Science.gov

Sample records for 10-day sequential regimen

  1. Advanced neuroblastoma: improved response rate using a multiagent regimen (OPEC) including sequential cisplatin and VM-26.

    PubMed

    Shafford, E A; Rogers, D W; Pritchard, J

    1984-07-01

    Forty-two children, all over one year of age, were given vincristine, cyclophosphamide, and sequentially timed cisplatin and VM-26 (OPEC) or OPEC and doxorubicin (OPEC-D) as initial treatment for newly diagnosed stage III or IV neuroblastoma. Good partial response was achieved in 31 patients (74%) overall and in 28 (78%) of 36 patients whose treatment adhered to the chemotherapy protocol, compared with a 65% response rate achieved in a previous series of children treated with pulsed cyclophosphamide and vincristine with or without doxorubicin. Only six patients, including two of the six children whose treatment did not adhere to protocol, failed to respond, but there were five early deaths from treatment-related complications. Tumor response to OPEC, which was the less toxic of the two regimens, was at least as good as tumor response to OPEC-D. Cisplatin-induced morbidity was clinically significant in only one patient and was avoided in others by careful monitoring of glomerular filtration rate and hearing. Other centers should test the efficacy of OPEC or equivalent regimens in the treatment of advanced neuroblastoma.

  2. Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia

    PubMed Central

    Mohty, Mohamad; Malard, Florent; Blaise, Didier; Milpied, Noel; Socié, Gérard; Huynh, Anne; Reman, Oumédaly; Yakoub-Agha, Ibrahim; Furst, Sabine; Guillaume, Thierry; Tabrizi, Resa; Vigouroux, Stéphane; Peterlin, Pierre; El-Cheikh, Jean; Moreau, Philippe; Labopin, Myriam; Chevallier, Patrice

    2017-01-01

    The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients’ outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33–71) at 1 year and 38% (95% CI: 18–46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26–64) at 1 year and 29% (95% CI: 13–48) at 2 years. The cumulative incidence of non-relapse mortality was 8% (95% CI: 1–24) at 1 year and 12% (95% CI: 3–19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174. PMID:27561720

  3. A sequential treatment regimen with melatonin and all-trans retinoic acid induces apoptosis in MCF-7 tumour cells.

    PubMed Central

    Eck, K. M.; Yuan, L.; Duffy, L.; Ram, P. T.; Ayettey, S.; Chen, I.; Cohn, C. S.; Reed, J. C.; Hill, S. M.

    1998-01-01

    Neoplastic events are marked by uncontrolled cell proliferation. One major focus of cancer research has been to identify treatments that reduce or inhibit cell growth. Over the years, various compounds, both naturally occurring and chemically synthesized, have been used to inhibit neoplastic cell proliferation. Two such oncostatic agents, melatonin and retinoic acid, have been shown to suppress the growth of hormone-responsive breast cancer. Currently, separate clinical protocols exist for the administration of retinoids and melatonin as adjuvant therapies for cancer. Using the oestrogen receptor (ER)-positive MCF-7 human breast tumour cell line, our laboratory has studied the effects of a sequential treatment regimen of melatonin followed by all-trans retinoic acid (atRA) on breast tumour cell proliferation in vitro. Incubation of hormonally responsive MCF-7 and T47D cells with melatonin (10(-9) M) followed 24 h later by atRA (10(-9) M) resulted in the complete cessation of cell growth as well as a reduction in the number of cells to below the initial plating density. This cytocidal effect is in contrast to the growth-suppressive effects seen with either hormone alone. This regimen of melatonin followed by atRA induced cytocidal effects on MCF-7 cells by activating pathways leading to apoptosis (programmed cell death) as evidenced by decreased ER and Bcl-2 and increased Bax and transforming growth factor beta 1 (TGF-beta1) expression. Apoptosis was reflected morphologically by an increase in the number of lysosomal bodies and perinuclear chromatin condensation, cytoplasmic blebbing and the presence of apoptotic bodies. The apoptotic effect of this sequential treatment with melatonin and atRA appears to be both cell and regimen specific as (a) ER-negative MDA-MB-231 and BT-20 breast tumour cells were unaffected, and (b) the simultaneous administration of melatonin and atRA was not associated with apoptosis in any of the breast cancer cell lines studied. Taken

  4. Modified Sequential Therapy Regimen versus Conventional Triple Therapy for Helicobacter Pylori Eradication in Duodenal Ulcer Patients in China: A Multicenter Clinical Comparative Study

    PubMed Central

    Zhou, Ying-Qun; Xu, Ling; Wang, Bing-Fang; Fan, Xiao-Ming; Wu, Jian-Ye; Wang, Chun-Yan; Guo, Chuan-Yong; Xu, Xuan-Fu

    2012-01-01

    Objective. Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. To observe the effect of eradicating Helicobacter pylori (H. pylori) and the treatment of duodenal ulcer by 2 kinds of modified sequential therapy through comparing with that of 10-day standard triple therapy. Methods. A total of 210 patients who were confirmed in duodenal ulcer active or heal period by gastroscopy and H. pylori positive confirmed by rapid urease test, serum anti-H. pylori antibody (ELASE), or histological examination enrolled in the study. All the patients were randomly divided into three groups: group A (70 cases) and group B (70 cases) were provided 10-day modified sequential therapy; group C (70 cases) was provided 10-day standard triple therapy. Patients of group A received 20 mg of Esomeprazole, 500 mg of Clarithromycin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group B received 20 mg of Esomeprazole, 1000 mg of Amoxicillin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group C received 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for standard 10-day therapy. All drugs were given twice daily. H. pylori eradication rate was checked four to eight weeks after taking the medicine by using a 13C urea breath test. In the first, second, third, seventh, twenty-first, thirty-fifth days respectively, the symptoms of patients such as epigastric gnawing, burning pain, and acidity were evaluated simultaneously. Results. Overall, 210 patients accomplished all therapy schemes, 9 case patients were excluded. The examination result indicated that the H. pylori eradication rate of each group was as follows: group A 92.5% (62/67), group B 86.8% (59/68), and group C 78.8% (52/66). The H. pylori eradication rate of

  5. Results of autologous transplantation in lymphoma are not improved by increasing the dose of etoposide in the BEAM regimen: a single-centre sequential-cohort study.

    PubMed

    Martín, A; Caballero, M D; Pérez-Simón, J A; López-Holgado, N; Mateos, M V; Cañizo, M C; Miguel, J F San

    2004-10-01

    We have undertaken a retrospective sequential-cohort analysis of 131 lymphoma patients treated with the BEAM regimen and autologous stem cell transplantation, to compare BEAM at standard doses (sBEAM; n = 67 from May 1990 to April 1995) and BEAM with escalated etoposide dose from 800 to 1600 mg/m(2) (eBEAM; n = 64 from May 1995 to June 1999). Transplant-related mortality and incidence of secondary malignancies were similar in both groups. Disease progression was significantly lower in indolent lymphoma (IL) patients receiving eBEAM (7 vs 43%), although survival was comparable due to a higher toxic mortality in the eBEAM group. The 5-year event-free survival and overall survival were better in Hodgkin's disease (HD) patients treated with eBEAM (70 and 77%, respectively) compared to sBEAM (58 and 69%, respectively), but the difference was not statistically significant. In aggressive lymphomas, no difference was detected between groups. Our results indicate that while escalation of the etoposide doses in the BEAM conditioning regimen does not appear to improve outcome, encouraging results in IL and HD may warrant further studies.

  6. 28 CFR 5.801 - Activity beyond 10-day period.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Activity beyond 10-day period. 5.801... AGENTS REGISTRATION ACT OF 1938, AS AMENDED § 5.801 Activity beyond 10-day period. A registrant who has within the 10-day period filed an amendment to his registration statement pursuant to a Notice...

  7. 28 CFR 5.801 - Activity beyond 10-day period.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Activity beyond 10-day period. 5.801... AGENTS REGISTRATION ACT OF 1938, AS AMENDED § 5.801 Activity beyond 10-day period. A registrant who has within the 10-day period filed an amendment to his registration statement pursuant to a Notice...

  8. 28 CFR 5.801 - Activity beyond 10-day period.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Activity beyond 10-day period. 5.801... AGENTS REGISTRATION ACT OF 1938, AS AMENDED § 5.801 Activity beyond 10-day period. A registrant who has within the 10-day period filed an amendment to his registration statement pursuant to a Notice...

  9. 28 CFR 5.801 - Activity beyond 10-day period.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Activity beyond 10-day period. 5.801... AGENTS REGISTRATION ACT OF 1938, AS AMENDED § 5.801 Activity beyond 10-day period. A registrant who has within the 10-day period filed an amendment to his registration statement pursuant to a Notice...

  10. 28 CFR 5.801 - Activity beyond 10-day period.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Activity beyond 10-day period. 5.801... AGENTS REGISTRATION ACT OF 1938, AS AMENDED § 5.801 Activity beyond 10-day period. A registrant who has within the 10-day period filed an amendment to his registration statement pursuant to a Notice...

  11. Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

    PubMed

    Závada, J; Sinikka Pesicková, S; Rysavá, R; Horák, P; Hrncír, Z; Lukác, J; Rovensky, J; Vítová, J; Havrda, M; Rychlík, I; Böhmova, J; Vlasáková, V; Slatinská, J; Zadrazil, J; Olejárová, M; Tegzova, D; Tesar, V

    2014-01-01

    Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term.

  12. Upfront allogeneic blood stem cell transplantation for patients with high-risk myelodysplastic syndrome or secondary acute myeloid leukemia using a FLAMSA-based high-dose sequential conditioning regimen.

    PubMed

    Saure, Christian; Schroeder, Thomas; Zohren, Fabian; Groten, Anke; Bruns, Ingmar; Czibere, Akos; Galonska, Lars; Kondakci, Mustafa; Weigelt, Christian; Fenk, Roland; Germing, Ulrich; Haas, Rainer; Kobbe, Guido

    2012-03-01

    Patients suffering from high-risk myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) secondary to MDS (sAML) are characterized by poor response to conventional cytotoxic chemotherapy. The purpose of our prospective single-center study was to examine the safety and efficacy of an allogeneic hematopoietic stem cell transplantation (HSCT) following a sequential conditioning regimen as first-line therapy for previously untreated patients with high-risk MDS or sAML. Between November 2003 and June 2010, 30 patients (20 high-risk MDS, 10 sAML) received fludarabine (4 × 30 mg/m(2)), amsacrine (4 × 100 mg/m(2)), and Ara-C (4 × 2 g/m(2), FLAMSA). After 2 to 3 days of rest, patients received high-dose melphalan alone (200 mg/m(2) for patients with an age <50 years, 150 mg/m(2) for patients with an age between 50 and 60 years, and 100 mg/m(2) for patients with an age >60 years; n = 24) or melphalan and thiotepa (10 mg/kg, Mel/Thio, n = 6). Following these high-dose conditioning regimens, a median number of 7.7 × 10(6) CD34(+) cells/kg body weight (range: 2.9 × 10(6)-17.2 × 10(6)) were transplanted from 13 related or 17 unrelated donors. Antithymocyte globulin (Fresenius 30-60 mg/kg) as well as tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. All patients except 1 with primary graft failure achieved complete remission after HSCT. After a median follow-up time of 28 months (range: 7-81), 21 patients (70%) were alive and free of disease. Overall, 4 patients relapsed. At 2 years, overall survival, event-free survival, and treatment-related mortality were 70%, 63%, and 30%, respectively. Because of undue toxicity, thiotepa is no longer part of the conditioning regimen. Our results add to the body of evidence that a FLAMSA-based sequential conditioning therapy is effective for previously untreated patients with high-risk MDS or sAML.

  13. Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen).

    PubMed

    Gianni, Alessandro M; Magni, Michele; Martelli, Maurizio; Di Nicola, Massimo; Carlo-Stella, Carmelo; Pilotti, Silvana; Rambaldi, Alessandro; Cortelazzo, Sergio; Patti, Caterina; Parvis, Guido; Benedetti, Fabio; Capria, Saveria; Corradini, Paolo; Tarella, Corrado; Barbui, Tiziano

    2003-07-15

    Mantle cell lymphoma (MCL) is rarely cured with standard-dose chemotherapy. From January 1997 to February 2000, 28 previously untreated advanced-stage MCL patients younger than 61 years of age were treated at 9 Italian hematologic departments with 3 cycles of standard-dose debulking chemotherapy followed by a high-dose rituximab-supplemented sequence (R-HDS) including intravenous administration of high-dose cyclophosphamide, high-dose cytarabine, high-dose melphalan, and high-dose mitoxantrone plus melphalan. Study end points included toxicity, clinical and molecular response rates, long-term event-free survival (EFS), and overall survival (OS) rates, as well as the ability to harvest tumor-free peripheral blood stem cells. Optimal amounts of polymerase chain reaction-negative (PCR-negative) CD34+ cells were collected from all 20 informative patients. One patient died of toxicity. All 27 patients assessable for response achieved a complete response (CR), of which 24 remain in continuous complete remission (CCR) after a median follow-up of 35 months. Three patients had transient evidence of PCR-detectable disease in the bone marrow. The OS and EFS rates at 54 months were 89% and 79%, respectively. These results compare with the 42% OS rate and the 18% EFS rate observed in 35 age-matched historic controls treated with standard-dose chemotherapy at the participating centers. The use of rituximab in combination with high-dose chemotherapy represents a very effective in vivo purging method. The R-HDS regimen can be safely applied in a multicenter hematology setting and leads to long-term EFS and OS in the majority of patients with an otherwise incurable disease.

  14. Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study

    PubMed Central

    Tsuruta, Atsushi; Yamashita, Kazuki; Tanioka, Hiroaki; Tsuji, Akihito; Inukai, Michio; Yamakawa, Toshiki; Yamatsuji, Tomoki; Yoshimitsu, Masanori; Toyota, Kazuhiro; Yamano, Taketoshi; Nagasaka, Takeshi; Okajima, Masazumi

    2016-01-01

    Background Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. Patients and methods Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were eligible. Patients were treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) for 3 months followed by capecitabine (2,500 mg/m2 on days 1–14 every 3 weeks) for 3 months. Primary end points were frequency and the grade of oxaliplatin-induced neurotoxicity as evaluated using the physician-based Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) grading and the patient-based scale, self-reported Patient Neurotoxicity Questionnaire. Results Ninety-one patients were enrolled and 86 patients assessed. Eighty-four percent of patients completed the planned oxaliplatin-based therapy for 3 months, and 63% of patients completed all treatments for the full 6 months. Overall incidences of grade 3 or 4 peripheral sensory or motor neuropathy according to the CTCAE were 3.5% and 1.2%, respectively. Regarding the peripheral sensory neuropathy, the proportion of Patient Neurotoxicity Questionnaire (grade C–E) and CTCAE (grade 2–4) at months 1.5/3/6 were 11.3/22.1/29.4% and 5.3/4.4/11.3%, respectively (Spearman correlation coefficient: 0.47). Conclusion A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of

  15. Comparative study of 5-day cefcapene-pivoxil and 10-day amoxicillin or cefcapene-pivoxil for treatment of group A streptococcal pharyngitis in children.

    PubMed

    Sakata, Hiroshi

    2008-06-01

    In order to compare the bacteriological and clinical efficacy and safety of cefcapene-pivoxil (CFPN-PI) for 5 days, CFPN-PI for 10 days, and amoxicillin (AMPC) for 10 days for the treatment of pharyngitis due to group A beta-hemolytic streptococcus (GAS) in children, a prospective multicenter randomized open-label comparative study was performed with 12 pediatric clinics in Asahikawa between June 2006 and February 2007. Two hundred and fifty children (age range 6 months to 12 years) with signs and symptoms of acute pharyngitis were enrolled. All had a positive throat culture for GAS and were fully evaluable. Eighty-two patients received CFPN-PI 9-10 mg/kg/day three times a day for 5 days, 88 received CFPN-PI three times a day for 10 days, and 80 received AMPC three times a day for 10 days. The CFPN-PI for 5 days regimen, the CFPN-PI for 10 days regimen, and the AMPC for 10 days regimen produced bacteriological eradication at the end of treatment in 93.8%, 96.2%, and 91.7% of the patients, respectively. The clinical cure rate observed at the end of therapy was 100% of the patients in the three groups. Relapse rates were 1.3% in CFPN-PI for 5 days, 4.0% in CFPN-PI for 10 days, and 2.9% in AMPC for 10 days. There were no significant differences in eradication rate, clinical cure rate, and relapse rate between the three treatment groups. The only adverse effects were infrequent diarrhea in all three groups, and a rash which occurred in 6 patients (8.0%) of the AMPC treatment group. Five days of treatment with CFPN-PI was as efficacious in bacteriological eradication and clinical response as 10 days of CFPN-PI or AMPC treatment.

  16. [Principles of organizing efficient work and rest regimens for crews on prolonged space flights].

    PubMed

    Litsov, A N; Bulyko, V I

    1983-01-01

    The work-rest cycles of Salyut-6 crews were investigated. Several modifications were detected: 24-hour static regimens (65-70%) and altered regimens (35-30%) with longer or shorter work-rest cycles. It is concluded that in prolonged space flights two regimens are allowed: principal regimens (normal static regimens of work and rest) used throughout the flight, and operational regimens (differing from 24-hour ones) used no more than once every 7-10 days.

  17. Enhancing Commitment Improves Adherence to a Medical Regimen.

    ERIC Educational Resources Information Center

    Putnam, Dana E.; And Others

    1994-01-01

    Evaluated commitment-based intervention for improvement of adherence to 10-day antibiotic regimen. Subjects were 60 college students. Experimental subjects made verbal and written commitments for adherence and completed tasks designed to increase their investment in medication regimen. Controls performed similarly structured tasks unrelated to…

  18. Randomized, double-blind study of short-course (5 day) grepafloxacin versus 10 day clarithromycin in patients with acute bacterial exacerbations of chronic bronchitis.

    PubMed

    Langan, C E; Zuck, P; Vogel, F; McIvor, A; Peirzchala, W; Smakal, M; Staley, H; Marr, C

    1999-10-01

    The efficacy and safety of grepafloxacin were compared with clarithromycin in a randomized, double-blind, multicentre clinical trial of 805 patients with acute bacterial exacerbations of chronic bronchitis (ABECB). Patients were randomized to receive grepafloxacin 400 mg od for either 5 (n = 273) or 10 days (n = 268) or clarithromycin 250 mg bd for 10 days (n = 261). Patients were assessed pre-treatment, 3-5 days during treatment, 1-3 days post-treatment and at follow-up (21-28 days post-treatment). The clinical success rates for the evaluable patients were 91% in the 5 day grepafloxacin group, 95% in the 10 day grepafloxacin group and 86% in the clarithromycin group. At follow-up, respective rates were 72%, 81% and 73%. A total of 513 pathogens were isolated from the pre-treatment sputum specimens of 400 (49%) patients. The primary pathogens were Haemophilus influenzae (36% of isolates), Haemophilus parainfluenzae (27%), Moraxella catarrhalis (12%), Streptococcus pneumoniae (11%) and Staphylococcus aureus (3%). Pathogens were eradicated or presumed eradicated at post-treatment in 85%, 91% and 58% of evaluable patients treated with grepafloxacin for 5 days, grepafloxacin 10 days and clarithromycin 10 days, respectively. The eradication rates in both grepafloxacin groups were significantly greater than the clarithromycin group (P<0.001). All treatments were well tolerated and incidence of drug-related adverse events in each group was comparable. This study demonstrates that both a 5 and a 10 day regimen of grepafloxacin 400 mg od are as clinically and bacteriologically effective as in the treatment of ABECB clarithromycin 250 mg bd. for 10 days.

  19. 78 FR 69703 - 10-Day Notice of Proposed Information Collection: Generic Customer Satisfaction Surveys; Physical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT 10-Day Notice of Proposed Information Collection: Generic Customer Satisfaction... Customer Satisfaction Surveys Physical Inspection Alignment Pilot Program--Expansion Announcement....

  20. OBSERVATIONS ON THE 10-DAY CHIRONOMUS TENTANS SURVIVAL AND GROWTH BIOASSAY IN EVALUATING GREAT LAKES SEDIMENTS

    EPA Science Inventory

    A 10-day bioassay with larval chironomids (Chironomus tentans) was used to evaluate sediment samples from harbors at Michigan City, IN, St. Joseph, MI, Grand Haven, MI and Toledo, OH for toxicity, based on the endpoints of survival, dry weight, and growth. Larval responses in se...

  1. Colles' fracture: dorsal splint or complete cast during the first 10 days?

    PubMed

    Wik, Tina Strømdal; Aurstad, Ase T; Finsen, Vilhjalmur

    2009-04-01

    In a prospective randomised trial of conservatively treated Colles' fractures, we compared radiological outcomes and complication rates for two immobilisation methods, either complete cast (34 cases) or dorsal splint (38 cases), during the first 10 days after reduction. Radiographs were evaluated for dorsal tilt, radial tilt and radial shortening; results were almost identical in the two groups. There was a mean difference of 3.4 degrees in dorsal angulation in favour of dorsal splinting 10 days after reduction and a mean difference of 1.6mm in radial length in favour of complete casting at 5 weeks. There was no difference between the two treatments groups in reported pain or cast problems. Thus individual preference may be followed in choice of immobilisation method.

  2. [Alternative hemodialysis regimens].

    PubMed

    Matos, Jorge Paulo Strogoff de; Lugon, Jocemir Ronaldo

    2010-03-01

    The mortality rate among patients on hemodialysis (HD) is extremely high. Remaining life expectancy for a patient initiating HD is only approximately one quarter of that of the general population at the same age bracket. The conventional HD regimen based on four-hour sessions three times a week was empirically established nearly four decades ago and needs to be revisited. Since the failure of the HEMO Study to demonstrate the clinical benefits of higher urea Kt/V for patients on conventional HD, an increasing interest for alternative HD regimens has emerged aiming at providing a treatment for improving survival rates. Short daily HD and long nocturnal HD stand out as the most promising alternative regimens. Economical obstacles which could hinder the clinical application of emerging knowledge in the field should be overcome.

  3. BOREAS RSS-7 Regional LAI and FPAR Images From 10-Day AVHRR-LAC Composites

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Nickeson, Jaime (Editor); Chen, Jing; Cihlar, Josef

    2000-01-01

    The BOReal Ecosystem-Atmosphere Study Remote Sensing Science (BOREAS RSS-7) team collected various data sets to develop and validate an algorithm to allow the retrieval of the spatial distribution of Leaf Area Index (LAI) from remotely sensed images. Advanced Very High Resolution Radiometer (AVHRR) level-4c 10-day composite Normalized Difference Vegetation Index (NDVI) images produced at CCRS were used to produce images of LAI and the Fraction of Photosynthetically Active Radiation (FPAR) absorbed by plant canopies for the three summer IFCs in 1994 across the BOREAS region. The algorithms were developed based on ground measurements and Landsat Thematic Mapper (TM) images. The data are stored in binary image format files.

  4. Field validation of 10-day freshwater sediment toxicity tests using Hyalella azteca and Chironomus tentans

    SciTech Connect

    Becker, D.S.; Bigham, G.N.

    1995-12-31

    Two of the toxicity tests commonly used to evaluate freshwater sediments are the 10-day amphipod (Hyalella azteca) and chironomid (Chironomus tentans) tests. EPA and ASTM have recently developed standardized protocols for these tests. Although both tests are considered sensitive indicators of sediment toxicity, little information exists on how well test results correspond to adverse biological effects in the field. In this study, the lethal and sublethal (i.e., biomass) responses of the two toxicity tests were compared with alterations of benthic macroinvertebrate assemblages (i.e., benthic effects) at 56 stations in Onondaga Lake, New York. The lake has received municipal and industrial discharges for more than 100 years, and sediment chemical concentrations range widely throughout the lake. Toxicity results for Onondaga Lake were compared with reference conditions using the t-test, and benthic effects were determined using classification analysis of log-transformed taxa abundances. In general, a relatively high level of agreement was found between results of the toxicity tests and alterations of benthic assemblages. Significant (P < 0.05) correlations were found between all toxicity test endpoints and taxa richness of benthic assemblages. In addition, significant concordance (P {le} 0.01, binomial test) was found between toxicity designations for the 56 stations based on toxicity tests and toxicity designations based on benthic effects. Despite the general level of agreement among the various biological indicators, chironomid biomass and benthic effects were found to be the most sensitive indicators of toxicity, whereas amphipod survival and biomass were the least sensitive indicators. This study suggests that results of the 10-day amphipod and chironomid toxicity tests are highly predictive of adverse biological effects in the field.

  5. Relationship between Mean Winds and Large 10-day Precipitation Anomalies over the Continental U.S.

    NASA Technical Reports Server (NTRS)

    Helfand, H. Mark

    2008-01-01

    To better understand the role of surface boundary forcing upon interannual and decadal variability of droughts and precipitation excesses over the continental U. S., an observational study has been carried out to better investigate the dynamical linkages between surface boundary forcing and droughts/floods. This study examines the relationship during the warm season between observed mean wind patterns on the 10-15 day time scale and anomalies in precipitation on that same time scale over the U. S. Each of the 7 cases of significant 10-day, warm-season drought over the U, S. since 1948 that has been investigated was accompanied by significant continental-scale ridging of the mean 10-day 250 mb wind pattern over the continental U.S. and a mid-Pacific relative maximum of 250 mb wind speed of at least 30 m/sec within 20 degrees of the international Date Line. This perhaps suggests the presence of a wave-guide phenomenon over the Pacific. The drought signal for each of these cases was still quite evident when averaged over the monthly time scale. While peak magnitudes of the precipitation anomalies were much larger for the 7 chosen cases of significant of precipitation excess were than for the drought cases none of the patterns of precipitation excess were as unambiguous or wide-spread as the drought cases. In only 2 to 3 cases was there evidence of a continental trough in the 250 mb winds. In fact, one case showed slight ridging over Canada and the extreme northern U.S. Strong southerly low-level jets, however, were evident in the 925 mb winds over south-central Texas or the nearby Gulf of Mexico in virtually all of the excessive precipitation cases, while the Great Plains LLJ was weak or displaced to the north of Texas in most of the drought cases. We will further investigate the asymmetry between droughts and precipitation excesses in their horizontal homogeneity and extent, in their temporal evolution, and in how the are forced by the combined effects of the mean

  6. WASP-117b: a 10-day-period Saturn in an eccentric and misaligned orbit

    NASA Astrophysics Data System (ADS)

    Lendl, M.; Triaud, A. H. M. J.; Anderson, D. R.; Collier Cameron, A.; Delrez, L.; Doyle, A. P.; Gillon, M.; Hellier, C.; Jehin, E.; Maxted, P. F. L.; Neveu-VanMalle, M.; Pepe, F.; Pollacco, D.; Queloz, D.; Ségransan, D.; Smalley, B.; Smith, A. M. S.; Udry, S.; Van Grootel, V.; West, R. G.

    2014-08-01

    We report the discovery of WASP-117b, the first planet with a period beyond 10 days found by the WASP survey. The planet has a mass of Mp = 0.2755 ± 0.0089 MJ, a radius of Rp= 1.021_{-0.065+0.076 Rjup} and is in an eccentric (e = 0.302 ± 0.023), 10.02165 ± 0.00055 d orbit around a main-sequence F9 star. The host star's brightness (V = 10.15 mag) makes WASP-117 a good target for follow-up observations, and with a periastron planetary equilibrium temperature of Teq= 1225_{-39+36} K and a low planetary mean density (ρp= 0.259_{-0.048+0.054 ρjup}) it is one of the best targets for transmission spectroscopy among planets with periods around 10 days. From a measurement of the Rossiter-McLaughlin effect, we infer a projected angle between the planetary orbit and stellar spin axes of β = -44 ± 11 deg, and we further derive an orbital obliquity of ψ = 69.6 +4.7-4.1 deg. Owing to the large orbital separation, tidal forces causing orbital circularization and realignment of the planetary orbit with the stellar plane are weak, having had little impact on the planetary orbit over the system lifetime. WASP-117b joins a small sample of transiting giant planets with well characterized orbits at periods above 8 days. Based on data obtained with WASP-South, CORALIE and EulerCam at the Euler-Swiss telescope, TRAPPIST, and HARPS at the ESO 3.6 m telescope (Prog. IDs 087.C-0649, 089.C-0151, 090.C-0540)Photometric and radial velocities are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/568/A81

  7. Prolonged use for at least 10 days of intraaortic balloon pumping (IABP) for heart failure.

    PubMed

    Oshima, Kiyohiro; Morishita, Yasuo; Hinohara, Hiroshi; Kadoi, Yuji; Hayashi, Yoshiro; Tajima, Yukio; Kunimoto, Fumio

    2005-11-01

    Intraaortic balloon pumping (IABP) is a useful therapy for refractory heart failure. However, the safe duration of this therapy and possible complications due to long-term IABP support remain unclear. In this study, we reviewed retrospectively patients requiring the long-term use of IABP, defined here as 10 days or more, to estimate the background and prognosis of patients undergoing long-term use of IABP. The characteristics and perioperative status were compared between survivors and nonsurvivors. A total of 18 patients including 12 males and 6 females required long-term IABP use. IABP was induced in 13 patients (72%) following cardiac surgery and in 5 without cardiac surgery. The mean duration of IABP support was 17 +/- 7 days. Seven patients survived and 11 died of heart failure and/or associated other organ failure. Multiple organ failure (MOF) was recognized in 10 patients, and the incidence of MOF was significantly (P = 0.005) lower in the survivors (14%) compared to the nonsurvivors (82%). The percentage of postcardiac surgery patients was also significantly (P = 0.027) higher in nonsurvivors (91%) than in survivors (43%). Logistic regression analysis identified MOF and cardiac surgery as independent predictors for death. Femoral arterial-venous fistula was the only IABP-related complication. In patients receiving long-term IABP, attention should be paid to other organ complications associated with heart failure, and the use of other circulatory supports such as PCPS or VAD to avoid MOF should be considered if necessary.

  8. A toxicity scoring system for the 10-day whole sediment test with Corophium insidiosum (Crawford).

    PubMed

    Prato, Ermelinda; Biandolino, Francesca; Libralato, Giovanni

    2015-04-01

    This study developed a tool able to evaluate the potential contamination of marine sediments detecting the presence or absence of toxicity supporting environmental decision-making processes. When the sample is toxic, it is important to classify its level of toxicity to understand its subsequent effects and management practices. Corophium insidiosum is a widespread and frequently recorded species along the Mediterranean Sea, North Sea and western Baltic Sea with records also in the Atlantic Ocean and Pacific Ocean. This amphipod is found in high abundance in shallow brackish inshore areas and estuaries also with high turbidity. At Italian level, C. insidiosum is more frequently collectable than Corophium orientale, making routine toxicity tests easier to be performed. Moreover, according to the international scientific literature, C. insidiosum is more sensitive than C. orientale. Whole sediment toxicity data (10 days) with C. insidiosum were organised in a species-specific toxicity score on the basis of the minimum significance difference (MSD) approach. Thresholds to rank samples as non-toxic and toxic were based on sediment samples (n=84) from the Gulf of Taranto (Italy). A five-class toxicity score (absent, low, medium, high and very high toxicity) was developed, considering the distribution of the 90th percentile of the MSD normalised to the effects on the negative controls (samples from reference sites). This toxicity score could be useful for interpreting sediment potential impacts and providing quick responsive management information.

  9. Effect of 10-day broccoli consumption on inflammatory status of young healthy smokers.

    PubMed

    Riso, Patrizia; Vendrame, Stefano; Del Bo', Cristian; Martini, Daniela; Martinetti, Antonia; Seregni, Ettore; Visioli, Francesco; Parolini, Marina; Porrini, Marisa

    2014-02-01

    This study evaluated the effects of 10-day broccoli (250 g/day) intake on dietary markers and markers of inflammations in young male smokers. A dietary intervention study with a repeated measures crossover design was conducted. Circulating levels of carotenoids, folate, C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 6 receptor (IL-6sR) and adiponectin were measured. Broccoli intake significantly increased plasma levels of folate (+17%) and lutein (+39%), while no significant effect was observed for TNF-α, IL-6, IL-6sR or adiponectin. Plasma CRP decreased by 48% (post-hoc analysis, p <  0.05) following broccoli diet; this resulted to be independent from the plasma variations in lutein and folate. An inverse correlation between lycopene, TNF-α and IL-6sR was observed at baseline. In conclusion, broccoli consumption may reduce CRP levels in smokers, consistent with epidemiologic observations that fruit and vegetable intake is associated with lower circulating CRP concentrations.

  10. Assessment of four different test designs for Hyalella azteca 10 days sediment toxicity test

    SciTech Connect

    Ramirez-Romero, P. |; Oris, J.T.; Bailer, J.; DePoy, M.

    1995-12-31

    The purpose of this study was to assess the adequacy of four experimental designs of the Hyalella azteca 10 days sediment toxicity test. The authors conducted a series of sediment toxicity tests using an EPA recommended experimental design (8 chambers with 10 organisms per treatment) and three other designs. These had the same total number of organisms (80) per treatment and the same sediment:water ratio (1:1.5) but different number of chambers (4,2,1). The number of organisms recovered, the time to sort and count the animals, as well as the time to make a water change were compared for these four designs. Logistic regression was used to analyze the recovery data while one-way analysis of variance methods were used to analyze the time responses. The results showed that the four treatments were comparable in terms of proportion of organisms recovered. However, the sorting time and the water change time decreased as the number of chambers decreased, making those designs with less chambers more desirable.

  11. 10-Day survival of Hyalella azteca as a function of water quality parameters.

    PubMed

    Javidmehr, Alireza; Kass, Philip H; Deanovic, Linda A; Connon, Richard E; Werner, Inge

    2015-05-01

    Estuarine systems are among the most impacted ecosystems due to anthropogenic contaminants; however, they present unique challenges to toxicity testing with regard to varying water quality parameters. The euryhaline amphipod species, Hyalella azteca, is widely used in toxicity testing and well suited for testing estuarine water samples. Nevertheless, the influence of relevant water quality parameters on test endpoints must be quantified in order to efficiently use this species for routine monitoring. Here, we studied the influence of five water quality parameters: electrical conductivity, pH, un-ionized ammonia, dissolved oxygen and temperature, on H. azteca survival in a water column toxicity test. A model was developed to quantify and predict the independent and interacting effects of water quality variables on 10-day survival. The model allows simultaneous assessment of multiple potential predictors recorded during the tests. Data used for modeling came from 1089 tests performed on ambient water samples over a period of three years (2006-2008). The final model reflects significant effects of predictors and their two-way interactions. The effect of each level of all predictors on survival probability of H. azteca was examined by comparing levels of each predictor at a time, while holding all others at their lowest (reference) level. This study showed that predictors of survival in water column tests should not be evaluated in isolation in the interpretation of H. azteca water column tests. Our model provides a useful tool to predict expected control survival based on relevant water quality parameters, and thus enables the use of H. azteca tests for toxicity monitoring in estuaries with a wide range of water quality conditions.

  12. [Assessment of changes in physiological status of alcohol-dependent patients in the course of 10-day detoxication treatment].

    PubMed

    Slósarska, M; Wójcik, M; Habrat, B

    1994-01-01

    Heart rate, respiratory rate, postural muscle tone and tapping in 14 alcohol dependent patients (type II ac. Cloninger) during 10 days of detoxification were investigated. Despite subjective mood increased, no longer observed were tachycardia and clinical symptoms of alcohol withdrawal; increased muscle tonus and faster respiration rhythm were observed. The observed physiological changes in alcohol dependent patients after 10 days of abstinence suggest that continuation of pharmacotherapy and psychotherapy after detoxification in acute alcohol withdrawal is recommended.

  13. Whole body and regional body composition changes following 10-day hypoxic confinement and unloading-inactivity.

    PubMed

    Debevec, Tadej; McDonnell, Adam C; Macdonald, Ian A; Eiken, Ola; Mekjavic, Igor B

    2014-03-01

    Future planetary habitats will expose inhabitants to both reduced gravity and hypoxia. This study investigated the effects of short-term unloading and normobaric hypoxia on whole body and regional body composition (BC). Eleven healthy, recreationally active, male participants with a mean (SD) age of 24 (2) years and body mass index of 22.4 (3.2) kg·m(-2) completed the following 3 10-day campaigns in a randomised, cross-over designed protocol: (i) hypoxic ambulatory confinement (HAMB; FIO2 = 0.147 (0.008); PIO2 = 93.8 (0.9) mm Hg), (ii) hypoxic bed rest (HBR; FIO2 = 0.147 (0.008); PIO2 = 93.8 (0.9) mm Hg), and (iii) normoxic bed rest (NBR; FIO2 = 0.209; PIO2 = 133.5 (0.7) mm Hg). Nutritional requirements were individually precalculated and the actual intake was monitored throughout the study protocol. Body mass, whole body, and regional BC were assessed before and after the campaigns using dual-energy X-ray absorptiometry. The calculated daily targeted energy intake values were 2071 (170) kcal for HBR and NBR and 2417 (200) kcal for HAMB. In both HBR and NBR campaigns the actual energy intake was within the targeted level, whereas in the HAMB the intake was lower than targeted (-8%, p < 0.05). Body mass significantly decreased in all 3 campaigns (-2.1%, -2.8%, and -2.0% for HAMB, HBR, and NBR, respectively; p < 0.05), secondary to a significant decrease in lean mass (-3.8%, -3.8%, -4.3% for HAMB, HBR, and NBR, respectively; p < 0.05) along with a slight, albeit not significant, increase in fat mass. The same trend was observed in the regional BC regardless of the region and the campaign. These results demonstrate that, hypoxia per se, does not seem to alter whole body and regional BC during short-term bed rest.

  14. Stacked Sequential Learning

    DTIC Science & Technology

    2005-07-01

    a constant factor of K + 2. (To see this, note sequential stacking requires training K+2 classifiers: the classifiers f1, . . . , fK used in cross...on the non- sequential learners (ME and VP) but improves per- formance of the sequential learners (CRFs and VPH - MMs) less consistently. This pattern

  15. FLASH SPECTROSCOPY: EMISSION LINES FROM THE IONIZED CIRCUMSTELLAR MATERIAL AROUND <10-DAY-OLD TYPE II SUPERNOVAE

    SciTech Connect

    Khazov, D.; Yaron, O.; Gal-Yam, A.; Manulis, I.; Rubin, A.; Ofek, E. O.; Horesh, A.; Kulkarni, S. R.; Kasliwal, M. M.; Cao, Y.; Perley, D.; Arcavi, I.; Howell, D. A.; Sollerman, J.; Sullivan, M.; Filippenko, A. V.; Nugent, P. E.; Cenko, S. B.; Silverman, J. M.; Ebeling, H.; and others

    2016-02-10

    Supernovae (SNe) embedded in dense circumstellar material (CSM) may show prominent emission lines in their early-time spectra (≤10 days after the explosion), owing to recombination of the CSM ionized by the shock-breakout flash. From such spectra (“flash spectroscopy”), we can measure various physical properties of the CSM, as well as the mass-loss rate of the progenitor during the year prior to its explosion. Searching through the Palomar Transient Factory (PTF and iPTF) SN spectroscopy databases from 2009 through 2014, we found 12 SNe II showing flash-ionized (FI) signatures in their first spectra. All are younger than 10 days. These events constitute 14% of all 84 SNe in our sample having a spectrum within 10 days from explosion, and 18% of SNe II observed at ages <5 days, thereby setting lower limits on the fraction of FI events. We classified as “blue/featureless” (BF) those events having a first spectrum that is similar to that of a blackbody, without any emission or absorption signatures. It is possible that some BF events had FI signatures at an earlier phase than observed, or that they lack dense CSM around the progenitor. Within 2 days after explosion, 8 out of 11 SNe in our sample are either BF events or show FI signatures. Interestingly, we found that 19 out of 21 SNe brighter than an absolute magnitude M{sub R} = −18.2 belong to the FI or BF groups, and that all FI events peaked above M{sub R} = −17.6 mag, significantly brighter than average SNe II.

  16. Flash Spectroscopy: Emission Lines from the Ionized Circumstellar Material Around <10-Day-Old Type II Supernovae

    DOE PAGES

    Khazov, Daniel; Yaron, O.; Gal-Yam, A.; ...

    2016-02-02

    Supernovae (SNe) embedded in dense circumstellar material (CSM) may show prominent emission lines in their early-time spectra (≤10 days after the explosion), owing to recombination of the CSM ionized by the shock-breakout flash. From such spectra ("flash spectroscopy"), we can measure various physical properties of the CSM, as well as the mass-loss rate of the progenitor during the year prior to its explosion. In this paper, by searching through the Palomar Transient Factory (PTF and iPTF) SN spectroscopy databases from 2009 through 2014, we found 12 SNe II showing flash-ionized (FI) signatures in their first spectra. All are younger thanmore » 10 days. These events constitute 14% of all 84 SNe in our sample having a spectrum within 10 days from explosion, and 18% of SNe II observed at ages <5 days, thereby setting lower limits on the fraction of FI events. We classified as "blue/featureless" (BF) those events having a first spectrum that is similar to that of a blackbody, without any emission or absorption signatures. It is possible that some BF events had FI signatures at an earlier phase than observed, or that they lack dense CSM around the progenitor. Within 2 days after explosion, 8 out of 11 SNe in our sample are either BF events or show FI signatures. Finally and interestingly, we found that 19 out of 21 SNe brighter than an absolute magnitude MR = -18.2 belong to the FI or BF groups, and that all FI events peaked above MR = -17.6 mag, significantly brighter than average SNe II.« less

  17. Flash Spectroscopy: Emission Lines from the Ionized Circumstellar Material Around <10-Day-Old Type II Supernovae

    SciTech Connect

    Khazov, Daniel; Yaron, O.; Gal-Yam, A.; Manulis, I.; Rubin, A.; Kulkarni, S. R.; Arcavi, I.; Kasliwal, M. M.; Ofek, E. O.; Cao, Y.; Perley, D.; Sollerman, J.; Horesh, A.; Sullivan, M.; Filippenko, A. V.; Nugent, P. E.; Howell, D. A.; Cenko, S. B.; Silverman, J. M.; Ebeling, H.; Taddia, F.; Johansson, J.; Laher, R. R.; Surace, J.; Rebbapragada, U. D.; Wozniak, Przemyslaw R.; Matheson, T.

    2016-02-02

    Supernovae (SNe) embedded in dense circumstellar material (CSM) may show prominent emission lines in their early-time spectra (≤10 days after the explosion), owing to recombination of the CSM ionized by the shock-breakout flash. From such spectra ("flash spectroscopy"), we can measure various physical properties of the CSM, as well as the mass-loss rate of the progenitor during the year prior to its explosion. In this paper, by searching through the Palomar Transient Factory (PTF and iPTF) SN spectroscopy databases from 2009 through 2014, we found 12 SNe II showing flash-ionized (FI) signatures in their first spectra. All are younger than 10 days. These events constitute 14% of all 84 SNe in our sample having a spectrum within 10 days from explosion, and 18% of SNe II observed at ages <5 days, thereby setting lower limits on the fraction of FI events. We classified as "blue/featureless" (BF) those events having a first spectrum that is similar to that of a blackbody, without any emission or absorption signatures. It is possible that some BF events had FI signatures at an earlier phase than observed, or that they lack dense CSM around the progenitor. Within 2 days after explosion, 8 out of 11 SNe in our sample are either BF events or show FI signatures. Finally and interestingly, we found that 19 out of 21 SNe brighter than an absolute magnitude MR = -18.2 belong to the FI or BF groups, and that all FI events peaked above MR = -17.6 mag, significantly brighter than average SNe II.

  18. A 10-day confinement to normobaric hypoxia impairs toe, but not finger temperature response during local cold stress.

    PubMed

    Kounalakis, Stylianos N; Keramidas, Michail E; Amon, Mojca; Eiken, Ola; Mekjavic, Igor B

    2017-02-01

    The study examined the effects of a 10-day normobaric hypoxic confinement on the finger and toe temperature responses to local cooling. Eight male lowlanders underwent a normoxic (NC) and, in a separate occasion, a normobaric hypoxic confinement (HC; FO2: 0.154; simulated altitude ~3400m). Before and after each confinement, subjects immersed for 30min their right hand and, in a different session, their right foot in 8°C water, while breathing either room air (AIR) or a hypoxic gas mixture (HYPO). Throughout the cold-water immersion tests, thermal responses were monitored with thermocouples on fingers and toes. Neither confinement influenced thermal responses in the fingers during the AIR or HYPO test. In the foot, by contrast, HC, but not NC, reduced the average toe temperature by ~1.5°C (p=0.03), both during the AIR and HYPO test. We therefore conclude that a 10-day confinement to normobaric hypoxia per se augments cold-induced vasoconstriction in the toes, but not in the fingers. The mechanism underlying this dissimilarity remains to be established.

  19. Efficacy and safety of grepafloxacin 600 mg daily for 10 days in patients with community-acquired pneumonia.

    PubMed

    Topkis, S; Swarz, H; Breisch, S A; Maroli, A N

    1997-01-01

    The efficacy and safety of grepafloxacin in treating patients with community-acquired pneumonia (CAP) was assessed in an open-label, noncomparative study. Patients (N = 273) received grepafloxacin 600 mg QD for 10 days. A total of 237 patients (87%) completed the study. In assessable patients, the clinical success rate at follow-up (4 to 6 weeks after the last dose) was 89% (211/238 patients). In microbiologically assessable patients, the eradication rate at follow-up was 95% (86/91 isolates). Grepafloxacin was highly effective in the treatment of bacterial CAP caused by Streptococcus pneumoniae (irrespective of penicillin susceptibility), Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, and Staphylococcus aureus and in the therapy of atypical pneumonia caused by Mycoplasma pneumoniae and Legionella pneumophila. Grepafloxacin was well tolerated, with the most frequently reported drug-related adverse events being taste perversion and nausea. Grepafloxacin 600 mg QD for 10 days was highly effective and well tolerated in the treatment of patients with CAP.

  20. Ensuring compliance with drug regimens.

    PubMed

    Clarence, M

    This article explores the difficulties patients encounter in complying with prescribed drug regimens, and describes some of the compliance aids which are commonly available. A sensitive understanding of patients' individual difficulties by health care staff is an essential precursor to successful compliance behaviour.

  1. Efficacy and safety of a 10-day course of 400 or 600 milligrams of grepafloxacin once daily for treatment of acute bacterial exacerbations of chronic bronchitis: comparison with a 10-day course of 500 milligrams of ciprofloxacin twice daily.

    PubMed

    Chodosh, S; Lakshminarayan, S; Swarz, H; Breisch, S

    1998-01-01

    A randomized, prospective, double-blind, double-dummy, multicenter study investigated the efficacy and safety of 10 days of oral therapy with grepafloxacin at 400 mg once daily, grepafloxacin at 600 mg once daily, or ciprofloxacin at 500 mg twice daily in 624 patients with acute bacterial exacerbations of chronic bronchitis. At the end of treatment, clinical success (cure or improvement) was achieved for 93% (140 of 151), 88% (137 of 156), and 91% (145 of 160) of patients in the groups receiving grepafloxacin at 400 mg, grepafloxacin at 600 mg, and ciprofloxacin, respectively (clinically evaluable population). At follow-up (14 to 28 days posttreatment), the clinical success rates were 87% (124 of 143), 81% (122 of 151), and 80% (123 of 154) in the groups receiving grepafloxacin at 400 mg and 600 mg and ciprofloxacin, respectively. A total of 379 pathogens were isolated from 290 patients, with the most common isolates being Moraxella catarrhalis (21%), Staphylococcus aureus (20%), Haemophilus influenzae (18%), and Streptococcus pneumoniae (7%). For the evaluable population, successful bacteriologic response was obtained at the end of treatment for 96% (92 of 96), 98% (87 of 89), and 92% (82 of 90) of patients receiving grepafloxacin at 400 mg, grepafloxacin at 600 mg, and ciprofloxacin, respectively, and was maintained in 86% (82 of 95), 88% (78 of 89), and 82% (69 of 84) of patients, respectively, at follow-up. All pretreatment S. pneumoniae isolates were susceptible to grepafloxacin, but two strains were resistant to ciprofloxacin. All treatments were well tolerated, with the most frequently reported drug-related adverse events being nausea, taste perversion, and headache. All drug-related adverse events in the grepafloxacin groups were mild or moderate in severity. This study demonstrates that 10-day courses of grepafloxacin given at 400 or 600 mg once daily were as effective, clinically and bacteriologically, as ciprofloxacin given at 500 mg twice daily for the

  2. A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia

    PubMed Central

    2012-01-01

    Introduction The aim of this study was to compare a 7-day course of doripenem to a 10-day course of imipenem-cilastatin for ventilator-associated pneumonia (VAP) due to Gram-negative bacteria. Methods This was a prospective, double-blinded, randomized trial comparing a fixed 7-day course of doripenem one gram as a four-hour infusion every eight hours with a fixed 10-day course of imipenem-cilastatin one gram as a one-hour infusion every eight hours (April 2008 through June 2011). Results The study was stopped prematurely at the recommendation of the Independent Data Monitoring Committee that was blinded to treatment arm assignment and performed a scheduled review of data which showed signals that were close to the pre-specified stopping limits. The final analyses included 274 randomized patients. The clinical cure rate at the end of therapy (EOT) in the microbiological intent-to-treat (MITT) population was numerically lower for patients in the doripenem arm compared to the imipenem-cilastatin arm (45.6% versus 56.8%; 95% CI, -26.3% to 3.8%). Similarly, the clinical cure rate at EOT was numerically lower for patients with Pseudomonas aeruginosa VAP, the most common Gram-negative pathogen, in the doripenem arm compared to the imipenem-cilastatin arm (41.2% versus 60.0%; 95% CI, -57.2 to 19.5). All cause 28-day mortality in the MITT group was numerically greater for patients in the doripenem arm compared to the imipenem-cilastatin arm (21.5% versus 14.8%; 95% CI, -5.0 to 18.5) and for patients with P. aeruginosa VAP (35.3% versus 0.0%; 95% CI, 12.6 to 58.0). Conclusions Among patients with microbiologically confirmed late-onset VAP, a fixed 7-day course of doripenem was found to have non-significant higher rates of clinical failure and mortality compared to a fixed 10-day course of imipenem-cilastatin. Consideration should be given to treating patients with VAP for more than seven days to optimize clinical outcome. Trial Registration ClinicalTrials.gov: NCT00589693

  3. Twenty years of interplanetary magnetic field variations with periods in the range of 10 days to 3 years

    SciTech Connect

    Szabo, A.; Lepping, R.P.; King, J.H.

    1995-06-01

    Twenty years of interplanetary magnetic field data collected primarily by the IMP-8 spacecraft near Earth has been analyzed by a dynamic periodogram method in search of significant periodicities in the range of 10 days to 3 years. The method has the advantage of detecting variations with time in the periodicities besides determining the power and phase of the dominant variations. It has been found that the well known periodicities near 1 year and 27 days are strongly modulated by the solar cycle. Both of these periodicities are only detected during solar minimum. During solar maximum. a number of unusual variations are observed. Special emphasis will be placed on the recently reported 1.3 year variation in solar wind parameters besides periods in the interplanetary magnetic field near 51, 73 and 154 days. Correlations with solar wind plasma and solar index variations will also be presented.

  4. Twenty years of interplanetary magnetic field variations with periods in the range of 10 days to 3 years

    NASA Technical Reports Server (NTRS)

    Szabo, A.; Lepping, R. P.; King, J. H.

    1995-01-01

    Twenty years of interplanetary magnetic field data collected primarily by the IMP-8 spacecraft near Earth has been analyzed by a dynamic periodogram method in search of significant periodicities in the range of 10 days to 3 years. The method has the advantage of detecting variations with time in the periodicities besides determining the power and phase of the dominant variations. It has been found that the well known periodicities near 1 year and 27 days are strongly modulated by the solar cycle. Both of these periodicities are only detected during solar minimum. During solar maximum. a number of unusual variations are observed. Special emphasis will be placed on the recently reported 1.3 year variation in solar wind parameters besides periods in the interplanetary magnetic field near 51, 73 and 154 days. Correlations with solar wind plasma and solar index variations will also be presented.

  5. 10 day flight performance of the plant generic bioprocessing apparatus (PGBA) plant growth facility aboard STS-77

    NASA Astrophysics Data System (ADS)

    Hoehn, Alex; Chamberlain, Dale J.; Forsyth, Sasha W.; Hanna, David S.; Scovazzo, Paul; Horner, Michael B.; Stodieck, Louis S.; Todd, Paul; Heyenga, A. Gerard; Kliss, Mark H.; Bula, Raymond; Yetka, Robert

    1997-01-01

    PGBA, a plant growth facility developed for space flight biotechnology research, successfully grew a total of 30 plants in a closed, multi-crop chamber for 10 days aboard the Space Shuttle Endeavor (STS-77). Artemisia annua, Catharanthus roseus, Pinus taeda, Spinacia oleracea and Trifolium repens were the five species studied during this mission. The primary mission objectives were to study the effects of microgravity for commercial and pharmaceutical production purposes. PGBA is a payload that represents a consortium of interests including BioServe Space Technologies (payload sponsor), NASA Ames Research Center (Controlled Ecological Life Support System, CELSS, Flight Program), Wisconsin Center for Space Automation and Robotics (WCSAR), and industrial affiliates (spaceflight effects on plants and formation of plant products such as pharmaceuticals). Although BioServe is responsible for the flight hardware development and integration of PGBA, NASA Ames, WSCAR and industrial affiliates provide significant hardware subsystems and technical biological expertise support.

  6. 10 day flight performance of the plant generic bioprocessing apparatus (PGBA) plant growth facility aboard STS-77

    SciTech Connect

    Hoehn, A.; Chamberlain, D.J.; Forsyth, S.W.; Hanna, D.S.; Scovazzo, P.; Horner, M.B.; Stodieck, L.S.; Todd, P.; Heyenga, A.G.; Kliss, M.H.

    1997-01-01

    PGBA, a plant growth facility developed for space flight biotechnology research, successfully grew a total of 30 plants in a closed, multi-crop chamber for 10 days aboard the Space Shuttle Endeavor (STS-77). {ital Artemisia annua, Catharanthus roseus, Pinus taeda, Spinacia oleracea and Trifolium repens} were the five species studied during this mission. The primary mission objectives were to study the effects of microgravity for commercial and pharmaceutical production purposes. PGBA is a payload that represents a consortium of interests including BioServe Space Technologies (payload sponsor), NASA Ames Research Center (Controlled Ecological Life Support System, CELSS, Flight Program), Wisconsin Center for Space Automation and Robotics (WCSAR), and industrial affiliates (spaceflight effects on plants and formation of plant products such as pharmaceuticals). Although BioServe is responsible for the flight hardware development and integration of PGBA, NASA Ames, WSCAR and industrial affiliates provide significant hardware subsystems and technical biological expertise support. {copyright} {ital 1997 American Institute of Physics.}

  7. Sequential document visualization.

    PubMed

    Mao, Yi; Dillon, Joshua; Lebanon, Guy

    2007-01-01

    Documents and other categorical valued time series are often characterized by the frequencies of short range sequential patterns such as n-grams. This representation converts sequential data of varying lengths to high dimensional histogram vectors which are easily modeled by standard statistical models. Unfortunately, the histogram representation ignores most of the medium and long range sequential dependencies making it unsuitable for visualizing sequential data. We present a novel framework for sequential visualization of discrete categorical time series based on the idea of local statistical modeling. The framework embeds categorical time series as smooth curves in the multinomial simplex summarizing the progression of sequential trends. We discuss several visualization techniques based on the above framework and demonstrate their usefulness for document visualization.

  8. Helicobacter pylori eradication: Sequential therapy and Lactobacillus reuteri supplementation

    PubMed Central

    Efrati, Cesare; Nicolini, Giorgia; Cannaviello, Claudio; O’Sed, Nicole Piazza; Valabrega, Stefano

    2012-01-01

    AIM: To evaluate the role of sequential therapy and Lactobacillus reuteri (L. reuteri) supplementation, in the eradication treatment of Helicobacter pylori (H. pylori). METHODS: H. pylori infection was diagnosed in 90 adult dyspeptic patients. Patients were excluded if previously treated for H. pylori infection or if they were taking a proton pump inhibitor (PPI), H2-receptor antagonist or antibiotics. Patients were assigned to receive one of the following therapies: (1) 7-d triple therapy (PPI plus clarithromycin and amoxicillin or metronidazole) plus L. reuteri supplementation during antibiotic treatment; (2) 7-d triple therapy plus L. reuteri supplementation after antibiotic treatment; (3) sequential regimen (5-d PPI plus amoxicillin therapy followed by a 5-d PPI, clarithromycin and tinidazole) plus L. reuteri supplementation during antibiotic treatment; and (4) sequential regimen plus L. reuteri supplementation after antibiotic treatment. Successful eradication therapy was defined as a negative urea breath test at least 4 wk following treatment. RESULTS: Ninety adult dyspeptic patients were enrolled, and 83 (30 male, 53 female; mean age 57 ± 13 years) completed the study. Nineteen patients were administered a 7-d triple treatment: 11 with L. reuteri supplementation during and 8 after therapy. Sixty-four patients were administered a sequential regimen: 32 with L. reuteri supplementation during and 32 after therapy. The eradication rate was significantly higher in the sequential group compared with the 7-d triple regimen (88% vs 63%, P = 0.01). No difference was found between two types of PPI. No difference in eradication rates was observed between patients submitted to L. reuteri supplementation during or after antibiotic treatment. Compliance with therapy was excellent in all patients. No difference in adverse effects was observed between the different antibiotic treatments and between patients submitted to L. reuteri supplementation during and after

  9. Comparison of the differential expression miRNAs in Wistar rats before and 10 days after S.japonicum infection

    PubMed Central

    2013-01-01

    Background When compared to the murine permissive host of Schistosoma japonicum, Wistar rats are less susceptible to Schistosoma japonicum infection, and are considered to provide a less suitable microenvironment for parasite growth and development. MicroRNAs (miRNAs), are a class of endogenous, non-coding small RNAs, that impose an additional, highly significant, level of gene regulation within eukaryotes. Methods To investigate the regulatory mechanisms provided by miRNA in the schistosome-infected rat model, we utilized a miRNA microarray to compare the progression of miRNA expression within different host tissues both before and 10 days after cercarial infection, in order to identify potential miRNAs with roles in responding to a schistosome infection. Results Among the analysed miRNAs, 16 within the liver, 61 within the spleen and 10 within the lung, were differentially expressed in infected Wistar rats. Further analysis of the differentially expressed miRNAs revealed that many important signal pathways are triggered after infection with S. japonicum in Wistar rats. These include the signal transduction mechanisms associated with the Wnt and MAPK signaling pathways, cellular differentiation, with a particular emphasis on adipocyte and erythroid differentiation. Conclusions The results presented here include the identification of specific differentially expressed miRNAs within the liver, lungs and spleen of Wistar rats. These results highlighted the function of host miRNA regulation during an active schistosome infection. Our study provides a better understanding of the regulatory role of miRNA in schistosome infection, and host–parasite interactions in a non-permissive host environment. PMID:23617945

  10. Endothelial function after 10 days of bed rest in individuals at risk for type 2 diabetes and cardiovascular disease.

    PubMed

    Sonne, Mette P; Højbjerre, Lise; Alibegovic, Amra C; Nielsen, Lars B; Stallknecht, Bente; Vaag, Allan A; Dela, Flemming

    2011-10-01

    Physical inactivity is considered to be deleterious to vascular health, and in particular in first-degree relatives to patients with type 2 diabetes (FDR) and persons born with low birth weight (LBW), who may later in life develop cardiovascular disease. A period of imposed physical inactivity could unmask this risk. We hypothesized that the impact of physical inactivity on endothelial function would be more marked in subjects at increased risk for type 2 diabetes and cardiovascular disease (LBW and FDR) compared with a matched control group (CON), all of whom were recruited via advertisements and via the Danish Birth Registry. Twenty LBW, 20 CON and 13 FDR were studied before and after 10 days of bed rest. Forearm blood flow (FBF) was measured by venous occlusion plethysmography during brachial intra-arterial infusion of acetylcholine or adenosine at baseline and with superimposed hyperinsulinaemia. Markers of endothelial activation and inflammation were measured in plasma. Bed rest did not change the vasodilator responses to adenosine or acetylcholine alone in any group, but reduced vasodilator responses to adenosine or acetylcholine during hyperinsulinaemia in LBW. Bed rest impaired insulin-mediated vasodilatation in CON and LBW and increased endothelial activation markers in FDR and LBW but not in CON. Vasodilator responses were very low in FDR prior to bed rest, and did not decrease further during bed rest. Physical inactivity does not impair endothelium-dependent vasodilatation per se, but the vascular vasodilator effect of insulin diminished in CON and LBW after bed rest. In FDR, a further deterioration of FBF with inactivity is not possible.

  11. Components of the Goeckerman regimen.

    PubMed

    Le Vine, M J; White, H A; Parrish, J A

    1979-08-01

    Although application of tar products and subsequent exposure to ultraviolet radiation (the Goeckerman regimen) has repeatedly been demonstrated to be effective therapy for psoriasis, the therapeutic role of each component has remained uncertain. Utilizing the bilateral comparison technique in 30 hospitalized patients with chronic stable plaque-type psoriasis vulgaris, we closely monitored the clinical responses to ultraviolet radiation (Westinghouse fluorescent FS40 bulbs, 290--400 nm) and a variety of tar preparations and lubricant vehicles in combination and separately. We found that: 1) 4 weeks of maximally-aggressive exposure to ultraviolet radiation alone will markedly improve, but not completely clear, psoriasis unless combined with a tar preparation or lubricating base; 2) 5% crude coal tar plus ultraviolet radiation offers no clear advantage or benefit over lubricating base plus ultraviolet radiation; and 3) none of the tar preparations tested offered any consistent advantage over any other preparation.

  12. Single-dose (30 mg/kg) azithromycin compared with 10-day amoxicillin/clavulanate for the treatment of uncomplicated acute otitis media: a double-blind, placebo-controlled, randomized clinical trial☆

    PubMed Central

    Block, Stan L; Arrieta, Antonio; Seibel, Matthew; McLinn, Samuel; Eppes, Stephen; Murphy, Mary J

    2003-01-01

    Background: The long half-life of azithromycin allows for single-dose oral therapy for acute otitis media (AOM). Objective: This study was designed to compare the efficacy and tolerability of single-dose azithromycin with 10-day, twice-daily amoxicillin/clavulanate for the treatment of new-onset, uncomplicated AOM in children. Methods: Children aged 6 months to 12 years with new-onset AOM were randomly assigned to receive either a single 30-mg/kg dose of azithromycin or standard-dose amoxicillin/clavulanate (45 mg/kg administered BID for 10 days) in a double-blind, double-placebo, multicenter clinical trial. The diagnosis of AOM was based on specific clinical signs and symptoms, and was confirmed by pneumatic otoscopy and acoustic reflectometry (level ≥3). Clinical response was assessed on days 12–16 and 28–32. Results: Mean (SD) age of children receiving azithromycin (n = 173) or amoxicillin/clavulanate (n = 173) was 2.7 (2.3) years and 3.4 (2.8) years, respectively, with 43% and 36% ≤2 years of age. Most (53.2%) of the children were boys, and most (51.2%) were white. Clinical success rates (intent-to-treat) for azithromycin and amoxicillin/clavulanate, respectively, were 87% and 88% (95% CI, −9.2 to 6.5) on day 12–16 and 75% and 75% (95% CI, −10.2 to 10.5) on day 28–32. The incidences of treatment-related adverse events for azithromycin and amoxicillin/clavulanate were 16.8% and 22.5%, respectively. Corresponding rates of diarrhea were 6.4% and 12.7%, respectively. Vomiting, which was generally mild, occurred in 7 children in each group. One azithromycin patient and 5 amoxicillin/clavulanate patients discontinued treatment because of adverse events. The compliance rate for azithromycin was significantly higher than that for amoxicillin/clavulanate (99% vs 83%; P<0.001). Conclusions: In this trial comparing the efficacy of single-dose azithromycin (30 mg/kg) with twice-daily amoxicillin/clavulanate (45 mg/kg) for the treatment of new

  13. Sequential inductive learning

    SciTech Connect

    Gratch, J.

    1996-12-31

    This article advocates a new model for inductive learning. Called sequential induction, it helps bridge classical fixed-sample learning techniques (which are efficient but difficult to formally characterize), and worst-case approaches (which provide strong statistical guarantees but are too inefficient for practical use). Learning proceeds as a sequence of decisions which are informed by training data. By analyzing induction at the level of these decisions, and by utilizing the only enough data to make each decision, sequential induction provides statistical guarantees but with substantially less data than worst-case methods require. The sequential inductive model is also useful as a method for determining a sufficient sample size for inductive learning and as such, is relevant to learning problems where the preponderance of data or the cost of gathering data precludes the use of traditional methods.

  14. Sequential elution process

    DOEpatents

    Kingsley, I.S.

    1987-01-06

    A process and apparatus are disclosed for the separation of complex mixtures of carbonaceous material by sequential elution with successively stronger solvents. In the process, a column containing glass beads is maintained in a fluidized state by a rapidly flowing stream of a weak solvent, and the sample is injected into this flowing stream such that a portion of the sample is dissolved therein and the remainder of the sample is precipitated therein and collected as a uniform deposit on the glass beads. Successively stronger solvents are then passed through the column to sequentially elute less soluble materials. 1 fig.

  15. Remission-Induction Regimens in Acute Nonlymphocytic Leukemia

    PubMed Central

    Brennan, Donald C.; Lewis, Jerry P.

    1980-01-01

    A sequential study was carried out involving 40 adults with acute nonlymphocytic leukemia (ANLL). The first 20 patients were treated with cytarabine (Ara-C) and 6-thioguanine (6-TG), the second 20 with a regimen that added a three-day course of daunomycin (DNM) to the Ara-C and 6-TG therapy. With both groups well matched for age, patients in the DNM-treated group had a higher complete remission (CR) rate but failed to survive longer than those in the Ara-C and 6-TG treatment group. In a comprehensive literature review of various treatments for adult ANLL, a higher CR rate but not significantly better survival for patients initially treated with DNM-combined regimens was found. Our analysis of cases and literature review suggest that while DNM is a very active drug, its use in the initial treatment of adult ANLL has not produced a significant improvement in overall survival or in survival of those brought into complete remission. PMID:7347042

  16. Sequential Dependencies in Driving

    ERIC Educational Resources Information Center

    Doshi, Anup; Tran, Cuong; Wilder, Matthew H.; Mozer, Michael C.; Trivedi, Mohan M.

    2012-01-01

    The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find…

  17. Sequential Reliability Tests.

    ERIC Educational Resources Information Center

    Eiting, Mindert H.

    1991-01-01

    A method is proposed for sequential evaluation of reliability of psychometric instruments. Sample size is unfixed; a test statistic is computed after each person is sampled and a decision is made in each stage of the sampling process. Results from a series of Monte-Carlo experiments establish the method's efficiency. (SLD)

  18. Sequential memory: Binding dynamics

    NASA Astrophysics Data System (ADS)

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

    2015-10-01

    Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

  19. Three-day regimen of oseltamivir for postexposure prophylaxis of influenza in wards.

    PubMed

    Ishiguro, N; Oyamada, R; Nasuhara, Y; Yamada, T; Miyamoto, T; Imai, S; Akizawa, K; Fukumoto, T; Iwasaki, S; Iijima, H; Ono, K

    2016-10-01

    Inpatients who had been in close contact with patients with influenza were given oseltamivir [75mg capsules once daily for adults or 2mg/kg (maximum of 75mg) once daily for children] for three days as postexposure prophylaxis (PEP). The index patients with influenza were prescribed a neuraminidase inhibitor and were discharged immediately or transferred to isolation rooms. The protective efficacy of oseltamivir for three days was 93% overall [95% confidence interval (CI) 53-99%; P=0.023] and 94% for influenza A (95% CI 61-99%; P=0.017), which is comparable to that of seven- to 10-day regimens of oseltamivir as PEP.

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

    PubMed

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

    1986-01-01

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

  1. Intestinal Microbiota of Broiler Chickens As Affected by Litter Management Regimens.

    PubMed

    Wang, Lingling; Lilburn, Mike; Yu, Zhongtang

    2016-01-01

    Poultry litter is a mixture of bedding materials and enteric bacteria excreted by chickens, and it is typically reused for multiple growth cycles in commercial broiler production. Thus, bacteria can be transmitted from one growth cycle to the next via litter. However, it remains poorly understood how litter reuse affects development and composition of chicken gut microbiota. In this study, the effect of litter reuse on the microbiota in litter and in chicken gut was investigated using 2 litter management regimens: fresh vs. reused litter. Samples of ileal mucosa and cecal digesta were collected from young chicks (10 days of age) and mature birds (35 days of age). Based on analysis using DGGE and pyrosequencing of bacterial 16S rRNA gene amplicons, the microbiota of both the ileal mucosa and the cecal contents was affected by both litter management regimen and age of birds. Faecalibacterium, Oscillospira, Butyricicoccus, and one unclassified candidate genus closely related to Ruminococcus were most predominant in the cecal samples, while Lactobacillus was predominant in the ileal samples at both ages and in the cecal samples collected at day 10. At days 10 and 35, 8 and 3 genera, respectively, in the cecal luminal microbiota differed significantly in relative abundance between the 2 litter management regimens. Compared to the fresh litter, reused litter increased predominance of halotolerant/alkaliphilic bacteria and Faecalibacterium prausnitzii, a butyrate-producing gut bacterium. This study suggests that litter management regimens affect the chicken GI microbiota, which may impact the host nutritional status and intestinal health.

  2. Sequential measurements of conjugate observables

    NASA Astrophysics Data System (ADS)

    Carmeli, Claudio; Heinosaari, Teiko; Toigo, Alessandro

    2011-07-01

    We present a unified treatment of sequential measurements of two conjugate observables. Our approach is to derive a mathematical structure theorem for all the relevant covariant instruments. As a consequence of this result, we show that every Weyl-Heisenberg covariant observable can be implemented as a sequential measurement of two conjugate observables. This method is applicable both in finite- and infinite-dimensional Hilbert spaces, therefore covering sequential spin component measurements as well as position-momentum sequential measurements.

  3. Sequential cloning of chromosomes

    SciTech Connect

    Lacks, S.A.

    1991-12-31

    A method for sequential cloning of chromosomal DNA and chromosomal DNA cloned by this method are disclosed. The method includes the selection of a target organism having a segment of chromosomal DNA to be sequentially cloned. A first DNA segment, having a first restriction enzyme site on either side. homologous to the chromosomal DNA to be sequentially cloned is isolated. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  4. Sequential cloning of chromosomes

    DOEpatents

    Lacks, Sanford A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism's chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  5. Sequential cloning of chromosomes

    DOEpatents

    Lacks, S.A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes. 9 figs.

  6. Gonzalez Regimen (PDQ®)—Patient Version

    Cancer.gov

    Expert-reviewed information summary about the Gonzalez regimen as a treatment for people with cancer. Note: The information in this summary is no longer being updated and is provided for reference purposes only.

  7. Inference for the median residual life function in sequential multiple assignment randomized trials.

    PubMed

    Kidwell, Kelley M; Ko, Jin H; Wahed, Abdus S

    2014-04-30

    In survival analysis, median residual lifetime is often used as a summary measure to assess treatment effectiveness; it is not clear, however, how such a quantity could be estimated for a given dynamic treatment regimen using data from sequential randomized clinical trials. We propose a method to estimate a dynamic treatment regimen-specific median residual life (MERL) function from sequential multiple assignment randomized trials. We present the MERL estimator, which is based on inverse probability weighting, as well as, two variance estimates for the MERL estimator. One variance estimate follows from Lunceford, Davidian and Tsiatis' 2002 survival function-based variance estimate and the other uses the sandwich estimator. The MERL estimator is evaluated, and its two variance estimates are compared through simulation studies, showing that the estimator and both variance estimates produce approximately unbiased results in large samples. To demonstrate our methods, the estimator has been applied to data from a sequentially randomized leukemia clinical trial.

  8. Reliable VLSI sequential controllers

    NASA Technical Reports Server (NTRS)

    Whitaker, S.; Maki, G.; Shamanna, M.

    1990-01-01

    A VLSI architecture for synchronous sequential controllers is presented that has attractive qualities for producing reliable circuits. In these circuits, one hardware implementation can realize any flow table with a maximum of 2(exp n) internal states and m inputs. Also all design equations are identical. A real time fault detection means is presented along with a strategy for verifying the correctness of the checking hardware. This self check feature can be employed with no increase in hardware. The architecture can be modified to achieve fail safe designs. With no increase in hardware, an adaptable circuit can be realized that allows replacement of faulty transitions with fault free transitions.

  9. Generalized random sequential adsorption

    NASA Astrophysics Data System (ADS)

    Tarjus, G.; Schaaf, P.; Talbot, J.

    1990-12-01

    Adsorption of hard spherical particles onto a flat uniform surface is analyzed by using generalized random sequential adsorption (RSA) models. These models are defined by releasing the condition of immobility present in the usual RSA rules to allow for desorption or surface diffusion. Contrary to the simple RSA case, generalized RSA processes are no longer irreversible and the system formed by the adsorbed particles on the surface may reach an equilibrium state. We show by using a distribution function approach that the kinetics of such processes can be described by means of an exact infinite hierarchy of equations reminiscent of the Kirkwood-Salsburg hierarchy for systems at equilibrium. We illustrate the way in which the systems produced by adsorption/desorption and by adsorption/diffusion evolve between the two limits represented by ``simple RSA'' and ``equilibrium'' by considering approximate solutions in terms of truncated density expansions.

  10. Front-loaded linezolid regimens result in increased killing and suppression of the accessory gene regulator system of Staphylococcus aureus.

    PubMed

    Tsuji, Brian T; Brown, Tanya; Parasrampuria, Ridhi; Brazeau, Daniel A; Forrest, Alan; Kelchlin, Pamela A; Holden, Patricia N; Peloquin, Charles A; Hanna, Debra; Bulitta, Jurgen B

    2012-07-01

    Front loading is a strategy used to optimize the pharmacodynamic profile of an antibiotic through the administration of high doses early in therapy for a short duration. Our aims were to evaluate the impact of front loading of linezolid regimens on bacterial killing and suppression of resistance and on RNAIII, the effector molecule of the accessory gene regulator system (encoded by agr) in methicillin-resistant Staphylococcus aureus (MRSA). Time-killing experiments over 48 h were utilized for linezolid against four strains of MRSA: USA100, USA300, USA400, and ATCC 29213. A hollow-fiber infection model simulated traditional and front-loaded human therapeutic regimens of linezolid versus USA300 at 10(6) CFU/ml over 240 h. Over 48 h in time-kill experiments, linezolid displayed bacteriostatic activity, with reductions of >1 log(10) CFU/ml for all strains. Front-loaded regimens that were administered over 5 days, 1,200 mg every 12 h (q12h) (total, 10 doses) and 2,400 mg q12h (total, 10 doses) followed by 300 mg q12h thereafter, resulted in sustained bactericidal activity, with reductions of the area under the CFU curve of -6.15 and -6.03, respectively, reaching undetectable limits at the 10-day study endpoint. All regimens displayed a reduction in RNAIII relative expression at 24 h and 240 h compared with that of the growth control. Monte Carlo simulations predicted a <1.27× increase in the fractional decreases in platelets for all front-loaded regimens versus the 600 mg q12h regimen, except for the highest-dose front-loaded regimen. Front-loading strategies for linezolid are promising and may be of utility in severe MRSA infections, where early aggressive therapy is necessary.

  11. Influence of a 10-Day Mimic of Our Ancient Lifestyle on Anthropometrics and Parameters of Metabolism and Inflammation: The “Study of Origin”

    PubMed Central

    Ruiz-Núñez, Begoña; Raison, Charles L.; Muskiet, Frits A. J.

    2016-01-01

    Chronic low-grade inflammation and insulin resistance are intimately related entities that are common to most, if not all, chronic diseases of affluence. We hypothesized that a short-term intervention based on “ancient stress factors” may improve anthropometrics and clinical chemical indices. We executed a pilot study of whether a 10-day mimic of a hunter-gatherer lifestyle favorably affects anthropometrics and clinical chemical indices. Fifty-five apparently healthy subjects, in 5 groups, engaged in a 10-day trip through the Pyrenees. They walked 14 km/day on average, carrying an 8-kilo backpack. Raw food was provided and self-prepared and water was obtained from waterholes. They slept outside in sleeping bags and were exposed to temperatures ranging from 12 to 42°C. Anthropometric data and fasting blood samples were collected at baseline and the study end. We found important significant changes in most outcomes favoring better metabolic functioning and improved anthropometrics. Coping with “ancient mild stress factors,” including physical exercise, thirst, hunger, and climate, may influence immune status and improve anthropometrics and metabolic indices in healthy subjects and possibly patients suffering from metabolic and immunological disorders. PMID:27366752

  12. Influence of a 10-Day Mimic of Our Ancient Lifestyle on Anthropometrics and Parameters of Metabolism and Inflammation: The "Study of Origin".

    PubMed

    Pruimboom, Leo; Ruiz-Núñez, Begoña; Raison, Charles L; Muskiet, Frits A J

    2016-01-01

    Chronic low-grade inflammation and insulin resistance are intimately related entities that are common to most, if not all, chronic diseases of affluence. We hypothesized that a short-term intervention based on "ancient stress factors" may improve anthropometrics and clinical chemical indices. We executed a pilot study of whether a 10-day mimic of a hunter-gatherer lifestyle favorably affects anthropometrics and clinical chemical indices. Fifty-five apparently healthy subjects, in 5 groups, engaged in a 10-day trip through the Pyrenees. They walked 14 km/day on average, carrying an 8-kilo backpack. Raw food was provided and self-prepared and water was obtained from waterholes. They slept outside in sleeping bags and were exposed to temperatures ranging from 12 to 42°C. Anthropometric data and fasting blood samples were collected at baseline and the study end. We found important significant changes in most outcomes favoring better metabolic functioning and improved anthropometrics. Coping with "ancient mild stress factors," including physical exercise, thirst, hunger, and climate, may influence immune status and improve anthropometrics and metabolic indices in healthy subjects and possibly patients suffering from metabolic and immunological disorders.

  13. Comparative trial of 3 days of azithromycin versus 10 days of clarithromycin in the treatment of children with acute otitis media with effusion.

    PubMed

    Arguedas, A; Loaiza, C; Rodriguez, F; Herrera, M L; Mohs, E

    1997-02-01

    The authors compared the efficacy, safety and tolerance of azithromycin and clarithromycin in pediatric patients with acute otitis media. A randomized, open clinical trial was performed comparing azithromycin and clarithromycin in children aged 6 months to 12 years of age with acute otitis media with effusion. Patients were allocated to azithromycin at 10 mg/kg once daily for 3 days or to clarithromycin at 15 mg/kg day divided into two equal doses for 10 days. Clinical examinations and tympanometric evaluations were performed at baseline, day 3-5, day 10-14, day 28-30 and day 50-60. Tympanocentesis fluid cultures were collected at enrollment and urine and blood samples were obtained at baseline and day 10-14. Of 100 patients enrolled, 97 were considered evaluable. The most common middle ear pathogens were Streptococcus pneumoniae (60%), Haemophilus influenzae (15%) and Staphylococcus aureus (13%). Fifty patients (100%) treated with azithromycin and 45 (95.7%) patients treated with clarithromycin had a satisfactory clinical response. Rates of persistence of middle ear effusion and possible drug related side effects were comparable. Based on the efficacy and safety results, azithromycin for 3 days and clarithromycin for 10 days are considered to represent an attractive alternative for the treatment of children with acute otitis media.

  14. Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA (``Ecstasy'')

    NASA Astrophysics Data System (ADS)

    Ricaurte, George A.; Yuan, Jie; Hatzidimitriou, George; Cord, Branden J.; McCann, Una D.

    2002-09-01

    The prevailing view is that the popular recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, or ``ecstasy'') is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic neurotoxicity. MDMA neurotoxicity was associated with increased vulnerability to motor dysfunction secondary to dopamine depletion. These results have implications for mechanisms of MDMA neurotoxicity and suggest that recreational MDMA users may unwittingly be putting themselves at risk, either as young adults or later in life, for developing neuropsychiatric disorders related to brain dopamine and/or serotonin deficiency.

  15. Multi-Attribute Sequential Search

    ERIC Educational Resources Information Center

    Bearden, J. Neil; Connolly, Terry

    2007-01-01

    This article describes empirical and theoretical results from two multi-attribute sequential search tasks. In both tasks, the DM sequentially encounters options described by two attributes and must pay to learn the values of the attributes. In the "continuous" version of the task the DM learns the precise numerical value of an attribute when she…

  16. Adaptive sequential controller

    DOEpatents

    El-Sharkawi, Mohamed A.; Xing, Jian; Butler, Nicholas G.; Rodriguez, Alonso

    1994-01-01

    An adaptive sequential controller (50/50') for controlling a circuit breaker (52) or other switching device to substantially eliminate transients on a distribution line caused by closing and opening the circuit breaker. The device adaptively compensates for changes in the response time of the circuit breaker due to aging and environmental effects. A potential transformer (70) provides a reference signal corresponding to the zero crossing of the voltage waveform, and a phase shift comparator circuit (96) compares the reference signal to the time at which any transient was produced when the circuit breaker closed, producing a signal indicative of the adaptive adjustment that should be made. Similarly, in controlling the opening of the circuit breaker, a current transformer (88) provides a reference signal that is compared against the time at which any transient is detected when the circuit breaker last opened. An adaptive adjustment circuit (102) produces a compensation time that is appropriately modified to account for changes in the circuit breaker response, including the effect of ambient conditions and aging. When next opened or closed, the circuit breaker is activated at an appropriately compensated time, so that it closes when the voltage crosses zero and opens when the current crosses zero, minimizing any transients on the distribution line. Phase angle can be used to control the opening of the circuit breaker relative to the reference signal provided by the potential transformer.

  17. Short-term effects on bone turnover of replacing milk with cola beverages: a 10-day interventional study in young men.

    PubMed

    Kristensen, Mette; Jensen, Marlene; Kudsk, Jane; Henriksen, Marianne; Mølgaard, Christian

    2005-12-01

    In the Western world, increased consumption of carbonated soft drinks combined with a decreasing intake of milk may increase the risk of osteoporosis. This study was designed to reflect the trend of replacing milk with carbonated beverages in a group of young men on a low-calcium diet and studies the effects of this replacement on calcium homeostasis and bone turnover. This controlled crossover intervention study included 11 healthy men (22-29 years) who were given a low-calcium basic diet in two 10-day intervention periods with an intervening 10-day washout. During one period, they drank 2.5 l of Coca Cola per day and during the other period 2.5 l of semi-skimmed milk. Serum concentrations of calcium, phosphate, 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol (1,25(OH)2D), osteocalcin, bone-specific alkaline phosphatase (B-ALP) and cross-linked C-telopeptides (CTX), plasma intact parathyroid hormone (PTH) and urinary cross-linked N-telopeptides (NTX) were determined at baseline and endpoint of each intervention period. An increase in serum phosphate (P<0.001), 1,25(OH)2D (P<0.001), PTH (P=0.046) and osteocalcin (P<0.001) was observed in the cola period compared to the milk period. Also, bone resorption was significantly increased following the cola period, seen as increased serum CTX (P<0.001) and urinary NTX (P<0.001) compared to the milk period. No changes were observed in serum concentrations of calcium or B-ALP. This study demonstrates that over a 10-day period high intake of cola with a low-calcium diet induces increased bone turnover compared to a high intake of milk with a low-calcium diet. Thus, the trend towards a replacement of milk with cola and other soft drinks, which results in a low calcium intake, may negatively affect bone health as indicated by this short-term study.

  18. Sequential biases in accumulating evidence

    PubMed Central

    Huggins, Richard; Dogo, Samson Henry

    2015-01-01

    Whilst it is common in clinical trials to use the results of tests at one phase to decide whether to continue to the next phase and to subsequently design the next phase, we show that this can lead to biased results in evidence synthesis. Two new kinds of bias associated with accumulating evidence, termed ‘sequential decision bias’ and ‘sequential design bias’, are identified. Both kinds of bias are the result of making decisions on the usefulness of a new study, or its design, based on the previous studies. Sequential decision bias is determined by the correlation between the value of the current estimated effect and the probability of conducting an additional study. Sequential design bias arises from using the estimated value instead of the clinically relevant value of an effect in sample size calculations. We considered both the fixed‐effect and the random‐effects models of meta‐analysis and demonstrated analytically and by simulations that in both settings the problems due to sequential biases are apparent. According to our simulations, the sequential biases increase with increased heterogeneity. Minimisation of sequential biases arises as a new and important research area necessary for successful evidence‐based approaches to the development of science. © 2015 The Authors. Research Synthesis Methods Published by John Wiley & Sons Ltd. PMID:26626562

  19. Intestinal Microbiota of Broiler Chickens As Affected by Litter Management Regimens

    PubMed Central

    Wang, Lingling; Lilburn, Mike; Yu, Zhongtang

    2016-01-01

    Poultry litter is a mixture of bedding materials and enteric bacteria excreted by chickens, and it is typically reused for multiple growth cycles in commercial broiler production. Thus, bacteria can be transmitted from one growth cycle to the next via litter. However, it remains poorly understood how litter reuse affects development and composition of chicken gut microbiota. In this study, the effect of litter reuse on the microbiota in litter and in chicken gut was investigated using 2 litter management regimens: fresh vs. reused litter. Samples of ileal mucosa and cecal digesta were collected from young chicks (10 days of age) and mature birds (35 days of age). Based on analysis using DGGE and pyrosequencing of bacterial 16S rRNA gene amplicons, the microbiota of both the ileal mucosa and the cecal contents was affected by both litter management regimen and age of birds. Faecalibacterium, Oscillospira, Butyricicoccus, and one unclassified candidate genus closely related to Ruminococcus were most predominant in the cecal samples, while Lactobacillus was predominant in the ileal samples at both ages and in the cecal samples collected at day 10. At days 10 and 35, 8 and 3 genera, respectively, in the cecal luminal microbiota differed significantly in relative abundance between the 2 litter management regimens. Compared to the fresh litter, reused litter increased predominance of halotolerant/alkaliphilic bacteria and Faecalibacterium prausnitzii, a butyrate-producing gut bacterium. This study suggests that litter management regimens affect the chicken GI microbiota, which may impact the host nutritional status and intestinal health. PMID:27242676

  20. Sequential or combination antifungal therapy with voriconazole and liposomal amphotericin B in a Guinea pig model of invasive aspergillosis.

    PubMed

    Kirkpatrick, William R; Coco, Brent J; Patterson, Thomas F

    2006-04-01

    We evaluated combinations of voriconazole (VRC) and liposomal amphotericin B (L-AMB) in a guinea pig invasive aspergillosis model. Simultaneous VRC and L-AMB was most effective, although VRC monotherapy was also effective. These regimens as well as sequential L-AMB followed by VRC were more effective than L-AMB alone or VRC followed by L-AMB.

  1. Sequential Testing: Basics and Benefits

    DTIC Science & Technology

    1978-03-01

    103-109 44. A. Wald , Sequential Analysis, John Wiley and Sons, 1947 45. A Wald and J. Wolfowitz , "Optimum Character of The Sequential Probability Ratio...work done by A. Wald [44].. Wald’s work on sequential analysis can be used virtually’without modification in a situation where decisions are made... Wald can be used. The decision to accept, reject, or continue the test depends on: 8 < (8 0/el)r exp [-(1/01 - 1/0 0 )V(t)] < A (1) where 0 and A are

  2. Prophylactic antibiotic regimens in tumour surgery (PARITY)

    PubMed Central

    Investigators, The PARITY

    2015-01-01

    Objective Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. Methods We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. Results We screened 96 patients and enrolled 60 participants (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. Conclusions It is feasible to conduct a definitive multi-centre RCT of post-operative antibiotic regimens in patients with bone sarcomas, but further expansion of our collaborative network will be critical. We have demonstrated an ability to coordinate in multiple countries, enrol participants, maintain protocol adherence, and minimise losses to follow-up. Cite this article: Bone Joint Res;4:154–162 PMID:26423584

  3. Augment railgun and sequential discharge

    NASA Astrophysics Data System (ADS)

    Kobayashi, K.

    1993-01-01

    Proprietary R&D efforts toward the creation of tactical weapon systems-applicable railguns are presented. Attention is given to measures taken for projectile velocity maximization and sequential-discharge operation, and to an augmenting railgun which has demonstrated a 66-percent efficiency improvement over the two-rail baseline railgun system. This device is characterized by strong interaction between capacitor bank submodules during sequential discharge.

  4. Sequentially pulsed traveling wave accelerator

    DOEpatents

    Caporaso, George J.; Nelson, Scott D.; Poole, Brian R.

    2009-08-18

    A sequentially pulsed traveling wave compact accelerator having two or more pulse forming lines each with a switch for producing a short acceleration pulse along a short length of a beam tube, and a trigger mechanism for sequentially triggering the switches so that a traveling axial electric field is produced along the beam tube in synchronism with an axially traversing pulsed beam of charged particles to serially impart energy to the particle beam.

  5. LunHab: Interactive effects of a 10-day sustained exposure to hypoxia and bedrest on aerobic exercise capacity in male lowlanders.

    PubMed

    Keramidas, Michail E; Mekjavic, Igor B; Eiken, Ola

    2017-04-09

    The study examined the interactive effects of a 10-day exposure to hypoxia and bedrest on the whole body peak oxygen uptake (V˙O2 peak ) during maximal exercise, and on skeletal-muscle and cerebral oxygenation during submaximal exercise. Nine males underwent three 10-day confinements, in a Latin-square order: (i) a normoxic bedrest [NBR; partial pressure of inspired O2 (PI O2 ) = 134.2 ± 0.7 mmHg], (ii) a hypoxic bedrest (HBR; PI O2  = 102.9 ± 0.1 mmHg at day 1, 91.5 ± 1.2 mmHg at days 3-10), and (iii) a hypoxic ambulation (HAMB; PI O2 as in HBR). Before, one (R + 1) and three (R+3) days after each confinement, subjects performed exhaustive, incremental-load and moderate-intensity constant-load (CLTs) cycle-ergometry trials, while breathing either room air, or a hypoxic gas mixture. During the CLTs, changes in the regional oxygenation of the cerebral frontal cortex, and the vastus lateralis and intercostal muscles were monitored with near-infrared spectroscopy. At R+1, the confinement-related impairment in V˙O2 peak was greater after HBR than after NBR or HAMB, regardless of whether the trial was performed in room-air or hypoxia (HBR: -16.2%, NBR: -8.3%, HAMB: -4.1%; P = 0.001). During the CLTs, bedrest aggravated the exercise-induced reduction in locomotor- and respiratory-muscle oxygenation (P ≤ 0.05); an effect that was less after HBR than after NBR (P ≤ 0.05). The hypoxia exercise-induced cerebral vasodilatatory response was blunted by HBR, likely due to the marked hyperventilation-dependent hypocapnea, attendant to the sustained hypoxic stimulus. Hence, short-term exposure to hypoxia potentiates the reduction in V˙O2 peak , but it mitigates the impairment in skeletal-muscle oxidative capacity induced by bedrest. This article is protected by copyright. All rights reserved.

  6. Comparison of clinical efficacy between 3-day combined clavulanate/amoxicillin preparation treatment and 10-day amoxicillin treatment in children with pharyngolaryngitis or tonsillitis.

    PubMed

    Kuroki, Haruo; Ishiwada, Naruhiko; Inoue, Nobue; Ishikawa, Nobuyasu; Suzuki, Hiroshi; Himi, Kyoko; Kurosaki, Tomomichi

    2013-02-01

    The efficacy of 3-day treatment with a combined clavulanate/amoxicillin preparation (Clavamox combination dry syrup for pediatric cases) and 10-day treatment with amoxicillin against pediatric pharyngolaryngitis and tonsillitis caused by Group A β-hemolytic Streptococcus was compared. Among the patients included in the efficacy evaluation (54 from the clavulanate/amoxicillin group and 43 from the amoxicillin group), the clinical response rate on completion of treatment was 98.1 % in the clavulanate/amoxicillin group and 92.9 % in the amoxicillin group, thus supporting the equivalent efficacy of these two therapies. The Group A β-hemolytic Streptococcus eradication rate at approximately 1-2 weeks after completion/discontinuation of treatment was 65.4 % in the clavulanate/amoxicillin group and 85.4 % in the amoxicillin group. Even in cases from which the pathogen continued to be isolated, relapse/recurrence of clinical symptoms was seldom seen. Urinalysis, conducted to assess the presence or absence of acute glomerulonephritis, revealed no abnormality in any patient. These results suggest that 3-day treatment with this clavulanate/amoxicillin preparation is expected to provide a valid means of treating pediatric pharyngolaryngitis and tonsillitis caused by Group A β-hemolytic Streptococcus.

  7. EPIC 211391664b: A 32 M ⊕ Neptune-size Planet in a 10 Day Orbit Transiting an F8 Star

    NASA Astrophysics Data System (ADS)

    Barragán, Oscar; Grziwa, Sascha; Gandolfi, Davide; Fridlund, Malcolm; Endl, Michael; Deeg, Hans J.; Cagigal, Manuel P.; Lanza, Antonino F.; Prada Moroni, Pier G.; Smith, Alexis M. S.; Korth, Judith; Bedell, Megan; Cabrera, Juan; Cochran, William D.; Cusano, Felice; Csizmadia, Szilard; Eigmüller, Philipp; Erikson, Anders; Guenther, Eike W.; Hatzes, Artie P.; Nespral, David; Pätzold, Martin; Prieto-Arranz, Jorge; Rauer, Heike

    2016-12-01

    We report the discovery of K2-98b (EPIC 211391664b), a transiting Neptune-size planet monitored by the K2 mission during its Campaign 5. We combine the K2 time-series data with ground-based photometric and spectroscopic follow-up observations to confirm the planetary nature of the object and derive its mass, radius, and orbital parameters. K2-98b is a warm Neptune-like planet in a 10 day orbit around a V = 12.2 mag F-type star with M ⋆ = 1.074 ± 0.042 M ⊙, R ⋆ = {1.311}-0.048+0.083 R ⊙, and age of {5.2}-1.0+1.2 {Gyr}. We derive a planetary mass and radius of M p = 32.2 ± 8.1 M ⊕ and R p = {4.3}-0.2+0.3 R ⊕. K2-98b joins the relatively small group of Neptune-size planets whose mass and radius have been derived with a precision better than 25%. We estimate that the planet will be engulfed by its host star in ∼3 Gyr, due to the evolution of the latter toward the red giant branch.

  8. Effects of 10 days 6 degrees head-down tilt on the responses to fluid loading and lower body negative pressure

    NASA Technical Reports Server (NTRS)

    Baisch, F.; Heer, M.; Beck, L.; Blomqvist, C. G.; Kropp, J.; Schulz, H.; Hillebrecht, A.; Meyer, M.

    1991-01-01

    In an international collaborative project six normal male subjects were studied before, during and after 10 days 6 degrees HDT. Fluid intake was controlled at 40 ml/(kgbw day). Urine volume and body weight were determined daily. Fluid loading and LBNP were performed in all three phases of the study. Body weight diminished by 2.6% because of fluid loss. Blood volume diminished by 13%. The responses to fluid loading were similar in the three phases of the study. Sixty minutes after end of infusion only 5.5% of the infused saline remained in the intravascular compartment. Excess interstitial fluid was eliminated in the next 24 hs but a negative balance was recorded also in the following day. The compliance of the lower limbs expressed as the rate of limb volume change/unit LBNP change was increased at the end of the HDT phase and during the post HDT phase. The set point of intravascular volume was defended, as shown by the response to FL. HDT increased the compliance of the lower limbs.

  9. Treatment of mites folliculitis with an ornidazole-based sequential therapy

    PubMed Central

    Luo, Yang; Sun, Yu-Jiao; Zhang, Li; Luan, Xiu-Li

    2016-01-01

    Abstract Objective: Treatment of Demodex infestations is often inadequate and associated with low effective rate. We sought to evaluate the efficacy of an ornidazole-based sequential therapy for mites folliculitis treatment. Methods: Two-hundred patients with mites folliculitis were sequentially treated with either an ornidazole- or metronidazole-based regimen. Sebum cutaneum was extruded from the sebaceous glands of each patient's nose and the presence of Demodex mites were examined by light microscopy. The clinical manifestations of relapse of mites folliculitis were recorded and the subjects were followed up at 2, 4, 8, and 12 weeks post-treatment. Results: Patients treated with the ornidazole-based regimen showed an overall effective rate of 94.0%. Additionally, at the 2, 4, 8, and 12-week follow-up, these patients had significantly lower rates of Demodex mite relapse and new lesion occurrence compared with patients treated with the metronidazole-based regimen (P < 0.05). Conclusion: Sequential therapy using ornidazole, betamethasone, and recombinant bovine basic fibroblast growth factor (rbFGF) gel is highly effective for treating mites folliculitis. PMID:27399141

  10. Sequential Syndrome Decoding of Convolutional Codes

    NASA Technical Reports Server (NTRS)

    Reed, I. S.; Truong, T. K.

    1984-01-01

    The algebraic structure of convolutional codes are reviewed and sequential syndrome decoding is applied to those codes. These concepts are then used to realize by example actual sequential decoding, using the stack algorithm. The Fano metric for use in sequential decoding is modified so that it can be utilized to sequentially find the minimum weight error sequence.

  11. Blocking for Sequential Political Experiments.

    PubMed

    Moore, Ryan T; Moore, Sally A

    2013-10-01

    In typical political experiments, researchers randomize a set of households, precincts, or individuals to treatments all at once, and characteristics of all units are known at the time of randomization. However, in many other experiments, subjects "trickle in" to be randomized to treatment conditions, usually via complete randomization. To take advantage of the rich background data that researchers often have (but underutilize) in these experiments, we develop methods that use continuous covariates to assign treatments sequentially. We build on biased coin and minimization procedures for discrete covariates and demonstrate that our methods outperform complete randomization, producing better covariate balance in simulated data. We then describe how we selected and deployed a sequential blocking method in a clinical trial and demonstrate the advantages of our having done so. Further, we show how that method would have performed in two larger sequential political trials. Finally, we compare causal effect estimates from differences in means, augmented inverse propensity weighted estimators, and randomization test inversion.

  12. A bit serial sequential circuit

    NASA Technical Reports Server (NTRS)

    Hu, S.; Whitaker, S.

    1990-01-01

    Normally a sequential circuit with n state variables consists of n unique hardware realizations, one for each state variable. All variables are processed in parallel. This paper introduces a new sequential circuit architecture that allows the state variables to be realized in a serial manner using only one next state logic circuit. The action of processing the state variables in a serial manner has never been addressed before. This paper presents a general design procedure for circuit construction and initialization. Utilizing pass transistors to form the combinational next state forming logic in synchronous sequential machines, a bit serial state machine can be realized with a single NMOS pass transistor network connected to shift registers. The bit serial state machine occupies less area than other realizations which perform parallel operations. Moreover, the logical circuit of the bit serial state machine can be modified by simply changing the circuit input matrix to develop an adaptive state machine.

  13. Chronic central administration of apelin-13 over 10 days increases food intake, body weight, locomotor activity and body temperature in C57BL/6 mice.

    PubMed

    Valle, A; Hoggard, N; Adams, A C; Roca, P; Speakman, J R

    2008-01-01

    The peptide apelin has been located in a wide range of tissues, including the gastrointestinal tract, stomach and adipose tissue. Apelin and its receptor has also been detected in the arcuate and paraventricular nuclei of the hypothalamus, which are involved in the control of feeding behaviour and energy expenditure. This distribution suggests apelin may play a role in energy homeostasis, but previous attempts to discern the effects of apelin by acute injection into the brain have yielded conflicting results. We examined the effect of a chronic 10-day intracerebroventricular (i.c.v.) infusion of apelin-13 into the third ventricle on food intake, body temperature and locomotor activity in C57BL/6 mice. Apelin-13 (1 microg/day) increased food intake significantly on days 3-7 of infusion; thereafter, food intake of treated and control individuals converged. This convergence was potentially because of progressive conversion of apelin-13 to [Pyr(1)]apelin-13 which has a four-fold lower receptor binding affinity at the orphan G protein-coupled receptor, APJ. Locomotor activity was also higher in the apelin-treated mice, especially during the nocturnal peak, when most feeding occurs, and the first hours of the light phase. Body temperature was also elevated during this increased period of activity, but was otherwise unaffected. Apelin-13-infused animals gained more weight than the saline-infused controls, suggesting the elevated locomotor activity did not offset the increased food intake. Elevated locomotion and the consequent increases in body temperature were probably secondary effects to the increased food intake. These results suggest that apelin-13 may play a central role in the control of feeding behaviour and is one of only two peripheral ligands known to stimulate rather than inhibit intake. As apelin production is elevated during obesity, this may provide an important feed-forward mechanism exacerbating the problem. Antagonists of the apelin receptor may

  14. Complementary sequential measurements generate entanglement

    NASA Astrophysics Data System (ADS)

    Coles, Patrick J.; Piani, Marco

    2014-01-01

    We present a paradigm for capturing the complementarity of two observables. It is based on the entanglement created by the interaction between the system observed and the two measurement devices used to measure the observables sequentially. Our main result is a lower bound on this entanglement and resembles well-known entropic uncertainty relations. Besides its fundamental interest, this result directly bounds the effectiveness of sequential bipartite operations—corresponding to the measurement interactions—for entanglement generation. We further discuss the intimate connection of our result with two primitives of information processing, namely, decoupling and coherent teleportation.

  15. Evaluation Using Sequential Trials Methods.

    ERIC Educational Resources Information Center

    Cohen, Mark E.; Ralls, Stephen A.

    1986-01-01

    Although dental school faculty as well as practitioners are interested in evaluating products and procedures used in clinical practice, research design and statistical analysis can sometimes pose problems. Sequential trials methods provide an analytical structure that is both easy to use and statistically valid. (Author/MLW)

  16. Sequential Effects in Essay Ratings

    ERIC Educational Resources Information Center

    Attali, Yigal

    2011-01-01

    Contrary to previous research on sequential ratings of student performance, this study found that professional essay raters of a large-scale standardized testing program produced ratings that were drawn toward previous ratings, creating an assimilation effect. Longer intervals between the two adjacent ratings and higher degree of agreement with…

  17. Effect of 10 days of bedrest on metabolic and vascular insulin action: a study in individuals at risk for type 2 diabetes.

    PubMed

    Sonne, Mette P; Alibegovic, Amra C; Højbjerre, Lise; Vaag, Allan; Stallknecht, Bente; Dela, Flemming

    2010-04-01

    Physical inactivity is a known risk factor for type 2 diabetes. We studied whole body and forearm insulin sensitivity in subjects at increased risk for type 2 diabetes [persons with low birth weight (LBW group; n = 20) and first-degree relatives to type 2 diabetic patients (FDR group; n = 13)] as well as a control (CON) group (n = 20) matched for body mass index, age, and physical activity levels before and after 10 days of bedrest. Subjects were studied by hyperinsulinemic isoglycemic clamp combined with arterial and deep venous catheterization of the forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. All groups responded with a decrease in whole body insulin sensitivity in response to bedrest [CON group: 6.8 +/- 0.5 to 4.3 +/- 0.3 mg x min(-1) x kg(-1) (P < 0.0001), LBW group: 6.2 +/- 0.5 to 4.3 +/- 0.3 mg x min(-1) x kg(-1) (P < 0.0001), and FDR group: 4.3 +/- 0.7 to 3.1 +/- 0.3 mg x min(-1) x kg(-1) (P = 0.068)]. The percent decrease was significantly greater in the CON group compared with the FDR group (CON group: 34 +/- 4%, LBW group: 27 +/- 4%, and FDR group: 10 +/- 13%). Forearm insulin-stimulated glucose clearance decreased significantly in the CON and LBW groups in response to bedrest; in the FDR group, clearance was very low before bedrest and no change was observed. Before bedrest, the CON and LBW groups demonstrated a significant increase in FBF during hyperinsulinemia; after bedrest, an increase in FBF was observed only in the CON group. In conclusion, bedrest induced a pronounced reduction in whole body, skeletal muscle, and vascular insulin sensitivity in the CON and LBW groups. The changes were most pronounced in the CON group. In the FDR group, insulin resistance was already present before bedrest, but even this group displayed a high sensitivity to changes in daily physical activity.

  18. A Comparison of Breast Cancer Treatment Regimens by Demographic Characteristics

    DTIC Science & Technology

    1998-10-01

    Cancer Treatment Regimens by Demographic Characteristics PRINCIPAL INVESTIGATOR: Marianne E. Ulcickas Yood, M.P.H. CONTRACTING ORGANIZATION: Henry...NUMBERS A Comparison of Breast Cancer Treatment Regimens by Demographic Characteristics DAMD17-97-1-7302 6. AUTHOR(S) Marianne E. Ulcickas Yood, M.P.H. 7... Cancer Treatment Regimens by Demographic Characteristics (DAMD17-97-1-7302), Annual Report October, 1998 TABLE OF CONTENTS Introduction

  19. Prevalence of inappropriate tuberculosis treatment regimens: a systematic review

    PubMed Central

    Langendam, M.W.; van der Werf, M.J.; Huitric, E.; Manissero, D.

    2012-01-01

    A potential threat to the success of new tuberculosis (TB) drugs is the development of resistance. Using drugs in appropriate regimens, such as those recommended in the World Health Organization (WHO) treatment guidelines, prevents the development of resistance. We performed a systematic review to assess the prevalence of inappropriate prescription of TB drugs for the treatment of TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Observational studies published from 2000 that included TB patients receiving treatment were selected. A treatment regimen was considered inappropriate if the regimen was not a WHO recommended regimen. 37 studies were included. Inappropriate treatment regimens were prescribed in 67% of studies. The percentage of patients receiving inappropriate regimens varied between 0.4% and 100%. In 19 studies the quality of treatment regimen reporting was low. Despite the fact that assessment of inappropriate treatment was hampered by low quality of reporting, our data indicate a reasonable amount of inappropriate prescription of TB treatment regimens. Thus, there is a risk that new drugs will be used in inappropriate treatment regimens, even with WHO guidelines in place, introducing the risk of resistance development. This article highlights the need to improve implementation of the WHO treatment of TB guidelines. PMID:22005923

  20. Dynamics of Sequential Decision Making

    NASA Astrophysics Data System (ADS)

    Rabinovich, Mikhail I.; Huerta, Ramón; Afraimovich, Valentin

    2006-11-01

    We suggest a new paradigm for intelligent decision-making suitable for dynamical sequential activity of animals or artificial autonomous devices that depends on the characteristics of the internal and external world. To do it we introduce a new class of dynamical models that are described by ordinary differential equations with a finite number of possibilities at the decision points, and also include rules solving this uncertainty. Our approach is based on the competition between possible cognitive states using their stable transient dynamics. The model controls the order of choosing successive steps of a sequential activity according to the environment and decision-making criteria. Two strategies (high-risk and risk-aversion conditions) that move the system out of an erratic environment are analyzed.

  1. On Disturbed Sequential Hypothesis Testing

    DTIC Science & Technology

    1991-06-01

    procedures over the classical single sensor schemes. 14. SUBJECT TERMS iS NUMBER OF PAGES Sensor Fusion, Signal Processing, Detection Comunication 150...matrix. Proakis [28] described the random walk formulation approach and derived the exact distribution of the test length T and the ASN for quantized...Trans. Inform. Theory vol. IT-26, No. 2, pp. 255-259, March 1980. 141 [28] J. G. Proakis , "Exact distribution functions of test length for sequential

  2. Sequential cyclophosphamide-bortezomib-dexamethasone unmasks the harmful cardiac effect of dexamethasone in primary light-chain cardiac amyloidosis.

    PubMed

    Le Bras, Fabien; Molinier-Frenkel, Valerie; Guellich, Aziz; Dupuis, Jehan; Belhadj, Karim; Guendouz, Soulef; Ayad, Karima; Colombat, Magali; Benhaiem, Nicole; Tissot, Claire Marie; Hulin, Anne; Jaccard, Arnaud; Damy, Thibaud

    2017-03-20

    Chemotherapy combining cyclophosphamide, bortezomib and dexamethasone is widely used in light-chain amyloidosis. The benefit is limited in patients with cardiac amyloidosis mainly because of adverse cardiac events. Retrospective analysis of our cohort showed that 39 patients died with 42% during the first month. A new escalation-sequential regimen was set to improve the outcomes. Nine newly-diagnosed patients were prospectively treated with close monitoring of serum N-terminal pro-brain natriuretic peptide, troponin-T and free light chains. The results show that corticoids may destabilise the heart through fluid retention. Thus, a sequential protocol may be a promising approach to treat these patients.

  3. Individualizing phenytoin dosage regimens using a programmable calculator.

    PubMed

    Ng, P K

    1980-04-01

    A programmable calculator procedure for the determination of individualized phenytoin dosage regimens is described. The calculator is programmed based on a one-compartment, open model using the Michaelis-Menten equation. A detailed description of the programs and user instructions are presented. The programs allow calculation of oral dosage regimens and steady-state phenytoin levels. The first two programs require a given dose and one corresponding steady-state minimum concentration point to estimate a dosage regimen and steady-state serum level. The second two programs, which provide a more accurate prediction of dosage regimen and steady-state serum levels, require two dose and steady-state minimum concentration poits. The calculator programs provide a rapid and reliable means of estimating a patient's phenytoin dosage regimens and steady-state serum levels.

  4. In silico evaluation and exploration of antibiotic tuberculosis treatment regimens

    DOE PAGES

    Pienaar, Elsje; Dartois, Véronique; Linderman, Jennifer J.; ...

    2015-11-14

    Improvement in tuberculosis treatment regimens requires selection of antibiotics and dosing schedules from a large design space of possibilities. Incomplete knowledge of antibiotic and host immune dynamics in tuberculosis granulomas impacts clinical trial design and success, and variations among clinical trials hamper side-by-side comparison of regimens. Our objective is to systematically evaluate the efficacy of isoniazid and rifampin regimens, and identify modifications to these antibiotics that improve treatment outcomes. We pair a spatio-temporal computational model of host immunity with pharmacokinetic and pharmacodynamic data on isoniazid and rifampin. The model is calibrated to plasma pharmacokinetic and granuloma bacterial load data frommore » non-human primate models of tuberculosis and to tissue and granuloma measurements of isoniazid and rifampin in rabbit granulomas. We predict the efficacy of regimens containing different doses and frequencies of isoniazid and rifampin. We predict impacts of pharmacokinetic/pharmacodynamic modifications on antibiotic efficacy. We demonstrate that suboptimal antibiotic concentrations within granulomas lead to poor performance of intermittent regimens compared to daily regimens. Improvements from dose and frequency changes are limited by inherent antibiotic properties, and we propose that changes in intracellular accumulation ratios and antimicrobial activity would lead to the most significant improvements in treatment outcomes. Results suggest that an increased risk of drug resistance in fully intermittent as compared to daily regimens arises from higher bacterial population levels early during treatment. In conclusion, our systems pharmacology approach complements efforts to accelerate tuberculosis therapeutic development.« less

  5. Random sequential adsorption on fractals.

    PubMed

    Ciesla, Michal; Barbasz, Jakub

    2012-07-28

    Irreversible adsorption of spheres on flat collectors having dimension d < 2 is studied. Molecules are adsorbed on Sierpinski's triangle and carpet-like fractals (1 < d < 2), and on general Cantor set (d < 1). Adsorption process is modeled numerically using random sequential adsorption (RSA) algorithm. The paper concentrates on measurement of fundamental properties of coverages, i.e., maximal random coverage ratio and density autocorrelation function, as well as RSA kinetics. Obtained results allow to improve phenomenological relation between maximal random coverage ratio and collector dimension. Moreover, simulations show that, in general, most of known dimensional properties of adsorbed monolayers are valid for non-integer dimensions.

  6. Sequential ranging: How it works

    NASA Technical Reports Server (NTRS)

    Baugh, Harold W.

    1993-01-01

    This publication is directed to the users of data from the Sequential Ranging Assembly (SRA), and to others who have a general interest in range measurements. It covers the hardware, the software, and the processes used in acquiring range data; it does not cover analytical aspects such as the theory of modulation, detection, noise spectral density, and other highly technical subjects. In other words, it covers how ranging is done, but not the details of why it works. The publication also includes an appendix that gives a brief discussion of PN ranging, a capability now under development.

  7. A high speed sequential decoder

    NASA Technical Reports Server (NTRS)

    Lum, H., Jr.

    1972-01-01

    The performance and theory of operation for the High Speed Hard Decision Sequential Decoder are delineated. The decoder is a forward error correction system which is capable of accepting data from binary-phase-shift-keyed and quadriphase-shift-keyed modems at input data rates up to 30 megabits per second. Test results show that the decoder is capable of maintaining a composite error rate of 0.00001 at an input E sub b/N sub o of 5.6 db. This performance has been obtained with minimum circuit complexity.

  8. The Sequential Parameter Optimization Toolbox

    NASA Astrophysics Data System (ADS)

    Bartz-Beielstein, Thomas; Lasarczyk, Christian; Preuss, Mike

    The sequential parameter optimization toolbox (SPOT) is one possible implementation of the SPO framework introduced in Chap. 2. It has been successfully applied to numerous heuristics for practical and theoretical optimization problems. We describe the mechanics and interfaces employed by SPOT to enable users to plug in their own algorithms. Furthermore, two case studies are presented to demonstrate how SPOT can be applied in practice, followed by a discussion of alternative metamodels to be plugged into it.We conclude with some general guidelines.

  9. Increasing aclarubicin dosage of the conventional CAG (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor) regimen is more efficacious as a salvage therapy than CAG for relapsed/refractory acute myeloid leukemia.

    PubMed

    Qu, Qi; Liu, Limin; Zhang, Yanming; Li, Xiaoli; Wu, Depei

    2015-12-01

    The efficacy and safety of a modified CAG (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor) regimen with an increased aclarubicin dosage [high-dose (HD)-CAG] were observed in 145 patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and compared to the results of 172 patients treated with a conventional CAG regimen. The HD-CAG regimen showed both a higher complete remission (CR) rate (60.7% vs. 46.5%, P=0.013) and overall response (OR) rate (74.5% vs. 63.4%, P=0.039) than CAG. For patients aged <60 years, HD-CAG manifested an efficacy advantage over the CAG regimen (62.6% vs. 47.4%, P=0.015). The 4-year overall survival (OS) rate was 30.3%±13.2% with a median survival time of 19.0±5.4 months for patients re-induced with the HD-CAG regimen, which showed no significant difference compared to the CAG regimen (with a 4-year OS rate of 18.2%±5.3% and a median survival time of 16.0±3.6 months, P=0.485). The main adverse effect was myelosuppression; platelet recovery over 50×10(9)/L was extended by the HD-CAG regimen (15 days vs. 10 days of the CAG regimen, P=0.003), which was tolerable and manageable. HD-CAG can safely improve efficacy compared to the CAG regimen and thus serves as an alternative treatment for R/R AML.

  10. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Cancer.gov

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  11. Gonzalez Regimen (PDQ®)—Health Professional Version

    Cancer.gov

    Expert-reviewed information summary about the Gonzalez regimen as a treatment for people with cancer. Note: The information in this summary is no longer being updated and is provided for reference purposes only.

  12. What to Start: Selecting a First HIV Regimen

    MedlinePlus

    ... medicines to treat HIV infection is called antiretroviral therapy (ART). People on ART take a combination of HIV ... treat HIV infection. HIV treatment (also called antiretroviral therapy or ART) begins with choosing an HIV regimen. People on ...

  13. Controlled-protein dietary regimens for Parkinson's disease.

    PubMed

    Cereda, Emanuele; Barichella, Michela; Pezzoli, Gianni

    2010-02-01

    Continuous levodopa replacement still is the most efficacious treatment for patients with Parkinson's disease. Unfortunately, the neutral aromatic amino acids contained in dietary proteins may compete with this drug for intestinal absorption and transport across the blood-brain barrier, thus limiting its efficacy and being responsible for the occurrence of motor fluctuations. Current guidelines recommend low-protein dietary regimens with protein redistribution, as shifting protein intake to the evening has proved to ameliorate the response to levodopa. However, adherence to this dietary regimen does not seem to be satisfactory and response is variable. Recent studies have shown that low-protein products designed for chronic renal failure patients are safe, tasty, well-tolerated and useful in improving both adherence to low-protein dietary regimens and levodopa-related motor fluctuations. However, there still is the need to define the selection criteria for the patients who may benefit the most from adherence to this regimen.

  14. Moving East: the Euro-Lupus Nephritis regimen in Asia.

    PubMed

    Houssiau, Frédéric A

    2016-01-01

    Treatment of lupus nephritis is more evidenced-based than ever. Yet many areas of uncertainty persist. The article by Rathi et al. brings a piece to the puzzle by comparing, in a group of Indian patients, the Euro-Lupus low-dose i.v. cyclophosphamide regimen with mycophenolate mofetil. Although some caveats must be raised, the results suggest that, after crossing the Atlantic, the Euro-Lupus regimen may well be moving East.

  15. Sequential visibility-graph motifs

    NASA Astrophysics Data System (ADS)

    Iacovacci, Jacopo; Lacasa, Lucas

    2016-04-01

    Visibility algorithms transform time series into graphs and encode dynamical information in their topology, paving the way for graph-theoretical time series analysis as well as building a bridge between nonlinear dynamics and network science. In this work we introduce and study the concept of sequential visibility-graph motifs, smaller substructures of n consecutive nodes that appear with characteristic frequencies. We develop a theory to compute in an exact way the motif profiles associated with general classes of deterministic and stochastic dynamics. We find that this simple property is indeed a highly informative and computationally efficient feature capable of distinguishing among different dynamics and robust against noise contamination. We finally confirm that it can be used in practice to perform unsupervised learning, by extracting motif profiles from experimental heart-rate series and being able, accordingly, to disentangle meditative from other relaxation states. Applications of this general theory include the automatic classification and description of physical, biological, and financial time series.

  16. Sequential detection of web defects

    DOEpatents

    Eichel, Paul H.; Sleefe, Gerard E.; Stalker, K. Terry; Yee, Amy A.

    2001-01-01

    A system for detecting defects on a moving web having a sequential series of identical frames uses an imaging device to form a real-time camera image of a frame and a comparitor to comparing elements of the camera image with corresponding elements of an image of an exemplar frame. The comparitor provides an acceptable indication if the pair of elements are determined to be statistically identical; and a defective indication if the pair of elements are determined to be statistically not identical. If the pair of elements is neither acceptable nor defective, the comparitor recursively compares the element of said exemplar frame with corresponding elements of other frames on said web until one of the acceptable or defective indications occur.

  17. Sequential power-up circuit

    DOEpatents

    Kronberg, James W.

    1992-01-01

    A sequential power-up circuit for starting several electrical load elements in series to avoid excessive current surge, comprising a voltage ramp generator and a set of voltage comparators, each comparator having a different reference voltage and interfacing with a switch that is capable of turning on one of the load elements. As the voltage rises, it passes the reference voltages one at a time and causes the switch corresponding to that voltage to turn on its load element. The ramp is turned on and off by a single switch or by a logic-level electrical signal. The ramp rate for turning on the load element is relatively slow and the rate for turning the elements off is relatively fast. Optionally, the duration of each interval of time between the turning on of the load elements is programmable.

  18. Sequentially Executed Model Evaluation Framework

    SciTech Connect

    2015-10-20

    Provides a message passing framework between generic input, model and output drivers, and specifies an API for developing such drivers. Also provides batch and real-time controllers which step the model and I/O through the time domain (or other discrete domain), and sample I/O drivers. This is a library framework, and does not, itself, solve any problems or execute any modeling. The SeMe framework aids in development of models which operate on sequential information, such as time-series, where evaluation is based on prior results combined with new data for this iteration. Has applications in quality monitoring, and was developed as part of the CANARY-EDS software, where real-time water quality data is being analyzed for anomalies.

  19. Sequentially Executed Model Evaluation Framework

    SciTech Connect

    2014-02-14

    Provides a message passing framework between generic input, model and output drivers, and specifies an API for developing such drivers. Also provides batch and real-time controllers which step the model and 1/0 through the time domain (or other discrete domain), and sample 1/0 drivers. This is a Framework library framework, and does not, itself, solve any problems or execute any modelling. The SeMe framework aids in development of models which operate on sequential information, such as time-series, where evaluation is based on prior results combined with new data for this iteration. Ha) applications in quality monitoring, and was developed as part of the CANARY-EDS software, where real-time water quality data is being analyzed

  20. Antiplatelet Effect of Sequential Administration of Cilostazol in Patients with Acetylsalycilic Acid Resistance

    PubMed Central

    Cakmak, Muzaffer; Demircelik, Bora; Cetin, Mustafa; Cetin, Zehra; Isık, Serhat; Cıcekcıoglu, Hulya; Ulusoy, Feridun Vasfi; Eryonucu, Beyhan

    2016-01-01

    Background Acetylsalicylic acid (ASA) resistance in patients with coronary artery disease is an important medical problem that can affect treatment decision-making and outcomes. Cilostazol has been investigated to determine its effectiveness in patients with acetylsalicylic acid resistance. The aim of this study was to evaluate the antiplatelet efficacy of sequential administration of CLZ in patients with ASA resistance. Methods A total of 180 patients were enrolled in our study. Patients with stable coronary artery disease were first given orally ASA 100 for 10 days, followed by collagen/epinephrine induced closure time (CTCEPI) measurements. Those who were found to be resistant to orally 100 mg of ASA were given orally 300 mg of ASA for an additional 10 days after which we repeated CTCEPI measurements. Those patients with resistance to orally 300 mg ASA were then given CLZ at a daily dose of orally 200 mg for 10 days followed by a final CTCEPI measurement. Results The rate of resistance to 100 mg ASA was 81/180 (45%) compared to a rate of 35/81 (43.2%) with 300 mg ASA. Of the 35 patients found to be resistant to 300 mg ASA, 22 (62.9%) also failed to respond to CLZ treatment. Overall, sequential administration of 300 mg ASA and 200 mg CLZ resulted in a reduction in the number of non-responders from 45% to 12.2%. Conclusions Initiation of CLZ could be of benefit in some patients with ASA-resistance for whom an effective anti-aggregant effect is of clinical importance. PMID:27274173

  1. Novel calcium infusion regimen after parathyroidectomy for renal hyperparathyroidism

    PubMed Central

    Tan, Jih Huei; Tan, Henry Chor Lip; Arulanantham, Sarojah A/P

    2017-01-01

    Abstract Aim Calcium infusion is used after parathyroid surgery for renal hyperparathyroidism to treat postoperative hypocalcaemia. We compared a new infusion regimen to one commonly used in Malaysia based on 2003 K/DOQI guidelines. Methods Retrospective data on serum calcium and infusion rates was collected from 2011–2015. The relationship between peak calcium efflux (PER) and time was determined using a scatterplot and linear regression. A comparison between regimens was made based on treatment efficacy (hypocalcaemia duration, total infusion amount and time) and calcium excursions (outside target range, peak and trough calcium) using bar charts and an unpaired t‐test. Results Fifty‐one and 34 patients on the original and new regimens respectively were included. Mean PER was lower (2.16 vs 2.56 mmol/h; P = 0.03) and occurred earlier (17.6 vs 23.2 h; P = 0.13) for the new regimen. Both scatterplot and regression showed a large correlation between PER and time (R‐square 0.64, SE 1.53, P < 0.001). The new regimen had shorter period of hypocalcaemia (28.9 vs 66.4 h, P = 0.04), and required less calcium infusion (67.7 vs 127.2 mmol, P = 0.02) for a shorter duration (57.3 vs 102.9 h, P = 0.001). Calcium excursions, peak and trough calcium were not significantly different between regimens. Early postoperative high excursions occurred when the infusion was started in spite of elevated peri‐operative calcium levels. Conclusion The new infusion regimen was superior to the original in that it required a shorter treatment period and resulted in less hypocalcaemia. We found that early aggressive calcium replacement is unnecessary and raises the risk of rebound hypercalcemia. PMID:26952689

  2. Measuring Sequential Processing Skills in Young Children.

    ERIC Educational Resources Information Center

    McDaniel, Ernest D.

    This study investigates (1) the relationship of two potentially valuable measures of sequential processing to each other and to a measure of digit span, and (2) the relationships among tests of sequential processing and other measures of cognitive functioning. Subjects were 188 first grade students who had been screened in kindergarten for risk of…

  3. Trial Sequential Methods for Meta-Analysis

    ERIC Educational Resources Information Center

    Kulinskaya, Elena; Wood, John

    2014-01-01

    Statistical methods for sequential meta-analysis have applications also for the design of new trials. Existing methods are based on group sequential methods developed for single trials and start with the calculation of a required information size. This works satisfactorily within the framework of fixed effects meta-analysis, but conceptual…

  4. Efficacy of a “Rescue” Ciprofloxacin-Based Regimen for Eradication of Helicobacter pylori Infection after Treatment Failures

    PubMed Central

    Dore, Maria Pina; Tadeu, Vincenza; Are, Bianca; Mura, Ida; Fanciulli, Giuseppe; Massarelli, Giovannino; Piana, Andrea

    2012-01-01

    The aim of our study was to evaluate the efficacy and tolerability of a ciprofloxacin-based regimen for H. pylori eradication failures as an alternative to bismuth based quadruple therapy. Methods. Design: prospective single-center study. Patients in whom a first eradication trial with omeprazole/esomeprazole, clarithromycin plus amoxicillin or tinidazole/metronidazole had failed were included. H. pylori status: established by histology, rapide urease test and polymerase chain reaction. Intervention: esomeprazole 20 mg, ciprofloxacin 500 mg, and metronidazole 500 mg, administered together before breakfast and dinner for 10 days. Susceptibility testing was performed by the Epsilometer test. Ciprofloxacin resistance was defined as a MIC of ≥1 μg/mL. Eradication was established by a negative 13C-UBT and 4–6 weeks post-therapy. Efficacy and side effects were determined. Results. 34 patients were enrolled, 32 completed the study. Compliance was excellent (100%). Side effects were mild. Ciprofloxacin-based therapy cured 65% (22/34) of patients by intention to treat and 69% (22/32) per protocol analysis. The prevalence of ciprofloxacin resistance was 8%. Conclusions. The effectiveness of ciprofloxacin-based therapy was greatly reduced despite the high prevalence of ciprofloxacin sensitive H. pylori strains. Bismuth based quadruple therapy still remain the best choice as a “rescue” regimen in our region. PMID:22666234

  5. Comparison of Acute and Late Toxicity of Two Regimens of 3- and 5-Week Concomitant Boost Prone IMRT to Standard 6-Week Breast Radiotherapy

    PubMed Central

    Raza, Shahzad; Lymberis, Stella C.; Ciervide, Raquel; Axelrod, Deborah; Fenton-Kerimian, Maria; Magnolfi, Chiara; Rosenstein, Barry; DeWyngaert, J. Keith; Formenti, Silvia C.

    2012-01-01

    Purpose: Limited information is available comparing toxicity of accelerated radiotherapy (RT) to that of standard fractionation RT for early stage breast cancer. We report early and late toxicities of two prone regimens of accelerated intensity-modulated radiation therapy (IMRT) with a concomitant boost (CB) to the tumor bed delivered over 3 or 5 weeks as compared to standard 6 week RT with a sequential electron boost. Methods: From 2/2003 to 12/2007, 169 consecutive patients with Stage I–II breast cancer were offered the choice to undergo prone RT with either: a 6-week standard RT regimen of 46 Gy/23 fractions (fx) to the whole breast (WB), followed by a14 Gy sequential boost (SB) to the tumor bed (6wSB), a 5-week regimen of 50 Gy to WB with an IMRT CB of 6.25 Gy in 25 fx (5wCB); or a 3-week protocol of 40.5 Gy to WB with an IMRT CB of 7.5 Gy in 15 fx (3wCB). These regimens were estimated as biologically equivalent, based on alpha/beta = 4 for tumor control. Toxicities were reported using RTOG and LENT/SOMA scoring. Results: 51/169 patients chose standard 6wSB, 28 selected 5wCB, and 90 enrolled in 3wCB protocol. Maximum acute toxicity was Grade 3 dermatitis in 4% of the patients in the 6wSB compared 1% in 3wCB. In general, acute complications (breast pain, fatigue, and dermatitis) were significantly less in the 3wCB than in the other schedules (P < 0.05). With a median follow-up of 61 months, the only Grade 3 late toxicity was telangiectasia in two patients: one in 3wCB and one in 5wCB group. Notably, fibrosis was comparable among the three groups (P = NS). Conclusion: These preliminary data suggest that accelerated regimens of breast RT over 3 or 5 weeks in the prone position, with an IMRT tumor bed CB, result in comparable late toxicity to standard fractionation with a sequential tumor boost delivered over 6 weeks. As predicted by radiobiological modeling the shorter regimen was associated with less acute effects. PMID:22649788

  6. Effects of a 10-Day Intensive Health Promotion Program Combining Diet and Physical Activity on Body Composition, Physical Fitness, and Blood Factors of Young Adults: A Randomized Pilot Study.

    PubMed

    Lee, Kyoung Soon; Lee, Jae Koo; Yeun, Young Ran

    2017-04-11

    BACKGROUND A lifestyle characterized by poor eating habits and physical inactivity is a risk factor for multiple lifestyle diseases in young adults. This study assessed the effects of implementing an intensive 10-day health promotion program combining diet and physical activities on body composition, physical fitness, and biochemical parameters of young adults. MATERIAL AND METHODS In this randomized pilot study, 30 female undergraduate students were randomly allocated to an intervention and a control group. The health promotion program consisted of unlimited amounts of vegetarian food; aerobic, flexibility, and strength exercises (3 hours/day); lectures on health (3 hours/day); massage practice (2 hours/day); and healthy cooking practice (1 hour/day). The effects of the intervention were analyzed using the Mann-Whitney U test and the Wilcoxon signed-rank test. RESULTS The intensive 10-day health promotion program significantly reduced body weight, body mass index, triglyceride, total cholesterol, low-density lipoprotein cholesterol, blood glucose, and the homeostasis model assessment of insulin resistance. At the same time, participants demonstrated increased back muscle, leg muscle, and grip strength; waist and shoulder flexibility; balance; and cardiorespiratory endurance. CONCLUSIONS The intensive 10-day health promotion program is a viable intervention for improving body composition, physical fitness, glycemic control, and blood lipid levels in young adults.

  7. Drug-Drug Interaction between the Direct-Acting Antiviral Regimen of Ombitasvir-Paritaprevir-Ritonavir plus Dasabuvir and the HIV Antiretroviral Agent Dolutegravir or Abacavir plus Lamivudine.

    PubMed

    Khatri, Amit; Trinh, Roger; Zhao, Weihan; Podsadecki, Thomas; Menon, Rajeev

    2016-10-01

    The direct-acting antiviral regimen of 25 mg ombitasvir-150 mg paritaprevir-100 mg ritonavir once daily (QD) plus 250 mg dasabuvir twice daily (BID) is approved for the treatment of hepatitis C virus genotype 1 infection, including patients coinfected with human immunodeficiency virus. This study was performed to evaluate the pharmacokinetic, safety, and tolerability effects of coadministering the regimen of 3 direct-acting antivirals with two antiretroviral therapies (dolutegravir or abacavir plus lamivudine). Healthy volunteers (n = 24) enrolled in this phase I, single-center, open-label, multiple-dose study received 50 mg dolutegravir QD for 7 days or 300 mg abacavir plus 300 mg lamivudine QD for 4 days, the 3-direct-acting-antiviral regimen for 14 days, followed by the 3-direct-acting-antiviral regimen with dolutegravir or abacavir plus lamivudine for 10 days. Pharmacokinetic parameters were calculated to compare combination therapy with 3-direct-acting-antiviral or antiretroviral therapy alone, and safety/tolerability were assessed throughout the study. Coadministration of the 3-direct-acting-antiviral regimen increased the geometric mean maximum plasma concentration (Cmax) and the area under the curve (AUC) of dolutegravir by 22% (central value ratio [90% confidence intervals], 1.219 [1.153, 1.288]) and 38% (1.380 [1.295, 1.469]), respectively. Abacavir geometric mean Cmax and AUC values decreased by 13% (0.873 [0.777, 0.979]) and 6% (0.943 [0.901, 0.986]), while those for lamivudine decreased by 22% (0.778 [0.719, 0.842]) and 12% (0.876 [0.821, 0.934]). For the 3-direct-acting-antiviral regimen, geometric mean Cmax and AUC during coadministration were within 18% of measurements made during administration of the 3-direct-acting-antiviral regimen alone, although trough concentrations for paritaprevir were 34% (0.664 [0.585, 0.754]) and 27% (0.729 [0.627, 0.847]) lower with dolutegravir and abacavir-lamivudine, respectively. All study treatments were generally

  8. The First 10 Days; Interest Centers.

    ERIC Educational Resources Information Center

    Gordon, Sandra L.; Fulton, Jean

    Interest centers are designed to meet the needs of the other children in the class while a small group works with the teacher on the Oral Language Program. This manual is intended to assist teachers in organizing the centers, which will be used for about an hour each day. Arrangement of furniture is discussed, suggestions are made for an art…

  9. Development of antibiotic regimens using graph based evolutionary algorithms.

    PubMed

    Corns, Steven M; Ashlock, Daniel A; Bryden, Kenneth M

    2013-12-01

    This paper examines the use of evolutionary algorithms in the development of antibiotic regimens given to production animals. A model is constructed that combines the lifespan of the animal and the bacteria living in the animal's gastro-intestinal tract from the early finishing stage until the animal reaches market weight. This model is used as the fitness evaluation for a set of graph based evolutionary algorithms to assess the impact of diversity control on the evolving antibiotic regimens. The graph based evolutionary algorithms have two objectives: to find an antibiotic treatment regimen that maintains the weight gain and health benefits of antibiotic use and to reduce the risk of spreading antibiotic resistant bacteria. This study examines different regimens of tylosin phosphate use on bacteria populations divided into Gram positive and Gram negative types, with a focus on Campylobacter spp. Treatment regimens were found that provided decreased antibiotic resistance relative to conventional methods while providing nearly the same benefits as conventional antibiotic regimes. By using a graph to control the information flow in the evolutionary algorithm, a variety of solutions along the Pareto front can be found automatically for this and other multi-objective problems.

  10. Sequential binary collision ionization mechanisms

    NASA Astrophysics Data System (ADS)

    van Boeyen, R. W.; Watanabe, N.; Doering, J. P.; Moore, J. H.; Coplan, M. A.; Cooper, J. W.

    2004-03-01

    Fully differential cross sections for the electron-impact ionization of the magnesium 3s orbital have been measured in a high-momentum-transfer regime wherein the ionization mechanisms can be accurately described by simple binary collision models. Measurements where performed at incident-electron energies from 400 to 3000 eV, ejected-electron energies of 62 eV, scattering angle of 20 °, and momentum transfers of 2 to 5 a.u. In the out-of-plane geometry of the experiment the cross section is observed far off the Bethe ridge. Both first- and second-order processes can be clearly distinguished as previously observed by Murray et al [Ref. 1] and Schulz et al [Ref. 2]. Owing to the relatively large momentum of the ejected electron, the second order processes can be modeled as sequential binary collisions involving a binary elastic collision between the incident electron and ionic core and a binary knock-out collision between the incident electron and target electron. At low incident-electron energies the cross section for both first and second order processes are comparable, while at high incident energies second-order processes dominate. *Supported by NSF under grant PHY-99-87870. [1] A. J. Murray, M. B. J. Woolf, and F. H. Read J. Phys. B 25, 3021 (1992). [2] M. Schulz, R. Moshammer, D. Fischer, H. Kollmus, D. H. Madison. S. Jones and J. Ullrich, Nature 422, 48 (2003).

  11. Multilevel sequential Monte Carlo samplers

    SciTech Connect

    Beskos, Alexandros; Jasra, Ajay; Law, Kody; Tempone, Raul; Zhou, Yan

    2016-08-24

    Here, we study the approximation of expectations w.r.t. probability distributions associated to the solution of partial differential equations (PDEs); this scenario appears routinely in Bayesian inverse problems. In practice, one often has to solve the associated PDE numerically, using, for instance finite element methods and leading to a discretisation bias, with the step-size level hL. In addition, the expectation cannot be computed analytically and one often resorts to Monte Carlo methods. In the context of this problem, it is known that the introduction of the multilevel Monte Carlo (MLMC) method can reduce the amount of computational effort to estimate expectations, for a given level of error. This is achieved via a telescoping identity associated to a Monte Carlo approximation of a sequence of probability distributions with discretisation levels ${\\infty}$ >h0>h1 ...>hL. In many practical problems of interest, one cannot achieve an i.i.d. sampling of the associated sequence of probability distributions. A sequential Monte Carlo (SMC) version of the MLMC method is introduced to deal with this problem. In conclusion, it is shown that under appropriate assumptions, the attractive property of a reduction of the amount of computational effort to estimate expectations, for a given level of error, can be maintained within the SMC context.

  12. Multienzyme kinetics and sequential metabolism.

    PubMed

    Wienkers, Larry C; Rock, Brooke

    2014-01-01

    Enzymes are the catalysts of biological systems and are extremely efficient. A typical enzyme accelerates the rate of a reaction by factors of at least a million compared to the rate of the same reaction in the absence of the enzyme. In contrast to traditional catalytic enzymes, the family of cytochrome P450 (CYP) enzymes are catalytically promiscuous, and thus they possess remarkable versatility in substrates. The great diversity of reactions catalyzed by CYP enzymes appears to be based on two unique properties of these heme proteins, the ability of their iron to exist under multiple oxidation states with different reactivities and a flexible active site that can accommodate a wide variety of substrates. Herein is a discussion of two distinct types of kinetics observed with CYP enzymes. The first example is of CYP complex kinetic profiles when multiple CYP enzymes form the sample product. The second is sequential metabolism, in other words, the formation of multiple products from one CYP enzyme. Given the degree of CYP enzyme promiscuity, it is hardly surprising that there is also a high degree of complex kinetic profiles generated during the catalytic cycle.

  13. Multilevel sequential Monte Carlo samplers

    DOE PAGES

    Beskos, Alexandros; Jasra, Ajay; Law, Kody; ...

    2016-08-24

    Here, we study the approximation of expectations w.r.t. probability distributions associated to the solution of partial differential equations (PDEs); this scenario appears routinely in Bayesian inverse problems. In practice, one often has to solve the associated PDE numerically, using, for instance finite element methods and leading to a discretisation bias, with the step-size level hL. In addition, the expectation cannot be computed analytically and one often resorts to Monte Carlo methods. In the context of this problem, it is known that the introduction of the multilevel Monte Carlo (MLMC) method can reduce the amount of computational effort to estimate expectations, for a given level of error. This is achieved via a telescoping identity associated to a Monte Carlo approximation of a sequence of probability distributions with discretisation levelsmore » $${\\infty}$$ >h0>h1 ...>hL. In many practical problems of interest, one cannot achieve an i.i.d. sampling of the associated sequence of probability distributions. A sequential Monte Carlo (SMC) version of the MLMC method is introduced to deal with this problem. In conclusion, it is shown that under appropriate assumptions, the attractive property of a reduction of the amount of computational effort to estimate expectations, for a given level of error, can be maintained within the SMC context.« less

  14. Design of initial dosage regimen using a programmable calculator.

    PubMed

    Ritschel, W A; Eldon, M A

    1985-07-01

    A programmable calculator procedure for the determination of dosage regimens to achieve desired steady state concentrations is described. The dosage regimen prediction is based on data from the literature on pharmacokinetic parameters of drugs and correction factors specific for the patient's condition, such as renal failure, geriatric patient and congestive heart failure. The program is designed to generate dosage regimens based on desired steady state trough level, desired steady state peak level, desired mean steady state level, or to fluctuate between desired steady state peak and trough levels. The program can be used for I.V. and extravascular route of administration. A detailed program description and user instructions are presented and illustrated by three examples.

  15. Principles for designing future regimens for multidrug-resistant tuberculosis.

    PubMed

    Brigden, Grania; Nyang'wa, Bern-Thomas; du Cros, Philipp; Varaine, Francis; Hughes, Jennifer; Rich, Michael; Horsburgh, C Robert; Mitnick, Carole D; Nuermberger, Eric; McIlleron, Helen; Phillips, Patrick P J; Balasegaram, Manica

    2014-01-01

    Fewer than 20% of patients with multidrug-resistant (MDR) tuberculosis are receiving treatment and there is an urgent need to scale up treatment programmes. One of the biggest barriers to scale-up is the treatment regimen, which is lengthy, complex, ineffective, poorly tolerated and expensive. For the first time in over 50 years, new drugs have been developed specifically to treat tuberculosis, with bedaquiline and potentially delamanid expected to be available soon for treatment of MDR cases. However, if the new drugs are merely added to the current treatment regimen, the new regimen will be at least as lengthy, cumbersome and toxic as the existing one. There is an urgent need for strategy and evidence on how to maximize the potential of the new drugs to improve outcomes and shorten treatment. We devised eight key principles for designing future treatment regimens to ensure that, once they are proven safe in clinical trials, they will be clinically effective and programmatically practicable. Regimens should contain at least one new class of drug; be broadly applicable for use against MDR and extensively drug-resistant Mycobacterium tuberculosis complex strains; contain three to five effective drugs, each from a different drug class; be delivered orally; have a simple dosing schedule; have a good side-effect profile that allows limited monitoring; last a maximum of 6 months; and have minimal interaction with antiretrovirals. Following these principles will maximize the potential of new compounds and help to overcome the clinical and programmatic disadvantages and scale-up constraints that plague the current regimen.

  16. Adjuvant, neoadjuvant, and experimental regimens in overcoming pancreatic ductal adenocarcinoma

    PubMed Central

    Wysocka, Olga; Kulbacka, Julita; Saczko, Jolanta

    2016-01-01

    Pancreatic cancer is one of the most aggressive and deadly malignancies. Despite better understanding of its biology and pathogenesis, contemporary treatment regimens are still insufficient. Along with the introduction of new treatment agents and combination therapy, the response rates are increasing, but these scores do not go with overall survival, and results are frequently conflicting. Therefore, contemporary medicine faces the challenge of expanding the knowledge base and practice on all grounds – pathology, factor risk, diagnosis, and finally surgical and palliative treatment of this disease. This paper provides a review of current adjuvant and neoadjuvant regimens and the role of experimental therapies in pancreatic ductal adenocarcinoma. PMID:27713776

  17. Hepatitis C Virus Infection: Looking for Interferon Free Regimens

    PubMed Central

    González-Moreno, J.; Payeras-Cifre, A.

    2013-01-01

    Recent developments of new drugs' combinations are changing the treatment paradigm in hepatitis C virus infection. Due to the side effect profile of pegylated interferons, interferon-sparing regimens have become the main target in chronic hepatitis C treatment research. Recent proofs of concept studies have suggested that cure of chronic hepatitis C can be achieved without interferon. The purpose of this paper is to provide an overview of the clinical results recently reported for the treatment of hepatitis C virus infection with interferon-free regimens, focusing on the most promising new compounds and combinations. PMID:23710151

  18. Zagreb Regimen, an Abbreviated Intramuscular Schedule for Rabies Vaccination

    PubMed Central

    Ren, Jiangping; Yao, Linong; Sun, Jimin

    2014-01-01

    The Zagreb regimen, an abbreviated intramuscular schedule for rabies vaccination, was developed by I. Vodopija and colleagues of the Zagreb Institute of Public Health in Croatia in the 1980s. It was recommended by WHO as one of the intramuscular (IM) schedules for rabies vaccination in 2010. We reviewed the literature on the immunogenicity, safety, economic burden, and compliance of the Zagreb 2-1-1 regimen. Compared to Essen, another IM schedule recommended by WHO, Zagreb has higher compliance, lower medical cost, and better immunogenicity at an early stage. PMID:25392012

  19. Using Monte Carlo simulation to determine optimal dosing regimen for cefetamet sodium for injection.

    PubMed

    Li, Caizheng; Sun, Jiayu; Miao, Jia; Qin, Yongping; Wang, Ying; Yu, Rujia; Xiao, Yonghong

    2016-06-01

    The objective of the study was to use Monte Carlo simulation to determine the optimal treatment dosing regimen of the cefetamet sodium for injection by analysing the pharmacokinetics (PK) parameters in healthy Chinese volunteers, and antibacterial activity in vitro was also examined. A three-cross Latin square single-dose PK study was designed. Twelve healthy volunteers were randomized to receive 500, 1000, and 2000 mg of cefetamet sodium for IV infusion over 30 minutes in three periods sequentially; and the washout time in between periods was 3 days. The drug concentrations in plasma were analysed by high-performance liquid chromatography, and the PK parameters were calculated using DAS2.0 PK software. The peak concentrations (Cmax) at 0.5 hours were 37.78±7.29, 76.18±12.81, and 149.32±29.94 mg/l, the areas under concentration-time curve (AUC0-t) were 69.75±14.44, 139.06±22.62, and 278.54±53.12 mg h/l, and the elimination half-life (t1/2) were 1.69±0.19, 1.69±0.27, and 1.81±0.23 hours for 500, 1000, and 2000 mg of cefetamet sodium for injection, respectively. The disposition of cefetamet was appear to fit a two-compartment model with linear kinetics. Antibacterial activity in vitro showed that most Gram-negative bacteria, including non-extended-spectrum beta-lactamases (ESBL)-producing Enterobacter, Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae, were sensitive to cefetamet. The result of Monte Carlo simulation showed that the probability of target attainment for bactericidal response (%fT>MIC≧50%) for susceptible bacteria was reached at all three dosing regimens of 500 mg, q6h, 1000 and 2000 mg, q8h and q6h. Considering the efficacy, safety, and pharmacoeconomy comprehensively, we recommended the dosing regimen of 500 mg, q6h for further clinical treatment based on the principle of minimum daily dosage.

  20. Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma.

    PubMed

    Gu, Mo-Fa; Liu, Li-Zhi; He, Long-Jun; Yuan, Wen-Xin; Zhang, Rong; Luo, Guang-Yu; Xu, Guo-Liang; Zhang, Hua-Man; Yan, Chao-Xian; Li, Jian-Jun

    2013-01-01

    We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin-gemcitabine (GC) regimen (800 mg/m(2) gemcitabine on Days 1 and 8 and 20 mg/m(2) cisplatin on Days 1-5, every 4 weeks) (sGC-RT); sequential chemoradiotherapy with a cisplatin-fluorouracil (PF) regimen (20 mg/m(2) DDP and 500 mg/m(2) 5-FU on Days 1-5, every 4 weeks) (sPF-RT) and cisplatin-based concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con-RT + PF). The complete response rate was higher in the sGC + RT group than in the other two groups (98.75% vs. 92.50%, p < 0.01). The 3-year overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates in the sGC-RT group were significantly higher than those observed in the Con-RT group (OS, 95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs. 76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS, 89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no significant differences in 3-year OS, DFS and MFS rates between the Con-RT and the sPF-RT groups. The GC-RT group experienced more hematologic toxicity, constipation and rash; however, there were no differences in late RT toxicity between the groups. These results demonstrate that a sGC-RT regimen is effective and well tolerated in patients with locoregionally advanced NPC.

  1. Partition algebraic design of asynchronous sequential circuits

    NASA Technical Reports Server (NTRS)

    Maki, Gary K.; Chen, Kristen Q.; Gopalakrishnan, Suresh K.

    1993-01-01

    Tracey's Theorem has long been recognized as essential in generating state assignments for asynchronous sequential circuits. This paper shows that partitioning variables derived from Tracey's Theorem also has a significant impact in generating the design equations. Moreover, this theorem is important to the fundamental understanding of asynchronous sequential operation. The results of this work simplify asynchronous logic design. Moreover, detection of safe circuits is made easier.

  2. Stationary Anonymous Sequential Games with Undiscounted Rewards.

    PubMed

    Więcek, Piotr; Altman, Eitan

    Stationary anonymous sequential games with undiscounted rewards are a special class of games that combine features from both population games (infinitely many players) with stochastic games. We extend the theory for these games to the cases of total expected reward as well as to the expected average reward. We show that in the anonymous sequential game equilibria correspond to the limits of those of related finite population games as the number of players grows to infinity. We provide examples to illustrate our results.

  3. Automated ILA design for synchronous sequential circuits

    NASA Technical Reports Server (NTRS)

    Liu, M. N.; Liu, K. Z.; Maki, G. K.; Whitaker, S. R.

    1991-01-01

    An iterative logic array (ILA) architecture for synchronous sequential circuits is presented. This technique utilizes linear algebra to produce the design equations. The ILA realization of synchronous sequential logic can be fully automated with a computer program. A programmable design procedure is proposed to fullfill the design task and layout generation. A software algorithm in the C language has been developed and tested to generate 1 micron CMOS layouts using the Hewlett-Packard FUNGEN module generator shell.

  4. Are calcineurin inhibitors-free regimens ready for prime time?

    PubMed

    Vincenti, Flavio

    2012-11-01

    The goal of research in transplant therapeutics is to achieve safe and effective immunosuppression strategies that allow durable engraftment free of toxicities. The calcineurin inhibitors (CNIs) regimens, because of their inherent toxicities (including nephrotoxicity), have been unable to meet these promises. Over the past decade acute cellular rejection decreased dramatically with a concomitant robust increase in 1-year graft survival; however, long-term graft outcome showed only modest improvement. This is due in part to the toxicities of the immunosuppressive drugs. The quest for a toxicity-free-CNI-free regimen has been both intense and frustrating. A turning point in CNIs-free therapy may have occurred with the recent approval of belatacept, which represents a new paradigm in immunosuppression: biological therapy for chronic immunosuppression devoid of the usual toxicities associated with the CNIs. Belatacept, a fusion receptor protein, blocks costimulation signals necessary for the activation of T cells. Although costimulation blockade has not been shown to induce tolerance, it can provide safe and effective immunosuppression without renal or cardiovascular toxicities. The approval of belatacept in both the United States and Europe for use in renal transplantation will finally push CNI-free regimens into prime time. Novel biologics such as ASKP1240 (a human anti-CD40 monoclonal antibody) and one small molecule, tofacitinib, may advance further the use of CNI-free regimens in organ transplantation.

  5. Tuberculosis 2: exploring methods of diagnosis, treatment regimens and concordance.

    PubMed

    Jarvis, Miles

    The second in this two part unit on tuberculosis examines diagnosis and treatment options. Part I outlined background on epidemiology and control of this disease. This part draws on the guidance set out by the National Institute for Health and Clinical Excellence. Diagnostic methods are discussed and the standard treatment regimen is outlined.

  6. Heterologous Prime-Boost Immunisation Regimens Against Infectious Diseases

    DTIC Science & Technology

    2006-08-01

    Heterologous Prime-Boost Immunisation Regimens Against Infectious Diseases Susan Shahin and David Proll Human Protection and... diseases (such as malaria, tuberculosis and HIV) has been hindered by the lack of effective immunisation strategies that induce the cellular arm of...different animal and disease models. Since several intracellular pathogens are considered potential biowarfare threats, the objective of this review

  7. Roughage level and limited maximum intake regimens for feedlot steers.

    PubMed

    Bartle, S J; Preston, R L

    1992-11-01

    Hereford steers (n = 280, BW = 371 +/- 29 kg; 40 pens) were used to evaluate two alternatives to ad libitum access to feed and constant roughage levels in finishing diets. The eight treatments were as follows: two treatments in which intake was limited to a multiple of the maintenance (MM) energy requirement (2.1, 2.3, 2.5, and 2.7, [2.7MM] and 2.3, 2.5, 2.7, and 2.9 [2.9MM] times maintenance for wk 1, 2, 3, and 4 and thereafter, respectively) and six roughage regimen and grain source treatments (10% roughage equivalent [RE] fed during the mid- and late-finishing periods [10/10], respectively, 2% RE followed by 10% RE [2/10], and 10% RE followed by 2% RE [10/2] fed with steam-flaked sorghum grain [SFSG] or whole-shelled corn [WSC]). The 2.7MM treatment tended to improve ADG (6%, P = .08) and gain efficiency (4%, P = .15) relative to ad libitum access to feed. The 2.9MM treatment was intermediate. Steers fed WSC diets consumed approximately 12% more DM (9.2 vs 8.2 kg/d) and gained 4% more (1.45 vs 1.39 kg/d, P < .05) but had lower gain efficiency (7%, 159 and 170 g/kg, P < .001) than steers fed SFSG diets. For SFSG diets, the 2/10 regimen resulted in similar gains, a 3.6% decrease (P = .10) in DMI, an 8.6% improvement (P < .01) in gain efficiency, and reduced roughage use (40 kg per steer) compared with the 10/10 regimen. With WSC diets, the 2/10 regimen did not (P > .2) affect gain efficiency but did reduce roughage use (48 kg) compared with the 10/10 regimen. The 10/2 regimen did not differ (P > .2) from the 10/10 regimen. Few differences in carcass characteristics were noted among treatments. Roughage use and cost of gain can be reduced by feeding 2% roughage during the mid-finishing period followed by a return to 10% roughage.

  8. Adenovirus vector-induced immune responses in nonhuman primates: responses to prime boost regimens.

    PubMed

    Tatsis, Nia; Lasaro, Marcio O; Lin, Shih-Wen; Haut, Larissa H; Xiang, Zhi Q; Zhou, Dongming; Dimenna, Lauren; Li, Hua; Bian, Ang; Abdulla, Sarah; Li, Yan; Giles-Davis, Wynetta; Engram, Jessica; Ratcliffe, Sarah J; Silvestri, Guido; Ertl, Hildegund C; Betts, Michael R

    2009-05-15

    In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with preexisting neutralizing Abs against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine's efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine. Here, we compared two vaccine regimens based on sequential use of AdHu5 vectors or two different chimpanzee-derived Ad vectors in rhesus macaques that were AdHu5 seropositive or seronegative at the onset of vaccination. Our results show that heterologous booster immunizations with the chimpanzee-derived Ad vectors induced higher T and B cell responses than did repeated immunizations with the AdHu5 vector, especially in AdHu5-preexposed macaques.

  9. Adherence to treatment of chronic hepatitis C: from interferon containing regimens to interferon and ribavirin free regimens

    PubMed Central

    Younossi, Zobair M.; Stepanova, Maria; Henry, Linda; Nader, Fatema; Younossi, Youssef; Hunt, Sharon

    2016-01-01

    Abstract Patients’ experience during treatment may affect treatment adherence. Our aim was to assess the impact of patient-reported outcomes (PROs) on adherence to different anti-hepatitis C virus (HCV) regimens. Clinical, demographic, and PRO data (short form-36 [SF-36], chronic liver disease questionnaire-hepatitis C version [CLDQ-HCV], functional assessment of chronic illness therapy-fatigue [FACIT-F], work productivity and activity impairment: specific health problem [WPAI:SHP]) from 13 multinational clinical trials of anti-HCV treatment were available. Treatment adherence was defined as >80% of prescribed doses taken. Included were 4825 HCV patients. Regimens were grouped into: interferon- and ribavirin (RBV)-containing (±sofosbuvir [SOF]), interferon-free RBV-containing (RBV + SOF ± ledipasvir [LDV]), and interferon-free RBV-free (LDV/SOF). The adherence to these regimens were 77.6%, 84.3%, and 96.2%, respectively (P < 0.0001). Nonadherent patients were more likely to be unemployed and to have a greater PRO impairment at baseline (up to −5.3% lower PRO scores, P < 0.0001). During treatment with interferon- or RBV-based regimens, nonadherent patients experienced lower PROs and had larger decrements from their baseline PRO scores. In contrast, there were no significant declines in PRO scores (all P > 0.05) for the small number of patients who were nonadherent to LDV/SOF. In multivariate analysis, being treatment-naive, longer treatment duration, and receiving an interferon- or RBV-containing regimen were associated with a lower likelihood of adherence (all P < 0.003). Better baseline and on-treatment PRO scores were associated with a higher likelihood of adherence to interferon and RBV. The use of interferon and/or RBV, longer duration of treatment, and lower baseline and on-treatment PRO scores were linked to a decreased likelihood of being adherent to interferon + RBV-containing or interferon-free RBV-containing antiviral

  10. A comparison between standard triple therapy and sequential therapy on eradication of Helicobacter pylori in uremic patients: A randomized clinical trial

    PubMed Central

    Makhlough, Atieh; Fakheri, Hafez; Farkhani, Ahmad Ramezani; Seddighi, Omid; Hossieni, Seyed Vahid; Khademloo, Mohammad; Bari, Zohreh

    2014-01-01

    Background: The prevalence of peptic ulcer disease in hemodialysis dependent patients is higher than the general population. These patients are also more prone to upper gastrointestinal bleeding. The aim of this study was to compare the effects of a standard triple therapy with a sequential therapy on Helicobacter pylori eradication in azotemic and hemodialysis patients. Materials and Methods: Forty nine hemodialysis and azotemic patients, naïve to H. pylori treatment, were randomized into two groups to receive either standard triple therapy (pantoprazole 40 mg, amoxicillin 500 mg and clarithromycin 250 mg twice a day for 14 days) or a sequential therapy (pantoprazole 40 mg for 10 days, amoxicillin 500 mg twice a day for the first 5 days and clarithromycin 250 mg + tinidazole 500 mg twice a day just during the second 5 days). H. pylori eradication was evaluated by fecal H. pylori antigen assessment 8 weeks after the treatment. Results: Of 49 patients, 45 patients (21 in triple therapy group and 24 in the sequential group) completed the study. Based on intention to treat analysis, H. pylori eradication rates were 66.7% (95% confidence interval [CI]: 47.8-85.5%) in standard triple therapy group and 84% (95% CI: 69.6-98.3%) in sequential therapy group (P = 0.34). Per-protocol (PP) eradication rates were (95% CI: 76.2%. 6-89.3%) 54 and 87.5% (95% CI: 68.8-95.5%), respectively (P = 0.32). Conclusion: According to Maastricht III consensus report, the results of our study showed that sequential therapy might be a better choice compared with the standard triple therapy in azotemic and hemodialysis patients Iran. We propose to assess the effects of shorter-duration sequential therapy (less than 10 days) for H. pylori eradication. PMID:25590026

  11. Modern Sequential Analysis and Its Applications to Computerized Adaptive Testing

    ERIC Educational Resources Information Center

    Bartroff, Jay; Finkelman, Matthew; Lai, Tze Leung

    2008-01-01

    After a brief review of recent advances in sequential analysis involving sequential generalized likelihood ratio tests, we discuss their use in psychometric testing and extend the asymptotic optimality theory of these sequential tests to the case of sequentially generated experiments, of particular interest in computerized adaptive testing. We…

  12. Sequential Heterotrophy-Dilution-Photoinduction Cultivation of Haematococcus pluvialis for efficient production of astaxanthin.

    PubMed

    Wan, Minxi; Zhang, Zhen; Wang, Jun; Huang, Jianke; Fan, Jianhua; Yu, Anquan; Wang, Weiliang; Li, Yuanguang

    2015-12-01

    A novel cultivation strategy called "Sequential Heterotrophy-Dilution-Photoinduction" was successfully applied in the cultivation of Haematococcus pluvialis to produce astaxanthin effectively. Cells were first cultivated heterotrophically to achieve a high cell density, then were diluted to a suitable concentration and switched to a favorable environment for cells acclimation. Finally, the culture was transferred to high light environment for astaxanthin accumulation. By this strategy, the dry cell weight of 26 g/L and biomass productivity of 64.1mg/L/h were obtained in heterotrophy stage which surpassed ever before reported in literatures. Meanwhile, the cells could accumulate considerable astaxanthin up to 4.6% of dry cell weight after 10 days of photoinduction. Furthermore, the application prospects of the strategy were confirmed further by outdoor experiments. Therefore, this novel strategy provided a promising approach for high-efficient production of natural astaxanthin from H. pluvialis to meet the huge demand of this high value product.

  13. Long-term survival of advanced triple-negative breast cancers with a dose-intense cyclophosphamide/anthracycline neoadjuvant regimen

    PubMed Central

    Giacchetti, S; Porcher, R; Lehmann-Che, J; Hamy, A-S; de Roquancourt, A; Cuvier, C; Cottu, P-H; Bertheau, P; Albiter, M; Bouhidel, F; Coussy, F; Extra, J-M; Marty, M; de Thé, H; Espié, M

    2014-01-01

    Background: Triple-negative (TN) breast cancers exhibit major initial responses to neoadjuvant chemotherapy, but generally have a poor outcome. Because of the lack of validated drug targets, chemotherapy remains an important therapeutic tool in these cancers. Methods: We report the survival of two consecutive series of 267 locally advanced breast cancers (LABC) treated with two different neoadjuvant regimens, either a dose-dense and dose-intense cyclophosphamide–anthracycline (AC) association (historically called SIM) or a conventional sequential association of cyclophosphamide and anthracycline, followed by taxanes (EC-T). We compared pathological responses and survival rates of these two groups and studied their association with tumours features. Results: Although the two regimens showed equivalent pathological complete response (pCR) in the whole population (16 and 12%), the SIM regimen yielded a non-statistically higher pCR rate than EC-T (48% vs 24%, P=0.087) in TN tumours. In the SIM protocol, DFS was statistically higher for TN than for non-TN patients (P=0.019), although we showed that the TN status was associated with an increased initial risk of recurrence in both regimens. This effect gradually decreased and after 2 years, TN was associated with a significantly decreased likelihood of relapse in SIM-treated LABC (hazard ratio (HR)=0.25 (95% CI: 0.07–0.86), P=0.028). Conclusions: AC dose intensification treatment is associated with a very favourable long-term survival rate in TN breast cancers. These observations call for a prospective assessment of such dose-intense AC-based regimens in locally advanced TN tumours. PMID:24569467

  14. Intensified hemodialysis regimens: neglected treatment options for children and adolescents.

    PubMed

    Müller, Dominik; Zimmering, Miriam; Chan, Christopher T; McFarlane, Philip A; Pierratos, Andreas; Querfeld, Uwe

    2008-10-01

    During recent years, the importance of intensified dialysis regimens has gathered increasing interest, especially after the Hemodialysis (HEMO) Study Group reported that a higher dose of thrice-weekly hemodialysis failed to improve clinical outcomes. Long nocturnal hemodialysis (three to six times per week) or short daily hemodialysis are the currently used forms of intensified dialysis. There is substantial evidence for cardiovascular and quality-of-life improvements as well as financial benefits with intensified hemodialysis. Preliminary experience with daily hemodialysis and hemodiafiltration in children has been reported. Given the continuing shortage of donor organs for kidney transplantation, the increasing incidence of end-stage renal disease (ESRD) and recognition of the deleterious effects of long-lasting ESRD, growth retardation, and poor social rehabilitation, more intensified dialysis regimens are a much-needed therapeutical option in both adults and children.

  15. Initial dosage regimens of gentamicin in patients with burns.

    PubMed

    Zaske, D E; Chin, T; Kohls, P R; Solem, L D; Strate, R G

    1991-01-01

    For 95 patients with burns the gentamicin dosage regimen necessary to achieve optimal serum concentrations was determined. Individual elimination rates and distribution volumes for gentamicin were determined and correlated with renal function parameters and age. In patients with burns who had normal serum creatinine levels (less than 1.5 mg/dl), gentamicin clearance and thus dosage regimens can be stratified by age. Gentamicin's clearance decreased inversely with age. Initial dosage guidelines were calculated for different age groups of patients with normal levels of serum creatinine. The guidelines were developed to assist the clinician in attaining therapeutic concentrations with initial doses of gentamicin. Therapeutic serum concentrations were reached in most patients with burns dosed by these guidelines. Serum gentamicin concentrations should always be monitored during therapy, and dosages should be adjusted to ensure optimal concentrations during the course of therapy.

  16. Basis for selecting optimum antibiotic regimens for secondary peritonitis.

    PubMed

    Maseda, Emilio; Gimenez, Maria-Jose; Gilsanz, Fernando; Aguilar, Lorenzo

    2016-01-01

    Adequate management of severely ill patients with secondary peritonitis requires supportive therapy of organ dysfunction, source control of infection and antimicrobial therapy. Since secondary peritonitis is polymicrobial, appropriate empiric therapy requires combination therapy in order to achieve the needed coverage for both common and more unusual organisms. This article reviews etiological agents, resistance mechanisms and their prevalence, how and when to cover them and guidelines for treatment in the literature. Local surveillances are the basis for the selection of compounds in antibiotic regimens, which should be further adapted to the increasing number of patients with risk factors for resistance (clinical setting, comorbidities, previous antibiotic treatments, previous colonization, severity…). Inadequate antimicrobial regimens are strongly associated with unfavorable outcomes. Awareness of resistance epidemiology and of clinical consequences of inadequate therapy against resistant bacteria is crucial for clinicians treating secondary peritonitis, with delicate balance between optimization of empirical therapy (improving outcomes) and antimicrobial overuse (increasing resistance emergence).

  17. [Malaria and life at sea: prophylactic regimens on merchant ships].

    PubMed

    Michot, S

    2011-02-01

    The purpose of this article is to describe requirements for protection/treatment of malaria on merchant ships. The first part of the article reviews recent data on the incidence of malaria in seagoing personnel. The second part provides advice on mosquito-bite prevention on merchant ships. The third part presents the most important information on prophylaxis for seafarers working in malarial risk areas. Several regimens are proposed. The last part of the article discusses curative treatment for malaria on merchant ships.

  18. “Rescue” regimens after Helicobacter pylori treatment failure

    PubMed Central

    Gisbert, Javier P

    2008-01-01

    Helicobacter pylori (H pylori) infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After more than 20 years of experience in H pylori treatment, in my opinion, the ideal regimen to treat this infection is still to be found. Currently, apart from having to know first-line eradication regimens well, we must also be prepared to face treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. The choice of a “rescue” treatment depends on which treatment is used initially. If a clarithromycin-based regimen was used initially, a subsequent metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin-based combination would be a third “rescue” option. Alternatively, it has recently been suggested that levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, a quadruple regimen may be reserved as a third-line rescue option. Finally, rifabutin-based rescue therapy constitutes an encouraging empirical fourth-line strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin. Even after two consecutive failures, several studies have demonstrated that H pylori eradication can finally be achieved in almost all patients if several rescue therapies are consecutively given. Therefore, the attitude in H pylori eradication therapy failure, even after two or more unsuccessful attempts, should be to fight and not to surrender. PMID:18803350

  19. Bowel preparation regimens for colon capsule endoscopy: a review

    PubMed Central

    Nigar, Sofia; Paleti, Vani; Lane, Devin; Duddempudi, Sushil

    2014-01-01

    Colon capsule endoscopy (CCE) is being actively evaluated as an emerging complementary or alternative procedure for evaluation of the colon. The yield of CCE is significantly dependent on the quality of bowel preparation. In addition to achieving a stool-free colon the bowel preparation protocols need to decrease bubble effect and aid propulsion of the capsule. An extensive English literature search was done using PubMed with search terms of colon capsule endoscopy, PillCam and bowel preparation. Full-length articles which met the criteria were included for review. A total of 12 studies including 1149 patients were reviewed. There was significant variability in the type of bowel preparation regimens. Large-volume (3–4 liters) polyethylene glycol (PEG) was the most widely used laxative. Lower volumes of PEG showed comparable results but larger studies are needed to determine efficacy. Sodium phosphate was used as an effective booster in most studies. Magnesium citrate and ascorbic acid are emerging as promising boosters to replace sodium phosphate when it is contraindicated. The potential benefit of prokinetics needs further evaluation. Over the past decade there has been significant improvement in the bowel preparation regimens for CCE. Further experience and studies are likely to standardize the bowel preparation regimens before CCE is adopted into routine clinical practice. PMID:24790642

  20. Batch sequential designs for computer experiments

    SciTech Connect

    Moore, Leslie M; Williams, Brian J; Loeppky, Jason L

    2009-01-01

    Computer models simulating a physical process are used in many areas of science. Due to the complex nature of these codes it is often necessary to approximate the code, which is typically done using a Gaussian process. In many situations the number of code runs available to build the Guassian process approximation is limited. When the initial design is small or the underlying response surface is complicated this can lead to poor approximations of the code output. In order to improve the fit of the model, sequential design strategies must be employed. In this paper we introduce two simple distance based metrics that can be used to augment an initial design in a batch sequential manner. In addition we propose a sequential updating strategy to an orthogonal array based Latin hypercube sample. We show via various real and simulated examples that the distance metrics and the extension of the orthogonal array based Latin hypercubes work well in practice.

  1. Optimal sequential Bayesian analysis for degradation tests.

    PubMed

    Rodríguez-Narciso, Silvia; Christen, J Andrés

    2016-07-01

    Degradation tests are especially difficult to conduct for items with high reliability. Test costs, caused mainly by prolonged item duration and item destruction costs, establish the necessity of sequential degradation test designs. We propose a methodology that sequentially selects the optimal observation times to measure the degradation, using a convenient rule that maximizes the inference precision and minimizes test costs. In particular our objective is to estimate a quantile of the time to failure distribution, where the degradation process is modelled as a linear model using Bayesian inference. The proposed sequential analysis is based on an index that measures the expected discrepancy between the estimated quantile and its corresponding prediction, using Monte Carlo methods. The procedure was successfully implemented for simulated and real data.

  2. Sequential Path Entanglement for Quantum Metrology

    PubMed Central

    Jin, Xian-Min; Peng, Cheng-Zhi; Deng, Youjin; Barbieri, Marco; Nunn, Joshua; Walmsley, Ian A.

    2013-01-01

    Path entanglement is a key resource for quantum metrology. Using path-entangled states, the standard quantum limit can be beaten, and the Heisenberg limit can be achieved. However, the preparation and detection of such states scales unfavourably with the number of photons. Here we introduce sequential path entanglement, in which photons are distributed across distinct time bins with arbitrary separation, as a resource for quantum metrology. We demonstrate a scheme for converting polarization Greenberger-Horne-Zeilinger entanglement into sequential path entanglement. We observe the same enhanced phase resolution expected for conventional path entanglement, independent of the delay between consecutive photons. Sequential path entanglement can be prepared comparably easily from polarization entanglement, can be detected without using photon-number-resolving detectors, and enables novel applications.

  3. Drug regimens identified and optimized by output-driven platform markedly reduce tuberculosis treatment time

    PubMed Central

    Lee, Bai-Yu; Clemens, Daniel L.; Silva, Aleidy; Dillon, Barbara Jane; Masleša-Galić, Saša; Nava, Susana; Ding, Xianting; Ho, Chih-Ming; Horwitz, Marcus A.

    2017-01-01

    The current drug regimens for treating tuberculosis are lengthy and onerous, and hence complicated by poor adherence leading to drug resistance and disease relapse. Previously, using an output-driven optimization platform and an in vitro macrophage model of Mycobacterium tuberculosis infection, we identified several experimental drug regimens among billions of possible drug-dose combinations that outperform the current standard regimen. Here we use this platform to optimize the in vivo drug doses of two of these regimens in a mouse model of pulmonary tuberculosis. The experimental regimens kill M. tuberculosis much more rapidly than the standard regimen and reduce treatment time to relapse-free cure by 75%. Thus, these regimens have the potential to provide a markedly shorter course of treatment for tuberculosis in humans. As these regimens omit isoniazid, rifampicin, fluoroquinolones and injectable aminoglycosides, they would be suitable for treating many cases of multidrug and extensively drug-resistant tuberculosis. PMID:28117835

  4. Drug regimens identified and optimized by output-driven platform markedly reduce tuberculosis treatment time.

    PubMed

    Lee, Bai-Yu; Clemens, Daniel L; Silva, Aleidy; Dillon, Barbara Jane; Masleša-Galić, Saša; Nava, Susana; Ding, Xianting; Ho, Chih-Ming; Horwitz, Marcus A

    2017-01-24

    The current drug regimens for treating tuberculosis are lengthy and onerous, and hence complicated by poor adherence leading to drug resistance and disease relapse. Previously, using an output-driven optimization platform and an in vitro macrophage model of Mycobacterium tuberculosis infection, we identified several experimental drug regimens among billions of possible drug-dose combinations that outperform the current standard regimen. Here we use this platform to optimize the in vivo drug doses of two of these regimens in a mouse model of pulmonary tuberculosis. The experimental regimens kill M. tuberculosis much more rapidly than the standard regimen and reduce treatment time to relapse-free cure by 75%. Thus, these regimens have the potential to provide a markedly shorter course of treatment for tuberculosis in humans. As these regimens omit isoniazid, rifampicin, fluoroquinolones and injectable aminoglycosides, they would be suitable for treating many cases of multidrug and extensively drug-resistant tuberculosis.

  5. Test pattern generation for ILA sequential circuits

    NASA Technical Reports Server (NTRS)

    Feng, YU; Frenzel, James F.; Maki, Gary K.

    1993-01-01

    An efficient method of generating test patterns for sequential machines implemented using one-dimensional, unilateral, iterative logic arrays (ILA's) of BTS pass transistor networks is presented. Based on a transistor level fault model, the method affords a unique opportunity for real-time fault detection with improved fault coverage. The resulting test sets are shown to be equivalent to those obtained using conventional gate level models, thus eliminating the need for additional test patterns. The proposed method advances the simplicity and ease of the test pattern generation for a special class of sequential circuitry.

  6. Allocation Rules for Sequential Clinical Trials.

    DTIC Science & Technology

    1982-07-01

    AD-AIN 354 STANFORD UNIV CA DEPT OF STATISTICS F/V 12/1 ALLOCATION RULES FOR SEQUENTIAL CLINICAL TRIALS .(U) JUL 82 D SIEGMUND N00V11577-C-V306...UNCLASSIFIED TR 18 NL ALLOCATION RULES FOR SEQUENTIAL CLINICAL TRIALS BY D. SIEGMUND TECHNICAL REPORT NO. 18 JULY 1982 PREPARED UNDER CONTRACT N00014-77-C...at all. Rere me. discuss (I) and (11) or mes"s 9f a Monte Carlo experiment. The advantages of randomization in clinical trials has been discussed at

  7. Probing Angular Correlations in Sequential Double Ionization

    SciTech Connect

    Fleischer, A.; Woerner, H. J.; Arissian, L.; Liu, L. R.; Meckel, M.; Rippert, A.; Doerner, R.; Villeneuve, D. M.; Corkum, P. B.; Staudte, A.

    2011-09-09

    We study electron correlation in sequential double ionization of noble gas atoms and HCl in intense, femtosecond laser pulses. We measure the photoelectron angular distributions of Ne{sup +} relative to the first electron in a pump-probe experiment with 8 fs, 800 nm, circularly polarized laser pulses at a peak intensity of a few 10{sup 15} W/cm{sup 2}. Using a linear-linear pump-probe setup, we further study He, Ar, and HCl. We find a clear angular correlation between the two ionization steps in the sequential double ionization intensity regime.

  8. Automatic defensive control of asynchronous sequential machines

    NASA Astrophysics Data System (ADS)

    Hammer, Jacob

    2016-01-01

    Control theoretic techniques are utilised to develop automatic controllers that counteract robotic adversarial interventions in the operation of asynchronous sequential machines. The scenario centres on automatic protection against pre-programmed adversarial agents that attempt to subvert the operation of an asynchronous computing system. Necessary and sufficient conditions for the existence of defensive controllers that automatically defeat such adversarial agents are derived. These conditions are stated in terms of skeleton matrices - matrices of zeros and ones obtained directly from the given description of the asynchronous sequential machine being protected. When defensive controllers exist, a procedure for their design is outlined.

  9. Non-recursive sequential input deconvolution

    NASA Astrophysics Data System (ADS)

    Bernal, Dionisio

    2017-01-01

    A scheme for sequential deconvolution of inputs from measured outputs is presented. The key feature in the formulation is elimination of the initial state from the input-output relations by projecting the output in the left null space of the observability block. Removal of the initial state allows the sequential format of the deconvolution, essential for computational reasons, to be implemented non-recursively, assuring unconditional stability. Identifiability is realized when the input-output arrangement does not have transmission zeros, and observability and controllability are shown immaterial. Comparison of results from the scheme with those from Dynamic Programming highlights the benefits of eliminating the initial state.

  10. Toxicities of different first-line chemotherapy regimens in the treatment of advanced ovarian cancer

    PubMed Central

    Qu, Chang-Ping; Sun, Gui-Xia; Yang, Shao-Qin; Tian, Jun; Si, Jin-Ge; Wang, Yi-Feng

    2017-01-01

    Abstract Background: Ovarian cancer (OC) is the 5th leading cause of cancer-related deaths around the world, and several chemotherapy regimens have been applied in the treatment of OC. We aim to compare toxicities of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) using network meta-analysis. Methods: Literature research in Cochrane Library, PubMed, and EMBASE was performed up to November 2015. Eligible randomized controlled trials (RCTs) of different chemotherapy regimens were included. Network meta-analysis combined direct and indirect evidence to assess pooled odds ratios (ORs) and draw the surface under the cumulative ranking (SUCRA) curves. Results: Thirteen eligible RCTs were included in this network meta-analysis, including 8 chemotherapy regimens (paclitaxel + carboplatin [PC], pegylated liposomal doxorubicin [PLD] + carboplatin, carboplatin, gemcitabine + carboplatin, paclitaxel, PC + epirubicin, PC + topotecan, docetaxel + carboplatin). Gemcitabine + carboplatin regimen exerted higher incidence of anemia when compared with carboplatin and paclitaxel regimens. The incidence of febrile neutropenia of gemcitabine + carboplatin regimen was higher than that of PC, PLD + carboplatin, carboplatin, and PC + topotecan regimens. Topotecan PC + epirubicin regimen had a higher toxicity, comparing with PC, PLD + carboplatin, and PC + topotecan regimens. As for thrombocytopenia, gemcitabine + carboplatin chemotherapy regimen produced an obviously higher toxicity than PC and carboplatin. As for nausea, PLD + carboplatin chemotherapy regimen had a significantly higher toxicity than that of carboplatin chemotherapy regimen. Moreover, when compared with PC and carboplatin chemotherapy regimens, the toxicity of PC + epirubicin was greatly higher to patients with AOC. Conclusion: The nonhematologic toxicity of PLD + carboplatin regimen was higher than other regimens, which

  11. Strategies of sequential therapies in unresectable metastatic colorectal cancer: a meta-analysis

    PubMed Central

    Asmis, T.; Berry, S.; Cosby, R.; Chan, K.; Coburn, N.; Rother, M.

    2014-01-01

    Background Before the emergence of first-line combination chemotherapy, the standard of care for unresectable metastatic colorectal cancer (mcrc) was first-line monotherapy with modulated 5-fluorouracil. Several large phase iii randomized controlled trials, now completed, have assessed whether a planned sequential chemotherapy strategy—beginning with fluoropyrimidine monotherapy until treatment failure, followed by another regimen (either monotherapy or combination chemotherapy) until treatment failure—could result in the same survival benefit produced with an upfront combination chemotherapy strategy, but with less toxicity for patients. Methods The medline and embase databases, and abstracts from meetings of the American Society for Clinical Oncology and the European Society for Medical Oncology, were searched for reports comparing a sequential strategy of chemotherapy with an upfront combination chemotherapy in adult patients with mcrc. Publications that reported efficacy or toxicity data (or both) were included. Results The five eligible trials that were identified included 4532 patients. A meta-analysis of those trials demonstrates a statistically significant survival advantage for combination chemotherapy (hazard ratio: 0.92; 95% confidence interval: 0.86 to 0.99). However, the median survival advantage (3–6 weeks in most trials) is small and of questionable clinical significance. Three trials reported first-line toxicities. Upfront combination chemotherapy results in significantly more neutropenia, febrile neutropenia, thrombocytopenia, diarrhea, nausea, vomiting, and sensory neuropathy. Sequential chemotherapy results in significantly more hand–foot syndrome. Conclusions Given the small survival advantage associated with upfront combination chemotherapy, planned sequential chemotherapy and upfront combination chemotherapy can both be considered treatment strategies. Treatment should be chosen on an individual basis considering patient and tumour

  12. A Randomised Trial of empiric 14-day Triple, five-day Concomitant, and ten-day Sequential Therapies for Helicobacter pylori in Seven Latin American Sites

    PubMed Central

    Greenberg, E. Robert; Anderson, Garnet L.; Morgan, Douglas R.; Torres, Javier; Chey, William D.; Bravo, Luis Eduardo; Dominguez, Ricardo L.; Ferreccio, Catterina; Herrero, Rolando; Lazcano-Ponce, Eduardo C.; Meza-Montenegro, Mercedes María; Peña, Rodolfo; Peña, Edgar M.; Salazar-Martínez, Eduardo; Correa, Pelayo; Martínez, María Elena; Valdivieso, Manuel; Goodman, Gary E.; Crowley, John J.; Baker, Laurence H.

    2011-01-01

    Summary Background Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradicating Helicobacter pylori (H. pylori) infection than five-day concomitant and ten-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses and thus may be suitable for eradication programs in low-resource settings. Studies are limited from Latin America, however, where the burden of H. pylori-associated diseases is high. Methods We randomised 1463 men and women ages 21–65 selected from general populations in Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites) who tested positive for H. pylori by a urea breath test (UBT) to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); five days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or five days of lansoprazole and amoxicillin followed by five of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by UBT six–eight weeks after randomisation. Findings In intention-to-treat analyses, the probability of eradication with standard therapy was 82·2%, which was 8·6% higher (95% adjusted CI: 2·6%, 14·5%) than with concomitant therapy (73·6%) and 5·6% higher (95% adjusted CI: −0·04%, 11·6%) than with sequential therapy (76·5%). In analyses limited to the 1314 participants who adhered to their assigned therapy, the probabilities of eradication were 87·1%, 78·7%, and 81·1% with standard, concomitant, and sequential therapies, respectively. Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites. Interpretation Standard 14-day triple-drug therapy is preferable to five-day concomitant or ten-day sequential four-drug regimens as empiric therapy for H. pylori

  13. Sequential protein NMR assignments in the liquid state via sequential data acquisition

    NASA Astrophysics Data System (ADS)

    Wiedemann, Christoph; Bellstedt, Peter; Kirschstein, Anika; Häfner, Sabine; Herbst, Christian; Görlach, Matthias; Ramachandran, Ramadurai

    2014-02-01

    Two different NMR pulse schemes involving sequential 1H data acquisition are presented for achieving protein backbone sequential resonance assignments: (i) acquisition of 3D {HCCNH and HNCACONH} and (ii) collection of 3D {HNCOCANH and HNCACONH} chemical shift correlation spectra using uniformly 13C,15N labelled proteins. The sequential acquisition of these spectra reduces the overall experimental time by a factor of ≈2 as compared to individual acquisitions. The suitability of this approach is experimentally demonstrated for the C-terminal winged helix (WH) domain of the minichromosome maintenance (MCM) complex of Sulfolobus solfataricus.

  14. Reusing sequential software in a distributed environment

    NASA Astrophysics Data System (ADS)

    Bartoli, A.; Dini, G.; Luise, M.; Pazzaglia, G.; Prete, C. A.; D'Andrea, A.

    1995-03-01

    In this paper we present and discuss a real experience of reusing sequential software in a parallel and physically distributed computing environment. Specifically, we have combined the functionalities of two existing systems previously developed at our Department. One, Tracs, is a programming environment for networked, heterogeneous machines that, among other things, is able to generate process farms out of a pure sequential code. The other, SPACE, is a graphical tool that generates sequential Fortran programs for simulating digital transmission systems. We have implemented a tool that restructures SPACE-generated programs to let them match the input required by the Tracs process farm generator. The result is that users of SPACE can transparently take advantage of networked and heterogeneous workstations to run their simulations. We have tackled the problems arising from both parallelism and distribution. The techniques we have used can be easily applied to any problem that can be modelled according to the process farm paradigm. Moreover, our experience shows that the Tracs framework may constitute a sound basis for facilitating engineering efforts on the reuse of sequential software in distributed environments.

  15. Sequential Geoacoustic Filtering and Geoacoustic Inversion

    DTIC Science & Technology

    2014-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Sequential Geoacoustic Filtering and Geoacoustic Inversion ...geoacoustic inversion methods, their use in the analysis of shallow water experimental data, and evaluation of geoacoustic model and parameter...uncertainties including the mapping of these uncertainties through to system performance uncertainties. OBJECTIVES Analysis of geoacoustic inversion

  16. Adult Word Recognition and Visual Sequential Memory

    ERIC Educational Resources Information Center

    Holmes, V. M.

    2012-01-01

    Two experiments were conducted investigating the role of visual sequential memory skill in the word recognition efficiency of undergraduate university students. Word recognition was assessed in a lexical decision task using regularly and strangely spelt words, and nonwords that were either standard orthographically legal strings or items made from…

  17. A Bayesian sequential design with binary outcome.

    PubMed

    Zhu, Han; Yu, Qingzhao; Mercante, Donald E

    2017-03-02

    Several researchers have proposed solutions to control type I error rate in sequential designs. The use of Bayesian sequential design becomes more common; however, these designs are subject to inflation of the type I error rate. We propose a Bayesian sequential design for binary outcome using an alpha-spending function to control the overall type I error rate. Algorithms are presented for calculating critical values and power for the proposed designs. We also propose a new stopping rule for futility. Sensitivity analysis is implemented for assessing the effects of varying the parameters of the prior distribution and maximum total sample size on critical values. Alpha-spending functions are compared using power and actual sample size through simulations. Further simulations show that, when total sample size is fixed, the proposed design has greater power than the traditional Bayesian sequential design, which sets equal stopping bounds at all interim analyses. We also find that the proposed design with the new stopping for futility rule results in greater power and can stop earlier with a smaller actual sample size, compared with the traditional stopping rule for futility when all other conditions are held constant. Finally, we apply the proposed method to a real data set and compare the results with traditional designs.

  18. An Inexpensive Remote Sequential Air Sampler

    ERIC Educational Resources Information Center

    Griffith, George A.; And Others

    1974-01-01

    Describes a remote air sampling device constructed of a number of spring loaded syringes which are released sequentially by the motion of a rotary mechanical timer. The unit can take accurate samples automatically and contain the samples without leakage for periods up to 18 hours in an outdoor environment. (SLH)

  19. Terminating Sequential Delphi Survey Data Collection

    ERIC Educational Resources Information Center

    Kalaian, Sema A.; Kasim, Rafa M.

    2012-01-01

    The Delphi survey technique is an iterative mail or electronic (e-mail or web-based) survey method used to obtain agreement or consensus among a group of experts in a specific field on a particular issue through a well-designed and systematic multiple sequential rounds of survey administrations. Each of the multiple rounds of the Delphi survey…

  20. Drying leather with vacuum and toggling sequentially

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigated a drying method that will enable leather to be dried under vacuum and stretch sequentially to improve area yield. Vacuum drying offers fast speed at a low temperature, which would be advantageous to heat-vulnerable chrome-free leather. Adding a toggle action after vacuum drying cou...

  1. Immune Interference After Sequential Alphavirus Vaccine Vaccinations

    DTIC Science & Technology

    2009-01-01

    REPORT DATE 11 MAR 2009 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Immune interference after sequential alphavirus ...of administration of investigational alphavirus vaccines on neutralizing antibody response. Volunteers who received the inactivated eastern and...vaccine strategy among those receiving multiple alphavirus vaccines and those developing next generation vaccines for these threats. 15. SUBJECT TERMS

  2. Mathematical Problem Solving through Sequential Process Analysis

    ERIC Educational Resources Information Center

    Codina, A.; Cañadas, M. C.; Castro, E.

    2015-01-01

    Introduction: The macroscopic perspective is one of the frameworks for research on problem solving in mathematics education. Coming from this perspective, our study addresses the stages of thought in mathematical problem solving, offering an innovative approach because we apply sequential relations and global interrelations between the different…

  3. Passive baited sequential filth fly trap

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Filth fly control measures may be optimized with a better understanding of fly population dynamics measured throughout the day. We describe the modification of a commercial motorized sequential mosquito trap to accept liquid odorous bait and leverage a classic inverted cone design to passively confi...

  4. Early Astronomical Sequential Photography, 1873-1923

    NASA Astrophysics Data System (ADS)

    Bonifácio, Vitor

    2011-11-01

    In 1873 Jules Janssen conceived the first automatic sequential photographic apparatus to observe the eagerly anticipated 1874 transit of Venus. This device, the 'photographic revolver', is commonly considered today as the earliest cinema precursor. In the following years, in order to study the variability or the motion of celestial objects, several instruments, either manually or automatically actuated, were devised to obtain as many photographs as possible of astronomical events in a short time interval. In this paper we strive to identify from the available documents the attempts made between 1873 and 1923, and discuss the motivations behind them and the results obtained. During the time period studied astronomical sequential photography was employed to determine the time of the instants of contact in transits and occultations, and to study total solar eclipses. The technique was seldom used but apparently the modern film camera invention played no role on this situation. Astronomical sequential photographs were obtained both before and after 1895. We conclude that the development of astronomical sequential photography was constrained by the reduced number of subjects to which the technique could be applied.

  5. Broad Phenotypic Cross-Resistance to Elvitegravir in HIV-Infected Patients Failing on Raltegravir-Containing Regimens

    PubMed Central

    Villacian, Jorge; Zahonero, Natalia; Pattery, Theresa; Garcia, Federico; Gutierrez, Felix; Caballero, Estrella; Van Houtte, Margriet; de Mendoza, Carmen

    2012-01-01

    The failure of raltegravir (RAL) is generally associated with the selection of mutations at integrase position Y143, Q148, or N155. However, a relatively high proportion of failures occurs in the absence of these changes. Here, we report the phenotypic susceptibilities to RAL and elvitegravir (EVG) for a large group of HIV-infected patients failing on RAL-containing regimens. Plasma from HIV-infected individuals failing on RAL-containing regimens underwent genotypic and phenotypic resistance testing (Antivirogram v2.5.01; Virco). A control group of patients failing on other regimens was similarly tested. Sixty-one samples were analyzed, 40 of which belonged to patients failing on RAL-containing regimens. Full RAL susceptibility was found in 20/21 controls, while susceptibility to EVG was diminished in 8 subjects, with a median fold change (FC) of 2.5 (interquartile range [IQR], 2.1 to 3.1). Fourteen samples from patients with RAL failures showed diminished RAL susceptibility, with a median FC of 38.5 (IQR, 10.8 to 103.2). Primary integrase resistance mutations were found in 11 of these samples, displaying a median FC of 68.5 (IQR, 23.5 to 134.3). The remaining 3 samples showed a median FC of 2.5 (IQR, 2 to 2.7). EVG susceptibility was diminished in 19/40 samples from patients with RAL failures (median FC, 7.71 [IQR, 2.48 to 99.93]). Cross-resistance between RAL and EVG was high (R2 = 0.8; P < 0.001), with drug susceptibility being more frequently reduced for EVG than for RAL (44.3% versus 24.6%; P = 0.035). Susceptibility to RAL and EVG is rarely affected in the absence of primary integrase resistance mutations. There is broad cross-resistance between RAL and EVG, which should preclude their sequential use. Resistance to EVG seems to be more frequent and might be more influenced by integrase variability. PMID:22450969

  6. Broad phenotypic cross-resistance to elvitegravir in HIV-infected patients failing on raltegravir-containing regimens.

    PubMed

    Garrido, Carolina; Villacian, Jorge; Zahonero, Natalia; Pattery, Theresa; Garcia, Federico; Gutierrez, Felix; Caballero, Estrella; Van Houtte, Margriet; Soriano, Vincent; de Mendoza, Carmen

    2012-06-01

    The failure of raltegravir (RAL) is generally associated with the selection of mutations at integrase position Y143, Q148, or N155. However, a relatively high proportion of failures occurs in the absence of these changes. Here, we report the phenotypic susceptibilities to RAL and elvitegravir (EVG) for a large group of HIV-infected patients failing on RAL-containing regimens. Plasma from HIV-infected individuals failing on RAL-containing regimens underwent genotypic and phenotypic resistance testing (Antivirogram v2.5.01; Virco). A control group of patients failing on other regimens was similarly tested. Sixty-one samples were analyzed, 40 of which belonged to patients failing on RAL-containing regimens. Full RAL susceptibility was found in 20/21 controls, while susceptibility to EVG was diminished in 8 subjects, with a median fold change (FC) of 2.5 (interquartile range [IQR], 2.1 to 3.1). Fourteen samples from patients with RAL failures showed diminished RAL susceptibility, with a median FC of 38.5 (IQR, 10.8 to 103.2). Primary integrase resistance mutations were found in 11 of these samples, displaying a median FC of 68.5 (IQR, 23.5 to 134.3). The remaining 3 samples showed a median FC of 2.5 (IQR, 2 to 2.7). EVG susceptibility was diminished in 19/40 samples from patients with RAL failures (median FC, 7.71 [IQR, 2.48 to 99.93]). Cross-resistance between RAL and EVG was high (R(2) = 0.8; P < 0.001), with drug susceptibility being more frequently reduced for EVG than for RAL (44.3% versus 24.6%; P = 0.035). Susceptibility to RAL and EVG is rarely affected in the absence of primary integrase resistance mutations. There is broad cross-resistance between RAL and EVG, which should preclude their sequential use. Resistance to EVG seems to be more frequent and might be more influenced by integrase variability.

  7. Multi-step sequential batch two-phase anaerobic composting of food waste.

    PubMed

    Shin, H S; Han, S K; Song, Y C; Lee, C Y

    2001-03-01

    This study was conducted to evaluate the newly devised process, called MUlti-step Sequential batch Two-phase Anaerobic Composting (MUSTAC). The MUSTAC process consisted of several leaching beds for hydrolysis, acidification and post-treatment, and a UASB reactor for methane recovery. This process to treat food waste was developed with a high-rate anaerobic composting technique based on the rate-limiting step approach. Rumen microorganisms were inoculated to improve the low efficiency of acidogenic fermentation. Both two-phase anaerobic digestion and sequential batch operation were used to control environmental constraints in anaerobic degradation. The MUSTAC process demonstrated excellent performance as it resulted in a large reduction in volatile solids (VS) (84.7%) and high methane conversion efficiency (84.4%) at high organic loading rates (10.8 kg VS m(-3) d(-1)) in a short SRT (10 days). Methane yield was 0.27 m3 kg(-1) VS, while methane gas production rate was 2.27 m3 m(-3) d(-1). The output from the post-treatment could be used as a soil amendment, which was produced at the same acidogenic fermenter without troublesome moving. The main advantages of the MUSTAC process were simple operation and high efficiency. The MUSTAC process proved stable, reliable and effective in resource recovery as well as waste stabilization.

  8. The Washington Regimen: rehabilitation of the hand following flexor tendon injuries.

    PubMed

    Dovelle, S; Heeter, P K

    1989-12-01

    This article describes the use of the "Washington Regimen" of early controlled motion in the rehabilitation of flexor tendon injuries of the hand. This regimen is derived from a combination of Kleinert's controlled active extension with rubber-hand passive flexion, Duran's controlled passive techniques, and the modification of the Kleinert orthosis that uses a palmar pulley system. Based on results of clinical investigations, this regimen of early controlled motion appears effective in inhibiting peritendinous scarring, joint contractures, and other complications that commonly occur secondary to flexor tendon repairs. A six-week staged regimen of postoperative rehabilitation is presented. Splint design, exercise regimen, and rationale for treatment are reviewed.

  9. Forecasting Flooding in the Brahmaputra and Ganges Delta of Bangladesh on Short (1-10 days), Medium (20-30 days) and Seasonal Time Scales (1-6 months)

    NASA Astrophysics Data System (ADS)

    Webster, P. J.; Hoyos, C. D.; Hopson, T. M.; Chang, H.; Jian, J.

    2007-12-01

    Following the devastating flood years of 1998 during which 60% of Bangladesh was under water for a period of 3 months, the Climate Forecast Applications in Bangladesh (CFAB) project was formed with funding by USAID and NSF which eventually resulted in a joint project with the European Centre for Medium Range Weather Forecasting (ECMWF), the Asian Disaster Preparedness Centre (ADPC) and the Bangladesh Flood Forecasting and Warning Centre. The project was organized and developed through the Georgia Institute of Technology. The aim of CFAB was to develop innovative methods of extending the warning of flooding in Bangladesh noting that there was a unique problem: India provided no upstream discharge data to Bangladesh so that before CFAB the maximum lead time of a forecast was that given by measuring river discharge at the India-Bangladesh border: no lead-time at the border and 2 days in the southern parts of the country. Given that the Brahmaputra and Ganges catchment areas had to be regarded as essentially unguaged, it was clear that innovative techniques had to be developed. On of the basic criterion was that the system should provide probabilistic forecasts in order for the Bangladeshis to assess risk. A three-tier system was developed to allow strategic and tactical decisions to be made for agricultural purposes and disaster mitigation: seasonal (1-6 months: strategic), medium range (20-30 days: strategic/tactical) and short range (1-10 days: tactical). The system that has been developed brings together for the first time operational meteorological forecasts (ensemble forecasts from ECMWF), with satellite and discharge data and a suite of hydrological models. In addition, with ADPC and FFWC we have developed an in-country forecast dispersion system that allows a rapid dissemination. The system has proven to be rather successful, especially in the short range. The flooding events of 2004 were forecast with all forecasting tiers at the respective lead time. In

  10. Management of patients using unproven regimens for arthritis.

    PubMed

    Wolman, P G

    1987-09-01

    Such treatments as vegetarian diets, fresh or raw diets, allergy diets, no-dairy-products diets, fasting, vitamin and mineral supplementation, apple cider vinegar, and honey drinks are touted in the popular press as effective for the treatment of arthritis. In contrast to conventional therapies, the unproven treatments promise not only relief from symptoms but freedom from the disease as long as the diet regimen is followed. Several of the remedies appear to be harmless, but others are dangerous, especially if followed for prolonged periods. Nutrition professionals should be aware of the nature of these treatments and be prepared to offer sound, scientifically based but nonjudgmental care and information.

  11. Rifaximin Plus Levofloxacin-Based Rescue Regimen for the Eradication of Helicobacter pylori

    PubMed Central

    Yun, Sang-Pil; Seon, Han Gyung; Ok, Chang Soo; Yoo, Kwang Ho; Kang, Min Kyung; Kim, Won Hee; Kwon, Chang Il; Ko, Kwang Hyun; Hwang, Seong Gyu; Park, Pil Won

    2012-01-01

    Background/Aims This study assessed the efficacy of a rifaximin plus levofloxacin-based rescue regimen in patients that had failed both triple and quadruple standard regimens for the eradication of Helicobacter pylori. Methods We treated patients for H. pylori between August 2009 and April 2011. The triple regimen consisted of combined treatment with amoxicillin, clarithromycin, and pantoprazole for 1 week. For failed cases, a quadruple regimen of tetracycline, metronidazole, bismuth dicitrate, and lansoprazole for 1 week was administered. The rescue regimen for persistently refractory cases was rifaximin 200 mg t.i.d., levofloxacin 500 mg q.d., and lansoprazole 15 mg b.i.d. for 1 week. Results In total, 482 patients were enrolled in this study. The eradication rates associated with the first and second regimens were 58% and 60%, respectively. Forty-seven out of 58 patients who failed with the second-line regimen received rifaximin plus levofloxacin-based third-line therapy. The eradication rate for the third regimen was 65%. The cumulative eradication rates were 58%, 85%, and 96% for each regimen, respectively. Conclusions A rifaximin plus levofloxacin-based regimen could be an alternative rescue therapy in patients with resistance to both triple and quadruple regimens for the eradication of H. pylori. PMID:23170149

  12. Sequential Analysis: A Tool for Monitoring Program Delivery.

    ERIC Educational Resources Information Center

    Howe, Holly L.; Hoff, Margaret B.

    1981-01-01

    The sensitivity and simplicity of Wald's sequential analysis test in monitoring a preventive health care program are discussed. Data exemplifying the usefulness and expedience of employing sequential methods are presented. (Author/GK)

  13. Logistics of therapy with the ibritumomab tiuxetan regimen

    SciTech Connect

    Meredith, Ruby F. . E-mail: rmeredith@uabmc.edu

    2006-10-01

    Radioimmunotherapy is an important new modality for treating patients with B-cell non-Hodgkin's lymphoma (NHL). Clinical trials have shown the safety and efficacy of agents that deliver radiation directly to malignant cells by attaching the {sup 131}I or {sup 9}Y radionuclide to monoclonal antibodies against CD20. In clinical trials, {sup 9}Y ibritumomab tiuxetan has produced rates of response as high as 83% in patients with relapsed or refractory CD20+ NHL. The ibritumomab tiuxetan regimen is conveniently given in an outpatient setting over the course of 7-9 days. This article describes the logistics for initiating treatment, coordinating a multidisciplinary team, identifying eligible patients, and delivering the imaging and therapeutic doses of ibritumomab tiuxetan. The standard radiation safety procedures to protect family members and healthcare professionals involved in the care of patients treated with {sup 9}Y ibritumomab tiuxetan are also reviewed. Treatment with the ibritumomab tiuxetan regimen involves only standard precautions needed to minimize radiation exposure to other persons.

  14. New anti-tuberculosis drugs and regimens: 2015 update

    PubMed Central

    D'Ambrosio, Lia; Centis, Rosella; Sotgiu, Giovanni; Pontali, Emanuele; Spanevello, Antonio; Migliori, Giovanni Battista

    2015-01-01

    Over 480 000 cases of multidrug-resistant (MDR) tuberculosis (TB) occur every year globally, 9% of them being affected by extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. The treatment of MDR/XDR-TB is unfortunately long, toxic and expensive, and the success rate largely unsatisfactory (<20% among cases with resistance patterns beyond XDR). The aim of this review is to summarise the available evidence-based updated international recommendations to manage MDR/XDR-TB, and to update the reader on the role of newly developed drugs (delamanid, bedaquiline and pretomanid) as well as repurposed drugs (linezolid and meropenem clavulanate, among others) used to treat these conditions within new regimens. A nonsystematic review based on historical trials results as well as on recent literature and World Health Organization (WHO) guidelines has been performed, with special focus on the approach to managing MDR/XDR-TB. The new, innovative global public health interventions, recently approved by WHO and known as the “End TB Strategy”, support the vision of a TB-free world with zero death, disease and suffering due to TB. Adequate, universally accessed treatment is a pre-requisite to reach TB elimination. New shorter, cheap, safe and effective anti-TB regimens are necessary to boost TB elimination. PMID:27730131

  15. A truncated-dose regimen of daclizumab for prevention of acute rejection in kidney transplant recipients: a single-center experience.

    PubMed

    Soltero, Liliana; Carbajal, Hector; Sarkissian, Nadine; Khan, Abdul-Jabbar; Brennan, Stephen; Gonzalez, Juan M; Truong, Luan D; Suki, Wadi N

    2004-11-27

    Daclizumab can decrease the incidence of acute rejection (AR) in renal transplant (RTx) recipients. In this prospective study, 52 RTx patients were divided into two groups according to the dose of daclizumab: 1 mg/kg on day 0 and every 14 days for five doses (group 1, n = 30) or a truncated regimen of 2 mg/kg on day 0 and on the day of discharge (group 2, n = 22). The following variables were recorded: demographics; delayed graft function; AR at 3, 6, and 12 months; time to AR; chronic allograft nephropathy (CAN); and serum creatinine. The overall incidences of AR were 23% and 27% (P = 0.76) in groups 1 and 2, respectively, whereas at 6 months they were 21% and 18% (P = 1.0). Median time to AR was 10 days in group 1 and 94 days in group 2 (P = 0.09). The incidence of CAN was 6.6% in group 1 and 13% in group 2 (P = 0.63). These data suggest that the truncated dose of daclizumab is as effective as the standard regimen for AR prophylaxis.

  16. Sequential stopping for high-throughput experiments.

    PubMed

    Rossell, David; Müller, Peter

    2013-01-01

    In high-throughput experiments, the sample size is typically chosen informally. Most formal sample-size calculations depend critically on prior knowledge. We propose a sequential strategy that, by updating knowledge when new data are available, depends less critically on prior assumptions. Experiments are stopped or continued based on the potential benefits in obtaining additional data. The underlying decision-theoretic framework guarantees the design to proceed in a coherent fashion. We propose intuitively appealing, easy-to-implement utility functions. As in most sequential design problems, an exact solution is prohibitive. We propose a simulation-based approximation that uses decision boundaries. We apply the method to RNA-seq, microarray, and reverse-phase protein array studies and show its potential advantages. The approach has been added to the Bioconductor package gaga.

  17. Sequential motif profile of natural visibility graphs

    NASA Astrophysics Data System (ADS)

    Iacovacci, Jacopo; Lacasa, Lucas

    2016-11-01

    The concept of sequential visibility graph motifs—subgraphs appearing with characteristic frequencies in the visibility graphs associated to time series—has been advanced recently along with a theoretical framework to compute analytically the motif profiles associated to horizontal visibility graphs (HVGs). Here we develop a theory to compute the profile of sequential visibility graph motifs in the context of natural visibility graphs (VGs). This theory gives exact results for deterministic aperiodic processes with a smooth invariant density or stochastic processes that fulfill the Markov property and have a continuous marginal distribution. The framework also allows for a linear time numerical estimation in the case of empirical time series. A comparison between the HVG and the VG case (including evaluation of their robustness for short series polluted with measurement noise) is also presented.

  18. Sequential shrink photolithography for plastic microlens arrays.

    PubMed

    Dyer, David; Shreim, Samir; Jayadev, Shreshta; Lew, Valerie; Botvinick, Elliot; Khine, Michelle

    2011-07-18

    Endeavoring to push the boundaries of microfabrication with shrinkable polymers, we have developed a sequential shrink photolithography process. We demonstrate the utility of this approach by rapidly fabricating plastic microlens arrays. First, we create a mask out of the children's toy Shrinky Dinks by simply printing dots using a standard desktop printer. Upon retraction of this pre-stressed thermoplastic sheet, the dots shrink to a fraction of their original size, which we then lithographically transfer onto photoresist-coated commodity shrink wrap film. This shrink film reduces in area by 95% when briefly heated, creating smooth convex photoresist bumps down to 30 µm. Taken together, this sequential shrink process provides a complete process to create microlenses, with an almost 99% reduction in area from the original pattern size. Finally, with a lithography molding step, we emboss these bumps into optical grade plastics such as cyclic olefin copolymer for functional microlens arrays.

  19. Lung Volume Measured during Sequential Swallowing in Healthy Young Adults

    ERIC Educational Resources Information Center

    Hegland, Karen Wheeler; Huber, Jessica E.; Pitts, Teresa; Davenport, Paul W.; Sapienza, Christine M.

    2011-01-01

    Purpose: Outcomes from studying the coordinative relationship between respiratory and swallow subsystems are inconsistent for sequential swallows, and the lung volume at the initiation of sequential swallowing remains undefined. The first goal of this study was to quantify the lung volume at initiation of sequential swallowing ingestion cycles and…

  20. Heat accumulation during sequential cortical bone drilling.

    PubMed

    Palmisano, Andrew C; Tai, Bruce L; Belmont, Barry; Irwin, Todd A; Shih, Albert; Holmes, James R

    2016-03-01

    Significant research exists regarding heat production during single-hole bone drilling. No published data exist regarding repetitive sequential drilling. This study elucidates the phenomenon of heat accumulation for sequential drilling with both Kirschner wires (K wires) and standard two-flute twist drills. It was hypothesized that cumulative heat would result in a higher temperature with each subsequent drill pass. Nine holes in a 3 × 3 array were drilled sequentially on moistened cadaveric tibia bone kept at body temperature (about 37 °C). Four thermocouples were placed at the center of four adjacent holes and 2 mm below the surface. A battery-driven hand drill guided by a servo-controlled motion system was used. Six samples were drilled with each tool (2.0 mm K wire and 2.0 and 2.5 mm standard drills). K wire drilling increased temperature from 5 °C at the first hole to 20 °C at holes 6 through 9. A similar trend was found in standard drills with less significant increments. The maximum temperatures of both tools increased from <0.5 °C to nearly 13 °C. The difference between drill sizes was found to be insignificant (P > 0.05). In conclusion, heat accumulated during sequential drilling, with size difference being insignificant. K wire produced more heat than its twist-drill counterparts. This study has demonstrated the heat accumulation phenomenon and its significant effect on temperature. Maximizing the drilling field and reducing the number of drill passes may decrease bone injury.

  1. Sequential decision analysis for nonstationary stochastic processes

    NASA Technical Reports Server (NTRS)

    Schaefer, B.

    1974-01-01

    A formulation of the problem of making decisions concerning the state of nonstationary stochastic processes is given. An optimal decision rule, for the case in which the stochastic process is independent of the decisions made, is derived. It is shown that this rule is a generalization of the Bayesian likelihood ratio test; and an analog to Wald's sequential likelihood ratio test is given, in which the optimal thresholds may vary with time.

  2. Adaptive Networks For Sequential Decision Problems

    DTIC Science & Technology

    1992-09-01

    Problems of this kind can be viewed as discrete-time stochastic control problems. The theory of stochastic sequential decision making and the computational...is to use reinforcement learning as a component of a more complex system. We experimented with a kind of " bahavior based" reinforcement learning in...navigatiwn functions that are computed by using the harmonic function approach t,, path- planning recently developed by Connolly and Grupen

  3. Sequential learning for robot vision terrain classification

    NASA Astrophysics Data System (ADS)

    Witus, Gary; Karlsen, Robert; Hunt, Shawn

    2009-05-01

    Terrains have widely varying visual appearance depending on the type of foliage, season, current weather conditions, recent precipitation, time of day, relative direction of lighting, presence of man-made structures and artifacts, landscaping, etc. It is difficult, if not impossible, to specify in advance the appearance of the different terrains that will be encountered while operating a robot in urban or rural environments. Yet people, having accumulated wide-ranging experience, have little trouble recognizing familiar terrain types and learning to recognize new, previously unfamiliar, terrains. Robots typically accumulate experience in "chunks" and do not have the luxury of years of training. This paper presents recent results in sequential learning methods applied to robot terrain recognition. In this paper we explore different sequential learning problem formulations and alternative machine learning algorithms. The investigations are based on the same data set. We report on the initial development of an incremental fuzzy c-means clustering algorithm capable of learning new information. We report on an approach to convert regression tree modeling, normally a batch learning method, to batch-incremental learning. We investigate issues in formulating the sequential learning problem and the performance of these algorithms. We also compare performance to four incremental learning classifiers. All investigations were conducted using the same set of image features, extracted from on-board video from a small robot traversing different terrains.

  4. Immunosuppressive Total Lymphoid Irradiation-Based Reconditioning Regimens Enable Engraftment After Graft Rejection or Graft Failure in Patients Treated With Allogeneic Hematopoietic Stem Cell Transplantation

    SciTech Connect

    Heinzelmann, Frank; Lang, Peter J.; Ottinger, Hellmut; Faul, Christoph; Bethge, Wolfgang; Handgretinger, Rupert; Bamberg, Michael; Belka, Claus

    2008-02-01

    Purpose: To retrospectively evaluate the efficacy of total lymphoid irradiation (TLI)-based reconditioning regimens in patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation. Methods and Materials: The results of 14 patients (7 adults and 7 children) with a variety of hematologic malignant diseases treated with a TLI-based reconditioning regimen with 7-Gy single-dose application plus anti-T-lymphocyte antibody OKT3 (n = 11) and/or antithymocyte globulin (n = 7)/fludarabine (n = 9), followed by an infusion of peripheral blood stem cells (n = 13) or bone marrow stem cells (n = 1) from related or unrelated donors, were retrospectively analyzed. Results: Of the 14 recipients, the data from 11 were evaluable for engraftment after TLI-based reconditioning because 3 adults died early (at Day 2, 5, and 15) after the second transplantation of infectious complications. Engraftment in 4 adults was seen after a median of 12 days (range, 10-18) and occurred after a median of 10 days (range, 9-32) in the 7 children. TLI-based reconditioning was well-tolerated with no severe toxicity. The median overall survival and disease-free survival for the whole cohort was 140 days (range, 5-1,268). After a median follow-up of 681 days, the disease-free survival and overall survival rate was 85.7% and 85.7%, respectively, in the children. Despite engraftment in the 4 remaining adults, 1 died of fatal graft-vs.-host disease, 1 of infectious complications, 1 of disease relapse, and 1 of acute respiratory distress syndrome. Conclusions: In patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation, TLI-based reconditioning regimens allow sustained engraftment, paralleled by a favorable toxicity profile, potentially leading to long-term survival.

  5. [Antibiotic therapy against acute tonsillopharyngitis in children due to group A beta-hemolytic streptococci: comparison of clinical efficacy, the bactericidal effects, and effects on oral flora between cefditoren pivoxil for 5 days and amoxicillin for 10 days].

    PubMed

    Tsumura, Naoki; Nagai, Kensuke; Hidaka, Hidenobu; Otsu, Yasushi; Tanaka, Yuhei; Ikezawa, Shigeru; Honma, Shinichi; Shindo, Shizuo; Ubukata, Kimiko

    2011-06-01

    We compared the clinical efficacy, the bactericidal effects, effect on the oral microbial flora, and adverse reactions between cefditoren pivoxil (CDTR-PI) for 5 days and amoxicillin (AMPC) for 10 days in children with acute group A beta-hemolytic streptococci (GAS) tonsillopharyngitis, and simultaneously examined the emm genotype and drug susceptibility of the isolated GAS. The results showed that the clinical efficacy was 100% for CDTR-PI and 97.9% for AMPC, with no difference between the two groups, and the bacterial elimination rate was 100% in both groups. No serious adverse event was noted in either group. On the other hand, concerning changes in the oral microbial flora between before and after treatment, the amount of bacteria showed no change in the CDTR-PI group (p = 0.5761) but clearly decreased in the AMPC group (p = 0.0049). This indicates that CDTR-PI does not disturb the oral microbial flora compared with AMPC. Also, the emm types determined in the 112 GAS strains isolated in this study were similar to those that have recently been isolated frequently in Japan. Concerning the drug resistance, none of the isolates showed resistance to beta-lactam antibiotics, but 45% of them were resistant to macrolides. The advantages of short-term treatment are considered to include a lower cost, improvement in drug compliance, decrease in the frequency of the occurrence of adverse reactions, decrease in the frequency of the appearance of drug-resistant strains, and alleviation of the psychological burden of patients and their parents. For these reasons, we conclude that CDTR-PI for 5 days is a useful option for the treatment of acute GAS tonsillopharyngitis in children.

  6. Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants

    PubMed Central

    Churchyard, Gavin; Mlisana, Koleka; Karuna, Shelly; Williamson, Anna-Lise; Williamson, Carolyn; Morris, Lynn; Tomaras, Georgia D.; De Rosa, Stephen C.; Gilbert, Peter B.; Gu, Niya; Yu, Chenchen; Mkhize, Nonhlanhla N.; Hermanus, Tandile; Allen, Mary; Pensiero, Michael; Barnett, Susan W.; Gray, Glenda; Bekker, Linda-Gail; Montefiori, David C.; Kublin, James; Corey, Lawrence

    2016-01-01

    Background The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 109 pfu IM) and Novartis V2-deleted subtype C gp140 (100 mcg) with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa. Methods Participants at three South African sites were randomized (1:1:1:1) to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P); concurrent MVA/gp140 (MP/MP); DNA prime, sequential MVA boost (D/D/M/M); DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP) or placebo. Peak HIV specific humoral and cellular responses were measured. Results 184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18–42 years) and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens. Conclusions The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen. Trial Registration ClinicalTrials.gov NCT01418235 PMID:27583368

  7. Sequential Treatment of Biofilms with Aztreonam and Tobramycin Is a Novel Strategy for Combating Pseudomonas aeruginosa Chronic Respiratory Infections

    PubMed Central

    Macià, María D.; Rubio, Rosa; Moyà, Bartolomé; Cabot, Gabriel; López-Causapé, Carla; Pérez, José L.; Cantón, Rafael; Oliver, Antonio

    2016-01-01

    Traditional therapeutic strategies to control chronic colonization in cystic fibrosis (CF) patients are based on the use of a single nebulized antibiotic. In this study, we evaluated the therapeutic efficacy and dynamics of antibiotic resistance in Pseudomonas aeruginosa biofilms under sequential therapy with inhaled aztreonam (ATM) and tobramycin (TOB). Laboratory strains PAO1, PAOMS (hypermutable), PAOMA (mucoid), and PAOMSA (mucoid and hypermutable) and two hypermutable CF strains, 146-HSE (Liverpool epidemic strain [LES-1]) and 1089-HSE (ST1089), were used. Biofilms were developed using the flow cell system. Mature biofilms were challenged with peak and 1/10-peak concentrations of ATM (700 mg/liter and 70 mg/liter), TOB (1,000 mg/liter and 100 mg/liter), and their alternations (ATM/TOB/ATM and TOB/ATM/TOB) for 2 (t = 2), 4 (t = 4), and 6 days (t = 6). The numbers of viable cells (CFU) and resistant mutants were determined. Biofilm structural dynamics were monitored by confocal laser scanning microscopy and processed with COMSTAT and IMARIS software programs. TOB monotherapy produced an intense decrease in CFU that was not always correlated with a reduction in biomass and/or a bactericidal effect on biofilms, particularly for the CF strains. The ATM monotherapy bactericidal effect was lower, but effects on biofilm biomass and/or structure, including intense filamentation, were documented. The alternation of TOB and ATM led to an enhancement of the antibiofilm activity against laboratory and CF strains compared to that with the individual regimens, potentiating the bactericidal effect and/or the reduction in biomass, particularly at peak concentrations. Resistant mutants were not documented in any of the regimens at the peak concentrations and only anecdotally at the 1/10-peak concentrations. These results support the clinical evaluation of sequential regimens with inhaled antibiotics in CF, as opposed to the current maintenance treatments with just one

  8. Comparison Between Sequential Therapy and Modified Bismuth-Included Quadruple Therapy for Helicobacter pylori Eradication in Chinese Patients.

    PubMed

    Yang, Xiuhong; Tan, Pengsheng; Song, Lianying; Lu, Zhanying

    To compare the efficacy and safety of sequential therapy and modified bismuth-included quadruple therapy as a first-line Helicobacter pylori eradication in China. The patients were randomized to receive sequential therapy [n = 90; rabeprazole (20 mg twice daily) and amoxicillin (1 g twice daily) for 5 days, followed by rabeprazole (20 mg twice daily), tinidazole (500 mg twice daily) plus clarithromycin (500 mg twice daily) for another 5 days] or modified bismuth-included quadruple therapy [n = 109; rabeprazole (20 mg twice daily), levofloxacin hydrochloride (400 mg twice daily), clarithromycin (500 mg twice daily), and colloidal bismuth pectin (200 mg 3 times a day) for 7 days]. A follow-up urea breath test was applied 4 weeks later. A total of 199 patients were diagnosed with H. pylori infection. The intention-to-treat and per-protocol (PP) eradication rates were 91.7% and 92.6%, respectively, in the modified bismuth-included quadruple therapy group, and 74.4% and 76.1%, respectively, in the sequential therapy group. The eradication rates were significantly higher in the modified bismuth-included quadruple therapy group, compared with the sequential therapy group (P = 0.001 for intention to treat and P = 0.001 for PP). Adverse effects were reported by patients from both groups, but the difference did not reach significant level (P = 0.280). The modified bismuth-included quadruple therapy seemed to be superior to the sequential therapy as the first-line regimen for H. pylori eradication in Chinese patients.

  9. Long-lasting alterations in 5-HT2A receptor after a binge regimen of methamphetamine in mice.

    PubMed

    Chiu, Hong-Yi; Chan, Ming-Huan; Lee, Mei-Yi; Chen, Shao-Tsu; Zhan, Zih-Yi; Chen, Hwei-Hsien

    2014-10-01

    The repeated administration of methamphetamine (MA) to animals in a single-day 'binge' dosing regimen produces damage to dopamine and serotonin terminals and psychosis-like behaviours similar to those observed in MA abusers. The present study aimed to examine the effects of MA binge exposure on 5-HT2A receptors, the subtype of serotonin receptors putatively involved in psychosis. ICR male mice were treated with MA (4 × 5 mg/kg) or saline at 2 h intervals. Recognition memory and social behaviours were sequentially evaluated by a novel location recognition test, a novel object recognition test, a social interaction and a nest-building test to confirm the persistent cognitive and behavioural impairments after this dosing regimen. Subsequently, a hallucinogenic 5-HT2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI)-induced head-twitch, molecular and electrophysiological responses were monitored. Finally, the levels of 5-HT2C, 5-HT1A, 5-HT2A and mGlu2 receptors in the medial prefrontal cortex were determined. MA binge exposure produced recognition memory impairment, reduced social behaviours, and increased DOI-induced head-twitch response, c-Fos and Egr-2 expression and field potentials in the medial prefrontal cortex. Furthermore, MA binge exposure increased 5-HT2A and decreased mGlu2 receptor expression in the medial frontal cortex, whereas 5-HT2C and 5-HT1A receptors were unaffected. These data reveal that the increased behavioural, molecular and electrophysiological responses to DOI might be associated with an up-regulation of 5-HT2A receptors in the medial prefrontal cortex after MA binge exposure. Identifying the biochemical alterations that parallel the behavioural changes in a mouse model of MA binge exposure may facilitate targeting therapies for treatment of MA-related psychiatric disorders.

  10. Sequential cancer immunotherapy: targeted activity of dimeric TNF and IL-8

    PubMed Central

    Adrian, Nicole; Siebenborn, Uta; Fadle, Natalie; Plesko, Margarita; Fischer, Eliane; Wüest, Thomas; Stenner, Frank; Mertens, Joachim C.; Knuth, Alexander; Ritter, Gerd; Old, Lloyd J.; Renner, Christoph

    2009-01-01

    Polymorphonuclear neutrophils (PMNs) are potent effectors of inflammation and their attempts to respond to cancer are suggested by their systemic, regional and intratumoral activation. We previously reported on the recruitment of CD11b+ leukocytes due to tumor site-specific enrichment of TNF activity after intravenous administration of a dimeric TNF immunokine with specificity for fibroblast activation protein (FAP). However, TNF-induced chemo-attraction and extravasation of PMNs from blood into the tumor is a multistep process essentially mediated by interleukin 8. With the aim to amplify the TNF-induced and IL-8-mediated chemotactic response, we generated immunocytokines by N-terminal fusion of a human anti-FAP scFv fragment with human IL-8 (IL-872) and its N-terminally truncated form IL-83-72. Due to the dramatic difference in chemotaxis induction in vitro, we favored the mature chemokine fused to the anti-FAP scFv for further investigation in vivo. BALB/c nu/nu mice were simultaneously xenografted with FAP-positive or -negative tumors and extended chemo-attraction of PMNs was only detectable in FAP-expressing tissue after intravenous administration of the anti-FAP scFv-IL-872 construct. As TNF-activated PMNs are likewise producers and primary targets for IL-8, we investigated the therapeutic efficacy of co-administration of both effectors: Sequential application of scFv-IL-872 and dimeric IgG1-TNF fusion proteins significantly enhanced anti-tumor activity when compared either to a single effector treatment regimen or sequential application of non-targeted cytokines, indicating that the tumor-restricted sequential application of IL-872 and TNF is a promising approach for cancer therapy. PMID:19267427

  11. Gefitinib, Fluorouracil, Oxaliplatin, and Leucovorin (IFOX) Regimen for Colorectal Cancer

    PubMed Central

    Chen, Alicia S.; Solimando, Dominic A.; Waddell, J. Aubrey

    2013-01-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. PMID:24474830

  12. Comparison of different regimens for surgical hand preparation.

    PubMed

    Larson, E L; Aiello, A E; Heilman, J M; Lyle, C T; Cronquist, A; Stahl, J B; Della-Latta, P

    2001-02-01

    Twenty surgical staff members participated in a clinical trial to compare the microbiology and skin condition of hands when using a traditional surgical scrub (TSS) with a detergent-based antiseptic containing 4% chlorhexidine gluconate (CHG) and a short application without scrub of a waterless hand preparation (HP) containing 61% ethyl alcohol, 1% CHG, and emollients. The HP was associated with less skin damage (P = .002) and lower microbial counts postscrub at days five (P = .002) and 19 (P = .02). The HP protocol had shorter contact time (HP mean [M] = 80.7 seconds; TSS M = 144.9 seconds; P < .0001), and more subjects preferred the HP regimen (P = .001). The HP performed better than the TSS, was less costly, and should be evaluated in larger trials and considered for widespread implementation.

  13. Toward the definition of immunosuppressive regimens with antitumor activity.

    PubMed

    Casadio, F; Croci, S; D'Errico Grigioni, A; Corti, B; Grigioni, W F; Landuzzi, L; Lollini, P-L

    2005-06-01

    Immunosuppressive therapies associated with organ transplantation produce an increased risk of cancer development. Malignancies are increased in transplant recipients because of the impaired immune system. Moreover, experimental data point to a tumor-promoting activity of various immunosuppressive agents. In this study, we compared the effects of 4 immunosuppressive agents with different mechanisms of action (cyclosporine, rapamycin, mycophenolic acid, and leflunomide) on the in vitro growth of various tumor cell lines and umbilical vein endothelial cells. To varying degrees rapamycin (10 ng/mL), mycophenolic acid (300 nmol/L), and leflunomide (30 micromol/L) highly inhibited the growth of human rhabdomyosarcoma, hepatocellular carcinoma, colorectal carcinoma, and endothelial cells. In contrast, cyclosporine (100 ng/mL) did not affect their growth. Our data suggest that regimens containing rapamycin, mycophenolic acid, or leflunomide, which have both immunosuppressive and antitumor activities, should be preferred in transplant recipients to minimize the risk of tumors.

  14. Levothyroxine Treatment in Pregnancy: Indications, Efficacy, and Therapeutic Regimen

    PubMed Central

    Klubo-Gwiezdzinska, Joanna; Burman, Kenneth D.; Van Nostrand, Douglas; Wartofsky, Leonard

    2011-01-01

    The prevalence of overt and subclinical hypothyroidism during pregnancy is estimated to be 0.3–0.5% and 2–3%, respectively. Thyroid autoantibodies are found in 5–18% of women in the childbearing age. The aim of this review is to underscore the clinical significance of these findings on the health of both the mother and her offspring. Methods of evaluation of thyroid function tests (TFTs) during pregnancy are described as are the threshold values for the diagnosis of overt and subclinical hypothyroidism or hypothyroxinemia. Anticipated differences in TFTs in iodine-sufficient and iodine-deficient areas are discussed and data are provided on potential complications of hypothyroidism/hypothyroxinemia and autoimmune thyroid disease during pregnancy and adverse effects for the offspring. The beneficial effects of levothyroxine therapy on pregnancy outcomes and offspring development are discussed with a proposed treatment regimen and follow up strategy. PMID:21876837

  15. Current regimens and novel agents for mantle cell lymphoma.

    PubMed

    Chen, Yiming; Wang, Michael; Romaguera, Jorge

    2014-10-01

    Mantle cell lymphoma is a heterogeneous subtype of non-Hodgkin lymphoma. Conventional treatment with immunochemotherapy followed by autologous stem cell transplantation or intensive immunochemotherapy alone has improved outcomes, but the disease remains incurable. Recent advances in basic and translational research have significantly enhanced our understanding of disease pathogenesis and have sparked the development of novel therapies. Novel agents include the proteasome inhibitor bortezomib, the immunomodulatory agent lenalidomide, the phosphatidylinositol-4,5-bisphosphate 3-kinase pathway inhibitor idelalisib and the Bruton tyrosine kinase inhibitor ibrutinib. Preliminary results from clinical trials, especially from studies of ibrutinib, have proven these agents to be effective. In ongoing studies, these agents are being integrated into conventional immunochemotherapy regimens to hopefully improve patient outcomes.

  16. Regimen selection in the OPTIONS trial of HIV salvage therapy: drug resistance, prior therapy, and race–ethnicity determine the degree of regimen complexity

    PubMed Central

    Tashima, Karen T.; Mollan, Katie R.; Na, Lumine; Gandhi, Rajesh T.; Klingman, Karin L.; Fichtenbaum, Carl J.; Andrade, Adriana; Johnson, Victoria A.; Eron, Joseph J.; Smeaton, Laura; Haubrich, Richard H.

    2015-01-01

    Background Regimen selection for highly treatment-experienced patients is complicated. Methods Using a web-based utility, study team members reviewed antiretroviral (ARV) history and resistance data and recommended individual ARV regimens and nucleoside reverse transcriptase inhibitor (NRTI) options for treatment-experienced participants consisting of 3–4 of the following agents: raltegravir (RAL), darunavir (DRV)/ritonavir, tipranavir (TPV)/ritonavir, etravirine (ETR), maraviroc (MVC), and enfuvirtide (ENF). We evaluated team recommendations and site selection of regimen and NRTIs. Associations between baseline factors and the selection of a complex regimen (defined as including four ARV agents or ENF) were explored with logistic regression. Results A total of 413 participants entered the study. Participants initiated the first or second recommended regimen 86% of the time and 21% of participants started a complex regimen. In a multivariable model, ARV resistance to NRTI (odds ratio [OR]=2.2), non-nucleoside reverse transcriptase inhibitor (NNRTI, OR=6.2) or boosted protease inhibitor (PI, OR=6.6), prior use of integrase strand transfer inhibitor (INSTI, OR=25), and race–ethnicity (all P≤0.01) were associated with selection of a complex regimen. Black non-Hispanic (OR=0.5) and Hispanic participants from the continental US (OR=0.2) were less likely to start a complex regimen, compared to white non-Hispanics. Conclusions In this multi-center trial, we developed a web-based utility that facilitated treatment recommendations for highly treatment-experienced patients. Drug resistance, prior INSTI use, and race–ethnicity were key factors in decisions to select a more complex regimen. PMID:26212575

  17. Sequential Bayesian Detection: A Model-Based Approach

    SciTech Connect

    Sullivan, E J; Candy, J V

    2007-08-13

    Sequential detection theory has been known for a long time evolving in the late 1940's by Wald and followed by Middleton's classic exposition in the 1960's coupled with the concurrent enabling technology of digital computer systems and the development of sequential processors. Its development, when coupled to modern sequential model-based processors, offers a reasonable way to attack physics-based problems. In this chapter, the fundamentals of the sequential detection are reviewed from the Neyman-Pearson theoretical perspective and formulated for both linear and nonlinear (approximate) Gauss-Markov, state-space representations. We review the development of modern sequential detectors and incorporate the sequential model-based processors as an integral part of their solution. Motivated by a wealth of physics-based detection problems, we show how both linear and nonlinear processors can seamlessly be embedded into the sequential detection framework to provide a powerful approach to solving non-stationary detection problems.

  18. Sequential Bayesian Detection: A Model-Based Approach

    SciTech Connect

    Candy, J V

    2008-12-08

    Sequential detection theory has been known for a long time evolving in the late 1940's by Wald and followed by Middleton's classic exposition in the 1960's coupled with the concurrent enabling technology of digital computer systems and the development of sequential processors. Its development, when coupled to modern sequential model-based processors, offers a reasonable way to attack physics-based problems. In this chapter, the fundamentals of the sequential detection are reviewed from the Neyman-Pearson theoretical perspective and formulated for both linear and nonlinear (approximate) Gauss-Markov, state-space representations. We review the development of modern sequential detectors and incorporate the sequential model-based processors as an integral part of their solution. Motivated by a wealth of physics-based detection problems, we show how both linear and nonlinear processors can seamlessly be embedded into the sequential detection framework to provide a powerful approach to solving non-stationary detection problems.

  19. Dilemma of first line regimens in metastatic pancreatic adenocarcinoma

    PubMed Central

    Ghosn, Marwan; Ibrahim, Tony; Assi, Tarek; El Rassy, Elie; Kourie, Hampig Raphael; Kattan, Joseph

    2016-01-01

    Pancreatic cancer is one of the deadliest cancers, ranking fourth among cancer-related deaths. Despite all the major molecular advances and treatment breakthroughs, mainly targeted therapies, the cornerstone treatment of metastatic pancreatic cancer (mPC) remains cytotoxic chemotherapy. In 2016, more than 40 years after the introduction of gemcitabine in the management of mPC, the best choice for first-line treatment has not yet been fully elucidated. Two main strategies have been adopted to enhance treatment efficacy. The first strategy is based on combining non-cross resistant drugs, while the second option includes the development of newer generations of chemotherapy. More recently, two new regimens, FOLFIRINOX and gemcitabine/nab-paclitaxel (GNP), have both been shown to improve overall survival in comparison with gemcitabine alone, at the cost of increased toxicity. Therefore, the best choice for first line therapy is a matter of debate. For some authors, FOLFIRINOX should be the first choice in patients with an Eastern Cooperative Oncology Group score (0-1) given its lower hazard ratio. However, others do not share this opinion. In this paper, we review the main comparison points between FOLFIRINOX and GNP. We analyze the two pivotal trials to determine the similarities and differences in study design. In addition, we compare the toxicity profile of the two regimens as well as the impact on quality of life. Finally, we present studies revealing real life experiences and review the advantages and disadvantages of possible second-line therapies including their cost effectiveness. PMID:28028360

  20. Superiority of Interferon-Free Regimens for Chronic Hepatitis C

    PubMed Central

    Younossi, Zobair M.; Stepanova, Maria; Esteban, Rafael; Jacobson, Ira; Zeuzem, Stefan; Sulkowski, Mark; Henry, Linda; Nader, Fatema; Cable, Rebecca; Afendy, Mariam; Hunt, Sharon

    2017-01-01

    Abstract Patient-reported outcomes (PROs) such as quality of life and work productivity are important for measuring patient's experience. We assessed PROs during and after treatment of hepatitis C virus (HCV) patients. Data were obtained from a phase 3 open label study of sofosbuvir and ribavirin (SOF + RBV) with and without interferon (IFN). Patients completed 4 PRO assessment instruments (SF-36, Functional Assessment of Chronic Illness Therapy—Fatigue, Chronic Liver Disease Questionnaire— HCV, Work Productivity and Activity—Specific Health Problem) before, during, and after treatment. A total of 533 patients with chronic HCV were enrolled; 28.9% treatment-naïve, 23.1% cirrhotic, 219 received IFN + SOF + RBV and 314 received IFN-free SOF + RBV. At baseline, there were no differences in PROs between the IFN-free and IFN-containing treatment arms (all P > 0.05). During treatment, patients receiving IFN + SOF + RBV had a substantial impairment in their PROs (up to −24.4% by treatment week 12, up to −8.3% at week 4 post-treatment). The PRO decrements seen in the SOF + RBV arm were smaller in magnitude (up to −7.1% by treatment week 12), and all returned to baseline or improved by post-treatment week 4. By 12 weeks after treatment cessation, patients who achieved sustained viral response-12 showed some improvement of PRO scores regardless of the regimen (up to +7.1%, P < 0.0001) or previous treatment experience. In multivariate analysis, the use of IFN was independently associated with lower PROs. IFN-based regimens have a profoundly negative impact to PROs. By contrast, the impact of RBV on these PROs is relatively modest. Achieving HCV cure is associated with improvement of most of the PRO scores. PMID:28207507

  1. A study of parenteral iron regimens in hemodialysis patients.

    PubMed

    Besarab, A; Kaiser, J W; Frinak, S

    1999-07-01

    The administration of parenteral iron dextran to hemodialysis patients is typically intermittent. We sought to determine the most appropriate intervals for sampling iron parameters during intermittent need-based and continuous maintenance regimens and to quantify differences in efficacy between such regimens during long-term therapy. After a single course of 10 consecutive 100-mg iron doses administered to 14 patients on 16 occasions, transferrin saturation (TSAT) and ferritin were unreliable indices of iron status for the next 2 and 6 weeks, respectively. TSAT and ferritin levels at 1 week were virtually identical to those at 2 weeks after the administration of a single 50-mg or 100-mg iron dextran dose to 16 other patients. Twelve patients on maintenance iron therapy (25 to 100 mg/wk; TSAT, 30% to 50%) had a statistically significant decrease in the amount of recombinant human erythropoietin (rHuEPO) needed to maintain hemoglobin (Hb) levels between 10 and 11 g/dL compared with 12 patients receiving intermittent need-based dosing, an effect that persisted from week 16 to week 72 of the study. Maintenance iron was feasible even in a third group of eight patients targeted to sustain an Hb level of 14 g/dL. In both iron maintenance groups, iron indices could be measured at weekly intervals, and ferritin levels did not progressively increase over time. Continuous maintenance iron dextran used to maintain TSATs of 30% to 50% significantly reduced rHuEPO requirements and resulted in no adverse side effects in chronic hemodialysis patients. After weekly maintenance 25- to 100-mg iron dextran doses, iron indices can be measured after 1 week; a delay of 2 weeks is not necessary.

  2. Extended regimen combined oral contraception: A review of evolving concepts and acceptance by women and clinicians

    PubMed Central

    Nappi, Rossella E.; Kaunitz, Andrew M.; Bitzer, Johannes

    2016-01-01

    ABSTRACT Objectives: The clinical utility of extended regimen combined oral contraceptives (COCs) is increasingly being recognised. Our objective was to understand the attitudes of women and clinicians about the use of these regimens. We present the rationale for extended regimen COCs from a historical perspective, and trace their evolution and growing popularity in light of their clinical benefits. We conclude by offering potential strategies for counselling women about extended regimen COC options. Methods: We conducted a MEDLINE search to identify and summarise studies of extended regimen COCs, focusing on attitudes of women and clinicians regarding efficacy, safety/tolerability and fewer scheduled bleeding episodes and other potential benefits. Results: The body of contemporary literature on extended regimen COCs suggests that their contraceptive efficacy is comparable to that of conventional 28-day (i.e., 21/7) regimens. For women seeking contraception that allows infrequent scheduled bleeding episodes, particularly those who suffer from hormone withdrawal symptoms and cyclical symptoms (e.g., headache, mood changes, dysmenorrhoea, heavy menstrual bleeding), extended regimen COCs are an effective and safe option. Although satisfaction with extended regimen COCs in clinical trials is high, misperceptions about continuous hormone use may still limit the widespread acceptance of this approach. Conclusions: Despite the widespread acceptance among clinicians of extended regimen COCs as an effective and safe contraceptive option, these regimens are underused, likely due to a lack of awareness about their availability and utility among women. Improved patient education and counselling regarding the safety and benefits of extended regimen COCs may help women make more informed contraceptive choices. PMID:26572318

  3. A sequential nonparametric pattern classification algorithm based on the Wald SPRT. [Sequential Probability Ratio Test

    NASA Technical Reports Server (NTRS)

    Poage, J. L.

    1975-01-01

    A sequential nonparametric pattern classification procedure is presented. The method presented is an estimated version of the Wald sequential probability ratio test (SPRT). This method utilizes density function estimates, and the density estimate used is discussed, including a proof of convergence in probability of the estimate to the true density function. The classification procedure proposed makes use of the theory of order statistics, and estimates of the probabilities of misclassification are given. The procedure was tested on discriminating between two classes of Gaussian samples and on discriminating between two kinds of electroencephalogram (EEG) responses.

  4. Treatment regimens and health care utilization in children with persistent asthma symptoms.

    PubMed

    Yoos, H Lorrie; Kitzman, Harriet; Halterman, Jill S; Henderson, Charles; Sidora-Arcoleo, Kimberly; McMullen, Ann

    2006-01-01

    This study evaluated the anti-inflammatory medication regimens in children with persistent asthma, determined their health care utilization patterns, and evaluated factors associated with failure to seek and/or receive appropriate treatment. Parents of 68% of children who qualified for anti-inflammatory medications by National Asthma Education and Prevention Program (NAEPP) guidelines reported their use. However, only 14% received an optimal regimen (mild intermittent symptoms), while 55% were still symptomatic despite reported medications (suboptimal regimen). Nearly half of symptomatic children did not have a health care visit; of those who did, 61% had no corrective action documented. Factors contributing to variations in regimen and utilization are discussed.

  5. Sequential tool use in great apes.

    PubMed

    Martin-Ordas, Gema; Schumacher, Lena; Call, Josep

    2012-01-01

    Sequential tool use is defined as using a tool to obtain another non-food object which subsequently itself will serve as a tool to act upon a further (sub)goal. Previous studies have shown that birds and great apes succeed in such tasks. However, the inclusion of a training phase for each of the sequential steps and the low cost associated with retrieving the longest tools limits the scope of the conclusions. The goal of the experiments presented here was, first to replicate a previous study on sequential tool use conducted on New Caledonian crows and, second, extend this work by increasing the cost of retrieving a tool in order to test tool selectivity of apes. In Experiment 1, we presented chimpanzees, orangutans and bonobos with an out-of-reach reward, two tools that were available but too short to reach the food and four out-of-reach tools differing in functionality. Similar to crows, apes spontaneously used up to 3 tools in sequence to get the reward and also showed a strong preference for the longest out-of reach tool independently of the distance of the food. In Experiment 2, we increased the cost of reaching for the longest out-of reach tool. Now apes used up to 5 tools in sequence to get the reward and became more selective in their choice of the longest tool as the costs of its retrieval increased. The findings of the studies presented here contribute to the growing body of comparative research on tool use.

  6. Compatibility and noncontextuality for sequential measurements

    SciTech Connect

    Guehne, Otfried; Kleinmann, Matthias; Cabello, Adan; Larsson, Jan-Aake; Kirchmair, Gerhard; Zaehringer, Florian; Gerritsma, Rene; Roos, Christian F.

    2010-02-15

    A basic assumption behind the inequalities used for testing noncontextual hidden variable models is that the observables measured on the same individual system are perfectly compatible. However, compatibility is not perfect in actual experiments using sequential measurements. We discuss the resulting 'compatibility loophole' and present several methods to rule out certain hidden variable models that obey a kind of extended noncontextuality. Finally, we present a detailed analysis of experimental imperfections in a recent trapped-ion experiment and apply our analysis to that case.

  7. Sequential decision rules for failure detection

    NASA Technical Reports Server (NTRS)

    Chow, E. Y.; Willsky, A. S.

    1981-01-01

    The formulation of the decision making of a failure detection process as a Bayes sequential decision problem (BSDP) provides a simple conceptualization of the decision rule design problem. As the optimal Bayes rule is not computable, a methodology that is based on the Baysian approach and aimed at a reduced computational requirement is developed for designing suboptimal rules. A numerical algorithm is constructed to facilitate the design and performance evaluation of these suboptimal rules. The result of applying this design methodology to an example shows that this approach is a useful one.

  8. Sequential Events Control System (SECS) Overview

    NASA Technical Reports Server (NTRS)

    Interbartolo, Michael

    2009-01-01

    This slide presentation will cover the Sequential Events Control System (SECS), which is the Apollo spacecraft subsystem that controls the automatically sequenced functions during the mission and during any a borts that could be performed. Included in this presentation are its general architecture, its integration into and use of the spacecraft' s other systems, and details on the functions it is responsible for c ontrolling during the mission. The objectives are to describe the system's architecture, the major components in the system, and the major system functions.

  9. Sequential cooling insert for turbine stator vane

    DOEpatents

    Jones, Russell B; Krueger, Judson J; Plank, William L

    2014-04-01

    A sequential impingement cooling insert for a turbine stator vane that forms a double impingement for the pressure and suction sides of the vane or a triple impingement. The insert is formed from a sheet metal formed in a zigzag shape that forms a series of alternating impingement cooling channels with return air channels, where pressure side and suction side impingement cooling plates are secured over the zigzag shaped main piece. Another embodiment includes the insert formed from one or two blocks of material in which the impingement channels and return air channels are machined into each block.

  10. Sequential quantum teleportation of optical coherent states

    SciTech Connect

    Yonezawa, Hidehiro; Furusawa, Akira; Loock, Peter van

    2007-09-15

    We demonstrate a sequence of two quantum teleportations of optical coherent states, combining two high-fidelity teleporters for continuous variables. In our experiment, the individual teleportation fidelities are evaluated as F{sub 1}=0.70{+-}0.02 and F{sub 2}=0.75{+-}0.02, while the fidelity between the input and the sequentially teleported states is determined as F{sup (2)}=0.57{+-}0.02. This still exceeds the optimal fidelity of one half for classical teleportation of arbitrary coherent states and almost attains the value of the first (unsequential) quantum teleportation experiment with optical coherent states.

  11. Sequential cooling insert for turbine stator vane

    SciTech Connect

    Jones, Russel B; Krueger, Judson J; Plank, William L

    2014-11-04

    A sequential impingement cooling insert for a turbine stator vane that forms a double impingement for the pressure and suction sides of the vane or a triple impingement. The insert is formed from a sheet metal formed in a zigzag shape that forms a series of alternating impingement cooling channels with return air channels, where pressure side and suction side impingement cooling plates are secured over the zigzag shaped main piece. Another embodiment includes the insert formed from one or two blocks of material in which the impingement channels and return air channels are machined into each block.

  12. Estimation After a Group Sequential Trial

    PubMed Central

    Milanzi, Elasma; Molenberghs, Geert; Alonso, Ariel; Kenward, Michael G.; Tsiatis, Anastasios A.; Davidian, Marie; Verbeke, Geert

    2014-01-01

    Group sequential trials are one important instance of studies for which the sample size is not fixed a priori but rather takes one of a finite set of pre-specified values, dependent on the observed data. Much work has been devoted to the inferential consequences of this design feature. Molenberghs et al (2012) and Milanzi et al (2012) reviewed and extended the existing literature, focusing on a collection of seemingly disparate, but related, settings, namely completely random sample sizes, group sequential studies with deterministic and random stopping rules, incomplete data, and random cluster sizes. They showed that the ordinary sample average is a viable option for estimation following a group sequential trial, for a wide class of stopping rules and for random outcomes with a distribution in the exponential family. Their results are somewhat surprising in the sense that the sample average is not optimal, and further, there does not exist an optimal, or even, unbiased linear estimator. However, the sample average is asymptotically unbiased, both conditionally upon the observed sample size as well as marginalized over it. By exploiting ignorability they showed that the sample average is the conventional maximum likelihood estimator. They also showed that a conditional maximum likelihood estimator is finite sample unbiased, but is less efficient than the sample average and has the larger mean squared error. Asymptotically, the sample average and the conditional maximum likelihood estimator are equivalent. This previous work is restricted, however, to the situation in which the the random sample size can take only two values, N = n or N = 2n. In this paper, we consider the more practically useful setting of sample sizes in a the finite set {n1, n2, …, nL}. It is shown that the sample average is then a justifiable estimator , in the sense that it follows from joint likelihood estimation, and it is consistent and asymptotically unbiased. We also show why simulations

  13. Hybrid Computerized Adaptive Testing: From Group Sequential Design to Fully Sequential Design

    ERIC Educational Resources Information Center

    Wang, Shiyu; Lin, Haiyan; Chang, Hua-Hua; Douglas, Jeff

    2016-01-01

    Computerized adaptive testing (CAT) and multistage testing (MST) have become two of the most popular modes in large-scale computer-based sequential testing. Though most designs of CAT and MST exhibit strength and weakness in recent large-scale implementations, there is no simple answer to the question of which design is better because different…

  14. Sequential processing during noun phrase production.

    PubMed

    Bürki, Audrey; Sadat, Jasmin; Dubarry, Anne-Sophie; Alario, F-Xavier

    2016-01-01

    This study examined whether the brain operations involved during the processing of successive words in multi word noun phrase production take place sequentially or simultaneously. German speakers named pictures while ignoring a written distractor superimposed on the picture (picture-word interference paradigm) using the definite determiner and corresponding German noun. The gender congruency and the phonological congruency (i.e., overlap in first phonemes) between target and distractor were manipulated. Naming responses and EEG were recorded. The behavioural performance replicated both the phonology and the gender congruency effects (i.e., shorter naming latencies for gender congruent than incongruent and for phonologically congruent than incongruent trials). The phonological and gender manipulations also influenced the EEG data. Crucially, the two effects occurred in different time windows and over different sets of electrodes. The phonological effect was observed substantially earlier than the gender congruency effect. This finding suggests that the processing of determiners and nouns during determiner noun phrase production occurs at least partly sequentially.

  15. Multiplexed protein profiling by sequential affinity capture

    PubMed Central

    Ayoglu, Burcu; Birgersson, Elin; Mezger, Anja; Nilsson, Mats; Uhlén, Mathias; Nilsson, Peter

    2016-01-01

    Antibody microarrays enable parallelized and miniaturized analysis of clinical samples, and have proven to provide novel insights for the analysis of different proteomes. However, there are concerns that the performance of such direct labeling and single antibody assays are prone to off‐target binding due to the sample context. To improve selectivity and sensitivity while maintaining the possibility to conduct multiplexed protein profiling, we developed a multiplexed and semi‐automated sequential capture assay. This novel bead‐based procedure encompasses a first antigen capture, labeling of captured protein targets on magnetic particles, combinatorial target elution and a read‐out by a secondary capture bead array. We demonstrate in a proof‐of‐concept setting that target detection via two sequential affinity interactions reduced off‐target contribution, while lowered background and noise levels, improved correlation to clinical values compared to single binder assays. We also compared sensitivity levels with single binder and classical sandwich assays, explored the possibility for DNA‐based signal amplification, and demonstrate the applicability of the dual capture bead‐based antibody microarray for biomarker analysis. Hence, the described concept enhances the possibilities for antibody array assays to be utilized for protein profiling in body fluids and beyond. PMID:26935855

  16. Sequential algorithm for fast clique percolation.

    PubMed

    Kumpula, Jussi M; Kivelä, Mikko; Kaski, Kimmo; Saramäki, Jari

    2008-08-01

    In complex network research clique percolation, introduced by Palla, Derényi, and Vicsek [Nature (London) 435, 814 (2005)], is a deterministic community detection method which allows for overlapping communities and is purely based on local topological properties of a network. Here we present a sequential clique percolation algorithm (SCP) to do fast community detection in weighted and unweighted networks, for cliques of a chosen size. This method is based on sequentially inserting the constituent links to the network and simultaneously keeping track of the emerging community structure. Unlike existing algorithms, the SCP method allows for detecting k -clique communities at multiple weight thresholds in a single run, and can simultaneously produce a dendrogram representation of hierarchical community structure. In sparse weighted networks, the SCP algorithm can also be used for implementing the weighted clique percolation method recently introduced by Farkas [New J. Phys. 9, 180 (2007)]. The computational time of the SCP algorithm scales linearly with the number of k -cliques in the network. As an example, the method is applied to a product association network, revealing its nested community structure.

  17. Sequential effects in Olympic synchronized diving scores

    PubMed Central

    2017-01-01

    When judging performances in a sequence, the current score is often influenced by the preceding score. Where athletes are perceived to be similar, a judgement is assimilated towards the previous one. However, if judges focus on the differences between the two athletes, this will result in a contrasting influence on their scores. Here, I investigate sequential effects during synchronized diving events at the 2012 and 2016 Olympic Games. Although previous research found assimilation in scores of gymnasts, the current data showed contrast effects—current scores benefited from following a poor performance but were at a disadvantage if they followed a high-scoring performance. One explanation may be that the processes involved in judging synchronized pairs results in a focus on the differences between athletes, producing a contrast effect across dives. That the specific direction of this sequential bias may depend on the particular sport has implications for how judges might approach their roles in a context-dependent manner, as well as how such biases should be addressed. PMID:28280583

  18. Noncommutative Biology: Sequential Regulation of Complex Networks

    PubMed Central

    Letsou, William; Cai, Long

    2016-01-01

    Single-cell variability in gene expression is important for generating distinct cell types, but it is unclear how cells use the same set of regulatory molecules to specifically control similarly regulated genes. While combinatorial binding of transcription factors at promoters has been proposed as a solution for cell-type specific gene expression, we found that such models resulted in substantial information bottlenecks. We sought to understand the consequences of adopting sequential logic wherein the time-ordering of factors informs the final outcome. We showed that with noncommutative control, it is possible to independently control targets that would otherwise be activated simultaneously using combinatorial logic. Consequently, sequential logic overcomes the information bottleneck inherent in complex networks. We derived scaling laws for two noncommutative models of regulation, motivated by phosphorylation/neural networks and chromosome folding, respectively, and showed that they scale super-exponentially in the number of regulators. We also showed that specificity in control is robust to the loss of a regulator. Lastly, we connected these theoretical results to real biological networks that demonstrate specificity in the context of promiscuity. These results show that achieving a desired outcome often necessitates roundabout steps. PMID:27560383

  19. Modifications of sequential designs in bioequivalence trials.

    PubMed

    Zheng, Cheng; Zhao, Lihui; Wang, Jixian

    2015-01-01

    Bioequivalence (BE) studies are designed to show that two formulations of one drug are equivalent and they play an important role in drug development. When in a design stage, it is possible that there is a high degree of uncertainty on variability of the formulations and the actual performance of the test versus reference formulation. Therefore, an interim look may be desirable to stop the study if there is no chance of claiming BE at the end (futility), or claim BE if evidence is sufficient (efficacy), or adjust the sample size. Sequential design approaches specially for BE studies have been proposed previously in publications. We applied modification to the existing methods focusing on simplified multiplicity adjustment and futility stopping. We name our method modified sequential design for BE studies (MSDBE). Simulation results demonstrate comparable performance between MSDBE and the original published methods while MSDBE offers more transparency and better applicability. The R package MSDBE is available at https://sites.google.com/site/modsdbe/.

  20. G-sequentially connectedness for topological groups with operations

    NASA Astrophysics Data System (ADS)

    Mucuk, Osman; Cakalli, Huseyin

    2016-08-01

    It is a well-known fact that for a Hausdorff topological group X, the limits of convergent sequences in X define a function denoted by lim from the set of all convergent sequences in X to X. This notion has been modified by Connor and Grosse-Erdmann for real functions by replacing lim with an arbitrary linear functional G defined on a linear subspace of the vector space of all real sequences. Recently some authors have extended the concept to the topological group setting and introduced the concepts of G-sequential continuity, G-sequential compactness and G-sequential connectedness. In this work, we present some results about G-sequentially closures, G-sequentially connectedness and fundamental system of G-sequentially open neighbourhoods for topological group with operations which include topological groups, topological rings without identity, R-modules, Lie algebras, Jordan algebras, and many others.

  1. New drugs and regimens for treatment of TB

    PubMed Central

    Leibert, Eric; Rom, William N

    2013-01-01

    Tools for effective TB control have been available for years. Case finding, active medications, case management and directly observed therapy are the foundations for the management of TB. The current TB epidemic, centered in resource-limited settings is fueled by the HIV-1 epidemic. Lack of ability to diagnose and treat drug-resistant TB has led to development of more extensive patterns of resistance. Among the currently available drugs, there is reason to hope that rifamycins paired with fluoroquinolones will lead to shorter treatment regimens for drug-susceptible TB. As the result of novel public-private collaborations and investments of resources, new drugs are being developed. These include TMC207, already shown to have activity early in the treatment of multidrug-resistant TB and others that are likely to be active against persistor organisms, and have the prospect to dramatically shorten treatment courses for active and latent TB. Given that these drugs have novel mechanisms of action, combinations have the prospect to be highly active even against multidrug-resistant organisms. PMID:20586565

  2. Optimization of anti-infective dosing regimens during online haemodiafiltration

    PubMed Central

    Zandvliet, Anthe S.; Touw, Daniel J.; Penne, Erik L.

    2017-01-01

    Abstract Online haemodiafiltration (HDF) is increasingly used in clinical practice as a routine intermittent dialysis modality. It is well known that renal impairment and renal replacement therapy can substantially affect the pharmacokinetic behaviour of several drugs. However, surprisingly few data are available on the need for specific dose adjustments during HDF. Due to convection, drug clearance may be increased during HDF as compared with standard haemodialysis. This may be of particular interest in patients undergoing anti-infective therapy, since under-dosing may compromise patient outcomes and promote the emergence of bacterial resistance. Drug clearance during HDF is determined by (i) dialysis characteristics, (ii) drug characteristics and (iii) patient characteristics. In this review, we will discuss these different determinants of drug clearance during HDF and advise on how to adjust the dose of antibacterial, antimycotic and antiviral agents in patients undergoing HDF. In addition, the possible added value of therapeutic drug monitoring is discussed. The review provides guidance for optimization of anti-infective dosing regimens in HDF patients.

  3. Pharmacoeconomic consequences of variable patient compliance with prescribed drug regimens.

    PubMed

    Urquhart, J

    1999-03-01

    Variable compliance with prescribed drug regimens is a leading source of variability in drug response. Specifics differ by drug and disease. The role of variable compliance was clearly defined in 2 trials of lipid-lowering agents, cholestyramine and gemfibrozil, in which exceptionally careful measurements of compliance were made, which has not been done in later trials. Economic consequences of variable compliance are estimated by converting dose-dependent changes in absolute risk of incident coronary disease into the unicohort format, which designates how many patients must be treated to prevent, in a given time, a defined 'coronary event'. Two strong influences on the costs of treatment are: (i) the shape of the relation between drug intake and risk reduction; and (ii) the strength of the linkage between intake and prescription refills. The intake-effect relation for cholestyramine is linear, making compliance-neutral the cost to prevent 1 coronary event, provided that refills match intake. If refills exceed intake, treatment costs rise. The intake-effect relation for gemfibrozil is more typically nonlinear, so poorer compliers purchase and take the drug in amounts that have little benefit, increasing the cost to prevent 1 coronary event. If refills run at a higher rate than intake, costs increase still further. A key question for future study is: do policies that encourage timely refills increase compliance enough to offset their potential to waste money in the purchasing of an untaken drug?

  4. Individualizing amikacin regimens: accurate method to achieve therapeutic concentrations.

    PubMed

    Zaske, D E; Cipolle, R J; Rotschafer, J C; Kohls, P R; Strate, R G

    1991-11-01

    Amikacin's pharmacokinetics and dosage requirements were studied in 98 patients receiving treatment for gram-negative infections. A wide interpatient variation in the kinetic parameters of the drug occurred in all patients and in patients who had normal serum creatinine levels or normal creatinine clearance. The half-life ranged from 0.7 to 14.4 h in 74 patients who had normal serum creatinine levels and from 0.7 to 7.2 h in 37 patients who had normal creatinine clearance. The necessary daily dose to obtain therapeutic serum concentrations ranged from 1.25 to 57 mg/kg in patients with normal serum creatinine levels and from 10 to 57 mg/kg in patients with normal creatinine clearance. In four patients (4%), a significant change in baseline serum creatinine level (greater than 0.5 mg/dl) occurred during or after treatment, which may have been amikacin-associated toxicity. Overt ototoxicity occurred in one patient. The method of individualizing dosage regimens provided a clinically useful means of rapidly attaining therapeutic peak and trough serum concentrations.

  5. Oxygen regimen in the human peripheral tissue during space flights

    NASA Astrophysics Data System (ADS)

    Haase, H.; Kovalenko, E. A.; Vacek, A.; Bobrovnickij, M. P.; Jarsumbeck, B.; Semencov, V. N.; Sarol, Z.; Hideg, J.; Zlatarev, K.

    A survey of the results of the experiment "Oxygen," carried out within the scope of the INTERKOSMOS program in members of the permanent crews and of international visiting expeditions to the Soviet orbital station Salyut-6, is given. During the 7-day space flights of the international visiting expeditions a significant decrease in pO 2 ic by 3.28 kPa was observed. Local oxygen utilization reduced significantly by 0.44 kPa. During hyperventilation testing after return to earth a statistically significant decrease in the peak value by 1.39 kPa was noted. In the long-term crews of the orbital station Salyut-6 the highest decrease in pO 2 ic of 3.8 kPa and the absolutely lowest value of 3.4 ± 0.5 kPa during space flight were observed. The decrease in local oxygen utilization during the flight of 0.8 kPa/min was greater than that of the visiting crews. The results indicate the importance of investigating the dynamics of the oxygen regimen for medical control of the crew members both during the space flight and during the readaptation phase after return to earth.

  6. Comparison of Non-myeloablative Conditioning Regimens for Lymphoproliferative Disorders

    PubMed Central

    Hong, Sanghee; Le-Rademacher, Jennifer; Artz, Andrew; McCarthy, Philip L.; Logan, Brent R.; Pasquini, Marcelo C.

    2014-01-01

    Hematopoietic cell transplantation (HCT) with non-myeloablative conditioning (NMA) for lymphoproliferative diseases (LD) includes fludarabine with and without low-dose total body irradiation (TBI). Transplant outcomes were compared among patients ≥40 years with LD who received a HCT with TBI (N=382) and no-TBI (N=515) NMA from 2001 to 2011. The groups were comparable except for donor, graft, prophylaxis for graft-versus-host disease (GVHD), disease status and year of HCT. Cumulative incidences of grades II–IV GVHD at 100 days, were 29% and 20% (p=0.001), and chronic GVHD at 1 year were 54% and 44% (p=0.004) for TBI and no-TBI, respectively. Multivariate analysis of progression/relapse, treatment failure and mortality showed no outcome differences by conditioning. Full donor chimerism at day 100 was observed in 82% vs. 64% in the TBI and no-TBI groups, respectively (p=0.006). Subset of four most common conditioning/ GVHD prophylaxis combinations demonstrated higher rates of grades II–IV acute (p<0.001) and chronic GVHD (p<0.001) among recipients of TBI-mycophenolate mofetil (MMF) compared to other combinations. TBI-based NMA conditioning induces faster full donor chimerism but overall survival outcomes are comparable to no-TBI regimens. Combination of TBI and MMF are associated with higher rates of GVHD without impact on survival outcomes in patients with LD. PMID:25437248

  7. Analytical verification of waterborne chemical treatment regimens in hatchery raceways

    USGS Publications Warehouse

    Rach, J.J.; Ramsay, R.T.

    2000-01-01

    Chemical therapy for control and prevention of fish diseases is a necessary and common practice in aquaculture. Many factors affect the accuracy of a chemical treatment application, such as the functioning of the chemical delivery system, calculation of chemical quantities to be delivered, water temperature, geometry of the culture unit, inlet-outlet structure, the influence of aerators, wind movement, and measurement of water volumes and flow rates. Three separate trials were conducted at the Osceola Fish Hatchery, a facility of the Wisconsin Department of Natural Resources, evaluating the accuracy of flow-through hydrogen peroxide treatments applied to 1, 3, or 9 raceways that were connected in series. Raceways were treated with 50 or 75 ??L/L of hydrogen peroxide for 30 min. Chemical concentrations were determined titrimetrically. The target treatment regimen was not realized in any of the applications. Chemical concentrations dropped and exposure times increased with each additional raceway treated in series. Single introduction of a therapeutant to more than three raceways in series is not recommended. Factors that interfered with the accuracy of the treatments were culture unit configuration, aeration, and flow rates. Several treatment modifications were identified that would result in more accurate chemical treatments.

  8. Polypathology, polypharmacy, medication regimen complexity and drug therapy appropriateness.

    PubMed

    Gómez Aguirre, N; Caudevilla Martínez, A; Bellostas Muñoz, L; Crespo Avellana, M; Velilla Marco, J; Díez-Manglano, J

    2017-02-16

    Polypathological patients are usually elderly and take numerous drugs. Polypharmacy affects 85% of these individuals and is not associated with greater survival. On the contrary, polypharmacy exposes these individuals to more adverse effects, such as weight loss, falls, functional and cognitive impairment and hospitalisations. The complexity of a drug regimen covers more aspects than the simple number of drugs consumed. The galenic form, the dosage and the method for preparing the drug can impede the understanding of and compliance with prescriptions. Both polypharmacy and therapeutic complexity are associated with poorer adherence by patients. To prevent polypharmacy, reduce complexity and improve adherence, the appropriate use of drugs is needed. Proper prescribing consists of selecting drugs that have clear evidence for their use in the indication, which are appropriate for the patient's circumstances, are well tolerated and cost-effective and whose benefits outweigh the risks. To improve the drug prescription, periodic reviews of the drugs need to be conducted, especially when the patient changes doctor and during healthcare transitions. The Beers and STOPP/START (Screening Tool of Older Person's potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment) criteria are effective tools for this improvement. Deprescription for polymedicated polypathological patients that considers their clinical circumstances, prognosis and preferences can contribute to a more appropriate use of drugs.

  9. Properties of Sequential Chromospheric Brightenings and Associated Flare Ribbons (Postprint)

    DTIC Science & Technology

    2012-05-10

    AFRL-RV-PS- AFRL-RV-PS- TP-2012-0055 TP-2012-0055 PROPERTIES OF SEQUENTIAL CHROMOSPHERIC BRIGHTENINGS AND ASSOCIATED FLARE RIBBONS...PROPERTIES OF SEQUENTIAL CHROMOSPHERIC BRIGHTENINGS AND ASSOCIATED FLARE RIBBONS (POSTPRINT) 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62601F 6...properties of solar sequential chromospheric brightenings (SCBs) observed in conjunction with moderate-sized chromospheric flares with associated Coronal

  10. Modified sequential therapy vs quadruple therapy as initial therapy in patients with Helicobacter infection

    PubMed Central

    Liao, Xiao-Min; Nong, Gao-Hui; Chen, Mei-Zu; Huang, Xue-Ping; Cong, Yun-Yan; Huang, Yi-Ying; Wu, Bai-He; Wei, Jin-Qi

    2015-01-01

    . Symptomatic improvements in the presentation of stomachache, acid regurgitation, and burning sensation were not significantly different between the two groups. CONCLUSION: Ilaprazole-based 10-d standard quadruple therapy does not offer an incremental benefit over modified sequential therapy for the treatment of H. pylori infection, as both treatment regimens appear to be effective, safe, and well-tolerated as initial treatment options. PMID:26034367

  11. Sequential generation of matrix-product states in cavity QED

    SciTech Connect

    Schoen, C.; Hammerer, K.; Wolf, M. M.; Cirac, J. I.; Solano, E.

    2007-03-15

    We study the sequential generation of entangled photonic and atomic multiqubit states in the realm of cavity QED. We extend the work of C. Schoen et al. [Phys. Rev. Lett. 95, 110503 (2005)], where it was shown that all states generated in a sequential manner can be classified efficiently in terms of matrix-product states. In particular, we consider two scenarios: photonic multiqubit states sequentially generated at the cavity output of a single-photon source and atomic multiqubit states generated by their sequential interaction with the same cavity mode.

  12. Sequential synchronization of chaotic systems with an application to communication.

    PubMed

    Kim, Chil-Min; Rim, Sunghwan; Kye, Won-Ho

    2002-01-07

    We propose a hierarchically structured communication system by using sequentially synchronized chaotic systems. Sequential synchronization is attained by first feeding a noiselike signal to a variable of the first transmitter and its receiver simultaneously and then feeding a variable of the first transmitter and its receiver to a variable of the second transmitter and its receiver, respectively, for subsequent feedings of variables in sequence. When this is applied to communication, the hierarchical structure enables selective protection of information due to the sequential property. We illustrate this in sequentially synchronized Navier-Stokes and Lorenz equations.

  13. Therapeutic efficacy of alternative primaquine regimens to standard treatment in preventing relapses by Plasmodium vivax

    PubMed Central

    Tamayo Perez, María-Eulalia; Aguirre-Acevedo, Daniel Camilo

    2015-01-01

    Objective: To compare efficacy and safety of primaquine regimens currently used to prevent relapses by P. vivax. Methods: A systematic review was carried out to identify clinical trials evaluating efficacy and safety to prevent malaria recurrences by P. vivax of primaquine regimen 0.5 mg/kg/ day for 7 or 14 days compared to standard regimen of 0.25 mg/kg/day for 14 days. Efficacy of primaquine according to cumulative incidence of recurrences after 28 days was determined. The overall relative risk with fixed-effects meta-analysis was estimated. Results: For the regimen 0.5 mg/kg/day/7 days were identified 7 studies, which showed an incidence of recurrence between 0% and 20% with follow-up 60-210 days; only 4 studies comparing with the standard regimen 0.25 mg/kg/day/14 days and no difference in recurrences between both regimens (RR= 0.977, 95% CI= 0.670 to 1.423) were found. 3 clinical trials using regimen 0.5 mg/kg/day/14 days with an incidence of recurrences between 1.8% and 18.0% during 330-365 days were identified; only one study comparing with the standard regimen (RR= 0.846, 95% CI= 0.484 to 1.477). High risk of bias and differences in handling of included studies were found. Conclusion: Available evidence is insufficient to determine whether currently PQ regimens used as alternative rather than standard treatment have better efficacy and safety in preventing relapse of P. vivax. Clinical trials are required to guide changes in treatment regimen of malaria vivax. PMID:26848199

  14. Iranian Low-dose Escalating Prophylaxis Regimen in Children with Severe Hemophilia A and B.

    PubMed

    Eshghi, Peyman; Sadeghi, Elham; Tara, S Zahra; Habibpanah, Behnaz; Hantooshzadeh, Razieh

    2017-01-01

    Establishing an appropriate prophylaxis regimen for children with hemophilia is a critical challenge in developing countries. Barriers including availability and affordability, catheter-related complications, and inhibitor development risks have led to the introduction of new tailored prophylaxis regimens in different countries. This study emphasizes on the benefits of the Iranian low-dose escalating prophylaxis regimen in a Hemophilia Comprehensive Care Center in Iran. Referred patients with hemophilia less than 15 years of age, who were subject to prophylaxis regimen, are studied retrospectively. A once-weekly prophylaxis regimen of 25 IU/kg was started for the patients primarily. Their prophylaxis regimen was changed to 25 IU/kg twice a week and then 3 times a week when they experienced 3 joint bleedings, 4 soft tissue bleedings, or a 1 life-threatening bleed without a specific trauma history. Overall, 25 patients with severe hemophilia and at least 6-month history of on-demand (OD) treatment were studied. A mean of 1754 IU/kg/yr of coagulation factors, used for OD and prophylaxis purposes, was sufficient to decrease the mean annual bleeding rate (ABR) to 1.86 after prophylaxis. It also reduced the mean hospitalization days and the mean number of target joints to 0.24 and 0.16, respectively. Overall, 19 (76%) patients were continuing their once-weekly regimen at the end of the follow-up. None of the patients needed 3-times-a-week regimen or central venous catheterization and none developed inhibitors in the follow-up. Benefits of the Iranian low-dose escalating prophylaxis regimen prove equal to some of the previous 3-times-a-week prophylaxis regimens in reducing the ABR and hospitalizations.

  15. Sequential composition of dynamically dexterous robot behaviors

    SciTech Connect

    Burridge, R.R.; Rizzi, A.A.; Koditschek, D.E.

    1999-06-01

    The authors report on efforts to develop a sequential robot controller-composition technique in the context of dexterous batting maneuvers. A robot with a flat paddle is required to strike repeatedly at a thrown ball until the ball is brought to rest on the paddle at a specified location. The robot`s reachable workspace is blocked by an obstacle that disconnects the free space formed when the ball and paddle remain in contact, forcing the machine to let go for a time to bring the ball to the desired state. The controller compositions the authors create guarantee that a ball introduced in the safe workspace remains there and is ultimately brought to the goal. They report on experimental results from an implementation of these formal composition methods, and present descriptive statistics characterizing the experiments.

  16. Prototype color field sequential television lens assembly

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The design, development, and evaluation of a prototype modular lens assembly with a self-contained field sequential color wheel is presented. The design of a color wheel of maximum efficiency, the selection of spectral filters, and the design of a quiet, efficient wheel drive system are included. Design tradeoffs considered for each aspect of the modular assembly are discussed. Emphasis is placed on achieving a design which can be attached directly to an unmodified camera, thus permitting use of the assembly in evaluating various candidate camera and sensor designs. A technique is described which permits maintaining high optical efficiency with an unmodified camera. A motor synchronization system is developed which requires only the vertical synchronization signal as a reference frequency input. Equations and tradeoff curves are developed to permit optimizing the filter wheel aperture shapes for a variety of different design conditions.

  17. Automatic exposure control for space sequential camera

    NASA Technical Reports Server (NTRS)

    Mcatee, G. E., Jr.; Stoap, L. J.; Solheim, C. D.; Sharpsteen, J. T.

    1975-01-01

    The final report for the automatic exposure control study for space sequential cameras, for the NASA Johnson Space Center is presented. The material is shown in the same sequence that the work was performed. The purpose of the automatic exposure control is to automatically control the lens iris as well as the camera shutter so that the subject is properly exposed on the film. A study of design approaches is presented. Analysis of the light range of the spectrum covered indicates that the practical range would be from approximately 20 to 6,000 foot-lamberts, or about nine f-stops. Observation of film available from space flights shows that optimum scene illumination is apparently not present in vehicle interior photography as well as in vehicle-to-vehicle situations. The evaluation test procedure for a breadboard, and the results, which provided information for the design of a brassboard are given.

  18. [Targeted therapies: sequential and combined treatments].

    PubMed

    Gross-Goupil, M; Escudier, B

    2010-01-01

    The treatment of metastatic kidney cancer has dramatically changed in the last three years, with demonstration of efficacy of sunitinib, sorafenib, temsirolimus, bevacizumab combined with interferon and more recently everolimus. Although the international guidelines have recently been reviewed, some major questions are still open. Particularly, the best order of administration of these targeted therapies should be considered, since sequential schedule becomes usual with the availability of these new agents. At the same time, the tolerability and efficacy of the combination of the targeted therapies are under investigation in clinical trials. We report recent studies, mainly presented during the ASCO 2007 and 2008 congress. Furthermore, other studies are ongoing to answer other important questions, to optimize the treatment of this disease, such as the role of nephrectomy in case of synchronous metastatic disease, or the efficacy of the targeted therapies in different histological subtype than clear cell carcinoma, or in neoadjuvant and adjuvant settings.

  19. Sequentially triggered star formation in OB associations

    NASA Astrophysics Data System (ADS)

    Preibisch, Thomas; Zinnecker, Hans

    We discuss observational evidence for sequential and triggered star formation in galactic and extragalactic OB associations. We will first review in detail the star formation process in the Scorpius-Centaurus OB association, the nearest OB association to the Sun, where several recent extensive studies have provided comprehensive information on the stellar content and the ages of the different OB subgroups. These data have allowed us to reconstruct the star formation history of the association in some detail and provided important insight into the activity in the rho Oph and Lupus dark clouds, and with the origin of several young stellar groups in the southern sky. After discussing evidence for triggered star formation in and around various other Galactic OB associations (e.g. Ori OB1, Per OB2) we will compare the observational results with recent models of rapid star formation in the turbulent interstellar medium (cf. Briceno et al. chapter in Protostars and Planets V, in press).

  20. Sequential state generation by model neural networks.

    PubMed Central

    Kleinfeld, D

    1986-01-01

    Sequential patterns of neural output activity form the basis of many biological processes, such as the cyclic pattern of outputs that control locomotion. I show how such sequences can be generated by a class of model neural networks that make defined sets of transitions between selected memory states. Sequence-generating networks depend upon the interplay between two sets of synaptic connections. One set acts to stabilize the network in its current memory state, while the second set, whose action is delayed in time, causes the network to make specified transitions between the memories. The dynamic properties of these networks are described in terms of motion along an energy surface. The performance of the networks, both with intact connections and with noisy or missing connections, is illustrated by numerical examples. In addition, I present a scheme for the recognition of externally generated sequences by these networks. PMID:3467316

  1. Collaborative, Sequential and Isolated Decisions in Design

    NASA Technical Reports Server (NTRS)

    Lewis, Kemper; Mistree, Farrokh

    1997-01-01

    The Massachusetts Institute of Technology (MIT) Commission on Industrial Productivity, in their report Made in America, found that six recurring weaknesses were hampering American manufacturing industries. The two weaknesses most relevant to product development were 1) technological weakness in development and production, and 2) failures in cooperation. The remedies to these weaknesses are considered the essential twin pillars of CE: 1) improved development process, and 2) closer cooperation. In the MIT report, it is recognized that total cooperation among teams in a CE environment is rare in American industry, while the majority of the design research in mathematically modeling CE has assumed total cooperation. In this paper, we present mathematical constructs, based on game theoretic principles, to model degrees of collaboration characterized by approximate cooperation, sequential decision making and isolation. The design of a pressure vessel and a passenger aircraft are included as illustrative examples.

  2. Random sequential adsorption on imprecise lattice

    NASA Astrophysics Data System (ADS)

    Privman, Vladimir; Yan, Han

    2016-06-01

    We report a surprising result, established by numerical simulations and analytical arguments for a one-dimensional lattice model of random sequential adsorption, that even an arbitrarily small imprecision in the lattice-site localization changes the convergence to jamming from fast, exponential, to slow, power-law, with, for some parameter values, a discontinuous jump in the jamming coverage value. This finding has implications for irreversible deposition on patterned substrates with pre-made landing sites for particle attachment. We also consider a general problem of the particle (depositing object) size not an exact multiple of the lattice spacing, and the lattice sites themselves imprecise, broadened into allowed-deposition intervals. Regions of exponential vs. power-law convergence to jamming are identified, and certain conclusions regarding the jamming coverage are argued for analytically and confirmed numerically.

  3. Sequential Therapy in Metastatic Renal Cell Carcinoma

    PubMed Central

    Burke, John M.; Agrawal, Manish; Hauke, Ralph J.; Hutson, Thomas E.; Doshi, Gury; Fleming, Mark T.; Vogelzang, Nicholas J.

    2016-01-01

    The treatment of metastatic renal cell carcinoma (mRCC) has changed dramatically in the past decade. As the number of available agents, and related volume of research, has grown, it is increasingly complex to know how to optimally treat patients. The authors are practicing medical oncologists at the US Oncology Network, the largest community-based network of oncology providers in the country, and represent the leadership of the Network’s Genitourinary Research Committee. We outline our thought process in approaching sequential therapy of mRCC and the use of real-world data to inform our approach. We also highlight the evolving literature that will impact practicing oncologists in the near future. PMID:28326277

  4. Sequential pattern formation governed by signaling gradients

    NASA Astrophysics Data System (ADS)

    Jörg, David J.; Oates, Andrew C.; Jülicher, Frank

    2016-10-01

    Rhythmic and sequential segmentation of the embryonic body plan is a vital developmental patterning process in all vertebrate species. However, a theoretical framework capturing the emergence of dynamic patterns of gene expression from the interplay of cell oscillations with tissue elongation and shortening and with signaling gradients, is still missing. Here we show that a set of coupled genetic oscillators in an elongating tissue that is regulated by diffusing and advected signaling molecules can account for segmentation as a self-organized patterning process. This system can form a finite number of segments and the dynamics of segmentation and the total number of segments formed depend strongly on kinetic parameters describing tissue elongation and signaling molecules. The model accounts for existing experimental perturbations to signaling gradients, and makes testable predictions about novel perturbations. The variety of different patterns formed in our model can account for the variability of segmentation between different animal species.

  5. Mechanistic studies on a sequential PDT protocol

    NASA Astrophysics Data System (ADS)

    Kessel, David

    2016-03-01

    A low (~LD15) PDT dose resulting in selective lysosomal photodamage can markedly promote photokilling by subsequent photodamage targeted to mitochondria. Experimental data are consistent with the proposal that cleavage of the autophagyassociated protein ATG5 to a pro-apoptotic fragment is responsible for this effect. This process is known to be dependent on the proteolytic activity of calpain. We have proposed that Ca2+ released from photodamaged lysosomes is the trigger for ATG5 cleavage. We can now document the conversion of ATG5 to the truncated form after lysosomal photodamage. Photofrin, a photosensitizer that targets both mitochondria and lysosomes, can be used for either phase of the sequential PDT process. The ability of Photofrin to target both loci may explain the well-documented efficacy of this agent.

  6. Prosody and alignment: a sequential perspective

    NASA Astrophysics Data System (ADS)

    Szczepek Reed, Beatrice

    2010-12-01

    In their analysis of a corpus of classroom interactions in an inner city high school, Roth and Tobin describe how teachers and students accomplish interactional alignment by prosodically matching each other's turns. Prosodic matching, and specific prosodic patterns are interpreted as signs of, and contributions to successful interactional outcomes and positive emotions. Lack of prosodic matching, and other specific prosodic patterns are interpreted as features of unsuccessful interactions, and negative emotions. This forum focuses on the article's analysis of the relation between interpersonal alignment, emotion and prosody. It argues that prosodic matching, and other prosodic linking practices, play a primarily sequential role, i.e. one that displays the way in which participants place and design their turns in relation to other participants' turns. Prosodic matching, rather than being a conversational action in itself, is argued to be an interactional practice (Schegloff 1997), which is not always employed for the accomplishment of `positive', or aligning actions.

  7. Classical sequential growth dynamics for causal sets

    NASA Astrophysics Data System (ADS)

    Rideout, D. P.; Sorkin, R. D.

    2000-01-01

    Starting from certain causality conditions and a discrete form of general covariance, we derive a very general family of classically stochastic, sequential growth dynamics for causal sets. The resulting theories provide a relatively accessible ``halfway house'' to full quantum gravity that possibly contains the latter's classical limit (general relativity). Because they can be expressed in terms of state models for an assembly of Ising spins residing on the relations of the causal set, these theories also illustrate how nongravitational matter can arise dynamically from the causal set without having to be built in at the fundamental level. Additionally, our results bring into focus some interpretive issues of importance for a causal set dynamics and for quantum gravity more generally.

  8. Differences in Sugar Accumulation and Mobilization between Sequential and Non-Sequential Senescence Wheat Cultivars under Natural and Drought Conditions

    PubMed Central

    Shi, Huarong; Wang, Bin; Yang, Piaojuan; Li, Yibo; Miao, Fang

    2016-01-01

    Wheat leaf non-sequential senescence at the late grain-filling stage involves the early senescence of younger flag leaves compared to that observed in older second leaves. On the other hand, sequential senescence involves leaf senescence that follows an age-related pattern, in which flag leaves are the latest to undergo senescence. The characteristics of sugar metabolism in two sequential senescence cultivars and two non-sequential senescence cultivars under both natural and drought conditions were studied to elucidate the underlying mechanism of drought tolerance in two different senescence modes. The results showed that compared to sequential senescence wheat cultivars, under natural and drought conditions, non-sequential senescence wheat cultivars showed a higher leaf net photosynthetic rate, higher soluble sugar levels in leaves, leaf sheaths, and internodes, higher leaf sucrose synthase (SS) and sucrose phosphate synthase (SPS) activity, and higher grain SS activity, thereby suggesting that non-sequential senescence wheat cultivars had stronger source activity. Spike weight, grain weight per spike, and 100-grain weight of non-sequential senescence cultivars at maturity were significantly higher than those of sequential senescence cultivars under both natural and drought conditions. These findings indicate that the higher rate of accumulation and the higher mobilization of soluble sugar in the leaves, leaf sheaths and internodes of non-sequential senescence cultivars improve grain weight and drought tolerance. At the late grain-filling stage, drought conditions adversely affected leaf chlorophyll content, net photosynthetic rate, soluble sugar and sucrose content, SS and SPS activity, gain SS activity, and weight. This study showed that higher rates of soluble sugar accumulation in the source was one of the reasons of triggering leaf non-sequential senescence, and higher rates of soluble sugar mobilization during leaf non-sequential senescence promoted high and

  9. Inefficacy of Triple Therapy and Comparison of Two Different Bismuth-containing Quadruple Regimens as a Firstline Treatment Option for Helicobacter pylori

    PubMed Central

    Kekilli, Murat; Onal, Ibrahim K.; Ocal, Serkan; Dogan, Zeynal; Tanoglu, Alpaslan

    2016-01-01

    Background/Aim: Increasing resistance of Helicobacter pylori to antimicrobials necessitated the development of new regimens and the modification of existing regimens. The present study aimed to compare the efficacy of two bismuth-containing quadruple regimens–one including clarithromycin (C) instead of metronidazole (M) and triple therapy. Patients and Methods: Patients with H. pylori infection given the following regimens were sequentially enrolled in this retrospective study: (1) Triple therapy: Lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and amoxicillin 1 g b.i.d., (2) bismuth group C: Lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., amoxicillin 1 g b.i.d., and bismuth subsalicylate 524 mg b.i.d., and (3) bismuth group M: Lansoprazole 30 mg b.i.d., amoxicillin 1 g b.i.d., metronidazole 500 mg t.i.d., and bismuth subsalicylate 524 mg b.i.d. for 14 days. Gastroscopy and 14C-urea breath test were performed before enrollment, and urea breath test was repeated four weeks after the treatment. Results: At per-protocol analysis, the eradication rates were 64.7% (95% confidence interval 60.4–68.7) with the triple therapy (n = 504), 95.4% (95% confidence interval 91.5–99.4) with the bismuth group C (n = 501), and 93.9% (95% confidence interval 89.7–98.7) with the bismuth group M (n = 505). The eradication rates were similar between the two bismuth groups (P > 0.05) but significantly greater than that of the triple therapy (P < 0.05). Conclusion: In our study, both of the bismuth-containing quadruple therapies reached high eradication rates, whereas triple therapy was shown to be ineffective. Moreover, clarithromycin may also be a component of bismuth-containing quadruple therapy. PMID:27748322

  10. Sequential imposed layer epitaxy of cuprate films

    SciTech Connect

    Laguees, M.; Tebbji, H.; Mairet, V.; Hatterer, C.; Beuran, C.F.; Hass, N.; Xu, X.Z. ); Cavellin, C.D. )

    1994-02-01

    Layer-by-layer epitaxy has been used to grow cuprate films since the discovery of high-Tc compounds. This deposition technique is in principle suitable for the growth of layered crystalline structures. However, the sequential deposition of atomic layer by atomic layer of cuprate compounds has presently not been optimized. Nevertheless, this deposition process is the only one which allows one to build artificial cell structures such as Bi[sub 2]Sr[sub 2]Ca[sub (n[minus]1)]Cu[sub n]O[sub y] with n as large as 10. This process will also be the best one to grow films of the so-called infinite layer phase compounds belonging to the Sr[sub 1[minus]x]Ca[sub x]CuO[sub 2] family, in order to improve the transport properties and the morphological properties of the cuprate films. When performed at high substrate temperature (typically more than 600[degree]C), the layer-by-layer epitaxy of cuprates exhibits usually 3D aggregate nucleation. Then the growth of the film no longer obeys the layer-by-layer sequence imposed during the deposition. We present here two experimental situations of true 2D sequential imposed layer epitaxy; the growth at 500[degree]C under atomic oxygen pressure of Bi[sub 2]Sr[sub 2]CuO[sub 6] and of Sr[sub 1[minus]x]Ca[sub y]CuO[sub 2] phases. 20 refs., 2 figs.

  11. Checking whether there is an increased risk of post-transplant lymphoproliferative disorder and other cancers with specific modern immunosuppression regimens in renal transplantation: Protocol for a network meta-analysis of randomized and observational studies

    PubMed Central

    2014-01-01

    Background Patients undergoing renal transplant procedures require multi-agent immunosuppressive regimens both short term (induction phase) and long term (maintenance phase) to minimize the risk of organ rejection. There are several drug classes and agents for immunosuppression. Use of these agents may increase the risk of different harms including not only infections, but also malignancies including post-transplant lymphoproliferative disorder. There is a need to identify which regimens minimize the risk of such outcomes. The objective of this systematic review and network meta-analysis of randomized and observational studies is to explore whether certain modern regimens of immunosuppression used to prevent organ rejection in renal transplant patients are associated with an increased risk of post-transplant lymphoproliferative disorder and other malignancies. Methods/design ‘Modern’ regimens were defined to be those evaluated in controlled studies beginning in 1990 or later. An electronic literature search of Medline, Embase and the Cochrane Central Register of Controlled Trials has been designed by an experienced information specialist and peer reviewed by a second information specialist. Study selection and data collection will be performed by two reviewers. The outcomes of interest will include post-transplant lymphoproliferative disorder and other incident forms of malignancy occurring in adult renal transplant patients. Network meta-analyses of data from randomized and observational studies will be performed where judged appropriate based on a review of the clinical and methodological features of included studies. A sequential approach to meta-analysis will be used to combine data from different designs. Discussion Our systematic review will include both single-agent and multi-agent modern pharmacotherapy regimens in patients undergoing renal transplantation. It will synthesize malignancy outcomes. Our work will also add to the development of methods for

  12. The effect of commercial sterilization regimens on micellar casein concentrates.

    PubMed

    Beliciu, C M; Sauer, A; Moraru, C I

    2012-10-01

    This work focused on evaluating the effects of UHT sterilization and in-container retorting on the stability and physical properties of micellar casein concentrates (MCC). The study was performed on MCC obtained by membrane separation, with casein concentrations between 5 and 10%. The UHT and retorting regimens were designed to achieve the same microbial inactivation effect. Ultra-high temperature treatment was performed in a pilot-scale MicroThermics heating system (MicroThermics Inc., Raleigh, NC), and retorting in an FMC multipurpose laboratory retort (Steritort; FMC Corp., San Jose, CA). The heat-treated and the non-heat-treated MCC controls were evaluated for pH, mineral profile, ζ-potential, particle size, and rheological properties for up to 24h after heat treatment. The treatments were performed in triplicate, and differences among samples were evaluated using statistical analyses. Retorting resulted in slight aggregation in the MCC, whereas UHT caused the formation of visible aggregates and coagulation. The UHT-treated MCC had higher viscosity than retorted MCC, and displayed predominantly solid-like rheological behavior, indicative of structure formation. These effects were, at least in part, attributed to a change in mineral equilibrium, which affected the stability of the casein micelles, but additional mechanisms such as κ-casein dissociation may also play a significant role in these heat-induced changes. Drying of MCC accentuated the observed instabilities, as dried and reconstituted micellar casein concentrates (R-MCC) were more unstable to UHT sterilization than the MCC that had not undergone drying. The results of this study provide valuable information about the sterilization behavior and physical properties of MCC, which can be useful to processors in the development and manufacture of shelf-stable casein-based products and beverages.

  13. Patient compliance with crucial drug regimens: implications for prostate cancer.

    PubMed

    Urquhart, J

    1996-01-01

    Understanding of patient compliance with crucial drug regimens has improved markedly since 1986, based on data from two objective methods for monitoring drug dosing by ambulatory patients. Electronic monitoring records times and dates of drug package use, and chemical markers, incorporated into drug dosage forms, are assayed in plasma. These methods remove the camouflage that masks many poor compliers. In contrast, other methods (returned tablet counts, interviews, questionnaires) allow patients easily to censor evidence for delayed or omitted doses. The new methods show many more and larger errors of omission in both trials and practice than previously believed. One patient in about six is punctually compliant, but a modest majority of patients make errors probably too small to attenuate or otherwise modify the actions of all but the most unforgiving medicines. About a third of patients delay or omit many prescribed doses, thus attenuating or otherwise modifying the actions of all but the most forgiving drugs. One patient in about six takes little medicine, though camouflaged as a good complier. Similar patterns of delayed and omitted does prevail, essentially independent of drug, disease, prognosis, or symptoms. In summary, patients take the prescribed dose at intervals longer than prescribed--often by hours, sometimes by days, occasionally by weeks. The clinical and economic consequences of these lapses in dosing are unique to the treatment situation and the severity of disease and comorbidity. The new methods have not yet been applied to androgen-blocking agents, but if the findings resemble those with, e.g. tamoxifen in breast cancer, it will doubtless trigger some rethinking about failed treatment, trial design, and clinical management.

  14. Optimization of dosing regimens and dosing in special populations.

    PubMed

    Sime, F B; Roberts, M S; Roberts, J A

    2015-10-01

    Treatment of infectious diseases is becoming increasingly challenging with the emergence of less-susceptible organisms that are poorly responsive to existing antibiotic therapies, and the unpredictable pharmacokinetic alterations arising from complex pathophysiologic changes in some patient populations. In view of this fact, there has been a progressive work on novel dose optimization strategies to renew the utility of forgotten old antibiotics and to improve the efficacy of those currently in use. This review summarizes the different approaches of optimization of antibiotic dosing regimens and the special patient populations which may benefit most from these approaches. The existing methods are based on monitoring of antibiotic concentrations and/or use of clinical covariates. Measured concentrations can be correlated with predefined pharmacokinetic/pharmacodynamic targets to guide clinicians in predicting the necessary dose adjustment. Dosing nomograms are also available to relate observed concentrations or clinical covariates (e.g. creatinine clearance) with optimal dosing. More precise dose prediction based on observed covariates is possible through the application of population pharmacokinetic models. However, the most accurate estimation of individualized dosing requirements is achieved through Bayesian forecasting which utilizes both measured concentration and clinical covariates. Various software programs are emerging to ease clinical application. Whilst more studies are warranted to clarify the clinical outcomes associated with the different dose optimization approaches, severely ill patients in the course of marked infections and/or inflammation including those with sepsis, septic shock, severe trauma, burns injury, major surgery, febrile neutropenia, cystic fibrosis, organ dysfunction and obesity are those groups which may benefit most from individualized dosing.

  15. Population pharmacokinetics and pharmacodynamics of hydroxyurea in sickle cell anemia patients, a basis for optimizing the dosing regimen

    PubMed Central

    2011-01-01

    Background Hydroxyurea (HU) is the first approved pharmacological treatment of sickle cell anemia (SCA). The objectives of this study were to develop population pharmacokinetic(PK)-pharmacodynamic(PD) models for HU in order to characterize the exposure-efficacy relationships and their variability, compare two dosing regimens by simulations and develop some recommendations for monitoring the treatment. Methods The models were built using population modelling software NONMEM VII based on data from two clinical studies of SCA adult patients receiving 500-2000 mg of HU once daily. Fetal hemoglobin percentage (HbF%) and mean corpuscular volume (MCV) were used as biomarkers for response. A sequential modelling approach was applied. Models were evaluated using simulation-based techniques. Comparisons of two dosing regimens were performed by simulating 10000 patients in each arm during 12 months. Results The PK profiles were described by a bicompartmental model. The median (and interindividual coefficient of variation (CV)) of clearance was 11.6 L/h (30%), the central volume was 45.3 L (35%). PK steady-state was reached in about 35 days. For a given dosing regimen, HU exposure varied approximately fivefold among patients. The dynamics of HbF% and MCV were described by turnover models with inhibition of elimination of response. In the studied range of drug exposures, the effect of HU on HbF% was at its maximum (median Imax was 0.57, CV was 27%); the effect on MCV was close to its maximum, with median value of 0.14 and CV of 49%. Simulations showed that 95% of the steady-state levels of HbF% and MCV need 26 months and 3 months to be reached, respectively. The CV of the steady-state value of HbF% was about 7 times larger than that of MCV. Simulations with two different dosing regimens showed that continuous dosing led to a stronger HbF% increase in some patients. Conclusions The high variability of response to HU was related in part to pharmacokinetics and to pharmacodynamics

  16. Sequential estimation of surface water mass changes from daily satellite gravimetry data

    NASA Astrophysics Data System (ADS)

    Ramillien, G. L.; Frappart, F.; Gratton, S.; Vasseur, X.

    2015-03-01

    We propose a recursive Kalman filtering approach to map regional spatio-temporal variations of terrestrial water mass over large continental areas, such as South America. Instead of correcting hydrology model outputs by the GRACE observations using a Kalman filter estimation strategy, regional 2-by-2 degree water mass solutions are constructed by integration of daily potential differences deduced from GRACE K-band range rate (KBRR) measurements. Recovery of regional water mass anomaly averages obtained by accumulation of information of daily noise-free simulated GRACE data shows that convergence is relatively fast and yields accurate solutions. In the case of cumulating real GRACE KBRR data contaminated by observational noise, the sequential method of step-by-step integration provides estimates of water mass variation for the period 2004-2011 by considering a set of suitable a priori error uncertainty parameters to stabilize the inversion. Spatial and temporal averages of the Kalman filter solutions over river basin surfaces are consistent with the ones computed using global monthly/10-day GRACE solutions from official providers CSR, GFZ and JPL. They are also highly correlated to in situ records of river discharges (70-95 %), especially for the Obidos station where the total outflow of the Amazon River is measured. The sparse daily coverage of the GRACE satellite tracks limits the time resolution of the regional Kalman filter solutions, and thus the detection of short-term hydrological events.

  17. Induction of simultaneous and sequential malolactic fermentation in durian wine.

    PubMed

    Taniasuri, Fransisca; Lee, Pin-Rou; Liu, Shao-Quan

    2016-08-02

    This study represented for the first time the impact of malolactic fermentation (MLF) induced by Oenococcus oeni and its inoculation strategies (simultaneous vs. sequential) on the fermentation performance as well as aroma compound profile of durian wine. There was no negative impact of simultaneous inoculation of O. oeni and Saccharomyces cerevisiae on the growth and fermentation kinetics of S. cerevisiae as compared to sequential fermentation. Simultaneous MLF did not lead to an excessive increase in volatile acidity as compared to sequential MLF. The kinetic changes of organic acids (i.e. malic, lactic, succinic, acetic and α-ketoglutaric acids) varied with simultaneous and sequential MLF relative to yeast alone. MLF, regardless of inoculation mode, resulted in higher production of fermentation-derived volatiles as compared to control (alcoholic fermentation only), including esters, volatile fatty acids, and terpenes, except for higher alcohols. Most indigenous volatile sulphur compounds in durian were decreased to trace levels with little differences among the control, simultaneous and sequential MLF. Among the different wines, the wine with simultaneous MLF had higher concentrations of terpenes and acetate esters while sequential MLF had increased concentrations of medium- and long-chain ethyl esters. Relative to alcoholic fermentation only, both simultaneous and sequential MLF reduced acetaldehyde substantially with sequential MLF being more effective. These findings illustrate that MLF is an effective and novel way of modulating the volatile and aroma compound profile of durian wine.

  18. Derivation of sequential, real-time, process-control programs

    NASA Technical Reports Server (NTRS)

    Marzullo, Keith; Schneider, Fred B.; Budhiraja, Navin

    1991-01-01

    The use of weakest-precondition predicate transformers in the derivation of sequential, process-control software is discussed. Only one extension to Dijkstra's calculus for deriving ordinary sequential programs was found to be necessary: function-valued auxiliary variables. These auxiliary variables are needed for reasoning about states of a physical process that exists during program transitions.

  19. Applications of Bayesian Decision Theory to Sequential Mastery Testing.

    ERIC Educational Resources Information Center

    Vos, Hans J.

    1999-01-01

    Formulates optimal sequential rules for mastery testing using an approach derived from Bayesian sequential decision theory to consider both threshold and linear loss structures. Adopts the binomial probability distribution as the psychometric model. Provides an empirical example for concept-learning in medicine. (SLD)

  20. Decision Making and Learning while Taking Sequential Risks

    ERIC Educational Resources Information Center

    Pleskac, Timothy J.

    2008-01-01

    A sequential risk-taking paradigm used to identify real-world risk takers invokes both learning and decision processes. This article expands the paradigm to a larger class of tasks with different stochastic environments and different learning requirements. Generalizing a Bayesian sequential risk-taking model to the larger set of tasks clarifies…

  1. Interaction of Hypertext Forms and Global Versus Sequential Learning Styles

    ERIC Educational Resources Information Center

    Dunser, Andreas; Jirasko, Marco

    2005-01-01

    In this study, the relevance of the distinction between sequential and global learners in the context of learning with hypertext was investigated. Learners with global learning style were expected to produce better results when learning with hypertext, whereas learners with sequential learning style should profit from a structural aid in form of a…

  2. Development of Decision Making: Sequential versus Integrative Rules

    ERIC Educational Resources Information Center

    Jansen, Brenda R. J.; van Duijvenvoorde, Anna C. K.; Huizenga, Hilde M.

    2012-01-01

    Decisions can be made by applying a variety of decision-making rules--sequential rules in which decisions are based on a sequential evaluation of choice dimensions and the integrative normative rule in which decisions are based on an integration of choice dimensions. In this study, we investigated the developmental trajectory of such…

  3. Sequential Dependencies in Categorical Judgments of Radiographic Images

    ERIC Educational Resources Information Center

    Beckstead, Jason W.; Boutis, Kathy; Pecaric, Martin; Pusic, Martin V.

    2017-01-01

    Sequential context effects, the psychological interactions occurring between the events of successive trials when a sequence of similar stimuli are judged, have interested psychologists for decades. It has been well established that individuals exhibit sequential context effects in psychophysical experiments involving unidimensional stimuli.…

  4. A Bayesian Theory of Sequential Causal Learning and Abstract Transfer

    ERIC Educational Resources Information Center

    Lu, Hongjing; Rojas, Randall R.; Beckers, Tom; Yuille, Alan L.

    2016-01-01

    Two key research issues in the field of causal learning are how people acquire causal knowledge when observing data that are presented sequentially, and the level of abstraction at which learning takes place. Does sequential causal learning solely involve the acquisition of specific cause-effect links, or do learners also acquire knowledge about…

  5. A Distance Measure for Automatic Document Classification by Sequential Analysis.

    ERIC Educational Resources Information Center

    Kar, Gautam; White, Lee J.

    1978-01-01

    Investigates the feasibility of using a distance measure for automatic sequential document classification. This property of the distance measure is used to design a sequential classification algorithm which classifies key words and analyzes them separately in order to assign primary and secondary classes to a document. (VT)

  6. Differences in Lipid Measurements by Antiretroviral Regimen Exposure in Cohorts from Asia and Australia

    PubMed Central

    Achhra, Amit C.; Amin, Janaki; Hoy, Jennifer; Tanuma, Junko; Sirisanthana, Thira; Nolan, David; Merati, Tuti; Giles, Michelle

    2012-01-01

    We explored the mean differences in routinely measured lipids (total cholesterol, triglycerides, and high-density lipoprotein cholesterol) according to exposure to different combination antiretroviral regimens in Asian (n = 2051) and Australian (predominantly Caucasian, n = 794) cohorts. The regimen was defined as at least 3 antiretroviral drugs with at least 2 nucleoside-reverse transcriptases (NRTIs) and either of at least one protease inhibitor (PI) or non-nucleoside-reverse transcriptases (NNRTIs). We categorised cART regimens as: NRTIs as tenofovir based or not; NNRTIs as nevirapine or efavirenz (but not both); and PI as atazanavir based or not. We found that the impact of various antiretroviral regimens on lipids in Asian and Australian cohorts was only different by cohort for total cholesterol (P for interaction between regimen and cohort: <0.001) but not in case of other lipids (P for interaction: >0.05). The differences in total cholesterol were however small and unlikely to be of clinical significance. Overall, tenofovir with nevirapine or atazanavir was associated with the most favorable lipids, while the PI regimens without tenofovir and atazanavir were associated with least favorable lipids. We conclude that the impact of various ART regimens on lipids is largely similar in Asian and Australian cohorts and that the newer drugs such as tenofovir and atazanavir are likely to provide similar benefit in terms of lipid profiles in both populations. PMID:22675613

  7. In silico evaluation and exploration of antibiotic tuberculosis treatment regimens

    SciTech Connect

    Pienaar, Elsje; Dartois, Véronique; Linderman, Jennifer J.; Kirschner, Denise E.

    2015-11-14

    Improvement in tuberculosis treatment regimens requires selection of antibiotics and dosing schedules from a large design space of possibilities. Incomplete knowledge of antibiotic and host immune dynamics in tuberculosis granulomas impacts clinical trial design and success, and variations among clinical trials hamper side-by-side comparison of regimens. Our objective is to systematically evaluate the efficacy of isoniazid and rifampin regimens, and identify modifications to these antibiotics that improve treatment outcomes. We pair a spatio-temporal computational model of host immunity with pharmacokinetic and pharmacodynamic data on isoniazid and rifampin. The model is calibrated to plasma pharmacokinetic and granuloma bacterial load data from non-human primate models of tuberculosis and to tissue and granuloma measurements of isoniazid and rifampin in rabbit granulomas. We predict the efficacy of regimens containing different doses and frequencies of isoniazid and rifampin. We predict impacts of pharmacokinetic/pharmacodynamic modifications on antibiotic efficacy. We demonstrate that suboptimal antibiotic concentrations within granulomas lead to poor performance of intermittent regimens compared to daily regimens. Improvements from dose and frequency changes are limited by inherent antibiotic properties, and we propose that changes in intracellular accumulation ratios and antimicrobial activity would lead to the most significant improvements in treatment outcomes. Results suggest that an increased risk of drug resistance in fully intermittent as compared to daily regimens arises from higher bacterial population levels early during treatment. In conclusion, our systems pharmacology approach complements efforts to accelerate tuberculosis therapeutic development.

  8. Weekly Moxifloxacin and Rifapentine Is More Active Than the Denver Regimen in Murine Tuberculosis

    PubMed Central

    Rosenthal, Ian M.; Williams, Kathy; Tyagi, Sandeep; Vernon, Andrew A.; Peloquin, Charles A.; Bishai, William R.; Grosset, Jacques H.; Nuermberger, Eric L.

    2005-01-01

    Rationale: Treatment of tuberculosis with an efficacious once-weekly regimen would be a significant achievement in improving patient adherence. Currently, the only recommended once-weekly continuation phase regimen of isoniazid plus rifapentine (10 mg/kg) is inferior to standard twice-weekly therapy with isoniazid plus rifampin and is, therefore, restricted to non–high-risk patients. The substitution of moxifloxacin, a new 8-methoxyfluoroquinolone, for isoniazid and an increase in the dose of rifapentine could augment the activity of once-weekly regimens. Methods: To test this hypothesis we evaluated the sterilizing activity of improved once-weekly rifapentine-based continuation phase regimens in a murine model that mimics the treatment of high-risk patients with tuberculosis. The bactericidal activity of standard daily therapy and standard intermittent therapy (“Denver” regimen) was also assessed to evaluate the effect of intermittent drug administration during the initial phase of therapy. Results: After 2 mo of treatment, lung colony-forming unit counts were 1 log10 lower in mice treated with standard daily therapy than with the Denver regimen. During the continuation phase, the sterilizing activity of once-weekly moxifloxacin plus rifapentine (15 mg/kg) was significantly greater than that of the predominantly twice-weekly Denver regimen of isoniazid plus rifampin. No significant difference in sterilizing activity was detected between once-weekly isoniazid plus rifapentine (15 mg/kg) and the Denver regimen. Conclusions: These results suggest that the efficacy of the once-weekly isoniazid plus rifapentine continuation phase regimen can be increased by substituting moxifloxacin for isoniazid and by increasing the dose of rifapentine to a clinically acceptable level of 15 mg/kg. PMID:16141439

  9. Congenital syphilis after treatment of maternal syphilis with a penicillin regimen exceeding CDC guidelines.

    PubMed Central

    Conover, C S; Rend, C A; Miller, G B; Schmid, G P

    1998-01-01

    BACKGROUND: Although congenital syphilis usually occurs as a result of a failure to detect and treat syphilis in pregnant women, failures of the currently recommended regimen to prevent congenital syphilis have been reported. CASE: This report describes an infant with congenital syphilis despite maternal treatment with a regimen exceeding current CDC guidelines. CONCLUSION: Regardless of the regimen used to treat syphilis during pregnancy, clinicians should recognize the possibility of occasional treatment failures and the importance of adequate follow-up of infants at risk for congenital syphilis. PMID:9785110

  10. Integrated pharmacokinetic-pharmacodynamic modeling and allometric scaling for optimizing the dosage regimen of the monoclonal ior EGF/r3 antibody.

    PubMed

    Duconge, Jorge; Castillo, Rubén; Crombet, Tania; Alvarez, Daniel; Matheu, Janet; Vecino, Gloria; Alonso, Katia; Beausoleil, Irene; Valenzuela, Carmen; Becquer, Maria A; Fernández-Sánchez, Eduardo

    2004-02-01

    The multiple-dose strategy with the monoclonal ior EGF/r3 antibody, in xenograft bearing nude mice, was supported upon the basis of its integrated pharmacokinetic-pharmacodynamic relationship, according to both the temporal (K(e0)=0.0015+/-0.000035h(-1)) and the time-independent sensitivity (C(50%)(ss), 9.23+/-0.17microg/ml; C(max,eff)(ss), 12.5microg/ml) components of its tumor growth delay action. This relationship was consistent with a sigmoidal E(max) pharmacodynamic model postulating a hypothetical effect compartment that permits us to estimate an effective steady-state concentration range (7.5-12microg/ml). Using this information we calculated both the cumulative and non-cumulative dosage regimens to compare their response patterns with respect to the control group. It follows that the differences in the estimated tumor growth inhibition ratio were statistically significant between the control group and either of the treated ones (P<0.05). The median survival time in treated mice under non-cumulative regimen (72+/-10 days), predicted an increase in this parameter as compared to the control one (55+/-6 days). Finally, using the allometric paradigm, the empiric power equation for dose scaling across mammalian species allowed the calculation of the dosage schedule for further clinical trial. The estimated maintenance dose in human (70kg) was 200mg/m(2) to be given weekly, and the corresponding loading dose was 600mg/m(2).

  11. Beam geometry selection using sequential beam addition

    SciTech Connect

    Popple, Richard A. Brezovich, Ivan A.; Fiveash, John B.

    2014-05-15

    Purpose: The selection of optimal beam geometry has been of interest since the inception of conformal radiotherapy. The authors report on sequential beam addition, a simple beam geometry selection method, for intensity modulated radiation therapy. Methods: The sequential beam addition algorithm (SBA) requires definition of an objective function (score) and a set of candidate beam geometries (pool). In the first iteration, the optimal score is determined for each beam in the pool and the beam with the best score selected. In the next iteration, the optimal score is calculated for each beam remaining in the pool combined with the beam selected in the first iteration, and the best scoring beam is selected. The process is repeated until the desired number of beams is reached. The authors selected three treatment sites, breast, lung, and brain, and determined beam arrangements for up to 11 beams from a pool comprised of 25 equiangular transverse beams. For the brain, arrangements were additionally selected from a pool of 22 noncoplanar beams. Scores were determined for geometries comprised equiangular transverse beams (EQA), as well as two tangential beams for the breast case. Results: In all cases, SBA resulted in scores superior to EQA. The breast case had the strongest dependence on beam geometry, for which only the 7-beam EQA geometry had a score better than the two tangential beams, whereas all SBA geometries with more than two beams were superior. In the lung case, EQA and SBA scores monotonically improved with increasing number of beams; however, SBA required fewer beams to achieve scores equivalent to EQA. For the brain case, SBA with a coplanar pool was equivalent to EQA, while the noncoplanar pool resulted in slightly better scores; however, the dose-volume histograms demonstrated that the differences were not clinically significant. Conclusions: For situations in which beam geometry has a significant effect on the objective function, SBA can identify

  12. Persistence to single-tablet regimen versus less-drug regimen in treatment experienced HIV-infected patients on antiretroviral therapy.

    PubMed

    Jiménez-Galán, Rocio; Cantudo Cuenca, Maria-Rosa; Robustillo-Cortés, María Aguas; Borrego Izquierdo, Y; Almeida-Gonzalez, Carmen Victoria; Morillo-Verdugo, Ramón

    2016-06-01

    Objetivos: Analizar y comparar la persistencia entre las estrategias basadas en Single-Tablet Regimen (STR) y Less Drug Regimen (LDR) en pacientes VIH+. El objetivo secundario del estudio fue determinar factores predictores de persistencia. Material y métodos: Estudio observacional retrospectivo que incluyo los siguientes criterios: pacientes VIH+ con tratamiento antirretroviral (TAR) con un regimen basado en STR o LDR. Se recogieron variables demograficas, factores de riesgo de adquisicion, consumo de drogas, presencia de algun trastorno psiquiatrico y coinfeccion por el virus de la hepatitis B o C. Para comparar la persistencia entre ambas estrategias se realizo un analisis de supervivencia de Kaplan-Meir y se aplico el metodo de log-rank. Se realizo un analisis de regresion de Cox para identificar los factores predictores de persistencia. Resultados: Se incluyeron 244 pacientes, 176 con STR y 68 con LDR. El 34,1% (n = 60) de los pacientes que recibieron un regimen STR abandonaron y en el LDR el 19,1% (n = 13). Los efectos adversos fueron la principal causa de abandono del tratamiento en los pacientes que recibieron STR y el fallo virologico en el regimen LDR. La persistencia de las estrategias STR y LDR fue similar, no encontrandose diferencias estadisticamente significativas entre ambas. El consumo de drogas fue el unico factor predictivo asociado con una menor persistencia (HR = 2,59; p = 0,005). Conclusiones: La persistencia entre los regimenes STR y LDR fue similar, no detectandose diferencias significativas entre ambos. El consumo de drogas fue el unico factor independiente asociado con una menor persistencia del tratamiento antirretroviral.

  13. Skin dose differences between intensity-modulated radiation therapy and volumetric-modulated arc therapy and between boost and integrated treatment regimens for treating head and neck and other cancer sites in patients

    SciTech Connect

    Penoncello, Gregory P.; Ding, George X.

    2016-04-01

    The purpose of this study was (1) to evaluate dose to skin between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) treatment techniques for target sites in the head and neck, pelvis, and brain and (2) to determine if the treatment dose and fractionation regimen affect the skin dose between traditional sequential boost and integrated boost regimens for patients with head and neck cancer. A total of 19 patients and 48 plans were evaluated. The Eclipse (v11) treatment planning system was used to plan therapy in 9 patients with head and neck cancer, 5 patients with prostate cancer, and 5 patients with brain cancer with VMAT and static-field IMRT. The mean skin dose and the maximum dose to a contiguous volume of 2 cm{sup 3} for head and neck plans and brain plans and a contiguous volume of 5 cm{sup 3} for pelvis plans were compared for each treatment technique. Of the 9 patients with head and neck cancer, 3 underwent an integrated boost regimen. One integrated boost plan was replanned with IMRT and VMAT using a traditional boost regimen. For target sites located in the head and neck, VMAT reduced the mean dose and contiguous hot spot most noticeably in the shoulder region by 5.6% and 5.4%, respectively. When using an integrated boost regimen, the contiguous hot spot skin dose in the shoulder was larger on average than a traditional boost pattern by 26.5% and the mean skin dose was larger by 1.7%. VMAT techniques largely decrease the contiguous hot spot in the skin in the pelvis by an average of 36% compared with IMRT. For the same target coverage, VMAT can reduce the skin dose in all the regions of the body, but more noticeably in the shoulders in patients with head and neck and pelvis cancer. We also found that using integrated boost regimens in patients with head and neck cancer leads to higher shoulder skin doses compared with traditional boost regimens.

  14. Skin dose differences between intensity-modulated radiation therapy and volumetric-modulated arc therapy and between boost and integrated treatment regimens for treating head and neck and other cancer sites in patients.

    PubMed

    Penoncello, Gregory P; Ding, George X

    2016-01-01

    The purpose of this study was (1) to evaluate dose to skin between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) treatment techniques for target sites in the head and neck, pelvis, and brain and (2) to determine if the treatment dose and fractionation regimen affect the skin dose between traditional sequential boost and integrated boost regimens for patients with head and neck cancer. A total of 19 patients and 48 plans were evaluated. The Eclipse (v11) treatment planning system was used to plan therapy in 9 patients with head and neck cancer, 5 patients with prostate cancer, and 5 patients with brain cancer with VMAT and static-field IMRT. The mean skin dose and the maximum dose to a contiguous volume of 2cm(3) for head and neck plans and brain plans and a contiguous volume of 5cm(3) for pelvis plans were compared for each treatment technique. Of the 9 patients with head and neck cancer, 3 underwent an integrated boost regimen. One integrated boost plan was replanned with IMRT and VMAT using a traditional boost regimen. For target sites located in the head and neck, VMAT reduced the mean dose and contiguous hot spot most noticeably in the shoulder region by 5.6% and 5.4%, respectively. When using an integrated boost regimen, the contiguous hot spot skin dose in the shoulder was larger on average than a traditional boost pattern by 26.5% and the mean skin dose was larger by 1.7%. VMAT techniques largely decrease the contiguous hot spot in the skin in the pelvis by an average of 36% compared with IMRT. For the same target coverage, VMAT can reduce the skin dose in all the regions of the body, but more noticeably in the shoulders in patients with head and neck and pelvis cancer. We also found that using integrated boost regimens in patients with head and neck cancer leads to higher shoulder skin doses compared with traditional boost regimens.

  15. Sequential Bottomonium Production at High Temperatures

    NASA Astrophysics Data System (ADS)

    Petreczky, Peter; Young, Clint

    2017-03-01

    Bottomonium production in heavy ion collisions is modified compared with any simple extrapolation from elementary collisions. This modification is most likely caused by the presence of a deconfined system of quarks and gluons for times of several fm/c. In such a medium, bottomonium can be destroyed, but the constituent bottom quarks will likely stay spatially correlated due to small mean free paths in this system. With these facts in mind, we describe bottomonium formation with a coupled set of equations. A rate equation describes the destruction of Υ (1S) particles, while a Langevin equation describes how the bottom quarks stay correlated for a sufficiently long time so that recombination into bottomonia is possible. We show that within this approach it is possible to understand the magnitude of Υ (1S) suppression in heavy ion collisions and the larger suppression of the Υ (2S) state, implying that the reduction in the ratio of Υ (1S)/Υ (2S) yield in heavy ion collision does not necessarily correspond to the sequential melting picture.

  16. Sequential experimental design based generalised ANOVA

    SciTech Connect

    Chakraborty, Souvik Chowdhury, Rajib

    2016-07-15

    Over the last decade, surrogate modelling technique has gained wide popularity in the field of uncertainty quantification, optimization, model exploration and sensitivity analysis. This approach relies on experimental design to generate training points and regression/interpolation for generating the surrogate. In this work, it is argued that conventional experimental design may render a surrogate model inefficient. In order to address this issue, this paper presents a novel distribution adaptive sequential experimental design (DA-SED). The proposed DA-SED has been coupled with a variant of generalised analysis of variance (G-ANOVA), developed by representing the component function using the generalised polynomial chaos expansion. Moreover, generalised analytical expressions for calculating the first two statistical moments of the response, which are utilized in predicting the probability of failure, have also been developed. The proposed approach has been utilized in predicting probability of failure of three structural mechanics problems. It is observed that the proposed approach yields accurate and computationally efficient estimate of the failure probability.

  17. Sequential growth of bacteria on crude oil.

    PubMed

    Horowitz, A; Gutnick, D; Rosenberg, E

    1975-07-01

    By modification of the enrichment culture procedure three bacterial strains capable of degrading crude oil in sea water were isolated in pure culture, UP-2, UP-3, and UP-4. Strain UP-2 appears to be highly specialized for growth on crude oil in sea water since it showed strong preference for oil or oil degradation products as substrates for growth, converted 66% of the oil into a form no longer extractable by organic solvents, quantitatively degraded the paraffinic fraction (gas chromatographic analysis), emulsified the oil during exponential growth, and produced 1.6 x 10-8 cells per mg of oil. After exhaustive growth of UP-2 on crude oil the residual oil supported the growth of UP-3 and UP-4, but not a previously isolated oil-degrading bacterium, RAG-1. Strains UP-2, UP-3, and UP-4 grew on RAG-1-degraded oil (specifically depleted of n-alkanes). The growth of UP-3 and UP-4 on UP-2 and RAG-1-degraded oil resulted in the production of new paraffinic compounds as revealed by gas chromatography. When the four strains were grown either together in a mixed culture or sequentially, there was over 75% oil conversion. By plating on selective media, growth of the individual strains was measured kinetically in the reconstituted mixed culture, revealing competition for common growth substances (UP-2 and RAG-1), emhanced die-off (UP-2), and stabilization (UP-4) during the stationary phase.

  18. Sequential self-folding of polymer sheets

    PubMed Central

    Liu, Ying; Shaw, Brandi; Dickey, Michael D.; Genzer, Jan

    2017-01-01

    Shape plays an important role in defining the function of materials, particularly those found in nature. Several strategies exist to program materials to change from one shape to another; however, few can temporally and spatially control the shape. Programming the sequence of shape transformation with temporal control has been driven by the desire to generate complex shapes with high yield and to create multiple shapes from the same starting material. This paper demonstrates a markedly simple strategy for programmed self-folding of two-dimensional (2D) polymer sheets into 3D objects in a sequential manner using external light. Printed ink on the surface of the polymer sheets discriminately absorbs light on the basis of the wavelength of the light and the color of the ink that defines the hinge about which the sheet folds. The absorbed light gradually heats the underlying polymer across the thickness of the sheet, which causes relief of strain to induce folding. These color patterns can be designed to absorb only specific wavelengths of light (or to absorb differently at the same wavelength using color hues), thereby providing control of sheet folding with respect to time and space. This type of shape programming may have numerous applications, including reconfigurable electronics, actuators, sensors, implantable devices, smart packaging, and deployable structures. PMID:28275736

  19. Sequential experimental design based generalised ANOVA

    NASA Astrophysics Data System (ADS)

    Chakraborty, Souvik; Chowdhury, Rajib

    2016-07-01

    Over the last decade, surrogate modelling technique has gained wide popularity in the field of uncertainty quantification, optimization, model exploration and sensitivity analysis. This approach relies on experimental design to generate training points and regression/interpolation for generating the surrogate. In this work, it is argued that conventional experimental design may render a surrogate model inefficient. In order to address this issue, this paper presents a novel distribution adaptive sequential experimental design (DA-SED). The proposed DA-SED has been coupled with a variant of generalised analysis of variance (G-ANOVA), developed by representing the component function using the generalised polynomial chaos expansion. Moreover, generalised analytical expressions for calculating the first two statistical moments of the response, which are utilized in predicting the probability of failure, have also been developed. The proposed approach has been utilized in predicting probability of failure of three structural mechanics problems. It is observed that the proposed approach yields accurate and computationally efficient estimate of the failure probability.

  20. Metamodel defined multidimensional embedded sequential sampling criteria.

    SciTech Connect

    Turner, C. J.; Campbell, M. I.; Crawford, R. H.

    2004-01-01

    Collecting data to characterize an unknown space presents a series of challenges. Where in the space should data be collected? What regions are more valuable than others to sample? When have sufficient samples been acquired to characterize the space with some level of confidence? Sequential sampling techniques offer an approach to answering these questions by intelligently sampling an unknown space. Sampling decisions are made with criteria intended to preferentially search the space for desirable features. However, N-dimensional applications need efficient and effective criteria. This paper discusses the evolution of several such criteria based on an understanding of the behaviors of existing criteria, and desired criteria properties. The resulting criteria are evaluated with a variety of planar functions, and preliminary results for higher dimensional applications are also presented. In addition, a set of convergence criteria, intended to evaluate the effectiveness of further sampling are implemented. Using these sampling criteria, an effective metamodel representation of the unknown space can be generated at reasonable sampling costs. Furthermore, the use of convergence criteria allows conclusions to be drawn about the level of confidence in the metamodel, and forms the basis for evaluating the adequacy of the original sampling budget.

  1. Sequential Auctions in Uncertain Information Settings

    NASA Astrophysics Data System (ADS)

    Fatima, Shaheen; Wooldridge, Michael; Jennings, Nicholas R.

    This paper analyzes sequential auctions for private value objects using second-price sealed-bid rules. Now, the equilibrium bids for such auctions depend on the information uncertainty of the bidders. Specifically, there are three key auction parameters that the bidders could be uncertain about: the valuations of the objects for sale, the number of objects for sale, and the number of participating bidders. We analyse the bidding behaviour for each of these three sources of uncertainty. For each setting, we first find the equilibrium bidding strategies for the individual auctions that comprise a series. Then we analyze the effect of these uncertainties on the computational and economic properties of the equilibrium solution. The former analysis is essential if we want to use software agents to bid on our behalf. The latter is essential because both the auctioneer and the bidders want to know how these uncertainties affect their profits. Thus we compare the outcomes for these settings from the perspective of the bidders (i.e., in terms of their profits), from the perspective of the auctioneer (i.e., in terms of his revenue), and from a global perspective (i.e., in terms of auction efficiency).

  2. Cooperation induced by random sequential exclusion

    NASA Astrophysics Data System (ADS)

    Li, Kun; Cong, Rui; Wang, Long

    2016-06-01

    Social exclusion is a common and powerful tool to penalize deviators in human societies, and thus to effectively elevate collaborative efforts. Current models on the evolution of exclusion behaviors mostly assume that each peer excluder independently makes the decision to expel the defectors, but has no idea what others in the group would do or how the actual punishment effect will be. Thus, a more realistic model, random sequential exclusion, is proposed. In this mechanism, each excluder has to pay an extra scheduling cost and then all the excluders are arranged in a random order to implement the exclusion actions. If one free rider has already been excluded by an excluder, the remaining excluders will not participate in expelling this defector. We find that this mechanism can help stabilize cooperation under more unfavorable conditions than the normal peer exclusion can do, either in well-mixed population or on social networks. However, too large a scheduling cost may undermine the advantage of this mechanism. Our work validates the fact that collaborative practice among punishers plays an important role in further boosting cooperation.

  3. Constraint-based evaluation of sequential procedures

    NASA Technical Reports Server (NTRS)

    Barry, Matthew R.

    1990-01-01

    Constraining the operation of an agent requires knowledge of the restrictions to physical and temporal capabilities of that agent, as well as an inherent understanding of the desires being processed by that agent. Usually a set of constraints are available that must be adhered to in order to foster safe operations. In the worst case, violation of a constraint may be cause to terminate operation. If the agent is carrying out a plan, then a method for predicting the agent's desires, and therefore possible constraint violations, is required. The conceptualization of constraint-based reasoning used herein assumes that a system knows how to select a constraint for application as well as how to apply that constraint once it is selected. The application of constraint-based reasoning for evaluating certain kinds of plans known as sequential procedures is discussed. By decomposing these plans, it is possible to apply context dependent constraints in production system fashion without incorporating knowledge of the original planning process.

  4. Sequential detection of learning in cognitive diagnosis.

    PubMed

    Ye, Sangbeak; Fellouris, Georgios; Culpepper, Steven; Douglas, Jeff

    2016-05-01

    In order to look more closely at the many particular skills examinees utilize to answer items, cognitive diagnosis models have received much attention, and perhaps are preferable to item response models that ordinarily involve just one or a few broadly defined skills, when the objective is to hasten learning. If these fine-grained skills can be identified, a sharpened focus on learning and remediation can be achieved. The focus here is on how to detect when learning has taken place for a particular attribute and efficiently guide a student through a sequence of items to ultimately attain mastery of all attributes while administering as few items as possible. This can be seen as a problem in sequential change-point detection for which there is a long history and a well-developed literature. Though some ad hoc rules for determining learning may be used, such as stopping after M consecutive items have been successfully answered, more efficient methods that are optimal under various conditions are available. The CUSUM, Shiryaev-Roberts and Shiryaev procedures can dramatically reduce the time required to detect learning while maintaining rigorous Type I error control, and they are studied in this context through simulation. Future directions for modelling and detection of learning are discussed.

  5. Particle morphology effects in random sequential adsorption

    NASA Astrophysics Data System (ADS)

    Budinski-Petković, Lj.; Lončarević, I.; Dujak, D.; Karač, A.; Šćepanović, J. R.; Jakšić, Z. M.; Vrhovac, S. B.

    2017-02-01

    The properties of the random sequential adsorption of objects of various shapes on a two-dimensional triangular lattice are studied numerically by means of Monte Carlo simulations. The depositing objects are formed by self-avoiding lattice steps, whereby the size of the objects is gradually increased by wrapping the walks in several different ways. The aim of this work is to investigate the impact of the geometrical properties of the shapes on the jamming density θJ and on the temporal evolution of the coverage fraction θ (t ) . Our results suggest that the order of symmetry axis of a shape exerts a decisive influence on adsorption kinetics near the jamming limit θJ. The decay of probability for the insertion of a new particle onto a lattice is described in a broad range of the coverage θ by the product between the linear and the stretched exponential function for all examined objects. The corresponding fitting parameters are discussed within the context of the shape descriptors, such as rotational symmetry and the shape factor (parameter of nonsphericity) of the objects. Predictions following from our calculations suggest that the proposed fitting function for the insertion probability is consistent with the exponential approach of the coverage fraction θ (t ) to the jamming limit θJ.

  6. Sleep memory processing: the sequential hypothesis

    PubMed Central

    Giuditta, Antonio

    2014-01-01

    According to the sequential hypothesis (SH) memories acquired during wakefulness are processed during sleep in two serial steps respectively occurring during slow wave sleep (SWS) and rapid eye movement (REM) sleep. During SWS memories to be retained are distinguished from irrelevant or competing traces that undergo downgrading or elimination. Processed memories are stored again during REM sleep which integrates them with preexisting memories. The hypothesis received support from a wealth of EEG, behavioral, and biochemical analyses of trained rats. Further evidence was provided by independent studies of human subjects. SH basic premises, data, and interpretations have been compared with corresponding viewpoints of the synaptic homeostatic hypothesis (SHY). Their similarities and differences are presented and discussed within the framework of sleep processing operations. SHY’s emphasis on synaptic renormalization during SWS is acknowledged to underline a key sleep effect, but this cannot marginalize sleep’s main role in selecting memories to be retained from downgrading traces, and in their integration with preexisting memories. In addition, SHY’s synaptic renormalization raises an unsolved dilemma that clashes with the accepted memory storage mechanism exclusively based on modifications of synaptic strength. This difficulty may be bypassed by the assumption that SWS-processed memories are stored again by REM sleep in brain subnuclear quantum particles. Storing of memories in quantum particles may also occur in other vigilance states. Hints are provided on ways to subject the quantum hypothesis to experimental tests. PMID:25565985

  7. Online Sequential Extreme Learning Machine With Kernels.

    PubMed

    Scardapane, Simone; Comminiello, Danilo; Scarpiniti, Michele; Uncini, Aurelio

    2015-09-01

    The extreme learning machine (ELM) was recently proposed as a unifying framework for different families of learning algorithms. The classical ELM model consists of a linear combination of a fixed number of nonlinear expansions of the input vector. Learning in ELM is hence equivalent to finding the optimal weights that minimize the error on a dataset. The update works in batch mode, either with explicit feature mappings or with implicit mappings defined by kernels. Although an online version has been proposed for the former, no work has been done up to this point for the latter, and whether an efficient learning algorithm for online kernel-based ELM exists remains an open problem. By explicating some connections between nonlinear adaptive filtering and ELM theory, in this brief, we present an algorithm for this task. In particular, we propose a straightforward extension of the well-known kernel recursive least-squares, belonging to the kernel adaptive filtering (KAF) family, to the ELM framework. We call the resulting algorithm the kernel online sequential ELM (KOS-ELM). Moreover, we consider two different criteria used in the KAF field to obtain sparse filters and extend them to our context. We show that KOS-ELM, with their integration, can result in a highly efficient algorithm, both in terms of obtained generalization error and training time. Empirical evaluations demonstrate interesting results on some benchmarking datasets.

  8. Priority-Setting for Novel Drug Regimens to Treat Tuberculosis: An Epidemiologic Model

    PubMed Central

    Cohen, Ted; Nuermberger, Eric; Dooley, Kelly E.; Gonzalez-Angulo, Lice; Churchyard, Gavin J.; Nahid, Payam; Rich, Michael L.; Bansbach, Cathy; Forissier, Thomas; Dowdy, David W.

    2017-01-01

    Background Novel drug regimens are needed for tuberculosis (TB) treatment. New regimens aim to improve on characteristics such as duration, efficacy, and safety profile, but no single regimen is likely to be ideal in all respects. By linking these regimen characteristics to a novel regimen’s ability to reduce TB incidence and mortality, we sought to prioritize regimen characteristics from a population-level perspective. Methods and Findings We developed a dynamic transmission model of multi-strain TB epidemics in hypothetical populations reflective of the epidemiological situations in India (primary analysis), South Africa, the Philippines, and Brazil. We modeled the introduction of various novel rifampicin-susceptible (RS) or rifampicin-resistant (RR) TB regimens that differed on six characteristics, identified in consultation with a team of global experts: (1) efficacy, (2) duration, (3) ease of adherence, (4) medical contraindications, (5) barrier to resistance, and (6) baseline prevalence of resistance to the novel regimen. We compared scale-up of these regimens to a baseline reflective of continued standard of care. For our primary analysis situated in India, our model generated baseline TB incidence and mortality of 157 (95% uncertainty range [UR]: 113–187) and 16 (95% UR: 9–23) per 100,000 per year at the time of novel regimen introduction and RR TB incidence and mortality of 6 (95% UR: 4–10) and 0.6 (95% UR: 0.3–1.1) per 100,000 per year. An optimal RS TB regimen was projected to reduce 10-y TB incidence and mortality in the India-like scenario by 12% (95% UR: 6%–20%) and 11% (95% UR: 6%–20%), respectively, compared to current-care projections. An optimal RR TB regimen reduced RR TB incidence by an estimated 32% (95% UR: 18%–46%) and RR TB mortality by 30% (95% UR: 18%–44%). Efficacy was the greatest determinant of impact; compared to a novel regimen meeting all minimal targets only, increasing RS TB treatment efficacy from 94% to 99

  9. Fewer doses of HPV vaccine result in immune response similar to three-dose regimen

    Cancer.gov

    NCI scientists report that two doses of a human papillomavirus (HPV) vaccine, trademarked as Cervarix, resulted in similar serum antibody levels against two of the most carcinogenic types of HPV (16 and 18), compared to a standard three dose regimen.

  10. Successful intraoperative spinal cord monitoring during scoliosis surgery using a total intravenous anesthetic regimen including dexmedetomidine.

    PubMed

    Anschel, David J; Aherne, Andrew; Soto, Roy G; Carrion, Wesley; Hoegerl, Carl; Nori, Palgun; Seidman, Peggy A

    2008-02-01

    Intraoperative neurophysiological monitoring (IONM) during corrective spinal surgery is widely used. Because of the possible interference with the recording of evoked potentials by inhalational anesthetics, total intravenous anesthetic (TIVA) regimens have been advocated. TIVA regimens may be difficult to use in pediatric populations due to metabolic factors. We report on the results of multimodality IONM during 18 cases in which a TIVA regimen incorporating dexmedetomidine (Precedex, Hespira, Lake Forest, IL) was used. Monitoring techniques included sensory (SSEP) and motor evoked potentials (MEP), as well as pedicle screw stimulation. SSEPs were maintained within an acceptable range of baseline amplitude (50%) and latency (10%), and MEPs remained elicitable throughout each case. We therefore found that the anesthetic regimen did not significantly interfere with any of the monitoring modalities used and conclude that IONM in the presence of dexmedetomidine is feasible under appropriate conditions.

  11. Efficacy and Optimization of Palivizumab Injection Regimens Against Respiratory Syncytial Virus Infection

    PubMed Central

    Gutfraind, Alexander; Galvani, Alison P.; Meyers, Lauren Ancel

    2015-01-01

    IMPORTANCE Infection with the respiratory syncytial virus (RSV) is the leading cause of hospitalizations in children, accounting for more than 90 000 hospitalizations every year in the United States. For children who are at risk for severe RSV infections, the American Academy of Pediatrics recommends immunoprophylaxis with a series of up to 5 injections of the antibody palivizumab administered monthly, beginning on November 1 of each year. However, many practitioners initiate injections at the onset of RSV season as indicated by local surveillance. OBJECTIVES To evaluate the effectiveness of current regimens for palivizumab injections across different cities and to design an optimized regimen. DESIGN, SETTING, AND PARTICIPANTS We performed a mathematical modeling study of the risk for hospitalization due to RSV infection. The model accounted for the pharmacokinetics of the antibody, the timing of the injections, and seasonal patterns of RSV, including geographic and year-to-year variability. We used the model to estimate the efficacy of current regimens, including the American Academy of Pediatrics recommendation, and to design a more effective injection regimen, the optimized fixed start (OFS), which uses city-specific initiation dates. Participants were the approximately 700 000 individuals who had specimens tested for RSV by National Respiratory and Enteric Virus Surveillance System laboratories in 18 US cities from July 1, 1994, through June 30, 2011 (a total of 725 741 tests). INTERVENTIONS Different palivizumab injection regimens. MAIN OUTCOMES AND MEASURES The primary outcome measure was reduction in hospitalizations due to RSV infections. The secondary measures were cost (number of palivizumab doses) and duration of protection (in days). RESULTS The American Academy of Pediatrics–recommended 5-injection regimen is expected to reduce hospitalization risk by a median of 2.7% (range, −2.2% to 6.1%) compared with the conventional regimen based on RSV

  12. Sequential control by speed drive for ac motor

    NASA Astrophysics Data System (ADS)

    Barsoum, Nader

    2012-11-01

    The speed drive for ac motor is widely used in the industrial field to allow direct control for the speed and torque without any feedback from the motor shaft. By using the ABB ACS800 speed drive unit, the speed and torque can be controlled using sequential control method. Sequential control is one of the application control method provided in the ABB ACS800 Drive, where a set of events or action performed in a particular order one after the other to control the speed and torque of the ac motor. It was claimed that sequential control method is using the preset seven constant speeds being provided in ABB ACS800 drive to control the speed and torque in a continuous and sequential manner. The characteristics and features of controlling the speed and torque using sequential control method can be investigated by observing the graphs and curves plotted which are obtained from the practical result. Sequential control can run either in the Direct Torque Control (DTC) or Scalar motor control mode. By using sequential control method, the ABB ACS800 drive can be programmed to run the motor automatically according to the time setting of the seven preset constant speeds. Besides, the intention of this project is to generate a new form of the experimental set up.

  13. Performance analysis of sequential tests in process control

    SciTech Connect

    Hoyer, K.K.

    1994-04-01

    In recent years, a great deal of emphasis has been placed on quality control of industrial processes. In particular, numerous statistical techniques exist which are designed to continually check an industrial process for machine or component failure, thereby determining if the process is under control, or if it is becoming out of control. In this study, the authors consider a very powerful class of quality control techniques known as sequential tests. Sequential tests classify a set of observations in a manner similar to statistical hypothesis tests, but are characterized by a random sample size. Perhaps the best known sequential test is Wald`s sequential probability ratio test. The sequential probability ratio test (SPRT) is a log likelihood ratio based test for simple or composite hypotheses. After taking each observation, the SPRT decides whether to accept the null hypothesis, reject the null hypothesis, or continue sampling. For the purpose of quality control, an SPRT can be conducted repeatedly over time as incoming observations are received. In the following section, the authors reviews the sequential probability ratio test and state some of its properties. In Section 3, they formulate a Markov additive model which allows them to study the sequential probability ratio test under various types of process behavior. Section 4 develops the theoretical results and the methodological approach that allows them to bound the first passage time distributions of their model. Section 5 illustrates their techniques through numerical examples.

  14. Isoniazid or Moxifloxacin in Rifapentine-based Regimens for Experimental Tuberculosis?

    PubMed Central

    Rosenthal, Ian M.; Zhang, Ming; Almeida, Deepak; Grosset, Jacques H.; Nuermberger, Eric L.

    2008-01-01

    Rationale: Recent studies have demonstrated that combined substitutions of rifapentine for rifampin and moxifloxacin for isoniazid in the standard, daily, short-course regimen of rifampin, isoniazid, and pyrazinamide produces stable cure in 12 weeks or less. This study was designed to more precisely evaluate the contribution of moxifloxacin and isoniazid to rifapentine-based regimens. Objectives: We compared bactericidal activity and treatment-shortening potential between regimens consisting of isoniazid or moxifloxacin plus rifapentine and pyrazinamide administered either thrice-weekly or daily. Methods: Using a mouse model of tuberculosis, we assessed bactericidal activity by performing quantitative cultures of lung homogenates over the first 12 weeks of treatment. Relapse rates were assessed after completing 8, 10, and 12 weeks of treatment to determine the duration of treatment necessary for stable cure. Measurements and Main Results: After 4 weeks of treatment, daily and thrice-weekly therapy with rifapentine, moxifloxacin, and pyrazinamide was significantly more active than treatment with rifapentine, isoniazid, and pyrazinamide. By 8 weeks of treatment, all mice receiving the moxifloxacin-containing regimens were lung culture negative, whereas those mice receiving the isoniazid-containing regimens continued to be lung culture positive. However, the duration of treatment necessary to achieve stable cure was 10 weeks for daily regimens and 12 weeks for thrice-weekly regimens, regardless of whether isoniazid or moxifloxacin was used. All mice receiving standard daily therapy with rifampin, isoniazid, and pyrazinamide relapsed after 12 weeks of treatment. Conclusions: These results suggest that regimens consisting of isoniazid or moxifloxacin plus rifapentine and pyrazinamide may dramatically shorten the duration of treatment needed to cure human tuberculosis. PMID:18723432

  15. Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson's Disease.

    PubMed

    Yun, Ji Young; Kim, Young Eun; Yang, Hui-Jun; Kim, Han-Joon; Jeon, Beomseok

    2017-01-01

    This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson's disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson's disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov.

  16. Cost description of chemotherapy regimens for the treatment of metastatic pancreas cancer.

    PubMed

    Goldstein, Daniel A; Krishna, Kavya; Flowers, Christopher R; El-Rayes, Bassel F; Bekaii-Saab, Tanios; Noonan, Anne M

    2016-05-01

    Multiple chemotherapy regimens are available for the treatment of metastatic pancreas cancer (mPCA). Choice of regimen is based on the patient's performance status and toxicity profile of the regimen. The objective of this study was to analyze the costs of first-line regimens to further aid in decision-making and develop a platform upon which to assess value. We calculated the monthly cost for individual standard regimens (gemcitabine, gemcitabine/nab-paclitaxel, gemcitabine/erlotinib and FOLFIRINOX) and the overall treatment cost for a course of therapy based on the median progression-free survival achieved in published studies. In addition to cost of drugs, we included administration costs and costs of toxicities (including growth factor support, blood product transfusion and hospitalization for toxicities). Costs for administration and management of adverse events were based on Medicare reimbursement rates for hospital and physician services. Drug costs were based on Medicare average sale prices (all 2014 US$). The monthly costs for gemcitabine, FOLFIRINOX, gemcitabine/erlotinib and gemcitabine/nab-paclitaxel were $1363, $7234, $8007 and $12,221, respectively. The overall treatment costs for a course of the same regimens based on median PFS were $5043, $46,298, $51,004 and $67,216, respectively. The choice of chemotherapy regimen for mPCA should be based on tolerability and efficacy of the regimen individualized to patient's performance status. Healthcare systems have finite resources; thus, there is increasing emphasis on metrics to define value in health care when outcomes of therapy are similar or produce marked differences in value. These data provide useful financial information to incorporate into the decision-making process.

  17. Dietary regimens of athletes competing at the Delhi 2010 Commonwealth Games.

    PubMed

    Pelly, Fiona E; Burkhart, Sarah J

    2014-02-01

    The aim of this study was to investigate the dietary regimens reported by athletes competing at a major international competition and report whether these were based on nutrient composition, religious beliefs, cultural eating style, food intolerance or avoidance of certain ingredients. A questionnaire was randomly distributed to 351 athletes in the main dining hall of the athletes' village over the three main meal periods during the Delhi 2010 Commonwealth Games (23rd Sept-14th Oct, 2010). The majority (n = 218, 62%) of athletes reported following one or more dietary regimens, with 50% (n = 174) following a diet based on the nutrient composition of the food. Significantly more athletes from weight category and aesthetic sports (28%, p = .005) and from power/sprint sports (41%, p = .004) followed low fat and high protein regimens respectively. Other specialized dietary regimens were followed by 33% of participants, with avoidance of red meat (13%), vegetarian (7%), Halal (6%), and low lactose regimens (5%) reported most frequently. Significantly more athletes from non-Western regions followed a vegetarian diet (p < .001), while more vegetarians reported avoiding additives (p = .013) and wheat (p ≤ .001). A Western style of eating was the most commonly reported cultural regimen (72% of total with 23% from non-Western regions). Those following a Western diet were significantly more likely to report following a regimen based on nutrient composition (p = .02). As a high proportion of athletes from differing countries and sports follow specialized dietary regimens, caterers and organizers should ensure that adequate nutrition support and food items are available at similar events.

  18. Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson's Disease

    PubMed Central

    Kim, Young Eun; Yang, Hui-Jun; Kim, Han-Joon

    2017-01-01

    This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson's disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson's disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov. PMID:28265478

  19. Altering Antimalarial Drug Regimens May Dramatically Enhance and Restore Drug Effectiveness

    PubMed Central

    Hastings, Ian M.

    2015-01-01

    There is considerable concern that malaria parasites are starting to evolve resistance to the current generation of antimalarial drugs, the artemisinin-based combination therapies (ACTs). We use pharmacological modeling to investigate changes in ACT effectiveness likely to occur if current regimens are extended from 3 to 5 days or, alternatively, given twice daily over 3 days. We show that the pharmacology of artemisinins allows both regimen changes to substantially increase the artemisinin killing rate. Malaria patients rarely contain more than 1012 parasites, while the standard dosing regimens allow approximately 1 in 1010 parasites to survive artemisinin treatment. Parasite survival falls dramatically, to around 1 in 1017 parasites if the dose is extended or split; theoretically, this increase in drug killing appears to be more than sufficient to restore failing ACT efficacy. One of the most widely used dosing regimens, artemether-lumefantrine, already successfully employs a twice-daily dosing regimen, and we argue that twice-daily dosing should be incorporated into all ACT regimen design considerations as a simple and effective way of ensuring the continued long-term effectiveness of ACTs. PMID:26239993

  20. Interferon-free regimens in patients with hepatitis C infection and renal dysfunction or kidney transplantation

    PubMed Central

    Cholongitas, Evangelos; Pipili, Chrysoula; Papatheodoridis, George V

    2017-01-01

    Treatment of patients with chronic kidney disease (CKD) and chronic hepatitis C (CHC) differs from that used in the general CHC population mostly when glomerular filtration rate (GFR) is below 30 mL/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile. In this setting, especially in the presence of advanced liver disease, sofosbuvir-based regimens are often used, despite sofosbuvir contraindication. It seems to have good overall safety with only 6% or 3.4% of CKD patients to discontinue therapy or develop serious adverse events without drug discontinuation. In addition, sustained virological response (SVR) rates with sofosbuvir based regimens in CKD patients appear to be comparable with SVR rates in patients with normal renal function. Treatment recommendations for kidney transplant recipients are the same with those for patients with CHC, taking into consideration potential drug-drug interactions and baseline GFR before treatment initiation. This review summarizes recent data on the current management of CHC in CKD patients highlighting their strengths and weaknesses and determining their usefulness in clinical practice. PMID:28217256

  1. Thalidomide-based induction regimens are as effective as bortezomib-based regimens in elderly patients with multiple myeloma with cereblon expression.

    PubMed

    Jung, Sung-Hoon; Choi, Hyun-Jung; Shin, Myung-Geun; Lee, Seung-Shin; Hwang, Eu Chang; Jung, Tae-Young; Cho, Min-Seok; Yang, Deok-Hwan; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Kim, Hyeoung-Joon; Lee, Je-Jung

    2016-10-01

    Cereblon (CRBN) has been identified as a primary target of immunomodulatory drugs and is considered a biomarker for the prediction of outcomes after thalidomide- or lenalidomide-based treatments. In this study, we evaluated CRBN expression in bone marrow (BM) tissue at diagnosis and investigated the relationship between CRBN expression and treatment outcomes after thalidomide- or bortezomib-based front-line therapies in 89 elderly patients with multiple myeloma (MM). CRBN expression at the time of diagnosis was evaluated with immunohistochemical (IHC) staining for myeloma cells in paraffin wax-embedded BM tissue. CRBN-immunostained slides were scored by intensity and diffuseness, and a total score of >6 was defined as CRBN-positive (CRBN(+)). Thirty-eight patients (45.2 %) were CRBN(+). Among patients treated with thalidomide-based regimens, CRBN(+) patients showed a better treatment response than did CRBN-negative patients (35.0 vs. 11.8 % complete response rate, respectively; HR = 4.038, P = 0.137). During a median follow-up of 31.8 months, patients treated with bortezomib-based regimens had a longer time to progression (TTP) than did patients treated with thalidomide-based regimens (15.6 vs. 13.2 months, respectively; P = 0.047), but early mortality occurred frequently in patients treated with bortezomib-based regimens. Additionally, there was no significant difference in survival outcomes between thalidomide- and bortezomib-based regimens in CRBN(+) patients (median TTP, 13.8 vs. 15.6 months, respectively; P = 0.842 and median OS, 39.3 vs. 30.1 months, respectively; P = 0.074). These data suggest that thalidomide-based regimens are as effective as bortezomib-based regimens in elderly patients with MM who are CRBN(+). Thus, CRBN positivity, by IHC staining, may be useful in deciding appropriate treatment options in elderly patients with MM.

  2. Post-treatment sequential ultrasound imaging of follicular cyst in a crossbred dairy cow.

    PubMed

    Khan, F A; Khan, Muqtaza Manzoor; Prasad, Shiv

    2015-03-01

    Several studies in dairy cattle have investigated the final outcome of different treatment regimens in follicular cyst condition. However, sequential monitoring of the response of follicular cysts to these treatments is rather scanty. In this paper, we present the response of a large follicular cyst in a pluriparous crossbred dairy cow with prolonged conception failure to human chorionic gonadotropin, hCG (3,000 IU; day 0) and cloprostenol (500 μg; day 9) treatment. Using transrectal ultrasonography (USG), reproductive tract was imaged daily beginning day 0 until day 11. The follicular cyst showed a consistent regression to a very small anechoic area on day 7 and was undetectable thereafter. Concurrently, there was development of a new dominant follicle that was first detected on day 4 and showed progressive growth to preovulatory stage. The cow was inseminated and ovulation occurred, as diagnosed by the presence of a corpus luteum (CL) 7 days later, but conception did not occur. The animal was re-inseminated after estrus detection in the estrous cycle that immediately followed. Pregnancy diagnosis was performed on 30 and 60 days post-insemination (DPI) and the cow was confirmed to be pregnant. This paper underscores the importance of diagnostic ultrasound in veterinary medicine, especially in the management of reproductive problems.

  3. Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice.

    PubMed

    Escolano, Amelia; Steichen, Jon M; Dosenovic, Pia; Kulp, Daniel W; Golijanin, Jovana; Sok, Devin; Freund, Natalia T; Gitlin, Alexander D; Oliveira, Thiago; Araki, Tatsuya; Lowe, Sarina; Chen, Spencer T; Heinemann, Jennifer; Yao, Kai-Hui; Georgeson, Erik; Saye-Francisco, Karen L; Gazumyan, Anna; Adachi, Yumiko; Kubitz, Michael; Burton, Dennis R; Schief, William R; Nussenzweig, Michel C

    2016-09-08

    A vaccine that elicits broadly neutralizing antibodies (bNAbs) against HIV-1 is likely to be protective, but this has not been achieved. To explore immunization regimens that might elicit bNAbs, we produced and immunized mice expressing the predicted germline PGT121, a bNAb specific for the V3-loop and surrounding glycans on the HIV-1 spike. Priming with an epitope-modified immunogen designed to activate germline antibody-expressing B cells, followed by ELISA-guided boosting with a sequence of directional immunogens, native-like trimers with decreasing epitope modification, elicited heterologous tier-2-neutralizing responses. In contrast, repeated immunization with the priming immunogen did not. Antibody cloning confirmed elicitation of high levels of somatic mutation and tier-2-neutralizing antibodies resembling the authentic human bNAb. Our data establish that sequential immunization with specifically designed immunogens can induce high levels of somatic mutation and shepherd antibody maturation to produce bNAbs from their inferred germline precursors.

  4. Sequential multiple assignment randomized trial (SMART) with adaptive randomization for quality improvement in depression treatment program.

    PubMed

    Cheung, Ying Kuen; Chakraborty, Bibhas; Davidson, Karina W

    2015-06-01

    Implementation study is an important tool for deploying state-of-the-art treatments from clinical efficacy studies into a treatment program, with the dual goals of learning about effectiveness of the treatments and improving the quality of care for patients enrolled into the program. In this article, we deal with the design of a treatment program of dynamic treatment regimens (DTRs) for patients with depression post-acute coronary syndrome. We introduce a novel adaptive randomization scheme for a sequential multiple assignment randomized trial of DTRs. Our approach adapts the randomization probabilities to favor treatment sequences having comparatively superior Q-functions used in Q-learning. The proposed approach addresses three main concerns of an implementation study: it allows incorporation of historical data or opinions, it includes randomization for learning purposes, and it aims to improve care via adaptation throughout the program. We demonstrate how to apply our method to design a depression treatment program using data from a previous study. By simulation, we illustrate that the inputs from historical data are important for the program performance measured by the expected outcomes of the enrollees, but also show that the adaptive randomization scheme is able to compensate poorly specified historical inputs by improving patient outcomes within a reasonable horizon. The simulation results also confirm that the proposed design allows efficient learning of the treatments by alleviating the curse of dimensionality.

  5. Sequential UV-biological degradation of chlorophenols.

    PubMed

    Tamer, Essam; Hamid, Zilouei; Aly, Amin Magdy; Ossama, El Tayeb; Bo, Mattiasson; Benoit, Guieysse

    2006-04-01

    The sequential UV-biological degradation of a mixture of 4-chlorophenol (CP), 2,4-dichlorophenol (DCP), 2,4,6-trichlorophenol (TCP), and pentachlorophenol (PCP) was first tested with each pollutant supplied at an initial concentration of 50 mg l(-1). Under these conditions, the chlorophenols were photodegraded in the following order of removal rate: PCP>TCP>DCP>CP with only CP and DCP remaining after 40 h of irradiation. The remaining CP (41 mg l(-1)) and DCP (13 mg l(-1)) were then completely removed by biological treatment with an activated sludge mixed culture. Biodegradation did not occur in similar tests conducted with a non-irradiated mixture due to the high microbial toxicity of the solution. UV treatment lead to a significant reduction of the phytotoxicity to Lipedium sativum but no further reduction of phytotoxicity was observed after biological treatment. Evidence was found that the pollutants were partially photodegraded into toxic and non-biodegradable products. When the pollutants were tested individually (initial concentration of 50 mg l(-1)), PCP, TCP, DCP, 4-CP were photodegraded according to first order kinetic model (r2>99) with half-lives of 2.2, 3.3, 5.7, and 54 h, respectively. The photoproducts were subsequently biodegraded. This study illustrates the potential of UV as pre-treatment for biological treatment in order to remove toxicity and enhance the biodegradability of organic contaminants. However, it also shows that UV treatment must be carefully optimized to avoid the formation of toxic and/or recalcitrant photoproducts and results from studies conducted on single contaminants cannot be extrapolated to mixtures.

  6. Sequential Hybrid Procedure for Persistent Atrial Fibrillation

    PubMed Central

    Bulava, Alan; Mokracek, Ales; Hanis, Jiri; Kurfirst, Vojtech; Eisenberger, Martin; Pesl, Ladislav

    2015-01-01

    Background Catheter ablation of persistent atrial fibrillation yields an unsatisfactorily high number of failures. The hybrid approach has recently emerged as a technique that overcomes the limitations of both surgical and catheter procedures alone. Methods and Results We investigated the sequential (staged) hybrid method, which consists of a surgical thoracoscopic radiofrequency ablation procedure followed by radiofrequency catheter ablation 6 to 8 weeks later using the CARTO 3 mapping system. Fifty consecutive patients (mean age 62±7 years, 32 males) with long‐standing persistent atrial fibrillation (41±34 months) and a dilated left atrium (>45 mm) were included and prospectively followed in an unblinded registry. During the electrophysiological part of the study, all 4 pulmonary veins were found to be isolated in 36 (72%) patients and a complete box‐lesion was confirmed in 14 (28%) patients. All gaps were successfully re‐ablated. Twelve months after the completed hybrid ablation, 47 patients (94%) were in normal sinus rhythm (4 patients with paroxysmal atrial fibrillation required propafenone and 1 patient underwent a redo catheter procedure). The majority of arrhythmias recurred during the first 3 months. Beyond 12 months, there were no arrhythmia recurrences detected. The surgical part of the procedure was complicated by 7 (13.7%) major complications, while no serious adverse events were recorded during the radiofrequency catheter part of the procedure. Conclusions The staged hybrid epicardial–endocardial treatment of long‐standing persistent atrial fibrillation seems to be extremely effective in maintenance of normal sinus rhythm compared to radiofrequency catheter or surgical ablation alone. Epicardial ablation alone cannot guarantee durable transmural lesions. Clinical Trial Registration URL: www.ablace.cz Unique identifier: cz‐060520121617 PMID:25809548

  7. “Shotgun” Versus Sequential Testing

    PubMed Central

    Carr, Phyllis L; Rothberg, Michael B; Friedman, Robert H; Felsenstein, Donna; Pliskin, Joseph S

    2005-01-01

    Background Although vaginitis is a common outpatient problem, only 60% of patients can be diagnosed at the initial office visit of a primary care provider using the office procedures of pH testing, whiff tests, normal saline, and potassium hydroxide preps. Objective To determine the most cost-effective diagnostic and treatment approach for the medical management of vaginitis. Design Decision and cost-effectiveness analyses. Participants Healthy women with symptoms of vaginitis undiagnosed after an initial pelvic exam, wet mount preparations, pH, and the four criteria to diagnose bacterial vaginosis. Setting General office practice. Methods We evaluated 28 diagnostic strategies comprised of combinations of pH testing, vaginal cultures for yeast and Trichomonas vaginalis, Gram's stain for bacterial vaginosis, and DNA probes for Neisseria gonorrhoeae and Chlamydia. Data sources for the study were confined to English language literature. Measurement The outcome measures were symptom-days and costs. Results The least expensive strategy was to perform yeast culture, gonorrhoeae and Chlamydia probes at the initial visit, and Gram's stain and Trichomonas culture only when the vaginal pH exceeded 4.9 ($330, 7.30 symptom days). Other strategies cost $8 to $76 more and increased duration of symptoms by up to 1.3 days. In probabilistic sensitivity analysis, this strategy was always the most effective strategy and was also least expensive 58% of the time. Conclusions For patients with vaginitis symptoms undiagnosed by pelvic examination, wet mount preparations and related office tests, a comprehensive, pH-guided testing strategy at the initial office visit is less expensive and more effective than ordering tests sequentially. PMID:16117745

  8. Large-scale sequential quadratic programming algorithms

    SciTech Connect

    Eldersveld, S.K.

    1992-09-01

    The problem addressed is the general nonlinear programming problem: finding a local minimizer for a nonlinear function subject to a mixture of nonlinear equality and inequality constraints. The methods studied are in the class of sequential quadratic programming (SQP) algorithms, which have previously proved successful for problems of moderate size. Our goal is to devise an SQP algorithm that is applicable to large-scale optimization problems, using sparse data structures and storing less curvature information but maintaining the property of superlinear convergence. The main features are: 1. The use of a quasi-Newton approximation to the reduced Hessian of the Lagrangian function. Only an estimate of the reduced Hessian matrix is required by our algorithm. The impact of not having available the full Hessian approximation is studied and alternative estimates are constructed. 2. The use of a transformation matrix Q. This allows the QP gradient to be computed easily when only the reduced Hessian approximation is maintained. 3. The use of a reduced-gradient form of the basis for the null space of the working set. This choice of basis is more practical than an orthogonal null-space basis for large-scale problems. The continuity condition for this choice is proven. 4. The use of incomplete solutions of quadratic programming subproblems. Certain iterates generated by an active-set method for the QP subproblem are used in place of the QP minimizer to define the search direction for the nonlinear problem. An implementation of the new algorithm has been obtained by modifying the code MINOS. Results and comparisons with MINOS and NPSOL are given for the new algorithm on a set of 92 test problems.

  9. On sequential dynamical systems and simulation

    SciTech Connect

    Barrett, C.L.; Mortveit, H.S.; Reidys, C.M.

    1999-06-01

    The generic structure of computer simulations motivates a new class of discrete dynamical systems that captures this structure in a mathematically precise way. This class of systems consists of (1) a loopfree graph {Upsilon} with vertex set {l_brace}1,2,{hor_ellipsis},n{r_brace} where each vertex has a binary state, (2) a vertex labeled set of functions (F{sub i,{Upsilon}}:F{sub 2}{sup n} {r_arrow} F{sub 2}{sup n}){sub i} and (3) a permutation {pi} {element_of} S{sub n}. The function F{sub i,{Upsilon}} updates the state of vertex i as a function of the states of vertex i and its {Upsilon}-neighbors and leaves the states of all other vertices fixed. The permutation {pi} represents the update ordering, i.e., the order in which the functions F{sub i,{Upsilon}} are applied. By composing the functions F{sub i,{Upsilon}} in the order given by {pi} one obtains the dynamical system (equation given in paper) which the authors refer to as a sequential dynamical system, or SDS for short. The authors will present bounds for the number of functionally different systems and for the number of nonisomorphic digraphs {Gamma}[F{sub {Upsilon}},{pi}] that can be obtained by varying the update order and applications of these to specific graphs and graph classes. This will be done using both combinatorial/algebraic techniques and probabilistic techniques. Finally the authors give results on dynamical system properties for some special systems.

  10. Comparative Impact of Suppressive Antiretroviral Regimens on the CD4/CD8 T-Cell Ratio

    PubMed Central

    Masiá, Mar; Padilla, Sergio; Barber, Xavier; Sanchis, Marina; Terol, Gertrudis; Lidón, Fernando; Gutiérrez, Félix

    2016-01-01

    Abstract Although different factors have been implicated in the CD4/CD8 T-cell ratio recovery in HIV-infected patients who receive effective antiretroviral therapy (ART), limited information exists on the influence of the regimen composition. A longitudinal study carried out in a prospective, single-center cohort of HIV-infected patients. ART regimens including non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), or integrase strand transfer inhibitors (INSTI) from patients who achieved long-term (≥6-month duration) virological suppression (HIV-RNA < 400 copies/mL) from January 1998 to June 2014 were analyzed. The impact of ART composition on the changes of the CD4/CD8 T-cell ratio was modeled using a mixed linear approach with adjustment for possible confounders. A total of 1068 ART regimens from 570 patients were analyzed. Mean (SD) age of the patients was 42.15 (10.68) years and 276 (48.42%) had hepatitis C virus (HCV) coinfection. Five hundred fifty-eight (52.25%) regimens were PI-based, 439 (40.10%) NNRTI-based, and 71 (6.65%) INSTI-based; 487 (45.60%) were initial regimens, 476 (44.57%) simplification, and 105 (9.83%) salvage regimens. Median (IQR) number of regimens was 1 (1–2) per patient, of 29 (14–58) months duration, and 4 (3–7) CD4/CD8 measurements per regimen. The median baseline CD4/CD8 ratio was 0.42, 0.50, and 0.54, respectively, with the PI-, NNRTI-, and INSTI-based regimens (P = 0.0073). Overall median (IQR) increase of CD4/CD8 ratio was 0.0245 (−0.0352–0.0690) per year, and a CD4/CD8 ratio ≥1 was achieved in 19.35% of the cases with PI-based, 25.97% with NNRTI-based, and 22.54% with INSTI-based regimens (P = 0.1406). In the adjusted model, the mean CD4/CD8 T-cell ratio increase was higher with NNRTI-based regimens compared for PI-based (estimated coefficient for PI [95% CI], −0.0912 [−0.1604 to −0.0219], P = 0.009). Also, a higher CD4/CD8 baseline ratio was associated with higher

  11. [Clinical curative efficacy of inducing remission for the newly diagnosed aged AML patients by chemotherapy with IA and DA regimens].

    PubMed

    Tian, Dong-Hua; Gan, Si-Lin; Xing, Hai-Zhou; Liu, Yan-Fang; Xie, Xin-Sheng; Sun, Hui

    2014-10-01

    This study was aimed to explore the clinical efficacy and toxicity of idarubicin (IA regimen) and daunoru-bicin combined with cytarabine (DA regimen) for treating aged patients with AML as induction chemotherapy. The clinical data of 60 newly diagnosed AML aged patients treated with IA or DA regimen were analyzed retrospectively. IA regimen group included 22 patients (8 male and 14 females with median age of 66 yrs), while the DA regimen group included 38 patients (20 males and 18 females with median age of 64 yrs). The complete remission rate, total effective rate and adverse effects after one chemotherapy course were compared. The results showed that the CR rate in IA regimen group was 63.63%, which was significantly higer than that in DA regimen group (31.58%) (P < 0.05). The total effective rate was 63.63% and 36.84% respectively in IA and DA regimen groups, there was significant difference between the two groups (P < 0.05). Both the hematological and non-hematological adverse effects were observed and no difference was found in the two regimen groups, neither in myelosupression (P > 0.05), the major hematological adverse effects, nor in non-hematological adverse effects (P > 0.05). It is concluded that for aged AML patients, IA regimen can achieve a higher CR rate and higher total effective rate than that in DA regimen without increase of adverse effects after one induction chemotherapy course.

  12. Short duration, high dose, alternating chemotherapy in metastatic neuroblastoma. (ENSG 3C induction regimen). The European Neuroblastoma Study Group.

    PubMed Central

    Pinkerton, C. R.; Zucker, J. M.; Hartmann, O.; Pritchard, J.; Broadbent, V.; Morris-Jones, P.; Breatnach, F.; Craft, A. E.; Pearson, A. D.; Wallendszus, K. R.

    1990-01-01

    Fifty-one children, aged from 15 months to 13 years 5 months with metastatic neuroblastoma presenting sequentially at the participating institutions received four 3 to 4 weekly courses of high dose multiagent chemotherapy. High dose cisplatin (200 mg m-2) combined with etoposide (500 mg m-2), HIPE, was alternated with ifosfamide (9 g m-2), vincristine (1.5 mg m-2), and adriamycin (60 mg m-1), IVAd. Disease status was re-evaluated 3 to 4 weeks after the fourth course and the response classified according to the International Neuroblastoma Response Criteria (INRC). The overall response rate in evaluable patients was 55% and response rates by site were: bone marrow 67% (complete response 47%); bone scan 68%; primary tumour 61%, and urinary catecholamine metabolites (VMA/HVA) 95%. Serial 51Cr EDTA renal clearance studies showed a glomerular filtration rate (GFR) decline in 40% of patients but in only seven cases to below 50% of the pretreatment value. There was no instance of renal failure during induction, though two patients developed severe renal failure following 'megatherapy' given to consolidate remission. Serial audiometry showed a significant decline in hearing at frequencies above 2,000 Hz in 37% of children but at or below 2,000 Hz in only 17%. Neutropenia and thrombocytopenia were severe and intravenous antibiotics were required after 30% of courses. Each of two treatment-related deaths occurred during pancytopenia following courses of IVAd. Complete, or greater than 90%, removal of primary site tumour was possible in 70% of cases following this induction regimen and 75% of patients proceeded to elective megatherapy within a median time of 24 weeks after diagnosis. This short intensive induction programme is highly effective at achieving cytoreduction, enabling early surgery and early megatherapy procedures. It is, however, too early to draw firm conclusions about the impact of this approach to treatment on the cure rate. PMID:2386751

  13. Improvement in morning hyperglycaemia with basal human ultratard and prandial human actrapid insulin--a comparison of multiple injection regimens.

    PubMed

    Davies, R R; McEwen, J; Moreland, T A; Durnin, C; Newton, R W

    1988-10-01

    Three 'pen'-administered multiple injection regimens have been compared with twice daily insulin injection regimens by means of 24-h profiles of plasma glucose and free insulin concentrations. Ten Type 1 diabetic patients received their usual twice daily insulin regimen and were then randomized to receive the same total daily insulin dose in four divided doses using (1) 50:50 premixed soluble and isophane, (2) 30:70 premixed soluble and isophane, and (3) preprandial soluble and evening crystalline-zinc insulins. Profiles were performed after 1 week on each regimen. Plasma glucose concentrations were similar during the twice daily regimen and the two premixed regimens, rising during the early hours of the morning to a peak between 0900 and 0930 h of 13.8 +/- 2.8 (+/- SD) mmol l-1 on the twice daily regimen, 13.6 +/- 5.3 mmol l-1 on the premixed 50:50 regimen, and 13.5 +/- 4.2 mmol-1 on the premixed 30:70 regimen. With the basal and prandial regimen, overnight plasma glucose concentrations were higher than with the other regimens between 2400 and 0300 h (p less than 0.05). Concentrations then fell until breakfast, and rose after this meal to a peak of 9.5 +/- 4.3 mmol l-1 (p less than 0.01). Mean plasma glucose concentrations were significantly lower than on the other three regimens between 0830 and 1100 h (p less than 0.05). Less variability was observed in 24-h mean plasma glucose concentrations during the basal and prandial regimen than during the other three regimens.

  14. Optimizing Standard Sequential Extraction Protocol With Lake And Ocean Sediments

    EPA Science Inventory

    The environmental mobility/availability behavior of radionuclides in soils and sediments depends on their speciation. Experiments have been carried out to develop a simple but robust radionuclide sequential extraction method for identification of radionuclide partitioning in sed...

  15. Age-related differences in arithmetic strategy sequential effects.

    PubMed

    Lemaire, Patrick

    2016-03-01

    In this article, I review a series of new findings concerning how age-related changes in strategic variations are modulated by sequential effects. Sequential effects refer to how strategy selection and strategy execution on current problems are influenced by which strategy is used on immediately preceding problems. Two sequential effects during strategy selection (i.e., strategy revisions and strategy perseverations) and during strategy execution (i.e., strategy switch costs and modulations of poorer strategy effects) are presented. I also discuss how these effects change with age during adulthood. These phenomena are important, as they shed light on arithmetic processes and how these processes change with age during adulthood. In particular, they speak to the role of executive control while participants select and execute arithmetic strategies. Finally, I discuss the implications of sequential effects for theories of strategies and of arithmetic.

  16. Ligand Binding to Macromolecules: Allosteric and Sequential Models of Cooperativity.

    ERIC Educational Resources Information Center

    Hess, V. L.; Szabo, Attila

    1979-01-01

    A simple model is described for the binding of ligands to macromolecules. The model is applied to the cooperative binding by hemoglobin and aspartate transcarbamylase. The sequential and allosteric models of cooperative binding are considered. (BB)

  17. Asynchronous sequential circuit design using pass transistor iterative logic arrays

    NASA Technical Reports Server (NTRS)

    Liu, M. N.; Maki, G. K.; Whitaker, S. R.

    1991-01-01

    The iterative logic array (ILA) is introduced as a new architecture for asynchronous sequential circuits. This is the first ILA architecture for sequential circuits reported in the literature. The ILA architecture produces a very regular circuit structure. Moreover, it is immune to both 1-1 and 0-0 crossovers and is free of hazards. This paper also presents a new critical race free STT state assignment which produces a simple form of design equations that greatly simplifies the ILA realizations.

  18. Sequential unilateral lung volume reduction for emphysema - Stretching the benefit.

    PubMed

    Khorramnia, Sadie; Holsworth, Lynda; Mestitz, Hugh; Westall, Glen P; Williams, Trevor J; Gooi, Julian H; Snell, Gregory I

    2017-01-01

    Bronchoscopic Lung Volume Reduction (BLVR) and Surgical Lung Volume Reduction (SLVR) and are two different approaches used to remodel severely emphysematous lungs to improve lung function and quality-of-life. We present a case initially referred for lung transplantation, where sequential left upper lobe BLVR and 7 years later right upper lobe SLVR, providing enduring physiological and functional improvement. The potential for sustained benefit via sequential unilateral lung volume reduction is under-appreciated.

  19. Effects of preset sequential administrations of sunitinib and everolimus on tumour differentiation in Caki-1 renal cell carcinoma

    PubMed Central

    Santos, C D; Tijeras-Raballand, A; Serova, M; Sebbagh, S; Slimane, K; Faivre, S; de Gramont, A; Raymond, E

    2015-01-01

    Background: Sunitinib (VEGFR/PDGFR inhibitor) and everolimus (mTOR inhibitor) are both approved for advanced renal cell carcinoma (RCC) as first-line and second-line therapy, respectively. In the clinics, sunitinib treatment is limited by the emergence of acquired resistance, leading to a switch to second-line treatment at progression, often based on everolimus. No data have been yet generated on programmed alternating sequential strategies combining alternative use of sunitinib and everolimus before progression. Such strategy is expected to delay the emergence of acquired resistance and improve tumour control. The aim of our study was to assess the changes in tumours induced by three different sequences administration of sunitinib and everolimus. Methods: In human Caki-1 RCC xenograft model, sunitinib was alternated with everolimus every week, every 2 weeks, or every 3 weeks. Effects on necrosis, hypoxia, angiogenesis, and EMT status were assessed by immunohisochemistry and immunofluorescence. Results: Sunitinib and everolimus programmed sequential regimens before progression yielded longer median time to tumour progression than sunitinib and everolimus monotherapies. In each group of treatment, tumour growth control was associated with inhibition of mTOR pathway and changes from a mesenchymal towards an epithelial phenotype, with a decrease in vimentin and an increase in E-cadherin expression. The sequential combinations of these two agents in a RCC mouse clinical trial induced antiangiogenic effects, leading to tumour necrosis. Conclusions: In summary, our study showed that alternate sequence of sunitinib and everolimus mitigated the development of mesenchymal phenotype compared with sunitinib as single agent. PMID:25422908

  20. Bioavailability of the Yuzpe and levonorgestrel regimens of emergency contraception: vaginal vs. oral administration.

    PubMed

    Kives, Sari; Hahn, Philip M; White, Emily; Stanczyk, Frank Z; Reid, Robert L

    2005-03-01

    Separate crossover studies compared the bioavailability of oral vs. vaginal routes of administration for the Yuzpe (n=5) and levonorgestrel regimens (n=4) of emergency contraception. Twice the standard dose of the Yuzpe regimen (200 microg of ethinyl estradiol, 1000 microg of levonorgestrel) or the levonorgestrel regimen (1500 microg of levonorgestrel) was self-administered vaginally. One week later, each subject received orally the standard dose of the assigned medication. Serial blood samples were collected over 24 h and assayed for levonorgestrel and ethinyl estradiol (for the Yuzpe regimen only). Paired t tests were used to compare oral vs. vaginal administration for maximum concentration (Cmax), time to maximum concentration (Tmax) and area under the curve over 24 h (AUC0-24). Relative bioavailability (vaginal/oral) was derived from AUC0-24. Vaginal administration of double the standard dose of the Yuzpe regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=14.6 ng/mL, p=.038) and a later Tmax (5.9 vs. 2.0 h, p=.066) for levonorgestrel, compared to oral administration. Corresponding ethinyl estradiol concentrations were higher (786 vs. 391 pg/mL, p=.039) and peaked later (4.0 vs. 1.9 hr, p=.154) with vaginal administration. Relative bioavailabilities for levonorgestrel and ethinyl estradiol were 58% and 175%, respectively. Similarly, vaginal administration of the levonorgestrel regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=15.2 ng/mL, p=.006) and a later Tmax (7.4 vs. 1.3 h, p=.037) for levonorgestel, compared to oral administration. The relative bioavailability was 62%. Our preliminary data suggest that vaginal administration of these emergency contraception regimens appears to require at least three times the standard oral dose to achieve equivalent systemic levonorgestrel concentrations.

  1. Sterilizing Activity of Fully Oral Intermittent Regimens against Mycobacterium Ulcerans Infection in Mice

    PubMed Central

    Robert, Jérôme; Veziris, Nicolas; Aubry, Alexandra; Jarlier, Vincent

    2016-01-01

    Background The treatment of Buruli ulcer (BU) that is caused by Mycobacterium ulcerans, is currently based on a daily administration of rifampin and streptomycin (RIF-STR). A fully oral intermittent regimen would greatly simplify its treatment on the field. Methodology/Principal findings The objective of this study was to assess the bactericidal and sterilizing activities of intermittent oral regimens in a murine model of established M. ulcerans infection. Regimens combining rifapentine (RFP 20 mg/kg) with either moxifloxacin (MXF 200 mg/kg), clarithromycin (CLR 100 mg/kg) or bedaquiline (BDQ 25 mg/kg) were administrated twice (2/7) or three (only for RFP-CLR 3/7) times weekly during 8 weeks. The bactericidal but also the sterilizing activities of these four intermittent oral regimens were at least as good as those obtained with control weekdays regimens, i.e. RFP-CLR 5/7 or RIF-STR 5/7. A single mouse from the RFP-MFX 2/7 group had culture-positive relapse at the end of the 28 weeks following treatment completion among the 157 mice treated with one of the four intermittent regimens (40 RFP-CLR 2/7, 39 RFP-CLR 3/7, 39 RFP-MXF 2/7, 39 RFP-BDQ 2/7). Conclusions/Significance These results open the door for a fully intermittent oral drug regimen for BU treatment avoiding intramuscular injections and facilitating supervision by health care workers. PMID:27755552

  2. Effect of light/dark regimen on N-nitrosoethylurea-induced transplacental carcinogenesis in rats.

    PubMed

    Beniashvili, D S; Benjamin, S; Baturin, D A; Anisimov, V N

    2001-02-10

    Pregnant females were randomly subdivided into three groups (24 rats per group) and kept at the 12:12 h light/dark regimen (group 1), at the constant light illumination (24 h a day, group 2) or at the continuous darkness (group 3). N-nitrosoethylurea (NEU) has been injected into the tail vein of all rats (80 mg/kg) on the 18-19th day of the pregnancy. After the delivery the lacting dams and their progeny during the lactation period (1 month after delivery) were kept also at the three different light/dark regimens. Then all offspring from each group was kept at the 12:12 h light/dark regimen, males and females separately, and were observed until natural death. The exposure to constant light significantly promoted the transplacental carcinogenesis whereas the exposure to constant darkness inhibited it. The incidence of total tumors, tumors of both a peripheral nervous system and kidney was 2.6; 2.5 and 8.5 times higher, and survival significantly shorter, correspondingly, in rats from the group 2 exposed to the constant light regimen as compared to the group 1 (12:12 h light/dark regimen) (P<0.05). On the other hand, the exposure to the continuous darkness during the pregnancy and the lactation period significantly inhibited the transplacental carcinogenesis in the offspring of rats treated with NEU. The incidence of total tumors, tumors of a peripheral nervous system was by 2.4 and 2.7 times less, and survival longer, respectively, in exposed to the darkness rats from the group 3 as compared to the group 1 (12:12 h light/dark regimen) (P<0.05). Thus, our data firstly have shown the modifying effect of light-dark regimen on the realization of the transplacental carcinogenesis induced by NEU in rats.

  3. Effects of different temperature regimens on the development of Aedes aegypti (L.) (Diptera: Culicidae) mosquitoes.

    PubMed

    Mohammed, Azad; Chadee, Dave D

    2011-07-01

    This study was conducted to determine the effects of increased water temperatures on the development of Aedes aegypti immatures under laboratory conditions in Trinidad, West Indies using temperature regulated water baths to cover a range of temperatures from 24-25°C to 34-35°C at a relative humidity of 80%. Two experiments were designed: (1) at constant temperature regimens and (2) under diurnal temperature regimens ranging from 24-25°C to 34-35°C. At 24-25°C egg hatching success was 98% at 48 h, however at 34-35°C egg hatching rates declined to 1.6% after 48 h. Ae. aegypti larvae reared under constant temperature regimens showed pupation on day 4 with highest pupation occurring at 30°C (78.4%) However, under diurnal temperature regimens, pupation began on day 4 but only at the higher temperatures of 30-35°C. Under diurnal temperature regimens ranging from 24°C to 35°C significantly more females emerged at higher temperatures, than males. In contrast, at constant temperatures of 24-35°C no significant difference in M/F ratios were observed. The body size of Ae. aegypti reared at constant temperature regimens was significantly larger than males and females larvae reared under diurnal temperature regimens of 25-30°C. The results of this study are discussed in the context of changing or increasing water temperatures, seasonal changes in vector populations and vector competence. Using these key factors control strategies are recommended to manage vector populations as expected increases in temperatures impact the Caribbean region.

  4. Sequential spatial frequency discrimination is consistently impaired among adult dyslexics.

    PubMed

    Ben-Yehudah, Gal; Ahissar, Merav

    2004-05-01

    The degree and nature of dyslexics' difficulties in performing basic visual tasks have been debated for more than thirty years. We recently found that dyslexics' difficulties in detecting temporally modulated gratings are specific to conditions that require accurate comparisons between sequentially presented stimuli [Brain 124 (2001) 1381]. We now examine dyslexics' spatial frequency discrimination (rather than detection), under simultaneous (spatial forced choice) and sequential (temporal forced choice) presentations. Sequential presentation (at SOAs of 0.5, 0.75 and 2.25 s) yielded better discrimination thresholds among the majority of controls (around 0.5 c/ degrees reference), but not among dyslexics. Consequently, there was a (large and significant) group effect only for the sequential conditions. Within the same dyslexic group, performance on a sequential auditory task, two-tone frequency discrimination, was impaired in a smaller proportion of the participants. Taken together, our findings indicate that visual paradigms requiring sequential comparisons are difficult for the majority of dyslexic individuals, perhaps because deficits either in visual perception or in visual memory could both lead to difficulties on these paradigms.

  5. Robust sequential working memory recall in heterogeneous cognitive networks

    PubMed Central

    Rabinovich, Mikhail I.; Sokolov, Yury; Kozma, Robert

    2014-01-01

    Psychiatric disorders are often caused by partial heterogeneous disinhibition in cognitive networks, controlling sequential and spatial working memory (SWM). Such dynamic connectivity changes suggest that the normal relationship between the neuronal components within the network deteriorates. As a result, competitive network dynamics is qualitatively altered. This dynamics defines the robust recall of the sequential information from memory and, thus, the SWM capacity. To understand pathological and non-pathological bifurcations of the sequential memory dynamics, here we investigate the model of recurrent inhibitory-excitatory networks with heterogeneous inhibition. We consider the ensemble of units with all-to-all inhibitory connections, in which the connection strengths are monotonically distributed at some interval. Based on computer experiments and studying the Lyapunov exponents, we observed and analyzed the new phenomenon—clustered sequential dynamics. The results are interpreted in the context of the winnerless competition principle. Accordingly, clustered sequential dynamics is represented in the phase space of the model by two weakly interacting quasi-attractors. One of them is similar to the sequential heteroclinic chain—the regular image of SWM, while the other is a quasi-chaotic attractor. Coexistence of these quasi-attractors means that the recall of the normal information sequence is intermittently interrupted by episodes with chaotic dynamics. We indicate potential dynamic ways for augmenting damaged working memory and other cognitive functions. PMID:25452717

  6. Sequential unconstrained minimization algorithms for constrained optimization

    NASA Astrophysics Data System (ADS)

    Byrne, Charles

    2008-02-01

    The problem of minimizing a function f(x):RJ → R, subject to constraints on the vector variable x, occurs frequently in inverse problems. Even without constraints, finding a minimizer of f(x) may require iterative methods. We consider here a general class of iterative algorithms that find a solution to the constrained minimization problem as the limit of a sequence of vectors, each solving an unconstrained minimization problem. Our sequential unconstrained minimization algorithm (SUMMA) is an iterative procedure for constrained minimization. At the kth step we minimize the function G_k(x)=f(x)+g_k(x), to obtain xk. The auxiliary functions gk(x):D ⊆ RJ → R+ are nonnegative on the set D, each xk is assumed to lie within D, and the objective is to minimize the continuous function f:RJ → R over x in the set C=\\overline D , the closure of D. We assume that such minimizers exist, and denote one such by \\hat x . We assume that the functions gk(x) satisfy the inequalities 0\\leq g_k(x)\\leq G_{k-1}(x)-G_{k-1}(x^{k-1}), for k = 2, 3, .... Using this assumption, we show that the sequence {f(xk)} is decreasing and converges to f({\\hat x}) . If the restriction of f(x) to D has bounded level sets, which happens if \\hat x is unique and f(x) is closed, proper and convex, then the sequence {xk} is bounded, and f(x^*)=f({\\hat x}) , for any cluster point x*. Therefore, if \\hat x is unique, x^*={\\hat x} and \\{x^k\\}\\rightarrow {\\hat x} . When \\hat x is not unique, convergence can still be obtained, in particular cases. The SUMMA includes, as particular cases, the well-known barrier- and penalty-function methods, the simultaneous multiplicative algebraic reconstruction technique (SMART), the proximal minimization algorithm of Censor and Zenios, the entropic proximal methods of Teboulle, as well as certain cases of gradient descent and the Newton-Raphson method. The proof techniques used for SUMMA can be extended to obtain related results for the induced proximal

  7. Sequential beamforming for synthetic aperture imaging.

    PubMed

    Kortbek, Jacob; Jensen, Jørgen Arendt; Gammelmark, Kim Løkke

    2013-01-01

    Synthetic aperture sequential beamforming (SASB) is a novel technique which allows to implement synthetic aperture beamforming on a system with a restricted complexity, and without storing RF-data. The objective is to improve lateral resolution and obtain a more depth independent resolution compared to conventional ultrasound imaging. SASB is a two-stage procedure using two separate beamformers. The initial step is to construct and store a set of B-mode image lines using a single focal point in both transmit and receive. The focal points are considered virtual sources and virtual receivers making up a virtual array. The second stage applies the focused image lines from the first stage as input data, and take advantage of the virtual array in the delay and sum beamforming. The size of the virtual array is dynamically expanded and the image is dynamically focused in both transmit and receive and a range independent lateral resolution is obtained. The SASB method has been investigated using simulations in Field II and by off-line processing of data acquired with a commercial scanner. The lateral resolution increases with a decreasing F#. Grating lobes appear if F#≤2 for a linear array with λ-pitch. The performance of SASB with the virtual source at 20mm and F#=1.5 is compared with conventional dynamic receive focusing (DRF). The axial resolution is the same for the two methods. For the lateral resolution there is improvement in FWHM of at least a factor of 2 and the improvement at -40dB is at least a factor of 3. With SASB the resolution is almost constant throughout the range. For DRF the FWHM increases almost linearly with range and the resolution at -40dB is fluctuating with range. The theoretical potential improvement in SNR of SASB over DRF has been estimated. An improvement is attained at the entire range, and at a depth of 80mm the improvement is 8dB.

  8. Hand hygiene regimens for the reduction of risk in food service environments.

    PubMed

    Edmonds, Sarah L; McCormack, Robert R; Zhou, Sifang Steve; Macinga, David R; Fricker, Christopher M

    2012-07-01

    Pathogenic strains of Escherichia coli and human norovirus are the main etiologic agents of foodborne illness resulting from inadequate hand hygiene practices by food service workers. This study was conducted to evaluate the antibacterial and antiviral efficacy of various hand hygiene product regimens under different soil conditions representative of those in food service settings and assess the impact of product formulation on this efficacy. On hands contaminated with chicken broth containing E. coli, representing a moderate soil load, a regimen combining an antimicrobial hand washing product with a 70% ethanol advanced formula (EtOH AF) gel achieved a 5.22-log reduction, whereas a nonantimicrobial hand washing product alone achieved a 3.10log reduction. When hands were heavily soiled from handling ground beef containing E. coli, a wash-sanitize regimen with a 0.5% chloroxylenol antimicrobial hand washing product and the 70% EtOH AF gel achieved a 4.60-log reduction, whereas a wash-sanitize regimen with a 62% EtOH foam achieved a 4.11-log reduction. Sanitizing with the 70% EtOH AF gel alone was more effective than hand washing with a nonantimicrobial product for reducing murine norovirus (MNV), a surrogate for human norovirus, with 2.60- and 1.79-log reductions, respectively. When combined with hand washing, the 70% EtOH AF gel produced a 3.19-log reduction against MNV. A regimen using the SaniTwice protocol with the 70% EtOH AF gel produced a 4.04-log reduction against MNV. These data suggest that although the process of hand washing helped to remove pathogens from the hands, use of a wash-sanitize regimen was even more effective for reducing organisms. Use of a high-efficacy sanitizer as part of a wash-sanitize regimen further increased the efficacy of the regimen. The use of a well-formulated alcohol-based hand rub as part of a wash-sanitize regimen should be considered as a means to reduce risk of infection transmission in food service facilities.

  9. Efficacy and toxicity of different concurrent chemoradiotherapy regimens in the treatment of advanced cervical cancer

    PubMed Central

    Fu, Zhan-Zhao; Li, Kun; Peng, Yong; Zheng, Yue; Cao, Li-Yan; Zhang, Yun-Jie; Sun, Yong-Mei

    2017-01-01

    Abstract Objective: The aim of this study was to compare the efficacy and toxicity of different concurrent chemoradiotherapy (CCRT) regimens in the treatment of advanced cervical cancer (CC) by adopting a network meta-analysis. Methods: We searched PubMed and Cochrane Library from the inception of these databases to September 2016, and all cohort studies (CSs) related to different CCRT regimens in the treatment of CC were included. A network analysis was adopted to compare the combination of direct and indirect evidence, to analyze the odds ratio (OR), and to draw a surface under the cumulative ranking curve of the efficacy and toxicity of different CCRT regimens for CC. Cluster analyses were used to group each category based on similar treatment regimens. Results: Nineteen CSs were enrolled in this network meta-analysis, including 12 CCRT regimens (radiotherapy [RT], CCRT [cisplatin], CCRT [vinorelbine], CCRT [paclitaxel], CCRT [hydroxyurea], CCRT [cisplatin + FU], CCRT [cisplatin + gemcitabine], CCRT [cisplatin + docetaxel], CCRT [cisplatin + paclitaxel], CCRT [cisplatin + amifostine], CCRT [cisplatin + FU + hydroxyurea], and CCRT [cisplatin + vincristine + bleomycin]). The results of the network meta-analysis showed that regarding efficacy, the overall response rate of CCRT (cisplatin + docetaxel) was higher than RT, and the 5-year overall survival (OS) rate of CCRT (cisplatin + FU + hydroxyurea) was relatively higher than CCRT (hydroxyurea). As for toxicity, CCRT (cisplatin) had a lower incidence of leukopenia than CCRT (hydroxyurea), CCRT (cisplatin + FU) and CCRT (cisplatin + paclitaxel), and the incidences of diarrhea and vomiting in CCRT (cisplatin) were lower than those in CCRT (cisplatin + gemcitabine). Additionally, the cluster analysis showed that CCRT (cisplatin) had relatively lower incidences of both hematotoxicity and gastrointestinal toxicity, and CCRT (paclitaxel) had lower

  10. Additional Drug Resistance Patterns among Multidrug-Resistant Tuberculosis Patients in Korea: Implications for Regimen Design

    PubMed Central

    2017-01-01

    Detailed information on additional drug resistance patterns of multidrug-resistant tuberculosis (MDR-TB) is essential to build an effective treatment regimen; however, such data are scarce in Korea. We retrospectively analyzed the results of phenotypic drug susceptibility testing (DST) of culture confirmed-TB patients from January 2010 to December 2014 in 7 university hospitals in Korea. MDR-TB was identified among 6.8% (n = 378) of 5,599 isolates. A total of 57.1% (n = 216) of the MDR-TB patients had never been treated for TB. Strains from MDR-TB patients showed additional resistance to pyrazinamide (PZA) (35.7%), any second-line injectable drug (19.3%), and any fluoroquinolone (26.2%). Extensively drug resistant TB comprised 12.4% (n = 47) of the MDR-TB patients. Of 378 MDR-TB patients, 50.3% (n = 190) were eligible for the shorter MDR-TB regimen, and 50.0% (n = 189) were fully susceptible to the 5 drugs comprising the standard conventional regimen (PZA, kanamycin, ofloxoacin, prothionamide, and cycloserine). In conclusion, the proportion of new patients and the levels of additional drug resistance were high in MDR-TB patients. Considering the high levels of drug resistance, the shorter MDR-TB treatment regimen may not be feasible; instead, an individually tailored regimen based on the results of molecular and phenotypic DST may be more appropriate in MDR-TB patients in Korea. PMID:28244290

  11. Potential Economic Viability of Two Proposed Rifapentine-Based Regimens for Treatment of Latent Tuberculosis Infection

    PubMed Central

    Holland, David P.; Sanders, Gillian D.; Hamilton, Carol D.; Stout, Jason E.

    2011-01-01

    Rationale Rifapentine-based regimens for treating latent tuberculosis infection (LTBI) are being considered for future clinical trials, but even if they prove effective, high drug costs may limit their economic viability. Objectives To inform clinical trial design by estimating the potential costs and effectiveness of rifapentine-based regimens for treatment of latent tuberculosis infection (LTBI). Methods We used a Markov model to estimate cost and societal benefits for three regimens for treating LTBI: Isoniazid/rifapentine daily for one month, isoniazid/rifapentine weekly for three months (self-administered and directly-observed), and isoniazid daily for nine months; a strategy of “no treatment” used for comparison. Costs, quality-adjusted life-years gained, and instances of active tuberculosis averted were calculated for all arms. Results Both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months were less expensive and more effective than other strategies under a wide variety of clinically plausibly parameter estimates. Daily isoniazid/rifapentine for one month was the least expensive and most effective regimen. Conclusions Daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months should be studied in a large-scale clinical trial for efficacy. Because both regimens performed well even if their efficacy is somewhat reduced, study designers should consider relaxing non-inferiority boundaries. PMID:21789248

  12. Potent Twice-Weekly Rifapentine-containing Regimens in Murine Tuberculosis

    PubMed Central

    Rosenthal, Ian M.; Williams, Kathy; Tyagi, Sandeep; Peloquin, Charles A.; Vernon, Andrew A.; Bishai, William R.; Grosset, Jacques H.; Nuermberger, Eric L.

    2006-01-01

    Rationale: Recent studies have demonstrated that intermittent administration of rifamycin-based regimens results in higher rates of tuberculosis relapse and treatment failure compared with daily therapy. Twice-weekly treatment with rifampin, isoniazid, and pyrazinamide may be improved by increasing Mycobacterium tuberculosis exposure to rifamycin by substituting rifapentine for rifampin. Methods: To test this hypothesis, we compared the activities of standard daily and twice-weekly rifampin plus isoniazid-based regimens to those of twice-weekly rifapentine plus isoniazid- or moxifloxacin-containing regimens in the murine model of tuberculosis. Relapse rates were assessed after 4, 5, and 6 mo of treatment to assess stable cure. Single- and multiple-dose pharmacokinetics of rifampin and rifapentine were also determined. Results: After 2 mo of treatment, twice-weekly therapy with rifapentine (15 or 20 mg/kg), moxifloxacin, and pyrazinamide was significantly more active than standard daily or twice-weekly therapy with rifampin, isoniazid, and pyrazinamide. Stable cure was achieved after 4 mo of twice-weekly rifapentine plus isoniazid- or moxifloxacin-containing therapy, but only after 6 mo of standard daily therapy. Twice-weekly rifapentine (15 mg/kg) displayed more favorable pharmacodynamics than did daily rifampin (10 mg/kg). Conclusions: By virtue of the enhanced rifamycin exposure, twice-weekly regimens containing rifapentine (15 or 20 mg/kg) may permit shortening the current treatment duration by 2 mo. Such regimens warrant clinical investigation. PMID:16574936

  13. Experimental endocrine manipulation by contraceptive regimen in the male marmoset (Callithrix jacchus).

    PubMed

    Wistuba, Joachim; Luetjens, C Marc; Ehmcke, Jens; Redmann, Klaus; Damm, Oliver S; Steinhoff, Antje; Sandhowe-Klaverkamp, Reinhild; Nieschlag, Eberhard; Simoni, Manuela; Schlatt, Stefan

    2013-04-01

    Marmosets are used as preclinical model in reproductive research. In contrast to other primates, they display short gestation times rendering this species valid for exploration of effects on fertility. However, their peculiar endocrine regulation differs from a those of macaques and humans. We subjected male marmosets to previously clinically tested hormonal regimens that are known to effectively suppress spermatogenesis. Beside a control group, seven groups (each n=6) were investigated for different periods of up to 42 months: regimen I, (four groups) received testosterone undecanoate (TU) and norethisterone enanthate (NETE); regimen II, (two groups) received TU and NETE followed by NETE only; and regimen III, (one group) received NETE only. Testicular volume, cell ploidy and histology, endocrine changes and fertility were monitored weekly. TU and NETE and initial TU and NETE treatment followed by NETE failed to suppress spermatogenesis and fertility. Testicular volumes dropped, although spermatogenesis was only mildly affected; however, testicular cellular composition remained stable. Serum testosterone dropped when NETE was given alone but the animals remained fertile. Compared with controls, no significant changes were observed in sperm motility and fertility. Administration of TU and NETE affected testicular function only mildly, indicating that the regulatory role of chorionic gonadotrophin and testosterone on spermatogenesis is obviously limited and testicular function is maintained, although the endocrine axis is affected by the treatment. In conclusion, marmosets showed a different response to regimens of male contraception from macaques or men and have to be considered as a problematic model for preclinical trials of male hormonal contraception.

  14. Effect of different bleaching regimens on the flexural strength of hybrid composite resin

    PubMed Central

    Feiz, Atiyeh; Samanian, Noushmehr; Davoudi, Amin; Badrian, Hamid

    2016-01-01

    Background: The entire effects of different bleaching regimens on the mechanical properties of composite resins have remained unknown. The purpose of this study was to evaluate the effects of different bleaching regimens on the flexural strength (FS) of hybrid composite resins. Materials and Methods: In this in vitro study, 80 bar-shaped specimens of hybrid composite resins were fabricated and randomly divided into four groups, 20 specimens in each group. First group (C) was considered as control. The other groups were treated by home bleaching (HB) agent, in-office bleaching (IB) agent, and the combination regimens (HIB), respectively. The FS was evaluated by three-point bending test by using a Universal Testing Machine. All data were analyzed by using Statistical Package for the Social Sciences (SPSS) software version 18, analysis of variance (ANOVA), and Turkey's post hoc statistical tests (α = 0.05). Results: The maximum mean value of FS was seen in HB group with significant differences to other groups (P < 0.05). Also, the minimum FS was observed in group HIB. Conclusion: Application of different bleaching regimens does not have any adverse effect on the FS of hybrid composite resins. However, the administration of HB regimens seemed to have lesser negative impact on the FS. PMID:27099423

  15. Cleansing the colon in gallium-67 scintigraphy: a prospective comparison of regimens

    SciTech Connect

    Novetsky, G.J.; Turner, D.A.; Ali, A.; Raynor, W.J. Jr.; Fordham, E.W.

    1981-01-01

    Colonic accumulation of gallium-67 frequently complicates the interpretation of gallium-67 scintigrams. Although various modes of cleansing the colon prior to scintigraphy have been suggested, there is controversy over their efficacy and none have been tested prospectively. Three hundred nine patients undergoing gallium-67 scintigraphy were randomly assigned to one of four cleansing regimens: (1) a high fiber diet (78 patients); (2) castor oil (76); (3) milk of magnesia and cascara (76); and (4) not preparation (79). Patient compliance rates for the four regimens were 17%, 32%, 36%, and 46%, respectively. After noncompliant patients were excluded, gallium-67 scintigrams were graded for colonic activity on a scale of 0-3 by three independent, experienced observers. Gallium-67 activity in the colon was significantly less after administration of castor oil than after no preparation (p . 0.047). A high fiber diet also resulted in a substantial reduction of colonic activity when compared with no preparation; the difference, however, was not statistically significant (p . 0.083). Regimen 3 did not produce significantly better results than regimen 4 (p . 0.42). A major impediment to the success of any cleansing regimen seems to be poor compliance of patients.

  16. Cleansing the colon in gallium-67 scintigraphy: a prospective comparison of regimens

    SciTech Connect

    Novetsky, G.J.; Turner, D.A.; Ali, A.; Raynor, W.J.; Fordham, E.W.

    1981-11-01

    Colonic accumulation of gallium-67 frequently complicates the interpretation of gallium-67 scintigrams. Although various modes of cleansing the colon prior to scintigraphy have been suggested, there is controversy over their efficacy and none have been tested prospectively. Three hundred nine patients undergoing gallium-67 scintigraphy were randomly assigned to one of four cleansing regimens: (1) a high fiber diet (78 patients); (2) castor oil (76); (3) milk of magnesia and cascara (76); and (4) no preparation (79). Patient compliance rates for the four regimens were 17%, 32%, 36%, and 46%, respectively. After noncompliant patients were excluded, gallium-67 scintigrams were graded for colonic activity on a scale of 0-3 by three independent, experienced observers. Gallium-67 activity in the colon was significantly less after adminstration of castor oil than after no prepartion (p = 0.083). Regimen 3 did not produce significantly better results than regimen 4 (p = 0.42). A major impediment to the success of any cleansing regimen seems to be poor compliance of patients.

  17. Dentine microhardness changes following conventional and alternate irrigation regimens: An in vitro study

    PubMed Central

    Das, Anusree; Kottoor, Jojo; Mathew, Joy; Kumar, Sanjana; George, Saira

    2014-01-01

    Aim: To compare the changes in microhardness of root dentin caused by two novel irrigation regimens with conventional irrigation. Materials and Methods: Forty extracted human permanent incisor teeth were selected. Decoronated roots were separated longitudinally to get 80 specimens that were embedded in autopolymerizing acrylic resin and grounded flat with silicon carbide abrasive papers. Of these, 60 root segments without any cracks or defects were selected and divided into four groups according to the irrigation regimen used (n = 15). Group I: 5% sodium hypochlorite (NaOCl) + 17% ethylenediaminetetraacetic acid (EDTA) + 0.2% chlorhexidine digluconate (CHX) (conventional). Group II: 6% Morinda Citrifolia Juice + 17% EDTA (MCJ). Group III: 5% NaOCl + Q Mix 2 in 1 (QMix). Group IV: Distilled water (control). Irrigation regimens were performed for 5 minutes. Dentin microhardness was measured with a Vickers indenter under a 200-g load and a 20-s dwell time at the midroot level of root dentin. The data were analyzed using Kruskal Wallis test and Dunn's multiple comparison tests. Results: A significant difference was seen in the median values of the four groups. The control group showed the least reduction in microhardness when comparison with the other groups. Except for Group III (Q Mix), the other groups that were tested (MCJ and conventional regimens) showed statistically significant difference from the control group. Conclusion: Within the limitation of this study, it was concluded that NaOCl + Q Mix were least detrimental to root dentin microhardness when compared with MCJ and conventional irrigation regimens. PMID:25506142

  18. Evaluation of antimicrobial activities of sequential spray applications of decontamination treatments on chicken carcasses.

    PubMed

    Benli, Hakan; Sanchez-Plata, Marcos X; Ilhak, Osman Irfan; Núñez De González, Maryuri T; Keeton, Jimmy T

    2015-03-01

    The objective of this study was to evaluate the effects of sequential applications of ɛ-polylysine (EPL) or lauramide arginine ethyl ester (LAE) sprays followed by an acidic calcium sulfate (ACS) spray on inoculated chicken carcasses to reduce Salmonella (Salmonella enterica serovars including Salmonella typhimurium and Salmonella enteritidis) contamination during 6 days of storage (4.4°C). Secondly, reductions of the resident microflora were studied on uninoculated chicken carcasses following the sequential application of the treatments, chilling and 10 days of storage at 4.4°C. The treatment of Salmonella inoculated carcasses with 300 mg/L EPL followed by 30% ACS (EPL300-ACS30) sprays reduced Salmonella counts initially by 1.5 log cfu/mL and then by 1.2 log cfu/mL (p<0.05) following 6 days of storage at 4.4°C. Likewise, 200 mg/L LAE followed by 30% ACS (LAE200-ACS30) treatment reduced initial Salmonella counts on poultry carcasses by 1.8, 1.4 and 1.8 log cfu/mL (p<0.05), respectively, after 0, 3, and 6 days storage. Immediately after the treatments, EPL300-ACS30 and LAE200-ACS30 both reduced Escherichia coli counts significantly by 2.6 and 2.9 log cfu/mL, respectively. EPL300-ACS30 and LAE200-ASC30 were effective in lowering psychrotroph counts by 1 log cfu/mL on day 10 when compared to the control and distilled water treatments. This study demonstrated that EPL300-ACS30 and LAE200-ACS30 were effective in reducing Salmonella on inoculated chicken carcasses both after treatment and during the storage at 4.4°C for up to 6 days. In addition, reductions in psychrotroph counts indicated that these treatments might have the potential to increase the shelf-life of poultry carcasses.

  19. A Bayesian Theory of Sequential Causal Learning and Abstract Transfer.

    PubMed

    Lu, Hongjing; Rojas, Randall R; Beckers, Tom; Yuille, Alan L

    2016-03-01

    Two key research issues in the field of causal learning are how people acquire causal knowledge when observing data that are presented sequentially, and the level of abstraction at which learning takes place. Does sequential causal learning solely involve the acquisition of specific cause-effect links, or do learners also acquire knowledge about abstract causal constraints? Recent empirical studies have revealed that experience with one set of causal cues can dramatically alter subsequent learning and performance with entirely different cues, suggesting that learning involves abstract transfer, and such transfer effects involve sequential presentation of distinct sets of causal cues. It has been demonstrated that pre-training (or even post-training) can modulate classic causal learning phenomena such as forward and backward blocking. To account for these effects, we propose a Bayesian theory of sequential causal learning. The theory assumes that humans are able to consider and use several alternative causal generative models, each instantiating a different causal integration rule. Model selection is used to decide which integration rule to use in a given learning environment in order to infer causal knowledge from sequential data. Detailed computer simulations demonstrate that humans rely on the abstract characteristics of outcome variables (e.g., binary vs. continuous) to select a causal integration rule, which in turn alters causal learning in a variety of blocking and overshadowing paradigms. When the nature of the outcome variable is ambiguous, humans select the model that yields the best fit with the recent environment, and then apply it to subsequent learning tasks. Based on sequential patterns of cue-outcome co-occurrence, the theory can account for a range of phenomena in sequential causal learning, including various blocking effects, primacy effects in some experimental conditions, and apparently abstract transfer of causal knowledge.

  20. Low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor priming regimen versus idarubicin plus cytarabine regimen as induction therapy for older patients with acute myeloid leukemia.

    PubMed

    Jin, Jie; Chen, Jian; Suo, Shanshan; Qian, Wenbin; Meng, Haitao; Mai, Wenyuan; Tong, Hongyan; Huang, Jian; Yu, Wenjuan; Wei, Juyin; Lou, Yinjun

    2015-06-01

    With limited data available on the low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor (CAG) regimen in newly diagnosed older patients with acute myeloid leukemia (AML), this study aimed at comparing the efficacy and toxicity of CAG with idarubicin plus cytarabine (IA) remission induction therapy in these patients. A total of 154 consecutive patients (52 with CAG and 102 with IA) were retrospectively analyzed. The patients in the CAG group had a higher median age (68 vs. 65 years, p = 0.002) and a higher proportion of previous myelodysplastic syndrome (25.0% vs. 2.9%, p < 0.0001) compared to those in the IA group. The complete remission rates with the CAG and IA regimens were 55.8% and 52.9% (p = 0.864). The median overall survival (12.1 vs. 11.7 months, p = 0.650) and 3-year disease-free survival rates (29.6% vs. 48.6%, p = 0.657) were not statistically different in the two groups. The CAG regimen might be an alternative to conventional chemotherapy in older patients with AML.

  1. Enhancing Resilience in Youth through a 10-Day Developmental Voyage

    ERIC Educational Resources Information Center

    Hayhurst, Jill; Hunter, John A.; Kafka, Sarah; Boyes, Mike

    2015-01-01

    The present study sought to examine the potential for resilience to be enhanced in a group of youth participating in a developmental voyage, and to identify the factors that contribute to increased resilience following the voyage. Two studies are reported. Study 1 revealed that voyage participants experienced increased resilience over the course…

  2. Syncom 4 deploy, LDEF retrieval highlight 10-day Columbia flight

    NASA Technical Reports Server (NTRS)

    1989-01-01

    The objectives of Space Shuttle Mission STS-32 are described along with major flight activities, prelaunch and launch operations, trajectory sequence of events, and landing and post-landing operations. The primary objectives of STS-32 are the deployment of a Navy synchronous communications satellite (Syncom 4) and the retrieval of the Long Duration Exposure Facility (LDEF) launched from the Challenger in April 1984. Secondary STS-32 payloads include a protein crystal growth experiment, the Fluids Experiment Apparatus (FEA) for the investigation of microgravity materials processing, the Mesoscale Lighting Experiment, the Latitude-Longitude Locator Experiment, the Americal Flight Echocardiograph, and an experiment to investigate neurospora circadian rhythms in a microgravity environment.

  3. Stress monitoring in a Guinness 10-day scuba dive

    NASA Astrophysics Data System (ADS)

    Puiu, A.; Giubileo, G.; Addolorato, G.; Revelli, L.; Gasbarrini, G.; Bellantone, R.; D'Amore, A.; Lombardi, C. P.; Carrozza, C.

    2007-04-01

    Nowadays, there is high demand for sensitive gas sensors both for human and environmental monitoring. This paper deals with a high-resolution (0.2 ppb) laser-based photoacoustic spectroscopic system realized at ENEA Frascati, Italy, applied for monitoring stress in scuba divers during sustained immersion by analyzing breath samples. Blood tests and psychometric tests for scuba divers were performed at Catholic University in Rome. Results will be reported and discussed.

  4. The pharmacokinetics of three multiple dose regimens of chloroquine: implications for malaria chemoprophylaxis.

    PubMed Central

    Wetsteyn, J C; De Vries, P J; Oosterhuis, B; Van Boxtel, C J

    1995-01-01

    The pharmacokinetics of chloroquine were studied in healthy volunteers who received one of three different multiple-dose regimens for 3 weeks: once weekly 300 mg, twice weekly 200 mg and once daily 50 mg chloroquine. Plasma concentrations of chloroquine and metabolites were determined by h.p.l.c. with fluorescence detection. The concentration-time course was fitted to a multiple-dose pharmacokinetic model. Volume of distribution, elimination half-life and clearance were not different for the three regimens, ranging from 250-302 l kg-1, 374-479 h and 0.44-0.58 l h-1 kg-1 respectively. After the first week of all dosage regimens, peak and trough concentrations of chloroquine were above 16 micrograms l-1, sufficiently suppressive for chloroquine-sensitive P. falciparum strains. These data suggest that once daily chloroquine could be combined with proguanil in a single tablet and should improve compliance when given for malaria chemoprophylaxis. PMID:7654492

  5. Efficacy and tolerability of 5-day azacytidine dose-intensified regimen in higher-risk MDS.

    PubMed

    Pierdomenico, Francesca; Esteves, Susana; Almeida, Antonio

    2013-09-01

    Higher-risk myelodysplastic syndromes (MDS) are aggressive disorders with rapid progression to AML and short survival. Azacitidine has shown unprecedented survival advantage in these patients but its treatment schedule involves daily hospital administrations for 7 days every 4 weeks. Due to patient and staffing constraints, we have treated 50 patients with a 5-day dose-intensified (500 mg/m(2) total monthly dose divided in 5 days) azacitidine schedule in our center. The regimen was well tolerated, with Grade 3/4 adverse events seen in 24 % patients and only two discontinuations due to toxicity. The response rate was similar to that reported with the 7-day schedule: 16 % complete remissions, 32 % partial remissions, and 62 % transfusion independence. The median survival was 19.2 months from diagnosis. In addition, this regimen reduced hospital visits by 28 % and drug use by 30 %. Our results demonstrate the safety and efficacy of a dose-intensified 5-day regimen.

  6. Benznidazole and Posaconazole in Experimental Chagas Disease: Positive Interaction in Concomitant and Sequential Treatments

    PubMed Central

    Diniz, Lívia de Figueiredo; Urbina, Julio A.; de Andrade, Isabel Mayer; Mazzeti, Ana Lia; Martins, Tassiane Assíria F.; Caldas, Ivo Santana; Talvani, André; Ribeiro, Isabela; Bahia, Maria Terezinha

    2013-01-01

    Background Current chemotherapy for Chagas disease is unsatisfactory due to its limited efficacy, particularly in the chronic phase, with frequent side effects that can lead to treatment discontinuation. Combined therapy is envisioned as an ideal approach since it may improve treatment efficacy whilst decreasing toxicity and the likelihood of resistance development. We evaluated the efficacy of posaconazole in combination with benznidazole on Trypanosoma cruzi infection in vivo. Methods and Findings Benznidazole and posaconazole were administered individually or in combination in an experimental acute murine infection model. Using a rapid treatment protocol for 7 days, the combined treatments were more efficacious in reducing parasitemia levels than the drugs given alone, with the effects most evident in combinations of sub-optimal doses of the drugs. Subsequently, the curative action of these drug combinations was investigated, using the same infection model and 25, 50, 75 or 100 mg/kg/day (mpk) of benznidazole in combination with 5, 10 or 20 mpk of posaconazole, given alone or concomitantly for 20 days. The effects of the combination treatments on parasitological cures were higher than the sum of such effects when the drugs were administered separately at the same doses, indicating synergistic activity. Finally, sequential therapy experiments were carried out with benznidazole or posaconazole over a short interval (10 days), followed by the second drug administered for the same period of time. It was found that the sequence of benznidazole (100 mpk) followed by posaconazole (20 mpk) provided cure rates comparable to those obtained with the full (20 days) treatments with either drug alone, and no cure was observed for the short treatments with drugs given alone. Conclusions Our data demonstrate the importance of investigating the potential beneficial effects of combination treatments with marketed compounds, and showed that combinations of benznidazole with

  7. Sequential determination of fat- and water-soluble vitamins in green leafy vegetables during storage.

    PubMed

    Santos, J; Mendiola, J A; Oliveira, M B P P; Ibáñez, E; Herrero, M

    2012-10-26

    The simultaneous analysis of fat- and water-soluble vitamins from foods is a difficult task considering the wide range of chemical structures involved. In this work, a new procedure based on a sequential extraction and analysis of both types of vitamins is presented. The procedure couples several simple extraction steps to LC-MS/MS and LC-DAD in order to quantify the free vitamins contents in fresh-cut vegetables before and after a 10-days storage period. The developed method allows the correct quantification of vitamins C, B(1), B(2), B(3), B(5), B(6), B(9), E and provitamin A in ready-to-eat green leafy vegetable products including green lettuce, ruby red lettuce, watercress, swiss chard, lamb's lettuce, spearmint, spinach, wild rocket, pea leaves, mizuna, garden cress and red mustard. Using this optimized methodology, low LOQs were attained for the analyzed vitamins in less than 100 min, including extraction and vitamin analysis using 2 optimized procedures; good repeatability and linearity was achieved for all vitamins studied, while recoveries ranged from 83% to 105%. The most abundant free vitamins found in leafy vegetable products were vitamin C, provitamin A and vitamin E. The richest sample on vitamin C and provitamin A was pea leaves (154 mg/g fresh weight and 14.4 mg/100g fresh weight, respectively), whereas lamb's lettuce was the vegetable with the highest content on vitamin E (3.1 mg/100 g fresh weight). Generally, some losses of vitamins were detected after storage, although the behavior of each vitamin varied strongly among samples.

  8. Partnerships to Design Novel Regimens to Treat Childhood Tuberculosis, Sui Generis: The Road Ahead

    PubMed Central

    Gumbo, Tawanda; Makhene, Mamodikoe K.; Seddon, James A.

    2016-01-01

    There has been a recent expansion of preclinical models to predict the efficacy of regimens to treat adults with tuberculosis. Despite increasing global interest in childhood tuberculosis, these same tools have not been employed to develop pediatric regimens. Children differ from adults in bacillary burden, spectrum of disease, the metabolism and distribution of antituberculosis drugs, and the toxicity experienced. The studies documented in this series describe a proof-of-concept approach to pediatric regimen development. We propose a program of investigation that would take this forward into a systematic and comprehensive method to find optimal drug combinations to use in children, ideal exposures, and required dosing. Although the number of possible drug combinations is extensive, a series of principles could be employed to select likely effective regimens. Regimens should avoid drugs with overlapping toxicity or linked mechanisms of resistance and should aim to include drugs with different mechanisms of action and ones that are able to target different subpopulations of mycobacteria. Finally drugs should penetrate into body sites necessary for treating pediatric disease. At an early stage, this body of work would need to engage with regulatory agencies and bodies that formulate guidelines, so that once regimens and dosages are identified, translation into clinical studies and clinical practice can be rapid. The development of child-friendly drug formulations would need to be carried out in parallel so that pharmacokinetic studies can be undertaken as formulations are created. Significant research and development would be required and a wide range of stakeholders would need to be engaged. The time is right to consider a more thoughtful and systematic approach toward identifying, testing, and comparing combinations of drugs for children with tuberculosis. PMID:27742642

  9. Clofazimine shortens the duration of the first-line treatment regimen for experimental chemotherapy of tuberculosis.

    PubMed

    Tyagi, Sandeep; Ammerman, Nicole C; Li, Si-Yang; Adamson, John; Converse, Paul J; Swanson, Rosemary V; Almeida, Deepak V; Grosset, Jacques H

    2015-01-20

    A key drug for the treatment of leprosy, clofazimine has recently been associated with highly effective and significantly shortened regimens for the treatment of multidrug-resistant tuberculosis (TB). Consequently, we hypothesized that clofazimine may also shorten the duration of treatment for drug-susceptible TB. We conducted a controlled trial in the mouse model of TB chemotherapy comparing the activity of the 6-mo standard regimen for TB treatment, i.e., 2 mo of daily rifampin, isoniazid, pyrazinamide, and ethambutol followed by 4 mo of rifampin and isoniazid, with a 4-mo clofazimine-containing regimen: 2 mo of daily rifampin, isoniazid, pyrazinamide, and clofazimine followed by 2 mo of rifampin, isoniazid, and clofazimine. Treatment efficacy was assessed on the basis of Mycobacterium tuberculosis colony counts in the lungs and spleens during treatment and on the proportion of mice with culture-positive relapse 6 mo after treatment cessation. No additive effect of clofazimine was observed after the first week of treatment, but, by the second week of treatment, the colony counts were significantly lower in the clofazimine-treated mice than in the mice receiving the standard regimen. Lung culture conversion was obtained after 3 and 5 mo in mice treated with the clofazimine-containing and standard regimens, respectively, and relapse-free cure was obtained after 3 and 6 mo of treatment with the clofazimine-containing and standard regimens, respectively. Thus, clofazimine is a promising anti-TB drug with the potential to shorten the duration of TB chemotherapy by at least half (3 mo vs. 6 mo) in the mouse model of TB.

  10. Sterilizing Activity of Second-Line Regimens Containing TMC207 in a Murine Model of Tuberculosis

    PubMed Central

    Lounis, Nacer; Andries, Koen; Jarlier, Vincent

    2011-01-01

    Rationale The sterilizing activity of the regimen used to treat multidrug resistant tuberculosis (MDR TB) has not been studied in a mouse model. Objective and Methods Swiss mice were intravenously inoculated with 6 log10 of Mycobacterium tuberculosis (TB) strain H37Rv, treated with second-line drug combinations with or without the diarylquinoline TMC207, and then followed without treatment for 3 more months to determine relapse rates (modified Cornell model). Measurements Bactericidal efficacy was assessed by quantitative lung colony-forming unit (CFU) counts. Sterilizing efficacy was assessed by measuring bacteriological relapse rates 3 months after the end of treatment. Main Results The relapse rate observed after 12 months treatment with the WHO recommended MDR TB regimen (amikacin, ethionamide, pyrazinamide and moxifloxacin) was equivalent to the relapse rate observed after 6 months treatment with the recommended drug susceptible TB regimen (rifampin, isoniazid and pyrazinamide). When TMC207 was added to this MDR TB regimen, the treatment duration needed to reach the same relapse rate dropped to 6 months. A similar relapse rate was also obtained with a 6-month completely oral regimen including TMC207, moxifloxacin and pyrazinamide but excluding both amikacin and ethionamide. Conclusions In this murine model the duration of the WHO MDR TB treatment could be reduced to 12 months instead of the recommended 18–24 months. The inclusion of TMC207 in the WHO MDR TB treatment regimen has the potential to further shorten the treatment duration and at the same time to simplify treatment by eliminating the need to include an injectable aminoglycoside. PMID:21408613

  11. Dietary roughage regimen for feedlot steers: reduced roughage level (2%) during the mid-finishing period.

    PubMed

    Bartle, S J; Preston, R L

    1991-09-01

    Because roughage in feedlot diets is one of the most expensive ingredients on an energy basis, regimens that minimize roughage usage are of interest. Crossbred steers of British breeds (n = 112, initial BW = 405 kg) were used to compare the feeding of diets containing 2% roughage from d 22 through 84 and 10% roughage from d 85 to finish (d 133; 2/10%) to the feeding of 10% roughage throughout the finishing period (10/10%); all diets were based on steam-flaked sorghum grain and contained monensin and tylosin. When the 2% roughage diet was fed, steers consumed less feed (6.8 vs 7.8 kg/d, P less than .01), tended to gain less (1.11 vs 1.20 kg/d, P = .13), and were numerically more efficient (16.5 vs 15.5 kg of gain/100 kg of DMI, P greater than .2) than steers fed the 10% roughage diet (10/10%). After the roughage content was increased from 2 to 10% on d 85 (all steers fed 10% roughage), steers fed the 2/10% regimen had greater DMI (8.4 vs 8.0 kg/d, P = .08) and ADG (1.29 vs 1.09 kg, P = .06), and tended to be more efficient (15.4 vs 13.6 kg of gain/100 kg of DMI, P = .10) than steers fed the 10/10% regimen. Steers fed the two regimens had similar (P greater than .2) overall gain performance. The 2/10% regimen tended to have a greater percentage of Choice carcasses (58 vs 42%, P = .14) and numerically more liver abscesses (24 vs 15%, P greater than .2) than the 10/10% regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Increasing efficiency of preclinical research by group sequential designs.

    PubMed

    Neumann, Konrad; Grittner, Ulrike; Piper, Sophie K; Rex, Andre; Florez-Vargas, Oscar; Karystianis, George; Schneider, Alice; Wellwood, Ian; Siegerink, Bob; Ioannidis, John P A; Kimmelman, Jonathan; Dirnagl, Ulrich

    2017-03-01

    Despite the potential benefits of sequential designs, studies evaluating treatments or experimental manipulations in preclinical experimental biomedicine almost exclusively use classical block designs. Our aim with this article is to bring the existing methodology of group sequential designs to the attention of researchers in the preclinical field and to clearly illustrate its potential utility. Group sequential designs can offer higher efficiency than traditional methods and are increasingly used in clinical trials. Using simulation of data, we demonstrate that group sequential designs have the potential to improve the efficiency of experimental studies, even when sample sizes are very small, as is currently prevalent in preclinical experimental biomedicine. When simulating data with a large effect size of d = 1 and a sample size of n = 18 per group, sequential frequentist analysis consumes in the long run only around 80% of the planned number of experimental units. In larger trials (n = 36 per group), additional stopping rules for futility lead to the saving of resources of up to 30% compared to block designs. We argue that these savings should be invested to increase sample sizes and hence power, since the currently underpowered experiments in preclinical biomedicine are a major threat to the value and predictiveness in this research domain.

  13. Description and effects of sequential behavior practice in teacher education.

    PubMed

    Sharpe, T; Lounsbery, M; Bahls, V

    1997-09-01

    This study examined the effects of a sequential behavior feedback protocol on the practice-teaching experiences of undergraduate teacher trainees. The performance competencies of teacher trainees were analyzed using an alternative opportunities for appropriate action measure. Data support the added utility of sequential (Sharpe, 1997a, 1997b) behavior analysis information in systematic observation approaches to teacher education. One field-based undergraduate practicum using sequential behavior (i.e., field systems analysis) principles was monitored. Summarized are the key elements of the (a) classroom instruction provided as a precursor to the practice teaching experience, (b) practice teaching experience, and (c) field systems observation tool used for evaluation and feedback, including multiple-baseline data (N = 4) to support this approach to teacher education. Results point to (a) the strong relationship between sequential behavior feedback and the positive change in four preservice teachers' day-to-day teaching practices in challenging situational contexts, and (b) the relationship between changes in teacher practices and positive changes in the behavioral practices of gymnasium pupils. Sequential behavior feedback was also socially validated by the undergraduate participants and Professional Development School teacher supervisors in the study.

  14. Increasing efficiency of preclinical research by group sequential designs

    PubMed Central

    Piper, Sophie K.; Rex, Andre; Florez-Vargas, Oscar; Karystianis, George; Schneider, Alice; Wellwood, Ian; Siegerink, Bob; Ioannidis, John P. A.; Kimmelman, Jonathan; Dirnagl, Ulrich

    2017-01-01

    Despite the potential benefits of sequential designs, studies evaluating treatments or experimental manipulations in preclinical experimental biomedicine almost exclusively use classical block designs. Our aim with this article is to bring the existing methodology of group sequential designs to the attention of researchers in the preclinical field and to clearly illustrate its potential utility. Group sequential designs can offer higher efficiency than traditional methods and are increasingly used in clinical trials. Using simulation of data, we demonstrate that group sequential designs have the potential to improve the efficiency of experimental studies, even when sample sizes are very small, as is currently prevalent in preclinical experimental biomedicine. When simulating data with a large effect size of d = 1 and a sample size of n = 18 per group, sequential frequentist analysis consumes in the long run only around 80% of the planned number of experimental units. In larger trials (n = 36 per group), additional stopping rules for futility lead to the saving of resources of up to 30% compared to block designs. We argue that these savings should be invested to increase sample sizes and hence power, since the currently underpowered experiments in preclinical biomedicine are a major threat to the value and predictiveness in this research domain. PMID:28282371

  15. Kidney Injury Associated with Telavancin Dosing Regimen in an Animal Model

    PubMed Central

    Ledesma, Kimberly R.; Bowers, Dana R.; Zhou, Jian; Truong, Luan D.

    2015-01-01

    The elevation of serum creatinine levels is a concern with telavancin therapy. We examined the onset of kidney injury associated with telavancin in an animal model. Urine samples were collected at baseline and daily to determine the concentrations of kidney injury molecule 1 (KIM-1), a marker for early kidney injury. When a clinically relevant exposure of telavancin was given daily to rats, some differences in kidney injury were attributed to the dosing regimen. Further investigations of alternative telavancin dosing regimens are warranted. PMID:25712358

  16. Remission induction and remission maintenance in adult acute nonlymphocytic leukemia employing a modified cytostatic (COAP) regimen.

    PubMed

    Gerecke, D; Hirschmann, W D; Voigtmann, R; Gross, R

    1979-07-01

    Thirty adult patients suffering from acute nonlymphocytic leukemia (ANLL) were treated according to a modified COAP regimen. Vincristine, cyclophosphamide, and prednisone were given by push injection, while cytosine arabinoside was infused over periods of 8 h. Nineteen patients (63%) achieved complete remission. Remission maintenance therapy consisted of 6-mercaptopurine daily and methotrexate twice weekly. Later in the study, COAP consolidation and reinduction was added, which improved the median duration of complete remission from 7 to 24 months. Comparison of the results with the literature shows that the modified COAP regimen is one of the most effective treatment schedules for adult ANLL.

  17. Efavirenz versus boosted atazanavir-containing regimens and immunologic, virologic, and clinical outcomes

    PubMed Central

    Cain, Lauren E.; Caniglia, Ellen C.; Phillips, Andrew; Olson, Ashley; Muga, Roberto; Pérez-Hoyos, Santiago; Abgrall, Sophie; Costagliola, Dominique; Rubio, Rafael; Jarrín, Inma; Bucher, Heiner; Fehr, Jan; van Sighem, Ard; Reiss, Peter; Dabis, François; Vandenhende, Marie-Anne; Logan, Roger; Robins, James; Sterne, Jonathan A. C.; Justice, Amy; Tate, Janet; Touloumi, Giota; Paparizos, Vasilis; Esteve, Anna; Casabona, Jordi; Seng, Rémonie; Meyer, Laurence; Jose, Sophie; Sabin, Caroline; Hernán, Miguel A.

    2016-01-01

    Abstract Objective: To compare regimens consisting of either ritonavir-boosted atazanavir or efavirenz and a nucleoside reverse transcriptase inhibitor (NRTI) backbone with respect to clinical, immunologic, and virologic outcomes. Design: Prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States included in the HIV-CAUSAL Collaboration. Methods: HIV-positive, antiretroviral therapy-naive, and acquired immune deficiency syndrome (AIDS)-free individuals were followed from the time they started an atazanavir or efavirenz regimen. We estimated an analog of the “intention-to-treat” effect for efavirenz versus atazanavir regimens on clinical, immunologic, and virologic outcomes with adjustment via inverse probability weighting for time-varying covariates. Results: A total of 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths) and 18,786 individuals started an efavirenz regimen (389 deaths, 825 AIDS-defining illnesses or deaths). During a median follow-up of 31 months, the hazard ratios (95% confidence intervals) were 0.98 (0.77, 1.24) for death and 1.09 (0.91, 1.30) for AIDS-defining illness or death comparing efavirenz with atazanavir regimens. The 5-year survival difference was 0.1% (95% confidence interval: −0.7%, 0.8%) and the AIDS-free survival difference was −0.3% (−1.2%, 0.6%). After 12 months, the mean change in CD4 cell count was 20.8 (95% confidence interval: 13.9, 27.8) cells/mm3 lower and the risk of virologic failure was 20% (14%, 26%) lower in the efavirenz regimens. Conclusion: Our estimates are consistent with a smaller 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with atazanavir regimens. No overall differences could be detected with respect to 5-year survival or AIDS-free survival. PMID:27741139

  18. Sequential changes of extracellular matrix and proliferation of Ito cells with enhanced expression of desmin and actin in focal hepatic injury.

    PubMed Central

    Ogawa, K.; Suzuki, J.; Mukai, H.; Mori, M.

    1986-01-01

    Immunohistochemical investigations were carried out on the properties of the cells and extracellular matrix (ECM) in focal hepatic injuries. A liquid nitrogen-cooled syringe needle was thrust into the rat liver. Necrotic areas became permeated with plasma within 24-hour period. Areas became strongly positive for fibronectin and were infiltrated with inflammatory cells positive for lysozyme. By the third day, Ito cells were proliferated in the peripheral portions of the damaged areas. These Ito cells showed enhanced immunostaining for desmin and actin but were negative for lysozyme. Interstitial fibers which were immunochemically positive for Types I and IV collagens, laminin, and fibronectin, began to increase from Day 3. They appeared on the rim of the hepatocytes adjacent to the damaged areas and extended into the injured regions with the Ito cells. An increase in basal laminas associated with capillaries and bile ducts also increased with a 1-day delay. The damaged areas were replaced by granulation tissue by Day 5. A rapid diminution then occurred in the granulation tissue, and normal hepatic tissue was restored in 7-10 days. These observations demonstrate that ECM changed in a sequential manner and then finally disappeared from the damaged site within 10 days. Although various cells, including parenchymal cells, macrophages, endothelial cells, and cholangiolar cells contributed to the healing of the damaged area, Ito cells, which exhibit unique phenotypic changes, presumably had a major role in the process. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:3799820

  19. Direct versus sequential immunoglobulin switch in allergy and antiviral responses.

    PubMed

    Svirshchevskaya, E; Fattakhova, G; Khlgatian, S; Chudakov, D; Kashirina, E; Ryazantsev, D; Kotsareva, O; Zavriev, S

    2016-09-01

    Allergy is characterized by IgE production to innocuous antigens. The question whether the switch to IgE synthesis occurs via direct or sequential pathways is still unresolved. The aim of this work was to analyze the distribution of immunoglobulins (Ig) to house dust mite D. farinae and A. alternata fungus in allergic children with primarily established diagnosis and compare it to Epstein-Barr antiviral (EBV) response in the same patients. In allergy patients the only significant difference was found in allergen specific IgE, likely mediated by a direct isotype switch, while antiviral response was dominated by EBV specific IgG and low level of concordant IgA and IgG4 production consistent with a minor sequential Ig switches. Taken collectively, we concluded that sequential isotype switch is likely to be a much rarer event than a direct one.

  20. Optimal adaptive sequential designs for crossover bioequivalence studies.

    PubMed

    Xu, Jialin; Audet, Charles; DiLiberti, Charles E; Hauck, Walter W; Montague, Timothy H; Parr, Alan F; Potvin, Diane; Schuirmann, Donald J

    2016-01-01

    In prior works, this group demonstrated the feasibility of valid adaptive sequential designs for crossover bioequivalence studies. In this paper, we extend the prior work to optimize adaptive sequential designs over a range of geometric mean test/reference ratios (GMRs) of 70-143% within each of two ranges of intra-subject coefficient of variation (10-30% and 30-55%). These designs also introduce a futility decision for stopping the study after the first stage if there is sufficiently low likelihood of meeting bioequivalence criteria if the second stage were completed, as well as an upper limit on total study size. The optimized designs exhibited substantially improved performance characteristics over our previous adaptive sequential designs. Even though the optimized designs avoided undue inflation of type I error and maintained power at ≥ 80%, their average sample sizes were similar to or less than those of conventional single stage designs.

  1. Ancilla-assisted sequential approximation of nonlocal unitary operations

    SciTech Connect

    Saberi, Hamed

    2011-09-15

    We consider the recently proposed (no-go) theorem of Lamata et al.[Phys. Rev. Lett. 101, 180506 (2008)] on the impossibility of sequential implementation of global unitary operations with the aid of an itinerant ancillary system and view the claim within the language of Kraus representation. By virtue of an extremely useful tool for analyzing entanglement properties of quantum operations, namely, operator-Schmidt decomposition, we provide alternative proof to the no-go theorem and also study the role of initial correlations between the qubits and ancilla in sequential preparation of unitary entanglers. Despite the negative response from the no-go theorem, we demonstrate explicitly how the matrix-product operator (MPO) formalism provides a flexible structure to develop protocols for sequential implementation of such entanglers with an optimal fidelity. The proposed numerical technique, which we call variational matrix-product operator (VMPO), offers a computationally efficient tool for characterizing the ''globalness'' and entangling capabilities of nonlocal unitary operations.

  2. Measuring Incompatible Observables by Exploiting Sequential Weak Values

    NASA Astrophysics Data System (ADS)

    Piacentini, F.; Avella, A.; Levi, M. P.; Gramegna, M.; Brida, G.; Degiovanni, I. P.; Cohen, E.; Lussana, R.; Villa, F.; Tosi, A.; Zappa, F.; Genovese, M.

    2016-10-01

    One of the most intriguing aspects of quantum mechanics is the impossibility of measuring at the same time observables corresponding to noncommuting operators, because of quantum uncertainty. This impossibility can be partially relaxed when considering joint or sequential weak value evaluation. Indeed, weak value measurements have been a real breakthrough in the quantum measurement framework that is of the utmost interest from both a fundamental and an applicative point of view. In this Letter, we show how we realized for the first time a sequential weak value evaluation of two incompatible observables using a genuine single-photon experiment. These (sometimes anomalous) sequential weak values revealed the single-operator weak values, as well as the local correlation between them.

  3. A Bayesian sequential processor approach to spectroscopic portal system decisions

    SciTech Connect

    Sale, K; Candy, J; Breitfeller, E; Guidry, B; Manatt, D; Gosnell, T; Chambers, D

    2007-07-31

    The development of faster more reliable techniques to detect radioactive contraband in a portal type scenario is an extremely important problem especially in this era of constant terrorist threats. Towards this goal the development of a model-based, Bayesian sequential data processor for the detection problem is discussed. In the sequential processor each datum (detector energy deposit and pulse arrival time) is used to update the posterior probability distribution over the space of model parameters. The nature of the sequential processor approach is that a detection is produced as soon as it is statistically justified by the data rather than waiting for a fixed counting interval before any analysis is performed. In this paper the Bayesian model-based approach, physics and signal processing models and decision functions are discussed along with the first results of our research.

  4. Sequential and combined acceleration tests for crystalline Si photovoltaic modules

    NASA Astrophysics Data System (ADS)

    Masuda, Atsushi; Yamamoto, Chizuko; Uchiyama, Naomi; Ueno, Kiyoshi; Yamazaki, Toshiharu; Mitsuhashi, Kazunari; Tsutsumida, Akihiro; Watanabe, Jyunichi; Shirataki, Jyunko; Matsuda, Keiko

    2016-04-01

    The sequential combination test for photovoltaic modules is effective for accelerating degradation to shorten the test time and for reproducing degradation phenomena observed in modules exposed outdoors for a long time. The damp-heat (DH) test, thermal-cycle (TC) test, humidity-freeze (HF) test or dynamic mechanical load (DML) test is combined for the test modules. It was confirmed that chemical corrosion degradation or physical mechanical degradation is reproduced by the combination of the above tests. Cracks on the back sheet and delamination, often observed upon outdoor exposure, were well reproduced by the combination of DH and TC tests and TC and HF tests, respectively. Sequential DH and TC tests and DML and TC tests accelerated the degradation. These sequential tests are expected to be effective in reducing the required time of indoor testing for ensuring long-term reliability.

  5. Sequential behavior in the rat: role of skill and attention.

    PubMed

    Domenger, Dorothée; Schwarting, Rainer K W

    2007-09-01

    The serial reaction time task (SRTT) is a well-established experimental tool to study cognitive and neural mechanisms of sequential performance in humans. We have recently developed a rodent version of the human serial reaction time task, in which rats have to respond to visual stimuli by nose-poking into one of four spatial locations in order to obtain food reward. In this task, rats display superior performance under sequential as compared to random conditions of stimulus presentation. Specifically, the subjects are able to profit from sequential regularities in terms of faster reaction times and higher response accuracy. Here, we studied the effects of violating a single stimulus in rats, which had been intensively trained under sequential conditions, and we asked whether these subjects, when confronted with sequence violations, still attend to the actual stimulus order (that is, show correct responses), or whether their behavior has become fully automated (leading to specific incorrect responses to violated stimulus positions). In two independent experiments using partly differing instrumental set-ups, we found that the responses to non-cued violations of single stimulus positions were mostly correct, that is, the animals were apparently attending to the stimuli. Nevertheless, these reaction times were slowed, which probably reflects cognitive resources necessary to respond correctly to the unexpected irregularities. When quantifying the minority of responses, which were incorrect, we found that most of them were directed to the position, where the stimulus would have appeared if the sequence had not been violated. These responses were faster than the correct ones (to the violated stimulus), which indicates that sequential responding had become partly automated. Together, our data show that both, attention and skill play a role for sequential performance in our SRT task, and that they can be dissected by quantification of specific response types. In future work

  6. Composite system reliability evaluation using sequential Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Jonnavithula, Annapoorani

    Monte Carlo simulation methods can be effectively used to assess the adequacy of composite power system networks. The sequential simulation approach is the most fundamental technique available and can be used to provide a wide range of indices. It can also be used to provide estimates which can serve as benchmarks against which other approximate techniques can be compared. The focus of this research work is on the reliability evaluation of composite generation and transmission systems with special reference to frequency and duration related indices and estimated power interruption costs at each load bus. One of the main objectives is to use the sequential simulation method to create a comprehensive technique for composite system adequacy evaluation. This thesis recognizes the need for an accurate representation of the load model at the load buses which depends on the mix of customer sectors at each bus. Chronological hourly load curves are developed in this thesis, recognizing the individual load profiles of the customers at each load bus. Reliability worth considerations are playing an ever increasing role in power system planning and operation. Different methods for bus outage cost evaluation are proposed in this thesis. It may not be computationally feasible to use the sequential simulation method with time varying loads at each bus in large electric power system networks. Time varying load data may also not be available at each bus. This research work uses the sequential methodology as a fundamental technique to calibrate other non sequential methods such as the state sampling and state transition sampling techniques. Variance reduction techniques that improve the efficiency of the sequential simulation procedure are investigated as a part of this research work. Pertinent features that influence reliability worth assessment are also incorporated. All the proposed methods in this thesis are illustrated by application to two reliability test systems. In addition

  7. [A clinical study of cryptococcal meningitis--sequential changes of cryptococcal antigen titers].

    PubMed

    Kishi, Kazuma; Homma, Sakae; Nakatani, Tatsuo; Nakata, Koichiro

    2003-03-01

    We reviewed the clinical manifestations, sequential changes in cryptococcal antigen titers in serum and cerebrospinal fluid (CSF), and the antifungal drug susceptibility of Cryptococcus neoformans in three patients with cryptococcal meningitis between 1996 and 2000. Cryptococcal antigen titers were measured using the latex agglutination method with Pastrex Cryptococcus (Fuji Mebio, Tokyo) and Serodirect Cryptococcus (Eiken Chemical, Tokyo). The underlying systemic diseases in the three patients were liver cirrhosis, non-Hodgkin's lymphoma associated with miliary tuberculosis, and malignant thymoma associated with systemic lupus erythymatosus. The CSF samples showed positive indian ink staining in two of the three patients and C. neoformans was cultured from all three. The cryptococcal antigen titers in serum were higher than those in the CSF. The serum and CSF cryptococcal antigen titers measured by Serodirect Cryptococcus were higher than those measured by Pastrex Cryptococcus. The maximum titers of antigen in serum and CSF measured by Serodirect Cryptococcus were greater than 1,024 in all three patients. The treatment regimens used for the three patients were amphotericin-B (AMPH-B) and flucytosine (5-FC), fluconazole (FLCZ) and intrathecal AMPH-B, FLCZ and 5-FC, and intrathecal AMPH-B, respectively. The antigen titers in serum and CSF decreased after treatment in all three patients. The antigen titers decreased slowly over 7.3 months in the most seriously ill patient who had non-Hodgkin's lymphoma associated with miliary tuberculosis. The time between the beginning of treatment and CSF cryptococal antigen titers falling to less than 8 was 1.7 to 7.3 months in the three patients, but the serum titers did not decrease to less than 8 during this period. The minimum inhibitory concentration was 0.06-0.25 microgram/ml for AMPH-B, 4-8 micrograms/ml for 5-FC, 2-8 micrograms/ml for FLCZ, 0.125-0.5 microgram/ml for miconazole and 0.03-0.125 microgram/ml for itraconazole

  8. Analysis of filter tuning techniques for sequential orbit determination

    NASA Technical Reports Server (NTRS)

    Lee, T.; Yee, C.; Oza, D.

    1995-01-01

    This paper examines filter tuning techniques for a sequential orbit determination (OD) covariance analysis. Recently, there has been a renewed interest in sequential OD, primarily due to the successful flight qualification of the Tracking and Data Relay Satellite System (TDRSS) Onboard Navigation System (TONS) using Doppler data extracted onboard the Extreme Ultraviolet Explorer (EUVE) spacecraft. TONS computes highly accurate orbit solutions onboard the spacecraft in realtime using a sequential filter. As the result of the successful TONS-EUVE flight qualification experiment, the Earth Observing System (EOS) AM-1 Project has selected TONS as the prime navigation system. In addition, sequential OD methods can be used successfully for ground OD. Whether data are processed onboard or on the ground, a sequential OD procedure is generally favored over a batch technique when a realtime automated OD system is desired. Recently, OD covariance analyses were performed for the TONS-EUVE and TONS-EOS missions using the sequential processing options of the Orbit Determination Error Analysis System (ODEAS). ODEAS is the primary covariance analysis system used by the Goddard Space Flight Center (GSFC) Flight Dynamics Division (FDD). The results of these analyses revealed a high sensitivity of the OD solutions to the state process noise filter tuning parameters. The covariance analysis results show that the state estimate error contributions from measurement-related error sources, especially those due to the random noise and satellite-to-satellite ionospheric refraction correction errors, increase rapidly as the state process noise increases. These results prompted an in-depth investigation of the role of the filter tuning parameters in sequential OD covariance analysis. This paper analyzes how the spacecraft state estimate errors due to dynamic and measurement-related error sources are affected by the process noise level used. This information is then used to establish

  9. Sequential and Concurrent Chemoradiation: State of the Art.

    PubMed

    Chau, Nicole G; Haddad, Robert I

    2015-12-01

    Most patients diagnosed with head and neck cancer have locally advanced disease. Sequential and concurrent chemoradiation are standard, nonsurgical, curative-intent treatment options. Controversy remains regarding the superiority of one approach to another. Definitive management strategies are evolving with increasing efforts to pursue deintensification of therapy for low-risk patients, and to pursue therapeutic intensification for high-risk patients. Both sequential therapy and concurrent chemoradiation play important roles in shaping treatment paradigms because both approaches may be used to investigate deintensification or intensification strategies. This article examines the latest evidence and state-of-the-art approaches, highlighting ongoing controversies and future directions.

  10. Testing sequential quantum measurements: how can maximal knowledge be extracted?

    PubMed Central

    Nagali, Eleonora; Felicetti, Simone; de Assis, Pierre-Louis; D'Ambrosio, Vincenzo; Filip, Radim; Sciarrino, Fabio

    2012-01-01

    The extraction of information from a quantum system unavoidably implies a modification of the measured system itself. In this framework partial measurements can be carried out in order to extract only a portion of the information encoded in a quantum system, at the cost of inducing a limited amount of disturbance. Here we analyze experimentally the dynamics of sequential partial measurements carried out on a quantum system, focusing on the trade-off between the maximal information extractable and the disturbance. In particular we implement two sequential measurements observing that, by exploiting an adaptive strategy, is possible to find an optimal trade-off between the two quantities. PMID:22720131

  11. Training neural networks using sequential extended Kalman filtering

    SciTech Connect

    Plumer, E.S.

    1995-03-01

    Recent work has demonstrated the use of the extended Kalman filter (EKF) as an alternative to gradient-descent backpropagation when training multi-layer perceptrons. The EKF approach significantly improves convergence properties but at the cost of greater storage and computational complexity. Feldkamp et al. have described a decoupled version of the EKF which preserves the training advantages of the general EKF but which reduces the storage and computational requirements. This paper reviews the general and decoupled EKF approaches and presents sequentialized versions which provide further computational savings over the batch forms. The usefulness of the sequentialized EKF algorithms is demonstrated on a pattern classification problem.

  12. The effect of sequential therapy for postmenopausal women with osteoporosis

    PubMed Central

    Lou, Shenghan; Lv, Houchen; Wang, Guoqi; Li, Zhirui; Li, Ming; Zhang, Licheng; Tang, Peifu

    2016-01-01

    Abstract Background: Osteoporosis, more likely to occur in postmenopausal women, is a chronic condition that usually requires a long-term treatment strategy, but the use of either antiresorptive or anabolic drugs should be limited to 18 to 24 months. Discontinuing antiosteoporosis drugs may result in rapidly declining bone mineral density (BMD). Therefore, many patients are treated with the sequential use of 2 or more drugs. However, whether switching treatment from anabolic to antiresorptive drugs or the reverse could maintain or further increase BMD; and whether the sequential therapy could outperform the monotherapy under the same treatment duration still remains unclear. Nowadays, no firm conclusions were drawn. Methods: We searched Medline, Embase, and Cochrane Library from January 1, 1974 until February 1, 2016 to identify all randomized controlled trials for evaluating the effectiveness of sequential therapy of antiresorptive and anabolic drugs in postmenopausal osteoporosis women with the BMD changes of lumbar spine, femoral neck, and total hip as the outcomes. We evaluated the methodological quality and abstracted relevant data according to the Cochrane Handbook. Results: Eight trials involving 1509 patients were included. The pooled data showed that after switching treatment, the alternative drugs maintained the BMD and significantly increased the percentage change in BMD at the lumbar spine (MD, 3.59; 95% CI, 2.26–4.93), femoral neck (MD, 1.44; 95% CI, 0.60–2.27), and total hip (MD, 1.24; 95% CI, −0.12 to 2.60), although change in BMD was not significantly increased at the total hip. The sequential therapy significantly increased BMD from baseline at the lumbar spine (SMD, 0.59; 95% CI, 0.26–0.91), femoral neck (SMD, 0.22; 95% CI, 0.06–0.37), and total hip (SMD, 0.28; 95% CI, 0.01–0.56). Conclusions: After switching treatment, sequential therapy further increased BMD. The sequential therapy showed a more significant improvement in BMD

  13. Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen

    SciTech Connect

    Sharabi, Y.; Sachs, D.H.

    1989-02-01

    The use of allogeneic bone marrow transplantation as a means of inducing donor-specific tolerance across MHC barriers could provide an immunologically specific conditioning regimen for organ transplantation. However, a major limitation to this approach is the toxicity of whole body irradiation as currently used to abrogate host resistance and permit marrow engraftment. The present study describes methodology for abrogating host resistance and permitting marrow engraftment without lethal irradiation. Our preparative protocol involves administration of anti-CD4 and anti-CD8 mAbs in vivo, 300-rad WBI, 700-rad thymic irradiation, and unmanipulated fully MHC-disparate bone marrow. B10 mice prepared by this regimen developed stable mixed lymphohematopoetic chimerism without any clinical evidence of graft-vs.-host disease. Engraftment was accompanied by induction of specific tolerance to donor skin grafts (B10.D2), while third-party skin grafts (B10.BR) were promptly rejected. Mice treated with the complete regimen without bone marrow transplantation appeared healthy and enjoyed long-term survival. This study therefore demonstrates that stable mixed chimerism with donor-specific tolerance can be induced across an MHC barrier after a nonlethal preparative regimen, without clinical GVHD and without the risk of aplasia.

  14. Autotransplant conditioning regimens for aggressive lymphoma: are we on the right road?

    PubMed

    Fernandez, H F; Escalón, M P; Pereira, D; Lazarus, H M

    2007-09-01

    High-dose chemotherapy and autologous stem cell transplant (ASCT) is the standard approach for chemosensitive, relapsed aggressive non-Hodgkin's lymphoma (NHL). Various conditioning regimens have been used as treatment before ASCT and disease-free (DFS) and overall survival (OS) rates range from 34 to 60% and 26 to 46%, respectively. To date, few comparative randomized trials have been performed and no regimen has demonstrated superiority to another. Reduction of disease relapse remains the major hurdle for improving patient outcome and in vitro and in vivo purging of lymphoma cells has not necessarily enhanced results. Rituximab pre-mobilization and post-transplant appear to provide better response rates with OS approaching 87-91% at 2-3 years. Newer approaches with radioimmunotherapy may raise DFS to 78% and OS to 93%, albeit with short follow-up. Advances in the conditioning regimens and supportive care have reduced transplant-related mortality to less than 10%. In this review we discuss commonly utilized conditioning regimens, describe their pros and cons and address purging and present conditioning strategies. Owing to the poor outcome with conventional chemotherapy in mantle cell, Burkitt's and T-cell lymphoma, we propose the standard approach of front-line ASCT for these high-risk lymphoma patients. Finally, we will present novel strategies, which can enhance the anti-lymphoma effect, at the same time reducing toxicity, to improve the outcome of ASCT in NHL patients.

  15. Evidence-Based Nursing of the 3C Therapeutic Regimen for Type 1 Diabetes.

    PubMed

    Wu, Jianya; Zou, Ling

    2015-05-01

    The aim of this study is to explore the efficacy of the 3C therapeutic regimen for type 1 diabetes. Thirty-nine patients with type 1 diabetes, who were hospitalized from January 2013 to April 2014, were included to receive 3C therapeutic regimen. Evidence-based nursing was performed in the treatment period and the efficacy was observed 6 days after therapy. Six days after the administration of the 3C therapeutic regimen, the fasting glucose levels in all 39 patients were controlled to be 4.4-6.0 mmol/L and 2h-postprandial glucose levels to be 4.4-7.8 mmol/L. Three patients had a glucose level <3.9 mmol/L, which was corrected after adjusting the dose of insulin infusion. Evidence-based nursing was provided in the treatment period and no nursing-associated complication occurred. All patients were satisfied with the nursing service. The efficacy of the 3C therapeutic regimen for type 1 diabetes is satisfactory. The evidence-based nursing can help to ensure the efficacy and improve the quality of nursing service.

  16. Adverse Reactions to Daily and Intermittent Rifampicin Regimens for Pulmonary Tuberculosis in Hong Kong*

    PubMed Central

    Aquinas, Sister Mary; Allan, W. G. L.; Horsfall, P. A. L.; Jenkins, P. K.; Hung-Yan, Wong; Girling, David; Tall, Ruth; Fox, Wallace

    1972-01-01

    This paper reports the nature, incidence, and severity of adverse reactions to regimens of rifampicin and ethambutol given once weekly, twice weekly, or daily and to a standard reserve regimen in a total of 330 Chinese failure patients who completed at least six months' chemotherapy in a therapeutic comparison in Hong Kong. The adverse reactions which occurred on the regimens of intermittent rifampicin were termed cutaneous, abdominal, “flu”, and respiratory; in addition, purpura and abnormal liver function tests were encountered. There was an association of adverse reactions with the interval between doses and with the dose size of rifampicin, the highest incidence occurring with once-weekly rifampicin in high dosage. A procedure was developed for managing adverse reactions to intermittent rifampicin. Of 202 patients treated with intermittent rifampicin 60 developed adverse reactions, but in only 7 (3%) was it necessary to terminate the drug, though a further 10 (5%) were changed to daily rifampicin. On daily rifampicin, generalized hypersensitivity, cutaneous reactions, (one with purpura), and impaired liver function were encountered. Adverse reactions on the standard ethionamide, pyrazinamide, and cycloserine regimen were frequent and some were serious. PMID:4259217

  17. PROPOSAL OF ANTI-TUBERCULOSIS REGIMENS BASED ON SUSCEPTIBILITY TO ISONIAZID AND RIFAMPICIN

    PubMed Central

    Mendoza-Ticona, Alberto; Moore, David AJ; Alarcón, Valentina; Samalvides, Frine; Seas, Carlos

    2014-01-01

    Objective To elaborate optimal anti-tuberculosis regimens following drug susceptibility testing (DST) to isoniazid (H) and rifampicin (R). Design 12 311 M. tuberculosis strains (National Health Institute of Peru 2007-2009) were classified in four groups according H and R resistance. In each group the sensitivity to ethambutol (E), pirazinamide (Z), streptomycin (S), kanamycin (Km), capreomycin (Cm), ciprofloxacin (Cfx), ethionamide (Eto), cicloserine (Cs) and p-amino salicilic acid (PAS) was determined. Based on resistance profiles, domestic costs, and following WHO guidelines, we elaborated and selected optimal putative regimens for each group. The potential efficacy (PE) variable was defined as the proportion of strains sensitive to at least three or four drugs for each regimen evaluated. Results Selected regimes with the lowest cost, and highest PE of containing 3 and 4 effective drugs for TB sensitive to H and R were: HRZ (99,5%) and HREZ (99,1%), respectively; RZECfx (PE=98,9%) and RZECfxKm (PE=97,7%) for TB resistant to H; HZECfx (96,8%) and HZECfxKm (95,4%) for TB resistant to R; and EZCfxKmEtoCs (82.9%) for MDR-TB. Conclusion Based on resistance to H and R it was possible to select anti-tuberculosis regimens with high probability of success. This proposal is a feasible alternative to tackle tuberculosis in Peru where the access to rapid DST to H and R is improving progressively. PMID:23949502

  18. The effects of a discretionary food allowance during a caloric restriction regimen with provided food

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of self-selected discretionary foods in a structured energy restricted diet on adherence to a caloric restriction (CR) regimen, dietary satisfaction, and weight loss were studied in 32 healthy, overweight (BMI 25-30 kg/m2) adults, aged 20-42y participating in the CALERIE trial. Subjects ...

  19. Effect of feeding regimens on circadian rhythms: Implications for aging and longevity

    PubMed Central

    Froy, Oren; Miskin, Ruth

    2010-01-01

    Increased longevity and improved health can be achieved in mammals by two feeding regimens, caloric restriction (CR), which limits the amount of daily calorie intake, and intermittent fasting (IF), which allows the food to be availablead libitum every other day. The precise mechanisms mediating these beneficial effects are still unresolved. Resetting the circadian clock is another intervention that can lead to increased life span and well being, while clock disruption is associated with aging and morbidity. Currently, a large body of evidence links circadian rhythms with metabolism and feeding regimens. In particular, CR, and possibly also IF, can entrain the master clock located in the suprachiasmatic nuclei (SCN) of the brain hypothalamus. These findings raise the hypothesis that the beneficial effects exerted by these feeding regimens could be mediated, at least in part, through resetting of the circadian clock, thus leading to synchrony in metabolism and physiology. This hypothesis is reinforced by a transgenic mouse model showing spontaneously reduced eating alongside robust circadian rhythms and increased life span. This review will summarize recent findings concerning the relationships between feeding regimens, circadian rhythms, and metabolism with implications for ageing attenuation and life span extension. PMID:20228939

  20. [Treatment of malignant pheochromocytoma by combination of CVD regimen and transarterial embolization].

    PubMed

    Takeda, M; Katagiri, A; Kanai, T; Komeyama, T; Tsutsui, T; Katayama, Y; Kawakami, Y; Sato, S; Kimura, M; Odano, I

    1991-05-01

    We performed combination therapy with cyclophosphamide, Vincristine and Dacarbazine (CVD) regimen and transarterial embolization (TAE) in 2 cases of malignant pheochromocytoma with metastases. Case 1: 59-year-old female. After primary left adrenal lesion had been removed, recurrence at the left renal hilar region and metastases to the right iliac bone and 5th cervical vertebra occurred. We took 3 courses of CVD regimen after TAE for the lesions in the right iliac bone. Her endocrinological data has been normal for more than 1 year after treatment. Case 2: 29-year-old male. Total cystectomy, ileal conduit and pelvic lymphadenectomy had been performed for the primary lesion of the urinary bladder. 2 years after the 1st operation, metastases to the right obturator nodes and multiple bones occurred. We gave 3 courses of CVD regimen followed by TAE for the lesions in the right obturator nodes. Just after treatment, we could stop insulin and reduce anti-hypertension drugs, but the effect of treatment was temporary. In conclusion, combination of CVD regimen and TAE is effective for malignant pheochromocytoma with metastases.

  1. Caregiver Resources and Facilitation of Elderly Care Recipient Adherence to Health Regimens

    ERIC Educational Resources Information Center

    Greenberger, Haya; Litwin, Howard

    2003-01-01

    We studied the relationship between caregivers' personal and social resources and facilitation of adherence by elderly care recipients to a prescribed health regimen. Adherence facilitation was measured among 240 caregivers on a 45-item instrument constructed for this research. The facilitation score was regressed on caregivers' role-specific…

  2. Comparative effects of constant versus fluctuating thermal regimens on yellow perch growth, feed conversion and survival

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of fluctuating or constant thermal regimens on growth, mortality, and feed conversion were determined for juvenile yellow perch (Perca flavescens). Yellow perch averaging 156mm total length and 43g body weight were held in replicate 288L circular tanks for 129 days under: 1) a diel therm...

  3. Protection by low-dose kanamycin against noise-induced hearing loss in mice: dependence on dosing regimen and genetic background.

    PubMed

    Ohlemiller, Kevin K; Rybak Rice, Mary E; Rosen, Allyson D; Montgomery, Scott C; Gagnon, Patricia M

    2011-10-01

    We recently demonstrated that sub-chronic low-dose kanamycin (KM, 300 mg/kg sc, 2×/day, 10 days) dramatically reduces permanent noise-induced hearing loss (NIHL) and hair cell loss in 1 month old CBA/J mice (Fernandez et al., 2010, J. Assoc. Res. Otolaryngol. 11, 235-244). Protection by KM remained for at least 48 h after the last dose, and appeared to involve a cumulative effect of multiple doses as part of a preconditioning process. The first month of life lies within the early 'sensitive period' for both cochlear noise and ototoxic injury in mice, and CBA/J mice appear exquisitely vulnerable to noise during this period (Ohlemiller et al., 2011; Hearing Res. 272, 13-20). From our initial data, we could not rule out 1) that less rigorous treatment protocols than the intensive one we applied may be equally-or more-protective; 2) that protection by KM is tightly linked to processes unique to the sensitive period for noise or ototoxins; or 3) that protection by KM is exclusive to CBA/J mice. The present experiments address these questions by varying the number and timing of fixed doses (300 mg/kg sc) of KM, as well as the age at treatment in CBA/J mice. We also tested for protection in young C57BL/6J (B6) mice. We find that nearly complete protection against at least 2 h of intense (110 dB SPL) broadband noise can be observed in CBA/J mice at least for ages up to 1 year. Reducing dosing frequency to as little as once every other day (a four-fold decrease in dosing frequency) appeared as protective as twice per day. However, reducing the number of doses to just 1 or 2, followed by noise 24 or 48 h later greatly reduced protection. Notably, hearing thresholds and hair cells in young B6 mice appeared completely unprotected by the same regimen that dramatically protects CBA/J mice. We conclude that protective effects of KM against NIHL in CBA/J mice can be engaged by a wide range of dosing regimens, and are not exclusive to the sensitive period for noise or ototoxins

  4. Temozolomide chemoresistance heterogeneity in melanoma with different treatment regimens: DNA damage accumulation contribution.

    PubMed

    Boeckmann, Lars; Nickel, Ann-Christin; Kuschal, Christiane; Schaefer, Annika; Thoms, Kai-Martin; Schön, Michael P; Thomale, Jürgen; Emmert, Steffen

    2011-06-01

    The efficacy of temozolomide in melanoma treatment is low (response rate <20%) and may depend on the activity of O-methylguanine DNA methyltransferase (MGMT) and mismatch repair. We identified melanoma cell lines with different sensitivities to single versus prolonged clinical dosing regimens of temozolomide treatment and assessed a variety of potential resistance mechanisms using this model. We measured mRNA expression and promoter methylation of MGMT and essential mismatch repair genes (MLH1, MSH2). Cell cycle distribution, apoptosis/necrosis induction, O-methylguanine-adduct formation, and ABCB1 gene expression were assessed. We found that three cell lines, MelA, MelB, and MelC, were more sensitive to a single dose regimen than to a prolonged regimen, which would be expected to exhibit higher cytotoxicity. KAII and LIBR cell sensitivity was higher with regard to the prolonged treatment regimen, as expected. Only MelC expressed MGMT. Gene expression correlated well with promoter methylation. Temozolomide exposure did not alter mRNA expression. Different sensitivities to temozolomide were caused neither by delayed apoptosis induction due to early cell cycle arrest nor by O-methylguanine-adduct formation or efflux transporter expression. MelC was the most resistant cell line with rapid elimination of O-methylguanine adducts. This was in good agreement with its MGMT expression. The sensitive cell lines KAII and LIBR accumulated O-methylguanine adducts after a second treatment cycle with temozolomide in contrast with the other three cell lines. We conclude that MGMT expression and DNA adduct accumulation are relevant factors in temozolomide chemosensitivity. Considering individualized temozolomide treatment regimens either by quantification of DNA adducts or by chemosensitivity testing seems worthwhile clinically.

  5. Efficient intermittent rifapentine-moxifloxacin-containing short-course regimen for treatment of tuberculosis in mice.

    PubMed

    Veziris, N; Lounis, N; Chauffour, A; Truffot-Pernot, C; Jarlier, V

    2005-10-01

    Long-half-life drugs raise the hope of once-a-week administration of antituberculous treatment. In a previous study with the murine model of tuberculosis, the most active intermittent regimen which contained rifapentine (RFP), isoniazid (INH), and moxifloxacin (MXF) given once a week during 5.5 months, preceded by 2 weeks of daily treatment with INH, rifampin (RIF), pyrazinamide (PZA), and MXF, was less active than the standard 6-month daily RIF-INH-PZA regimen. We evaluated with the same model similar regimens in which we increased the dosing of rifapentine from 10 to 15 mg/kg of body weight and of moxifloxacin from 100 to 400 mg/kg. Mice infected intravenously by 6.2 x10(6) CFU of Mycobacterium tuberculosis H37Rv were treated 2 weeks later when infection was established. After 6 months of treatment, all mice had negative lung culture. After 3 months of follow-up, no relapse occurred in the two groups that received moxifloxacin at 400 mg/kg, whatever the dosage of RFP, and in the group receiving the standard RIF-INH-PZA control regimen. In contrast, in the two groups receiving moxifloxacin at a lower dosage, the relapse rate was significantly higher (13% in mice receiving RFP at 15 mg/kg and 27% in those receiving RFP at 10 mg/kg). Finally, the fully intermittent once-a-week regimen (26 drug ingestions) of INH, RFP (15 mg/kg), and MXF (400 mg/kg) led to a relapse rate of 11%. In conclusion, when used at high dosage, rifapentine and moxifloxacin are very efficient when combined with isoniazid in a once-a-week treatment in mouse tuberculosis.

  6. Efficient Intermittent Rifapentine-Moxifloxacin-Containing Short-Course Regimen for Treatment of Tuberculosis in Mice

    PubMed Central

    Veziris, N.; Lounis, N.; Chauffour, A.; Truffot-Pernot, C.; Jarlier, V.

    2005-01-01

    Long-half-life drugs raise the hope of once-a-week administration of antituberculous treatment. In a previous study with the murine model of tuberculosis, the most active intermittent regimen which contained rifapentine (RFP), isoniazid (INH), and moxifloxacin (MXF) given once a week during 5.5 months, preceded by 2 weeks of daily treatment with INH, rifampin (RIF), pyrazinamide (PZA), and MXF, was less active than the standard 6-month daily RIF-INH-PZA regimen. We evaluated with the same model similar regimens in which we increased the dosing of rifapentine from 10 to 15 mg/kg of body weight and of moxifloxacin from 100 to 400 mg/kg. Mice infected intravenously by 6.2 ×106 CFU of Mycobacterium tuberculosis H37Rv were treated 2 weeks later when infection was established. After 6 months of treatment, all mice had negative lung culture. After 3 months of follow-up, no relapse occurred in the two groups that received moxifloxacin at 400 mg/kg, whatever the dosage of RFP, and in the group receiving the standard RIF-INH-PZA control regimen. In contrast, in the two groups receiving moxifloxacin at a lower dosage, the relapse rate was significantly higher (13% in mice receiving RFP at 15 mg/kg and 27% in those receiving RFP at 10 mg/kg). Finally, the fully intermittent once-a-week regimen (26 drug ingestions) of INH, RFP (15 mg/kg), and MXF (400 mg/kg) led to a relapse rate of 11%. In conclusion, when used at high dosage, rifapentine and moxifloxacin are very efficient when combined with isoniazid in a once-a-week treatment in mouse tuberculosis. PMID:16189074

  7. Assessing the effectiveness of antiretroviral regimens in cohort studies involving HIV-positive injection drug users

    PubMed Central

    Lima, Viviane Dias; Nosyk, Bohdan; Wood, Evan; Kozai, Tsubasa; Zhang, Wendy; Chan, Keith; Montaner, Julio S.G.

    2015-01-01

    Objective We compared the effectiveness of different highly active antiretroviral therapy (HAART) regimens considering, separately, history of injection drug use (IDU) (yes/no). Design, methods A total of 1163 HIV-infected patients initiated HAART between 1 January 2000 and 28 February 2009 in British Columbia, Canada, and were followed until 28 February 2010. HAART effectiveness was measured by the ability to achieve viral suppression below 50 copies/ml at 6 months. We compared HAART regimens containing efavirenz and boosted atazanavir. We developed logistic regression models using different techniques to control for potential confounders. Results Among the 1163 patients, 796 (68%) achieved viral suppression at 6 months (32% reporting a history of IDU). Different confounding models yielded very similar odds ratios for achieving viral suppression. Boosted atazanavir-based HAART demonstrated to be the most effective regimen, showing a surprisingly higher benefit for patients with a history of IDU (odds ratios from different models ranged from 1.74–1.95 to 1.45–1.51). Conclusions The literature has conflicting results regarding the effectiveness of HAART to treat HIV infection among those with a history of IDU. We have shown that most patients, with and without a history of IDU, were able to achieve viral suppression at 6 months. Boosted atazanavir-based HAART was the most resilient regimen and it was more effective than efavirenz-based HAART among IDUs. Given the limited inclusion of IDU in clinical trials of HAART’s efficacy, a randomized clinical trial comparing different first-line HAART regimens among IDU is warranted based on these results. PMID:22555161

  8. The impact of bismuth addition to sequential treatment on Helicobacter pylori eradication: A pilot study.

    PubMed

    Basyigit, Sebahat; Kefeli, Ayse; Sapmaz, Ferdane; Yeniova, Abdullah Ozgür; Asilturk, Zeliha; Hokkaomeroglu, Murat; Uzman, Metin; Nazligul, Yasar

    2015-10-25

    The success of the current anti-Helicobacter pylori (H. pylori) treatment protocols is reported to decrease by years, and research is needed to strengthen the H. pylori eradication treatment. Sequential treatment (ST), one of the treatment modalities for H. pylori eradication, includes amoxicillin 1 gr b.i.d and proton pump inhibitor b.i.d for first 5 days and then includes clarithromycin 500 mg b.i.d, metronidazole 500 mg b.i.d and a proton pump inhibitor b.i.d for remaining 5 days. In this study, we investigated efficacy and tolerability of bismuth addition in to ST. We included patients that underwent upper gastrointestinal endoscopy in which H. pylori infection was diagnosed by histological examination of antral and corporal gastric mucosa biopsy. Participants were randomly administered ST or bismuth containing ST (BST) protocols for the first-line H. pylori eradication therapy. Participants have been tested by urea breath test for eradication success 6 weeks after the completion of treatment. One hundred and fifty patients (93 female, 57 male) were enrolled. There were no significant differences in eradication rates for both intention to treat population (70.2%, 95% confidence interval [CI]: 66.3-74.1% vs. 71.8%, 95% CI: 61.8-81.7%, for ST and BST, respectively, p>0.05) and per protocol population (74.6%, 95% CI: 63.2-85.8% vs. 73.7%, 95% CI: 63.9-83.5% for ST and BST, respectively, p>0.05). Despite the undeniable effect of bismuth, there may be several possible reasons of unsatisfactory eradication success. Drug administration time, coadministration of other drugs, possible H. pylori resistance to bismuth may affect the eradication success. The addition of bismuth subcitrate to ST regimen does not provide significant increase in eradication rates.

  9. Sequential Dependencies in Interresponse Times and Reinforcement/Response-Cost

    ERIC Educational Resources Information Center

    Kawashima, Kentaro

    2004-01-01

    This study investigates sequential dependencies in interresponse times (IRTs) produced by human subjects under random-ratio (RR) and staircase stochastic reinforcement of waiting (staircase SRW) schedules using autocorrelation and relative frequencies of IRT[subscript n] *IRT[subscript n+1] pairs. In the first of two experiments conducted for this…

  10. Harmonizing and Improvising in the Choral Rehearsal: A Sequential Approach

    ERIC Educational Resources Information Center

    Bell, Cindy L.

    2004-01-01

    This article challenges choral teachers to motivate their choirs to a new level of choral singing and harmonic creativity and outlines a sequential process for introducing improvisation into the daily warm-up. It argues that students can learn to harmonize and improvise by ear as part of each day's warm-up period. Sections include: (1) Chord…

  11. Decomposition of Copper (II) Sulfate Pentahydrate: A Sequential Gravimetric Analysis.

    ERIC Educational Resources Information Center

    Harris, Arlo D.; Kalbus, Lee H.

    1979-01-01

    Describes an improved experiment of the thermal dehydration of copper (II) sulfate pentahydrate. The improvements described here are control of the temperature environment and a quantitative study of the decomposition reaction to a thermally stable oxide. Data will suffice to show sequential gravimetric analysis. (Author/SA)

  12. Proportion Congruent Effects in the Absence of Sequential Congruent Effects

    ERIC Educational Resources Information Center

    Torres-Quesada, Maryem; Milliken, Bruce; Lupiáñez, Juan; Funes, María Jesús

    2014-01-01

    A debated question in the cognitive control field is whether cognitive control is best conceptualized as a collection of distinct control mechanisms or a single general purpose mechanism. In an attempt to answer this question, previous studies have dissociated two well-known effects related to cognitive control: sequential congruence and…

  13. Sequential decision plans, benthic macroinvertebrates, and biological monitoring programs

    NASA Astrophysics Data System (ADS)

    Jackson, John K.; Resh, Vincent H.

    1989-07-01

    A common obstacle to the inclusion of benthic macroinvertebrates in water quality monitoring programs is that numerous sample units must be examined in order to distinguish between impacted and unimpacted conditions, which can add significantly to the total cost of a monitoring program. Sequential decision plans can be used to reduce this cost because the number of sample units needed to classify a site as impacted or unimpacted is reduced by an average of 50%. A plan is created using definitions of unimpacted and impacted conditions, a description of the mathematical distribution of the data, and definitions of acceptable risks of type I and II errors. The applicability of using sequential decision plans and benthic macroinvertebrates in water quality monitoring programs is illustrated with several examples (e.g., identifying moderate and extreme changes in species richness in response to acid mine drainage; assessing the impact of a crude oil contamination on the density of two benthic populations; monitoring the effect of geothermal effluents on species diversity). These examples use data conforming to the negative binomial, Poisson, and normal distributions and define impact as changes in population density, species richness, or species diversity based on empirical data or the economic feasibility of the sequential decision plan. All mathematical formulae and intermediate values are provided for the step-by-step calculation of each sequential decision plan.

  14. Consequences of sequential sampling for meta-analysis.

    PubMed

    Braschi, Lorenzo; Botella, Juan; Suero, Manuel

    2014-12-01

    Sequential stopping rules allow hypotheses to be tested using smaller sample sizes than are possible under conventional methods, while controlling the Type I and II error rates. However, the consequences of using such procedures when combining studies in a meta-analysis have rarely been discussed. For a primary study to be included in a meta-analysis, it must provide an estimate of the effect size, and it must be possible to calculate the variance of this estimate, which is used for weighting the study. It is therefore crucial to know whether the use of sequential stopping rules introduces any bias in the estimate of the effect size and/or modifies the variance of the estimate. In the present research, both aspects were studied for the CLAST rule, as applied to testing the difference between two means from paired samples, in a variety of scenarios of sample size and population effect size. The results show that although the bias is small, but still larger than that for the fixed-sample rule, the variance of the estimate is much higher with the CLAST sequential stopping rule. The implications of these results for the incorporation of such studies into meta-analyses are discussed. It is recommended to incorporate such studies into meta-analyses by taking only the information conveyed in the initial sample. The authors of primary studies employing sequential rules should report that information when publishing their results.

  15. Nonspherical supernova remnants. IV - Sequential explosions in OB associations

    NASA Technical Reports Server (NTRS)

    Tenorio-Tagle, G.; Bodenheimer, P.; Rozyczka, M.

    1987-01-01

    Multisupernova remnants, driven by sequential supernova explosions in OB associations, are modelled by means of two-dimensional hydrodynamical calculations. It is shown that due to the Rayleigh-Taylor instability the remnants quickly evolve into highly irregular structures. A critical evaluation of the multisupernova model as an explanation for supershells is given.

  16. Statistical Studies on Sequential Probability Ratio Test for Radiation Detection

    SciTech Connect

    Warnick Kernan, Ding Yuan, et al.

    2007-07-01

    A Sequential Probability Ratio Test (SPRT) algorithm helps to increase the reliability and speed of radiation detection. This algorithm is further improved to reduce spatial gap and false alarm. SPRT, using Last-in-First-Elected-Last-Out (LIFELO) technique, reduces the error between the radiation measured and resultant alarm. Statistical analysis determines the reduction of spatial error and false alarm.

  17. Orthographic Processing and Visual Sequential Memory in Unexpectedly Poor Spellers

    ERIC Educational Resources Information Center

    Holmes, Virginia M.; Malone, Aisling M.; Redenbach, Holly

    2008-01-01

    Does unexpectedly poor spelling in adults result from inferior visual sequential memory? In one experiment, unexpectedly poor spellers performed significantly worse than better spellers in the immediate reproduction of sequences of visual symbols, but in a second experiment, the effect was not replicated. Poor spellers were also no worse at the…

  18. Applications of Bayesian Decision Theory to Sequential Mastery Testing.

    ERIC Educational Resources Information Center

    Vos, Hans J.

    The purpose of this paper is to formulate optimal sequential rules for mastery tests. The framework for this approach is derived from empirical Bayesian decision theory. Both a threshold and linear loss structure are considered. The binomial probability distribution is adopted as the psychometric model involved. Conditions sufficient for…

  19. Application of Sequential Interval Estimation to Adaptive Mastery Testing

    ERIC Educational Resources Information Center

    Chang, Yuan-chin Ivan

    2005-01-01

    In this paper, we apply sequential one-sided confidence interval estimation procedures with beta-protection to adaptive mastery testing. The procedures of fixed-width and fixed proportional accuracy confidence interval estimation can be viewed as extensions of one-sided confidence interval procedures. It can be shown that the adaptive mastery…

  20. Sequential growth for lifetime extension in biomimetic polypyrrole actuator systems

    NASA Astrophysics Data System (ADS)

    Sarrazin, J. C.; Mascaro, Stephen A.

    2015-04-01

    Electroactive polymers (EAPs) present prospective use in actuation and manipulation devices due to their low electrical activation requirements, biocompatibility, and mechanical performance. One of the main drawbacks with EAP actuators is a decrease in performance over extended periods of operation caused by over-oxidation of the polymer and general polymer degradation. Synthesis of the EAP material, polypyrrole with an embedded metal helix allows for sequential growth of the polymer during operation. The helical metal electrode acts as a scaffolding to support the polymer, and direct the 3-dimensional change in volume of the polymer along the axis of the helix during oxidative and reductive cycling. The metal helix also provides a working metal electrode through the entire length of the polymer actuator to distribute charge for actuation, as well as for sequential growth steps during the lifetime of operation of the polymer. This work demonstrates the method of sequential growth can be utilized after extended periods of use to partially restore electrical and mechanical performance of polypyrrole actuators. Since the actuation must be temporarily stopped to allow for a sequential growth cycle to be performed and reverse some of the polymer degradation, these actuator systems more closely mimic natural muscle in their analogous maintenance and repair.

  1. Functionalized sorbent for chemical separations and sequential forming process

    DOEpatents

    Fryxell, Glen E [Kennewick, WA; Zemanian, Thomas S [Richland, WA

    2012-03-20

    A highly functionalized sorbent and sequential process for making are disclosed. The sorbent includes organic short-length amino silanes and organic oligomeric polyfunctional amino silanes that are dispersed within pores of a porous support that form a 3-dimensional structure containing highly functionalized active binding sites for sorption of analytes.

  2. Sequential Mathematics Course III. Part 1. Pilot Edition.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Div. of Curriculum and Instruction.

    This document outlines part one of the third year course of the newly implemented New York State Mathematics Curriculum. The three-year Sequential Mathematics sequence designed by New York State is a move in the direction of fusing the formerly separate topics found in algebra, geometry, and intermediate algebra/trigonometry, and introducing…

  3. Sequential color video to parallel color video converter

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The engineering design, development, breadboard fabrication, test, and delivery of a breadboard field sequential color video to parallel color video converter is described. The converter was designed for use onboard a manned space vehicle to eliminate a flickering TV display picture and to reduce the weight and bulk of previous ground conversion systems.

  4. Variations on Stochastic Curtailment in Sequential Mastery Testing

    ERIC Educational Resources Information Center

    Finkelman, Matthew David

    2010-01-01

    In sequential mastery testing (SMT), assessment via computer is used to classify examinees into one of two mutually exclusive categories. Unlike paper-and-pencil tests, SMT has the capability to use variable-length stopping rules. One approach to shortening variable-length tests is stochastic curtailment, which halts examination if the probability…

  5. Episodic Contributions to Sequential Control: Learning from a Typist's Touch

    ERIC Educational Resources Information Center

    Crump, Matthew J. C.; Logan, Gordon D.

    2010-01-01

    Sequential control over routine action is widely assumed to be controlled by stable, highly practiced representations. Our findings demonstrate that the processes controlling routine actions in the domain of skilled typing can be flexibly manipulated by memory processes coding recent experience with typing particular words and letters. In two…

  6. Color Breakup In Sequentially-Scanned LC Displays

    NASA Technical Reports Server (NTRS)

    Arend, L.; Lubin, J.; Gille, J.; Larimer, J.; Statler, Irving C. (Technical Monitor)

    1994-01-01

    In sequentially-scanned liquid-crystal displays the chromatic components of color pixels are distributed in time. For such displays eye, head, display, and image-object movements can cause the individual color elements to be visible. We analyze conditions (scan designs, types of eye movement) likely to produce color breakup.

  7. Parallel canonical Monte Carlo simulations through sequential updating of particles

    NASA Astrophysics Data System (ADS)

    O'Keeffe, C. J.; Orkoulas, G.

    2009-04-01

    In canonical Monte Carlo simulations, sequential updating of particles is equivalent to random updating due to particle indistinguishability. In contrast, in grand canonical Monte Carlo simulations, sequential implementation of the particle transfer steps in a dense grid of distinct points in space improves both the serial and the parallel efficiency of the simulation. The main advantage of sequential updating in parallel canonical Monte Carlo simulations is the reduction in interprocessor communication, which is usually a slow process. In this work, we propose a parallelization method for canonical Monte Carlo simulations via domain decomposition techniques and sequential updating of particles. Each domain is further divided into a middle and two outer sections. Information exchange is required after the completion of the updating of the outer regions. During the updating of the middle section, communication does not occur unless a particle moves out of this section. Results on two- and three-dimensional Lennard-Jones fluids indicate a nearly perfect improvement in parallel efficiency for large systems.

  8. Parallel canonical Monte Carlo simulations through sequential updating of particles.

    PubMed

    O'Keeffe, C J; Orkoulas, G

    2009-04-07

    In canonical Monte Carlo simulations, sequential updating of particles is equivalent to random updating due to particle indistinguishability. In contrast, in grand canonical Monte Carlo simulations, sequential implementation of the particle transfer steps in a dense grid of distinct points in space improves both the serial and the parallel efficiency of the simulation. The main advantage of sequential updating in parallel canonical Monte Carlo simulations is the reduction in interprocessor communication, which is usually a slow process. In this work, we propose a parallelization method for canonical Monte Carlo simulations via domain decomposition techniques and sequential updating of particles. Each domain is further divided into a middle and two outer sections. Information exchange is required after the completion of the updating of the outer regions. During the updating of the middle section, communication does not occur unless a particle moves out of this section. Results on two- and three-dimensional Lennard-Jones fluids indicate a nearly perfect improvement in parallel efficiency for large systems.

  9. The Motivating Language of Principals: A Sequential Transformative Strategy

    ERIC Educational Resources Information Center

    Holmes, William Tobias

    2012-01-01

    This study implemented a Sequential Transformative Mixed Methods design with teachers (as recipients) and principals (to give voice) in the examination of principal talk in two different school accountability contexts (Continuously Improving and Continuously Zigzag) using the conceptual framework of Motivating Language Theory. In phase one,…

  10. Futility rules in bioequivalence trials with sequential designs.

    PubMed

    Fuglsang, Anders

    2014-01-01

    Health Canada, the US Food and Drug Administration, as well as the European Medicines Agency consider sequential designs acceptable for bioequivalence studies as long as the type I error is controlled at 5%. The EU guideline explicitly asks for specification of stopping rules, so the goal of this work is to investigate how stopping rules may affect type I errors and power for recently published sequential bioequivalence trial designs. Using extensive trial simulations, five different futility rules were evaluated for their effect on type I error rates and power in two-stage scenarios. Under some circumstances, notably low sample size in stage 1 and/or high variability power may be very severely affected by the stopping rules, whereas type I error rates appear less affected. Because applicants may initiate sequential studies when the variability is not known in advance, achieving sufficient power and thereby complying with certain guideline requirements may be challenging and application of optimistic futility rules could possibly be unethical. This is the first work to investigate how futility rules affect type I errors and power in sequential bioequivalence trials.

  11. The Sequential Probability Ratio Test and Binary Item Response Models

    ERIC Educational Resources Information Center

    Nydick, Steven W.

    2014-01-01

    The sequential probability ratio test (SPRT) is a common method for terminating item response theory (IRT)-based adaptive classification tests. To decide whether a classification test should stop, the SPRT compares a simple log-likelihood ratio, based on the classification bound separating two categories, to prespecified critical values. As has…

  12. Alternating and Sequential Motion Rates in Older Adults

    ERIC Educational Resources Information Center

    Pierce, John E.; Cotton, Susan; Perry, Alison

    2013-01-01

    Background: Alternating motion rate (AMR) and sequential motion rate (SMR) are tests of articulatory diadochokinesis that are widely used in the evaluation of motor speech. However, there are no quality normative data available for adults aged 65 years and older. Aims: There were two aims: (1) to obtain a representative, normative dataset of…

  13. Adherence to Medical Regimens: Understanding the Effects of Cognitive Appraisal, Quality of Life, and Perceived Family Resiliency

    ERIC Educational Resources Information Center

    Frain, Michael P.; Bishop, Malachy; Tschopp, Molly K.; Ferrin, Micheal J.; Frain, Judy

    2009-01-01

    Adherence studies have taken center stage due to the life-threatening risks associated with nonadherence to highly active antiretroviral therapy (HAART) regimens for people with HIV/AIDS. This study examines adherence through self-report of individuals on HAART regimens in a manner to account for demand characteristic bias, while still attempting…

  14. A Combination Regimen Design Program Based on Pharmacodynamic Target Setting for Childhood Tuberculosis: Design Rules for the Playground

    PubMed Central

    Srivastava, Shashikant; Deshpande, Devyani; Pasipanodya, Jotam G.; Thomas, Tania; Swaminathan, Soumya; Nuermberger, Eric; Gumbo, Tawanda

    2016-01-01

    Children with tuberculosis are treated with drug regimens copied from adults despite significant differences in antibiotic pharmacokinetics, pathology, and the microbial burden between childhood and adult tuberculosis. We sought to develop a new and effective oral treatment regimen specific to children of different ages. We investigated and validated the concept that target drug concentrations associated with therapy failure and death in children are different from those of adults. On that basis, we proposed a 4-step program to rapidly develop treatment regimens for children. First, target drug concentrations for optimal efficacy are derived from preclinical models of disseminated tuberculosis that recapitulate pediatric pharmacokinetics, starting with monotherapy. Second, 2-drug combinations were examined for zones of synergy, antagonism, and additivity based on a whole exposure–response surface. Exposures associated with additivity or synergy were then combined and the regimen was compared to standard therapy. Third, several exposures of the third drug were added, and a 3-drug regimen was identified based on kill slopes in comparison to standard therapy. Fourth, computer-aided clinical trial simulations are used to identify clinical doses that achieve these kill rates in children in different age groups. The proposed program led to the development of a 3-drug combination regimen for children from scratch, independent of adult regimens, in <2 years. The regimens and doses can be tested in animal models and in clinical trials. PMID:27742637

  15. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection.

    PubMed

    2011-12-09

    Preventing tuberculosis (TB) by treating latent Mycobacterium tuberculosis infection (LTBI) is a cornerstone of the U.S. strategy for TB elimination. Three randomized controlled trials have shown that a new combination regimen of isoniazid (INH) and rifapentine (RPT) administered weekly for 12 weeks as directly observed therapy (DOT) is as effective for preventing TB as other regimens and is more likely to be completed than the U.S. standard regimen of 9 months of INH daily without DOT. This report provides CDC recommendations for using the INH-RPT regimen. The new regimen is recommended as an equal alternative to the 9-month INH regimen for otherwise healthy patients aged≥12 years who have LTBI and factors that are predictive of TB developing (e.g., recent exposure to contagious TB). The new regimen also can be considered for other categories of patients when it offers practical advantages. Although the INH-RPT regimen was well tolerated in treatment trials, monitoring for adverse effects is recommended. Severe adverse effects should be reported to the Food and Drug Administration (FDA) and CDC.

  16. The Role of Health Beliefs in the Regimen Adherence and Metabolic Control of Adolescents and Adults with Diabetes Mellitus.

    ERIC Educational Resources Information Center

    Brownlee-Duffeck, Martha; And Others

    1987-01-01

    Examined the role of health beliefs in diabetic regimen adherence and metabolic control. Health beliefs accounted for a statistically significant portion of the variance in both. For older patients perceived benefits of adhering to the diabetic regimen was most significant. For younger patients costs figured prominently in adherence and perceived…

  17. A Review of Myeloablative vs Reduced Intensity/Non-Myeloablative Regimens in Allogeneic Hematopoietic Stem Cell Transplantations

    PubMed Central

    Atilla, Erden; Ataca Atilla, Pınar; Demirer, Taner

    2017-01-01

    Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment option for both malignant and some benign hematological diseases. During the last decade, many of the newer high-dose regimens in different intensity have been developed specifically for patients with hematologic malignancies and solid tumors. Today there are three main approaches used prior to allogeneic transplantation: Myeloablative (MA), Reduced Intensity Conditioning (RIC) and Non-MA (NMA) regimens. MA regimens cause irreversible cytopenia and there is a requirement for stem cell support. Patients who receive NMA regimen have minimal cytopenia and this type of regimen can be given without stem cell support. RIC regimens do not fit the criteria of MA and NMA: the cytopenia is reversible and the stem cell support is necessary. NMA/RIC for Allo-HSCT has opened a new era for treating elderly patients and those with comorbidities. The RIC conditioning was used for 40% of all Allo-HSCT and this trend continue to increase. In this paper, we will review these regimens in the setting of especially allogeneic HSCT and our aim is to describe the history, features and impact of these conditioning regimens on specific diseases. PMID:28251017

  18. Sequential magnetic resonance imaging analysis of the maxillary sinuses: implications for a model of gene therapy in cystic fibrosis.

    PubMed

    Graham, S M; Launspach, J L; Welsh, M J; Zabner, J

    1999-04-01

    Serial maxillary sinus aminoglycoside lavage is an adjunctive technique increasingly employed in a variety of areas in cystic fibrosis (CF). It may be helpful in reducing revision rates for sinus surgery, in lowering rates of bronchial pseudomonal colonization after lung transplantation and in the evolving field of gene therapy for CF. The goal of this study was to assess the utility of the maxillary sinus as a model for gene transfer in cystic fibrosis. We performed serial maxillary sinus lavage, in accordance with published protocols, using tobramycin in a randomized series of five CF subjects. Lavage was performed for up to 10 days and sequential magnetic resonance imaging (MRI) scans were taken at zero, 10, 30, 60, 120 and 180 days. The 30 MRI scans were blindly scored by two examiners on the parameters of maxillary sinus aeration, averaged over the five time intervals, was significantly improved (p < 0.05) in the lavaged sinus. This study provides the first systematic image-based measure of efficacy of maxillary sinus aminoglycoside lavage, a major element of a number of clinical protocols used in the treatment of CF. The prolonged increase in aeration after lavage suggests that any further improvement potentially achievable after gene transfer would be difficult to detect, limiting the value of this system as a model of clinical efficacy of gene transfer in CF.

  19. Sequential Treatments with Tongsai and Bufei Yishen Granules Reduce Inflammation and Improve Pulmonary Function in Acute Exacerbation-Risk Window of Chronic Obstructive Pulmonary Disease in Rats

    PubMed Central

    Lu, Xiaofan; Li, Ya; Wang, Haifeng; Wu, Zhaohuan; Li, Hangjie; Wang, Yang

    2016-01-01

    Background. Sequential treatments of Chinese medicines for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) risk window (RW) have benefits for preventing reoccurrences of AEs; however, the effects on pulmonary function, pulmonary, and systemic inflammatory biomarkers remain unclear. Methods. Cigarette-smoke/bacterial infections induced rats were randomized into Control, COPD, AECOPD, Tongsai Granule/normal saline (TSG/NS), moxifloxacin + salbutamol/NS (MXF+STL/NS), TSG/Bufei Yishen Granule (BYG), MXF+STL/STL, and TSG+MXF+STL/BYG+STL groups and given corresponding medicine(s) in AE- and/or RW phase. Body temperature, pulmonary function, blood cytology, serum amyloid A (SAA) and C-reactive protein (CRP), pulmonary histomorphology and myeloperoxidase (MPO), polymorphonuclear (PMN) elastase, interleukins IL-1β, IL-6, and IL-10, and tumor necrosis factor- (TNF-) α expressions were determined. Results. Body temperature, inflammatory cells and cytokines, SAA, CRP, and pulmonary impairment were higher in AECOPD rats than stable COPD, while pulmonary function declined and recovered to COPD level in 14–18 days. All biomarkers were improved in treated groups with shorter recovery times of 4–10 days, especially in TSG+MXF+STL/BYG+STL group. Conclusion. Sequential treatments with Tongsai and Bufei Yishen Granules, during AECOPD-RW periods, can reduce inflammatory response and improve pulmonary function and shorten the recovery courses of AEs, especially the integrated Chinese and Western medicines. PMID:27563333

  20. Research on parallel algorithm for sequential pattern mining

    NASA Astrophysics Data System (ADS)

    Zhou, Lijuan; Qin, Bai; Wang, Yu; Hao, Zhongxiao

    2008-03-01

    Sequential pattern mining is the mining of frequent sequences related to time or other orders from the sequence database. Its initial motivation is to discover the laws of customer purchasing in a time section by finding the frequent sequences. In recent years, sequential pattern mining has become an important direction of data mining, and its application field has not been confined to the business database and has extended to new data sources such as Web and advanced science fields such as DNA analysis. The data of sequential pattern mining has characteristics as follows: mass data amount and distributed storage. Most existing sequential pattern mining algorithms haven't considered the above-mentioned characteristics synthetically. According to the traits mentioned above and combining the parallel theory, this paper puts forward a new distributed parallel algorithm SPP(Sequential Pattern Parallel). The algorithm abides by the principal of pattern reduction and utilizes the divide-and-conquer strategy for parallelization. The first parallel task is to construct frequent item sets applying frequent concept and search space partition theory and the second task is to structure frequent sequences using the depth-first search method at each processor. The algorithm only needs to access the database twice and doesn't generate the candidated sequences, which abates the access time and improves the mining efficiency. Based on the random data generation procedure and different information structure designed, this paper simulated the SPP algorithm in a concrete parallel environment and implemented the AprioriAll algorithm. The experiments demonstrate that compared with AprioriAll, the SPP algorithm had excellent speedup factor and efficiency.

  1. Ecological niches in sequential generations of eastern North American monarch butterflies (Lepidoptera: Danaidae): the ecology of migration and likely climate change implications.

    PubMed

    Batalden, Rebecca V; Oberhauser, Karen; Peterson, A Townsend

    2007-12-01

    Eastern North American monarch butterflies (Danaus plexippus L.) show a series of range shifts during their breeding season. Using ecological niche modeling, we studied the environmental context of these shifts by identifying the ecological conditions that monarchs use in successive summer months. Monarchs use a consistent ecological regimen through the summer, but these conditions contrast strikingly with those used during the winter. Hence, monarchs exhibit niche-following among sequential breeding generations but niche-switching between the breeding and overwintering stages of their annual cycle. We projected their breeding ecological niche onto monthly future climate scenarios, which indicated northward shifts, particularly at the northern extreme of their summer movements, over the next 50 yrs; if both monarchs and their milkweed host plants cannot track these changing climates, monarchs could lose distributional area during critical breeding months.

  2. The Efficacy of Moxifloxacin-Containing Triple Therapy after Standard Triple, Sequential, or Concomitant Therapy Failure for Helicobacter pylori Eradication in Korea

    PubMed Central

    Chung, Kwang Hyun; Lee, Dong Ho; Jin, Eunhyo; Cho, Yuri; Seo, Ji Yeon; Kim, Nayoung; Jeong, Sook Hyang; Kim, Jin Wook; Hwang, Jin-Hyeok; Shin, Cheol Min

    2014-01-01

    Background/Aims Retreatment after initial treatment failure for Helicobacter pylori is very challenging. The purpose of this study was to evaluate the efficacies of moxifloxacin-containing triple and bismuth-containing quadruple therapy. Methods A total of 151 patients, who failed initial H. pylori treatment, were included in this retrospective cohort study. The initial regimens were standard triple, sequential, or concomitant therapy, and the efficacies of the two following second-line treatments were evaluated: 7-day moxifloxacin-containing triple therapy (rabeprazole 20 mg twice a day, amoxicillin 1,000 mg twice a day, and moxifloxacin 400 mg once daily) and 7-day bismuth-containing quadruple therapy (rabeprazole 20 mg twice a day, tetracycline 500 mg 4 times a day, metronidazole 500 mg 3 times a day, and tripotassium dicitrate bismuthate 300 mg 4 times a day). Results The overall eradication rates after moxifloxacin-containing triple therapy and bismuth-containing quadruple therapy were 69/110 (62.7%) and 32/41 (78%), respectively. Comparison of the two regimens was performed in the patients who failed standard triple therapy, and the results revealed eradication rates of 14/28 (50%) and 32/41 (78%), respectively (p=0.015). The frequency of noncompliance was not different between the two groups, and there were fewer adverse effects in the moxifloxacin-containing triple therapy group (2.8% vs 7.3%, p=0.204 and 25.7% vs 43.9%, p=0.031, respectively). Conclusions Moxifloxacin-containing triple therapy, a recommended second-line treatment for initial concomitant or sequential therapy failure, had insufficient efficacy. PMID:25368747

  3. Combination of everolimus and tacrolimus: a potentially effective regimen for recalcitrant psoriasis.

    PubMed

    Wei, Kai-Che; Lai, Ping-Chin

    2015-01-01

    Severe forms of psoriasis that are refractory to conventional therapies are often difficult to manage. The mammalian target of rapamycin (mTOR) inhibitors potentially have versatile effects toward putative psoriatic pathologic pathways. Therefore, mTOR inhibitors may offer a range of new therapeutic options for patients with psoriasis. We describe a 55-year-old male renal transplant patient with refractory psoriasis. We adjusted his antirejection regimen and put him on everolimus (Certican(®); Novartis, Basel, Switzerland; a semisynthetic macrolide, belonging to the mTOR inhibitors family) with low-dose tacrolimus. This combination regimen maintained his graft function and successfully controlled his psoriasis. His skin lesions never recurred in the next 18 months. To our knowledge, this is the first report showing that the combination of everolimus and tacrolimus could be used to treat recalcitrant psoriasis. The relative benefit-risk profiles of such therapies worth further investigation.

  4. Optimal biologic dose of metronomic chemotherapy regimens is associated with maximum antiangiogenic activity.

    PubMed

    Shaked, Yuval; Emmenegger, Urban; Man, Shan; Cervi, Dave; Bertolini, Francesco; Ben-David, Yaacov; Kerbel, Robert S

    2005-11-01

    Low-dose metronomic chemotherapy is a promising therapeutic cancer treatment strategy thought to have an antiangiogenic basis. However, the advantages of reduced toxicity, increased efficacy in some cases, and ability to combine chemotherapy administered long term in this way with targeted therapies can be compromised by the empiricism associated with determining the optimum biologic dose (OBD). Using 4 distinct metronomic chemotherapy regimens in 4 different preclinical tumor models, including a hematologic malignancy, we established the OBD by determining the maximum efficacy associated with minimum or no toxicity. We then found each OBD to be strikingly correlated with the maximum reduction in viable peripheral blood circulating vascular endothelial growth factor receptor 2-positive (VEGFR-2+) endothelial precursors (CEPs). These results suggest that CEPs may serve as a pharmacodynamic biomarker to determine the OBD of metronomic chemotherapy regimens.

  5. Modelling and analysis of the feeding regimen induced entrainment of hepatocyte circadian oscillators using petri nets.

    PubMed

    Tareen, Samar Hayat Khan; Ahmad, Jamil

    2015-01-01

    Circadian rhythms are certain periodic behaviours exhibited by living organism at different levels, including cellular and system-wide scales. Recent studies have found that the circadian rhythms of several peripheral organs in mammals, such as the liver, are able to entrain their clocks to received signals independent of other system level clocks, in particular when responding to signals generated during feeding. These studies have found SIRT1, PARP1, and HSF1 proteins to be the major influencers of the core CLOCKBMAL1:PER-CRY circadian clock. These entities, along with abstracted feeding induced signals were modelled collectively in this study using Petri Nets. The properties of the model show that the circadian system itself is strongly robust, and is able to continually evolve. The modelled feeding regimens suggest that the usual 3 meals/day and 2 meals/day feeding regimens are beneficial with any more or less meals/day negatively affecting the system.

  6. Modelling and Analysis of the Feeding Regimen Induced Entrainment of Hepatocyte Circadian Oscillators Using Petri Nets

    PubMed Central

    Tareen, Samar Hayat Khan; Ahmad, Jamil

    2015-01-01

    Circadian rhythms are certain periodic behaviours exhibited by living organism at different levels, including cellular and system-wide scales. Recent studies have found that the circadian rhythms of several peripheral organs in mammals, such as the liver, are able to entrain their clocks to received signals independent of other system level clocks, in particular when responding to signals generated during feeding. These studies have found SIRT1, PARP1, and HSF1 proteins to be the major influencers of the core CLOCKBMAL1:PER-CRY circadian clock. These entities, along with abstracted feeding induced signals were modelled collectively in this study using Petri Nets. The properties of the model show that the circadian system itself is strongly robust, and is able to continually evolve. The modelled feeding regimens suggest that the usual 3 meals/day and 2 meals/day feeding regimens are beneficial with any more or less meals/day negatively affecting the system. PMID:25789928

  7. Effects of sequential paclitaxel–carboplatin followed by gemcitabine-based chemotherapy compared with paclitaxel-carboplatin therapy administered to patients with advanced epithelial ovarian cancer

    PubMed Central

    Wang, Fei; Du, Xuelian; Li, Xiaoxia; Liu, Naifu; Yu, Hao; Sheng, Xiugui

    2016-01-01

    Abstract We aimed to compare the efficacy of paclitaxel and carboplatin followed by gemcitabine-based combination chemotherapy with paclitaxel–carboplatin for treating advanced epithelial ovarian cancer in this retrospective, STROBE-compliant study. Patients’ tolerance to treatment was also assessed. We retrospectively analyzed the records of 178 women who underwent initial optimal debulking surgery between January 2003 and December 2011 to treat FIGO stage IIIc epithelial ovarian cancer. Patients in arm 1 (n = 88) received 4 cycles of paclitaxel and carboplatin followed by 2 to 4 cycles of gemcitabine-based combination chemotherapy. Patients in arm 2 (n = 90) received 6 to 8 cycles of paclitaxel and carboplatin. The granulocyte-colony stimulating factor was administered prophylactically to all patients. The median follow-up for both arms was 62 months. Medianprogression-free survival (PFS) between arms 1 and 2 (28 and 19 months [P = 0.003]) as well as 5-year OS (34.1% and 18.9% [P = 0.021]) differed significantly. The neurotoxicity rate was significantly higher in arm 2 than in arm 1 (45.2% vs 27.1%, P = 0.026). There was no significant difference between study arms in hematological toxicity. The sequential regimen significantly improved PFS and 5-year OS with tolerable toxicity compared with the single regimen, and offers an alternative for treating patients with advanced epithelial ovarian cancer. PMID:28002342

  8. Clinical study of Mito-FLAG regimen in treatment of relapsed acute myeloid leukemia.

    PubMed

    Luo, Sheng; Cai, Fangfang; Jiang, Lei; Zhang, Shenghui; Shen, Zhijian; Sun, Lan; Gao, Shenmeng

    2013-03-01

    Patients with relapsed acute myeloid leukemia (AML) have unfavorable prognosis and require innovative therapeutic approaches. In this study we used fludarabine combined with a middle dose of cytosine arabinoside (Ara-C), mitoxantrone and granulocyte-colony stimulating factor (G-CSF) as a salvage therapy for patients with relapsed AML in China. Forty-five patients with relapsed AML were treated with the Mito-FLAG regimen consisting of mitoxantrone (7 mg/m(2), day 1, 3 and 5), fludarabine (30 mg/m(2), days 1-5), Ara-C (1 g/m(2), over 3 h every 12 h, days 1-5) and G-CSF [5 μg/kg/day subcutaneously from day 0 until the white blood count (WBC) was >20×10(9)/l]. Patients with a partial response (PR) received another course of the same regimen. Patients with a suitable donor and aged <50 years received allogeneic stem cell transplantation (allo-SCT). Twenty-three patients (51%) and 3 patients (7%) achieved complete remission (CR) and PR, respectively, following one or two courses of Mito-FLAG, and the overall response (OR) rate was 58%. Nine patients (20%) received allo-SCT and 4 patients (9%) succumbed early. Hematological toxicity and infections were the most prominent toxicities of this regimen. Other toxicities included nausea, vomiting, bleeding, hyperbilirubinemia, renal toxicity and arrhythmia. The probability of overall survival (OS) at 4 years was 19% (95% CI, 11-26%) and the probability of 4-year disease-free survival (DFS) was 29% for all 23 patients in CR (95% CI, 18-41%). Our data suggest that Mito-FLAG is a highly effective and well-tolerated salvage regimen for relapsed AML.

  9. Vildagliptin with metformin once-daily regimen-insights from a single-center analysis.

    PubMed

    Chatterjee, Sanjay; Chatterjee, Saurav

    2015-01-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitors have been well established as an adjunctive treatment to metformin. Most guidelines recommend treatment with a DPP-4 inhibitor, vildagliptin, in addition to metformin in a twice-daily regimen. However, the twice-daily regimen has difficulty with medication adherence, increased cost of therapy, and possibility of more side effects. Our objective was to evaluate, by means of retrospective analysis, the efficacy of once-daily metformin and vildagliptin (a DPP-4 inhibitor) in reducing blood glucose for patients on combination therapy. We analyzed data from our database of outpatients attending the diabetic clinic at a tertiary care center in Kolkata, India. We had data on once-daily combination of metformin and vildagliptin for 154 patients between September 2008 and May 2012. We followed up these patients for a median of 17.6 months and evaluated posttherapy glucose levels and hemoglobin A1c. Continuous variables were compared with t tests. Once-daily metformin-vildagliptin combination was found to be associated with a mean reduction of 27.52 mg/dL of fasting plasma glucose, 71.70 mg/dL of postprandial plasma glucose, and 1.41% reduction of HbA1c (P < 0.05 for all). Metformin-vildagliptin combination in a once-daily regimen seems to be associated with significant reductions in plasma glucose and HbA1c and may be a viable and cost-effective alternative to a twice-daily regimen as starting therapy.

  10. BK virus replication following kidney transplant: does the choice of immunosuppressive regimen influence outcomes?

    PubMed

    Acott, Phillip; Babel, Nina

    2012-01-01

    The increasing prevalence of BK virus nephropathy (BKVN) observed in recent years, with its consequent impact on kidney allograft survival rates, has focused attention on the relationship between immunosuppression regimens and risk of BK virus reactivation. The adoption of more potent immunosuppressive regimens over the last two decades, notably tacrolimus with mycophenolic acid and corticosteroids, appears to be associated with higher rates of BK activation. There is also evidence of a specific increase in risk for tacrolimus-based immunosuppression vs. cyclosporine, which in vitro data suggest may be at least partly due to differences in antiviral activity. Early concerns that mammalian target of rapamycin (mTOR) inhibitor use was associated with development of BKVN do not appear to have been borne out. Protocol-driven BK virus screening is recommended to facilitate early diagnosis and intervention, which primarily comprises the controlled reduction or discontinuation of immunosuppressive drugs. Although a consensus on the optimal strategy for immunosuppression modification is still lacking, early diagnosis of BK reactivation and pre-emptive modification of immunosuppression has resulted in a marked improvement in graft outcomes. Typically, intervention consists of reducing calcineurin inhibitor exposure before or after antimetabolite dose reduction, withdrawal of one agent from a triple therapy regimen, or switching between agents within a therapeutic class. A benefit for antiviral therapy is not yet confirmed. While more data are required, the current evidence base is adequate to justify routine screening with early modification of the intensity and nature of the immunosuppression regimen to reduce the toll of BKVN in the kidney transplant population.

  11. TAC-TIC use of tacrolimus-based regimens in lupus nephritis.

    PubMed

    Kraaij, Tineke; Bredewold, Obbo W; Trompet, Stella; Huizinga, Tom W J; Rabelink, Ton J; de Craen, Anton J M; Teng, Y K Onno

    2016-01-01

    Current guidelines do not mention tacrolimus (TAC) as a treatment option and no consensus has been reported on the role of TAC in lupus nephritis (LN). The present study aimed to guide clinical judgement on the use of TAC in patients with LN. A meta-analysis was performed for clinical studies investigating TAC regimens in LN on the basis of treatment target (induction or maintenance), concomitant immunosuppression and quality of the data. 23 clinical studies performed in patients with LN were identified: 6 case series, 9 cohort studies, 2 case-control studies and 6 randomised controlled trials (RCTs). Of the 6 RCTs, 5 RCTs investigated TAC regimens as induction treatment and 1 RCT as maintenance treatment. Five RCTs investigated TAC in combination with steroids and 2 TAC with mycophenolate plus steroids. All RCTs were performed in patients of Asian ethnicity. In a meta-analysis, TAC regimens achieved a significantly higher total response (relative risk (RR) 1.23, 95% CI 1.12 to 1.34, p<0.05) and significantly higher complete response (RR 1.48, 95% CI 1.23 to 1.77, p<0.05). The positive outcome was predominantly defined by the largest RCT investigating TAC with mycophenolate plus steroids. Regarding safety, the occurrence of leucopoenia was significantly lower, while the occurrence of increased creatine was higher. Clinical studies on TAC regimens for LN are limited to patients of Asian ethnicity and hampered by significant heterogeneity. The positive results on clinical efficacy of TAC as induction treatment in LN cannot be extrapolated beyond Asian patients with LN. Therefore, further confirmation in multiethnic, randomised trials is mandatory. Until then, TAC can be considered in selected patients with LN.

  12. Do Glioma Patients Derive Any Therapeutic Benefit From Taking a Higher Cumulative Dose of Temozolomide Regimens?

    PubMed Central

    Sun, Hao; Du, Shasha; Liao, Guixiang; Xie, Xiao; Ren, Chen; Yuan, Ya Wei

    2015-01-01

    Abstract Temozolomide (TMZ) is an oral alkylating agent with established effects on the central nervous system of glioblastoma (GBM) patients. Clinical trials have demonstrated a significant impact on overall survival (OS) with TMZ. Ever since, several TMZ regimens have been designed to improve treatment efficacy by increasing the cumulative dose per cycle. We report a meta-analysis to systematically evaluate different treatment schedules of TMZ in GBM patients. All searches that were conducted in the Cochrane library, Science Direct, and PubMed Databases, and 3 randomized controlled trials (1141 patients) were included. OS and progression-free survival (PFS) were the primary outcomes to be pooled. Unexpectedly, this analysis did not reveal any OS or PFS advantage for the high cumulative dose (HCD) regimen compared with the normal cumulative dose regimen (1141 total patients; hazard ratio [HR] 1.07, 95% CI 0.94–1.22, P = 0.31). Then after analyzing the characteristics of the results from each trial, we found that the regimen with a higher peak concentration during a short-term period (daily doses ≥150 mg/m2/d within ≤7 days/cycle) always had a more superior clinical benefit. So we generated a new pooled HR of 1.10 with a 95% CI of 0.96–1.25 (P = 0.17), which prefers the high peak concentration schedule even without a significant difference. The adverse outcome also indicates a significant increased risk of leukopenia (risk ratio 1.59, 95% CI 1.03–2.46, P = 0.04) among the HCD group. Our study suggests that increasing the cumulative dose per cycle is not an ideal way to improve the efficacy of TMZ, and it will lead to increased risk for leukopenia. Future trials should be designed to examine schedules of higher peak concentration rather than the cumulative dose per cycle. PMID:25997057

  13. A Modified Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers

    DTIC Science & Technology

    2013-10-01

    regimen of two to three times daily while in a saturation environment. However, on two occasions during a 1000 feet of sea water ( fsw ) dry saturation...dive and during a 150 fsw dive in the U.S. Navy Saturation Flyaway Diving System (SATFADS), two different divers noted bilateral ear itching and...irritation. During the 1000 fsw dive, one diver reported bilateral ear itching and irritation of the left ear that was greater than the right ear on

  14. Drugs for treatment of vulvovaginal candidiasis: comparative efficacy of agents and regimens.

    PubMed

    Doering, P L; Santiago, T M

    1990-11-01

    Various agents are available for the treatment of vulvovaginal candidiasis. Imidazole agents (clotrimazole, miconazole, butoconazole, and terconazole) are preferred because of their greater efficacy, shorter treatment regimens, and ease of administration. Although the various imidazole compounds are equally efficacious, different treatment schedules are recommended depending on clinical situations. Additionally, different formulations are available that provide clinicians and patients with the opportunity to select the most appropriate agent.

  15. Combination regimens using doxorubicin and pegylated liposomal doxorubicin prior to autologous transplantation in multiple myeloma.

    PubMed

    Moreau, Philippe

    2009-07-01

    Doxorubicin and pegylated liposomal doxorubicin are key compounds of several induction regimens used prior to autologous stem cell transplantation in patients with de novo multiple myeloma, such as vincristine, doxorubicin, dexamethasone (VAD), vincristine, pegylated liposomal doxorubicin/Doxil, dexamethasone (DVd) or PS-341/bortezomib, doxorubicin, dexamethasone (PAD). The aim of this article is to summarize the more recent data available on the efficacy of these combinations and to discuss their role as part of initial therapy.

  16. TAC-TIC use of tacrolimus-based regimens in lupus nephritis

    PubMed Central

    Bredewold, Obbo W; Trompet, Stella; Huizinga, Tom W J; Rabelink, Ton J; de Craen, Anton J M; Teng, Y K Onno

    2016-01-01

    Current guidelines do not mention tacrolimus (TAC) as a treatment option and no consensus has been reported on the role of TAC in lupus nephritis (LN). The present study aimed to guide clinical judgement on the use of TAC in patients with LN. A meta-analysis was performed for clinical studies investigating TAC regimens in LN on the basis of treatment target (induction or maintenance), concomitant immunosuppression and quality of the data. 23 clinical studies performed in patients with LN were identified: 6 case series, 9 cohort studies, 2 case-control studies and 6 randomised controlled trials (RCTs). Of the 6 RCTs, 5 RCTs investigated TAC regimens as induction treatment and 1 RCT as maintenance treatment. Five RCTs investigated TAC in combination with steroids and 2 TAC with mycophenolate plus steroids. All RCTs were performed in patients of Asian ethnicity. In a meta-analysis, TAC regimens achieved a significantly higher total response (relative risk (RR) 1.23, 95% CI 1.12 to 1.34, p<0.05) and significantly higher complete response (RR 1.48, 95% CI 1.23 to 1.77, p<0.05). The positive outcome was predominantly defined by the largest RCT investigating TAC with mycophenolate plus steroids. Regarding safety, the occurrence of leucopoenia was significantly lower, while the occurrence of increased creatine was higher. Clinical studies on TAC regimens for LN are limited to patients of Asian ethnicity and hampered by significant heterogeneity. The positive results on clinical efficacy of TAC as induction treatment in LN cannot be extrapolated beyond Asian patients with LN. Therefore, further confirmation in multiethnic, randomised trials is mandatory. Until then, TAC can be considered in selected patients with LN. PMID:28123768

  17. Contribution of Oxazolidinones to the Efficacy of Novel Regimens Containing Bedaquiline and Pretomanid in a Mouse Model of Tuberculosis.

    PubMed

    Tasneen, Rokeya; Betoudji, Fabrice; Tyagi, Sandeep; Li, Si-Yang; Williams, Kathy; Converse, Paul J; Dartois, Véronique; Yang, Tian; Mendel, Carl M; Mdluli, Khisimuzi E; Nuermberger, Eric L

    2015-10-26

    New regimens based on two or more novel agents are sought to shorten or simplify treatment of tuberculosis (TB). Pretomanid (PMD) is a nitroimidazole in phase 3 trials that has significant bactericidal activity alone and in combination with bedaquiline (BDQ) and/or pyrazinamide (PZA). We previously showed that the novel combination of BDQ+PMD plus the oxazolidinone sutezolid (SZD) had sterilizing activity superior to that of the first-line regimen in a murine model of TB. The present experiments compared the activity of different oxazolidinones in combination with BDQ+PMD with or without PZA in the same model. The 3-drug regimen of BDQ+PMD plus linezolid (LZD) had sterilizing activity approaching that of BDQ+PMD+SZD and superior to that of the first-line regimen. The addition of PZA further enhanced activity. Reducing the duration of LZD to 1 month did not significantly affect the activity of the regimen. Halving the LZD dose or replacing LZD with RWJ-416457 modestly reduced activity over the first month but not after 2 months. AZD5847 and tedizolid also increased the bactericidal activity of BDQ+PMD, but they were less effective than the other oxazolidinones. These results provide optimism for safe, short-course oral regimens for drug-resistant TB that may also be superior to the current first-line regimen for drug-susceptible TB.

  18. Supralethal poisoning by any of the classical nerve agents is effectively counteracted by procyclidine regimens in rats.

    PubMed

    Myhrer, Trond; Mariussen, Espen; Enger, Siri; Aas, Pål

    2015-09-01

    A treatment regimen consisting of HI-6, levetiracetam, and procyclidine (termed the triple regimen) has previously been shown to work as a universal therapy against soman poisoning in rats, since it has capacities to function as both prophylactic and therapeutic measure. The purpose of the present study was to examine whether the triple regimen may have antidotal efficacy against intoxication by other classical nerve agents than soman. The treatment was given 1 and 5 min after exposure to a supralethal dose of nerve agents, and the results showed that the triple regimen successfully prevented or terminated seizures and preserved the lives of rats exposed to 5×LD50 of soman, sarin, cyclosarin, or VX, but solely 3×LD50 of tabun was managed by this regimen. To meet the particular antidotal requirements of tabun, the triple regimen was reinforced with obidoxime and was made to a quadruple regimen that effectively treated rats intoxicated by 5×LD50 of tabun. The rats recovered very well and the majority gained pre-exposure body weight within 7 days. Neuropathology was seen in all groups regardless of whether the rats seized or not. The most extensive damage was produced by sarin and cyclosarin. Differentiation between the nerve agents' potency to cause lesions was probably seen because the efficacious treatments ensured survival of supralethal poisoning. A combination of 2 oximes and 2 anticonvulsants may be a prerequisite to counteract effectively high levels of poisoning by any classical nerve agent.

  19. Fecal Bacterial Communities in treated HIV infected individuals on two antiretroviral regimens

    PubMed Central

    Pinto-Cardoso, Sandra; Lozupone, Catherine; Briceño, Olivia; Alva-Hernández, Selma; Téllez, Norma; Adriana, Aguilar; Murakami-Ogasawara, Akio; Reyes-Terán, Gustavo

    2017-01-01

    Intestinal microbiome changes that occur in HIV positive individuals on different antiretroviral therapy (ART) regimens are important to understand, as they are potentially linked with chronic inflammation and microbiome-linked comorbidities that occur at increased incidence in this population. We conducted a cross-sectional study comparing the fecal microbiomes of HIV-uninfected (HIV SN) to HIV-infected individuals on long-term ART (HIV+ LTART) from Mexico using 16S ribosomal RNA (16sRNA) targeted sequencing. These individuals were on two ART regimens based on either Non-Nucleoside Reverse Transcriptase Inhibitors (EFV) or ritonavir-boosted Protease Inhibitors (PI) with the same backbone of Nucleoside Reverse Transcriptase Inhibitors. Microbiome diversity was reduced in treated HIV infection compared to HIV SN (p < 0.05). Several operational taxonomic units (OTUs) related to the Ruminococcaceae family including Faecalibacterium prausnitzii were depleted in EFV and PI compared to HIV SN and negatively correlated with intestinal gut dysfunction as measured by the intestinal fatty binding protein (p < 0.05). This is the first report to address the fecal bacterial communities in HIV-infected individuals on two ARV regimens from Mexico. PMID:28262770

  20. Combined-modality therapy of rectal cancer with irinotecan-based regimens.

    PubMed

    Minsky, Bruce D

    2004-12-01

    There are two conventional treatments for clinically resectable rectal cancer. The first is surgery followed by postoperative combined-modality therapy if the tumor is T3 and/or N1/2. The second, if the tumor is ultrasound T3 or clinical T4, is preoperative combined-modality therapy followed by surgery and postoperative chemotherapy. There are a number of new chemotherapeutic agents that have been developed for the treatment of colorectal cancer. Phase I/II trials are examining the use of new chemotherapeutic agents in combination with pelvic radiation therapy, most commonly in the preoperative setting. There is considerable interest in integrating irinotecan (Camptosar) into preoperative combined-modality therapy regimens for rectal cancer. Based on these trials, the recommended regimen for patients who receive irinotecan-based combined-modality therapy is continuous infusion fluorouracil (5-FU), irinotecan, and pelvic radiation. New trials examining preoperative combined-modality therapy regimens substituting capecitabine (Xeloda) for continuous infusion 5-FU are in progress.

  1. Using clinically approved cyclophosphamide regimens to control the humoral immune response to oncolytic viruses

    PubMed Central

    Peng, K-W; Myers, R; Greenslade, A; Mader, E; Greiner, S; Federspiel, MJ; Dispenzieri, A; Russell, SJ

    2013-01-01

    Oncolytic viruses can be neutralized in the bloodstream by antiviral antibodies whose titers increase progressively with each exposure, resulting in faster virus inactivation and further reductions in efficacy with each successive dose. A single dose of cyclophosphamide (CPA) at 370 mg m−2 was not sufficient to control the primary antiviral immune responses in mice, squirrel monkeys and humans. We therefore tested clinically approved multidose CPA regimens, which are known to kill proliferating lymphocytes, to determine if more intensive CPA therapy can more effectively suppress antiviral antibody responses during virotherapy. In virus-susceptible mice, primary antibody responses to intravenously (i.v.) administered oncolytic measles virus (MV) or vesicular stomatitis virus (VSV) were partially or completely suppressed, respectively, by oral (1 mg × 8 days) or systemic (3 mg × 4 days) CPA regimens initiated 1 day before virus. When MV- or VSV-immune mice were re-challenged with the respective viruses and concurrently treated with four daily systemic doses of CPA, their anamnestic antibody responses were completely suppressed and antiviral antibody titers fell significantly below pre-booster levels. We conclude that the CPA regimen of four daily doses at 370 mg m−2 should be evaluated clinically with i.v. virotherapy to control the antiviral antibody response and facilitate effective repeat dosing. PMID:22476202

  2. Using clinically approved cyclophosphamide regimens to control the humoral immune response to oncolytic viruses.

    PubMed

    Peng, K-W; Myers, R; Greenslade, A; Mader, E; Greiner, S; Federspiel, M J; Dispenzieri, A; Russell, S J

    2013-03-01

    Oncolytic viruses can be neutralized in the bloodstream by antiviral antibodies whose titers increase progressively with each exposure, resulting in faster virus inactivation and further reductions in efficacy with each successive dose. A single dose of cyclophosphamide (CPA) at 370 mg m(-2) was not sufficient to control the primary antiviral immune responses in mice, squirrel monkeys and humans. We therefore tested clinically approved multidose CPA regimens, which are known to kill proliferating lymphocytes, to determine if more intensive CPA therapy can more effectively suppress antiviral antibody responses during virotherapy. In virus-susceptible mice, primary antibody responses to intravenously (i.v.) administered oncolytic measles virus (MV) or vesicular stomatitis virus (VSV) were partially or completely suppressed, respectively, by oral (1 mg × 8 days) or systemic (3 mg × 4 days) CPA regimens initiated 1 day before virus. When MV- or VSV-immune mice were re-challenged with the respective viruses and concurrently treated with four daily systemic doses of CPA, their anamnestic antibody responses were completely suppressed and antiviral antibody titers fell significantly below pre-booster levels. We conclude that the CPA regimen of four daily doses at 370 mg m(-2) should be evaluated clinically with i.v. virotherapy to control the antiviral antibody response and facilitate effective repeat dosing.

  3. Effect of an immunomodulatory regimen for cancer prevention: A case report

    PubMed Central

    Wang, Wenbo; Wang, Wei; Liu, Bing; Suo, Zhuoyao; Zhou, Lin; Liu, Guangxian

    2016-01-01

    In the present case study, an immunomodulatory regimen for cancer prevention is reported. A patient with an abnormally high level of the tumor markers, carbohydrate antigen-724 (CA724), CA19–9 and carcinoembryonic antigen (CEA), although without any detectable tumor, was treated with an immunomodulatory therapy featuring an infusion of cytokine-induced autologous killer cells (CIKs) at the request of the patient. Following the therapy, the three tumor markers rapidly decreased to below the normal reference level, although there still were slight fluctuations within a narrow range frequently. The patient was monitored for 21 months to the present day and no abnormality was observed. The results indicated that this therapy may be applied as a novel strategy that is effective and reliable for cancer prevention. As there is no promising regimen for the prevention of malignancies to date, such a treatment may become a major cancer prophylactic regimen, particularly for patients who are at a high risk of cancer. PMID:27900080

  4. Effectiveness of Once-Weekly Rifapentine and Moxifloxacin Regimens against Mycobacterium tuberculosis in Mice

    PubMed Central

    Lounis, Nacer; Bentoucha, Abdelhalim; Truffot-Pernot, Chantal; Ji, Baohong; O'Brien, Richard J.; Vernon, Andrew; Roscigno, Giorgio; Grosset, Jacques

    2001-01-01

    Mice infected with 1.6 × 107 CFU of Mycobacterium tuberculosis were treated 14 days later for 6 months with a regimen of once-weekly 10 mg of rifapentine and 75 mg of isoniazid per kg of body weight supplemented with either 150 mg of streptomycin per kg or 100 mg of moxifloxacin per kg during either both the 2-week daily initial and once-weekly continuation phases or only in the daily 2-week initial phase. On completion of treatment, all lung cultures were negative, except for three mice, each with a single colony: two whose rifapentine-isoniazid regimen was supplemented with streptomycin during the whole course of therapy and one whose rifapentine-isoniazid regimen had no initial daily phase, but was supplemented with streptomycin and moxifloxacin during the whole course of therapy. After 3 months of follow-up, positive lung cultures were obtained from 61 and 56% of mice supplemented with streptomycin during either the full course of therapy or only the daily 2-week initial phase, respectively, and 15 and 50% of mice supplemented with moxifloxacin during either the full course of therapy or only the daily 2-week initial phase, respectively. These results suggest that moxifloxacin has sterilizing activity against M. tuberculosis. PMID:11709328

  5. Effects of the Yuzpe regimen, given during the follicular phase, on ovarian function.

    PubMed

    Croxatto, H B; Fuentealba, B; Brache, V; Salvatierra, A M; Alvarez, F; Massai, R; Cochon, L; Faundes, A

    2002-02-01

    This study was conducted to assess to what extent the Yuzpe regimen, or half the dose, given in the follicular phase, prevents ovulation during the ensuing 5 days. Sixty women were divided into six groups. All groups received placebo in one cycle and drug in another, in a randomized order. Groups differed by the dose and size of the leading follicle at the time of treatment (12-14, 15-17, or 18-20 mm). Ovulation was absent during the ensuing 5 days in 13 of 20 participants (65%) and in 8 of 20 participants (40%) who received the full and the half dose, respectively, when follicles were 12-17 mm. No ovulation occurred, within the critical period, in 7 of 39 placebo cycles (18%). When follicles were 18-20 mm, treatment did not prevent ovulation. In most drug-treated cycles, plasma gonadotropin and sex steroid levels were significantly depressed within the 5-day period, even when follicular rupture occurred within that period. In conclusion, the Yuzpe regimen can suppress or postpone ovulation to an extent that exceeds the fertile life of spermatozoa. Lack of ovulation within the critical period and dysfunction of the ovulatory process probably account for the contraceptive effect of this method in most cases. The present data do not warrant the use of half the dose of the Yuzpe regimen.

  6. Influence of feeding regimens on rat gut fluids and colonic metabolism of diclofenac-β-cyclodextrin.

    PubMed

    Vieira, Amélia C F; Murdan, Sudaxshina; Serra, Arménio C; Veiga, Francisco J; Gonsalves, António M d'A Rocha; Basit, Abdul W

    2014-11-04

    Feeding states may affect the performance of colonic prodrugs. The aim is to investigate the influence of feeding regimen in Wistar rats on: (i) distribution and pH contents along the gut and (ii) metabolism of two colonic prodrugs, diclofenac-β-cyclodextrin and a commercially available control, sulfasalazine, within the caecal and colonic contents. Male Wistar rats were subject to four different feeding regimens, the gut contents characterized (mass and pH) and the metabolism of prodrugs investigated. The feeding regimen affects gut contents (mass and pH), more specifically in the stomach and lower intestine, and affects the rate of metabolism of diclofenac-β-cyclodextrin, but not that of sulfasalazine. The latter's degradation is much faster than that of diclofenac-β-cyclodextrin while the metabolism of both prodrugs is faster in colonic (versus caecal) contents. Fasting results in most rapid degradation of diclofenac-β-cyclodextrin, possibly due to lack of competition (absence of food) for microbial enzymatic activity.

  7. Allogeneic stem cell transplantation for severe acquired aplastic anaemia using a fludarabine-based preparative regimen.

    PubMed

    Resnick, Igor B; Aker, Memet; Shapira, Michael Y; Tsirigotis, Panagiotis D; Bitan, Menachem; Abdul-Hai, Ali; Samuel, Simcha; Ackerstein, Aliza; Gesundheit, Benjamin; Zilberman, Irina; Miron, Svetlana; Yoffe, Luba; Lvovich, Alex; Slavin, Shimon; Or, Reuven

    2006-06-01

    We reviewed our experience in the treatment of 13 patients with severe acquired aplastic anaemia, using a newly developed non-myeloablative regimen consisting of fludarabine (total dose 180 mg/m2), cyclophosphamide (total dose 120 mg/kg), and antithymocyte globulin (total dose 40 mg/kg). All except one patient received multiple transfusions and had failed prior immunosuppressive treatment. Twelve out of 13 patients achieved sustained engraftment. One patient was not evaluable for engraftment because of early death on day +10. None of the patients developed graft failure. Mucositis of mild-to-moderate severity was the only observed regimen-related toxicity. The cumulative incidence of acute graft-versus-host disease (GvHD) grade II-IV and III-IV was 8.3% and 0%, respectively. With a median follow-up period of 45 months, the 5-year overall survival probability was 84%. Eight out of 11 surviving patients have been followed for more than 1 year and only one developed limited chronic GvHD. All patients enjoy a normal life style, with a Karnofsky score of 100%, and all except three, followed for 3, 5 and 6 months respectively, are free of any immunosuppressive medication. The results of this study look promising, while prospective clinical trials may be required to confirm the benefits of this regimen as an alternative to existing protocols.

  8. A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa

    PubMed Central

    Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

    2015-01-01

    Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (Isc). Subsequent Isc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. Isc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation. PMID:26038704

  9. Ofloxacin containing combined drug regimens in the treatment of multibacillary leprosy.

    PubMed

    Sampoonachot, P; Bundit, C; Kuhacharoen, N; Peerapakorn, S; Kampirapap, K; Poomlek, A; Bampenyu, S; Tiasiri, S; Rungruang, S; Surasondhi, S; Supanwanit, S; Wiriyawipart, S

    1997-12-01

    The results of ofloxacin containing combined drug regimens in the treatment of 60 multibacillary leprosy cases from January 1989 to June 1995 are reported. The objective of the trial is to compare the antileprotic property of ofloxacin and rifampicin in multibacillary leprosy patients and to study the killing rate of M. leprae by ofloxacin and rifampicin before mass treatment can be recommended. The complications and side-effects of ofloxacin and rifampicin were of a mild nature and both drugs were well tolerated. Moderate to marked clinical improvement was noticed in a short period with ofloxacin containing regimens in multibacillary leprosy patients. No persisters were detected in any of the 33 specimens (of mouse footpads) that had been obtained after treatment for 6 months. Ofloxacin if added to the currently used WHO recommended MB-MDT regimen may shorten the duration of treatment. Ofloxacin, therefore, may be considered as a suitable alternative in suspected/proven rifampicin resistant cases and where rifampicin is contraindicated. The results were evaluated on the basis of the clinical conditions, mycobactericidal effectiveness, signs of drug toxicity and side effects.

  10. Evaluation of Blood Regimen on the Survival of Cimex lectularius L. Using Life Table Parameters

    PubMed Central

    Barbarin, Alexis M; Gebhardtsbauer, Ron; Rajotte, Edwin G.

    2013-01-01

    Knowledge of bed bug development under varying conditions can lead to more sophisticated management techniques. Development rate, age and stage-specific life tables were compared for a laboratory strain (HS) and field strain (ECL-05) of bed bug Cimex lectularius L. (Hemiptera: Heteroptera) reared on two blood regimens: human or rabbit blood. Harlan and ECL-05 bed bugs reared on human blood had a life expectancy of 207 and 208 days respectively from the egg stage. Egg to adult development of HS bed bugs reared on human blood (~35 days) was significantly longer than that of the ECL-05 strain (~33 days) in the third, fourth, and fifth instars. The HS and ECL-05 bed bugs reared on rabbit blood had a life expectancy of 149 and 174 days respectively. Egg to adult development time of HS on rabbit blood (~52 days) was significantly longer than ECL-05 (~37 days) in every instar, and HS total life span was significantly shorter compared to ECL-05. Developmental differences based on strain and blood regimen suggest rabbit blood is an inferior blood source for colony maintenance, and strain has variable effects on bed bug development. Findings suggest that blood regimen should strongly be considered in bed bug colony maintenance. PMID:26464390

  11. Fecal Bacterial Communities in treated HIV infected individuals on two antiretroviral regimens.

    PubMed

    Pinto-Cardoso, Sandra; Lozupone, Catherine; Briceño, Olivia; Alva-Hernández, Selma; Téllez, Norma; Adriana, Aguilar; Murakami-Ogasawara, Akio; Reyes-Terán, Gustavo

    2017-03-06

    Intestinal microbiome changes that occur in HIV positive individuals on different antiretroviral therapy (ART) regimens are important to understand, as they are potentially linked with chronic inflammation and microbiome-linked comorbidities that occur at increased incidence in this population. We conducted a cross-sectional study comparing the fecal microbiomes of HIV-uninfected (HIV SN) to HIV-infected individuals on long-term ART (HIV+ LTART) from Mexico using 16S ribosomal RNA (16sRNA) targeted sequencing. These individuals were on two ART regimens based on either Non-Nucleoside Reverse Transcriptase Inhibitors (EFV) or ritonavir-boosted Protease Inhibitors (PI) with the same backbone of Nucleoside Reverse Transcriptase Inhibitors. Microbiome diversity was reduced in treated HIV infection compared to HIV SN (p < 0.05). Several operational taxonomic units (OTUs) related to the Ruminococcaceae family including Faecalibacterium prausnitzii were depleted in EFV and PI compared to HIV SN and negatively correlated with intestinal gut dysfunction as measured by the intestinal fatty binding protein (p < 0.05). This is the first report to address the fecal bacterial communities in HIV-infected individuals on two ARV regimens from Mexico.

  12. Evaluating the Effect of Zingiber Officinalis on Nausea and Vomiting in Patients Receiving Cisplatin Based Regimens

    PubMed Central

    Fahimi, Fanak; Khodadad, Kian; Amini, Somayeh; Naghibi, Farzaneh; Salamzadeh, Jamshid; Baniasadi, Shadi

    2011-01-01

    Ginger, the rhizome of Zingiber officinalis, has long been used as herbal medicine for its antiemetic effect. For evaluating the effect of zingiber officinalis on nausea and vomiting (N and V) in patients receiving cisplatin based regimens, a randomized double-blind placebo-controlled cross-over clinical trial was carried out in patients receiving cisplatin in combination with other chemotherapeutic agents. The patients were randomly assigned to receive ginger capsules (rhizome of zingiber officinalis) or placebo in their first cycle of the study. All patients received standard antiemetics for chemotherapy induced nausea and vomiting (CINV). The patients were crossed-over to receive ginger or placebo in their next cycle of chemotherapy. Among 36 eligible patients who received both cycles of treatment, there were no difference in prevalence, severity, and duration of both acute and delayed N and V. Addition of ginger to the standard antiemetic regimen has shown no advantage in reducing acute and delayed N and V in patients with cisplatin-based regimen in this study. PMID:24250368

  13. Efficacy of traditional treatment regimen on Kati Shoola with special reference to lumbar spondylolisthesis.

    PubMed

    Ediriweera, E R H S S; Gunathilka, H D P; Weerasinghe, K D C M; Kalawana, O T M R K S B

    2013-01-01

    According to Ayurveda, Kati Shoola is a disease with pain in lumbar region. Lumbar spondylolisthesis, anterior displacement of a vertebra or the vertebral column in relation to the vertebrae below, is one of the common causes. Current case study was carried out at Ayurveda Teaching hospital, Borella, to evaluate the efficacy of a treatment regimen used by Sri Lankan traditional physician family "Weerasinghe." A 59-year-old female with a 9-month history of lumbar spondylolisthesis was treated with this regimen. The patient had progressive pain in left lower back, right and left buttocks, and difficulty in bending forward over 5°. X-ray of lumbo sacral region indicated that patient was suffering from Grade 3 lumbar spondylolisthesis. She was treated for 65 days with four treatment packages consisting of 13 prepared medicines. The response to the treatment was recorded and therapeutic effects were evaluated through symptomatic relief. Clinical symptoms were significantly reduced and degree of anterior flexion increased from 5° to 90°. However, X-rays indicated that the patient was still suffering from Grade 3 lumbar spondylolisthesis. This regimen is effective in successfully treating Kati Shoola (lumbar spondylolisthesis) by helping to reduce the symptoms and improving the degree of anterior flexion.

  14. Efficacy of traditional treatment regimen on Kati Shoola with special reference to lumbar spondylolisthesis

    PubMed Central

    Ediriweera, E. R. H. S. S.; Gunathilka, H. D. P.; Weerasinghe, K. D. C. M.; Kalawana, O. T. M. R. K. S. B.

    2013-01-01

    According to Ayurveda, Kati Shoola is a disease with pain in lumbar region. Lumbar spondylolisthesis, anterior displacement of a vertebra or the vertebral column in relation to the vertebrae below, is one of the common causes. Current case study was carried out at Ayurveda Teaching hospital, Borella, to evaluate the efficacy of a treatment regimen used by Sri Lankan traditional physician family “Weerasinghe.” A 59-year-old female with a 9-month history of lumbar spondylolisthesis was treated with this regimen. The patient had progressive pain in left lower back, right and left buttocks, and difficulty in bending forward over 5°. X-ray of lumbo sacral region indicated that patient was suffering from Grade 3 lumbar spondylolisthesis. She was treated for 65 days with four treatment packages consisting of 13 prepared medicines. The response to the treatment was recorded and therapeutic effects were evaluated through symptomatic relief. Clinical symptoms were significantly reduced and degree of anterior flexion increased from 5° to 90°. However, X-rays indicated that the patient was still suffering from Grade 3 lumbar spondylolisthesis. This regimen is effective in successfully treating Kati Shoola (lumbar spondylolisthesis) by helping to reduce the symptoms and improving the degree of anterior flexion. PMID:24049411

  15. A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa.

    PubMed

    Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

    2015-03-01

    Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (I sc). Subsequent I sc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. I sc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation.

  16. Safeguarding a Lunar Rover with Wald's Sequential Probability Ratio Test

    NASA Technical Reports Server (NTRS)

    Furlong, Michael; Dille, Michael; Wong, Uland; Nefian, Ara

    2016-01-01

    The virtual bumper is a safeguarding mechanism for autonomous and remotely operated robots. In this paper we take a new approach to the virtual bumper system by using an old statistical test. By using a modified version of Wald's sequential probability ratio test we demonstrate that we can reduce the number of false positive reported by the virtual bumper, thereby saving valuable mission time. We use the concept of sequential probability ratio to control vehicle speed in the presence of possible obstacles in order to increase certainty about whether or not obstacles are present. Our new algorithm reduces the chances of collision by approximately 98 relative to traditional virtual bumper safeguarding without speed control.

  17. Sequential sputtered Co-HfO2 granular films

    NASA Astrophysics Data System (ADS)

    Chadha, M.; Ng, V.

    2017-03-01

    A systematic study of magnetic, magneto-transport and micro-structural properties of Co-HfO2 granular films fabricated by sequential sputtering is presented. We demonstrate reduction in ferromagnetic-oxide formation by using HfO2 as the insulting matrix. Microstructure evaluation of the films showed that the film structure consisted of discrete hcp-Co grains embedded in HfO2 matrix. Films with varying compositions were prepared and their macroscopic properties were studied. We correlate the variation in these properties to the variation in film microstructure. Our study shows that Co-HfO2 films with reduced cobalt oxide and varying properties can be prepared using sequential sputtering technique.

  18. Sequential Generalized Likelihood Ratio Tests for Vaccine Safety Evaluation

    PubMed Central

    Shih, Mei-Chiung; Lai, Tze Leung; Heyse, Joseph F.; Chen, Jie

    2010-01-01

    SUMMARY The evaluation of vaccine safety involves pre-clinical animal studies, pre-licensure randomized clinical trials and post-licensure safety studies. Sequential design and analysis are of particular interest because they allow early termination of the trial or quick detection that the vaccine exceeds a prescribed bound on the adverse event rate. After a review of recent developments in this area, we propose a new class of sequential generalized likelihood ratio tests for evaluating adverse event rates in two-armed pre-licensure clinical trials and single-armed post-licensure studies. The proposed approach is illustrated using data from the Rotavirus Efficacy and Safety Trial (REST). Simulation studies of the performance of the proposed approach and other methods are also given. PMID:20799244

  19. Sequential anaerobic-adsorption treatment of chemical industry wastewater.

    PubMed

    Daga, Kailash; Pallavi, V; Patel, Dharmendra

    2011-10-01

    Treatment technologies needed to reduce the pollutant load of chemical industry effluent have been found to involve exorbitantly high costs. The present investigation aimed to treat the wastewater from chemical industry by cost effective sequential anaerobic-adsorption treatment. Wastewaters from chemical industry that are rich in biodegradable organics are tested for anaerobic treatability. The efficiency of anaerobic reactor is relatively lower 79.3%, and therefore post treatment of effluent was done by adsorption using Poly vinyl alcohol coated Datura stramonium (PVAC-DS) as an adsorbent. An overall COD removal of 93.8 % was achieved after sequential Anaerobic-Adsorption treatment, which lead to a better final effluent and a more economical treatment system.

  20. Microfluidic IEF technique for sequential phosphorylation analysis of protein kinases

    NASA Astrophysics Data System (ADS)

    Choi, Nakchul; Song, Simon; Choi, Hoseok; Lim, Bu-Taek; Kim, Young-Pil

    2015-11-01

    Sequential phosphorylation of protein kinases play the important role in signal transduction, protein regulation, and metabolism in living cells. The analysis of these phosphorylation cascades will provide new insights into their physiological functions in many biological functions. Unfortunately, the existing methods are limited to analyze the cascade activity. Therefore, we suggest a microfluidic isoelectric focusing technique (μIEF) for the analysis of the cascade activity. Using the technique, we show that the sequential phosphorylation of a peptide by two different kinases can be successfully detected on a microfluidic chip. In addition, the inhibition assay for kinase activity and the analysis on a real sample have also been conducted. The results indicate that μIEF is an excellent means for studies on phosphorylation cascade activity.

  1. Plasmon-driven sequential chemical reactions in an aqueous environment

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Wang, Peijie; Zhang, Zhenglong; Fang, Yurui; Sun, Mengtao

    2014-06-01

    Plasmon-driven sequential chemical reactions were successfully realized in an aqueous environment. In an electrochemical environment, sequential chemical reactions were driven by an applied potential and laser irradiation. Furthermore, the rate of the chemical reaction was controlled via pH, which provides indirect evidence that the hot electrons generated from plasmon decay play an important role in plasmon-driven chemical reactions. In acidic conditions, the hot electrons were captured by the abundant H+ in the aqueous environment, which prevented the chemical reaction. The developed plasmon-driven chemical reactions in an aqueous environment will significantly expand the applications of plasmon chemistry and may provide a promising avenue for green chemistry using plasmon catalysis in aqueous environments under irradiation by sunlight.

  2. Parametric study on sequential deconvolution for force identification

    NASA Astrophysics Data System (ADS)

    Lai, Tao; Yi, Ting-Hua; Li, Hong-Nan

    2016-09-01

    The force identification can be mathematically viewed as the mapping from the observed responses to external forces through a matrix filled with system Markov parameters, which makes it difficult or even impossible for long time duration. A potentially efficient solution is to sequentially perform the identification processing. This paper presents a parametric study on the sequential deconvolution input reconstruction (SDR) method, which was proposed by Bernal. The behavior of the SDR method due to the effects of window parameters, noise levels and sensor configurations is investigated. In addition, a new normalized standard deviation of the reconstruction error over time is derived to cover the effect of only independent noise entries. The sinusoidal and band-limited white noise excitations are tested to be identified with good accuracy even with 10% noise. The simulation results yield various conclusions that may be helpful to engineering practitioners.

  3. Sequential analysis of autonomic arousal and self-injurious behavior.

    PubMed

    Hoch, John; Sng, Sylvia; Symons, Frank

    2013-11-01

    There have been limited direct tests of the hypothesis that self-injurious behavior (SIB) regulates arousal. In this study, two autonomic biomarkers for physiological arousal (heart rate [HR] and the high-frequency [HF] component of heart rate variability [HRV]) were investigated in relation to SIB for 3 participants with intellectual disabilities. Second-by-second correlations were examined using time series statistical models. The probabilities of HR changes preceding or following SIB were derived using sequential analyses and compared using resampling procedures. Significant correlations and sequential dependencies were found between SIB and arousal parameters. Combining within-subject statistical methods with single-subject experimental designs may provide a replicable methodology for use across larger samples to examine relationships between SIB and arousal in real-world settings.

  4. Sequential segmental classification of feline congenital heart disease.

    PubMed

    Scansen, Brian A; Schneider, Matthias; Bonagura, John D

    2015-12-01

    Feline congenital heart disease is less commonly encountered in veterinary medicine than acquired feline heart diseases such as cardiomyopathy. Understanding the wide spectrum of congenital cardiovascular disease demands a familiarity with a variety of lesions, occurring both in isolation and in combination, along with an appreciation of complex nomenclature and variable classification schemes. This review begins with an overview of congenital heart disease in the cat, including proposed etiologies and prevalence, examination approaches, and principles of therapy. Specific congenital defects are presented and organized by a sequential segmental classification with respect to their morphologic lesions. Highlights of diagnosis, treatment options, and prognosis are offered. It is hoped that this review will provide a framework for approaching congenital heart disease in the cat, and more broadly in other animal species based on the sequential segmental approach, which represents an adaptation of the common methodology used in children and adults with congenital heart disease.

  5. Plasmon-driven sequential chemical reactions in an aqueous environment.

    PubMed

    Zhang, Xin; Wang, Peijie; Zhang, Zhenglong; Fang, Yurui; Sun, Mengtao

    2014-06-24

    Plasmon-driven sequential chemical reactions were successfully realized in an aqueous environment. In an electrochemical environment, sequential chemical reactions were driven by an applied potential and laser irradiation. Furthermore, the rate of the chemical reaction was controlled via pH, which provides indirect evidence that the hot electrons generated from plasmon decay play an important role in plasmon-driven chemical reactions. In acidic conditions, the hot electrons were captured by the abundant H(+) in the aqueous environment, which prevented the chemical reaction. The developed plasmon-driven chemical reactions in an aqueous environment will significantly expand the applications of plasmon chemistry and may provide a promising avenue for green chemistry using plasmon catalysis in aqueous environments under irradiation by sunlight.

  6. Sequential organogenesis sets two parallel sensory lines in medaka

    PubMed Central

    Seleit, Ali; Krämer, Isabel; Ambrosio, Elizabeth; Dross, Nicolas; Engel, Ulrike

    2017-01-01

    Animal organs are typically formed during embryogenesis by following one specific developmental programme. Here, we report that neuromast organs are generated by two distinct and sequential programmes that result in parallel sensory lines in medaka embryos. A ventral posterior lateral line (pLL) is composed of neuromasts deposited by collectively migrating cells whereas a midline pLL is formed by individually migrating cells. Despite the variable number of neuromasts among embryos, the sequential programmes that we describe here fix an invariable ratio between ventral and midline neuromasts. Mechanistically, we show that the formation of both types of neuromasts depends on the chemokine receptor genes cxcr4b and cxcr7b, illustrating how common molecules can mediate different morphogenetic processes. Altogether, we reveal a self-organising feature of the lateral line system that ensures a proper distribution of sensory organs along the body axis. PMID:28087632

  7. Markov sequential pattern recognition : dependency and the unknown class.

    SciTech Connect

    Malone, Kevin Thomas; Haschke, Greg Benjamin; Koch, Mark William

    2004-10-01

    The sequential probability ratio test (SPRT) minimizes the expected number of observations to a decision and can solve problems in sequential pattern recognition. Some problems have dependencies between the observations, and Markov chains can model dependencies where the state occupancy probability is geometric. For a non-geometric process we show how to use the effective amount of independent information to modify the decision process, so that we can account for the remaining dependencies. Along with dependencies between observations, a successful system needs to handle the unknown class in unconstrained environments. For example, in an acoustic pattern recognition problem any sound source not belonging to the target set is in the unknown class. We show how to incorporate goodness of fit (GOF) classifiers into the Markov SPRT, and determine the worse case nontarget model. We also develop a multiclass Markov SPRT using the GOF concept.

  8. Visual tracker using sequential bayesian learning: discriminative, generative, and hybrid.

    PubMed

    Lei, Yun; Ding, Xiaoqing; Wang, Shengjin

    2008-12-01

    This paper presents a novel solution to track a visual object under changes in illumination, viewpoint, pose, scale, and occlusion. Under the framework of sequential Bayesian learning, we first develop a discriminative model-based tracker with a fast relevance vector machine algorithm, and then, a generative model-based tracker with a novel sequential Gaussian mixture model algorithm. Finally, we present a three-level hierarchy to investigate different schemes to combine the discriminative and generative models for tracking. The presented hierarchical model combination contains the learner combination (at level one), classifier combination (at level two), and decision combination (at level three). The experimental results with quantitative comparisons performed on many realistic video sequences show that the proposed adaptive combination of discriminative and generative models achieves the best overall performance. Qualitative comparison with some state-of-the-art methods demonstrates the effectiveness and efficiency of our method in handling various challenges during tracking.

  9. Mechanism of Sequential Swallowing during Straw Drinking in Healthy Young and Older Adults

    ERIC Educational Resources Information Center

    Daniels, Stephanie K.; Corey, David M.; Hadskey, Leslie D.; Legendre, Calli; Priestly, Daniel H.; Rosenbek, John C.; Foundas, Anne L.

    2004-01-01

    Recent research has revealed differences between isolated and sequential swallowing in healthy young adults; however, the influence of normal aging on sequential swallowing has not been studied. Thus, the purpose of this investigation was to examine the effects of normal aging on deglutition during sequential straw drinking. Videofluoroscopic…

  10. A Novel Method for Discovering Fuzzy Sequential Patterns Using the Simple Fuzzy Partition Method.

    ERIC Educational Resources Information Center

    Chen, Ruey-Shun; Hu, Yi-Chung

    2003-01-01

    Discusses sequential patterns, data mining, knowledge acquisition, and fuzzy sequential patterns described by natural language. Proposes a fuzzy data mining technique to discover fuzzy sequential patterns by using the simple partition method which allows the linguistic interpretation of each fuzzy set to be easily obtained. (Author/LRW)

  11. The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study

    PubMed Central

    2013-01-01

    Objective To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes. Design Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration. Methods Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the ‘intention-to-treat’ effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting. Results A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/μl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens. Conclusions Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine. PMID:22546987

  12. Sequential circuit design for radiation hardened multiple voltage integrated circuits

    SciTech Connect

    Clark, Lawrence T.; McIver, III, John K.

    2009-11-24

    The present invention includes a radiation hardened sequential circuit, such as a bistable circuit, flip-flop or other suitable design that presents substantial immunity to ionizing radiation while simultaneously maintaining a low operating voltage. In one embodiment, the circuit includes a plurality of logic elements that operate on relatively low voltage, and a master and slave latches each having storage elements that operate on a relatively high voltage.

  13. Efficient sequential and parallel algorithms for record linkage

    PubMed Central

    Mamun, Abdullah-Al; Mi, Tian; Aseltine, Robert; Rajasekaran, Sanguthevar

    2014-01-01

    Background and objective Integrating data from multiple sources is a crucial and challenging problem. Even though there exist numerous algorithms for record linkage or deduplication, they suffer from either large time needs or restrictions on the number of datasets that they can integrate. In this paper we report efficient sequential and parallel algorithms for record linkage which handle any number of datasets and outperform previous algorithms. Methods Our algorithms employ hierarchical clustering algorithms as the basis. A key idea that we use is radix sorting on certain attributes to eliminate identical records before any further processing. Another novel idea is to form a graph that links similar records and find the connected components. Results Our sequential and parallel algorithms have been tested on a real dataset of 1 083 878 records and synthetic datasets ranging in size from 50 000 to 9 000 000 records. Our sequential algorithm runs at least two times faster, for any dataset, than the previous best-known algorithm, the two-phase algorithm using faster computation of the edit distance (TPA (FCED)). The speedups obtained by our parallel algorithm are almost linear. For example, we get a speedup of 7.5 with 8 cores (residing in a single node), 14.1 with 16 cores (residing in two nodes), and 26.4 with 32 cores (residing in four nodes). Conclusions We have compared the performance of our sequential algorithm with TPA (FCED) and found that our algorithm outperforms the previous one. The accuracy is the same as that of this previous best-known algorithm. PMID:24154837

  14. Studies of flows through N-sequential orifices

    NASA Technical Reports Server (NTRS)

    Hendricks, R. C.; Stetz, T. T.

    1983-01-01

    Critical mass flux and axial pressure profile data for fluid nitrogen are presented for N = 20, 15, 10, and 7 N-sequential-orifice-inlet configurations uniformly spaced at 15.5 cm. These data correlate well over a wide range in reduced temperature and reduced pressure, and are in general agreement with previous studies of one to four inlets. Experimental and theoretical agreement is good for liquid and gas critical mass flux, but inconclusive in the near thermodynamic critical regions.

  15. Automatic sequential fluid handling with multilayer microfluidic sample isolated pumping

    PubMed Central

    Liu, Jixiao; Fu, Hai; Yang, Tianhang; Li, Songjing

    2015-01-01

    To sequentially handle fluids is of great significance in quantitative biology, analytical chemistry, and bioassays. However, the technological options are limited when building such microfluidic sequential processing systems, and one of the encountered challenges is the need for reliable, efficient, and mass-production available microfluidic pumping methods. Herein, we present a bubble-free and pumping-control unified liquid handling method that is compatible with large-scale manufacture, termed multilayer microfluidic sample isolated pumping (mμSIP). The core part of the mμSIP is the selective permeable membrane that isolates the fluidic layer from the pneumatic layer. The air diffusion from the fluidic channel network into the degassing pneumatic channel network leads to fluidic channel pressure variation, which further results in consistent bubble-free liquid pumping into the channels and the dead-end chambers. We characterize the mμSIP by comparing the fluidic actuation processes with different parameters and a flow rate range of 0.013 μl/s to 0.097 μl/s is observed in the experiments. As the proof of concept, we demonstrate an automatic sequential fluid handling system aiming at digital assays and immunoassays, which further proves the unified pumping-control and suggests that the mμSIP is suitable for functional microfluidic assays with minimal operations. We believe that the mμSIP technology and demonstrated automatic sequential fluid handling system would enrich the microfluidic toolbox and benefit further inventions. PMID:26487904

  16. Sequential activation of multiple grounding pads reduces skin heating.

    PubMed

    Schutt, D J; Haemmerich, D

    2006-01-01

    Radio frequency (RF) tumor ablation has become an accepted treatment modality for tumors not amenable to surgery. The need for larger ablation zones has required increase in RF generator power, with current generation devices delivering 200-250 W. Skin burns due to ground pad heating have become a common complication and are now a limiting factor for further increase in ablation zone and generator power. We performed ex vivo experiments with three ground pads (5 x 5 cm) placed on a tissue phantom. We applied 100 W of power for 12 min between the pads, and an RF electrode while we measured leading edge temperature below each pad, and temperature profile on the pads using temperature-sensitive LCD-paper. We compared conventional operation (i.e. simultaneous connection of all three pads) to sequential activation of the pads where each pad is only active for approximately 0.5 s. The timing during sequential activation was adjusted to keep leading edge temperature equal between the pads. Temperature rise below the leading edge for proximal, middle and distal ground pad was 10.7 +/- 1.04, 1.0 +/- 0.15 and 0.3 +/- 0.07 degrees C for conventional operation, and 4.8 +/- 0.16, 4.4 +/- 0.20 and 4.5 +/- 0.35 degrees C for sequentially activated operation. The maximum leading edge temperature rise was more than twice as high for conventional compared to switched operation (p<0.001). Sequential activation of multiple ground pads resulted in reduced maximum leading edge temperature, and allows control of each pad such that leading edge temperature of all pads is the same. This may reduce the incidence of ground pad burns by allowing each pad to reach same temperatures independent of location, and may allow higher power RF generators due to reduced skin heating.

  17. Sequential electrolytic oxidation and reduction of aqueous phase energetic compounds.

    PubMed

    Gilbert, David M; Sale, Tom C

    2005-12-01

    Contamination of soils and groundwater with energetic compounds has been documented at many former ammunition manufacturing plants and ranges. Recent research at Colorado State University (CSU) has demonstrated the potential utility of electrolytic degradation of organic compounds using an electrolytic permeable reactive barrier (e-barrier). In principle, an electrolytic approach to degrade aqueous energetic compounds such as hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) or 2,4,6-trinitrotoluene (TNT) can overcome limitations of management strategies that involve solely oxidation or reduction, through sequential oxidation-reduction or reduction-oxidation. The objective of this proof-of-concept research was to evaluate transformation of aqueous phase RDX and TNT in flow-through electrolytic reactors. Laboratory experiments were conducted using six identical column reactors containing porous media and expanded titanium-mixed-metal-oxide electrodes. Three columns tested TNT transformation and three tested RDXtransformation. Electrode sequence was varied between columns and one column for each contaminant acted as a no-voltage control. Over 97% of TNT and 93% of RDX was transformed in the reactors under sequential oxidation-reduction. Significant accumulation of known degradation intermediates was not observed under sequential oxidation-reduction. Removal of approximately 90% of TNT and 40% of RDX was observed under sequential reduction-oxidation. Power requirements on the order of 3 W/m2 were measured during the experiment. This suggests that an in-situ electrolytic approach may be cost-practical for managing groundwater contaminated with explosive compounds.

  18. Sequential Evaluation of QNDE Devices for Underground Storage Tanks

    NASA Astrophysics Data System (ADS)

    Michlin, Y. H.

    2003-03-01

    Data showing that QNDE devices for tightness testing of storage tanks require periodic precision checks under maximum reproduction of the field conditions. The measurement error was larger than the accuracy prescribed by standards, and much larger than that claimed by the manufacturer. In the paper, the algorithm based on the sequential approach for such tests, and the probability distributions of the number of measurements up to a positive/negative serviceability decision -are substantiated.

  19. Optimisation of beryllium-7 gamma analysis following BCR sequential extraction.

    PubMed

    Taylor, A; Blake, W H; Keith-Roach, M J

    2012-03-30

    The application of cosmogenic (7)Be as a sediment tracer at the catchment-scale requires an understanding of its geochemical associations in soil to underpin the assumption of irreversible adsorption. Sequential extractions offer a readily accessible means of determining the associations of (7)Be with operationally defined soil phases. However, the subdivision of the low activity concentrations of fallout (7)Be in soils into geochemical fractions can introduce high gamma counting uncertainties. Extending analysis time significantly is not always an option for batches of samples, owing to the on-going decay of (7)Be (t(1/2)=53.3 days). Here, three different methods of preparing and quantifying (7)Be extracted using the optimised BCR three-step scheme have been evaluated and compared with a focus on reducing analytical uncertainties. The optimal method involved carrying out the BCR extraction in triplicate, sub-sampling each set of triplicates for stable Be analysis before combining each set and coprecipitating the (7)Be with metal oxyhydroxides to produce a thin source for gamma analysis. This method was applied to BCR extractions of natural (7)Be in four agricultural soils. The approach gave good counting statistics from a 24 h analysis period (~10% (2σ) where extract activity >40% of total activity) and generated statistically useful sequential extraction profiles. Total recoveries of (7)Be fell between 84 and 112%. The stable Be data demonstrated that the extraction procedure had a high reproducibility (<1% RSD), thus gamma counting uncertainties dominated the overall uncertainty. In addition, extractions of soil equilibrated with stable Be at a concentration below the Cation Exchange Capacity (CEC) of the soil demonstrated that doubling the soil:solution ratio to enhance the mass of soil used in a sequential extraction scheme affects the apparent distribution of approximately 10% of the total Be. At high concentration, stable Be was found to be a poor proxy for

  20. Sequential-Impulse Generator Uses Fiber-Optics

    NASA Technical Reports Server (NTRS)

    Yang, L. C.

    1982-01-01

    Light pulse from a ruby or neodymium-glass laser enters miniature optics of repetitive-detonation apparatus. Traveling along a bundle of optical fibers, light strikes laser-sensitive microdetonator and charge explodes. Apparatus then advances next charge in train into position. Possible applications of sequential-impulse generator are in creating shock waves for aerodynamics research and in generating electrical power by magnetohydrodynamics.