advantage over conventional OCT images is discussed. Because all previous published studies regarding the Wigner function are carried out in the transmission geometry, it is important to note that the extended Huygens-Fresnel principle and the ABCD matrix formalism may be used successfully to describe this geometry (within the paraxial approximation). Therefore for completeness we present in an appendix the general closed-form solution for the Wigner phase-space distribution function in ABCD paraxial optical systems for direct propagation through random media, and in a second appendix absorption effects are included. PMID:11140505
NASA Astrophysics Data System (ADS)
Kaminsky, William; Lloyd, Seth
2006-03-01
We argue theoretically that adiabatic quantum computation using only polynomial resources can solve almost all members of a nontrivial randomly generated set of NP-complete problem instances, namely the problem of finding the ground states of spin glasses on 3D cubic lattices having independent, identically Gaussian-distributed couplings. The argument uses the droplet model of quantum spin glasses, particularly its prediction that the paramagnet-spin glass transition is unstable to even infinitesimal longitudinal fields. We then review the ongoing debate as to how well the droplet model describes 3D spin glasses and note that those inclined to view the intractability of NP-complete problems as a guiding physical intuition could take the results presented here as justifying greater suspicion toward the droplet model. Finally, due to this uncertainty as well as uncertainty in regard to the typical case classical complexity of this random NP-complete problem, we outline work using rigorous mean-field methods on a NP-complete problem whose typical-case classical complexity on random instances is better established, namely MAX CLIQUE on random graphs.
Twelves, Chris; Awada, Ahmad; Cortes, Javier; Yelle, Louise; Velikova, Galina; Olivo, Martin S.; Song, James; Dutcus, Corina E.; Kaufman, Peter A.
2016-01-01
PURPOSE AND METHODS Our secondary analyses compared survival with eribulin versus capecitabine in various patient subgroups from a phase 3, open-label, randomized study. Eligible women aged ≥18 years with advanced/metastatic breast cancer and ≤3 prior chemotherapies (≤2 for advanced/metastatic disease), including an anthracycline and taxane, were randomized 1:1 to intravenous eribulin mesylate 1.4 mg/m2 on days 1 and 8 or twice-daily oral capecitabine 1250 mg/m2 on days 1–14 (21-day cycles). RESULTS In the intent-to-treat population (eribulin 554 and capecitabine 548), overall survival appeared longer with eribulin than capecitabine in various subgroups, including patients with human epidermal growth factor receptor 2-negative (15.9 versus 13.5 months, respectively), estrogen receptor-negative (14.4 versus 10.5 months, respectively), and triple-negative (14.4 versus 9.4 months, respectively) disease. Progression-free survival was similar between the treatment arms. CONCLUSIONS Patients with advanced/metastatic breast cancer and human epidermal growth factor receptor 2-, estrogen receptor-, or triple-negative disease may gain particular benefit from eribulin as first-, second-, and third-line chemotherapies. TRIAL REGISTRATION (PRIMARY STUDY) This study reports the subgroup analyses of eribulin versus capecitabine from a phase 3, open-label, randomized study (www.clinicaltrials.gov; ClinicalTrials.gov identifier: NCT00337103). PMID:27398025
Ghosh, Arijit; Jana, Utpal; Khaowas, Ajoy; Das, Saumik; Mandal, Ananya; Das, Nina
2012-01-01
Objective: To compare the effectiveness and safety of cefpodoxime and ciprofloxacin for the treatment of mild to moderate cases of acute exacerbation of chronic suppurative otitis media (AECSOM). Materials and Methods: Adult patients diagnosed with AECSOM were screened and patients fulfilling the inclusion criteria were randomized to receive either cefpodoxime 200 mg twice daily or ciprofloxacin 500 mg twice daily orally for 7 days. The primary outcome of this randomized, open-labeled, phase IV clinical trial (Registration Number - CTRI/2011/10/002079) was clinical success rate at day 14 visit and the secondary outcome was incidence of adverse events (AEs). Forty-six patients were enrolled: 23 in the cefpodoxime group and 23 in the ciprofloxacin group. Results: The clinical success rates were 95.6% in the cefpodoxime group versus 90.9% in the ciprofloxacin group. These rates are comparable, but no statistically significant difference was observed between the groups. Few mild and self-limiting AEs were observed and the tolerability of both the drugs was also good. Conclusion: The results of this randomized, open-labeled phase IV clinical trial showed that a 7-day course of cefpodoxime is therapeutically comparable to ciprofloxacin in terms of both clinical effectiveness and safety for the treatment of patients with AECSOM. PMID:23326103
NASA Astrophysics Data System (ADS)
Piri, Mohammad; Blunt, Martin J.
2005-02-01
We present a three-dimensional network model to simulate two- and three-phase capillary dominated processes at the pore level. The displacement mechanisms incorporated in the model are based on the physics of multiphase flow observed in micromodel experiments. All the important features of immiscible fluid flow at the pore scale, such as wetting layers, spreading layers of the intermediate-wet phase, hysteresis, and wettability alteration are implemented in the model. Wettability alteration allows any values for the advancing and receding oil-water, gas-water, and gas-oil contact angles to be assigned. Multiple phases can be present in each pore or throat (element), in wetting and spreading layers, as well as occupying the center of the pore space. In all, some 30 different generic fluid configurations for two- and three-phase flow are analyzed. Double displacement and layer formation are implemented as well as direct two-phase displacement and layer collapse events. Every element has a circular, square, or triangular cross section. A random network that represents the pore space in Berea sandstone is used in this study. The model computes relative permeabilities, saturation paths, and capillary pressures for any displacement sequence. A methodology to track a given three-phase saturation path is presented that enables us to compare predicted and measured relative permeabilities on a point-by-point basis. A robust displacement-based clustering algorithm is also presented.
Piri, Mohammad; Blunt, Martin J
2005-02-01
We present a three-dimensional network model to simulate two- and three-phase capillary dominated processes at the pore level. The displacement mechanisms incorporated in the model are based on the physics of multiphase flow observed in micromodel experiments. All the important features of immiscible fluid flow at the pore scale, such as wetting layers, spreading layers of the intermediate-wet phase, hysteresis, and wettability alteration are implemented in the model. Wettability alteration allows any values for the advancing and receding oil-water, gas-water, and gas-oil contact angles to be assigned. Multiple phases can be present in each pore or throat (element), in wetting and spreading layers, as well as occupying the center of the pore space. In all, some 30 different generic fluid configurations for two- and three-phase flow are analyzed. Double displacement and layer formation are implemented as well as direct two-phase displacement and layer collapse events. Every element has a circular, square, or triangular cross section. A random network that represents the pore space in Berea sandstone is used in this study. The model computes relative permeabilities, saturation paths, and capillary pressures for any displacement sequence. A methodology to track a given three-phase saturation path is presented that enables us to compare predicted and measured relative permeabilities on a point-by-point basis. A robust displacement-based clustering algorithm is also presented. PMID:15783413
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.
Yong, Dingyu; He, Haiyan; Su, Longxing; Zhu, Yuan; Tang, Zikang; Zeng, Xiao Cheng; Pan, Bicai
2015-06-01
The usage of a BexZn1-xO alloy in ultraviolet (UV)-region optoelectronic devices is largely hindered by its intricate phase segregation of crystallites of different sizes. To understand the physical origin of this phase segregation phenomenon on the atomistic scale, we have undertaken an extensive study of the structural evolution of the segregation phases in the BexZn1-xO alloy at finite temperatures by using first-principles calculations combined with the cluster expansion approach. We find that a random alloy of BexZn1-xO tends to segregate into a mix-ordered phase below a critical temperature, by the growth of prototype and nano-sized structures. The segregated phases in BexZn1-xO entail not only ZnO or BeO crystallites, but also two as yet unreported phases with beryllium concentration of 1/3 and 2/3. Both new phases of BexZn1-xO are direct wide-gap semiconductors with band gap values of 4.88 eV and 6.78 eV respectively. We envisioned that the novel Be1/3Zn2/3O crystal is highly promising for solar-blind device applications. PMID:25966302
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.