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Sample records for 10-day sequential regimen

  1. Helicobacter pylori eradication with either seven-day or 10-day triple therapies, and with a 10-day sequential regimen

    PubMed Central

    Scaccianoce, Giuseppe; Hassan, Cesare; Panarese, Alba; Piglionica, Donato; Morini, Sergio; Zullo, Angelo

    2006-01-01

    BACKGROUND Helicobacter pylori eradication rates achieved by standard seven-day triple therapies are decreasing in several countries, while a novel 10-day sequential regimen has achieved a very high success rate. A longer 10-day triple therapy, similar to the sequential regimen, was tested to see whether it could achieve a better infection cure rate. METHODS Patients with nonulcer dyspepsia and H pylori infection were randomly assigned to one of the following three therapies: esomeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1 g for seven days or 10 days, or a 10-day sequential regimen including esomeprazole 20 mg plus amoxycillin 1 g for five days and esomeprazole 20 mg, clarithromycin 500 mg and tinidazole 500 mg for the remaining five days. All drugs were given twice daily. H pylori eradication was checked four to six weeks after treatment by using a 13C-urea breath test. RESULTS Overall, 213 patients were enrolled. H pylori eradication was achieved in 75.7% and 77.9%, in 81.7% and 84.1%, and in 94.4% and 97.1% of patients following seven-day or 10-day triple therapy and the 10-day sequential regimen, at intention-to-treat and per protocol analyses, respectively. The eradication rate following the sequential regimen was higher than either seven-day (P=0.002) or 10-day triple therapy (P=0.02), while no significant difference emerged between the latter two regimens (P=0.6). CONCLUSIONS The 10-day sequential regimen was significantly more effective than both triple regimens, while 10-day triple therapy failed to significantly increase the H pylori eradication rate achieved by the standard seven-day regimen. PMID:16482238

  2. 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. PMID:6539811

  3. Timed-sequential chemotherapy as induction and/or consolidation regimen for younger adults with acute myelogenous leukemia.

    PubMed

    Thomas, Xavier; Dombret, Hervé

    2007-02-01

    Increasing the intensity of induction chemotherapy has generated considerable recent interest in the treatment of acute myeloid leukemia. Achieving complete remission is a sine qua non condition for prolonged disease-free survival and may affect long-term outcome. In this setting, administering a repeat course of induction shortly after completion of the first course, known as timed-sequential chemotherapy (TSC), has been tested and may lead to an improved long-term outcome. Whether these results are due to the biologic recruitment of cell cycle-specific agents is unknown. However, this strategy to intensify induction may lead to more profound myelosuppression and to potential toxicities. Here we review the results of timed-sequential chemotherapy, used as induction regimen in de novo, relapsed or refractory AML or used as post-remission therapy, and compare them with those from other types of regimens.

  4. A Sequential Phase 2b Trial Design for Evaluating Vaccine Efficacy and Immune Correlates for Multiple HIV Vaccine Regimens

    PubMed Central

    Gilbert, Peter B.; Grove, Douglas; Gabriel, Erin; Huang, Ying; Gray, Glenda; Hammer, Scott M.; Buchbinder, Susan P.; Kublin, James; Corey, Lawrence; Self, Steven G.

    2012-01-01

    Five preventative HIV vaccine efficacy trials have been conducted over the last 12 years, all of which evaluated vaccine efficacy (VE) to prevent HIV infection for a single vaccine regimen versus placebo. Now that one of these trials has supported partial VE of a prime-boost vaccine regimen, there is interest in conducting efficacy trials that simultaneously evaluate multiple prime-boost vaccine regimens against a shared placebo group in the same geographic region, for accelerating the pace of vaccine development. This article proposes such a design, which has main objectives (1) to evaluate VE of each regimen versus placebo against HIV exposures occurring near the time of the immunizations; (2) to evaluate durability of VE for each vaccine regimen showing reliable evidence for positive VE; (3) to expeditiously evaluate the immune correlates of protection if any vaccine regimen shows reliable evidence for positive VE; and (4) to compare VE among the vaccine regimens. The design uses sequential monitoring for the events of vaccine harm, non-efficacy, and high efficacy, selected to weed out poor vaccines as rapidly as possible while guarding against prematurely weeding out a vaccine that does not confer efficacy until most of the immunizations are received. The evaluation of the design shows that testing multiple vaccine regimens is important for providing a well-powered assessment of the correlation of vaccine-induced immune responses with HIV infection, and is critically important for providing a reasonably powered assessment of the value of identified correlates as surrogate endpoints for HIV infection. PMID:23181167

  5. Comparing a motivational and a self-regulatory intervention to adopt an oral self-care regimen: a two-sequential randomized crossover trial.

    PubMed

    Lhakhang, Pempa; Gholami, Maryam; Knoll, Nina; Schwarzer, Ralf

    2015-01-01

    A sequential intervention to facilitate the adoption and maintenance of dental flossing was conducted among 205 students in India, aged 18-26 years. Two experimental groups received different treatment sequences and were observed at three assessment points, 34 days apart. One group received first a motivational intervention (intention, outcome expectancies, and risk perception, followed by a self-regulatory intervention (planning, self-efficacy, and action control). The second group received the same intervention in the opposite order. Both intervention sequences yielded gains in terms of flossing, planning, self-efficacy, and action control. However, at Time 2, those who had received the self-regulatory intervention first, were superior to their counterparts who had received the motivational intervention first. At Time 3, differences vanished as everyone had then received both interventions. Thus, findings highlight the benefits of a self-regulatory compared to a mere motivational intervention.

  6. First- and second-line Helicobacter pylori eradication with modified sequential therapy and modified levofloxacin-amoxicillin-based triple therapy

    PubMed Central

    Zullo, Angelo; Ridola, Lorenzo; Efrati, Cesare; Giorgio, Floriana; Nicolini, Giorgia; Cannaviello, Claudio; Alvaro, Domenico; Hassan, Cesare; Gatta, Luigi; Francesco, Vincenzo De

    2014-01-01

    Background Helicobacter pylori (H. pylori) treatment remains a challenge for physicians. Although highly effective, the standard sequential therapy fails in a certain number of patients. Moreover, the cure rate following a levofloxacin-amoxicillin second-line triple therapy seems to be decreasing. We tested the efficacy of modified 10-day sequential therapy, and an intensified levofloxacin-amoxicillin regimen as first- and second-line therapy respectively. Methods In this prospective, open label, multicenter, pilot study H. pylori-infected patients received a first-line modified 10-day sequential therapy regimen including rabeprazole 20 mg, and amoxicillin 1 g for the first 3 days, followed by rabeprazole 20 mg, clarithromycin 250 mg, and metronidazole 250 mg, for the remaining 7 days, all drugs given thrice daily. An 8-day therapy regimen with rabeprazole 20 mg, levofloxacin 250 mg, and amoxicillin 1 g, all thrice daily, was administered a second-line therapy. Results A total of 99 and 15 patients were enrolled for first- and second-line therapy. The eradication rates were 85.9% (95% CI 80-93) and 93.4% (95% CI 88-98) according to ITT and PP analyses following modified sequential therapy, and 60% (95% CI 35-86) and 64.3% (95% CI 39-89) following the intensified second-line therapy. Conclusion A modified sequential 3- plus 7-day regimen with thrice daily drug administration failed to achieve very high eradication rate at ITT analysis. The intensified second-line regimen achieved disappointingly low eradication rate. Novel levofloxacin-free second-line therapies are urged in Italy. PMID:25330819

  7. 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…

  8. 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....

  9. 19 CFR 141.82 - Invoice for installment shipments arriving within a period of 10 days.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Invoice for installment shipments arriving within a period of 10 days. 141.82 Section 141.82 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY OF MERCHANDISE Invoices §...

  10. 19 CFR 141.82 - Invoice for installment shipments arriving within a period of 10 days.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 2 2014-04-01 2014-04-01 false Invoice for installment shipments arriving within..., DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY OF MERCHANDISE Invoices § 141.82 Invoice for installment shipments arriving within a period of 10 days. (a) One invoice...

  11. 19 CFR 141.82 - Invoice for installment shipments arriving within a period of 10 days.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Invoice for installment shipments arriving within..., DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY OF MERCHANDISE Invoices § 141.82 Invoice for installment shipments arriving within a period of 10 days. (a) One invoice...

  12. 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.

  13. 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.

  14. Effect of acute hypercapnia during 10-day hypoxic bed rest on posterior eye structures.

    PubMed

    Jaki Mekjavic, Polona; Lenassi, Eva; Eiken, Ola; Mekjavic, Igor B

    2016-05-15

    To gain insights into microgravity-induced ophthalmic changes (microgravity ocular syndrome), and as part of a project investigating effects of future planetary habitats, we investigated the effect of acute hypercapnia following 10-day bed rest and hypoxia on posterior eye structures. Female subjects (N = 7) completed three 10-day experimental interventions: 1) normoxic bed rest [NBR; partial pressure of inspired O2 (PiO2 ) = 132.9 ± 0.3 Torr]; 2) hypoxic ambulatory confinement (HAMB; PiO2 = 90.4 ± 0.3 Torr); and 3) hypoxic bed rest (HBR; n = 12; PiO2 = 90.4 ± 0.3 Torr). Before and on the last day of each intervention, optical coherence tomography (OCT) of the optic disk was performed, and the thicknesses of the retinal nerve fiber layer (RNFL), retina, and choroid were measured. OCT examinations were conducted with the subjects breathing the prevailing normocapnic breathing mixture (either normoxic or hypoxic) and then following a 10-min period of breathing the same gas mixture, but with the addition of 1% CO2 Choroidal thickness was greater during both bed-rest conditions (NBR and HBR) compared with the ambulatory (HAMB) condition (ANOVA, P < 0.001). Increases in RNFL thickness compared with baseline were observed in the hypoxic trials (HBR, P < 0.001; and HAMB, P = 0.021), but not the normoxic trial (NBR). A further increase in RNFL thickness (P = 0.019) was observed after the 10-min hypercapnic trial in the NBR condition only. The fact that choroidal thickness was not affected by Po2 or Pco2, but increased by bed rest, suggests a hydrostatic rather than a vasoactive effect. The increments in RNFL thickness were most likely associated with local hypoxia and hypercapnia-induced dilatation of the retinal blood vessels. PMID:27013607

  15. 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

  16. Adverse effects of a 10-day course of ibuprofen in Holstein calves.

    PubMed

    Walsh, P; Carvallo Chaigneau, F R; Anderson, M; Behrens, N; McEligot, H; Gunnarson, B; Gershwin, L J

    2016-10-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for various conditions in cattle. Ibuprofen is an inexpensive short-acting NSAID and is readily available in liquid formulation for administration to bottle-fed calves. We compared the adverse effects of a 10-day course of ibuprofen and placebo in 16 five- to six-week-old Holstein bull calves that were being treated for experimentally induced bovine respiratory syncytial virus infection. Ibuprofen was administered as a liquid in milk replacer at 30 mg/kg divided three times daily. We found an increased prevalence of abomasal ulceration 5 of 8 in the ibuprofen compared to placebo group 2 of 6 (P = NS). There was one (1 of 8) case of mild interstitial nephritis in the ibuprofen and none (0 of 8) in the placebo group (P = NS). Renal function as measured by serum BUN and creatinine levels was not different between groups; no animal demonstrated an increase in creatinine.

  17. 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.

  18. 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. PMID:24552383

  19. Diet and regimen during pregnancy

    PubMed Central

    Girija, P.LT

    2008-01-01

    To rely on Ayurveda is the best way to ensure a safe and natural childbirth. Ayurveda understands all the factors, which bring about a hazard-free childbirth. By following a regulated diet and regimen, the pregnant mother is prepared for a natural delivery. By helping nature to take its course, women enjoy a risk-free childbirth. This paper provides a broad view of the diet and regimen during pregnancy PMID:22557297

  20. Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis.

    PubMed

    Hull, R D; Raskob, G E; Rosenbloom, D; Panju, A A; Brill-Edwards, P; Ginsberg, J S; Hirsh, J; Martin, G J; Green, D

    1990-05-01

    It is common practice to begin anticoagulant treatment of deep-vein thrombosis with a 10-day course of intravenous heparin, with warfarin added on day 5 to 10 and continued for several months. We performed a randomized, double-blind trial comparing a shorter course of continuous intravenous heparin (5 days, with warfarin sodium begun on the first day) with the conventional 10-day course of heparin (with warfarin sodium begun on the fifth day) in the initial treatment of 199 patients with acute proximal venous thrombosis documented by venography. The frequency of objectively documented recurrent venous thromboembolism was low and essentially the same in the two groups (7.1 percent in the short-course group vs. 7.0 percent in the long-course group). Because the observed difference between the groups was 0.1 percent in favor of the long-course group, it is unlikely (P less than 0.05) that a true difference in favor of this group would be greater than 7.5 percent; the difference could be as much as 7.3 percent in favor of the short-course group. Major bleeding episodes were infrequent, and the rate was similar in both groups. We conclude that a five-day course of heparin is as effective as a 10-day course in treating deep venous thrombosis. Furthermore, using the shorter course would permit earlier discharge from the hospital and thus offer substantial cost savings.

  1. 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.; Manulis, I.; Rubin, A.; Kulkarni, S. R.; Arcavi, I.; Kasliwal, M. M.; Ofek, E. O.; Cao, Y.; et al

    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

  2. Effect of 7-10 days of cycle ergometer exercise on skeletal muscle GLUT-4 protein content.

    PubMed

    Gulve, E A; Spina, R J

    1995-11-01

    Previous studies in animals and humans have shown that endurance exercise-training protocols of several weeks to many months in duration induce adaptive increases in skeletal muscle GLUT-4 protein concentration. It is generally assumed that the increase in GLUT-4 concentration is a long-term adaptation to training. The present study examined whether 7-10 days of cycle ergometer exercise could induce increases in skeletal muscle GLUT-4 levels. Eight healthy subjects (4 men, 4 women) aged 31 +/- 2 (SE) yr exercised 2 h daily at 65-70% of peak O2 uptake (VO2peak) for either 7 (n = 3) or 10 (n = 5) consecutive days. Muscle biopsies (vastus lateralis) were obtained before initiation of the exercise program and 36-48 h after the final bout of exercise. Glucose transporter protein was quantitated by Western blotting using antiserum specific for GLUT-4. VO2peak was increased by 10% (from 3.0 +/- 0.2 to 3.3 +/- 0.2 l/min; P < 0.01) in response to the training. Body weight did not change (74.3 +/- 4.6 before vs. 75.0 +/- 4.2 kg after) as a result of training. Muscle GLUT-4 immunoreactivity was increased 98% (from 584 +/- 50 to 1,154 +/- 40 counts per minute 125I/25 micrograms protein; P < 0.001) in response to training. Increase in VO2peak and GLUT-4 protein were similar for 7 and 10 days of training. These results suggest that, given an adequate training stimulus, adaptations in skeletal muscle GLUT-4 protein occur very rapidly. Furthermore, the increase in GLUT-4 after 7-10 days of exercise is as large as that reported in studies employing long-term training protocols.

  3. Twenty-four hours or 10 days? A prospective randomised controlled trial in children comparing head bandages following pinnaplasty.

    PubMed

    Ramkumar, S; Narayanan, V; Laing, J H E

    2006-01-01

    The perceived benefits of bandaging for 10 days following pinnaplasty have been questioned by previous studies. The problems arising from these dressings are many [Powell BWEM. The value of head dressings in the postoperative management of the prominent ear. Br J Plast Surg 1989;42:692-4. Bartley J. How long should ears be bandaged after otoplasty? J Laryngol Otol 1998;112:531-2. Wong MC, Sylaidis P. Head dressings for pinnaplasty: a tradition not supported by evidence. Br J Plast Surg 2001;54:81-2], including their slippage [Powell BWEM. The value of head dressings in the postoperative management of the prominent ear. Br J Plast Surg 1989;42:692-4. Bradbury ET, Hewison J, Timmons MJ. Psychological and social outcome of prominent ear correction in children. Br J Plast Surg 1992;45:97-100. Jeffery SLA. Complications following correction of prominent ears: an audit review of 122 cases. Br J Plast Surg 1999;52:588-90]. Eighty children were recruited into a prospective randomised controlled trial comparing the use of a head bandage for only 24 h with a standard practise of a 10-day head bandage. A preoperative measurement of the lateral ear projection (LEP) was made. The outcome measures recorded during the two planned postoperative visits at 10 days (visit 1) and 2 months (visit 2) were: patient satisfaction score, LEP, complications and any unscheduled hospital visits associated with the surgery. There was no significant difference in LEP and patient satisfaction between the two groups at both the scheduled postoperative visits. Differences between the groups in the number of unscheduled visits (p=0.21) did not reach statistical significance. The findings indicate that it is safe and effective to use head bandage for only 24 h following surgical correction of prominent ears. This study shows no benefit from the application of a formal head bandage for any longer than 1 day.

  4. Immunomodulatory nonablative conditioning regimen for B-cell lymphoid malignancies

    PubMed Central

    Chinratanalab, Wichai; Reddy, Nishitha; Greer, John P.; Morgan, David; Engelhardt, Brian; Kassim, Adetola; Brandt, Stephen J.; Jagasia, Madan; Goodman, Stacey; Savani, Bipin N.

    2013-01-01

    Twenty-six patients with recurrent CD20+ B-cell lymphoid malignancies received fludarabine, cyclophosphamide, and rituximab–based nonablative conditioning followed by either matched related (n = 18) or unrelated (n = 8) donor allogeneic stem cell transplantation (allo-SCT) between March 2008 and May 2011. Median age of patients at transplantation was 59 years (range, 41–64 years). At diagnosis, 20 (77%) had stage IV disease; 23 (88%) received ≥3 regimens, 14 (54%) received ≥4 regimens, and 4 (15%) had earlier autologous-SCT. All patients had either chemosensitive or stable disease and nine (35%) were in complete remission before transplantation. At the time of analysis, 17 patients were alive with an estimated 2-year overall survival and progression-free survival rate of 63% and nonrelapse mortality of 25%. Grade II to IV acute graft-vs-host-disease occurred in 8 (31%) and chronic graft-vs-host-disease in 6 (23%) patients (extensive, n = 3). Causes of death include progressive disease in four, acute graft-vs-host-disease in two (both after receiving donor lymphocyte infusion for mixed chimerism with residual disease), infection in one, and other (e.g., substance abuse, leukoencephalopathy) in two. Six patients required rehospitalization within 100 days of SCT (mean = 10 days; range, 3–18 days). Our data support fludarabine, cyclophosphamide, and rituximab–based nonablative conditioning allo-SCT in CD20+ B-cell lymphoid malignancies and it is time to compare this regimen with an alternative reduced-intensity conditioning regimen in B-cell malignancies. PMID:22269114

  5. 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

  6. 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.

  7. 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.}

  8. Tolerability of prophylactic Lariam regimens.

    PubMed

    Boudreau, E; Schuster, B; Sanchez, J; Novakowski, W; Johnson, R; Redmond, D; Hanson, R; Dausel, L

    1993-09-01

    Three hundred and fifty-nine US Marines participated in a randomized double-blind clinical trial to assess tolerance of two prophylactic mefloquine regimens [250 mg salt weekly (n = 157) or 250 mg daily for 3 days followed by 250 mg weekly (n = 46)] compared with 300 mg weekly chloroquine (n = 156) over a 12-week period. The study participants were seen daily for four days, then weekly for 11 weeks. On each visit, the subject answered two computerized questionnaires (a review of body systems and an evaluation of mood states), participated in a physician interview, and was administered medications under supervision. A random sample of each group was assigned to either pharmacokinetic sampling or two wear a wrist watch size computerized sleep monitor (actigraph). The frequencies of intercurrent illness and other concomitant medications were tabulated. End study mefloquine plasma levels were obtained on all study participants. The results obtained showed no compromise in function due to dizziness or incoordination in the mefloquine groups. Overall, both weekly mefloquine and loading dose mefloquine were well tolerated. Sleep disturbance and increased dream activity were detected in the mefloquine groups. Depressive feelings were noted in two to three times more individuals in the mefloquine groups than in the chloroquine group early in the course of the study, and resolved in the majority of subjects as tolerance developed. Steady state mefloquine plasma levels were attained rapidly with the loading dose regimen in four days versus seven weeks with weekly mefloquine.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Treatment of Wilson's disease with zinc XII: dose regimen requirements.

    PubMed

    Brewer, G J; Yuzbasiyan-Gurkan, V; Johnson, V; Dick, R D; Wang, Y

    1993-04-01

    A considerable body of data is now available indicating the efficacy and lack of toxicity of zinc treatment of Wilson's disease. Dose-response studies have shown that regimens of 50 mg of elemental zinc 3 times a day (50 mg x 3), 25 mg x 3, and 50 mg x 2 are effective, but 25 mg x 2 and 50 mg x 1 are not adequately effective. These studies indicate that 75 mg a day is close to the minimally effective dose, but do not address the question of necessary dose frequency. In the current study, the authors have used the minimally effective daily dose, 75 mg, and studied this daily dose in regimens of 25 mg x 3, 37.5 mg x 2, and 75 mg x 1 in treatment of four patients with Wilson's disease. These data have been supplemented with additional data from 11 patients treated with 25 mg 3 times a day and with data from 2 patients treated with 75 mg once a day. Efficacy was evaluated by 10-day copper balance and absorption of orally administered 64copper. The findings indicate that a daily dose of 75 mg must be divided into at least two doses to be effective, and that the 64copper procedure is more sensitive to zinc dose than copper balance.

  10. Detection of Aleutian mink disease virus DNA and antiviral antibodies in American mink (Neovison vison) 10 days postinoculation.

    PubMed

    Farid, A Hossain; Hussain, Irshad; Arju, Irin

    2015-05-01

    Early detection of infection by the Aleutian mink disease virus (AMDV; Carnivore amdoparvovirus 1) by polymerase chain reaction (PCR) or counterimmunoelectrophoresis (CIEP) has important ramifications in virus eradication programs. A spleen homogenate containing a local isolate of AMDV was injected intraperitoneally into black (n = 44) and sapphire (n = 12) American mink (Neovison vison). Animals were euthanized 10 days postinoculation and anti-AMDV antibodies and AMDV DNA were tested in plasma and 7 organs by CIEP and PCR, respectively. Viral DNA was detected in the plasma, spleen, lymph nodes, bone marrow, and lung samples of all inoculated mink, but was not detected in some small intestine, kidney, and liver samples. In contrast, antibodies were detected in the plasma of 3 sapphire (25.0%) and 19 black (43.2%) mink but not in any of the organs. The sensitivity of the CIEP test on plasma samples was 39.3%, implying that low levels of antibodies during the early stages of virus exposure resulted in failure to detect infection by the CIEP test. We concluded that CIEP is not a reliable test for early detection of AMDV infection in mink and that there were considerable differences among mink of each color type for production of detectable levels of antibodies. PCR tests on samples of saliva, rectal swabs, and feces did not produce consistent and reliable results. PMID:25862712

  11. Hand temperature responses to local cooling after a 10-day confinement to normobaric hypoxia with and without exercise.

    PubMed

    Keramidas, M E; Kölegård, R; Mekjavic, I B; Eiken, O

    2015-10-01

    The study examined the effects of a 10-day normobaric hypoxic confinement (FiO2: 0.14), with [hypoxic exercise training (HT); n = 8)] or without [hypoxic ambulatory (HA; n = 6)] exercise, on the hand temperature responses during and after local cold stress. Before and after the confinement, subjects immersed their right hand for 30 min in 8 °C water [cold water immersion (CWI)], followed by a 15-min spontaneous rewarming (RW), while breathing either room air (AIR), or a hypoxic gas mixture (HYPO). The hand temperature responses were monitored with thermocouples and infrared thermography. The confinement did not influence the hand temperature responses of the HA group during the AIR and HYPO CWI and the HYPO RW phases; but it impaired the AIR RW response (-1.3 °C; P = 0.05). After the confinement, the hand temperature responses were unaltered in the HT group throughout the AIR trial. However, the average hand temperature was increased during the HYPO CWI (+0.5 °C; P ≤ 0.05) and RW (+2.4 °C; P ≤ 0.001) phases. Accordingly, present findings suggest that prolonged exposure to normobaric hypoxia per se does not alter the hand temperature responses to local cooling; yet, it impairs the normoxic RW response. Conversely, the combined stimuli of continuous hypoxia and exercise enhance the finger cold-induced vasodilatation and hand RW responses, specifically, under hypoxic conditions.

  12. Sequential Metastatic Breast Cancer Chemotherapy: Should the Median be the Message?

    PubMed Central

    Jung, Su Yon; Rosenzweig, Margaret

    2013-01-01

    Background: Counseling and anticipatory guidance of the expected course of treatment for women newly diagnosed with metastatic breast cancer (MBC) are difficult due to multiple factors influencing survival following MBC therapy. In order to better tailor counseling at the onset and through the duration of MBC we used non-clinical trial data to better characterize real life experience of sequential MBC treatment. We examined the following aims: (1) What demographic and tumor characteristics are predictive of survival in MBC? (2) What is the median duration of each sequential chemotherapy regimen and subsequent survival of women following each sequence of chemotherapy regimen in MBC? Methods: Retrospective study included 792 women diagnosed from January 1999 through December 2009 at the University of Pittsburgh Cancer Institute Breast Cancer Program. Results: Median duration of sequential chemotherapy regimen and median survival from completion of sequence of chemotherapy regimens were relatively short with a wide range of treatment duration and survival. Characteristics for poor survival included hormone status, human epidermal growth factor receptor-2 (HER 2/neu) status, and increased number and type of metastatic sites. Women who took more than the second sequential chemotherapy regimens had no more than median 3 months of treatment duration and 6 months survival from treatment termination. Discussion: Median clinical response and survival shorten with sequential chemotherapy regimen but with wide ranges. The rare clinical response of the minority should not set the standard for treatment expectations. All cancer clinicians, including oncology nurses, must ensure that patients are receiving tailored counseling regarding their specific risks and benefits for sequential MBC chemotherapy. PMID:24350218

  13. A Comparison between Hybrid and Concomitant Regimens for Helicobacter Pylori Eradication: A Randomized Clinical Trial

    PubMed Central

    Alhooei, Saman; Tirgar Fakheri, Hafez; Hosseini, Vahid; Maleki, Iradj; Taghvaei, Tarang; Valizadeh, Seyed Mohammad; Bari, Zohreh

    2016-01-01

    BACKGROUND Helicobacter pylori (H. pylori) is one of the most common bacterial infections worldwide. We designed a study to compare the efficacy of 14-day hybrid regimen with 10-day concomitant therapy for H. pylori eradication in Iran. METHODS 252 patients with naïve H. pylori infection were randomly divided to receive either hybrid regimen (pantoprazole 40 mg, and amoxicillin 1 gr twice daily for 14 days, accompanied by clarithromycin 500 mg, and metronidazole 500 mg, twice daily just during the last 7 days) or concomitant regimen (pantoprazole 40 mg, amoxicillin 1 gr, clarithromycin 500 mg, and metronidazole 500 mg, all twice daily for 10 days). 8 weeks after therapy, 14C- urease breath test was performed to confirm eradication. RESULTS According to intention to treat analysis, the eradication rates were 87.3% (95% CI: 81.4–93.1) and 80.9% (95% CI: 74-87.8) in hybrid and concomitant groups, respectively (p=0.38). Per-protocol eradication rates were 89.3% (95% CI: 83.8-94.7) and 83.1% (95% CI: 76.3-89.8), respectively (p=0.19). The rates of severe side effects were not statistically different between the two groups (4% vs. 8.7%). CONCLUSION 14-day hybrid therapy can be considered as a nearly acceptable regimen with few severe side effects in Iran. However, it seems that the efficacy of this therapy is decreasing as the resistance rates to antibiotics are increasing. We suggest further studies to assess the efficacy of a more prolonged concomitant therapy for H. pylori eradication in Iran.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  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. 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…

  20. Sequential memory: Binding dynamics.

    PubMed

    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. PMID:26520084

  1. Sequential therapy: Understanding and appreciating sequential therapy for H. pylori eradication

    PubMed Central

    Graham, David Y.; Rimbara, Emiko

    2011-01-01

    Despite the fact that sequential therapy has been evaluated in more than 2,500 patients and has been shown to on average provide H. pylori eradication in 90 to 94%, some authorities still question whether it should be a first-line anti-H. pylori regimen. Here, we discuss H. pylori eradication using experience and expectations with other common bacterial infections as a frame of reference. H. pylori is no exception and near 100% success is expected for optimized regimens treating susceptible infections. As such, the proper comparator would be the relation to 100% eradication. Superiority to another, often proven inferior, therapy per se provides little or no useful information. Treatment failures in infectious diseases are typically easily explainable and most often relate to the presence of antimicrobial resistance or failure to take the drugs. We provide a model for predicting the results of H. pylori combination therapies in relation to the pattern and prevalence of resistance. The results are consistent with clinical practice and explain why sequential is typically superior and essentially never inferior to triple therapy. We also show when meta-analysis is an inappropriate technique for the analysis of H. pylori clinical trials and discuss how to appropriately use of the technique. Finally, we discuss why the location of studies (e.g., Italy), is unimportant and explain why, from the standpoint of a therapy for an infectious disease, sequential therapy is a significant advance and should be considered one of the replacements for the outdated legacy triple therapy (proton pump inhibitor – clarithromycin – amoxicillin). PMID:21389810

  2. 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.

  3. 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.

  4. 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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24254496

  6. 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. PMID:24254496

  7. Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT.

    PubMed

    De Britto, R L; Vanamail, P; Sankari, T; Vijayalakshmi, G; Das, L K; Pani, S P

    2015-06-01

    Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653). PMID:26691247

  8. 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.

  9. Concurrent versus Sequential Sorafenib Therapy in Combination with Radiation for Hepatocellular Carcinoma

    PubMed Central

    Chettiar, Sivarajan T.; Aziz, Khaled; Gajula, Rajendra P.; Williams, Russell D.; Kumar, Rachit; Taparra, Kekoa; Zeng, Jing; Cades, Jessica A.; Velarde, Esteban; Menon, Siddharth; Geschwind, Jean F.; Cosgrove, David; Pawlik, Timothy M.; Maitra, Anirban; Wong, John; Hales, Russell K.; Torbenson, Michael S.; Herman, Joseph M.; Tran, Phuoc T.

    2013-01-01

    Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design. PMID:23762417

  10. The structure of sequential effects.

    PubMed

    Gökaydin, Dinis; Navarro, Daniel J; Ma-Wyatt, Anna; Perfors, Amy

    2016-01-01

    There is a long history of research into sequential effects, extending more than one hundred years. The pattern of sequential effects varies widely with both experimental conditions as well as for different individuals performing the same experiment. Yet this great diversity of results is poorly understood, particularly with respect to individual variation, which save for some passing mentions has largely gone unreported in the literature. Here we seek to understand the way in which sequential effects vary by identifying the causes underlying the differences observed in sequential effects. In order to achieve this goal we perform principal component analysis on a dataset of 158 individual results from participants performing different experiments with the aim of identifying hidden variables responsible for sequential effects. We find a latent structure consisting of 3 components related to sequential effects-2 main and 1 minor. A relationship between the 2 main components and the separate processing of stimuli and of responses is proposed on the basis of previous empirical evidence. It is further speculated that the minor component of sequential effects arises as the consequence of processing delays. Independently of the explanation for the latent variables encountered, this work provides a unified descriptive model for a wide range of different types of sequential effects previously identified in the literature. In addition to explaining individual differences themselves, it is demonstrated how the latent structure uncovered here is useful in understanding the classical problem of the dependence of sequential effects on the interval between successive stimuli. PMID:26523425

  11. 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. PMID:27242676

  12. 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

  13. 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

  14. 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. PMID:27366752

  15. 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

  16. 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…

  17. Feedback in sequential machine realizations.

    NASA Technical Reports Server (NTRS)

    Harlow, C. A.; Coates, C. L., Jr.

    1972-01-01

    A method is described for determining the realizability of a sequential machine with trigger or set-reset flip-flop memory elements when the feedback of the machine is given by a Boolean function. Feedbacks in several types of sequential machines with different memory elements are compared, showing the memory specifications allowing the realization of such machines.

  18. 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.

  19. A study on the intra-annual variation and the spatial distribution of precipitation amount and duration over Greece on a 10 day basis

    NASA Astrophysics Data System (ADS)

    Bartzokas, A.; Lolis, C. J.; Metaxas, D. A.

    2003-02-01

    The intra-annual variation of precipitation amount and duration and their spatial distribution during the year are studied on a 10 day basis for the Greek region, using S-mode and T-mode factor analysis. (i) For the intra-annual variation of precipitation amount, two modes were revealed: the first shows one broad maximum during the conventional winter in stations affected by the sea; the second presents two maxima, the first during late autumn-early winter and the second during late spring, corresponding to the northern mainland stations. (ii) For the spatial distribution of precipitation, three main patterns were revealed: the first one is the winter pattern, with the maximum over the west windward area; the second is the summer pattern, with a maximum over the north inland region; and the third is the autumn pattern, with the maximum over northwestern Greece. (iii) For precipitation duration, two types of intra-annual variation were revealed. The first one is similar to the first of the analysis for precipitation amount; the second presents two maxima, the first during the beginning of December and the second during the middle of February, corresponding to the areas of northwestern and northeastern Greece. (iv) For the spatial distribution of precipitation duration, three main patterns were revealed: the first is the summer pattern, which is similar to the second of the analysis for precipitation amount; the second is the winter pattern, with the spatial maximum located over the eastern mainland and western Crete; finally, the third one is the autumn pattern, with the maximum in northwestern Greece. During the third 10 day period of October and the second 10 day period of February, precipitation seems to present singularities, possibly due to fluctuations in atmospheric circulation. The above intra-annual variations and spatial distribution patterns are connected to the seasonal variations of the depression trajectories, the atmospheric instability, the influence

  20. 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.

  1. 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

  2. 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.

  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. Evaluation of two oestrus synchronization regimens in eFSH-treated donor mares.

    PubMed

    Raz, Tal; Carley, Sylvia D; Green, Jodyne M; Card, Claire E

    2011-04-01

    Reliable methods for regulating oestrus and superovulation in equine embryo transfer (ET) programs are desirable. The objective in this study was to compare two oestrus synchronization methods combined with equine follicle-stimulating hormone (eFSH) treatment in an ET program. In the progesterone and estradiol-17β (P&E) group, mares (n=12) were given progesterone and estradiol-17β, daily for 10 days, followed by prostaglandin (PG)F(2α) on the last day. In the PG group, mares (n=12) were given PGF(2α) 5 days post-ovulation. In both groups donor mares were allocated to eFSH therapy, and were subsequently bred. Embryo recovery and transfer were performed routinely. The interval to ovulation (mean ± SEM, range) was not statistically different between donor mares in the P&E group (10.2±0.3, 9-12 days) and donor mares in the PG group (8.7±0.7, 4-12 days). Among donor mares, the synchrony of ovulations was higher following the P&E regimen (P<0.05); however, there was a tendency (P<0.06) for fewer ovulations than in the PG group (1.5±0.3 vs. 2.5±0.4 ovulations, respectively). Embryo recovery (0.9±0.3 vs. 1.4±0.3 embryo/recovery) and recipient pregnancy rate per transferred embryo (4/9, 44% vs. 4/15, 27%) were similar. It was concluded that the P&E regimen was more reliable for synchronization of oestrus in eFSH-treated mares but the fewer ovulations may curtail any advantage of this regimen.

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

    NASA Astrophysics Data System (ADS)

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

    In an international collaborative project six normal male subjects were studied before, during and after 10 days 6° HDT. Fluid intake was controlled at 40 ml/(kg bw·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.

  6. Radioprotection by WR-2721 of gamma-irradiated rat parotid gland: effect on gland weight and secretion at 8-10 days post irradiation.

    PubMed

    Menard, T W; Izutsu, K T; Ensign, W Y; Keller, P J; Morton, T H; Truelove, E L

    1984-09-01

    Changes in rat parotid salivary gland weight and functional parameters were evaluated at 8 to 10 days post irradiation in WR-2721 protected and non-protected animals following exposure to a single 15.3 Gy dose of Cs-137 radiation to the head. Glandular fluid secretory capacity was assessed by maximum flow rate, total volume of saliva and duration of secretion following pilocarpine stimulation. Protection against radiomucositis was also evaluated indirectly by daily monitoring of food and water intake, body weight and paraoral symptomatology. WR-2721 provided a significant degree of protection for all glandular functional parameters as well as gland weight. Relative protective factors (RPF) were computed for irradiated protected and non-protected animals compared to their sham-irradiated, pair-fed controls. The calculated RPFs were: Gland weight 1.9, maximum flow rate 2.9, volume of saliva 2.1 and duration of secretion 2.1 for a mean "relative protection" of 2.25. Substantial protection against radiomucositis in protected animals was evident by a progressive gain in body weight and lack of oral signs and symptoms as compared to non-protected animals. Protection against radiomucositis and preservation of residual parotid gland secretory capacity as determined by functional parameters suggests that WR-2721 may be of significant benefit in alleviating oral symptoms and maintaining salivary gland function for patients receiving radiotherapy for head and neck tumors. PMID:6090361

  7. Radioprotection by WR-2721 of gamma-irradiated rat parotid gland: effect on gland weight and secretion at 8-10 days post irradiation

    SciTech Connect

    Menard, T.W.; Izutsu, K.T.; Ensign, W.Y.; Keller, P.J.; Morton, T.H.; Truelove, E.L.

    1984-09-01

    Changes in rat parotid salivary gland weight and functional parameters were evaluated at 8 to 10 days post irradiation in WR-2721 protected and non-protected animals following exposure to a single 15.3 Gy dose of Cs-137 radiation to the head. Glandular fluid secretory capacity was assessed by maximum flow rate, total volume of saliva and duration of secretion following pilocarpine stimulation. Protection against radiomucositis was also evaluated indirectly by daily monitoring of food and water intake, body weight and paraoral symptomatology. WR-2721 provided a significant degree of protection for all glandular functional parameters as well as gland weight. Relative protective factors (RPF) were computed for irradiated protected and non-protected animals compared to their sham-irradiated, pair-fed controls. Protection against radiomucositis and preservation of residual parotid gland secretory capacity as determined by functional parameters suggests that WR-2721 may be of significant benefit in alleviating oral symptoms and maintaining salivary gland function for patients receiving radiotherapy for head and neck tumors.

  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. Replacement of clarithromycin with azithromycin in triple therapy regimens for the eradication of helicobacter pylori: A randomized clinical trial

    PubMed Central

    Khoshnood, A; Hakimi, P; Salman-Roghani, H; Reza Mirjalili, M

    2014-01-01

    Abstract Background: Eradication of helicobacter pylori is important for treatment of GU but an ideal regimen is not available. HP is resistant to metronidazole and clarithromycin. Clarithromycin is expensive and is not available in under developing countries. This study aimed to compare two regimens containing clarithromycin or azithromycin. Methods: Totally, seventy-eight patients with GU (confirmed with endoscopy) and infection of HP (Confirmed by Rapid Urease Test (RUT)) were allocated to one of the groups of study (35 participants in each group). Two weeks regimen of Clarithromycin (2×500 mg) + Amoxicillin (2×1 gr) + omeprazole (2×20 mg) was administered for group A of patients while group B got a 10 days regimen of Azithromycin (1×250 mg) + 14 days Amoxicillin (2×1 gr) + omeprazole (2×20 mg). At the end of the treatment course, the patients were evaluated according to the side effects of the drugs. In addition, two months after the end of therapy, patients underwent endoscopy and biopsy to evaluate HP eradication. Results: After two weeks, the side effects of the drug were: Nausea 8 patients in group A and 7 patients in group B, Diarrhea 2 patients in group A, 3 patients in group B and vomiting 2 patients in group A, 3 patients in group B. There were no serious side effects in any group. Eradication rate in group A was 82.9% (based on per protocol analysis (PPA)) and 84.6 % (intention to treat (ITT)). In group B, eradication rate was 77.1 % (PPA) and 79.5 % (ITT) (P=0.55). Conclusion: Based on our study results, azithromycin can be used in HP eradication regimen because of its similar efficacy to clarithromycin but also have lower cost, side effects and resistance. PMID:25408735

  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. Ocean-Atmosphere Environments of Antarctic-Region Cold-Air Mesocyclones: Evaluation of Reanalyses for Contrasting Adjacent 10-Day Periods ("Macro-Weather") in Winter.

    NASA Astrophysics Data System (ADS)

    Carleton, A. M.; Auger, J.; Birkel, S. D.; Maasch, K. A.; Mayewski, P. A.; Claud, C.

    2015-12-01

    Mesoscale cyclones in cold-air outbreaks (mesocyclones) feature in the weather and climate of the Antarctic (e.g., Ross Sea) and sub-antarctic (Drake Passage). They adversely impact field operations, and influence snowfall, the ice-sheet mass balance, and sea-air energy fluxes. Although individual mesocyclones are poorly represented on reanalyses, these datasets robustly depict the upper-ocean and troposphere environments in which multiple mesocyclones typically form. A spatial metric of mesocyclone activity—the Meso-Cyclogenesis Potential (MCP)—used ERA-40 anomaly fields of: sea surface temperature (SST) minus marine air temperature (MAT), near-surface winds, 500 hPa air temperature, and the sea-ice edge location. MCP maps composited by teleconnection phases for 1979-2001, broadly correspond to short-period satellite "climatologies" of mesocyclones. Here, we assess 3 reanalysis datasets (CFSR, ERA-I and MERRA) for their reliably to depict MCP patterns on weekly to sub-monthly periods marked by strong regional shifts in mesocyclone activity (frequencies, track densities) occurring during a La Niña winter: June 21-30, 1999 (SE Indian Ocean) and September 1-10, 1999 (Ross Sea sector). All reanalyses depict the marked variations in upper ocean and atmosphere variables between adjacent 10-day periods. Slight differences may owe to model resolution or internal components (land surface, coupled ocean models), and/or how the observations are assimilated. For June 21-30, positive SST-MAT, southerly winds, proximity to the ice edge, and negative T500, accompany increased meso-cyclogenesis. However, for September 1-10, surface forcing does not explain frequent comma cloud "polar lows" north-east of the Ross Sea. Inclusion of the upper-level diffluence (e.g., from Z300 field) in the MCP metric, better depicts the observed mesocyclone activity. MCP patterns on these "macro-weather" time scales appear relatively insensitive to the choice of reanalysis.

  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. Efficacy of a nonsurgical treatment regimen in patients with bisphosphonate-related osteonecrosis of the jaws in Saudi Arabia

    PubMed Central

    2014-01-01

    Objectives: The objective of this study was to evaluate the effectiveness of a nonsurgical treatment regimen in the long-term control of necrotic areas of the jaws and pain in such patients. Methods: A total of 96 patients suffering from the disease were included in this study. All patients received nonsurgical treatment regimen for 10 days, and repeated every 3 months for 2 years. The size of the osteonecrotic lesions was measured and the pain level was self-assessed with a visual analog scale. Results: The patients showed a statistically significant (F = 16.1; p < .01; r2 = .95) gradual decrease in the size of exposed bone areas during the nonsurgical therapy (from 12.5 to 8.8 mm). Pain scores ranged from 0 to 3 score scale. Complete resolution of the disease was observed in some patients. Conclusions: This conservative nonsurgical treatment regimen seems to provide successful treatment in reduction of the sizes of exposed bone areas in the majority of patients. PMID:26770707

  14. [Potential role of rilpivirine in simplification regimens].

    PubMed

    Casado, José L; Moreno, Santiago

    2013-06-01

    Antiretroviral simplification is a useful strategy to improve adherence and quality of life and prevent or reverse adverse effects in patients with HIV infection. The availability of new drugs with high efficacy and better tolerability in once-daily formulations or in fixed-dose combinations may be a better option for prolonged treatment. Rilpivirine, a new nonnucleoside reverse transcriptase inhibitor (NNRTI), has shown high antiviral efficacy in clinical trials with treatment-naïve patients, with a lower incidence of adverse effects and good tolerability. Its use in simplification regimens has been evaluated after the switch from efavirenz, demonstrating that dose adjustment is not required. In a large randomized study in patients who were receiving protease inhibitors, virological efficacy was maintained, with a lower incidence of adverse effects and improved lipid parameters and cardiovascular risk score. Given the ease of administration and good tolerability of this drug, recent communications at congresses have shown the rapid applicability of the results of studies in daily clinical practice in this scenario.

  15. Time Data Sequential Processor /TDSP/

    NASA Technical Reports Server (NTRS)

    Joseph, A. E.; Pavlovitch, T.; Roth, R. Y.; Sturms, F. M., Jr.

    1970-01-01

    Time Data Sequential Processor /TDSP/ computer program provides preflight predictions for lunar trajectories from injection to impact, and for planetary escape trajectories for up to 100 hours from launch. One of the major options TDSP performs is the determination of tracking station view periods.

  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. Sequential triangulation of orbital photography

    NASA Technical Reports Server (NTRS)

    Rajan, M.; Junkins, J. L.; Turner, J. D.

    1979-01-01

    The feasibility of structuring the satellite photogrammetric triangulation as an iterative Extended Kalman estimation algorithm is demonstrated. Comparative numerical results of the sequential against batch estimation algorithm are presented. Difficulty of accurately modeling of the attitude motion is overcome by utilizing the on-board angular rate measurements. Solutions of the differential equations and the evaluation of state transition matrix are carried out numerically.

  18. Manifestations of sequential electron transfer

    SciTech Connect

    Thurnauer, M.C.; Tang, J.

    1996-05-01

    An essential feature of efficient photo-initiated charge separation is sequential electron transfer. Charge separation is initiated by photoexcitation of an electron donor followed by rapid electron transfer steps from the excited donor through a series of electron acceptors, so that, after one or two successive steps, charge separation is stabilized by the physical separation between the oxidized donor and reduced acceptor. The prime example of this process is the sequential electron transfer that takes place in the purple photosynthetic bacterial reaction center, resulting in the charge separation between P{sup +} and Q{sub A}{sup -} across a biological membrane. We have developed magnetic resonance tools to monitor sequential electron transfer. We are applying these techniques to study charge separation in natural photo-synthetic systems in order to gain insights into the features of the reaction center proteins that promote efficient charge separation. As we establish what some of these factors are, we are beginning to design artificial photosynthetic systems that undergo photoinduced sequential electron transfer steps.

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

    DOE PAGES

    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 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

  20. Nonequilibrium structure in sequential assembly

    NASA Astrophysics Data System (ADS)

    Popov, Alexander V.; Craven, Galen T.; Hernandez, Rigoberto

    2015-11-01

    The assembly of monomeric constituents into molecular superstructures through sequential-arrival processes has been simulated and theoretically characterized. When the energetic interactions allow for complete overlap of the particles, the model is equivalent to that of the sequential absorption of soft particles on a surface. In the present work, we consider more general cases by including arbitrary aggregating geometries and varying prescriptions of the connectivity network. The resulting theory accounts for the evolution and final-state configurations through a system of equations governing structural generation. We find that particle geometries differ significantly from those in equilibrium. In particular, variations of structural rigidity and morphology tune particle energetics and result in significant variation in the nonequilibrium distributions of the assembly in comparison to the corresponding equilibrium case.

  1. Robustness of the Sequential Lineup Advantage

    ERIC Educational Resources Information Center

    Gronlund, Scott D.; Carlson, Curt A.; Dailey, Sarah B.; Goodsell, Charles A.

    2009-01-01

    A growing movement in the United States and around the world involves promoting the advantages of conducting an eyewitness lineup in a sequential manner. We conducted a large study (N = 2,529) that included 24 comparisons of sequential versus simultaneous lineups. A liberal statistical criterion revealed only 2 significant sequential lineup…

  2. Maintenance immunosuppression regimens: conversion, minimization, withdrawal, and avoidance.

    PubMed

    Yang, Harold

    2006-04-01

    A wide choice of drug combinations is available to clinicians for immunosuppression regimens for their kidney transplant patients. Although many protocols have minimized early graft loss, the optimal long-term regimen is unknown. Recent studies clearly showed that cardiovascular death is now the leading cause of graft loss. Strategies must be developed that address this risk while keeping immunologic events low. Transplant physicians have focused on exploring regimens that minimize or avoid the use of corticosteroids. Studies also have started to explore protocols that minimize calcineurin inhibitor therapy. PMID:16567240

  3. Blocking for Sequential Political Experiments

    PubMed Central

    Moore, Sally A.

    2013-01-01

    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. PMID:24143061

  4. 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.

  5. 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.

  6. New regimens for intravenous acetylcysteine, where are we now?

    PubMed

    Bateman, D Nicholas; Dear, James W; Thomas, Simon H L

    2016-01-01

    Acetylcysteine has been used as a treatment for paracetamol overdose as a 20.25- or 21-h infusion for nearly 40 years. These regimens give 50% of the dose in the first 15 min or 1 h, and are associated with high rates of adverse reactions. A randomised controlled trial has demonstrated that a shorter (12 h) and simpler (two infusions) acetylcysteine regimen using a slower initial infusion rate produces lower rates of adverse events than the original 20.25-h regimen. However, this study was not sufficiently large to show therapeutic equivalence as a hepatoprotective therapy in paracetamol overdose. Two further studies are now reported, which also suggest lower rates of adverse reactions with lower initial rates of acetylcysteine administration. These modified regimens can now be accepted as better tolerated, but it is unlikely that a randomised study of sufficient size to demonstrate non-inferiority of any novel regimen would ever be funded. Against this background we suggest what can be done to establish the efficacy of these less toxic and potentially shorter alternative acetylcysteine regimens and to establish them into routine clinical use. PMID:26666290

  7. 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.

  8. 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.

  9. Hypofractionation Regimens for Stereotactic Radiotherapy for Large Brain Tumors

    SciTech Connect

    Yuan Jiankui; Wang, Jian Z. Lo, Simon; Grecula, John C.; Ammirati, Mario; Montebello, Joseph F.; Zhang Hualin; Gupta, Nilendu; Yuh, William T.C.; Mayr, Nina A.

    2008-10-01

    Purpose: To investigate equivalent regimens for hypofractionated stereotactic radiotherapy (HSRT) for brain tumor treatment and to provide dose-escalation guidance to maximize the tumor control within the normal brain tolerance. Methods and Materials: The linear-quadratic model, including the effect of nonuniform dose distributions, was used to evaluate the HSRT regimens. The {alpha}/{beta} ratio was estimated using the Gammaknife stereotactic radiosurgery (GKSRS) and whole-brain radiotherapy experience for large brain tumors. The HSRT regimens were derived using two methods: (1) an equivalent tumor control approach, which matches the whole-brain radiotherapy experience for many fractions and merges it with the GKSRS data for few fractions; and (2) a normal-tissue tolerance approach, which takes advantages of the dose conformity and fractionation of HSRT to approach the maximal dose tolerance of the normal brain. Results: A plausible {alpha}/{beta} ratio of 12 Gy for brain tumor and a volume parameter n of 0.23 for normal brain were derived from the GKSRS and whole-brain radiotherapy data. The HSRT prescription regimens for the isoeffect of tumor irradiation were calculated. The normal-brain equivalent uniform dose decreased as the number of fractions increased, because of the advantage of fractionation. The regimens for potential dose escalation of HSRT within the limits of normal-brain tolerance were derived. Conclusions: The designed hypofractionated regimens could be used as a preliminary guide for HSRT dose prescription for large brain tumors to mimic the GKSRS experience and for dose escalation trials. Clinical studies are necessary to further tune the model parameters and validate these regimens.

  10. A standardized treatment regimen for patients with severe haemophilia A undergoing orthopaedic or trauma surgery: a single centre experience.

    PubMed

    Hart, Christina; Heindl, Bernhard; Spannagl, Michael; Lison, Susanne

    2015-06-01

    Recommendations on the administration of clotting factor concentrates in patients with severe haemophilia undergoing surgery are usually determined by monitoring target clotting factor levels. In this retrospective cohort study, we enrolled patients with severe haemophilia A who underwent major orthopaedic or trauma surgery. We wanted to evaluate the feasibility and the safety of a standardized medical treatment procedure. Further on, we wanted to assess whether our standardized treatment regimen enables surgical procedures in certain situations in which measuring clotting factor VIII (FVIII) activity is not available. We created a standardized medical treatment procedure that included a medical protocol and close cooperation with the Haemophilic Treatment Centre. Thirteen surgical procedures in nine patients were examined. The feasibility and safety of this standardized treatment concept were assessed by identifying perioperative complications and by means of a questionnaire. Depending on the surgery, the amount of FVIII administered within the first 10 days ranged between 653 and 1027 units/kg body weight. No allogeneic blood transfusion was required. The measurement of FVIII activity was performed repeatedly in five patients. In all patients activated partial thromboplastin time monitoring was performed during the hospital stays. The surgeons and patients were satisfied with our treatment concept and adhered to the medical regimen protocol. By means of a detailed, standardized medical protocol and by ensuring close cooperation between the patient, the surgeons and the Haemophilic Treatment Centre, we could show that elective and emergency operations can be safely performed even in situations in which FVIII activity could not be monitored.

  11. 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

  12. 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.

  13. Structural features of sequential weak measurements

    NASA Astrophysics Data System (ADS)

    Diósi, Lajos

    2016-07-01

    We discuss the abstract structure of sequential weak measurement (WM) of general observables. In all orders, the sequential WM correlations without postselection yield the corresponding correlations of the Wigner function, offering direct quantum tomography through the moments of the canonical variables. Correlations in spin-1/2 sequential weak measurements coincide with those in strong measurements, they are constrained kinematically, and they are equivalent with single measurements. In sequential WMs with postselection, an anomaly occurs, different from the weak value anomaly of single WMs. In particular, the spread of polarization σ ̂ as measured in double WMs of σ ̂ will diverge for certain orthogonal pre- and postselected states.

  14. 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

  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 Consequences of Therapists' Interventions

    PubMed Central

    Milbrath, Constance; Bond, Michael; Cooper, Steven; Znoj, Hans J.; Horowitz, Mardi J.; Perry, J. Christopher

    1999-01-01

    Using sequential analysis, the authors examined how therapists' actions related to the verbal disclosure and defensive patterns that followed therapists' interventions within a single therapy hour for 20 patients. At the same time, a new measure, the Psychodynamic Intervention Rating Scale (PIRS), was tested for reliability and construct validity. Results indicated that therapists fit their styles of intervention to patients' levels of distress and functioning. Within the session, patient's emotional elaboration was followed by therapist's defense interpretation, followed by more patient emotional elaboration. Patient elaboration of significance was followed by more transference interpretation, followed by more patient elaboration of significance. Noninterpretive interventions were followed by patient's disclosure of facts, not emotion. Both interpretive intervention process sequences and therapist's use of support predicted posttreatment symptom reduction. The PIRS was shown to have satisfactory reliability and construct validity. (The Journal of Psychotherapy Practice and Research 1999; 8:40–54) PMID:9888106

  17. 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.

  18. Experimental multiparty sequential state discrimination

    NASA Astrophysics Data System (ADS)

    Solís-Prosser, M. A.; González, P.; Fuenzalida, J.; Gómez, S.; Xavier, G. B.; Delgado, A.; Lima, G.

    2016-10-01

    Recently, a protocol for quantum state discrimination (QSD) in a multiparty scenario has been introduced [Phys. Rev. Lett. 111, 100501 (2013), 10.1103/PhysRevLett.111.100501]. In this protocol, Alice generates a quantum system in one of two predefined nonorthogonal qubit states, and the goal is to send the generated state information to different parties without classical communication exchanged between them during the protocol's session. The interesting feature is that, by resorting to sequential generalized measurements onto this single system, there is a nonvanishing probability that all observers identify the state prepared by Alice. Here, we present the experimental implementation of this protocol based on polarization single-photon states. Our scheme works over an optical network, and since QSD lies in the core of many protocols, it represents a step towards experimental multiparty quantum information processing.

  19. 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.

  20. 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

  1. Sequential power-up circuit

    DOEpatents

    Kronberg, J.W.

    1992-06-02

    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. 2 figs.

  2. 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.

  3. Sequentially Executed Model Evaluation Framework

    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, suchmore » 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« less

  4. Sequentially Executed Model Evaluation Framework

    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 asmore » 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.« less

  5. 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.

  6. 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

  7. An automatic, refrigerated, sequential precipitation sampler

    NASA Astrophysics Data System (ADS)

    Coscio, M. R.; Pratt, G. C.; Krupa, S. V.

    The design and characteristics of an automated, refrigerated, sequential precipitation sampler are described. This sampler can collect rainfall on an event basis or as sequential segments within a rain event. Samples are sealed upon collection to prevent gas exchange and are refrigerated in situ at 4 ± 2° C. This sampler is commercially available.

  8. 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…

  9. Extended and continuous combined contraceptive regimens for menstrual suppression.

    PubMed

    Jacobson, Janet C; Likis, Frances E; Murphy, Patricia Aikins

    2012-01-01

    Many women have medical indications for menstrual suppression or a personal preference to reduce or eliminate monthly bleeding, which can be achieved with extended and continuous regimens of combined estrogen and progestin contraceptives. Combined contraceptives are traditionally administered in a 28-day cycle, with 21 days of a contraceptive pill, vaginal ring, or transdermal patch followed by a hormone-free interval that is usually 7 days. During the hormone-free interval, women either take a placebo pill or do not use their combined contraceptive method. Hormone-related symptoms are significantly worse during the hormone-free interval than the days when the contraceptive is used. Alterations of the standard 28-day cyclic regimen for menstrual suppression include decreasing the frequency of the hormone-free interval, thus extending the time between withdrawal bleeding episodes (extended use), and eliminating the hormone-free interval altogether (continuous use). This article reviews menstrual suppression indications and physiology. Research demonstrating that the effectiveness, safety, and side effects of oral, vaginal, and transdermal extended and continuous regimens are comparable to cyclic regimens is summarized. Findings from studies of women's and health care providers' attitudes toward menstrual suppression also are reviewed. Important topics to include in evidence-based counseling for extended and continuous combined contraceptive use are presented.

  10. Health Beliefs and Regimen Adherence of the American Indian Diabetic.

    ERIC Educational Resources Information Center

    Miller, Patricia; And Others

    1987-01-01

    Examines compliance with a medical and behavioral regimen by 60 American Indian diabetics, as it relates to demographic and medical variables, attitudes, perceived beliefs of others, and coping strategies. Concludes that the patient's perceptions of significant others' belief is the best predictor of overall adherence. Contains 29 references. (SV)

  11. Multilevel sequential Monte Carlo samplers

    DOE PAGES

    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 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

  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. Stability models for sequential storage.

    PubMed

    Friedman, Emil M; Shum, Sam C

    2011-03-01

    Some drugs are intended for sequential storage under two different storage conditions. If the data for each condition are analyzed separately, predicting assay and other responses after T1 months at one condition followed by T2 months at the other condition is non-trivial for several reasons. First, the two analyses will give different intercept terms. What should one do about that? Second, how would one calculate the confidence limits for combined storage? Third, what if prior storage at one condition affects the slope at the other condition? This paper proposes a simple ANCOVA model containing two slope terms, one for each storage condition. When multiple batches and/or packages are involved, it is easily generalized to two sets of slope terms. Confidence limits are straightforward and can be calculated using existing commercial software. With properly designed data, one can test whether prior storage at one condition affects the slope at the other condition. If no such effect is significant, very useful extrapolations can be made. Temperature excursions, model reduction and curvilinear dependencies are discussed.

  14. 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

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

    PubMed

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

    2016-07-01

    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 regimens

  16. A universal property for sequential measurement

    NASA Astrophysics Data System (ADS)

    Westerbaan, Abraham; Westerbaan, Bas

    2016-09-01

    We study the sequential product the operation p ∗ q = √{ p } q √{ p } on the set of effects, [0, 1]𝒜, of a von Neumann algebra 𝒜 that represents sequential measurement of first p and then q. In their work [J. Math. Phys. 49(5), 052106 (2008)], Gudder and Latrémolière give a list of axioms based on physical grounds that completely determines the sequential product on a von Neumann algebra of type I, that is, a von Neumann algebra ℬ(ℋ) of all bounded operators on some Hilbert space ℋ. In this paper we give a list of axioms that completely determines the sequential product on all von Neumann algebras simultaneously (Theorem 4).

  17. 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).

  18. SOPIE: Sequential Off-Pulse Interval Estimation

    NASA Astrophysics Data System (ADS)

    Schutte, Willem D.

    2016-07-01

    SOPIE (Sequential Off-Pulse Interval Estimation) provides functions to non-parametrically estimate the off-pulse interval of a source function originating from a pulsar. The technique is based on a sequential application of P-values obtained from goodness-of-fit tests for the uniform distribution, such as the Kolmogorov-Smirnov, Cramér-von Mises, Anderson-Darling and Rayleigh goodness-of-fit tests.

  19. 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.

  20. Dosing regimens of cotrimoxazole (trimethoprim-sulfamethoxazole) for melioidosis.

    PubMed

    Cheng, Allen C; McBryde, Emma S; Wuthiekanun, Vanaporn; Chierakul, Wirongrong; Amornchai, Premjit; Day, Nicholas P J; White, Nicholas J; Peacock, Sharon J

    2009-10-01

    Melioidosis is an infectious disease with a propensity for relapse, despite prolonged antibiotic eradication therapy for 12 to 20 weeks. A pharmacokinetic (PK) simulation study was performed to determine the optimal dosing of cotrimoxazole (trimethoprim-sulfamethoxazole [TMP-SMX]) used in current eradication regimens in Thailand and Australia. Data for bioavailability, protein binding, and coefficients of absorption and elimination were taken from published literature. Apparent volumes of distribution were correlated with body mass and were estimated separately for Thai and Australian populations. In vitro experiments demonstrated concentration-dependent killing. In Australia, the currently used eradication regimen (320 [TMP]/1,600 [SMX] mg every 12 h [q12h]) was predicted to achieve the PK-pharmacodynamic (PD) target (an area under the concentration-time curve from 0 to 24 h/MIC ratio of >25 for both TMP and SMX) for strains with the MIC90 of Australian strains (< or = 1/19 mg/liter). In Thailand, the former regimen of 160/800 mg q12h would not be expected to attain the target for strains with an MIC of > or = 1/19 mg/liter, but the recently implemented weight-based regimen (<40 kg [body weight], 160/800 mg q12h; 40 to 60 kg, 240/1,200 mg q12h; >60 kg, 320/1,600 mg q12h) would be expected to achieve adequate concentrations for strains with an MIC of < or = 1/19 mg/liter. The results were sensitive to the variance of the PK parameters. Prospective PK-PD studies of Asian populations are needed to optimize TMP-SMX dosing in melioidosis.

  1. Care of Patients With HIV Infection: Antiretroviral Drug Regimens.

    PubMed

    Bolduc, Philip; Roder, Navid; Colgate, Emily; Cheeseman, Sarah H

    2016-04-01

    The advent of combination antiretroviral drug regimens has transformed HIV infection from a fatal illness into a manageable chronic condition. All patients with HIV infection should be considered for antiretroviral therapy, regardless of CD4 count or HIV viral load, for individual benefit and to prevent HIV transmission. Antiretroviral drugs affect HIV in several ways: entry inhibitors block HIV entry into CD4 T cells; nucleotide and nucleoside reverse transcriptase inhibitors prevent reverse transcription from RNA to DNA via chain-terminating proteins; nonnucleoside reverse transcriptase inhibitors prevent reverse transcription through enzymatic inhibition; integrase strand transfer inhibitors block integration of viral DNA into cellular DNA; protease inhibitors block maturation and production of the virus. Current guidelines recommend six combination regimens for initial therapy. Five are based on tenofovir and emtricitabine; the other uses abacavir and lamivudine. Five include integrase strand transfer inhibitors. HIV specialists should assist with treating patients with complicated HIV infection, including patients with treatment-resistant HIV infection, coinfection with hepatitis B or C virus, pregnancy, childhood infections, severe opportunistic infections, complex drug interactions, significant drug toxicity, or comorbidities. Family physicians can treat most patients with HIV infection effectively by choosing appropriate treatment regimens, monitoring patients closely, and retaining patients in care. PMID:27092564

  2. Preclinical Evaluations To Identify Optimal Linezolid Regimens for Tuberculosis Therapy

    PubMed Central

    Drusano, George L.; Adams, Jonathan R.; Rodriquez, Jaime L.; Jambunathan, Kalyani; Baluya, Dodge L.; Brown, David L.; Kwara, Awewura; Mirsalis, Jon C.; Hafner, Richard; Louie, Arnold

    2015-01-01

    ABSTRACT Linezolid is an oxazolidinone with potent activity against Mycobacterium tuberculosis. Linezolid toxicity in patients correlates with the dose and duration of therapy. These toxicities are attributable to the inhibition of mitochondrial protein synthesis. Clinically relevant linezolid regimens were simulated in the in vitro hollow-fiber infection model (HFIM) system to identify the linezolid therapies that minimize toxicity, maximize antibacterial activity, and prevent drug resistance. Linezolid inhibited mitochondrial proteins in an exposure-dependent manner, with toxicity being driven by trough concentrations. Once-daily linezolid killed M. tuberculosis in an exposure-dependent manner. Further, 300 mg linezolid given every 12 hours generated more bacterial kill but more toxicity than 600 mg linezolid given once daily. None of the regimens prevented linezolid resistance. These findings show that with linezolid monotherapy, a clear tradeoff exists between antibacterial activity and toxicity. By identifying the pharmacokinetic parameters linked with toxicity and antibacterial activity, these data can provide guidance for clinical trials evaluating linezolid in multidrug antituberculosis regimens. PMID:26530386

  3. Sequential effects in face-attractiveness judgment.

    PubMed

    Kondo, Aki; Takahashi, Kohske; Watanabe, Katsumi

    2012-01-01

    A number of studies have shown that current-trial responses are biased toward the response of the preceding trial in perceptual decisionmaking tasks (the sequential effect-Holland and Lockhead, 1968 Perception & Psychophysics 3 409-414). The sequential effect has been widely observed in evaluation of the physical properties of stimuli as well as more complex properties. However, it is unclear whether subjective decisions (e.g., attractiveness judgments) are also susceptible to the sequential effect. Here, we examined whether the sequential effect would occur in face-attractiveness judgments. Forty-eight pictures of male and female faces were presented successively. Participants rated the attractiveness of each face on a 7-point scale. The results showed that the attractiveness rating of a given face assimilated toward the rating of the preceding trial. In a separate experiment, we provided the average attractiveness rating by others for each trial as feedback. The feedback weakened the sequential effect. These findings suggest that attractiveness judgment is also biased toward the preceding judgment, and hence the sequential effect can be extended into the domain of subjective decisionmaking. PMID:22611662

  4. Eyewitness confidence in simultaneous and sequential lineups: a criterion shift account for sequential mistaken identification overconfidence.

    PubMed

    Dobolyi, David G; Dodson, Chad S

    2013-12-01

    Confidence judgments for eyewitness identifications play an integral role in determining guilt during legal proceedings. Past research has shown that confidence in positive identifications is strongly associated with accuracy. Using a standard lineup recognition paradigm, we investigated accuracy using signal detection and ROC analyses, along with the tendency to choose a face with both simultaneous and sequential lineups. We replicated past findings of reduced rates of choosing with sequential as compared to simultaneous lineups, but notably found an accuracy advantage in favor of simultaneous lineups. Moreover, our analysis of the confidence-accuracy relationship revealed two key findings. First, we observed a sequential mistaken identification overconfidence effect: despite an overall reduction in false alarms, confidence for false alarms that did occur was higher with sequential lineups than with simultaneous lineups, with no differences in confidence for correct identifications. This sequential mistaken identification overconfidence effect is an expected byproduct of the use of a more conservative identification criterion with sequential than with simultaneous lineups. Second, we found a steady drop in confidence for mistaken identifications (i.e., foil identifications and false alarms) from the first to the last face in sequential lineups, whereas confidence in and accuracy of correct identifications remained relatively stable. Overall, we observed that sequential lineups are both less accurate and produce higher confidence false identifications than do simultaneous lineups. Given the increasing prominence of sequential lineups in our legal system, our data argue for increased scrutiny and possibly a wholesale reevaluation of this lineup format.

  5. Eyewitness confidence in simultaneous and sequential lineups: a criterion shift account for sequential mistaken identification overconfidence.

    PubMed

    Dobolyi, David G; Dodson, Chad S

    2013-12-01

    Confidence judgments for eyewitness identifications play an integral role in determining guilt during legal proceedings. Past research has shown that confidence in positive identifications is strongly associated with accuracy. Using a standard lineup recognition paradigm, we investigated accuracy using signal detection and ROC analyses, along with the tendency to choose a face with both simultaneous and sequential lineups. We replicated past findings of reduced rates of choosing with sequential as compared to simultaneous lineups, but notably found an accuracy advantage in favor of simultaneous lineups. Moreover, our analysis of the confidence-accuracy relationship revealed two key findings. First, we observed a sequential mistaken identification overconfidence effect: despite an overall reduction in false alarms, confidence for false alarms that did occur was higher with sequential lineups than with simultaneous lineups, with no differences in confidence for correct identifications. This sequential mistaken identification overconfidence effect is an expected byproduct of the use of a more conservative identification criterion with sequential than with simultaneous lineups. Second, we found a steady drop in confidence for mistaken identifications (i.e., foil identifications and false alarms) from the first to the last face in sequential lineups, whereas confidence in and accuracy of correct identifications remained relatively stable. Overall, we observed that sequential lineups are both less accurate and produce higher confidence false identifications than do simultaneous lineups. Given the increasing prominence of sequential lineups in our legal system, our data argue for increased scrutiny and possibly a wholesale reevaluation of this lineup format. PMID:24188335

  6. 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…

  7. Antirelapse Efficacy of Various Primaquine Regimens for Plasmodium vivax

    PubMed Central

    Rajgor, D. D.; Gogtay, N. J.; Kadam, V. S.; Kocharekar, M. M.; Parulekar, M. S.; Dalvi, S. S.; Vaidya, A. B.; Kshirsagar, N. A.

    2014-01-01

    Background. Efficacy of standard dose of primaquine (PQ) as antirelapse for P. vivax has decreased. We aimed to assess efficacy of different PQ regimens. Methods. It was an open label, randomized, controlled, parallel group, assessor blind study comparing antirelapse efficacy of 3 PQ regimens (B = 15 mg/day × 14 days, C = 30 mg/day × 7 days, and D = 30 mg/day × 14 days) with no PQ group (A) in P. vivax patients. Paired primary and recurrence samples were subjected to 3 methods: (i) month of recurrence and genotyping, (ii) by PCR-RFLP, and (iii) PCR sequencing, to differentiate relapse and reinfection. The rates of recurrence relapse and reinfection were compared. Methods were compared for concordance between them. Results. The recurrence rate was 16.39%, 8.07%, 10.07%, and 6.62% in groups A, B, C, and D, respectively (P = 0.004). The relapse rate was 6.89%, 1.55%, 4%, and 3.85% as per the month of recurrence; 8.2%, 2%, 4.58%, and 3.68% (P = 0.007) as per PCR-RFLP; and 2.73%, 1.47%, 1.55%, and 1.53% as per PCR sequencing for groups A, B, C, and D, respectively. The concordance between methods was low, 45%. Conclusion. The higher recurrence rate in no PQ as compared to PQ groups documents PQ antirelapse activity. Regimens tested were safe. However, probable resistance to PQ warrants continuous monitoring and low concordance and limitations in the methods warrant caution in interpreting. PMID:25295216

  8. Galeazzi fractures: our modified classification and treatment regimen.

    PubMed

    Fayaz, H C; Jupiter, J B

    2014-02-01

    While diaphyseal fractures of the forearm are a common orthopedic injury, Galeazzi fractures are difficult to treat. The current knowledge on pathobiomechanics and modified therapeutic decisions implicate the need to devise an updated classification and treatment regimen of Galeazzi fractures. We challenge the concept that isolated fractures of the radius should be considered as a Galeazzi fractures as long as stability of the distal radioulnar joint is not proven. Contrary to others we demonstrate that the fracture location alone is not sufficient to determine the stability of the distal radioulnar joint.

  9. [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. PMID:21585106

  10. Benefits and Risks of Fosaprepitant in Patients Receiving Emetogenic Regimens.

    PubMed

    Pritchett, Wendy; Kinsley, Karen

    2016-10-01

    Fosaprepitant dimeglumine (Emend IV®) is an IV antiemetic that may be beneficial to patients receiving highly emetogenic regimens. Aprepitant (Emend®) is an oral medication that is administered for three consecutive days, whereas fosaprepitant is a single-dose IV medication that is administered on the day of chemotherapy for 20-30 minutes (depending on the IV access type). Fosaprepitant may be useful, yet it can also present a risk for hypersensitivity reactions and phlebitis. Oncology nurses must be aware of the signs and symptoms of these potential adverse events to properly care for their patients. 
. PMID:27668376

  11. 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.

  12. 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.

  13. Sequential sampling designs based on space reduction

    NASA Astrophysics Data System (ADS)

    Liu, Haitao; Xu, Shengli; Wang, Xiaofang

    2015-07-01

    In the field of engineering design and optimization, metamodels are widely used to replace expensive simulation models in order to reduce computing costs. To improve the accuracy of metamodels effectively and efficiently, sequential sampling designs have been developed. In this article, a sequential sampling design using the Monte Carlo method and space reduction strategy (MCSR) is implemented and discussed in detail. The space reduction strategy not only maintains good sampling properties but also improves the efficiency of the sampling process. Furthermore, a local boundary search (LBS) algorithm is proposed to efficiently improve the performance of MCSR, which is called LBS-MCSR. Comparative results with several sequential sampling approaches from low to high dimensions indicate that the space reduction strategy generates samples with better sampling properties (and thus better metamodel accuracy) in less computing time.

  14. 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.

  15. 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.

  16. 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

  17. Recent advances in tuberculosis: New drugs and treatment regimens.

    PubMed

    Sloan, Derek J; Davies, Geraint R; Khoo, Saye H

    2013-06-01

    The current treatment regimen against drug susceptible tuberculosis (DS-TB) was defined by the 1980s. Since then the emergence of the global HIV pandemic and the escalation of drug resistant (DR-) forms of TB have presented new challenges for therapeutic research. Priority goals include shortening DS-TB treatment, improving DR-TB treatment and making combined TB-HIV therapy easier. To help achieve these goals, a range of new drugs and treatment strategies are currently being evaluated. Phase IIb and III clinical trials are ongoing to assess combinations involving the high-dose rifamycins, the 8-methoxyquinolones, a diarylquinoline (bedaquiline) and the nitroimidazoles. Other compounds (e.g. novel oxazolidinones and ethylenediamines) are at earlier stages of clinical development. Overall, there are grounds for optimism that recent advances will contribute towards achievement of new treatment regimens in the foreseeable future. However, long-term investment, political commitment and scientific endeavour are crucial to ensure that progress is sustained and the benefits of recent advances reach those in the greatest need.

  18. Adherence With Therapeutic Regimens: Behavioral and Pharmacoeconomic Perspectives.

    PubMed

    Giannetti, Vincent J; Kamal, Khalid M

    2016-04-01

    There is an extensive literature regarding nonadherence with both therapeutic regimens and medication. This literature includes reviews of empirical research regarding the factors associated with nonadherence. Health care system, provider, and patient factors as well as the nature of the illness and therapeutic regimen all effect adherence rates. Different behavioral models for adherence counseling such as the Health Belief Model, the Theory of Reasoned Action, the Medication Interest Model, and Motivational Interviewing have also been reported in the research literature. This article will discuss the development of a brief model for patient counseling with specific techniques illustrated for pharmacists based on empirical findings that have demonstrated effectiveness in the adherence research literature. In addition, the article will address the measurement of the economic impact of medication nonadherence and propose a framework for assessing the cost-effectiveness of pharmacist counseling to increase adherence. The problem of nonadherence has significant effects upon health care expenditures through increase in physician's visits, emergency department incidents, rehospitalizations, and nursing home readmissions. Thus, the overall goal is to assist the pharmacist in developing a brief adherence counseling program in community pharmacy and evaluating the economic feasibility of the intervention demonstrating the value-added proposition of pharmacist intervention. PMID:25292442

  19. 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.

  20. Designing drug regimens for special intensive care unit populations

    PubMed Central

    Erstad, Brian L

    2015-01-01

    This review is intended to help clinicians design drug regimens for special populations of critically ill patients with extremes of body size, habitus and composition that make drug choice or dosing particularly challenging due to the lack of high-level evidence on which to make well-informed clinical decisions. The data sources included a literature search of MEDLINE and EMBASE with reviews of reference lists of retrieved articles. Abstracts of original research investigations and review papers were reviewed for their relevance to drug choice or dosing in the following special critically ill populations: patients with more severe forms of bodyweight or height, patients with amputations or missing limbs, pregnant patients, and patients undergoing extracorporeal membrane oxygenation or plasma exchange. Relevant papers were retrieved and evaluated, and their associated reference lists were reviewed for citations that may have been missed through the electronic search strategy. Relevant original research investigations and review papers that could be used to formulate general principles for drug choice or dosing in special populations of critically ill patients were extracted. Randomized studies with clinically relevant endpoints were not available for performing quantitative analyses. Critically ill patients with changes in body size, habitus and composition require special consideration when designing medication regimens, but there is a paucity of literature on which to make drug-specific, high-level evidence-based recommendations. Based on the evidence that is available, general recommendations are provided for drug choice or dosing in special critically ill populations. PMID:25938029

  1. 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...

  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. 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…

  4. 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…

  5. 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)

  6. Adaptive sequential testing for multiple comparisons.

    PubMed

    Gao, Ping; Liu, Lingyun; Mehta, Cyrus

    2014-01-01

    We propose a Markov process theory-based adaptive sequential testing procedure for multiple comparisons. The procedure can be used for confirmative trials involving multi-comparisons, including dose selection or population enrichment. Dose or subpopulation selection and sample size modification can be made at any interim analysis. Type I error control is exact. PMID:24926848

  7. 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

  8. 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.

  9. Comparative Effectiveness of Biologic Therapy Regimens for Ankylosing Spondylitis

    PubMed Central

    Chen, Chao; Zhang, XiaoLin; Xiao, Lu; Zhang, XueSong; Ma, XinLong

    2016-01-01

    Abstract To establish the comparative effectiveness of all available biologic therapy regimens for ankylosing spondylitis, we performed a systematic review and a Bayesian network meta-analysis of randomized controlled trials. PubMed, Medline, Embase, Cochrane library, and ClinicalTrials.gov were searched from the inception of each database to June 2015. Systematic review and network meta-analysis was reported according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses. The primary outcome was 20% improvement of Assessments in SpondyloArthritis International Society Response Criteria (ASAS20) at Week 12 or 14; secondary outcomes were ASAS40, ASAS5/6, ASAS partial remission and 50% improvement in baseline Bath ankylosing spondylitis (AS) disease activity index. We reported relative risks and 95% confidence intervals from direct meta-analysis and 95% credible intervals from Bayesian network meta-analysis, and ranked the treatment for outcomes. We also used Grading of Recommendations Assessment, Development and Evaluation criteria to appraise quality of evidence. Fourteen RCTs comprising 2672 active AS patients were included in the network meta-analysis. Most biologic therapy regimens were more effective than placebo regarding all the outcomes assessed, except for secukinumab and tocilizumab. No differences between biologic therapies in the treatment of AS could be found, except for the finding that infliximab 5 mg was superior to tocilizumab. Infliximab 5 mg/kg had the highest probability of being ranked the best for achieving ASAS20, whereas notably, secukinumab had the highest probability of being ranked the second best. Our study suggests that no differences between biologic therapies in the treatment of AS could be found except that infliximab 5 mg was superior to tocilizumab. Infliximab 5 mg/kg seems to be the better biologic therapy regimen

  10. 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

  11. Levothyroxine treatment in pregnancy: indications, efficacy, and therapeutic regimen.

    PubMed

    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.

  12. Clofarabine and Cytarabine Regimen for Acute Myeloid Leukemia.

    PubMed

    Ho, Kristin V; Solimando, Dominic A; Waddell, J Aubrey

    2015-11-01

    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:27621503

  13. Bevacizumab and Temozolomide Plus Radiation Regimen for Glioblastoma Multiforme

    PubMed Central

    Rutledge, Matthew R.; Waddell, J. Aubrey; Solimando, Dominic A.

    2015-01-01

    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:26823616

  14. 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

  15. New Regimens to Prevent Tuberculosis in Adults with HIV Infection

    PubMed Central

    Martinson, Neil A.; Barnes, Grace L.; Moulton, Lawrence H.; Msandiwa, Reginah; Hausler, Harry; Ram, Malathi; McIntyre, James A.; Gray, Glenda E.; Chaisson, Richard E.

    2012-01-01

    BACKGROUND Treatment of latent tuberculosis in patients infected with the human immunodeficiency virus (HIV) is efficacious, but few patients around the world receive such treatment. We evaluated three new regimens for latent tuberculosis that may be more potent and durable than standard isoniazid treatment. METHODS We randomly assigned South African adults with HIV infection and a positive tuberculin skin test who were not taking antiretroviral therapy to receive rifapentine (900 mg) plus isoniazid (900 mg) weekly for 12 weeks, rifampin (600 mg) plus isoniazid (900 mg) twice weekly for 12 weeks, isoniazid (300 mg) daily for up to 6 years (continuous isoniazid), or isoniazid (300 mg) daily for 6 months (control group). The primary end point was tuberculosis-free survival. RESULTS The 1148 patients had a median age of 30 years and a median CD4 cell count of 484 per cubic millimeter. Incidence rates of active tuberculosis or death were 3.1 per 100 person-years in the rifapentine–isoniazid group, 2.9 per 100 person-years in the rifampin–isoniazid group, and 2.7 per 100 person-years in the continuous-isoniazid group, as compared with 3.6 per 100 person-years in the control group (P>0.05 for all comparisons). Serious adverse reactions were more common in the continuous-isoniazid group (18.4 per 100 person-years) than in the other treatment groups (8.7 to 15.4 per 100 person-years). Two of 58 isolates of Mycobacterium tuberculosis (3.4%) were found to have multidrug resistance. CONCLUSIONS On the basis of the expected rates of tuberculosis in this population of HIV-infected adults, all secondary prophylactic regimens were effective. Neither a 3-month course of intermittent rifapentine or rifampin with isoniazid nor continuous isoniazid was superior to 6 months of isoniazid. PMID:21732833

  16. Eradication of Helicobacter pylori: are rifaximin-based regimens effective?

    PubMed

    Gasbarrini, Antonio; Gasbarrini, Giovanni; Pelosini, Iva; Scarpignato, Carmelo

    2006-01-01

    Rifaximin is a non-absorbed semisynthetic rifamycin derivative with a broad spectrum of antibacterial activity including Gram-positive and Gram-negative bacteria, both aerobes and anaerobes. Although originally developed for the treatment of infectious diarrhea, the appreciation of the pathogenic role of gut bacteria in several organic and functional gastrointestinal diseases has increasingly broadened its clinical use. Being the antibiotic active against Helicobacter pylori, even towards clarithromycin-resistant strain, and being the primary resistance very rare, several investigations explored its potential use for eradication of the microorganism. Rifaximin alone proved to be effective, but even the highest dose (1,200 mg daily) gave a cure rate of only 30%. Dual and triple therapies were also studied, with the better results obtained with rifaximin-clarithromycin and rifaximin-clarithromycin-esomeprazole combinations. However, the eradication rates (60-70%) obtained with these regimens were still below the standard set by the Maastricht Consensus guidelines. Although rifaximin-based eradication therapies are promising, new antimicrobial combinations (with and without proton pump inhibitors) need to be explored in well-designed clinical trials including a large cohort of H. pylori-infected patients. The remarkable safety of rifaximin will allow high-dose regimens of longer duration (e.g. 10 or 14 days) to be tested with confidence in the hope of achieving better eradication rates. A drawback of rifaximin could be its inability to reach sufficiently high concentrations in the gastric mucus layer under and within which H. pylori is commonly located and this would likely affect eradication rate. Taking these considerations into account, bioadhesive rifaximin formulations able to better and persistently cover gastric mucosa, or combination with mucolytic agents, such as pronase or acetylcysteine, need to be evaluated in order to better define the place of this

  17. 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

  18. 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)

  19. 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

  20. 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.

  1. Info-Greedy Sequential Adaptive Compressed Sensing

    NASA Astrophysics Data System (ADS)

    Braun, Gabor; Pokutta, Sebastian; Xie, Yao

    2015-06-01

    We present an information-theoretic framework for sequential adaptive compressed sensing, Info-Greedy Sensing, where measurements are chosen to maximize the extracted information conditioned on the previous measurements. We show that the widely used bisection approach is Info-Greedy for a family of $k$-sparse signals by connecting compressed sensing and blackbox complexity of sequential query algorithms, and present Info-Greedy algorithms for Gaussian and Gaussian Mixture Model (GMM) signals, as well as ways to design sparse Info-Greedy measurements. Numerical examples demonstrate the good performance of the proposed algorithms using simulated and real data: Info-Greedy Sensing shows significant improvement over random projection for signals with sparse and low-rank covariance matrices, and adaptivity brings robustness when there is a mismatch between the assumed and the true distributions.

  2. Sequential shrink photolithography for plastic microlens arrays

    NASA Astrophysics Data System (ADS)

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

    2011-07-01

    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.

  3. Hyperspectral target detection using sequential approach

    NASA Astrophysics Data System (ADS)

    Haskett, Hanna T.; Sood, Arun K.; Habib, Mohammad K.

    1999-08-01

    This paper describes an automatic target detection algorithm based on the sequential multi-stage approach. Each stage of the algorithm uses more spectral bands than the previous stage. To ensure high probability of detection and low false alarm rate, Chebyshev's inequality test is applied. The sequential approach enables a significant reduction in computational time of a hyperspectral detection system. The Forest Radiance I database collected with the HYDICE hyperspectral sensor at the U.S. Army Proving Ground in Aberdeen, Maryland is utilized. Scenarios include targets in the open, with footprints of 1 m and different times of day. The total area coverage and the number of targets used in this evaluation are approximately 6 km2 and 126, respectively.

  4. Sequential shrink photolithography for plastic microlens arrays

    PubMed Central

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

    2011-01-01

    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. PMID:21863126

  5. Applying the Minimax Principle to Sequential Mastery Testing. Research Report.

    ERIC Educational Resources Information Center

    Vos, Hans J.

    This paper derives optimal rules for sequential mastery tests. In a sequential mastery test, the decision is to classify a subject as a master or a nonmaster or to continue sampling and administering another random item. The framework of minimax sequential decision theory (minimum information approach) is used; that is, optimal rules are obtained…

  6. 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…

  7. GENERAL: Mutual Information and Relative Entropy of Sequential Effect Algebras

    NASA Astrophysics Data System (ADS)

    Wang, Jia-Mei; Wu, Jun-De; Cho, Minhyung

    2010-08-01

    In this paper, we introduce and investigate the mutual information and relative entropy on the sequential effect algebra, we also give a comparison of these mutual information and relative entropy with the classical ones by the venn diagrams. Finally, a nice example shows that the entropies of sequential effect algebra depend extremely on the order of its sequential product.

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

    PubMed

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

    2016-05-01

    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

  9. Comparative Study of Apo-Cetirizine Single Therapy and Intermittent Sequential Therapy with Cetirizine, Loratadine and Chlorpheniramine in Allergic Rhinitis.

    PubMed

    Safavi Naini, Ali; Ghorbani, Jahangir; Mazloom, Ebrahim

    2016-09-01

    There are limited numbers of articles, studying combined use of antihistamines. In this study, we compare single therapy of Apo-Cetirizine with a new regimen of intermittent sequential therapy with cetirizine, loratadine and chlorpheniramine in treatment of seasonal allergic rhinitis. This randomized clinical trial was performed between April and September at the peak prevalence of seasonal allergic rhinitis. Fifty-four eligible patients diagnosed clinically to have seasonal allergic rhinitis were randomized in two groups: 24 cases in single therapy arm, received Apo-Cetirizine 10 mg tablet daily and in other arm, 30 patients received sequential regimen of cetirizine 10 mg tablet, loratadine 10 mg tablet and chlorpheniramine 4 mg tablet, one tablet each day. Major Symptom Complex Score (MSCS) and Total Symptom Complex Score (TSCS) of patients were recorded before treatment and after 30 days of treatment in two groups. The average post-treatment MSCS and TSCS in combination therapy group showed better improvement than single therapy group but difference was not statistically significant (p value = 0.053 and p value = 0.104 respectively). Combination therapy regimen was better in improvement of nasal congestion (p value = 0.006). There were no significant difference between two groups in efficacy, side effects and patient's satisfaction. Combination therapy would be effective on a wide spectrum of symptoms with lower price and theoretically offers lower chance of tolerance and re-appearance of complaints. PMID:27508135

  10. Managing numerical errors in random sequential adsorption

    NASA Astrophysics Data System (ADS)

    Cieśla, Michał; Nowak, Aleksandra

    2016-09-01

    Aim of this study is to examine the influence of a finite surface size and a finite simulation time on a packing fraction estimated using random sequential adsorption simulations. The goal of particular interest is providing hints on simulation setup to achieve desired level of accuracy. The analysis is based on properties of saturated random packing of disks on continuous and flat surfaces of different sizes.

  11. 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.

  12. Analytic sequential methods for detecting network intrusions

    NASA Astrophysics Data System (ADS)

    Chen, Xinjia; Walker, Ernest

    2014-05-01

    In this paper, we propose an analytic sequential methods for detecting port-scan attackers which routinely perform random "portscans" of IP addresses to find vulnerable servers to compromise. In addition to rigorously control the probability of falsely implicating benign remote hosts as malicious, our method performs significantly faster than other current solutions. We have developed explicit formulae for quick determination of the parameters of the new detection algorithm.

  13. Sequential decision making and stochastic networks

    NASA Technical Reports Server (NTRS)

    Elmaghraby, S.

    1980-01-01

    To solve the problems inherent in working with sequential decision processes, it is proposed to (1) utilize concepts of dominance through bounding in the decision processes (DP) formalism to reduce the amount of computing required. This advocates the marrying of DP recursion and Branch-and-Bound methodology; and (2) relax the requirement of strict optimality in the search over the state space, and be content with a tolerable error.

  14. 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. PMID:26334198

  15. Compressive Sequential Learning for Action Similarity Labeling.

    PubMed

    Qin, Jie; Liu, Li; Zhang, Zhaoxiang; Wang, Yunhong; Shao, Ling

    2016-02-01

    Human action recognition in videos has been extensively studied in recent years due to its wide range of applications. Instead of classifying video sequences into a number of action categories, in this paper, we focus on a particular problem of action similarity labeling (ASLAN), which aims at verifying whether a pair of videos contain the same type of action or not. To address this challenge, a novel approach called compressive sequential learning (CSL) is proposed by leveraging the compressive sensing theory and sequential learning. We first project data points to a low-dimensional space by effectively exploring an important property in compressive sensing: the restricted isometry property. In particular, a very sparse measurement matrix is adopted to reduce the dimensionality efficiently. We then learn an ensemble classifier for measuring similarities between pairwise videos by iteratively minimizing its empirical risk with the AdaBoost strategy on the training set. Unlike conventional AdaBoost, the weak learner for each iteration is not explicitly defined and its parameters are learned through greedy optimization. Furthermore, an alternative of CSL named compressive sequential encoding is developed as an encoding technique and followed by a linear classifier to address the similarity-labeling problem. Our method has been systematically evaluated on four action data sets: ASLAN, KTH, HMDB51, and Hollywood2, and the results show the effectiveness and superiority of our method for ASLAN.

  16. Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy

    PubMed Central

    Guinto, Valerie T; De Guia, Blanca; Festin, Mario R; Dowswell, Therese

    2014-01-01

    Background Asymptomatic bacteriuria occurs in 5% to 10% of pregnancies and, if left untreated, can lead to serious complications. Objectives To assess which antibiotic is most effective and least harmful as initial treatment for asymptomatic bacteriuria in pregnancy. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (March 2010) and reference lists of retrieved studies. Selection criteria Randomized controlled trials comparing two antibiotic regimens for treating asymptomatic bacteriuria. Data collection and analysis Review authors independently screened the studies for inclusion and extracted data. Main results We included five studies involving 1140 women with asymptomatic bacteriuria. We did not perform meta-analysis; each trial examined different antibiotic regimens and so we were not able to pool results. In a study comparing a single dose of fosfomycin trometamol 3 g with a five-day course of cefuroxime, there was no significant difference in persistent infection (risk ratio (RR) 1.36, 95% confidence interval (CI) 0.24 to 7.75), shift to other antibiotics (RR 0.08, 95% CI 0.00 to 1.45), or in allergy or pruritus (RR 2.73, 95% CI 0.11 to 65.24). A comparison of seven-day courses of 400 mg pivmecillinam versus 500 mg ampicillin, both given four times daily, showed no significant difference in persistent infection at two weeks or recurrent infection, but there was an increase in vomiting (RR 4.57, 95% CI 1.40 to 14.90) and women were more likely to stop treatment early with pivmecillinam (RR 8.82, 95% CI 1.16 to 66.95). When cephalexin 1 g versus Miraxid® (pivmecillinam 200 mg and pivampicillin 250 mg) were given twice-daily for three days, there was no significant difference in persistent or recurrent infection. A one- versus seven-day course of nitrofurantoin resulted in more persistent infection with the shorter course (RR 1.76, 95% CI 1.29 to 2.40), but no significant difference in symptomatic infection at two weeks

  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. The Effects of Different Recess Timing Regimens on Preschoolers' Classroom Attention

    ERIC Educational Resources Information Center

    Holmes, Robyn M.; Pellegrini, Anthony D.; Schmidt, Susan L.

    2006-01-01

    This study examined the effects of different recess timing regimens on preschoolers classroom attention. Using cognitive immaturity theory, we predicted that attention to a classroom task would be greater after a recess break. We also examined the extent to which different recess timing regimens related to post-recess attention. Participants were…

  20. Following an HIV Regimen: Steps to Take Before and After Starting HIV Medicines

    MedlinePlus

    HIV Treatment Following an HIV Regimen: Steps to Take Before and After Starting HIV Medicines (Last updated 3/1/2016; last reviewed 3/1/2016) ... maintain long-term medication adherence. Before starting an HIV regimen, talk to your health care provider about ...

  1. 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

  2. Labile methyl balances for normal humans on various dietary regimens.

    PubMed

    Mudd, S H; Poole, J R

    1975-06-01

    Normal young adult male and female subjects were maintained on fixed dietary regimens which were either essentially normal or were semisynthetic and curtailed in methionine and choline intakes and virtually free of cystine. The subjects maintained stable weights and remained in positive nitrogen balance or within the zone of sulfur equilibrium. Choline intakes were calculated, and urinary excretions of creatinine, creatine, and sacrosine were measured. Creatinine excretions of male subjects on essentially normal diets outweighed the total intakes of labile methyl groups. Taking into account the excretions of additional methylated compounds, as judged from published values, it appears that methyl neogenesis must normally play a role in both males and females. When labile methyl intake is curtailed, de novo formation of methyl groups is quantitatively more significant than ingestion of preformed methyl moieties. On the normal diets used in these experiments, the average homocysteinyl moiety in males cycled between methionine and homocysteine at least 1.9 times before being converted to cystathionine. For females, the average number of cycles was at least 1.5. When labile methyl intake was curtailed, the average number of cycles rose to 3.9 for males and 3.0 for females under the conditions employed.

  3. 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.

  4. Various regimens for prophylactic treatment of patients with haemophilia.

    PubMed

    Schwarz, Rudolf; Ljung, Rolf; Tedgård, Ulf

    2015-02-01

    Haemophilia prophylaxis is superior to on-demand treatment to prevent joint damage. 'High-dose prophylaxis' as used in Sweden is more effective in preventing arthropathy than an 'intermediate-dose regimen' (the Netherlands) and the Canadian tailored primary prophylaxis. Prophylaxis may reduce the risk of developing inhibitors. There is no difference in inhibitor risk between plasma derived and recombinant factor VIII (rFVIII) products but the Rodin study showed increased risk with second-generation rFVIII products. MRI is a new and very sensitive tool to detect the symptoms of early arthropathy but some results (soft tissue changes in 'bleed-free joints') still need to be investigated. Ultrasound is a very helpful method to aid diagnosis especially during the acute phase of a bleed. The risk of infection with central venous access remains a matter of debate. A fully implanted central venous access device (CVAD) has a significant lower risk of infection compared to external CVADs. Patient's age under 6 yr and inhibitor presence are additional risk factors for infections. The role of arteriovenous fistulae needs to be investigated because significant complications have been reported. Disease-specific quality of life instruments are complementary to generic instruments evaluating QoL in patients with haemophilia and have become important health outcome measures.

  5. [Comparison of clinical efficacy between decitabine combined with CAG regimen and CAG regimen alone in patients with intermediate to high-risk myelodysplastic syndromes].

    PubMed

    Zhang, Yun-Ping; Wu, Wen-Zhong; Cui, Guo-Xing

    2014-10-01

    This study was purposed to compare the clinical efficacy and adverse reactions of low-dose decitabine combined with CAG regimen (aclarubicin, Ara-C, and G-CSF) and CAG regimen alone in intermediate to high-risk myelodysplastic syndromes (MDS), and evaluate the validity and efficacy of the former regimen as new treatment method of intermediate to high-risk myelodysplastic syndromes. A total of 12 patients with intermediate (IR) to high-risk (HR) MDS treated by low-dose decitabine combined with CAG regimen and 10 patients with IR to HR MDS treated by CAG regimen alone were evaluated after treatment of 1 cycle and at least after 2 cycles. The complete remission (CR) after 1 cycle, overall remission rate (ORR), progression free survival (PFS) and overall survival (OS) between them were analyzed. The results showed that 9 patients treated by low-dose decitabine combined with CAG regimen achieved complete remission after 1 cycle, 2 patients achieved partial remission, 1 patient did not show reaction. The complete remission rate was 75.0% and overall response rate was 91.7%. The median time of disease free survival was 9 months (0-27 months). The median overall survival time was 16 months (3-28 months). 4 patients suffered from pulmonary infection after treatment and then were all cured after treatment with anti-infective therapy. The 5 patients treated by CAG regimen alone achieved complete remission,3 patients achieved partial remission, 2 patients showed non-reaction. The complete remission rate was 50.0% and overall response rate was 80.0%. The median time of disease free survival was 6 months(0-18 months). The median overall survival time was 13 months(3-31 months), 4 patients suffered from pulmonary infection, 1 patient suffered from enteric infection and 1 patient suffered from Escherichia coli septicemia after treatment, all of them becomed better after active treatment. Two groups of patients all had no serious adverse reactions, All patients could tolerate, no

  6. Role of Taxane and Anthracycline Combination Regimens in the Management of Advanced Breast Cancer

    PubMed Central

    Zheng, Ruinian; Han, Shuai; Duan, Chongyang; Chen, Kexu; You, Zhijian; Jia, Jun; Lin, Shunhuan; Liang, Liming; Liu, Aixue; Long, Huidong; Wang, Senming

    2015-01-01

    Abstract The clinical benefits provided by using combined taxanes and anthracyclines in first-line chemotherapy for metastatic breast carcinoma (MBC) remain uncertain. This meta-analysis compares the benefits of using a combination of anthracyclines along with taxanes versus using single-agent-based chemotherapeutic regimens in the treatment of MBC. Relevant clinical trials as well as abstracts from articles presented at major cancer conferences were searched in various databases including PubMed, Embase, and Cochrane Library. The relevant studies had a primary endpoint of overall survival (OS) and secondary endpoints that included progression-free survival (PFS), time-to-treatment failure (TTF), time to progression (TTP), objective response rate (ORR), disease control rate (DCR), and safety. The hazard ratios of OS, PFS, TTF, and TTP, the odds ratios of ORR and DCR, and the risk ratios (RRs) for grades 1–2 and 3–4 toxicities were extracted from the retrieved studies and analyzed using various statistical methods. Meta-analytic estimates were derived from a random-effect model. Fifteen trials were included in the final meta-analysis, and the results suggest that chemotherapy with combined anthracyclines and taxanes does not significantly improve the OS of MBC patients when compared with the OS achieved using separate taxane or anthracycline-based regimens. Compared with taxane-based regimens, combined taxane along with anthracycline regimens failed to significantly improve TTP, ORR, or DCR, but did significantly improve TTP and ORR when compared with anthracycline-based regimens. Furthermore, both individual taxane-based and anthracycline-based regimens produced fewer toxic reactions compared to combined taxane along with anthracycline regimens. Taxane-based regimens had lower RRs for side effects of neutropenia, infection/febrile neutropenia, nausea, and vomiting, whereas patients receiving anthracycline-based regimens had lower RRs for neutropenia, infection

  7. Satisfaction with the Health Care Provider and Regimen Adherence in Minority Youth with Type 1 Diabetes.

    PubMed

    Taylor, Cortney J; La Greca, Annette; Valenzuela, Jessica M; Hsin, Olivia; Delamater, Alan M

    2016-09-01

    To assess whether satisfaction with the health-care provider is related to regimen adherence among primarily minority youth with type 1 diabetes. Youth with type 1 diabetes (n = 169; M age = 13.88; 52 % female; 70 % Hispanic) and their parents completed questionnaires that assessed their own satisfaction with the health-care provider and youths' adherence to diabetes self-care behaviors. Higher youth and parent patient-provider relationship satisfaction was associated with higher regimen adherence. Gender affected the relationship between satisfaction and regimen adherence, such that for girls, greater satisfaction was associated with better adherence; this was not the case for boys. Patient satisfaction with the health care provider is important for regimen adherence among primarily minority youth with type 1 diabetes, particularly for girls. Future research might focus on improving youths' relationships with their health care providers as a potential pathway to improve regimen adherence. PMID:27365095

  8. 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.

  9. 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

  10. A wireless sequentially actuated microvalve system

    NASA Astrophysics Data System (ADS)

    Baek, Seung-Ki; Yoon, Yong-Kyu; Jeon, Hye-Seon; Seo, Soonmin; Park, Jung-Hwan

    2013-04-01

    A wireless microvalve system was fabricated based on induction heating for flow control in microfluidics by sequential valve opening. In this approach, we used paraffin wax as a flow plug, which can be changed from solid to liquid with adjacent heating elements operated by induction heating. Programmable opening of valves was devised by using different thermal responses of metal discs to a magnetic field. Copper and nickel discs with a diameter of 2.5 mm and various thicknesses (50, 100 and 200 µm) were prepared as heating elements by a laser cutting method, and they were integrated in the microfluidic channel as part of the microvalve. A calorimetric test was used to measure the thermal properties of the discs in terms of kinds of metal and disc thickness. Sequential openings of the microvalves were performed using the difference in the thermal response of 100 µm thick copper disc and 50 µm thick nickel disc for short-interval openings and 200 µm thick copper disc and 100-µm-thick nickel disc for long-interval openings. The thermal effect on fluid samples as a result of induction heating of the discs was studied by investigating lysozyme denaturation. More heat was generated in heating elements made of copper than in those made of nickel, implying differences in the thermal response of heating elements made of copper and nickel. Also, the thickness of the heating elements affected the thermal response in the elements. Valve openings for short intervals of 1-5 s and long intervals of 15-23 s were achieved by using two sets of heating elements. There was no significant change in lysozyme activity by increasing the temperature of the heating discs. This study demonstrates that a wireless sequentially actuated microvalve system can provide programmed valve opening, portability, ease of fabrication and operation, disposability, and low cost.

  11. Random sequential adsorption of trimers and hexamers.

    PubMed

    Cieśla, Michał; Barbasz, Jakub

    2013-12-01

    Adsorption of trimers and hexamers built of identical spheres was studied numerically using the random sequential adsorption (RSA) algorithm. Particles were adsorbed on a two-dimensional, flat and homogeneous surface. Numerical simulations allowed us to determine the maximal random coverage ratio, RSA kinetics as well as the available surface function (ASF), which is crucial for determining the kinetics of the adsorption process obtained experimentally. Additionally, the density autocorrelation function was measured. All the results were compared with previous results obtained for spheres, dimers and tetramers.

  12. Sequential cooling insert for turbine stator vane

    SciTech Connect

    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.

  13. 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.

  14. Nonlinear sequential laminates reproducing hollow sphere assemblages

    NASA Astrophysics Data System (ADS)

    Idiart, Martín I.

    2007-07-01

    A special class of nonlinear porous materials with isotropic 'sequentially laminated' microstructures is found to reproduce exactly the hydrostatic behavior of 'hollow sphere assemblages'. It is then argued that this result supports the conjecture that Gurson's approximate criterion for plastic porous materials, and its viscoplastic extension of Leblond et al. (1994), may actually yield rigorous upper bounds for the hydrostatic flow stress of porous materials containing an isotropic, but otherwise arbitrary, distribution of porosity. To cite this article: M.I. Idiart, C. R. Mecanique 335 (2007).

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Sequential or alternating administration of docetaxel (Taxotere®) combined with FEC in metastatic breast cancer: a randomised phase II trial

    PubMed Central

    Spielmann, M; Tubiana-Hulin, M; Namer, M; Mansouri, H; Bougnoux, P h; Tubiana-Mathieu, N; Lotz, V; Eymard, J C

    2002-01-01

    The aim of this study, using a Fleming single-stage design, was to explore the efficacy and safety of Taxotere® 100 mg m−2 docetaxel and FEC 75 cyclophosphamide 500 mg m−2, fluorouracil 500 mg m−2 and epirubicin 75 mg m−2, in alternating and sequential schedules for the first-line treatment of metastatic breast cancer. One hundred and thirty-six women were randomly allocated, to one of three treatment regimens: DTX 100 plus FEC 75, alternated for eight courses (ALT); four courses of DTX 100 followed by four courses of FEC 75 (SEQ T); or four courses of FEC 75 followed by four courses of DTX 100 (SEQ F). One hundred and thirty-one women were evaluable for tumour response. Although the treatment outcome was equivalent in the two sequential arms and the alternating regimen (P=0.110, not significant), the response rate was less encouraging in the SEQ F arm (52.3%) than in the other two arms (71.1% for ALT and 70.5% for SEQ T), in which docetaxel was administered first. Time to progression was similar in the ALT, SEQ T and SEQ F arms (9.5, 9.3 and 10.4 months respectively). Grade 3–4 neutropenia was observed in nearly all patients; febrile neutropenia occurred in 9% (ALT), 16% (SEQ T) and 2% (SEQ F) of patients. Few patients (⩽9%) developed grade 3–4 non-haematological toxicities. Relative dose intensity was 97–99% for all regimens. All treatment regimens were active and well tolerated. British Journal of Cancer (2002) 86, 692–697. DOI: 10.1038/sj/bjc/6600165 www.bjcancer.com © 2002 Cancer Research UK PMID:11875727

  1. 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

  2. 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…

  3. Efficient Controls for Finitely Convergent Sequential Algorithms

    PubMed Central

    Chen, Wei; Herman, Gabor T.

    2010-01-01

    Finding a feasible point that satisfies a set of constraints is a common task in scientific computing: examples are the linear feasibility problem and the convex feasibility problem. Finitely convergent sequential algorithms can be used for solving such problems; an example of such an algorithm is ART3, which is defined in such a way that its control is cyclic in the sense that during its execution it repeatedly cycles through the given constraints. Previously we found a variant of ART3 whose control is no longer cyclic, but which is still finitely convergent and in practice it usually converges faster than ART3 does. In this paper we propose a general methodology for automatic transformation of finitely convergent sequential algorithms in such a way that (i) finite convergence is retained and (ii) the speed of convergence is improved. The first of these two properties is proven by mathematical theorems, the second is illustrated by applying the algorithms to a practical problem. PMID:20953327

  4. Continuous sequential boundaries for vaccine safety surveillance.

    PubMed

    Li, Rongxia; Stewart, Brock; Weintraub, Eric; McNeil, Michael M

    2014-08-30

    Various recently developed sequential methods have been used to detect signals for post-marketing surveillance in drug and vaccine safety. Among these, the maximized sequential probability ratio test (MaxSPRT) has been used to detect elevated risks of adverse events following vaccination using large healthcare databases. However, a limitation of MaxSPRT is that it only provides a time-invariant flat boundary. In this study, we propose the use of time-varying boundaries for controlling how type I error is distributed throughout the surveillance period. This is especially useful in two scenarios: (i) when we desire generally larger sample sizes before a signal is generated, for example, when early adopters are not representative of the larger population; and (ii) when it is desired for a signal to be generated as early as possible, for example, when the adverse event is considered rare but serious. We consider four specific time-varying boundaries (which we call critical value functions), and we study their statistical power and average time to signal detection. The methodology we present here can be viewed as a generalization or flexible extension of MaxSPRT. PMID:24691986

  5. 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

  6. Noncommutative Biology: Sequential Regulation of Complex Networks.

    PubMed

    Letsou, William; Cai, Long

    2016-08-01

    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

  7. 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

  8. Sequential Stenting for Extensive Malignant Airway Stenosis

    PubMed Central

    Takahama, Makoto; Nakajima, Ryu; Kimura, Michitaka; Tei, Keiko; Yamamoto, Ryoji

    2014-01-01

    Purpose: Malignant airway stenosis extending from the bronchial bifurcation to the lower lobar orifice was treated with airway stenting. We herein examine the effectiveness of airway stenting for extensive malignant airway stenosis. Methods: Twelve patients with extensive malignant airway stenosis underwent placement of a silicone Dumon Y stent (Novatech, La Ciotat, France) at the tracheal bifurcation and a metallic Spiral Z-stent (Medico’s Hirata, Osaka, Japan) at either distal side of the Y stent. We retrospectively analyzed the therapeutic efficacy of the sequential placement of these silicone and metallic stents in these 12 patients. Results: The primary disease was lung cancer in eight patients, breast cancer in two patients, tracheal cancer in one patient, and thyroid cancer in one patient. The median survival period after airway stent placement was 46 days. The Hugh–Jones classification and performance status improved in nine patients after airway stenting. One patient had prolonged hemoptysis and died of respiratory tract hemorrhage 15 days after the treatment. Conclusion: Because the initial disease was advanced and aggressive, the prognosis after sequential airway stent placement was significantly poor. However, because respiratory distress decreased after the treatment in most patients, this treatment may be acceptable for selected patients with extensive malignant airway stenosis. PMID:25273272

  9. 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.

  10. Paclitaxel-based regimens as first-line treatment in advanced gastric cancer.

    PubMed

    Guo, Zengqing; Wang, Xiaojie; Lin, Rongbo; Chen, Ling; Fan, Nanfeng; Chen, Yu; Lin, Jinyuan; Yu, Jiami

    2015-02-01

    The aim of this study was to evaluate the efficacy and safety of paclitaxel-based regimens as first-line treatments in advanced gastric cancer. We reviewed 397 previously untreated patients with advanced gastric cancer, who non-randomly received one of three paclitaxel-based regimens: paclitaxel plus fluorouracil/leucovorin (PF), paclitaxel plus oxaliplatin (PO), and paclitaxel plus oxaliplatin plus fluorouracil/leucovorin (POF) between January 2003 and December 2010. The PF, PO, and POF response rates were 47.13, 52.08, and 63.78%, respectively. Overall survivals (OS) were 11.2, 11.7, and 11.7 months, respectively. Progression-free survivals (PFS) were 6.6, 7.2, and 7.1 months, respectively. Leucopenia was higher on the triplet regimen than the doublet regimens. The paclitaxel-based regimens appeared to be effective in patients with advanced gastric cancer. The triplet regimen produced a higher response rate than either doublet regimen with more side effects, while survivals were similar among all three treatments.

  11. Sequential probability ratio controllers for safeguards radiation monitors

    SciTech Connect

    Fehlau, P.E.; Coop, K.L.; Nixon, K.V.

    1984-01-01

    Sequential hypothesis tests applied to nuclear safeguards accounting methods make the methods more sensitive to detecting diversion. The sequential tests also improve transient signal detection in safeguards radiation monitors. This paper describes three microprocessor control units with sequential probability-ratio tests for detecting transient increases in radiation intensity. The control units are designed for three specific applications: low-intensity monitoring with Poisson probability ratios, higher intensity gamma-ray monitoring where fixed counting intervals are shortened by sequential testing, and monitoring moving traffic where the sequential technique responds to variable-duration signals. The fixed-interval controller shortens a customary 50-s monitoring time to an average of 18 s, making the monitoring delay less bothersome. The controller for monitoring moving vehicles benefits from the sequential technique by maintaining more than half its sensitivity when the normal passage speed doubles.

  12. 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.

  13. 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.

  14. Antiretroviral Regimens in Pregnancy and Breast-Feeding in Botswana

    PubMed Central

    Shapiro, R.L.; Hughes, M.D.; Ogwu, A.; Kitch, D.; Lockman, S.; Moffat, C.; Makhema, J.; Moyo, S.; Thior, I.; McIntosh, K.; van Widenfelt, E.; Leidner, J.; Powis, K.; Asmelash, A.; Tumbare, E.; Zwerski, S.; Sharma, U.; Handelsman, E.; Mburu, K.; Jayeoba, O.; Moko, E.; Souda, S.; Lubega, E.; Akhtar, M.; Wester, C.; Tuomola, R.; Snowden, W.; Martinez-Tristani, M.; Mazhani, L.; Essex, M.

    2010-01-01

    BACKGROUND The most effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in pregnancy and its efficacy during breast-feeding are unknown. METHODS We randomly assigned 560 HIV-1–infected pregnant women (CD4+ count, ≥200 cells per cubic millimeter) to receive coformulated abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or lopinavir–ritonavir plus zidovudine-lamivudine (the protease-inhibitor group) from 26 to 34 weeks’ gestation through planned weaning by 6 months post partum. A total of 170 women with CD4+ counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine–lamivudine (the observational group). Infants received single-dose nevirapine and 4 weeks of zidovudine. RESULTS The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery (96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the observational group) or throughout the breast-feeding period (92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the observational group). By 6 months of age, 8 of 709 live-born infants (1.1%) were infected (95% confidence interval [CI], 0.5 to 2.2): 6 were infected in utero (4 in the NRTI group, 1 in the protease-inhibitor group, and 1 in the observational group), and 2 were infected during the breast-feeding period (in the NRTI group). Treatment-limiting adverse events occurred in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the observational group. CONCLUSIONS All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression, with an overall rate of mother-to-child transmission of 1.1%. (ClinicalTrials.gov number, NCT00270296.) PMID:20554983

  15. Daily feeding regimen impacts pig growth and behavior.

    PubMed

    Colpoys, Jessica D; Johnson, Anna K; Gabler, Nicholas K

    2016-05-15

    A primary swine production goal is to increase efficiency of lean tissue gains. While many swine production systems currently utilize ad libitum feeding, recent research suggests that altering feeding patterns may impact feed efficiency. Therefore, the objective of this study was to compare two feeding patterns and evaluate their impact on whole body tissue accretion, feeding behavior and activity in growing pigs. Forty eight individually housed gilts (55.9±5.2kg on test BW) were assigned into one of two feeding treatments: 1) Free access to the feeder (Free Access) or 2) twice daily access where gilts were allowed to eat ad libitum between 08:00-09:00h and again from 17:00-18:00h (2×). Pig performance was recorded weekly for 55days and average daily gain (ADG), average daily feed intake (ADFI), and gain:feed (G:F) was calculated. Body composition was assessed in 12 gilts per treatment using dual X-ray absorptiometry (DXA) at day -3 and 55 of treatment, and tissue accretion rates were calculated. Gilt behaviors were assessed via video analysis during week 7 and included time spent eating, feeding rate, enrichment interaction, postural changes, standing, sitting, and lying behaviors. Gilts fed 2× had lower ADG and ADFI compared to Free Access gilts (P≤0.01); however, no treatment difference in G:F was observed (P=0.83). At day 55 gilts fed 2× had a lower fat:protein compared to Free Access gilts (P=0.05). Fat, lean, and protein accretion rates were lower in gilts fed 2× compared to those fed Free Access (P=0.01). Gilts fed 2× ate less frequently and for a shorter duration of time, interacted with enrichment more frequently (P≤0.005), and tended to have less frequent postural changes compared to Free Access gilts (P=0.08). No treatment differences were observed in duration of time spent standing, sitting, or lying (P≥0.39). Although feed regimen did not alter feed efficiency, these data indicate that twice daily feeding reduced gilt adiposity and growth

  16. Discrimination between sequential and simultaneous virtual channels with electrical hearing

    PubMed Central

    Landsberger, David; Galvin, John J.

    2011-01-01

    In cochlear implants (CIs), simultaneous or sequential stimulation of adjacent electrodes can produce intermediate pitch percepts between those of the component electrodes. However, it is unclear whether simultaneous and sequential virtual channels (VCs) can be discriminated. In this study, CI users were asked to discriminate simultaneous and sequential VCs; discrimination was measured for monopolar (MP) and bipolar + 1 stimulation (BP + 1), i.e., relatively broad and focused stimulation modes. For sequential VCs, the interpulse interval (IPI) varied between 0.0 and 1.8 ms. All stimuli were presented at comfortably loud, loudness-balanced levels at a 250 pulse per second per electrode (ppse) stimulation rate. On average, CI subjects were able to reliably discriminate between sequential and simultaneous VCs. While there was no significant effect of IPI or stimulation mode on VC discrimination, some subjects exhibited better VC discrimination with BP + 1 stimulation. Subjects’ discrimination between sequential and simultaneous VCs was correlated with electrode discrimination, suggesting that spatial selectivity may influence perception of sequential VCs. To maintain equal loudness, sequential VC amplitudes were nearly double those of simultaneous VCs, presumably resulting in a broader spread of excitation. These results suggest that perceptual differences between simultaneous and sequential VCs might be explained by differences in the spread of excitation. PMID:21895094

  17. 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.

  18. Assessment of local skin reactions with a sequential regimen of cryosurgery followed by ingenol mebutate gel, 0.015%, in patients with actinic keratosis.

    PubMed

    Goldenberg, Gary; Berman, Brian

    2015-01-01

    Lesion-directed and field-directed therapies are used to treat actinic keratosis (AK). Therapeutic approaches that combine both types of therapies may improve the successful elimination of AKs. A randomized, double-blind, vehicle-controlled study evaluated the safety, tolerability, and efficacy of topical field treatment with ingenol mebutate gel, 0.015%, after cryosurgery to AKs on the face and scalp. Patients with 4-8 visible discrete AKs in a 25-cm(2) contiguous area received cryosurgery of all AKs at baseline. After a 3-week healing period, patients applied ingenol mebutate gel, 0.015%, or vehicle gel once daily for 3 consecutive days to the treatment area. The incidence, severity, and time course of the development and resolution of local skin reactions were measured from baseline to week 11. Local skin reactions peaked shortly after completion of ingenol mebutate treatment and generally resolved within 2 weeks. The mean (95% confidence interval) composite score (maximum range, 0-24) for these reactions was higher in patients with treatment of AKs on the face, 9.3 (8.5-10.1), as compared with the scalp, 5.8 (4.3-7.4). Erythema and flaking/scaling were the major contributors to the composite local skin reaction score. These results show that local skin reactions associated with ingenol mebutate treatment of the face or scalp are well tolerated after recent cryosurgery. PMID:25565875

  19. Assessment of local skin reactions with a sequential regimen of cryosurgery followed by ingenol mebutate gel, 0.015%, in patients with actinic keratosis

    PubMed Central

    Goldenberg, Gary; Berman, Brian

    2015-01-01

    Lesion-directed and field-directed therapies are used to treat actinic keratosis (AK). Therapeutic approaches that combine both types of therapies may improve the successful elimination of AKs. A randomized, double-blind, vehicle-controlled study evaluated the safety, tolerability, and efficacy of topical field treatment with ingenol mebutate gel, 0.015%, after cryosurgery to AKs on the face and scalp. Patients with 4–8 visible discrete AKs in a 25-cm2 contiguous area received cryosurgery of all AKs at baseline. After a 3-week healing period, patients applied ingenol mebutate gel, 0.015%, or vehicle gel once daily for 3 consecutive days to the treatment area. The incidence, severity, and time course of the development and resolution of local skin reactions were measured from baseline to week 11. Local skin reactions peaked shortly after completion of ingenol mebutate treatment and generally resolved within 2 weeks. The mean (95% confidence interval) composite score (maximum range, 0–24) for these reactions was higher in patients with treatment of AKs on the face, 9.3 (8.5–10.1), as compared with the scalp, 5.8 (4.3–7.4). Erythema and flaking/scaling were the major contributors to the composite local skin reaction score. These results show that local skin reactions associated with ingenol mebutate treatment of the face or scalp are well tolerated after recent cryosurgery. PMID:25565875

  20. Generic sequential sampling for metamodel approximations

    SciTech Connect

    Turner, C. J.; Campbell, M. I.

    2003-01-01

    Metamodels approximate complex multivariate data sets from simulations and experiments. These data sets often are not based on an explicitly defined function. The resulting metamodel represents a complex system's behavior for subsequent analysis or optimization. Often an exhaustive data search to obtain the data for the metalnodel is impossible, so an intelligent sampling strategy is necessary. While inultiple approaches have been advocated, the majority of these approaches were developed in support of a particular class of metamodel, known as a Kriging. A more generic, cotninonsense approach to this problem allows sequential sampling techniques to be applied to other types of metamodeis. This research compares recent search techniques for Kriging inetamodels with a generic, inulti-criteria approach combined with a new type of B-spline metamodel. This B-spline metamodel is competitive with prior results obtained with a Kriging metamodel. Furthermore, the results of this research highlight several important features necessary for these techniques to be extended to more complex domains.

  1. Lipid peroxidation in experimental uveitis: sequential studies.

    PubMed

    Goto, H; Wu, G S; Chen, F; Kristeva, M; Sevanian, A; Rao, N A

    1992-06-01

    Previously we have detected the occurrence of retinal lipid peroxidation initiated by phagocyte-derived oxygen radicals in experimental autoimmune uveitis (EAU). In the current studies, the confirmation of inflammation-mediated lipid peroxidation was proceeded further to include measurement of multiple parameters, including conjugated dienes, ketodienes, thiobarbituric acid reactive substances and fluorescent chromolipids. The assay for myeloperoxidase, a measure for the number of polymorphonuclear leukocytes in the inflammatory sites was also carried out. The levels of all these parameters were followed through the course of EAU development. The sequential evaluation of histologic changes using both light and electron microscopy was also carried out and the results were correlated with lipid peroxidation indices. These data suggest that the retinal lipid peroxidation plays a causative role in the subsequent retinal degeneration.

  2. 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.

  3. Sequential sampling and paradoxes of risky choice.

    PubMed

    Bhatia, Sudeep

    2014-10-01

    The common-ratio, common-consequence, reflection, and event-splitting effects are some of the best-known findings in decision-making research. They represent robust violations of expected utility theory, and together form a benchmark against which descriptive theories of risky choice are tested. These effects are not currently predicted by sequential sampling models of risky choice, such as decision field theory (Busemeyer & Townsend 1993). This paper, however, shows that a minor extension to decision field theory, which allows for stochastic error in event sampling, can provide a parsimonious, cognitively plausible explanation for these effects. Moreover, these effects are guaranteed to emerge for a large range of parameter values, including best-fit parameters obtained from preexisting choice data. PMID:24898202

  4. Particle smoothers in sequential geoacoustic inversion.

    PubMed

    Yardim, Caglar; Gerstoft, Peter; Hodgkiss, William S

    2013-08-01

    Sequential Bayesian methods such as particle filters have been used to track a moving source in an unknown and space/time-evolving ocean environment. These methods treat both the source and the ocean parameters as non-stationary unknown random variables and track them via the multivariate posterior probability density function. Particle filters are numerical methods that can operate on nonlinear systems with non-Gaussian probability density functions. Particle smoothers are a natural extension to these filters. A smoother is appropriate in applications where data before and after the time of interest are readily available. Both past and "future" measurements are exploited in smoothers, whereas filters just use past measurements. Geoacoustic and source tracking is performed here using two smoother algorithms, the forward-backward smoother and the two-filter smoother. Smoothing is demonstrated on experimental data from both the SWellEx-96 and SW06 experiments where the parameter uncertainty is reduced relative to just filtering alone.

  5. Adaptive sequential methods for detecting network intrusions

    NASA Astrophysics Data System (ADS)

    Chen, Xinjia; Walker, Ernest

    2013-06-01

    In this paper, we propose new sequential methods for detecting port-scan attackers which routinely perform random "portscans" of IP addresses to find vulnerable servers to compromise. In addition to rigorously control the probability of falsely implicating benign remote hosts as malicious, our method performs significantly faster than other current solutions. Moreover, our method guarantees that the maximum amount of observational time is bounded. In contrast to the previous most effective method, Threshold Random Walk Algorithm, which is explicit and analytical in nature, our proposed algorithm involve parameters to be determined by numerical methods. We have introduced computational techniques such as iterative minimax optimization for quick determination of the parameters of the new detection algorithm. A framework of multi-valued decision for detecting portscanners and DoS attacks is also proposed.

  6. 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.

  7. 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.

  8. Sequential monitoring of beach litter using webcams.

    PubMed

    Kako, Shin'ichiro; Isobe, Atsuhiko; Magome, Shinya

    2010-05-01

    This study attempts to establish a system for the sequential monitoring of beach litter using webcams placed at the Ookushi beach, Goto Islands, Japan, to establish the temporal variability in the quantities of beach litter every 90 min over a one and a half year period. The time series of the quantities of beach litter, computed by counting pixels with a greater lightness than a threshold value in photographs, shows that litter does not increase monotonically on the beach, but fluctuates mainly on a monthly time scale or less. To investigate what factors influence this variability, the time derivative of the quantity of beach litter is compared with satellite-derived wind speeds. It is found that the beach litter quantities vary largely with winds, but there may be other influencing factors. PMID:20392465

  9. 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.

  10. 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.

  11. Sequential Double lonization: The Timing of Release

    NASA Astrophysics Data System (ADS)

    Pfeiffer, A.

    2011-05-01

    The timing of electron release in strong field double ionization poses great challenges both for conceptual definition and for conducting experimental measurement. Here we present coincidence momentum measurements of the doubly charged ion and of the two electrons arising from double ionization of Argon using elliptically (close to circularly) polarized laser pulses. Based on a semi-classical model, the ionization times are calculated from the measured electron momenta across a large intensity range. Exploiting the attoclock technique we have direct access to timings on a coarse and on a fine scale, similar to the hour and the minute hand of a clock. In our attoclock, the magnitude of the electron momenta follows the envelope of the laser pulse and gives a coarse timing for the electron releases (the hour hand), while the fine timing (the minute hand) is provided by the emission angle of the electrons. The first of our findings is that due to depletion the averaged ionization time moves towards the beginning of the pulse with increasing intensity, confirming the results of Maharjan et al., and that the ion momentum distribution projected onto the minor polarization axis shows a bifurcation from a 3-peak to a 4-peak structure. This effect can be fully understood by modeling the process semi-classically in the independent electron approximation following the simple man's model. The ionization time measurement performed with the attoclock shows that the release time of the first electron is in good agreement with the semi-classical simulation performed on the basis of Sequential Double lonization (SDI), whereas the ionization of the second electron occurs significantly earlier than predicted. This observation suggests that electron correlation and other Non-Sequential Double lonization (NSDI) mechanisms may play an important role also in the case of strong field double ionization by close-to-circularly polarized laser pulses. The timing of electron release in strong

  12. 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.

  13. 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.

  14. Simultaneous better than sequential for brief presentations

    NASA Astrophysics Data System (ADS)

    Hung, George K.; Wilder, Joseph; Curry, Reates; Julesz, Bela

    1995-03-01

    During perceptually intensive tasks such as reading, there is a bottleneck in the information transfer between the large number of alphanumeric characters available and the acquiring of these characters. This is due mainly to the limited number of characters that one can report at a glance (also known as the "magic number 7 +/- 2") [Psychol. Rev. 63, 81 (1956)]. To examine where in the perceptual pathway this bottleneck occurred, several investigators tested and compared performance with simultaneous and with sequential target presentations [J. Exp. Psychol. 79, 1 (1969); 93, 72 (1972); Percept. Psychophys. 14, 231 (1973)]. They found that performance was nearly equal in the two cases and concluded that the bottleneck must be due to the limitation of short-term memory. However, these studies were

  15. Upper bounds on sequential decoding performance parameters

    NASA Technical Reports Server (NTRS)

    Jelinek, F.

    1974-01-01

    This paper presents the best obtainable random coding and expurgated upper bounds on the probabilities of undetectable error, of t-order failure (advance to depth t into an incorrect subset), and of likelihood rise in the incorrect subset, applicable to sequential decoding when the metric bias G is arbitrary. Upper bounds on the Pareto exponent are also presented. The G-values optimizing each of the parameters of interest are determined, and are shown to lie in intervals that in general have nonzero widths. The G-optimal expurgated bound on undetectable error is shown to agree with that for maximum likelihood decoding of convolutional codes, and that on failure agrees with the block code expurgated bound. Included are curves evaluating the bounds for interesting choices of G and SNR for a binary-input quantized-output Gaussian additive noise channel.

  16. Giant intracranial aneurysms: rapid sequential computed tomography

    SciTech Connect

    Pinto, R.S.; Cohen, W.A.; Kricheff, I.I.; Redington, R.W.; Berninger, W.H.

    1982-11-01

    Giant intracranial aneurysms often present as mass lesions rather than with subarachnoid hemorrhage. Routine computed tomographic (CT) scans with contrast material will generally detect them, but erroneous diagnosis of basal meningioma is possible. Rapid sequential scanning (dynamic CT) after bolus injection of 40 ml of Renografin-76 can conclusively demonstrate an intracranial aneurysm, differentiating it from other lesions by transit-time analysis of the passage of contrast medium. In five patients, the dynamics of contrast bolus transit in aneurysms were consistently different from the dynamics in pituitary tumors, craniopharyngiomas, and meningiomas, thereby allowing a specific diagnosis. Dynamic CT was also useful after treatment of the aneurysms by carotid artery ligation and may be used as an alternative to angiographic evaluation in determining luminal patency or thrombosis.

  17. Random sequential adsorption on imprecise lattice.

    PubMed

    Privman, Vladimir; Yan, Han

    2016-06-28

    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. PMID:27369530

  18. 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.

  19. Sequential scintigraphic staging of small cell carcinoma

    SciTech Connect

    Bitran, J.D.; Bekerman, C.; Pinsky, S.

    1981-04-15

    Thirty patients with small cell carcinoma (SCC) of the lung were sequentially staged following a history and physical exam with liver, bran, bone, and gallium-67 citrate scans. Scintigraphic evaluation disclosed 7 of 30 patients (23%) with advanced disease, stage IIIM1. When Gallium-67 scans were used as the sole criteria for staging, they proved to be accurate and identified six of the seven patients with occult metastatic disease. Gallium-67 scans proved to be accurate in detecting thoracic and extrathoracic metastases in the 30 patients with SCC, especially within the liver and lymph node-bearing area. The diagnostic accuracy of gallium-67 fell in regions such as bone or brain. Despite the limitations of gallium-67 scanning, the authors conclude that these scans are useful in staging patients with SCC and should be the initial scans used in staging such patients.

  20. 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.

  1. Longevity: potential life span and health span enhancement through practice of the basic yoga meditation regimen.

    PubMed

    Bushell, William C

    2009-08-01

    This chapter briefly reviews recent psychological, physiological, molecular biological, and anthropological research which has important implications, both direct and indirect, for the recognition and understanding of the potential life span and health span enhancing effects of the basic yoga meditational regimen. This regimen consists of meditation, yogic breath control practices, physical exercises (of both a postural- and movement-based, including aerobic nature), and dietary practices. While each of these component categories exhibit variations in different schools, lineages, traditions, and cultures, the focus of this chapter is primarily on basic forms of relaxation meditation and breath control, as well as postural and aerobic physical exercises (e.g., yogic prostration regimens, see below), and a standard form of yogic or ascetic diet, all of which constitute a basic form of regimen found in many if not most cultures, though with variations.

  2. Kidney injury associated with telavancin dosing regimen in an animal model.

    PubMed

    Tam, Vincent H; Ledesma, Kimberly R; Bowers, Dana R; Zhou, Jian; Truong, Luan D

    2015-05-01

    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.

  3. Evaluation of various gentamicin dosage regimens in geriatric patients: a simulation study.

    PubMed

    Bourguignon, Laurent; Goutelle, Sylvain; De Saint-Martin, Julie Burdin; Maire, Pascal; Ducher, Michel

    2010-02-01

    The aim of this simulation study was to evaluate the ability of three regimens proposed in official French recommendations for gentamicin to hit defined pharmacokinetic (PK) and pharmacodynamic targets in a population of elderly patients. The first drug regimen tested consisted of a loading dose of 1 mg/kg and a maintenance dose weighted by creatininemia, every 8 h. The second regimen consisted of a fixed dose of 1 mg/kg at various intervals of time, calculated from creatinine clearance. The last regimen was a fixed dose of 3 mg/kg once a day. All regimens were for 5 days. We used a bicompartmental PK model and implemented a Monte Carlo simulation to generate a large sample of geriatric subjects. The analysis examined three ranges of creatinine clearance. Simulations showed that for the two regimens using multiple doses per day, neither was able to reach an efficacy level without significant toxicity after 5 days of treatment, regardless of the level of renal function. The use of creatininemia or creatinine clearance to adjust the drug dose did not alter these findings. The once-a-day dosing regimen gave better results both in efficacy and toxicity, except for patients with creatinine clearance lower than 60 mL/min, where the incidence of potential toxicity was above 25%. These results strongly suggest that official French recommendations about aminoglycoside dosage regimens in elderly patients with renal impairment should be updated, and that the frequent need for therapeutic drug monitoring and dosage individualization should be clearly stated.

  4. 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. PMID:23918635

  5. Comparison of Two High-Dose Magnesium Infusion Regimens in the Treatment of Status Asthmaticus

    PubMed Central

    Vaiyani, Danish

    2016-01-01

    OBJECTIVES: To determine the feasibility and safety of a simplified high-dose magnesium sulfate infusion (sHDMI) for the treatment of status asthmaticus. METHODS: We retrospectively compared 2 different high-dose magnesium sulfate infusion regimens, as adjunctive treatment in status asthmatics, using data that were preciously collected. The initial high-dose, prolonged magnesium infusion (HDMI) regimen consisted of a loading dose of 75 mg/kg (weight ≤ 30 kg) or 50 mg/kg (weight > 30 kg) over a period of 30 to 45 minutes followed by a continuous infusion of 40 mg/kg/hr for an additional 4 hours. This was compared to the sHDMI regimen that consisted of 50 mg/kg/hr for 5 hours. No loading dose was given to the patients in the sHDMI arm. Obese patients were dosed by using ideal body weight. Physiologic parameters (i.e., heart rate, blood pressure, respiratory rate, oxygen saturation) and serum magnesium (SrMg) concentrations were monitored during administration of magnesium sulfate. RESULTS: Nineteen patients receiving the initial HDMI regimen were compared with 10 patients who received the sHDMI regimen. There was no significant difference in SrMg concentrations or physiologic parameters between the 2 dose regimens. CONCLUSIONS: The HDMI and sHDMI regimens both produced SrMg concentrations that are associated with bronchodilation. The safety profile was also similar for the 2 regimens. The unambiguity of sHDMI has the potential to reduce medication errors that are associated with calculation of the loading dose, product preparation, and ultimate administration. PMID:27453701

  6. 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.

  7. 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.

  8. Sequential Rift Valley Fever Outbreaks in Eastern Africa Caused by Multiple Lineages of the Virus

    PubMed Central

    Nderitu, Leonard; Lee, John S.; Omolo, Jared; Omulo, Sylvia; O'Guinn, Monica L.; Hightower, Allen; Mosha, Fausta; Mohamed, Mohamed; Munyua, Peninah; Nganga, Zipporah; Hiett, Kelli; Seal, Bruce; Feikin, Daniel R.; Breiman, Robert F.

    2011-01-01

    Background. During the Rift Valley fever (RVF) epidemic of 2006–2007 in eastern Africa, spatial mapping of the outbreaks across Kenya, Somalia, and Tanzania was performed and the RVF viruses were isolated and genetically characterized. Methods. Following confirmation of the RVF epidemic in Kenya on 19 December 2006 and in Tanzania on 2 February 2007, teams were sent to the field for case finding. Human, livestock, and mosquito specimens were collected and viruses isolated. The World Health Organization response team in Kenya worked with the WHO’s polio surveillance team inside Somalia to collect information and specimens from Somalia. Results. Seven geographical foci that reported hundreds of livestock and >25 cases in humans between December 2006 and June 2007 were identified. The onset of RVF cases in each epidemic focus was preceded by heavy rainfall and flooding for at least 10 days. Full-length genome analysis of 16 RVF virus isolates recovered from humans, livestock, and mosquitoes in 5 of the 7 outbreak foci revealed 3 distinct lineages of the viruses within and across outbreak foci. Conclusion. The findings indicate that the sequential RVF epidemics in the region were caused by multiple lineages of the RVF virus, sometimes independently activated or introduced in distinct outbreak foci. PMID:21282193

  9. Pushing the envelope—nonmyeloablative and reduced intensity preparative regimens for allogeneic hematopoietic transplantation

    PubMed Central

    Pingali, SR; Champlin, RE

    2016-01-01

    Allogeneic hematopoietic cell transplantation (HCT) was originally developed to allow delivery of myeloablative doses of chemotherapy and radiotherapy. With better understanding of disease pathophysiology, the graft vs malignancy (GVM) effect of allogeneic hematopoietic transplantation and toxicities associated with myeloablative conditioning (MAC) regimens, the focus shifted to developing less toxic conditioning regimens to reduce treatment-related morbidity without compromising survival. Although HCT with MAC is preferred to reduced intensity conditioning (RIC) for most patients ≤ 60 years with AML/myelodysplastic syndrome and ALL, RIC and nonmyeloablative (NMA) regimens allow HCT for many otherwise ineligible patients. Reduced intensity preparative regimens have produced high rates of PFS for diagnoses, which are highly sensitive to GVM. Relapse of the malignancy is the major cause of treatment failure with RIC/NMA HCT. Incorporation of novel agents like bortezomib or lenalidomide, addition of cellular immunotherapy and use of targeted radiation therapies could further improve outcome. In this review, we discuss commonly used RIC/NMA regimens and promising novel regimens. PMID:25985053

  10. Cardiovascular effects of Phaleria macrocarpa extracts combined with mainstay FAC regimen for breast cancer.

    PubMed

    Anggadiredja, Kusnandar; Tjandrawinata, Raymond R

    2015-01-01

    DLBS1425 is a bioactive compound extracted from Phaleria macrocarpa, with anti-proliferative, anti-inflammatory and anti-angiogenic properties against cancer cells. The present study was aimed to assess cardiotoxicity of DLBS1425, compared to the mainstay regimen for breast cancer, 5-fluorouracil:doxorubicin:cyclophosphamide (FAC, given at 500/50/500 mg/m(2)). Treatment with FAC regimen at standard dose resulted in very severe toxicity, so mice had no chance to survive for more than 7 days following initial drug treatment. Furthermore, histological examination on the heart revealed severe muscular damage when mice were given the FAC regimen alone (severe toxicity). FAC as chemotherapeutic regimen exerted high toxicity profile to the cardiovascular cells in this experiment. Meanwhile, treatment with DLBS1425 alone up to a dose equivalent to as high as 300 mg three times daily in human had no hazardous consequences on the heart, hematological feature, as well as general safety. In the cardiovascular cells, DLBS1425 in the presence of FAC regimen (one-eight of the initial dose) gave protection to the cardiac muscle cells as well as other hematological features. Taken together, results of the present study suggest that DLBS1425 is safe when used as adjuvant therapy for breast cancer and may be even protective against cardiac cellular damage produced by chemotherapeutic regimen. PMID:25158670

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

    PubMed

    Kay, Katherine; Hodel, Eva Maria; Hastings, Ian M

    2015-10-01

    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 10(12) parasites, while the standard dosing regimens allow approximately 1 in 10(10) parasites to survive artemisinin treatment. Parasite survival falls dramatically, to around 1 in 10(17) 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

  12. 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

  13. 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. PMID:27365142

  14. 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.

  15. 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)

  16. A sequential procedure for monitoring clinical trials against historical controls.

    PubMed

    Xiong, Xiaoping; Tan, Ming; Boyett, James

    2007-03-30

    In this paper, we develop a sequential procedure to monitor clinical trials against historical controls. When there is a strong ethical concern about randomizing patients to existing treatment because biological and medical evidence suggests that the new treatment is potentially superior to the existing one, or when the enrollment is too limited for randomization of subjects into experimental and control groups, one can monitor the trial sequentially against historical controls if the historical data with required quality and sample size are available to form a valid reference for the trial. This design of trial is sometimes the only alternative to a randomized phase III trial design that is intended but not feasible in situations such as above. Monitoring this type of clinical trial leads to a statistical problem of comparing two population means in a situation in which data from one population are sequentially collected and compared with all data from the other population at each interim look. The proposed sequential procedures is based on the sequential conditional probability ratio test (SCPRT) by which the conclusion of the sequential test would be virtually the same as that arrived at by a non-sequential test based on all data at the planned end of the trial. We develop the sequential procedure by proposing a Brownian motion that emulates the test statistic, and then proposing an SCPRT that is adapted to the special properties of the trial. PMID:16900551

  17. 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…

  18. The Relevance of Visual Sequential Memory to Reading.

    ERIC Educational Resources Information Center

    Crispin, Lisa; And Others

    1984-01-01

    Results of three visual sequential memory tests and a group reading test given to 19 elementary students are discussed in terms of task analysis and structuralist approaches to analysis of reading skills. Relation of visual sequential memory to other reading subskills is considered in light of current reasearch. (CMG)

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

    PubMed

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

    2016-08-01

    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. PMID:27104664

  20. Lineup Composition, Suspect Position, and the Sequential Lineup Advantage

    ERIC Educational Resources Information Center

    Carlson, Curt A.; Gronlund, Scott D.; Clark, Steven E.

    2008-01-01

    N. M. Steblay, J. Dysart, S. Fulero, and R. C. L. Lindsay (2001) argued that sequential lineups reduce the likelihood of mistaken eyewitness identification. Experiment 1 replicated the design of R. C. L. Lindsay and G. L. Wells (1985), the first study to show the sequential lineup advantage. However, the innocent suspect was chosen at a lower rate…

  1. 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…

  2. Effect of weaning status and implant regimen on growth, performance, and carcass characteristics of steers.

    PubMed

    Schoonmaker, J P; Fluharty, F L; Loerch, S C; Turner, T B; Moeller, S J; Wulf, D M

    2001-05-01

    One hundred forty-three Angus x Simmental crossbred steers (initial BW = 155.1 +/- 4.5 kg) were used in a 2-yr study (yr 1, n = 67; yr 2, n = 76) to determine the effects of weaning age, implant regimen, and the weaning age x implant regimen interaction on steer growth and performance, organ mass, carcass characteristics, and cooked beef palatability. Steers were early-weaned at an average age of 108 d (EW) or normally weaned at an average age of 202 d (NW) and allotted by weight to an aggressive or nonaggressive implant regimen. On their respective weaning dates, EW and NW steers were penned individually and fed a grain-based diet until they were slaughtered at a final BW of 546 kg. A subsample of steers (n = 2 per treatment) were slaughtered at 254 kg. At 254 kg, EW steers implanted with the aggressive implant regimen had 64% greater backfat depth than those implanted with the nonaggressive implant regimen; conversely, NW steers implanted with the aggressive implant regimen had 52% lower backfat depth than those implanted with the nonaggressive implant regimen (weaning status x implant regimen interaction; P < 0.01). A similar interaction was observed for empty visceral organ weights. Early-weaned steers were younger (354.7 vs 372.4 d; P < 0.01) at final slaughter but were in the feedlot longer (246.5 vs 169.6 d; P < 0.01) than NW steers, whereas the aggressive implant regimen decreased days fed (203.3 vs 212.7; P < 0.07) compared to the nonaggressive implant regimen. Overall ADG was greater for EW than for NW steers (1.61 vs 1.50 kg/d; P < 0.01) and for the aggressive compared with the nonaggressive implant regimen (1.59 vs 1.52 kg/d; P < 0.02). Early-weaned steers consumed less DM per day (7.4 vs 8.5 kg/d; P < 0.01) and were more efficient (0.217 vs 0.208 kg/kg; P < 0.02) but consumed more total DM (1,817 vs 1,429 kg; P < 0.01) than NW steers while in the feedlot. Implant regimen did not affect DMI (P > 0.37) or feed efficiency (P > 0.15). Weaning status did

  3. [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.

  4. Cost-Utility Analysis of IEV Drug Regimen Versus ESHAP Drug Regimen for the Patients With Relapsed and Refractory Hodgkin and Non-Hodgkin’s Lymphoma in Iran

    PubMed Central

    Hatam, Nahid; Dehghani, Mehdi; Habibian, Mostafa; Jafari, Abdosaleh

    2015-01-01

    Background: Chemotherapy for lymph nodes cancer is often composed of several drugs that are used in a treatment program. Objectives: The aim of this study was to perform a cost-utility analysis of IEV regimen (ifosfamide, epirubicin and etoposide) versus ESHAP regimen (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) in patients with lymphoma in the south of Iran. Patients and Methods: This was a cost-utility analysis done as a cross-sectional study in the south of Iran. Using decision tree, expected costs, quality -adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) were estimated. In addition, the robustness of results was examined by sensitivity analysis. Results: The results of this study indicated that the total lymphoma patients were about 65 people that 27 patients received IEV regimen and 38 patients ESHAP (43 patients with Hodgkin’s and 22 with non-Hodgkin lymphoma). The results of decision tree showed that in the IEV arm, the expected cost was $20952.93 and the expected QALYs was 3.89 and in the ESHAP arm, the expected cost was $31691.74 and the expected QALYs was 3.86. Based on the results of the study, IEV regimen was cost-effective alternative to the ESHAP regimen. Conclusions: According to the results of this study, it is recommended that oncologists use IEV instead of ESHAP in the treatment of patients with lymphoma and because of high costs of IEV drug costs, it is suggested that IEV drugs should be covered by insurance. PMID:26634115

  5. Influence of gender membership on sequential decisions of face attractiveness.

    PubMed

    Kondo, Aki; Takahashi, Kohske; Watanabe, Katsumi

    2013-10-01

    Responses in a current trial are biased by the stimulus and response in the preceding trial. In a mixed-category sequence, the sequential dependency is weaker when the stimuli of the current and preceding trials fall under different categories. In the present study, we investigated the influence of the gender membership of faces on the sequential dependency. Forty-eight pictures of male and female faces were presented successively. Participants rated the attractiveness, roundness, or intelligence of each face on a 7-point scale. The sequential effect was robustly observed, irrespective of the property to be judged. However, between-gender sequential dependency was weaker than within-gender dependency only in the attractiveness judgment. These findings suggest that the gender of faces serves as a cue for forming category representations when face attractiveness is of interest, and hence that the formation of categories in sequential decisions is an adaptive process that depends on the property to be judged.

  6. Influence of gender membership on sequential decisions of face attractiveness.

    PubMed

    Kondo, Aki; Takahashi, Kohske; Watanabe, Katsumi

    2013-10-01

    Responses in a current trial are biased by the stimulus and response in the preceding trial. In a mixed-category sequence, the sequential dependency is weaker when the stimuli of the current and preceding trials fall under different categories. In the present study, we investigated the influence of the gender membership of faces on the sequential dependency. Forty-eight pictures of male and female faces were presented successively. Participants rated the attractiveness, roundness, or intelligence of each face on a 7-point scale. The sequential effect was robustly observed, irrespective of the property to be judged. However, between-gender sequential dependency was weaker than within-gender dependency only in the attractiveness judgment. These findings suggest that the gender of faces serves as a cue for forming category representations when face attractiveness is of interest, and hence that the formation of categories in sequential decisions is an adaptive process that depends on the property to be judged. PMID:24037595

  7. 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

  8. Outcome after Transplantation According to Reduced-Intensity Conditioning Regimen in Patients Undergoing Transplantation for Myelofibrosis.

    PubMed

    Robin, Marie; Porcher, Raphael; Wolschke, Christine; Sicre de Fontbrune, Flore; Alchalby, Haefaa; Christopeit, Maximilian; Cassinat, Bruno; Zabelina, Tatjana; Peffault de Latour, Régis; Ayuk, Francis; Socié, Gérard; Kröger, Nicolaus

    2016-07-01

    Allogeneic hematopoietic stem cell transplantation remains the sole curative option for myelofibrosis. Many transplantation recipients receive a reduced-intensity conditioning (RIC) regimen owing to age or comorbidities; however, there is little published evidence to guide the choice of RIC regimen. In this study, we compared outcomes in patients who received 1 of 2 frequently used RIC regimens for patients with myelofibrosis: fludarabine-busulfan (FB) and fludarabine-melphalan (FM). A total of 160 patients underwent a RIC allograft procedure (FB group, n = 105; FM group, n = 55). We have developed a complex statistical model involving weighting and adjustment to permit comparison between these 2 groups. After weighting, the incidence of acute graft-versus-host disease (GVHD) was 62% in the FM group and 31% in the FB group (P = .001), and the corresponding incidence of chronic GVHD was 49% and 53%, respectively. The 7-year progression-free survival was were 52% in the FM group versus 33% in the FB group, and the 7-year overall survival rate 52% in the FM group versus 59% in the FB group. Nonrelapse mortality (NRM) was 43% in the FM group and 31% in the FB group. Multivariable analyses revealed no significant differences in PFS between the 2 groups; however, the relapse rate was significantly lower in the FM group (hazard ratio, 9.21; P = .008), whereas a trend toward reduced NRM was seen in the FB group (hazard ratio, 0.51; P = .068). In conclusion, both regimens appear to be efficient in mediating disease control and can be used to successfully condition patients with myelofibrosis. The FM regimen appears to induce more NRM than the FB regimen, but with augmented control of disease, leading to comparable overall survival rates for both regimens.

  9. Classifying insulin regimens--difficulties and proposal for comprehensive new definitions.

    PubMed

    Neu, A; Lange, K; Barrett, T; Cameron, F; Dorchy, H; Hoey, H; Jarosz-Chobot, P; Mortensen, H B; Robert, J-J; Robertson, K; de Beaufort, C

    2015-09-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1 diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin regimens reflecting current diabetes management in childhood and adolescence. The HSG--founded in 1994--is an international group representing 24 highly experienced pediatric diabetes centers, from Europe, Japan, North America and Australia. Different benchmarking studies of the HSG revealed a broad variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides the concepts 'conventional' and 'intensified', several other terms for the characterization of insulin regimens are in use: Basal Bolus Concept (BBC), multiple daily injections (MDI), and flexible insulin therapy (FIT) are most frequently used, although none of these expressions is clearly or consistently defined. The proposed new classification for insulin management will be comprehensive, simple, and catchy. Currently available terms were included. This classification may offer the opportunity to compare therapeutic strategies without the currently existing confusion on the insulin regimen. PMID:25865149

  10. Population-level impact of shorter-course regimens for tuberculosis: a model-based analysis.

    PubMed

    Fofana, Mariam O; Knight, Gwenan M; Gomez, Gabriela B; White, Richard G; Dowdy, David W

    2014-01-01

    Despite current control efforts, global tuberculosis (TB) incidence is decreasing slowly. New regimens that can shorten treatment hold promise for improving treatment completion and success, but their impact on population-level transmission remains unclear. Earlier models projected that a four-month regimen could reduce TB incidence by 10% but assumed that an entire course of therapy must be completed to derive any benefit. We constructed a dynamic transmission model of TB disease calibrated to global estimates of incidence, prevalence, mortality, and treatment success. To account for the efficacy of partial treatment, we used data from clinical trials of early short-course regimens to estimate relapse rates among TB patients who completed one-third, one-half, two-thirds, and all of their first-line treatment regimens. We projected population-level incidence and mortality over 10 years, comparing standard six-month therapy to hypothetical shorter-course regimens with equivalent treatment success but fewer defaults. The impact of hypothetical four-month regimens on TB incidence after 10 years was smaller than estimated in previous modeling analyses (1.9% [95% uncertainty range 0.6-3.1%] vs. 10%). Impact on TB mortality was larger (3.5% at 10 years) but still modest. Transmission impact was most sensitive to the proportion of patients completing therapy: four-month therapy led to greater incidence reductions in settings where 25% of patients leave care ("default") over six months. Our findings remained robust under one-way variation of model parameters. These findings suggest that novel regimens that shorten treatment duration may have only a modest effect on TB transmission except in settings of very low treatment completion.

  11. Classifying insulin regimens--difficulties and proposal for comprehensive new definitions.

    PubMed

    Neu, A; Lange, K; Barrett, T; Cameron, F; Dorchy, H; Hoey, H; Jarosz-Chobot, P; Mortensen, H B; Robert, J-J; Robertson, K; de Beaufort, C

    2015-09-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1 diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin regimens reflecting current diabetes management in childhood and adolescence. The HSG--founded in 1994--is an international group representing 24 highly experienced pediatric diabetes centers, from Europe, Japan, North America and Australia. Different benchmarking studies of the HSG revealed a broad variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides the concepts 'conventional' and 'intensified', several other terms for the characterization of insulin regimens are in use: Basal Bolus Concept (BBC), multiple daily injections (MDI), and flexible insulin therapy (FIT) are most frequently used, although none of these expressions is clearly or consistently defined. The proposed new classification for insulin management will be comprehensive, simple, and catchy. Currently available terms were included. This classification may offer the opportunity to compare therapeutic strategies without the currently existing confusion on the insulin regimen.

  12. 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

  13. DNA-nanostructure-assembly by sequential spotting

    PubMed Central

    2011-01-01

    Background The ability to create nanostructures with biomolecules is one of the key elements in nanobiotechnology. One of the problems is the expensive and mostly custom made equipment which is needed for their development. We intended to reduce material costs and aimed at miniaturization of the necessary tools that are essential for nanofabrication. Thus we combined the capabilities of molecular ink lithography with DNA-self-assembling capabilities to arrange DNA in an independent array which allows addressing molecules in nanoscale dimensions. Results For the construction of DNA based nanostructures a method is presented that allows an arrangement of DNA strands in such a way that they can form a grid that only depends on the spotted pattern of the anchor molecules. An atomic force microscope (AFM) has been used for molecular ink lithography to generate small spots. The sequential spotting process allows the immobilization of several different functional biomolecules with a single AFM-tip. This grid which delivers specific addresses for the prepared DNA-strand serves as a two-dimensional anchor to arrange the sequence according to the pattern. Once the DNA-nanoarray has been formed, it can be functionalized by PNA (peptide nucleic acid) to incorporate advanced structures. Conclusions The production of DNA-nanoarrays is a promising task for nanobiotechnology. The described method allows convenient and low cost preparation of nanoarrays. PNA can be used for complex functionalization purposes as well as a structural element. PMID:22099392

  14. Multifunctional Magnetoliposomes for Sequential Controlled Release.

    PubMed

    Salvatore, Annalisa; Montis, Costanza; Berti, Debora; Baglioni, Piero

    2016-08-23

    The simultaneous or sequential delivery of multiple therapeutic active principles to a specific target is one of the main challenges of nanomedicine. This goal requires the construction of complex devices often extremely time and cost consuming. Supramolecular self-assemblies, with building blocks of different nature, each providing a specific function to the final construct, can combine a facile synthetic route with a high tunability and structural control. In this study we provide the proof-of-principle of a drug delivery system, DDS, constituted of (i) liposomes, providing a fully biocompatible lipid scaffold suitable to host both hydrophobic and hydrophilic drugs; (ii) a double-stranded DNA conjugated with a cholesteryl unit that spontaneously inserts into the lipid membrane; and (iii) hydrophobic and hydrophilic superparamagnetic iron oxide nanoparticles (SPIONs) embedded inside the lipid membrane of liposomes or connected to the DNA, respectively. Upon application of an alternating magnetic field, the SPIONs can trigger, through thermal activation, the release of a DNA strand or of the liposomal payload, depending on the frequency and the application time of the field, as proved by both steady-state and time-resolved fluorescence studies. This feature is due to the different localization of the two kinds of SPIONS within the construct and demonstrates the feasibility of a multifunctional DDS, built up from self-assembly of biocompatible building blocks. PMID:27504891

  15. 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.

  16. Sequential dynamical systems with threshold functions.

    SciTech Connect

    Barrett, C. L.; Hunt, H. B.; Marathe, M. V.; Ravi, S. S.; Rosenkrantz, D. J.; Stearns, R. E.

    2001-01-01

    A sequential dynamical system (SDS) (see [BH+01] and the references therein) consists of an undirected graph G(V,E) where each node {nu} {epsilon} V is associated with a Boolean state (s{sub {nu}}) and a symmetric Boolean function f{sub {nu}} (called the local transition function at {nu}). The inputs to f{sub {nu}} are s{sub {nu}} and the states of all the nodes adjacent to {nu}. In each step of the SDS, the nodes update their state values using their local transition functions in the order specified by a given permutation {pi} of the nodes. A configuration of the SDS is an n-tuple (b{sub 1}, b{sub 2}...,b{sub n}) where n = |V| and b{sub i} {epsilon} {l_brace}0,1{r_brace} is the state value of node {nu}{sub i}. The system starts in a specified initial configuration and each step of the SDS produces a (possibly new) configuration.

  17. Social Influences in Sequential Decision Making

    PubMed Central

    Schöbel, Markus; Rieskamp, Jörg; Huber, Rafael

    2016-01-01

    People often make decisions in a social environment. The present work examines social influence on people’s decisions in a sequential decision-making situation. In the first experimental study, we implemented an information cascade paradigm, illustrating that people infer information from decisions of others and use this information to make their own decisions. We followed a cognitive modeling approach to elicit the weight people give to social as compared to private individual information. The proposed social influence model shows that participants overweight their own private information relative to social information, contrary to the normative Bayesian account. In our second study, we embedded the abstract decision problem of Study 1 in a medical decision-making problem. We examined whether in a medical situation people also take others’ authority into account in addition to the information that their decisions convey. The social influence model illustrates that people weight social information differentially according to the authority of other decision makers. The influence of authority was strongest when an authority's decision contrasted with private information. Both studies illustrate how the social environment provides sources of information that people integrate differently for their decisions. PMID:26784448

  18. 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).

  19. Multiscale sequentially-coupled arterial FSI technique

    NASA Astrophysics Data System (ADS)

    Tezduyar, Tayfun E.; Takizawa, Kenji; Moorman, Creighton; Wright, Samuel; Christopher, Jason

    2009-10-01

    Multiscale versions of the Sequentially-Coupled Arterial Fluid-Structure Interaction (SCAFSI) technique are presented. The SCAFSI technique was introduced as an approximate FSI approach in arterial fluid mechanics. It is based on the assumption that the arterial deformation during a cardiac cycle is driven mostly by the blood pressure. First we compute a “reference” arterial deformation as a function of time, driven only by the blood pressure profile of the cardiac cycle. Then we compute a sequence of updates involving mesh motion, fluid dynamics calculations, and recomputing the arterial deformation. The SCAFSI technique was developed and tested in conjunction with the stabilized space-time FSI (SSTFSI) technique. Beyond providing a computationally more economical alternative to the fully coupled arterial FSI approach, the SCAFSI technique brings additional flexibility, such as being able to carry out the computations in a spatially or temporally multiscale fashion. In the test computations reported here for the spatially multiscale versions of the SCAFSI technique, we focus on a patient-specific middle cerebral artery segment with aneurysm, where the arterial geometry is based on computed tomography images. The arterial structure is modeled with the continuum element made of hyperelastic (Fung) material.

  20. Optimal power flow using sequential quadratic programming

    NASA Astrophysics Data System (ADS)

    Nejdawi, Imad M.

    1999-11-01

    Optimal power flow (OPF) is an operational as well as a planning tool used by electric utilities to help them operate their network in the most economic and secure mode of operation. Various algorithms to solve the OPF problem evolved over the past three decades; linear programming (LP) techniques were among the major mathematical programming methods utilized. The linear models of the objective function and the linearization of the constraints are the main features of these techniques. The main advantages of the LP approach are simplicity and speed. Nonlinear programming techniques have been applied to OPF solution. The major drawback is the expensive solution of large sparse systems of equations. This research is concerned with the development of a new OPF solution algorithm using sequential quadratic programming (SQP). In this formulation, a small dense system the size of which is equal to the number of control variables is solved in an inner loop. The Jacobian and Hessian terms are calculated in an outer loop. The total number of outer loop iterations is comparable to those in an ordinary load flow in contrast to 20--30 iterations in other nonlinear methods. In addition, the total number of floating point operations is less than that encountered in direct methods by two orders of magnitude. We also model dispatch over a twenty four-hour time horizon in a transmission constrained power network that includes price-responsive loads where large energy customers can operate their loads in time intervals with lowest spot prices.

  1. Testing constrained sequential dominance models of neutrinos

    NASA Astrophysics Data System (ADS)

    Björkeroth, Fredrik; King, Stephen F.

    2015-12-01

    Constrained sequential dominance (CSD) is a natural framework for implementing the see-saw mechanism of neutrino masses which allows the mixing angles and phases to be accurately predicted in terms of relatively few input parameters. We analyze a class of CSD(n) models where, in the flavour basis, two right-handed neutrinos are dominantly responsible for the ‘atmospheric’ and ‘solar’ neutrino masses with Yukawa couplings to ({ν }e,{ν }μ ,{ν }τ ) proportional to (0,1,1) and (1,n,n-2), respectively, where n is a positive integer. These coupling patterns may arise in indirect family symmetry models based on A 4. With two right-handed neutrinos, using a χ 2 test, we find a good agreement with data for CSD(3) and CSD(4) where the entire Pontecorvo-Maki-Nakagawa-Sakata mixing matrix is controlled by a single phase η, which takes simple values, leading to accurate predictions for mixing angles and the magnitude of the oscillation phase | {δ }{CP}| . We carefully study the perturbing effect of a third ‘decoupled’ right-handed neutrino, leading to a bound on the lightest physical neutrino mass {m}1{{≲ }}1 meV for the viable cases, corresponding to a normal neutrino mass hierarchy. We also discuss a direct link between the oscillation phase {δ }{CP} and leptogenesis in CSD(n) due to the same see-saw phase η appearing in both the neutrino mass matrix and leptogenesis.

  2. Bilingual control: sequential memory in language switching.

    PubMed

    Declerck, Mathieu; Philipp, Andrea M; Koch, Iring

    2013-11-01

    To investigate bilingual language control, prior language switching studies presented visual objects, which had to be named in different languages, typically indicated by a visual cue. The present study examined language switching of predictable responses by introducing a novel sequence-based language switching paradigm. In 4 experiments, sequential responses (i.e., weekdays, numbers or new sequences) and an alternating language sequence (e.g., L1-L1-L2-L2) were implemented, both of which were memory based. Our data revealed switch costs, showing that a language switch is associated with worse performance compared with a language repetition, and mixing costs, which constitutes the performance difference between pure and mixed language blocks, even while producing entirely predictable responses (i.e., language and concept). Additionally, we found these switch costs with overlearned and new sequences and found that switch costs were reduced with longer preparation time. The obtained data are consistent with a proactive interference account, such as the inhibitory control model.

  3. 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

  4. 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.

  5. 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.

  6. Random sequential adsorption on partially covered surfaces

    NASA Astrophysics Data System (ADS)

    Adamczyk, Zbigniew; Weroński, Paweł

    1998-06-01

    The random sequential adsorption (RSA) approach was used to analyze adsorption of hard spheres at surfaces precovered with smaller sized particles. Numerical simulations were performed to determine the available surface function φl of larger particles for various particle size ratios λ=al/as and surface concentration of smaller particles θs. It was found that the numerical results were in a reasonable agreement with the formula stemming from the scaled particle theory with the modification for the sphere/sphere geometry. Particle adsorption kinetics was also determined in terms of the RSA simulations. By extrapolating the θl vs τ-1/2 dependencies, the jamming concentrations of larger spheres θl∞ were determined as a function of the initial smaller sphere concentration. It was found that θl∞ were considerably reduced by the presence of smaller sized particles, especially for λ≫1. The pair correlation function g of larger particles in the jamming state was also determined, showing more short range ordering (at the same θl) in comparison with monodisperse systems. The theoretical predictions stemming from our calculations suggest that the presence of trace amounts of very small particles may exert a decisive influence on adsorption of larger particles.

  7. Sequential half-body irradiation in childhood

    SciTech Connect

    Jenkin, R.D.T.; Berry, M.P.

    1983-12-01

    Single-dose half-body irradiation (HBI), introduced for the palliation of pain from widespread bone metastases in adults, has proved to be successful. The dose-limiting toxicity has proved to be acute radiation pneumonitis, with bone marrow tolerance of lesser importance, in spite of the fact that many patients received previous local irradiation and/or chemotherapy. Palliative HBI has not become a valuable treatment in pediatric malignancies, because of a shorter metastatic phase. Results are described in selected institutions, where HBI has been used in the treatment of pediatric malignancies. A single institution plot study was undertaken at the Princess Margaret Hospital involving 17 patients with Ewing's sarcoma of bone, without overt metastases at diagnosis. Results to date have not been obviously different from overall survival in the first intergroup Ewing's sarcoma study. Overall, the treatment has been shown to be well tolerated and can be given entirely on an out-patient basis. When compared on a historical basis with a previous single dose total body irradiation study, the one year survival rate was increased. HBI appears to be tolerable treatment, when given concurrently with or sequential to local and systemic treatment.

  8. Sequential Immune Responses: The Weapons of Immunity

    PubMed Central

    Mills, Charles D.; Ley, Klaus; Buchmann, Kurt; Canton, Johnathan

    2016-01-01

    Sequential immune responses (SIR) is a new model that describes what ‘immunity’ means in higher animals. Existing models, such as self/nonself discrimination or danger, focus on how immune responses are initiated. However, initiation is not protection. SIR describes the actual immune responses that provide protection. SIR resulted from a comprehensive analysis of the evolution of immune systems that revealed that several very different types of host innate responses occur (and at different tempos) which together provide host protection. SIR1 uses rapidly activated enzymes like the NADPH oxidases and is present in all animal cells. SIR2 is mediated by the first ‘immune’ cells: macrophage-like cells. SIR3 evolved in animals like invertebrates and provides enhanced protection through advanced macrophage recognition and killing of pathogens and through other innate immune cells such as neutrophils. Finally, in vertebrates, macrophages developed SIR4: the ability to present antigens to T cells. Though much slower than SIR1–3, adaptive responses provide a unique new protection for higher vertebrates. Importantly, newer SIR responses were added on top of older, evolutionarily conserved functions to provide ‘layers’ of host protection. SIR transcends existing models by elucidating the different weapons of immunity that provide host protection in higher animals. PMID:25871013

  9. The Origin of Sequential Chromospheric Brightening

    NASA Astrophysics Data System (ADS)

    Kirk, Michael S.; Balasubramaniam, K. S.; Jackiewicz, Jason; Gilbert, Holly

    2016-05-01

    Sequential Chromospheric Brightenings (SCBs) are often observed in the immediate vicinity of erupting flares and are associated with coronal mass ejections. When SCBs are observed, they routinely appear before the peak emission of the flare and several hours before the first detection of a coupled CME. Since their initial discovery in 2005, there have been several subsequent investigations of SCBs. In each case, these sudden, small-scale brightenings provide vital clues regarding the mechanisms of large-scale energy release in the solar atmosphere. We make use of an automated detection algorithm developed by Kirk et al. (2013) to extract the physical qualities of SCBs in 11 flares of varying size and intensity. Using complementary magnetic field measurements, we also model the potential field beneath these brightenings. We conclude that SCBs originate in the lower corona around 0.1 R⊙ above the photosphere, propagate away from the flare center at speeds 35 ‑ 85 km s‑1, and have typical photosphere magnetic intensities 257± 37 G. In light of these measurements, we conclude that SCBs are distinctive chromospheric signatures of erupting coronal mass ejections.

  10. 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.

  11. Evaluation of an Alternative Intravenous N-Acetylcysteine Regimen in Pediatric Patients

    PubMed Central

    Sandritter, Tracy L.; Lowry, Jennifer A.; Algren, D. Adam

    2015-01-01

    OBJECTIVE: Conventionally, intravenous N-acetylcysteine (IV-NAC) administration is a 3-bag regimen administered over the course of 21 hours, which increases the risk of reconstitution and administration errors. To minimize errors, an alternative IV-NAC regimen consists of a loading dose (150 mg/kg) followed by a maintenance infusion (15 mg/kg/hr) until termination criteria are met. The aim was to determine the clinical outcomes of an alternative IV-NAC regimen in pediatric patients. METHODS: A retrospective review of pharmacy dispensing records and diagnostic codes at a pediatric hospital identified patients who received alternative IV-NAC dosing from March 1, 2008, to September 10, 2012, for acetaminophen overdoses. Exclusion criteria included chronic liver disease, initiation of oral or other IV-NAC regimens, and initiation of standard IV-NAC infusion prior to facility transfer. Clinical and laboratory data were abstracted from the electronic medical record. Descriptive statistics were utilized. Clinical outcomes and adverse drug reaction incidences were compared between the alternative and Food and Drug Administration (FDA)–approved IV-NAC regimens. RESULTS: Fifty-nine patients (mean age 13.4 ± 4.3 years; range: 2 months-18 years) with acetaminophen overdoses were identified. Upon IV-NAC discontinuation, 45 patients had normal alanine transaminase (ALT) concentrations, while 14 patients' ALT concentrations remained elevated (median 140 units/L) but were trending downward. Two patients (3.4%) developed hepatotoxicity (aspartate transaminase/ALT > 1000 units/L). No patients developed hepatic failure, were listed for a liver transplant, were intubated, underwent hemodialysis, or died. Two patients (3.4%) developed anaphylactoid reactions. No known medication or administration errors occurred. Clinical outcome incidences of the studied endpoints with the alternative IV-NAC regimen are at the lower end of published incidence ranges compared to the FDA IV

  12. 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. PMID

  13. 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

    2016-09-01

    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. PMID:27610569

  14. 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

    2016-09-01

    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.

  15. [Sequential Chemoradiotherapy for Advanced Head and Neck Cancer: A Clinical Study with 33 Cases].

    PubMed

    Takahashi, Katsumasa; Nakajima, Kyoko; Murata, Takaaki; Shino, Masato; Nikkuni, Osamu; Toyoda, Minoru; Takayasu, Yukihiro; Chikamatsu, Kazuaki

    2016-05-01

    A total of 33 patients with advanced head and neck cancer (AHNC) treated with sequential chemoradiotherapy (SCRT) were retrospectively evaluated at Gunma University Hospital between 2009 and 2011. The regimen of SCRT was docetaxel, cisplatin, and fluorouracil (TPF)-based induction chemotherapy (ICT), accompanied by docetaxel and cisplatin-based concurrent chemoradiotherapy (CCRT), and oral administration of TS-1 after that. The response rate was 61%, the 3-year overall survival rate was 42%, the non-tumor-bearing survival rate was 27%, and the tumor-bearing survival rate was 15%. Fourteen of 33 patients were tumor-free, and their 3-year overall survival rate was surprisingly 86%. On the other hand, 3-year overall survival rate in the remaining 19 patients was significantly low. To select good response cases for ICT was important. In such cases, TPF should be applied repeatedly, which achieved a 61% response rate even in AHNC. A long-term TS-1 oral medication suppressed cancer regrowth and contributed to long-term survival. PMID:27459819

  16. The sequential trauma score - a new instrument for the sequential mortality prediction in major trauma*

    PubMed Central

    2010-01-01

    Background There are several well established scores for the assessment of the prognosis of major trauma patients that all have in common that they can be calculated at the earliest during intensive care unit stay. We intended to develop a sequential trauma score (STS) that allows prognosis at several early stages based on the information that is available at a particular time. Study design In a retrospective, multicenter study using data derived from the Trauma Registry of the German Trauma Society (2002-2006), we identified the most relevant prognostic factors from the patients basic data (P), prehospital phase (A), early (B1), and late (B2) trauma room phase. Univariate and logistic regression models as well as score quality criteria and the explanatory power have been calculated. Results A total of 2,354 patients with complete data were identified. From the patients basic data (P), logistic regression showed that age was a significant predictor of survival (AUCmodel p, area under the curve = 0.63). Logistic regression of the prehospital data (A) showed that blood pressure, pulse rate, Glasgow coma scale (GCS), and anisocoria were significant predictors (AUCmodel A = 0.76; AUCmodel P + A = 0.82). Logistic regression of the early trauma room phase (B1) showed that peripheral oxygen saturation, GCS, anisocoria, base excess, and thromboplastin time to be significant predictors of survival (AUCmodel B1 = 0.78; AUCmodel P +A + B1 = 0.85). Multivariate analysis of the late trauma room phase (B2) detected cardiac massage, abbreviated injury score (AIS) of the head ≥ 3, the maximum AIS, the need for transfusion or massive blood transfusion, to be the most important predictors (AUCmodel B2 = 0.84; AUCfinal model P + A + B1 + B2 = 0.90). The explanatory power - a tool for the assessment of the relative impact of each segment to mortality - is 25% for P, 7% for A, 17% for B1 and 51% for B2. A spreadsheet for the easy calculation of the sequential trauma score is

  17. Treatment of Wilson's disease with zinc. I. Oral zinc therapy regimens.

    PubMed

    Hill, G M; Brewer, G J; Prasad, A S; Hydrick, C R; Hartmann, D E

    1987-01-01

    The standard therapy for preventing copper accumulation in Wilson's disease, D-penicillamine, has been a life-saving drug, but it has many side effects and some patients are completely intolerant. We have been using oral zinc as another approach to the therapy for Wilson's disease, with copper balance studies as the key initial assessment of the adequacy of a given dose or regimen of zinc therapy. We earlier reported that an intensive regimen of zinc (zinc taken every 4 hr) was effective in controlling copper balance. We have now shown with balance studies that a simplified zinc therapy regimen of 50 mg zinc taken 3 times per day is effective in controlling copper balance. Preliminary work presented here with other simplified regimens also indicate their effectiveness. These studies increase the data base, in terms of copper balance, for zinc therapy of Wilson's disease, and expand the dose range and regimens of zinc which have been shown to control copper balance. PMID:3570163

  18. Niacin Alternatives for Dyslipidemia: Fool's Gold or Gold Mine? Part I: Alternative Niacin Regimens.

    PubMed

    Dunbar, Richard L; Goel, Harsh

    2016-02-01

    Niacin was the first drug demonstrating lowered cholesterol prevents coronary heart disease (CHD) events, with two clinical CHD outcome studies establishing a cardioprotective niacin regimen: 1 g thrice daily with meals. Though cardioprotective, skin toxicity limits niacin's use, fostering several variations to improve tolerability. One of these, an extended-release (ER) alternative, proved immensely successful commercially, dominating clinical practice despite departing from the established regimen in several critical ways. Hence, improved tolerability may have come at the cost of diminished efficacy, posing a conundrum: Does it still help the population at risk for CHD to broaden a drug's acceptance by "watering it down"? This question is crucial at this stage now that the ER alternative failed to recapitulate the benefits of the established cardioprotective niacin regimen in two trials of the alternative approach: AIM-HIGH and HPS2-THRIVE. Part I of this review discusses how vastly the ER alternative departs from the established cardioprotective regimen, why that is important physiologically, and how it may explain the findings of AIM-HIGH and HPS2-THRIVE. Given important gaps left by statin therapy, the established cardioprotective niacin regimen remains an important evidence-based therapy for the statin intolerant or statin averse.

  19. Evolution of HIV Resistance Mutations in Patients Maintained on a Stable Treatment Regimen After Virologic Failure

    PubMed Central

    Goetz, Matthew Bidwell; Ferguson, Monique R.; Han, Xueliang; McMillan, Greg; St. Clair, Marty; Pappa, Keith A.; McClernon, Daniel R.; O’Brien, William A.

    2007-01-01

    Objective We compared the rate of emergence of thymidine analogue mutations (TAMs) and major protease inhibitor mutations in adherent patients who remained on stable treatment with a thymidine analogue and/or protease inhibitor after the onset of virologic failure. Design Follow-up genotypic resistance testing was done using archived plasma obtained from patients having 0 or 1 TAM and/or 0 or 1 major protease inhibitor resistance mutation at the onset of virologic failure. Results The median duration of observed failure was 691 days. There were 41 thymidine analogue regimens and 34 protease inhibitor regimens; concomitant ritonavir was used 4 times. New major protease inhibitor mutations emerged more rapidly than did new TAMs (P = 0.0019); new TAMs emerged more rapidly in thymidine analogue regimens that did not include lamivudine (P = 0.0073). The emergence of TAMs and major protease inhibitor mutations did not differ if lamivudine was not part of the thymidine analogue regimen. The evolution of CD4+ cell counts and plasma viral loads (pVLs) during virologic failure was similar regardless of whether or not a new TAM or major protease inhibitor mutations emerged or, for thymidine analogue–containing regimens, whether lamivudine was or was not used. Conclusions Major protease inhibitor mutations arose more frequently and rapidly than did TAMs in patients with sustained virologic failure who received lamivudine. PMID:17075391

  20. Niacin Alternatives for Dyslipidemia: Fool's Gold or Gold Mine? Part I: Alternative Niacin Regimens.

    PubMed

    Dunbar, Richard L; Goel, Harsh

    2016-02-01

    Niacin was the first drug demonstrating lowered cholesterol prevents coronary heart disease (CHD) events, with two clinical CHD outcome studies establishing a cardioprotective niacin regimen: 1 g thrice daily with meals. Though cardioprotective, skin toxicity limits niacin's use, fostering several variations to improve tolerability. One of these, an extended-release (ER) alternative, proved immensely successful commercially, dominating clinical practice despite departing from the established regimen in several critical ways. Hence, improved tolerability may have come at the cost of diminished efficacy, posing a conundrum: Does it still help the population at risk for CHD to broaden a drug's acceptance by "watering it down"? This question is crucial at this stage now that the ER alternative failed to recapitulate the benefits of the established cardioprotective niacin regimen in two trials of the alternative approach: AIM-HIGH and HPS2-THRIVE. Part I of this review discusses how vastly the ER alternative departs from the established cardioprotective regimen, why that is important physiologically, and how it may explain the findings of AIM-HIGH and HPS2-THRIVE. Given important gaps left by statin therapy, the established cardioprotective niacin regimen remains an important evidence-based therapy for the statin intolerant or statin averse. PMID:26876225

  1. Practical application of genomics to the development of a topical cosmetic anti-aging regimen.

    PubMed

    Kaczvinsky, Joseph R; Bertucci, Vince; Fu, Juian-juian Jan

    2011-01-01

    The development of topical cosmetic anti-aging products is becoming increasingly sophisticated. This is demonstrated by the benefit agents selected and the scientific approaches used to identify them, treatment protocols that increasingly incorporate multi-product regimens, and the level of rigor in the clinical testing used to demonstrate efficacy. Consistent with these principles, a new cosmetic anti-aging regimen was recently developed. The key product ingredients were identified based on an understanding of the key mechanistic themes associated with aging at the genomic level coupled with appropriate in vitro testing. The products were designed to provide optimum benefits when used in combination in a regimen format. This cosmetic regimen was then tested for efficacy against the appearance of facial wrinkles in a 24-week clinical trial compared with 0.02% tretinoin, a recognized benchmark prescription treatment for facial wrinkling. The cosmetic regimen significantly improved wrinkle appearance after 8 weeks relative to tretinoin and was better tolerated. Wrinkle appearance benefits from the two treatments in cohorts of subjects who continued treatment through 24 weeks were also comparable.

  2. 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

  3. Comparing interval and continuous exercise training regimens on neurotrophic factors in rat brain.

    PubMed

    Afzalpour, Mohammad Esmaiel; Chadorneshin, Hossein Taheri; Foadoddini, Mohsen; Eivari, Hossein Abtahi

    2015-08-01

    The research literature suggests that oxidative stress and pro-inflammatory factors influence neurotrophins in vitro. However, there is insufficient information about their effects on exercise training conditions, especially during high intensity trainings. This study aimed to compare the effects of 6weeks of high intensity interval and continuous training regimens on brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), hydrogen peroxide (H2O2), and tumor necrosis factor alpha (TNF-α) in the rat brain. For this purpose, twenty-four Albino Wistar rats were divided into sedentary control (SC), high intensity interval training (HIIT), and continuous training (CT) groups. Both HIIT and CT regimens increased H2O2 level and TNF-α concentration in the brain, and the alterations made were greater following HIIT than CT. In addition, both HIIT and CT regimens increased BDNF and GDNF concentrations significantly, with a higher elevation following HIIT than CT. Furthermore, H2O2 level and TNF-α concentration correlated positively with both BDNF and GDNF concentrations. Generally, high intensity interval training regimen, rather than continuous training regimen, is highly potential to improve BDNF and GDNF through a greater increase in H2O2 and TNF-α as oxidative stress and pro-inflammatory factors.

  4. Cost-effectiveness of the sequential application of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.

    PubMed

    Rochau, Ursula; Sroczynski, Gaby; Wolf, Dominik; Schmidt, Stefan; Jahn, Beate; Kluibenschaedl, Martina; Conrads-Frank, Annette; Stenehjem, David; Brixner, Diana; Radich, Jerald; Gastl, Günther; Siebert, Uwe

    2015-01-01

    Several tyrosine kinase inhibitors (TKIs) are approved for chronic myeloid leukemia (CML) therapy. We evaluated the long-term cost-effectiveness of seven sequential therapy regimens for CML in Austria. A cost-effectiveness analysis was performed using a state-transition Markov model. As model parameters, we used published trial data, clinical, epidemiological and economic data from the Austrian CML registry and national databases. We performed a cohort simulation over a life-long time-horizon from a societal perspective. Nilotinib without second-line TKI yielded an incremental cost-utility ratio of 121,400 €/quality-adjusted life year (QALY) compared to imatinib without second-line TKI after imatinib failure. Imatinib followed by nilotinib after failure resulted in 131,100 €/QALY compared to nilotinib without second-line TKI. Nilotinib followed by dasatinib yielded 152,400 €/QALY compared to imatinib followed by nilotinib after failure. Remaining strategies were dominated. The sequential application of TKIs is standard-of-care, and thus, our analysis points toward imatinib followed by nilotinib as the most cost-effective strategy.

  5. Cost-effectiveness of the sequential application of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.

    PubMed

    Rochau, Ursula; Sroczynski, Gaby; Wolf, Dominik; Schmidt, Stefan; Jahn, Beate; Kluibenschaedl, Martina; Conrads-Frank, Annette; Stenehjem, David; Brixner, Diana; Radich, Jerald; Gastl, Günther; Siebert, Uwe

    2015-01-01

    Several tyrosine kinase inhibitors (TKIs) are approved for chronic myeloid leukemia (CML) therapy. We evaluated the long-term cost-effectiveness of seven sequential therapy regimens for CML in Austria. A cost-effectiveness analysis was performed using a state-transition Markov model. As model parameters, we used published trial data, clinical, epidemiological and economic data from the Austrian CML registry and national databases. We performed a cohort simulation over a life-long time-horizon from a societal perspective. Nilotinib without second-line TKI yielded an incremental cost-utility ratio of 121,400 €/quality-adjusted life year (QALY) compared to imatinib without second-line TKI after imatinib failure. Imatinib followed by nilotinib after failure resulted in 131,100 €/QALY compared to nilotinib without second-line TKI. Nilotinib followed by dasatinib yielded 152,400 €/QALY compared to imatinib followed by nilotinib after failure. Remaining strategies were dominated. The sequential application of TKIs is standard-of-care, and thus, our analysis points toward imatinib followed by nilotinib as the most cost-effective strategy. PMID:25393806

  6. Sequential or simultaneous visual processing deficit in developmental dyslexia?

    PubMed

    Lassus-Sangosse, Delphine; N'guyen-Morel, Marie-Ange; Valdois, Sylviane

    2008-03-01

    The ability of dyslexic children with or without phonological problems to process simultaneous and sequential visual information was assessed using two tasks requiring the oral report of simultaneously or sequentially displayed letter-strings. The two groups were found to exhibit a simultaneous visual processing deficit but preserved serial processing skills. However, the impairment in simultaneous processing was larger in the dyslexic group with no phonological disorder. Although sequential and simultaneous processing skills both related to reading performance, simultaneous processing alone significantly contributed to reading speed and accuracy. These findings suggest that a simultaneous processing disorder might contribute to developmental dyslexia.

  7. Sequential Administration of Methotrexate and Asparaginase in Relapsed or Refractory Pediatric Acute Myeloid Leukemia

    PubMed Central

    Buaboonnam, Jassada; Cao, Xueyuan; Pauley, Jennifer L.; Pui, Ching-Hon; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Inaba, Hiroto

    2014-01-01

    Background The efficacy of combination chemotherapy with methotrexate (MTX) and asparaginase is not well known in relapsed and refractory acute leukemia after contemporary therapy. Procedure A retrospective study of pediatric patients with relapsed or refractory acute myeloid leukemia (AML) who received MTX and asparaginase as a salvage therapy at St. Jude Children Research Hospital was performed. MTX was given intravenously followed by a dose of asparaginase intramuscularly or intravenously 24 hours later. The chemotherapy cycle was repeated every 7-10 days. Response, survival, and toxicities were evaluated. Results Fifteen patients, median age 10.5 years (range, 1.1-18.5 years), were treated. Median number of previous therapeutic regimens was 3 (range, 1-4). Six patients responded to treatment (3 had morphologic complete remission with incomplete blood count recovery, 2 had partial remission, and 1 had stable disease for 16 months), and 4 are still alive. Three of 6 responders had monoblastic leukemia, and also developed tumor lysis syndrome. The 1- and 2-year overall survival rates are 35.6% and 17.8%, respectively. The most common adverse event was transient elevation of transaminases (9 patients). Two patients developed pancreatitis. Episodes of febrile neutropenia were rare (2 patients), and most courses (75 out of 93 total courses) were given in an outpatient setting. Conclusions Combination chemotherapy with MTX and asparaginase appears to be an effective salvage therapy and well tolerated in patients with relapsed or refractory childhood AML, even in those heavily pretreated with contemporary frontline or salvage therapy. PMID:23335430

  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. “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

  10. 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

  11. Low vision reading with sequential word presentation.

    PubMed

    Rubin, G S; Turano, K

    1994-07-01

    Individuals with scotomas in the center of their visual fields usually read much more slowly than visually impaired individuals without central scotomas. This study determines the extent to which inefficient eye movements could account for this difference. Using a technique described previously [Rubin and Turano (1992) Vision Research, 32, 895-902] text was presented sequentially, one word at a time at the same location in the visual field. Reading performance for rapid serial visual presentation (RSVP) was compared to conventional text presentation (PAGE) in 14 subjects with dense central scotomas (central field loss, CFL) and 9 without central scotomas (noCFL). Reading rates were faster with RSVP compared to PAGE, but CFL subjects improved less (by a factor of 1.5 +/- 0.41) than noCFL subjects (by a factor of 2.1 +/- 0.38). When reading rate (words/min) was converted to average word duration (msec/word) the reduction in word duration for RSVP compared to PAGE text averaged 150 msec for normal subjects, 171 msec for noCFL subjects, and 250 msec for CFL subjects. We hypothesized that the reduction in word duration was attributable to a reduced number of saccades/word. We confirmed this hypothesis by measuring the number of saccades during RSVP and PAGE reading using a scanning laser ophthalmoscope in four subjects with CFL. All of the subjects made fewer saccades during RSVP than PAGE reading (average reduction = 1.3 +/- 0.5 saccades/word). But even with the reduced number of saccades, CFL subjects required longer word durations than noCFL subjects. These results indicate that inefficient eye movements account for only part of the reduction in reading speed caused by CFL. An additional and potentially more important factor is the limited rate at which peripheral retina can perform the pattern decoding tasks required for reading.

  12. Pharmacokinetic estimation for therapeutic dosage regimens (PETDR)--a software program designed to determine intravenous drug dosage regimens for veterinary applications.

    PubMed

    Riviere, J E; Frazier, D L; Tippitt, W L

    1988-12-01

    Pharmacokinetic estimation for therapeutic dosage regimens (PETDR) is a soft-ware program used to design individualized intravenous dosage regimens, determine concentration-time profiles, predict serum concentrations at a specific time after intravenous dosing and predict the time after the last dose to achieve a specified concentration of drug. The reference pharmacokinetic parameters may be based on an individual animal's pharmacokinetic disposition of drug or on FARAD (Food Animal Residue Avoidance Databank) mean population kinetic parameters. An individual animal's kinetic parameters may be input for predetermined analysis or the program can calculate these values by input of raw serum concentration-time data. The program allows the user to specify certain parameters of the dosage regimen, then calculates the other parameters (given desired maximum and minimum serum concentrations, dose and interval are calculated; given desired maximum serum concentration and interval, dose is calculated, etc.). Given the kinetic parameters, the dose and dosing interval, the program calculates and plots the serum concentration-time profile of the drug for that animal. The time and the number of doses to reach steady state can be calculated as well as the determination of loading dose. The percentage of the time of a dosing interval at steady state that the serum concentration is above a specific minimum inhibitory concentration (MIC) allows evaluation of efficacy of an antimicrobial regimen. Similarly, the time to reach a specific concentration (e.g. residue tolerance) or the MIC of a drug can be calculated. Legal tissue tolerances can be accessed from FARAD to aid in predicting for what period of time illegal residues will remain in the animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3210265

  13. Treatment regimens for rifampicin-resistant tuberculosis: highlighting a research gap.

    PubMed

    Stagg, H R; Hatherell, H-A; Lipman, M C; Harris, R J; Abubakar, I

    2016-07-01

    Treatment guidance for non-multidrug-resistant (MDR) rifampicin-resistant (RMP-R) tuberculosis (TB) is variable. We aimed to undertake a systematic review and meta-analysis of the randomised controlled trial (RCT) data behind such guidelines to identify the most efficacious treatment regimens. Ovid MEDLINE, the Web of Science and EMBASE were mined using search terms for TB, drug therapy and RCTs. Despite 12 604 records being retrieved, only three studies reported treatment outcomes by regimen for patients with non-MDR RMP-R disease, preventing meta-analysis. Our systematic review highlights a substantial gap in the literature regarding evidence-based treatment regimens for RMP-R TB.

  14. Principle approaches to selection of the short-arm centrifuge regimens for extended space flight.

    PubMed

    Vil-Viliams, I F

    1994-07-01

    Eight +Gz regimens on the SAC varying in their values (within 0.8 to 1.6 G), exposures, schedules, etc. were analyzed. Some regimens were combined with water-salt supplements (WSS) or veloergometer training (VE). Weightlessness was simulated by 3- to 28-day water immersion. +3 Gz loads on the centrifuge with the radius of 7.5 m were applied prior to and post immersion. Regimens for human runs on the SAC as a novel, perspective countermeasure for interplanetary expeditions should be selected with due regard of the human tolerance, their efficiency, and subsequent verification and specification in orbital flights. These approaches showed that 3 days of exposure to 1.2 G combined with WSS and 6 days of exposure to G-loads from 0.8 to 1.6 G together with VE were most optimal. PMID:11539526

  15. Antiretroviral regimen and suboptimal medication adherence are associated with low-level human immunodeficiency virus viremia.

    PubMed

    Konstantopoulos, Christina; Ribaudo, Heather; Ragland, Kathleen; Bangsberg, David R; Li, Jonathan Z

    2015-01-01

    Episodes of human immunodeficiency virus low-level viremia (LLV) are common in the clinical setting, but its association with antiretroviral therapy (ART) regimen and adherence remains unclear. Antiretroviral therapy adherence was evaluated in participants of the Research on Access to Care in the Homeless cohort by unannounced pill counts. Factors associated with increased risk of LLV include treatment with a protease inhibitor (PI)-based regimen (ritonavir-boosted PI vs nonnucleoside reverse-transcriptase inhibitor: adjusted hazard ratio [HR], 3.1; P = .01) and lower ART adherence over the past 3 months (HR, 1.1 per 5% decreased adherence, adjusted; P = .050). Patients with LLV may benefit from ART adherence counseling and potentially regimen modification. PMID:25884007

  16. Principle approaches to selection of the short-arm centrifuge regimens for extended space flight

    NASA Astrophysics Data System (ADS)

    Vil-Viliams, Inna F.

    Eight +Gz regimens on the SAC varying in their values (within 0.8 to 1.6 G), exposures, schedules, etc. were analyzed. Some regimens were combined with water-salt supplements (WSS) or veloergometer training (VE). Weightlessness was simulated by 3- to 28-day water immersion. +3 Gz loads on the centrifuge with the radius of 7.5 m were applied prior to and post immersion. Regimens for human runs on the SAC as a novel, perspective countermeasure for interplanetary expeditions should be selected with due regard of the human tolerance, their efficiency, and subsequent verification and specification in orbital flights. These approaches showed that 3 days of exposure to 1.2 G combined with WSS and 6 days of exposure to G-loads from 0.8 to 1.6 G together with VE were most optimal.

  17. Clinical benefits of bortezomib-containing regimens for newly diagnosed AL amyloidosis with severe cardiac impairment.

    PubMed

    Tsukune, Yutaka; Yahata, Yuriko; Sasaki, Makoto; Hiki, Makoto; Tsutsui, Miyuki; Hamano, Yasuharu; Itoh, Seigo; Miyazaki, Tetsuro; Dohi, Tomotaka; Maruyama, Masaki; Gotoh, Akihiko; Komatsu, Norio

    2016-08-01

    Cardiac amyloid light-chain amyloidosis (AL amyloidosis) is a rare disease with a very poor prognosis, associated with plasma cell dyscrasias such as monoclonal gammopathy of undetermined significance and multiple myeloma. Though bortezomib-containing regimens have achieved high hematologic response rates, there are still few reports describing the outcomes of Japanese patients. Six patients with severe cardiac AL amyloidosis were treated with bortezomib-containing regimens. Involved free light chain (iFLC) decreased immediately in most of these cases. However, the condition of heart failure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) worsened in the early phase of this treatment and then improved several months later. At 29 months, the median duration of follow-up (2-47months), all patients remain alive except one who died of sudden cardiac arrest. Bortezomib-containing regimens are considered to be among the effective treatments for severe cardiac AL amyloidosis. PMID:27599413

  18. Clinical benefits of bortezomib-containing regimens for newly diagnosed AL amyloidosis with severe cardiac impairment.

    PubMed

    Tsukune, Yutaka; Yahata, Yuriko; Sasaki, Makoto; Hiki, Makoto; Tsutsui, Miyuki; Hamano, Yasuharu; Itoh, Seigo; Miyazaki, Tetsuro; Dohi, Tomotaka; Maruyama, Masaki; Gotoh, Akihiko; Komatsu, Norio

    2016-08-01

    Cardiac amyloid light-chain amyloidosis (AL amyloidosis) is a rare disease with a very poor prognosis, associated with plasma cell dyscrasias such as monoclonal gammopathy of undetermined significance and multiple myeloma. Though bortezomib-containing regimens have achieved high hematologic response rates, there are still few reports describing the outcomes of Japanese patients. Six patients with severe cardiac AL amyloidosis were treated with bortezomib-containing regimens. Involved free light chain (iFLC) decreased immediately in most of these cases. However, the condition of heart failure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) worsened in the early phase of this treatment and then improved several months later. At 29 months, the median duration of follow-up (2-47months), all patients remain alive except one who died of sudden cardiac arrest. Bortezomib-containing regimens are considered to be among the effective treatments for severe cardiac AL amyloidosis.

  19. 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

  20. 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. PMID:25561537

  1. Comparative Effectiveness of First Antiretroviral Regimens in Clinical Practice Using a Causal Approach.

    PubMed

    Cuzin, Lise; Pugliese, Pascal; Allavena, Clotilde; Katlama, Christine; Cotte, Laurent; Cheret, Antoine; Cabié, André; Rey, David; Chirouze, Catherine; Bani-Sadr, Firouze; Flandre, Philippe

    2015-09-01

    The objective of this study was to estimate the cumulative incidences of failure by months 12 (M12) and 24 (M24) for the most prescribed first-line anti-retroviral regimens (ART). It is retrospective analysis of a prospectively collected database. All patients who initiated their first ART with the most prescribed regimens between 1st January 2004 and 30th June 2013 in 12 large HIV reference centers in France were included. The outcome was treatment failure--defined by any treatment modification for virological or tolerability reasons--and comparisons between regimens were carried out at M12 and M24. Adjusted and weighted methods via the propensity score (PS) were used to compare the effectiveness of the first antiretroviral regimens. Potential confounders of the treatment-outcome association were used to estimate PS with multinomial logistic regression. Overall, 3128 and 2690 patients were included in the M12 and M24 analyses, respectively. Patients received 5 different regimens (ABC/3TC with ATV/r or DRV/r, TDF/FTC with ATV/r, DRV/r, or EFV). Failure was reported in 25% and 42% at M12 and M24, respectively. Patients who received TDF/FTC/EFV had a significantly higher proportion of failure at M12 by comparison with TDF/FTC with DRV/r (reference), but not at M24. Patients in the 3 other groups had a trend toward a higher proportion of failure at M12 although not statistically significant. No difference was found at M24. Using data from a large prospective cohort, we found that boosted atazanavir and darunavir had comparable effectiveness, whatever the associated NRTIs, whereas efavirenz-based regimens were relatively less performing on the short term.

  2. Pharmacogenomics-based tailored versus standard therapeutic regimen for eradication of H. pylori.

    PubMed

    Furuta, T; Shirai, N; Kodaira, M; Sugimoto, M; Nogaki, A; Kuriyama, S; Iwaizumi, M; Yamade, M; Terakawa, I; Ohashi, K; Ishizaki, T; Hishida, A

    2007-04-01

    Helicobacter pylori eradication rates by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin at standard doses depend on bacterial susceptibility to clarithromycin and patient CYP2C19 genotypes. We examined the usefulness of a personalized therapy for H. pylori infection based on these factors as determined by genetic testing. First, optimal lansoprazole dosing schedules that would achieve sufficient acid inhibition to allow H. pylori eradication therapy in each of different CYP2C19 genotype groups were determined by a 24-h intragastric pH monitoring. Next, 300 H. pylori-positive patients were randomly assigned to the standard regimen group (lansoprazole 30 mg twice daily (b.i.d.)), clarithromycin 400 mg b.i.d., and amoxicillin 750 mg b.i.d. for 1 week) or the tailored regimen group based on CYP2C19 status and bacterial susceptibility to clarithromycin assessed by genetic testing. Patients with failure of eradication underwent the second-line regimen. The per-patient cost required for successful eradication was calculated for each of the groups. In the first-line therapy, the intention-to-treat eradication rate in the tailored regimen group was 96.0% (95% CI=91.5-98.2%, 144/150), significantly higher than that in the standard regimen group (70.0%: 95% CI=62.2-77.2%, 105/150) (P<0.001). Final costs per successful eradication in the tailored and standard regimen groups were $669 and $657, respectively. In conclusion, the pharmacogenomics-based tailored treatment for H. pylori infection allowed a higher eradication rate by the initial treatment without an increase of the final per-patient cost for successful eradication. However, the precise cost-effectiveness of this strategy remains to be determined. PMID:17215846

  3. Is Resection of Colorectal Liver Metastases after a Second-Line Chemotherapy Regimen Justified?

    PubMed Central

    Brouquet, Antoine; Overman, Michael J.; Kopetz, Scott; Maru, Dipen M.; Loyer, Evelyne M.; Andreou, Andreas; Cooper, Amanda; Curley, Steven A.; Garrett, Christopher R.; Abdalla, Eddie K.; Vauthey, Jean Nicolas

    2011-01-01

    Background Patients' outcomes following resection of colorectal liver metastases (CLM) after second-line chemotherapy regimen is unknown. Methods From August 1998 to June 2009, data from 1099 patients with CLM were collected prospectively. We retrospectively analyzed outcomes of patients who underwent resection of CLM after second-line (two or more) chemotherapy regimens. Results Sixty patients underwent resection of CLM after 2 or more chemotherapy regimens. Patients had advanced CLM (mean number of CLM ± standard deviation, 4 ± 3.5; mean maximum size of CLM, 5 ± 3.2 cm) and had received 17 ± 8 cycles of preoperative chemotherapy. In 54 patients (90%), the switch from the first regimen to another was motivated by tumor progression or suboptimal radiographic response. All patients received irinotecan or oxaliplatin and the majority (42/60, 70%) received a monoclonal antibody (bevacizumab or cetuximab) as part of the last preoperative regimen. Postoperative morbidity and mortality rates were 33% and 3%, respectively. At a median follow-up of 32 months, 1-year, 3-year, and 5-year overall survival rates were 83%, 41%, and 22%, respectively. Median chemotherapy-free survival following resection or completion of additional chemotherapy administered after resection was 9 months (95% confidence interval (CI) 4–14 months). Synchronous (v metachronous) CLM and minor (v major) pathologic response were independently associated with worse survival. Conclusion Resection of CLM after second-line chemotherapy regimen is safe and associated with a modest hope for definitive cure. This approach represents a viable option in patients with advanced CLM. PMID:21446046

  4. Spatial versus sequential correlations for random access coding

    NASA Astrophysics Data System (ADS)

    Tavakoli, Armin; Marques, Breno; Pawłowski, Marcin; Bourennane, Mohamed

    2016-03-01

    Random access codes are important for a wide range of applications in quantum information. However, their implementation with quantum theory can be made in two very different ways: (i) by distributing data with strong spatial correlations violating a Bell inequality or (ii) using quantum communication channels to create stronger-than-classical sequential correlations between state preparation and measurement outcome. Here we study this duality of the quantum realization. We present a family of Bell inequalities tailored to the task at hand and study their quantum violations. Remarkably, we show that the use of spatial and sequential quantum correlations imposes different limitations on the performance of quantum random access codes: Sequential correlations can outperform spatial correlations. We discuss the physics behind the observed discrepancy between spatial and sequential quantum correlations.

  5. Parallel versus Sequential Processing of Pictures and Words

    ERIC Educational Resources Information Center

    Snodgrass, Joan Gay; Antone, George

    1974-01-01

    The purpose of this experiment was to test a proposal by Paivio (1971) that visual memory images are specialized for parallel or spatiol processing, whereas verbal memory codes are specialized for sequential or temporal processing. (Author)

  6. 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...

  7. 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)

  8. Instrument sequentially samples ac signals from several accelerometers

    NASA Technical Reports Server (NTRS)

    Chapman, C. P.

    1967-01-01

    Scanner circuit sequentially samples the ac signals from accelerometers used in conducting noise vibration tests, and provides a time-averaged output signal. The scanner is used in conjunction with other devices for random noise vibration tests.

  9. 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.

  10. A Sequential Preparation of Organic Compounds for Senior Chemistry Classes

    ERIC Educational Resources Information Center

    Merrigan, Cecilia; Crotty, Patricia

    1971-01-01

    Describes procedures suitable for student preparation of benzaldehyde, benzoic acid, and ethyl benzoate sequentially from benzyl alcohol. Preparation for benzyl chloride also given. All reagents except benzyl alcohol are common inorganic chemicals. (AL)

  11. Heterosexual Relationship Development: Is It Really a Sequential Process?

    ERIC Educational Resources Information Center

    Cate, Rodney M.; Koval, James E.

    1983-01-01

    Reviews three existing sequential models of mate selection: Kerckhoff and Davis' Filter Model, Murstein's Stimulus-Value-Role Model, and Lewis's Premarital Dyadic Formation Model. Challenges the validity of these models and discusses implications for future research. (JAC)

  12. A Note on the Sequential Probability Ratio Test

    ERIC Educational Resources Information Center

    Thomas, Ewart A. C.

    1975-01-01

    Given reflection symmetry, the moment generating function symmetry is necessary and sufficient for the random walk model to be equivalent to a sequential probability ratio test. For a related article, see TM 501 715. (Author/RC)

  13. 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

  14. [Stability of high-dose etoposide dilutions for use in hematopoietic stem cell transplantation conditioning regimens].

    PubMed

    Bauters, T; Vandenbroucke, J; Commeyne, S

    2015-12-01

    High-dose etoposide is used in conditioning regimens for allogeneic stem cell transplantation. The limited stability of the drug induces barriers for its use for pharmacists, nurses and patients. When using a concentration of 10 mg/mL etoposide in physiologic saline, limitations can be overcome. This study provides stability data for etoposide in a high concentration that can be used in conditioning regimens. The solution was stable for 48h at 5°C, for 48h at 5°C followed by 8h at 25°C and for 24 h at 25°C.

  15. Comparison of adjuvant ED and EC-D regimens in operable breast invasive ductal carcinoma

    PubMed Central

    Jiang, Liyu; Jing, Chuyu; Kong, Xiaoli; Li, Xiaoyan; Ma, Tingting; Huo, Qiang; Chen, Junfei; Wang, Xiaoting; Yang, Qifeng

    2016-01-01

    In China, the adjuvant epirubicin and docetaxel (ED) regimen is widely used as a substitute for the epirubicin and cyclophosphamide followed by docetaxel (EC-D) regimen in patients with operable breast cancer. However, their equivalence has not yet been demonstrated. This retrospective study compared these two adjuvant regimens as regards feasibility, safety and efficacy. Data on consecutive patients who received either ED (70/75 mg/m2 every 3 weeks for 6 cycles) or EC-D (70/600 mg/m2 epirubicin/cyclophosphamide followed by 75 mg/m2 docetaxel every 3 weeks for 4 cycles each) as their adjuvant chemotherapy in our center from January 2009 to January 2014, were analyzed. A total of 374 patients was enrolled, among whom 250 patients received the ED regimen, and 124 patients received the EC-D regimen. The overall median follow-up time was 38.6 months. In total, 90 and 94.4% of patients in the ED and EC-D groups, respectively, completed full cycles of chemotherapy (P=0.174). There was no difference in efficacy in terms of disease-free survival (DFS) and overall survival (OS) (DFS, P=0.919; OS, P=0.069). The incidence of neutropenia in the ED group was similar to that in the EC-D group (81.2 vs. 78.9%, P=0.660) with a similar utilization rate of granulocyte-colony stimulating factor (G-CSF; 76.9 vs. 75.2%, P=0.850). However, grade 3/4 gastrointestinal reactions were more frequently observed in the patients who received the EC-D regimen (42.0 vs. 29.2%, P=0.058). The findings of our study indicate that with similar feasibility, safety and mid-term efficacy, the adjuvant ED regimen for 6 cycles may be an alternative to the EC-D regimen in operable breast cancer. PMID:27446451

  16. 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

  17. On some classes of sequential spiking neural p systems.

    PubMed

    Zhang, Xingyi; Zeng, Xiangxiang; Luo, Bin; Pan, Linqiang

    2014-05-01

    Spiking neural P systems (SN P systems) are a class of distributed parallel computing devices inspired by the way neurons communicate by means of spikes; neurons work in parallel in the sense that each neuron that can fire should fire, but the work in each neuron is sequential in the sense that at most one rule can be applied at each computation step. In this work, with biological inspiration, we consider SN P systems with the restriction that at each step, one of the neurons (i.e., sequential mode) or all neurons (i.e., pseudo-sequential mode) with the maximum (or minimum) number of spikes among the neurons that are active (can spike) will fire. If an active neuron has more than one enabled rule, it nondeterministically chooses one of the enabled rules to be applied, and the chosen rule is applied in an exhaustive manner (a kind of local parallelism): the rule is used as many times as possible. This strategy makes the system sequential or pseudo-sequential from the global view of the whole network and locally parallel at the level of neurons. We obtain four types of SN P systems: maximum/minimum spike number induced sequential/pseudo-sequential SN P systems with exhaustive use of rules. We prove that SN P systems of these four types are all Turing universal as number-generating computation devices. These results illustrate that the restriction of sequentiality may have little effect on the computation power of SN P systems. PMID:24555456

  18. Generalized Sequential Probability Ratio Test for Separate Families of Hypotheses

    PubMed Central

    Li, Xiaoou; Liu, Jingchen; Ying, Zhiliang

    2014-01-01

    In this paper, we consider the problem of testing two separate families of hypotheses via a generalization of the sequential probability ratio test. In particular, the generalized likelihood ratio statistic is considered and the stopping rule is the first boundary crossing of the generalized likelihood ratio statistic. We show that this sequential test is asymptotically optimal in the sense that it achieves asymptotically the shortest expected sample size as the maximal type I and type II error probabilities tend to zero. PMID:27418716

  19. 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

  20. Robust sequential working memory recall in heterogeneous cognitive networks.

    PubMed

    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.

  1. 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

  2. Bortezomib plus melphalan and prednisone (VMP regimen) as the initial treatment for IgE multiple myeloma: a case study.

    PubMed

    Sato, Hiroyuki; Komiya, Yusuke; Hoshino, Shigeru

    2014-06-01

    Patients with IgE multiple myeloma have poor prognosis. Due to the rarity of this condition, no standard treatment has been developed. As the VMP regimen (bortezomib plus melphalan and prednisone) has been reported to be highly effective in the treatment of other types of myeloma, we treated a patient with newly diagnosed IgE myeloma using the VMP regimen. Her myeloma responded well to VMP regimen. The results of this case report thus suggest that physicians may consider VMP regimen for use as the initial treatment for IgE myeloma.

  3. Evaluation of Antimicrobial Activities of Sequential Spray Applications of Decontamination Treatments on Chicken Carcasses

    PubMed Central

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

    2015-01-01

    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. PMID:25656180

  4. 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. PMID:25656180

  5. A Patient Education Program to Improve Adherence Rates with Antituberculosis Drug Regimens.

    ERIC Educational Resources Information Center

    Morisky, Donald E.; And Others

    1990-01-01

    An incentive scheme to reward positive health behaviors (adherence to antituberculosis drug regimens) was tested with 88 active and 117 preventive patients randomly assigned to intervention and control groups. Preventive patients who received incentives were significantly more likely to continue care and had higher adherence levels. Actives showed…

  6. Revisiting Dosing Regimen Using Pharmacokinetic/Pharmacodynamic Mathematical Modeling: Densification and Intensification of Combination Cancer Therapy.

    PubMed

    Meille, Christophe; Barbolosi, Dominique; Ciccolini, Joseph; Freyer, Gilles; Iliadis, Athanassios

    2016-08-01

    Controlling effects of drugs administered in combination is particularly challenging with a densified regimen because of life-threatening hematological toxicities. We have developed a mathematical model to optimize drug dosing regimens and to redesign the dose intensification-dose escalation process, using densified cycles of combined anticancer drugs. A generic mathematical model was developed to describe the main components of the real process, including pharmacokinetics, safety and efficacy pharmacodynamics, and non-hematological toxicity risk. This model allowed for computing the distribution of the total drug amount of each drug in combination, for each escalation dose level, in order to minimize the average tumor mass for each cycle. This was achieved while complying with absolute neutrophil count clinical constraints and without exceeding a fixed risk of non-hematological dose-limiting toxicity. The innovative part of this work was the development of densifying and intensifying designs in a unified procedure. This model enabled us to determine the appropriate regimen in a pilot phase I/II study in metastatic breast patients for a 2-week-cycle treatment of docetaxel plus epirubicin doublet, and to propose a new dose-ranging process. In addition to the present application, this method can be further used to achieve optimization of any combination therapy, thus improving the efficacy versus toxicity balance of such a regimen.

  7. Effects of an Aerobic Rowing Training Regimen in Young Adults with Down Syndrome.

    ERIC Educational Resources Information Center

    Varela, Ana Maria; Sardinha, Luis Bettencount; Pitetti, Kenneth H.

    2001-01-01

    Eight young adult males with Down syndrome received a 16-week rowing ergometry training regimen. Following training, no changes in cardiovascular fitness were found but participants did achieve significantly higher levels of work performance on both treadmill and rowing ergometer tests than did a control group. (Contains references.) (Author/DB)

  8. 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

  9. The effectiveness of existing and modified cleaning regimens in a Welsh hospital.

    PubMed

    Griffith, C J; Obee, P; Cooper, R A; Burton, N F; Lewis, M

    2007-08-01

    Hospital cleaning currently has a high media profile. The effectiveness of an existing ward-cleaning regimen was assessed at selected sites over a 14 day period and shown to be highly variable. The cleaning regimen was subsequently modified in two stages, both changes involving a rinse stage and substituting cloths with disposable paper towels. One modification continued using the existing detergent; the other replaced detergent with a quaternary ammonium sanitiser. Both modifications yielded significantly lower and more consistent bacterial counts. Assessment of residual organic soil using adenosine triphosphate (ATP) detection demonstrated that failure rates (measurements exceeding benchmark clean value of 500 relative light units (RLU)) fell from 86-100% after existing cleaning methods, to 0-14% after modified cleaning. Maximum ATP readings fell from 163,870 to 2289 RLU. Incorporating a quaternary ammonium sanitiser into the cleaning regimen produced a further slight, but not significant, improvement in cleaning efficacy. These findings suggest that simple improvements can be made to existing cleaning regimens to increase their efficacy. PMID:17655976

  10. 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.

  11. The Diabetes Regimen Responsibility Scale: Information on Internal Consistency and Validity in a Pediatric Sample.

    ERIC Educational Resources Information Center

    Carey, Tracy; Reid, Graham; Ruggiero, Laurie; Horner, James; Dubow, Eric

    1997-01-01

    The internal consistency and validity of the Diabetes Regimen Responsibility Scale (DRRS) (L. Ruggiero and others, 1991) were examined in a sample of 49 youths. The DRRS demonstrated adequate internal consistency, and most subscales correlated significantly with diabetes knowledge (health education issue). Only two reports correlated with…

  12. 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.

  13. 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...

  14. 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…

  15. 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.

  16. 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.

  17. 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…

  18. 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.

  19. Intermittent Versus Daily Pulmonary Tuberculosis Treatment Regimens: A Meta-Analysis

    PubMed Central

    Kasozi, Samuel; Clark, Justin; Doi, Suhail A. R.

    2015-01-01

    Background Several systematic reviews suggest that intermittent pulmonary tuberculosis (TB) chemotherapy is effective, but intensity (daily versus intermittent) and duration of rifampicin use (intensive phase only versus both phases) have not been distinguished. In addition, the various outcomes (success, failure, relapse, and default) have only selectively been evaluated. Methods We conducted a meta-analysis of proportions using all four outcomes as multi-category proportions to examine the effectiveness of WHO category 1 TB treatment regimens. Database searches of studies reporting treatment outcomes of HIV negative subjects were included and stratified by intensity of therapy and duration of rifampicin therapy. Using a bias-adjusted statistical model, we pooled proportions of the four treatment outcome categories using a method that handles multi-category proportions. Results A total of 27 studies comprising of 48 data sets with 10,624 participants were studied. Overall, treatment success was similar among patients treated with intermittent (I/I) (88%) (95% CI, 81–92) and daily (D/D) (90%) (95% CI, 84–95) regimens. Default was significantly less with I/I (0%) (95% CI, 0–2) compared to D/D regimens (5%) (95% CI, 1–9). Nevertheless, I/I relapse rates (7%) (95% CI, 3–11) were higher than D/D relapse rates (1%) (95% CI, 0–3). Conclusion Treatment regimens that are offered completely intermittently versus completely daily are associated with a trade-off between treatment relapse and treatment default. There is a possibility that I/I regimens can be improved by increasing treatment duration, and this needs to be urgently addressed by future studies. PMID:26056374

  20. An effective reinduction regimen for first relapse of adult acute lymphoblastic leukemia.

    PubMed

    Aldoss, Ibrahim; Pullarkat, Vinod; Patel, Ravindra; Watkins, Kristy; Mohrbacher, Ann; Levine, Alexandra M; Douer, Dan

    2013-12-01

    Current salvage regimens achieve complete remission (CR) in about a third of adults with relapsed/refractory acute lymphoblastic leukemia (ALL), and this represents a major barrier for performing allogeneic hematopoietic stem cell transplant (HSCT), the only potentially curative treatment. We conducted in adults with first relapse of ALL, a prospective clinical trial with intensive regimen derived from the pediatric Berlin-Frankfurt-Muenster-85 protocol, with addition of a continuous infusional multi-agent chemotherapy in phase II induction followed by consolidation with alternating monthly cycles. Objectives of this study included CR rate, leukemia-free survival (LFS) and toxicity of the regimen in adults. We report the outcome of 19 patients (19-51 years of age) treated prospectively on the study, as well as a subsequent cohort of 31 patients (18-53 years of age) treated off the study. Thirteen of 19 (68%) patients from the initial prospective study achieved CR, and the median overall survival (OS) of these 13 CR patients was 10.3 months. The median OS and LFS of all 19 patients were 5.6 and 4.3 months, respectively. The regimen was well tolerated, and no grade 4 non-hematological toxicity was observed. Of the 31 patients treated off the study and analyzed retrospectively, 16 (52%) achieved CR. After including all 50 patients, the CR rate was 58%. The regimen used in this trial appears to be feasible and effective salvage therapy option for adult patients younger than age 55 with relapsed ALL, produced a high CR rate and could facilitate subsequent allogeneic HSCT.

  1. Possible impact of the standardized Category IV regimen on multidrug-resistant tuberculosis patients in Mumbai

    PubMed Central

    Udwadia, Zarir F; Mullerpattan, Jai Bharat; Shah, Kushal D; Rodrigues, Camilla S

    2016-01-01

    Background: Treatment of multidrug-resistant tuberculosis (MDR-TB) in the Programmatic Management of Drug-resistant TB program involves a standard regimen with a 6-month intensive phase and an 18-month continuation phase. However, the local drug resistance patterns in high MDR regions such as Mumbai may not be adequately reflected in the design of the regimen for that particular area. Setting: The study was carried out at a private Tertiary Level Hospital in Mumbai in a mycobacteriology laboratory equipped to perform the second-line drug susceptibility testing (DST). Objective: We attempted to analyze the impact of prescribing the standardized Category IV regimen to all patients receiving a DST at our mycobacteriology laboratory. Materials and Methods: All samples confirmed to be MDR-TB and tested for the second-line drugs at Hinduja Hospital's Mycobacteriology Laboratory in the year 2012 were analyzed. Results: A total of 1539 samples were analyzed. Of these, 464 (30.14%) were MDR-TB, 867 (56.33%) were MDR with fluoroquinolone resistance, and 198 (12.8%) were extensively drug-resistant TB. The average number of susceptible drugs per sample was 3.07 ± 1.29 (assuming 100% cycloserine susceptibility). Taking 4 effective drugs to be the cut or an effective regimen, the number of patients receiving 4 or more effective drugs from the standardized directly observed treatment, short-course plus regimen would be 516 (33.5%) while 66.5% of cases would receive 3 or less effective drugs. Conclusion: Our study shows that a high proportion of patients will have resistance to a number of the first- and second-line drugs. Local epidemiology must be factored in to avoid amplification of resistance. PMID:27185987

  2. 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

  3. 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

  4. 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

  5. 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…

  6. 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…

  7. Deterministic sequential isolation of floating cancer cells under continuous flow.

    PubMed

    Tran, Quang D; Kong, Tian Fook; Hu, Dinglong; Marcos; Lam, Raymond H W

    2016-08-01

    Isolation of rare cells, such as circulating tumor cells, has been challenging because of their low abundance and limited timeframes of expressions of relevant cell characteristics. In this work, we devise a novel hydrodynamic mechanism to sequentially trap and isolate floating cells in biosamples. We develop a microfluidic device for the sequential isolation of floating cancer cells through a series of microsieves to obtain up to 100% trapping yield and >95% sequential isolation efficiency. We optimize the trappers' dimensions and locations through both computational and experimental analyses using microbeads and cells. Furthermore, we investigated the functional range of flow rates for effective sequential cell isolation by taking the cell deformability into account. We verify the cell isolation ability using the human breast cancer cell line MDA-MB-231 with perfect agreement with the microbead results. The viability of the isolated cells can be maintained for direct identification of any cell characteristics within the device. We further demonstrate that this device can be applied to isolate the largest particles from a sample containing multiple sizes of particles, revealing its possible applicability in isolation of circulating tumor cells in cancer patients' blood. Our study provides a promising sequential cell isolation strategy with high potential for rapid detection and analysis of general floating cells, including circulating tumor cells and other rare cell types. PMID:27387093

  8. A practical evaluation of sequential estimation for vision metrology

    NASA Astrophysics Data System (ADS)

    Edmundson, Kenneth; Fraser, Clive S.

    Parameter estimation in photogrammetry is generally accomplished by means of a simultaneous least-squares adjustment in which all observational data must be at hand prior to solution. It follows that, despite the rapid turnaround provided by digital imagery and current measurement technology, the simultaneous adjustment cannot offer an indication of quality until acquisition and measurement are complete. On-line quality control of single-sensor vision metrology (VM) can be implemented effectively through on-line triangulation (OLT) with sequential estimation. In combination with established network design principles, sequential estimation can have a significant positive influence on economy and productivity in the industrial environment. While enhancing the efficiency of the triangulation procedure, the risks of collecting either insufficient or surplus imagery are also diminished. Furthermore, localised weaknesses within the overall network can be isolated and corrected. Sequential estimation is applicable to a variety of VM tasks. Here, in addition to quality control for single-sensor VM, the calibration of real-time, multi-sensor systems is addressed. This paper presents an overview of sequential estimation for VM consisting of a description of the general sequential problem followed by the necessary mathematical derivations. Significant implementational aspects are discussed and evaluations of practical testing are given. Promising experimental results clearly demonstrate that OLT can be an effective and valuable tool in industrial VM.

  9. Sequential changes in the metabolic response in severely septic patients during the first 23 days after the onset of peritonitis.

    PubMed Central

    Plank, L D; Connolly, A B; Hill, G L

    1998-01-01

    OBJECTIVE: To quantify the sequential changes in metabolic response occurring in patients with severe sepsis after the onset of peritonitis. SUMMARY BACKGROUND DATA: Understanding the changes in energy expenditure and body composition is essential for the optimal management of severely septic patients; however, they have not been quantified in the context of modern surgical care. METHODS: Twelve patients with severe sepsis secondary to peritonitis (median APACHE II score = 21.5) had measurements of energy expenditure and body composition as soon as they were hemodynamically stable and 5, 10, and 21 days later. Sequential measurements of acute-phase proteins and cytokine responses were also made. RESULTS: Resting energy expenditure rose to 49% above predicted and remained elevated throughout the study period. Total energy expenditure was 1.25 x resting energy expenditure. Body fat was oxidized when energy intake was insufficient to achieve energy balance. There was a positive fluid balance of 12.5 1 over the first 2 days after onset of sepsis; thereafter, body water changes closely paralleled body weight changes and were largely accounted for by changes in extracellular water. During the 21 -day study period, there was a loss of 1.21 kg (13%) of total body protein. During the first 10 days, 67% of the protein lost came from skeletal muscle, but after this time it was predominantly from viscera. Intracellular potassium levels were low but did not deteriorate further after hemodynamic stability had been reached. There was a reprioritization of hepatic protein synthesis that was obligatory and independent of changes in total body protein. The cytokine responses demonstrated the complexity, redundancy, and overlap of mediators. CONCLUSIONS: The period of hypermetabolism in severely septic patients is similar to that previously described, but the fluid changes are larger and the protein loss is greater. Protein loss early on is predominantly from muscle, thereafter from

  10. Development of decision making: sequential versus integrative rules.

    PubMed

    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 decision-making rules. In the Gambling Machine Task, participants choose between options that differ in three dimensions: frequency of loss, amount of loss, and certain gain. The task was administered to 231 children and adolescents (age range=8-17 years). Latent group analysis of their performance allowed precise classification of the underlying decision rules. The majority of participants used sequential decision rules, and the number of evaluated dimensions in these rules increased with age. Integrative rule use decreased with age. We discuss these results in light of traditional developmental theories and fuzzy trace theory.

  11. 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.

  12. 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.

  13. Finding a Path for Segmentation Through Sequential Learning.

    PubMed

    Wang, Hongzhi; Cao, Yu; Syed-Mahmood, Tanveer F

    2015-01-01

    Sequential learning techniques, such as auto-context, that applies the output of an intermediate classifier as contextual features for its subsequent classifier has shown impressive performance for semantic segmentation. We show that these methods can be interpreted as an approximation technique derived from a Bayesian formulation. To improve the effectiveness of applying this approximation technique, we propose a new sequential learning approach for semantic segmentation that solves a segmentation problem by breaking it into a series of simplified segmentation problems. Sequentially solving each of the simplified problems along the path leads to a more effective way for solving the original segmentation problem. To achieve this goal, we also propose a learning-based method to generate simplified segmentation problems by explicitly controlling the complexities of the modeling classifiers. We report promising results on the 2013 SATA canine leg muscle segmentation dataset. PMID:26221697

  14. Hemodynamic results of acute thoracic aortomyoplasty in a canine model: comparison of stimulation regimens.

    PubMed

    Dumcius, Arimantas; Bavarskis, Egidijus; Bytautas, Algimantas; Chekanov, Valeri

    2003-01-01

    Our previous investigations in a sheep model demonstrated that when electrical stimulation (ES) was applied to a newly mobilized latissimus dorsi muscle (LDM) in a work-rest regimen and at a rate of 15 contractions per minute, it did not damage this muscle. This regimen was used twice during a 60 minute period, once a day for 16 days, with no LDM damage. The goal of our current investigation was to apply this regimen in studies of acute thoracic aortomyoplasty. In two experimental groups, we mobilized the LDM but left it in situ. Two hours later, contractile force (CF) testing (20 g/kg preload, six impulses per burst) was performed until CF dropped to 50% of baseline. Recovery time needed to completely restore CF was calculated. In one group (six sheep), we applied continuous ES; in another (six sheep), we applied ES in a work-rest regimen (1 min work, 1 min rest). In two other groups of six dogs each, aortomyoplasty was performed; the LDM flap was subjected to ES immediately postoperatively (six impulses per burst; ventricular-LDM delay, 290 ms). Again, one group received continuous ES, and the other received work-rest ES. In the mobilized LDM under continuous ES, CF decreased to 50% of baseline values after 52 +/- 8 minutes, and returned to baseline after 84 +/- 16 minutes of rest. Under the work-rest regimen, this decrease took 105 +/- 8 minutes, and the return to baseline took 25 +/- 6 minutes (p < 0.05). In LDM subjected to work-rest ES, light microscopy revealed no additional damage to LDM tissue than was seen immediately after mobilization. However, LDM subjected to continuous ES had evidence of increased basophilic degeneration and wavy fibers. After acute thoracic aortomyoplasty, assisted hemodynamic values under the continuous ES exceeded unassisted values for only 40 minutes, compared with 100 minutes for work-rest ES (p < 0.05). When counterpulsation was completed, for continuous ES, recovery time to baseline was 96 +/- 9 minutes; for work-rest ES, it

  15. Sequential extrusion-microwave pretreatment of switchgrass and big bluestem.

    PubMed

    Karunanithy, C; Muthukumarappan, K; Gibbons, W R

    2014-02-01

    Developing an effective and economical biomass pretreatment method is a significant roadblock to meeting the ever growing demand for transportation fuels. Earlier studies with different feedstocks revealed that in the absence of chemicals, neither extrusion nor microwave could be standalone pretreatments. However, there is potential that the advantages of these individual methods can be harnessed in a sequential pretreatment process. Accordingly, switchgrass and big bluestem were extruded and then subject to microwave pretreatment, under optimal conditions that had been separately determined in prior studies. Pretreated biomass was then subject to enzymatic hydrolysis to understand the effectiveness of the sequential pretreatment on sugar recovery and generation of fermentation inhibitors. Statistical analysis confirmed that moisture content, microwave power level, and exposure time (and their interactions) had significant influence on sugar recovery. Sequential pretreatment of switchgrass (25% moisture, 450W and 2.5min) resulted in a maximum glucose, xylose, and total sugar recovery of 52.6%, 75.5%, and 59.2%, respectively. This was higher by 1.27 and 2.71, 1.21 and 4.60, and 1.25 and 2.87 times compared to extrusion alone and the unpretreated control, respectively. The same sequential pretreatment conditions achieved maximum glucose, xylose, and total sugar recovery of 83.2%, 92.1%, and 68.1%, respectively, for big bluestem. This was 1.14 and 4.1, 1.18 and 2.7, and 1.20 and 3.0 times higher than extrusion alone and the unpretreated control, respectively. This sequential pretreatment process did not aggravate acetic acid formation over levels observed with the individual pretreatments. Furthermore, furfural, HMF, and formic acid were not detected in any of the treatments. Although the sequential pretreatment process enhanced sugar recovery without increasing the levels of potential fermentation inhibitors, the increased energy input for the microwave treatment may

  16. Fluorescence sensor for sequential detection of zinc and phosphate ions

    NASA Astrophysics Data System (ADS)

    An, Miran; Kim, Bo-Yeon; Seo, Hansol; Helal, Aasif; Kim, Hong-Seok

    2016-12-01

    A new, highly selective turn-on fluorescent chemosensor based on 2-(2‧-tosylamidophenyl)thiazole (1) for the detection of zinc and phosphate ions in ethanol was synthesized and characterized. Sensor 1 showed a high selectivity for zinc compared to other cations and sequentially detected hydrogen pyrophosphate and hydrogen phosphate. The fluorescence mechanism can be explained by two different mechanisms: (i) the inhibition of excited-state intramolecular proton transfer (ESIPT) and (ii) chelation-induced enhanced fluorescence by binding with Zn2 +. The sequential detection of phosphate anions was achieved by the quenching and subsequent revival of ESIPT.

  17. 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.

  18. 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

  19. 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.

  20. Improved treatment of a brain-tumor model. Part 2: Sequential therapy with BCNU and 5-fluorouracil.

    PubMed

    Gerosa, M A; Dougherty, D V; Wilson, C B; Rosenblum, M L

    1983-03-01

    A combination chemotherapy regimen for brain tumors was developed, based on investigations of the survival of animals harboring the intracerebral 9L rat brain-tumor model and on analyses of their clonogenic tumor cells. Fischer 344 rats harboring 9L brain tumors were treated with 2-day courses of 5-fluorouracil (5-FU), in order to expose all cycling tumor cells to the drug during DNA synthesis and achieve maximum anti-tumor activity for this cell-cycle-specific anti-metabolite. Although a 74% cell kill was obtained for a total dose of 45 mg/kg or greater, animal life span was not increased over that of untreated tumor-bearing controls. However, when 5-FU (48 to 96 mg/kg total dose over 2 days) was administered after a single LD10 dose of BCNU (13.3 mg/kg), additive cell kill was suggested. In three large series, long-term animal survivors and occasional tumor cures were observed with this drug combination, a result never observed following BCNU alone. Schedule dependency was not apparent. A previously published protocol for treating recurrent malignant gliomas with sequential courses of BCNU and 5-FU was partially planned based upon these initial observations. Anti-tumor activity with the combination of drugs was superior to therapy with BCNU alone. Both animal and human studies confirm that, contrary to presently accepted oncological tenets, a chemotherapeutic agent that kills significant numbers of tumor cells but is clinically ineffective when given alone might, nevertheless, be useful in combination therapy regimens.

  1. 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

  2. Sanguinaria toothpaste and oral rinse regimen clinical efficacy in short- and long-term trials.

    PubMed

    Kuftinec, M M; Mueller-Joseph, L J; Kopczyk, R A

    1990-01-01

    Short- and long-term testing of sanguinaria toothpaste and oral rinse used individually have yielded both positive and negative results. This review evaluates the results of a number of clinical trials testing the regimen use of sanguinaria products for periods ranging from 14 days to six months. Review of these trials establishes the clinical efficacy of the two products in combination. The regimen approach produces consistently positive reductions in plaque, gingival inflammation and bleeding parameters for up to six months with no adverse hard tissue effects and only one reversible adverse soft tissue effect observed among the 260 subjects tested. In addition, no adverse microbiological shifts in the normal oral flora were observed.

  3. Medication regimens of frail older adults after discharge from home healthcare.

    PubMed

    Lancaster, Rachelle; Marek, Karen Dorman; Bub, Linda Denison; Stetzer, Frank

    2014-10-01

    The purpose of this study was to examine the number and types of discrepancy errors present after discharge from home healthcare in older adults at risk for medication management problems following an episode of home healthcare. More than half of the 414 participants had at least one medication discrepancy error (53.2%, n = 219) with the participant's omission of a prescribed medication (n = 118, 30.17%) occurring most frequently. The results of this study support the need for home healthcare clinicians to perform frequent assessments of medication regimens to ensure that the older adults are aware of the regimen they are prescribed, and have systems in place to support them in managing their medications.

  4. Use of class I histone deacetylase inhibitor romidepsin in combination regimens.

    PubMed

    Petrich, Adam; Nabhan, Chadi

    2016-08-01

    Histone deacetylase (HDAC) inhibitors are epigenetic-modifying agents that have shown promise as anticancer therapies. Several HDAC inhibitors have been approved by the US Food and Drug Administration (FDA) as single-agent therapies to treat T-cell lymphoma. The synergistic combination of HDAC inhibitors with other anticancer agents has the potential to constitute treatment regimens with enhanced efficacy. Romidepsin is a structurally unique, potent, bicyclic class 1 selective HDAC inhibitor approved by the FDA for the treatment of patients with peripheral T-cell lymphoma who have had at least 1 prior therapy and patients with cutaneous T-cell lymphoma who have had at least 1 prior systemic therapy. Here, we review data that support the use of romidepsin in combination with other anticancer agents for the treatment of various malignancies. Promising results have emerged from early clinical studies, supporting the potential for romidepsin combination regimens to constitute safe and effective treatments for cancer.

  5. Use of class I histone deacetylase inhibitor romidepsin in combination regimens

    PubMed Central

    Petrich, Adam; Nabhan, Chadi

    2016-01-01

    Abstract Histone deacetylase (HDAC) inhibitors are epigenetic-modifying agents that have shown promise as anticancer therapies. Several HDAC inhibitors have been approved by the US Food and Drug Administration (FDA) as single-agent therapies to treat T-cell lymphoma. The synergistic combination of HDAC inhibitors with other anticancer agents has the potential to constitute treatment regimens with enhanced efficacy. Romidepsin is a structurally unique, potent, bicyclic class 1 selective HDAC inhibitor approved by the FDA for the treatment of patients with peripheral T-cell lymphoma who have had at least 1 prior therapy and patients with cutaneous T-cell lymphoma who have had at least 1 prior systemic therapy. Here, we review data that support the use of romidepsin in combination with other anticancer agents for the treatment of various malignancies. Promising results have emerged from early clinical studies, supporting the potential for romidepsin combination regimens to constitute safe and effective treatments for cancer. PMID:27118119

  6. 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.

  7. Efficacy and Safety of a Steroid-Free Immunosuppressive Regimen after Liver Transplantation for Hepatocellular Carcinoma

    PubMed Central

    Wei, Qiang; Xu, Xiao; Wang, Chao; Zhuang, Runzhou; Zhuang, Li; Zhou, Lin; Xie, Haiyang; Wu, Jian; Zhang, Min; Shen, Yan; Wang, Weilin; Zheng, Shusen

    2016-01-01

    Background/Aims We aimed to evaluate the efficacy and safety of an immunosuppressive regimen without steroids after liver transplantation (LT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods Sixty-six HCC patients who underwent an immunosuppressive regimen without steroids after LT were enrolled in the steroid-free group. The preoperative characteristics and postoperative outcomes of these patients were compared with those of 132 HCC recipients who were placed on an immunosuppressive regimen using steroids (steroid group). The incidence of acute rejection, HBV recurrence, infection, and new-onset diabetes mellitus and the overall and tumor-free survival rates were compared between the two groups. Results Differences were not observed in the 1-year (83.3% vs 97.0%, p=0.067), 3-year (65.4% vs 75.8%, p=0.067) or 5-year (56.3% vs 70.7%, p=0.067) patient survival rates or in the 1-year (62.1% vs 72.7%, p=0.067), 3-year (49.8% vs 63.6%, p=0.067) or 5-year (48.6% vs 63.6%, p=0.067) tumor-free survival rates between the two groups, respectively. In the steroid-free group, the patients who fulfilled the Milan criteria had higher overall and tumor-free survival rates than those in the steroid group (p<0.001). The prevalence of HBV recurrence (3.0% vs 13.6%, p=0.02) was significantly lower in the steroid-free group compared with the steroid group. Conclusions After LT, an immunosuppressive regimen without steroids could be a safe and feasible treatment for HBV-related HCC patients, thus resulting in the reduction of HBV recurrence. Based on the observed survival rates, patients who fulfill the Milan criteria may derive benefits from steroid-free immunosuppression. PMID:27074818

  8. Essential fatty acid deficiency while a patient receiving fat regimen total parenteral nutrition

    PubMed Central

    Roongpisuthipong, Wanjarus; Phanachet, Pariya; Roongpisuthipong, Chulaporn; Rajatanavin, Natta

    2012-01-01

    A 32-year-old man was diagnosed with lymphoma and underwent Billroth’s II operation because of upper gastrointestinal haemorrhage. Although the patient received fat regimen total parenteral nutrition (TPN), the patient developed typical skin rash of essential fatty acid deficiency after 2 weeks of starting TPN. The diagnosis was confirmed by biochemical and histological analyses. After increasing the lipid infusion, the rash was gradually improved with complete resolution after 19 days. PMID:22707694

  9. 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

  10. Immunoparesis status in immunoglobulin light chain amyloidosis at diagnosis affects response and survival by regimen type

    PubMed Central

    Muchtar, Eli; Dispenzieri, Angela; Kumar, Shaji K.; Dingli, David; Lacy, Martha Q.; Buadi, Francis K.; Hayman, Suzanne R.; Kapoor, Prashant; Leung, Nelson; Chakraborty, Rajshekhar; Russell, Stephen; Lust, John A.; Lin, Yi; Go, Ronald S.; Zeldenrust, Steven; Kyle, Robert A.; Rajkumar, S. Vincent; Gertz, Morie A.

    2016-01-01

    Clinical tools to guide in the appropriate treatment selection in immunoglobulin light chain (AL) amyloidosis are not well developed. We evaluated the response and outcome for various regimens at first-line treatment (n=681) and first progression (n=240) stratified by the immunoparesis status at diagnosis. Immunoparesis was assessed by the average relative difference of the uninvolved immunoglobulins, classifying patients into a negative average relative difference (i.e. significant immunoparesis) or a positive average relative difference (no/modest immunoparesis). Treatment was categorized as autologous stem cell transplant and four non-transplant regimens (melphalan-based; bortezomib-based, immunomodulatory drug-based and dexamethasone alone). Patients with significant immunoparesis who underwent stem cell transplant had a significantly lower rate of very good partial response or better response (58%), progression-free survival (median 30 months) and overall survival (108 months), compared to those without significant immunoparesis (80%, 127 months, median not reached, respectively; P<0.001 for all comparisons). Among the non-transplant regimens, melphalan resulted in an unfavorable progression-free survival (11 vs. 27 months; P<0.001) and overall survival (30 vs. 74 months; P=0.001) in patients with significant immunoparesis compared to those without significant immunoparesis. In contrast, no significant difference in outcomes between the immunoparesis groups was seen for those treated with bortezomib or immunomodulatory drugs. At first progression, immunoparesis status did not impact response or survival of any regimen. Melphalan at first-line provided poorer outcomes for patients with significant immunoparesis, while bortezomib or immunomodulatory drugs were more likely to overcome the adverse prognosis associated with significant immunoparesis. PMID:27479823

  11. Nanoparticulate delivery of novel drug combination regimens for the chemoprevention of colon cancer

    PubMed Central

    KANTHAMNENI, NAVEEN; CHAUDHARY, ABHISHEK; WANG, JEFFREY; PRABHU, SUNIL

    2010-01-01

    The purpose of this work was to assess synergistic inhibitory responses of a novel chemopreventive combination regimen of drugs namely, aspirin in combination with calcium and folic acid on two human colon cancer cell lines, HT-29 and SW-480. Subsequently, based on positive responses, nanotechnology-based formulations were developed for the targeted delivery of these combinatorial regimens to the colon for the chemoprevention of colon cancer. Additionally, conventional drug formulations using controlled release polymers chitosan, pectin and hydroxypropyl methylcellulose (HPMC) were tested for release of the drugs, for comparison purposes. Chemopreventive combination regimens demonstrated significant synergistic efficacy in both cell lines from XTT assay studies, when compared to the effects of individual agents. Approximately 45% decrease in cell viability for aspirin (15 mM) and calcium (30 mM) mixtures was observed in HT-29 cell lines, compared to ~55% decrease by the same combination in SW-480 cell lines. With combinations of aspirin (5 mM) and folic acid (1.5 mM), HT-29 cells demonstrated a 30% decrease in cell viability compared to ~38% decrease in the SW-480 cell line. Overall, all drug combinations demonstrated significant synergistic responses in the cell lines tested with the SW-480 cell line being more significantly affected by the drug regimens than the HT-29 cell line. Drug encapsulated nanoparticles demonstrated a spherical morphology, <125 nm average particle size (aspirin and folic acid) of nanoparticles and encapsulation efficiencies in the range of 80–91%. Drug release from nanoparticles was controlled with ~60% of the original amount released over a 96 h period. Conventional formulations exhibited faster kinetics of drug release when compared to the PLGA nanoparticles. Overall, the cell line studies demonstrate, for the first time, the ability of novel chemopreventive combinations to inhibit the growth of colon cancer cells whereas the

  12. Risk of Cardiovascular Events Among Patients Initiating Efavirenz-Containing Versus Efavirenz-Free Antiretroviral Regimens

    PubMed Central

    Rosenblatt, Lisa; Farr, Amanda M.; Johnston, Stephen S.; Nkhoma, Ella T.

    2016-01-01

    Background. Efavirenz (EFV), an antiretroviral medication used to treat human immunodeficiency virus (HIV) infection, can increase lipid levels. Because hyperlipidemia is associated with increased risk for cardiovascular (CV) events, this study compared the risk of CV events in patients initiating EFV-containing vs EFV-free antiretroviral regimens. Methods. Antiretroviral-naive HIV-positive (HIV+) patients ages 18–64 were selected from commercial and Medicaid insurance claims databases. Patients with ≥1 claim for antiretroviral medications between January 1, 2007 and December 31, 2013 were classified into 2 cohorts: EFV-containing or EFV-free regimens. Patients were required to have 6 months of continuous enrollment before initiation, with no evidence of a CV event during this time. Patients were observed from initiation until the occurrence of a CV event, disenrollment, or study end. Cardiovascular events were identified through diagnosis or procedure codes for myocardial infarction, stroke, percutaneous coronary intervention, or coronary artery bypass graft. We calculated unadjusted incidence rates (IRs) and fit propensity-score-weighted Cox proportional hazards models. Results. There were 22 212 patients (11 978 EFV-containing and 10 234 EFV-free) identified in the commercial database and 7400 patients identified (2943 EFV-containing and 4457 EFV-free) in the Medicaid database. Cardiovascular events were rare (commercial IR = 396 per 100 000 person-years; Medicaid IR = 973 per 100 000 person-years). In propensity-score-weighted models, hazards of CV events were significantly lower for EFV-containing regimens in the commercial database (hazard ratio [HR] = 0.68; 95% confidence interval [CI], .49–.93) No significant difference was found in the Medicaid database (HR = 0.83; 95% CI, .58–1.19). Conclusions. This analysis found no evidence of increased risk of CV events among HIV+ patients initiating EFV-containing regimens. PMID:27186585

  13. Phase I and pharmacological study of sequential intravenous topotecan and oral etoposide.

    PubMed Central

    Herben, V. M.; ten Bokkel Huinink, W. W.; Dubbelman, A. C.; Mandjes, I. A.; Groot, Y.; van Gortel-van Zomeren, D. M.; Beijnen, J. H.

    1997-01-01

    We performed a phase I and pharmacological study to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of a cytotoxic regimen of the novel topoisomerase I inhibitor topotecan in combination with the topoisomerase II inhibitor etoposide, and to investigate the clinical pharmacology of both compounds. Patients with advanced solid tumours were treated at 4-week intervals, receiving topotecan intravenously over 30 min on days 1-5 followed by etoposide given orally twice daily on days 6-12. Topotecan-etoposide dose levels were escalated from 0.5/20 to 1.0/20, 1.0/40, and 1.25/40 (mg m-2 day-1)/(mg bid). After encountering DLT, additional patients were treated at 3-week intervals with the topotecan dose decreased by one level to 1.0 mg m-2 and etoposide administration prolonged from 7 to 10 days to allow further dose intensification. Of 30 patients entered, 29 were assessable for toxicity in the first course and 24 for response. The DLT was neutropenia. At doses of topotecan-etoposide 1.25/40 (mg m-2)/(mg bid) two out of six patients developed neutropenia grade IV that lasted more than 7 days. Reduction of the treatment interval to 3 weeks and prolonging etoposide dosing to 10 days did not permit further dose intensification, as a time delay to retreatment owing to unrecovered bone marrow rapidly emerged as the DLT. Post-infusion total plasma levels of topotecan declined in a biphasic manner with a terminal half-life of 2.1 +/- 0.3 h. Total body clearance was 13.8 +/- 2.7 l h-1 m-2 with a steady-state volume of distribution of 36.7 +/- 6.2 l m-2. N-desmethyltopotecan, a metabolite of topotecan, was detectable in plasma and urine. Mean maximal concentrations ranged from 0.23 to 0.53 nmol l-1, and were reached at 3.4 +/- 1.0 h after infusion. Maximal etoposide plasma concentrations of 0.75 +/- 0.54 and 1.23 +/- 0.57 micromol l-1 were reached at 2.4 +/- 1.2 and 2.3 +/- 1.0 h after ingestion of 20 and 40 mg respectively. The topotecan area under

  14. In vivo prostacyclin biosynthesis and effects of different aspirin regimens in patients with essential thrombocythaemia.

    PubMed

    Cavalca, V; Rocca, B; Squellerio, I; Dragani, A; Veglia, F; Pagliaccia, F; Porro, B; Barbieri, S S; Tremoli, E; Patrono, C

    2014-07-01

    Essential thrombocythaemia (ET) is characterised by enhanced platelet generation and thrombosis. Once daily (od) aspirin incompletely inhibits platelet thromboxane (TX)A2 production in ET. A twice daily (bid) dosing is necessary to fully inhibit TXA2. Whether this dosing regimen affects in vivo prostacyclin (PGI2) biosynthesis is unknown. PGI2 biosynthesis was characterised in 50 ET patients on enteric-coated (EC) aspirin 100 mg od, by measuring its urinary metabolite, 2,3-dinor-6-keto-PGF1α (PGI-M). Moreover, in a crossover study 22 patients poorly responsive to standard aspirin based on serum TXB2 levels (≥4 ng/ml) were randomised to different seven-day aspirin regimens: EC aspirin 100 mg od, 100 mg bid, 200 mg od, or plain aspirin 100 mg od. PGI-M measured 24 hours after the last aspirin intake (EC, 100 mg od) was similar in patients and healthy subjects both on (n=10) and off (n=30) aspirin. PGI-M was unrelated to in vivo TXA2 biosynthesis, and not affected by EC aspirin 100 mg bid or 200 mg od as compared to EC 100 mg od. PGI2 biosynthesis in aspirin-treated ET patients appears unrelated to TXA2 biosynthesis, and not affected by an improved aspirin regimen, demonstrating its vascular safety for future trials. PMID:24671522

  15. Utilization of a Preemptive, Multimodal Analgesic Regimen in Adult Ambulatory Septoplasty Patients: A Quality Improvement Project.

    PubMed

    Morgan, Brett; Stanik-Hutt, Julie

    2015-01-01

    This paper describes a quality improvement project designed to decrease postoperative pain, decrease post-operative nausea and vomiting (PONV), decrease time in the recovery room, and increase patient satisfaction in adult ambulatory septoplasty patients using a multimodal, preemptive analgesic regimen. The project was conducted in a community hospital setting with nine operating rooms, and a twenty one bed recovery room. Project participants included certified registered nurse anesthetists, anesthesiologists, operating room nurses, recovery room nurses, and otolaryngology surgeons. Following a period of departmental education, adult patients scheduled for outpatient septoplasty surgery received a preoperative regimen of medications that included gabapentin, celecoxib, and acetaminophen. Using a pre-post test design, (intervention group n = 17, non-intervention group n = 17) data was collected from patient and analyzed using SPSS version 18.0. The change in practice resulted in a significant decrease in pain scores in the recovery room and on discharge from the recovery room. In addition, patients who received the preemptive regimen also required significantly fewer opioid medications and were ready to be discharged from the recovery room in less time.

  16. Possible fractionated regimens for image-guided intensity-modulated radiation therapy of large arteriovenous malformations

    NASA Astrophysics Data System (ADS)

    Qi, X. Sharon; Schultz, Christopher J.; Li, X. Allen

    2007-09-01

    The aim of this study was to estimate a plausible α/β ratio for arteriovenous malformations (AVMs) based on reported clinical data, and to design possible fractionation regimens suitable for image-guided intensity-modulated radiation therapy (IG-IMRT) for large AVMs based on the newly obtained α/β ratio. The commonly used obliteration rate (OR) for AVMs with a three year angiographic follow-up from many institutes was fitted to linear-quadratic (LQ) formalism and the Poisson OR model. The determined parameters were then used to calculate possible fractionation regimens for IG-IMRT based on the concept of a biologically effective dose (BED) and an equivalent uniform dose (EUD). The radiobiological analysis yields a α/β ratio of 2.2 ± 1.6 Gy for AVMs. Three sets of possible fractionated schemes were designed to achieve equal or better biological effectiveness than the single-fraction treatments while maintaining the same probability of normal brain complications. A plausible α/β ratio was derived for AVMs and possible fractionation regimens that may be suitable for IG-IMRT for large AVM treatment are proposed. The sensitivity of parameters on the calculation was also studied. The information may be useful to design new clinical trials that use IG-IMRT for the treatment of large AVMs.

  17. Evaluating the Survival Rate and the Secondary Malignancies after Treating Hodgkin's Lymphoma Patients with Chemotherapy Regimens

    PubMed Central

    Ahmadzadeh, Ahmad; Yekaninejad, Mir Saeed; Jalili, Mohamad H; Bahadoram, Mohammad; Efazat, Mehdi; Seghatoleslami, Mohammad; Yazdi, Fatemeh; Mahdipour, Mozhdeh; Valizadeh, Armita

    2014-01-01

    In this study we surveyed the average survival time of the treated Hodgkin's lymphoma patients and also the side effects and malignancies occurring secondary to the treatment. This is a retrospective study of patients referring to Ahwaz's Shafa hospital in a period of 10 years diagnosed with Hodgkin's lymphoma without any age restriction. After gathering all their data, we calculated their survival rate and the chance for a relapse and the secondary malignancies. 389 patients were included in the study with an average age of 27.5 years old and they had received only chemotherapy regimens. 87.9% of them had been treated by ABVD and 12.1 % by Stanford V regimen. 23.1% of them experienced a relapse and 13.1% of all patients, passed away during the study. Secondary malignancies were observed in 11 cases. An overall mean survival time of 295.31 months was resulted. The secondary malignancies after treating Hodgkin's lymphoma patients are different between chemotherapy regimens and chemotherapy – radiotherapy. PMID:24800035

  18. Effects of an overfeeding regimen--the affective component of the sweet sensation.

    PubMed

    Fantino, M; Baigts, F; Cabanac, M; Apfelbaum, M

    1983-09-01

    In some isolated parts of North Africa, there persists an ancient Berber custom of imposing an overfeeding regimen on young girls before marriage, to achieve an obesity which is regarded as aesthetically pleasing. We have studied the effect of such a regimen, lasting 12--16 weeks, on blood lipids and on the affective reactions to sweet tastes in nine subjects. It is known that the pleasantness of alimentary cues i.e., the feeding behaviour, depends on the subject's nutritional state. Only three subjects gained weight (by 3,5 and 8 kg), in spite of the strong pressure to overeat. No change in plasma lipid concentrations were observed. Nevertheless, at the end of the regimen every subject showed a highly significant decrease in the rated pleasantness of sweet stimuli when they were tested fasting. However, the reduction in sweet pleasantness induced by ingestion of a 200 ml load of 1.4 M glucose solution was not changed by the overfeeding. Thus, pressure to overfeed can reduce hunger, as seen in the attractiveness of sweet foods in fasted subjects, without modifying glucose-induced satiety. PMID:6582799

  19. Efficacy of cisplatin, 5-fluorouracil, and paclitaxel regimen for carcinoma of the esophagus.

    PubMed

    Belani, C P; Luketich, J D; Landreaneau, R J; Kim, R; Ramanathan, R K; Day, R; Ferson, P F; Keenan, R J; Posner, M; Seeger, J; Lembersky, B

    1997-12-01

    Eighteen patients with esophageal carcinoma (16 adenocarcinoma, two squamous cell carcinoma) were treated with two cycles of induction chemotherapy consisting of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 (3-hour infusion), cisplatin 20 mg/m2/d x 4 days, and 5-fluorouracil 1 g/m2/d (continuous infusion x 4 days) separated by a 28-day interval before surgical resection. After resection, patients received two more cycles of the same regimen. A thorough staging evaluation was performed before patients were enrolled in the study. The salient chemotherapy toxicities included grade 3 nausea (two patients), grade 3 vomiting (two patients), grades 3 and 4 diarrhea (one patient each), and grades 3 and 4 neutropenia (two and 10 patients, respectively). No deaths occurred due to toxicity. Surgical resection was attempted in all 18 patients (100%) after two cycles of induction chemotherapy. Esophageal resection was successfully completed in 17 patients. Liver metastases were noted at laparotomy in the one patient who subsequently did not undergo esophageal resection. Surgical complications were minor, and no postoperative deaths occurred. Fifteen patients received two additional cycles of the paclitaxel/5-fluorouracil/cisplatin regimen postoperatively, two received only one cycle, and one refused further therapy. Of 15 patients alive, 14 show no evidence of disease. The 1-year actuarial survival rate of this group of patients is 82%. In conclusion, the paclitaxel/5-fluorouracil/cisplatin combination is well tolerated and is an active regimen in esophageal carcinoma. PMID:9427275

  20. Food allergen selective thermal processing regimens may change oral tolerance in infancy.

    PubMed

    Kosti, R I; Triga, M; Tsabouri, S; Priftis, K N

    2013-01-01

    Food allergy can be considered a failure in the induction of oral tolerance. Recently, great interest has been focused on understanding the mechanisms and the contributing factors of oral tolerance development, hoping for new definitive interventions in the prevention and treatment of food allergy. Given that food processing may modify the properties and the nature of dietary proteins, several food processing methods could affect the allergenicity of these proteins and consequently may favour oral tolerance induction to food allergic children. Indeed, effective thermal food processing regimens of altering food proteins to reduce allergenicity have been recently reported in the literature. This article is mainly focused on the effect of selective thermal processing regimens on the main infant allergenic foods, with a potential clinical relevance on their allergenicity and therefore on oral tolerance induction. In the light of recent findings, the acquisition of tolerance in younger age and consequently the ability of young children to "outgrow" food allergy could be achieved through the application of selective thermal processing regimens on certain allergenic foods. Therefore, the ability of processed foods to circumvent clinical disease and at the same time to have an impact on the immune system and facilitate tolerance induction could be invaluable as a component of a successful therapeutic strategy. The opening in the new avenues of research in the use of processed foods in clinical practice for the amelioration of the impact on the quality of life of patients and possibly in food allergy prevention is warranted.

  1. 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

  2. Impact of tacrolimus and mycophenolate mofetil regimen vs. a conventional therapy with steroids on cardiovascular risk in liver transplant patients.

    PubMed

    Cuervas-Mons, Valentín; Herrero, J Ignacio; Gomez, Miguel A; González-Pinto, Ignacio; Serrano, Trinidad; de la Mata, Manuel; Fabregat, Joan; Gastaca, Mikel; Bilbao, Itxarone; Varo, Evaristo; Sánchez-Antolín, Gloria; Rodrigo, Juan; Espinosa, María Dolores

    2015-08-01

    The aim of this study was to evaluate the impact of a steroid-free regimen with tacrolimus and mycophenolate mofetil (modified therapy) vs. a standard regimen of tacrolimus and steroids on the cardiovascular risk score of liver transplant recipients. Patients who received a liver transplant were randomized to a modified therapy (n = 58) or a standard regimen (n = 59). Both groups were balanced at baseline, except for a higher prevalence of diabetes mellitus (DM) (p < 0.01) and a higher serum creatinine concentration (p < 0.05) in the modified therapy group. After 12 months, the prevalence of new-onset DM, arterial hypertension, hypercholesterolemia, hypertriglyceridemia, and changes in cardiovascular risk factors was similar in both groups. The increase in serum creatinine (mg/dL) compared to baseline at one yr post-transplantation was numerically lower in the modified therapy group (0.22 ± 0.42) than in the standard regimen group (0.41 ± 0.67) (p = 0.068). Although estimated cardiovascular risk score did not vary significantly compared to baseline in either group, there was a slight reduction in the modified regimen (-0.27 ± 2.87) vs. a mild increase (0.17 ± 2.94) in the standard regimen (p = 0.566). In conclusion, a steroid-free regimen with tacrolimus and mycophenolate mofetil was associated with a trend toward better preservation of kidney function and reduction of cardiovascular risk score.

  3. 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.

  4. Sequential organ failure assessment scoring and prediction of patient's outcome in Intensive Care Unit of a tertiary care hospital

    PubMed Central

    Jain, Aditi; Palta, Sanjeev; Saroa, Richa; Palta, Anshu; Sama, Sonu; Gombar, Satinder

    2016-01-01

    Background and Aims: The objective was to determine the accuracy of sequential organ failure assessment (SOFA) score in predicting outcome of patients in Intensive Care Unit (ICU). Material and Methods: Forty-four consecutive patients between 15 and 80 years admitted to ICU over 8 weeks period were studied prospectively. Three patients were excluded. SOFA score was determined 24 h postadmission to ICU and subsequently every 48 h for the first 10 days. Patients were followed till discharge/death/transfer from the ICU. Initial SOFA score, highest and mean SOFA scores were calculated and correlated with mortality and duration of stay in ICU. Results: The mortality rate was 39% and the mean duration of stay in the ICU was 9 days. The maximum score in survivors (3.92 ± 2.17) was significantly lower than nonsurvivors (8.9 ± 3.45). The initial SOFA score had a strong statistical correlation with mortality. Cardiovascular score on day 1 and 3, respiratory score on day 7, and coagulation profile on day 3 correlated significantly with the outcome. Duration of the stay did not correlate with the survival (P = 0.461). Conclusion: SOFA score is a simple, but effective prognostic indicator and evaluator for patient progress in ICU. Day 1 SOFA can triage the patients into risk categories. For further management, mean and maximum score help determine the severity of illness and can act as a guide for the intensity of therapy required for each patient. PMID:27625487

  5. 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

    Lu, Xiaofan; Li, Ya; Li, Jiansheng; 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

  6. 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

  7. 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

  8. 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…

  9. 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…

  10. Multivariate Multinomial Logit Models for Dyadic Sequential Interaction Data

    ERIC Educational Resources Information Center

    de Rooij, Mark; Kroonenberg, Pieter M.

    2003-01-01

    The analysis of discrete dyadic sequential behavior and, in particular, the problem of forecasting future behavior from current and past behavior in such data is the main theme of the present article. We propose to use multivariate multinomial logit models and the potential of which will be demonstrated with data on Imagery play therapy. In such a…

  11. Multiple-Category Classification Using a Sequential Probability Ratio Test.

    ERIC Educational Resources Information Center

    Spray, Judith A.

    Sequential probability ratio testing (PRT), which usually is applied in situations requiring a decision between two simple hypotheses or a single decision point, is extended to include situations involving k decision points and [(k + 1)-choose-2] sets of simultaneous, simple hypotheses, where k>1. The multiple-decision point or multiple-category…

  12. 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…

  13. Making Career Decisions--A Sequential Elimination Approach.

    ERIC Educational Resources Information Center

    Gati, Itamar

    1986-01-01

    Presents a model for career decision making based on the sequential elimination of occupational alternatives, an adaptation for career decisions of Tversky's (1972) elimination-by-aspects theory of choice. The expected utility approach is reviewed as a representative compensatory model for career decisions. Advantages, disadvantages, and…

  14. The sequential structure of brain activation predicts skill.

    PubMed

    Anderson, John R; Bothell, Daniel; Fincham, Jon M; Moon, Jungaa

    2016-01-29

    In an fMRI study, participants were trained to play a complex video game. They were scanned early and then again after substantial practice. While better players showed greater activation in one region (right dorsal striatum) their relative skill was better diagnosed by considering the sequential structure of whole brain activation. Using a cognitive model that played this game, we extracted a characterization of the mental states that are involved in playing a game and the statistical structure of the transitions among these states. There was a strong correspondence between this measure of sequential structure and the skill of different players. Using multi-voxel pattern analysis, it was possible to recognize, with relatively high accuracy, the cognitive states participants were in during particular scans. We used the sequential structure of these activation-recognized states to predict the skill of individual players. These findings indicate that important features about information-processing strategies can be identified from a model-based analysis of the sequential structure of brain activation. PMID:26707716

  15. Contextual view of Warner's Ranch. Second of three sequential views ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Contextual view of Warner's Ranch. Second of three sequential views (from west to east) of the buildings in relation to the surrounding geography. Ranch house and trading post/barn on left. Note approximate location of Overland Trail crossing left to right. Camera facing north. - Warner Ranch, Ranch House, San Felipe Road (State Highway S2), Warner Springs, San Diego County, CA

  16. Contextual view of Warner's Ranch. First of three sequential views ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Contextual view of Warner's Ranch. First of three sequential views (from west to east) of the buildings in relation to the surrounding geography. Ranch House on right. Note approximate locations of Overland Trail on right and San Diego cutoff branching off to left. Camera facing northwest. - Warner Ranch, Ranch House, San Felipe Road (State Highway S2), Warner Springs, San Diego County, CA

  17. Contextual view of Warner's Ranch. Third of three sequential views ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Contextual view of Warner's Ranch. Third of three sequential views (from west to east) of the buildings in relation to the surrounding geography. Note approximate location of Overland Trail crossing left to right. Camera facing northeast - Warner Ranch, Ranch House, San Felipe Road (State Highway S2), Warner Springs, San Diego County, CA

  18. 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.

  19. 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)

  20. 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…

  1. A Sequential and Comprehensive Method for Effective Substitute Teaching

    ERIC Educational Resources Information Center

    Byer, John L.

    2008-01-01

    This article dealt with methods for making substitute teaching more effective. The purpose was to articulate a sequential method for maximizing the effectiveness of substitute teaching while providing substitutes with a comprehensive method for diligently and flexibly earning respect and using reflection to continually improve substitute teaching.…

  2. ROC and Loss Function Analysis in Sequential Testing

    ERIC Educational Resources Information Center

    Muijtjens, Arno M. M.; Van Luijk, Scheltus J.; Van Der Vleuten, Cees P. M.

    2006-01-01

    Sequential testing is applied to reduce costs in SP-based tests (OSCEs). Initially, all candidates take a screening test consisting of a part of the OSCE. Candidates who fail the screen sit the complete test, whereas those who pass the screen are qualified as a pass of the complete test. The procedure may result in a reduction of testing…

  3. Comparison of sequential drug release in vitro and in vivo.

    PubMed

    Sundararaj, Sharath C; Al-Sabbagh, Mohanad; Rabek, Cheryl L; Dziubla, Thomas D; Thomas, Mark V; Puleo, David A

    2016-10-01

    Development of drug-delivery devices typically involves characterizing in vitro release performance with the inherent assumption that this will closely approximate in vivo performance. Yet, as delivery devices become more complex, for instance with a sequential drug release pattern, it is important to confirm that in vivo properties correlate with the expected "programming" achieved in vitro. In this work, a systematic comparison between in vitro and in vivo biomaterial erosion and sequential release was performed for a multilayered association polymer system comprising cellulose acetate phthalate and Pluronic F-127. After assessing the materials during incubation in phosphate-buffered saline, devices were implanted supracalvarially in rats. Devices with two different doses and with different erosion rates were harvested at increasing times post-implantation, and the in vivo thickness loss, mass loss, and the drug release profiles were compared with their in vitro counterparts. The sequential release of four different drugs observed in vitro was successfully translated to in vivo conditions. Results suggest, however, that the total erosion time of the devices was longer and that release rates of the four drugs were different, with drugs initially released more quickly and then more slowly in vivo. Many comparative studies of in vitro and in vivo drug release from biodegradable polymers involved a single drug, whereas this research demonstrated that sequential release of four drugs can be maintained following implantation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1302-1310, 2016.

  4. Sequential Research Needs in Evolving Disciplines of Social Practice.

    ERIC Educational Resources Information Center

    Knowles, Malcolm S.

    The author suggests that the emerging fields of social practice (such as recreation, social work, and adult education) must all go through a sequential pattern of research needs, first superficially, and then in ever deeper cycles. The six phases of these research needs are: definition of the field (survey and descriptive studies, census studies,…

  5. 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.

  6. 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,…

  7. Decision-Making Processes: Sensitivity to Sequentially Experienced Outcome Probabilities

    ERIC Educational Resources Information Center

    Boyer, Ty W.

    2007-01-01

    A computerized sequential event sampling decision-making task was administered to 187 5- to 10-year-olds and adults. Participants made a series of choices between alternatives that differed in win probability (Study 1) or win and loss probability (Study 2). Intuitive and more explicit measures were used. Study 1 revealed that, across ages,…

  8. Functionalized sorbent for chemical separations and sequential forming process

    DOEpatents

    Fryxell, Glen E.; Zemanian, Thomas S.

    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.

  9. 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.

  10. 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…

  11. Light-Weight Radioisotope Heater Unit (LWRHU) sequential impact tests

    SciTech Connect

    Reimus, M.A.H.; Rinehart, G.H.

    1997-08-01

    The light-weight radioisotope heater unit (LWRHU) is a {sup 238}PuO{sub 2}-fueled heat source designed to provide one thermal watt in each of various locations on a spacecraft. Los Alamos National Laboratory designed, fabricated, and safety tested the LWRHU. The heat source consists of a hot-pressed {sup 238}PuO{sub 2} fuel pellet, a Pt-30Rh vented capsule, a pyrolytic graphite insulator, and a fineweave-pierced fabric graphite aeroshell assembly. A series of sequential impacts tests using simulant-fueled LWRHU capsules was recently conducted to determine a failure threshold. Sequential impacting, in both end-on and side-on orientations, resulted in increased damage with each subsequent impact. Although the tests were conducted until the aeroshells were sufficiently distorted to be out of dimensional specification, the simulant-fueled capsules used in these tests were not severely deformed. Sequential impacting of the LWRHU appears to result in slightly greater damage than a single impact at the final impact velocity of 50 m/s. Postimpact examination revealed that the sequentially impacted capsules were slightly more deformed and were outside of dimensional specifications.

  12. Spontaneous sequential compartment syndrome of the lower limbs.

    PubMed

    Abisi, Said; Yong, Yao Pey; Beech, Andrew; Oluwole, Akin; Tennant, William

    2013-10-01

    Spontaneous compartment syndrome is a rare condition and requires urgent surgical treatment to achieve favorable outcome. Several cases have been reported in the literature, and it has been associated with patients with diabetes. We present a case of acute spontaneous sequential compartment syndrome of the lower limbs in a patient with poorly controlled type 1 diabetes.

  13. 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…

  14. 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.

  15. Buprenorphine-based regimens and methadone for the medical management of opioid dependence: selecting the appropriate drug for treatment.

    PubMed

    Maremmani, Icro; Gerra, Gilberto

    2010-01-01

    Maintenance therapy with methadone or buprenorphine-based regimens reduces opioid dependence and associated harms. The perception that methadone is more effective than buprenorphine for maintenance treatment has been based on low buprenorphine doses and excessively slow induction regimens used in early buprenorphine trials. Subsequent studies show that the efficacy of buprenorphine sublingual tablet (Subutex®) or buprenorphine/naloxone sublingual tablet (Suboxone®) is equivalent to that of methadone when sufficient buprenorphine doses, rapid induction, and flexible dosing are used. Although methadone remains an essential maintenance therapy option, buprenorphine-based regimens increase access to care and provide safer, more appropriate treatment than methadone for some patients. PMID:20958853

  16. Brazilian experience using high dose sequential chemotherapy followed by autologous hematopoietic stem cell transplantation for malignant lymphomas

    PubMed Central

    Duarte, Bruno Kosa Lino; Miranda, Eliana Cristina Martins; Nucci, Marcio; Vigorito, Afonso Celso; Penteado, Francisco José; Marques Jr, José Francisco Comenalli; Oliveira-Duarte, Gislaine Borba; Lorand-Metze, Irene Gyongyver Heidemarie; Pagnano, Katia Borgia; Delamain, Marcia Torresan; Baldissera, Renata; Valente, Isabella Salvetti; de Souza, Carmino Antonio

    2011-01-01

    Objective To evaluate the use of high-dose sequential chemotherapy in a Brazilian population. Methods High-dose cyclophosphamide followed by autologous hematopoietic stem cell transplantation is an effective and feasible therapy for refractory/relapsed lymphomas; this regimen has never before been evaluated in a Brazilian population. All patients (106 with high-grade non-Hodgkin lymphoma and 77 with Hodgkin's lymphoma) submitted to this treatment between 1998 and 2006 were analyzed. Chemotherapy consisted of the sequential administration of high-dose cyclophosphamide (4 or 7 g/m2) and granulocyte-colony stimulating factor (300 µg/day), followed by peripheral blood progenitor cell harvesting, administration of etoposide (2g/m2) and methotrexate (8 g/m2 only for Hodgkin's lymphoma) and autologous hematopoietic stem cell transplantation. Results At diagnosis, non-Hodgkin lymphoma patients had a median age of 45 (range: 8-65) years old, 78% had diffuse large B-cell lymphoma and 83% had stage III/IV disease. The Hodgkin's lymphoma patients had a median age of 23 (range: 7-68) years old, 64.9% had the nodular sclerosis subtype and 65% had stage III/IV disease. Nine Hodgkin's lymphoma patients (13%) and 10 (9%) non-Hodgkin lymphoma patients had some kind of cardiac toxicity. The overall survival, disease-free survival and progression-free survival in Hodgkin's lymphoma were 29%, 59% and 26%, respectively. In non-Hodgkin lymphoma, these values were 40%, 49% and 31%, respectively. High-dose cyclophosphamide-related mortality was 10% for Hodgkin's lymphoma and 5% for non-Hodgkin lymphoma patients. High-dose cyclophosphamide dosing had no impact on toxicity or survival for both groups. Conclusions Despite a greater prevalence of poor prognostic factors, our results are comparable to the literature. The incidence of secondary neoplasias is noteworthy. Our study suggests that this approach is efficient and feasible, regardless of toxicity-related mortality. PMID:23049359

  17. Evaluation of hippuric acid content in goat milk as a marker of feeding regimen.

    PubMed

    Carpio, A; Bonilla-Valverde, D; Arce, C; Rodríguez-Estévez, V; Sánchez-Rodríguez, M; Arce, L; Valcárcel, M

    2013-09-01

    Organic producers, traders, and consumers must address 2 issues related to milk: authentication of the production system and nutritional differentiation. The presence of hippuric acid (HA) in goat milk samples has been proposed as a possible marker to differentiate the feeding regimen of goats. The objective of this work is to check the hypothesis that HA could be a marker for the type of feeding regimen of goats by studying the influence of production system (conventional or organic) and feeding regimen (with or without grazing fodder). With this purpose, commercial cow and goat milk samples (n=27) and raw goat milk samples (n=185; collected from different breeds, localizations, and dates) were analyzed. Samples were grouped according to breed, feeding regimen, production system, and origin to compare HA content by ANOVA and honestly significant difference Tukey test at a confidence level of ≥95%. Hippuric acid content was obtained by analyzing milk samples with capillary electrophoresis. This method was validated by analyzing part of the samples with HPLC as a reference technique. Sixty-nine raw goat milk samples (of the total 158 samples analyzed in this work) were quantified by capillary electrophoresis. In these samples, the lowest average content for HA was 7±3 mg/L. This value corresponds to a group of conventional raw milk samples from goats fed with compound feed. The highest value of this group was 28±10 mg/L, corresponding to goats fed compound feed plus grass. Conversely, for organic raw goat milk samples, the highest concentration was 67±14 mg/L, which corresponds to goats fed grass. By contrast, the lowest value of this organic group was 26±10 mg/L, which belongs to goats fed organic compounds. Notice that the highest HA average content was found in samples from grazing animals corresponding to the organic group. This result suggests that HA is a good marker to determine the type of goats feeding regimen; a high content of HA represents a diet

  18. Adding Pioglitazone to Insulin Containing Regimens in Type 2 Diabetes: Systematic Review and Meta-Analysis

    PubMed Central

    Clar, Christine; Royle, Pamela; Waugh, Norman

    2009-01-01

    Background Type 2 diabetes is treated in a stepwise manner, progressing from diet and physical activity to oral antidiabetic agents and insulin. The oral agent pioglitazone is licensed for use with insulin when metformin is contraindicated or not tolerated. This systematic review and meta-analysis investigates the extent to which adding pioglitazone to insulin-containing regimens produces benefits in terms of patient-relevant outcomes. Methodology/Principal Findings Medline, Embase, and the Cochrane Library were searched for randomised controlled trials comparing pioglitazone in combination with any insulin-containing regimen in comparison with the same insulin regimen alone in patients with type 2 diabetes. Outcomes investigated included HbA1c, hypoglycaemia, weight, and adverse events. Studies were selected, assessed and summarised according to standard systematic review methodology and in a meta-analysis. We included eight trials that examined the benefits of adding pioglitazone to an insulin regimen and studied a total of 3092 patients with type 2 diabetes. All studies included patients with previously inadequate glucose control. Trial duration was between 12 weeks and 34.5 months. The trials used pioglitazone doses of up to 45 mg/day. In our meta-analysis, the mean reduction in HbA1c was 0.58% (95% CI: −0.70, −0.46, p<0.00001). Hypoglycaemic episodes were slightly more frequent in the pioglitazone arms (relative risk 1.27; 95% CI: 0.99, 1.63, p = 0.06). Where reported, HDL-cholesterol tended to be increased with pioglitazone. Patients on pioglitazone tended to gain more weight than those who were not, with an average difference of almost 3 kg. Peripheral oedema was more frequent in the pioglitazone groups. None of the studies reported on fractures in women, and data on cardiovascular events were inconclusive, with most studies being too short or too small to assess these long-term outcomes. Conclusions/Significance When added to insulin regimens

  19. Class-Sparing Regimens for Initial Treatment of HIV-1 Infection

    PubMed Central

    Riddler, Sharon A.; Haubrich, Richard; DiRienzo, A. Gregory; Peeples, Lynne; Powderly, William G.; Klingman, Karin L.; Garren, Kevin W.; George, Tania; Rooney, James F.; Brizz, Barbara; Lalloo, Umesh G.; Murphy, Robert L.; Swindells, Susan; Havlir, Diane; Mellors, John W.

    2013-01-01

    BACKGROUND The use of either efavirenz or lopinavir–ritonavir plus two nucleoside reverse-transcriptase inhibitors (NRTIs) is recommended for initial therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection, but which of the two regimens has greater efficacy is not known. The alternative regimen of lopinavir–ritonavir plus efavirenz may prevent toxic effects associated with NRTIs. METHODS In an open-label study, we compared three regimens for initial therapy: efavirenz plus two NRTIs (efavirenz group), lopinavir–ritonavir plus two NRTIs (lopinavir–ritonavir group), and lopinavir–ritonavir plus efavirenz (NRTI-sparing group). We randomly assigned 757 patients with a median CD4 count of 191 cells per cubic millimeter and a median HIV-1 RNA level of 4.8 log10 copies per milliliter to the three groups. RESULTS At a median follow-up of 112 weeks, the time to virologic failure was longer in the efavirenz group than in the lopinavir–ritonavir group (P = 0.006) but was not significantly different in the NRTI-sparing group from the time in either of the other two groups. At week 96, the proportion of patients with fewer than 50 copies of plasma HIV-1 RNA per milliliter was 89% in the efavirenz group, 77% in the lopinavir–ritonavir group, and 83% in the NRTI-sparing group (P = 0.003 for the comparison between the efavirenz group and the lopinavir–ritonavir group). The groups did not differ significantly in the time to discontinuation because of toxic effects. At virologic failure, antiretroviral resistance mutations were more frequent in the NRTI-sparing group than in the other two groups. CONCLUSIONS Virologic failure was less likely in the efavirenz group than in the lopinavir–ritonavir group. The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance. (ClinicalTrials.gov number, NCT00050895.) PMID:18480202

  20. FlexSnap: Flexible Non-sequential Protein Structure Alignment

    PubMed Central

    2010-01-01

    Background Proteins have evolved subject to energetic selection pressure for stability and flexibility. Structural similarity between proteins that have gone through conformational changes can be captured effectively if flexibility is considered. Topologically unrelated proteins that preserve secondary structure packing interactions can be detected if both flexibility and Sequential permutations are considered. We propose the FlexSnap algorithm for flexible non-topological protein structural alignment. Results The effectiveness of FlexSnap is demonstrated by measuring the agreement of its alignments with manually curated non-sequential structural alignments. FlexSnap showed competitive results against state-of-the-art algorithms, like DALI, SARF2, MultiProt, FlexProt, and FATCAT. Moreover on the DynDom dataset, FlexSnap reported longer alignments with smaller rmsd. Conclusions We have introduced FlexSnap, a greedy chaining algorithm that reports both sequential and non-sequential alignments and allows twists (hinges). We assessed the quality of the FlexSnap alignments by measuring its agreements with manually curated non-sequential alignments. On the FlexProt dataset, FlexSnap was competitive to state-of-the-art flexible alignment methods. Moreover, we demonstrated the benefits of introducing hinges by showing significant improvements in the alignments reported by FlexSnap for the structure pairs for which rigid alignment methods reported alignments with either low coverage or large rmsd. Availability An implementation of the FlexSnap algorithm will be made available online at http://www.cs.rpi.edu/~zaki/software/flexsnap. PMID:20047669

  1. Finger Tendon Travel Associated with Sequential Trigger Nail Gun Use

    PubMed Central

    Lowe, Brian; Albers, James; Hudock, Stephen; Krieg, Edward

    2015-01-01

    TECHNICAL ABSTRACT Background Pneumatic nail guns used in wood framing are equipped with one of two triggering mechanisms. Sequential actuation triggers have been shown to be a safer alternative to contact actuation triggers because they reduce traumatic injury risk. However, the sequential actuation trigger must be depressed for each individual nail fired as opposed to the contact actuation trigger, which allows the trigger to be held depressed as nails are fired repeatedly by bumping the safety tip against the workpiece. As such, concerns have been raised about risks for cumulative trauma injury, and reduced productivity, due to repetitive finger motion with the sequential actuation trigger. Purpose This study developed a method to predict cumulative finger flexor tendon travel associated with the sequential actuation trigger nail gun from finger joint kinematics measured in the trigger actuation and productivity standards for wood-frame construction tasks. Methods Finger motions were measured from six users wearing an instrumented electrogoniometer glove in a simulation of two common framing tasks–wall building and flat nailing of material. Flexor tendon travel was calculated from the ensemble average kinematics for an individual nail fired. Results Finger flexor tendon travel was attributable mostly to proximal interphalangeal and distal interphalangeal joint motion. Tendon travel per nail fired appeared to be slightly greater for a wall-building task than a flat nailing task. The present study data, in combination with construction industry productivity standards, suggest that a high-production workday would be associated with less than 60 m/day cumulative tendon travel per worker (based on 1700 trigger presses/day). Conclusion and Applications These results suggest that exposure to finger tendon travel from sequential actuation trigger nail gun use may be below levels that have been previously associated with high musculoskeletal disorder risk. PMID

  2. 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.

  3. Treatment-time regimen of hypertension medications significantly affects ambulatory blood pressure and clinical characteristics of patients with resistant hypertension.

    PubMed

    Hermida, Ramón C; Ríos, María T; Crespo, Juan J; Moyá, Ana; Domínguez-Sardiña, Manuel; Otero, Alfonso; Sánchez, Juan J; Mojón, Artemio; Fernández, José R; Ayala, Diana E

    2013-03-01

    Patients with resistant hypertension (RH) are at greater risk for stroke, renal insufficiency, and cardiovascular disease (CVD) events than are those for whom blood pressure (BP) is responsive to and well controlled by therapeutic interventions. Although all chronotherapy trials have compared the effects on BP regulation of full daily doses of medications when ingested in the morning versus at bedtime, prescription of the same medications in divided doses twice daily (BID) is frequent. Here, we investigated the influence of hypertension treatment-time regimen on the circadian BP pattern, degree of BP control, and relevant clinical and laboratory medicine parameters of RH patients evaluated by 48-h ambulatory BP monitoring (ABPM). This cross-sectional study evaluated 2899 such patients (1701 men/1198 women), 64.2 ± 11.8 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 1084 were ingesting all hypertension medications upon awakening (upon-awakening regimen), 1436 patients were ingesting the full daily dose of ≥1 of them at bedtime (bedtime regimen), and 379 were ingesting split doses of ≥1 medications BID upon awakening and at bedtime (BID regimen). Patients of the bedtime regimen compared with the other two treatment-time regimens had lower likelihood of microalbuminuria and chronic kidney disease; significantly lower albumin/creatinine ratio, glucose, total cholesterol, and low-density lipoprotein (LDL) cholesterol; plus higher estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol. The bedtime regimen was also significantly associated with lower asleep systolic (SBP) and diastolic (DBP) BP means than the upon-awakening and BID regimens. The sleep-time relative SBP and DBP decline was significantly attenuated by the upon-awakening and BID regimens (p < .001), resulting in significantly higher prevalence of non-dipping in these two treatment-time regimen groups (80.5% and 77.3%, respectively

  4. Sequential Reaction Channels of Metastable C{sup 4+}{sub 60}

    SciTech Connect

    Duenser, B.; Echt, O.; Scheier, P.; Maerk, T.D.

    1997-11-01

    We employ a two-sector-field mass spectrometer to identify sequential, unimolecular dissociation channels of C{sup 4+}{sub 60} . In addition to sequential {open_quotes}monomer evaporations{close_quotes} (loss of two C{sub 2} units), we observe two novel sequential channels which involve fissionlike events: loss of C{sup +}{sub 2} followed by evaporation, and sequential loss of two C{sup +}{sub 2} units. {copyright} {ital 1997} {ital The American Physical Society}

  5. Group Sequential Design for Randomized Phase III Trials under the Weibull Model

    PubMed Central

    Wu, Jianrong; Xiong, Xiaoping

    2014-01-01

    In this paper, a parametric sequential test is proposed under the Weibull model. The proposed test is asymptotically normal with an independent increments structure. The sample size for fixed sample test is derived for the purpose of group sequential trial design. In addition, a multi-stage group sequential procedure is given under the Weibull model by applying the Brownian motion property of the test statistic and sequential conditional probability ratio test methodology. PMID:25322440

  6. National Variation in Use of Immunosuppression for Kidney Transplantation: A Call for Evidence-Based Regimen Selection.

    PubMed

    Axelrod, D A; Naik, A S; Schnitzler, M A; Segev, D L; Dharnidharka, V R; Brennan, D C; Bae, S; Chen, J; Massie, A; Lentine, K L

    2016-08-01

    Immunosuppression management in kidney transplantation has evolved to include an increasingly diverse choice of medications. Although informed by patient and donor characteristics, choice of immunosuppression regimen varies widely across transplant programs. Using a novel database integrating national transplant registry and pharmacy fill records, immunosuppression use at 6-12 and 12-24 mo after transplant was evaluated for 22 453 patients transplanted in 249 U.S. programs in 2005-2010. Use of triple immunosuppression comprising tacrolimus, mycophenolic acid or azathioprine, and steroids varied widely (0-100% of patients per program), as did use of steroid-sparing regimens (0-77%), sirolimus-based regimens (0-100%) and cyclosporine-based regimens (0-78%). Use of triple therapy was more common in highly sensitized patients, women and recipients with dialysis duration >5 years. Sirolimus use appeared to diminish over the study period. Patient and donor characteristics explained only a limited amount of the observed variation in regimen use, whereas center choice explained 30-46% of the use of non-triple-therapy immunosuppression. The majority of patients who received triple-therapy (79%), cyclosporine-based (87.6%) and sirolimus-based (84.3%) regimens continued them in the second year after transplant. This population-based study of immunosuppression practice demonstrates substantial variation in center practice beyond that explained by differences in patient and donor characteristics. PMID:26901466

  7. Desirable Characteristics of Hepatitis C Treatment Regimens: A Review of What We Have and What We Need.

    PubMed

    Bidell, Monique R; McLaughlin, Milena; Faragon, John; Morse, Caroline; Patel, Nimish

    2016-09-01

    There have been dramatic advancements in the treatment of chronic hepatitis C (HCV) infection. This is largely due to the approval of several direct-acting antiviral agents (DAAs) from a variety of medication classes with novel mechanisms of action. These therapies are a welcomed advancement given their improved efficacy and tolerability compared to pegylated interferon and ribavirin (RBV)-based regimens. These convenient, all-oral regimens treat a variety of genotypes and often offer high cure rates in a variety of HCV-infected populations. While there are several benefits associated with these therapies, there are also notable shortcomings. Shortcomings include diminished response or need for adjunctive RBV in difficult-to-treat populations (decompensated cirrhosis, active substance abuse patients, advanced kidney disease, etc.), activity against select genotypes, substantial drug-drug interaction potential, and high cost. Therefore, while current DAA-based therapies have several favorable attributes, each also has its limitations. The purpose of this review is to (1) identify the characteristics of an ideal HCV treatment regimen, (2) describe desirable features of existing regimens, (3) summarize limitations of existing regimens, and (4) introduce promising emerging therapies. This manuscript will serve as a guide for evaluating the caliber of future HCV treatment regimens. PMID:27384319

  8. Tuberculosis--advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.

    PubMed

    Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin

    2016-04-01

    Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480,000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to

  9. Determination of Optimal Amikacin Dosing Regimens for Pediatric Patients With Burn Wound Sepsis.

    PubMed

    Yu, Tian; Stockmann, Chris; Healy, Daniel P; Olson, Jared; Wead, Stephanie; Neely, Alice N; Kagan, Richard J; Spigarelli, Michael G; Sherwin, Catherine M T

    2015-01-01

    This study aimed to develop optimal amikacin dosing regimens for the empirical treatment of Gram-negative bacterial sepsis in pediatric patients with burn injuries. A pharmacodynamic (PD) target in which the peak concentration (Cmax) is ≥8 times the minimum inhibitory concentration (MIC) (Cmax/MIC ≥ 8) is reflective of optimal bactericidal activity and has been used to predict clinical outcomes. Population pharmacokinetic modeling was performed in NONMEM 7.2 for pediatric patients with and without burn injuries. Amikacin pharmacokinetic parameters were compared between the two groups and multiple dosing regimens were simulated using MATLAB to achieve the PD target in ≥90% of patients with burn injuries. The pharmacokinetic analysis included 282 amikacin concentrations from 70 pediatric patients with burn injuries and 99 concentrations from 32 pediatric patients without burns. A one-compartment model with first-order elimination described amikacin pharmacokinetics well for both groups. Clearance (CL) was significantly higher in patients with burn injuries than in patients without (7.22 vs 5.36 L/h, P < .001). The volume of distribution (V) was also significantly increased in patients with burn injuries (22.7 vs 18.7 L, P < .01). Weight significantly influenced amikacin CL (P < .001) and V (P < .001) for both groups. Model-based simulations showed that a higher amikacin dose (≥25 mg/kg) achieved a Cmax/MIC ≥8 in ≥90% of patients with assumed infections of organisms with an MIC = 8 mg/L. Amikacin pharmacokinetics are altered in patients with burn injuries, including a significant increase in CL and V. In simulations, increased doses (≥25 mg/kg) led to improved PD target attainment rates. Further clinical evaluation of this proposed dosing regimen is warranted to assess clinical and microbiological outcomes in pediatric patients with burn wound sepsis.

  10. Cancer detection rates of different prostate biopsy regimens in patients with renal failure.

    PubMed

    Hoşcan, Mustafa Burak; Özorak, Alper; Oksay, Taylan; Perk, Hakkı; Armağan, Abdullah; Soyupek, Sedat; Serel, Tekin Ahmet; Koşar, Alim

    2014-07-01

    We aimed to evaluate the cancer detection rates of 6-, 10-, 12-core biopsy regimens and the optimal biopsy protocol for prostate cancer diagnosis in patients with renal failure. A total of 122 consecutive patients with renal failure underwent biopsy with age-specific prostate-specific antigen (PSA) levels up to 20 ng/mL. The 12-core biopsy technique (sextant biopsy + lateral base, lateral mid-zone, lateral apex, bilaterally) performed to all patients. Pathology results were examined separately for each sextant, 10-core that exclude parasagittal mid-zones from 12-cores (10a), 10-core that exclude apex zones from 12-cores (10b) and 12-core biopsy regimens. Of 122 patients, 37 (30.3%) were positive for prostate cancer. The cancer detection rates for sextant, 10a, 10b and 12 cores were 17.2%, 29%, 23.7% and 30.7%, respectively. Biopsy techniques of 10a, 10b and 12 cores increased the cancer detection rates by 40%, 27.5% and 43.2% among the sextant technique, respectively. Biopsy techniques of 10a and 12 cores increased the cancer detection rates by 17.1% and 21.6% among 10b biopsy technique, respectively. There were no statistical differences between 12 core and 10a core about cancer detection rate. Adding lateral cores to sextant biopsy improves the cancer detection rates. In our study, 12-core biopsy technique increases the cancer detection rate by 5.4% among 10a core but that was not statistically different. On the other hand, 12-core biopsy technique includes all biopsy regimens. We therefore suggest 12-core biopsy or minimum 10-core strategy incorporating six peripheral biopsies with elevated age- specific PSA levels up to 20 ng/mL in patients with renal failure. PMID:24797801

  11. Paste, wrap, and shimmy: a regimen for the prevention of gum disease.

    PubMed

    Jester, Craig W

    2013-01-01

    The body of evidence showing a possible correlation between gum infection and systemic diseases is well documented and growing. At the same time, the prevalence of gum infection is increasing in the general populace. Gum infection and disease are routinely seen in patients who adhere to regular dental hygiene regimens and see their dentists on a regular basis. One of the reasons typical daily dental care does not eradicate gum disease (gingivitis) is that the usual home care regimens do not attack a major underlying cause of gingivitis: the layer of biofilm in the sulcus surrounding the tooth's root. This biofilm harbors and protects the bacteria that cause gum disease and root decay. Research has shown that there are no "magic bullets" in the form of rinses, pills, or special tools that effectively destroy the bacteria and its protective calyx. Therefore, daily dental regimens must be changed until the absence of gum infection and inflammation becomes the standard of care. The Paste, Wrap, and Shimmy method is presented in a way that can be understood by all patients. It can be reproduced and used as a teaching supplement by the dental team. The method is conceptually simple and inexpensive, but not intuitive or easy. It must be coached and reinforced; however, if implemented, it can be very effective. The author's office has increased the length of new patient and recurring hygiene visits so that the method can be properly taught through repetitive practice and visual presentations. Prevention is not insurance-driven, so dentists most often provide it as a free service. The rewards are significant, however, and on initial exposure to this method, patients routinely ask: "Why haven't I been shown this before?" They will also have an expectation that the learning process will be repeated at each visit until they are free of infection. PMID:23302359

  12. The roles of past behavior and health beliefs in predicting medication adherence to a statin regimen

    PubMed Central

    Molfenter, Todd D; Bhattacharya, Abhik; Gustafson, David H

    2012-01-01

    Purpose: Current medication-adherence predictive tools are based on patient medication-taking beliefs, but studying past behavior may now be a more explanatory and accessible method. This study will evaluate if past medication-refill behavior for a statin regimen is more predictive of medication adherence than patient medication-taking health beliefs. Patients and methods: This prospective longitudinal study was implemented in a national managed care plan in the United States. A group of 1433 statin patients were identified and followed for 6 months. Medication-taking health beliefs, collected from self-reported mail questionnaires, and past medication-refill behavior, using proportion of days covered (PDC), were collected prior to 6-month follow-up. Outcomes were measured using categorical PDC variable (of adherence, PDC ≥ 85%, versus nonadherence, PDC < 85%), with model fit estimated using receiver operator characteristic analysis. Results: The area under the receiver operator characteristic curve for past behavior (Az = 0.78) was significantly greater (P < 0.05) than for patient health beliefs (Az = 0.69), indicating that past prescription-refill behavior is a better predictor of medication adherence than prospective health beliefs. Among health beliefs, the factor most related to medication adherence was behavioral intent (odds ratio, 5.12; 95% confidence interval, 1.84 to 15.06). The factor most strongly related to behavioral intent was impact of regimen on daily routine (odds ratio, 3.3; 95% confidence interval, 1.41 to 7.74). Conclusion: Electronic medical records and community health-information networks may make past prescription-refill rates more accessible and assist physicians with managing medication-regimen adherence. Health beliefs, however, may still play an important role in influencing medication-taking behaviors. PMID:23055697

  13. Dynamics of early histopathological changes in GVHD after busulphan/cyclophosphamide conditioning regimen.

    PubMed

    Al-Hashmi, Sulaiman; Hassan, Zuzana; Sadeghi, Behnam; Rozell, Björn; Hassan, Moustapha

    2011-08-15

    Hematopoietic stem cell transplantation (HSCT) is a curative treatment for otherwise incurable diseases. Conditioning regimen is an important part of HSCT and consists of chemotherapy with or without irradiation. Conditioning exerts myelosuppressive, immunosuppressive and antitumor effects, but also contributes to HSCT-related complications including graft-versus-host disease (GVHD). Since almost 50% of the transplanted patients are conditioned with cytostatics without irradiation, we developed and characterized a GVHD mouse model following conditioning with busulphan and cyclophosphamide. Recipient Balb/c female mice were treated with busulphan (20 mg/kg/day for 4 days) and cyclophosphamide (100 mg/kg/day for two days). After one day of rest, recipient mice were transplanted with 2×10(7) bone marrow and 3×10(7) spleen cells from male C57BL/6 (allogeneic group) or female Balb/c (syngeneic/control group) mice. The allogeneic, but not syngeneic transplanted mice developed GVHD. Histopathology of the major internal organs (liver, pancreas, spleen, lungs, heart and kidney) was examined before conditioning start, after conditioning's end and 5, 7 and 21 days after transplantation using hematoxylin-eosin staining. Decreased spleen cellularity and diminished glycogen content in the liver were observed after conditioning regimen. Histopathological changes such as vasculitis, inflammation and apoptotic cell forms in liver, spleen, pancreas, lungs and heart were observed in allogeneic transplanted mice, however, only hypocellular spleen and extramedullar hematopoiesis were detected in syngeneic transplanted animals. No morphological changes were observed in kidney in either HSCT setting. This is the first study describing early histopathological changes after conditioning regimen with busulphan/cyclophosphamide and dynamics of GVHD development in several major internal organs.

  14. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    SciTech Connect

    Van Beneden, Katrien; Geers, Caroline; Pauwels, Marina; Mannaerts, Inge; Wissing, Karl M.; Van den Branden, Christiane; Grunsven, Leo A. van

    2013-09-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.

  15. Transzonular vitreous injection vs a single drop compounded topical pharmaceutical regimen after cataract surgery

    PubMed Central

    Fisher, Bret L; Potvin, Rick

    2016-01-01

    Purpose To compare the relative effectiveness of a Tri-Moxi-Vanc intraocular solution injected transzonularly into the vitreous with the topical formulation of Pred-Moxi-Ketor (given for the first week postoperatively) followed by Pred-Ketor (given for weeks 2–4 after surgery). Patients and methods This was a single-site, single-surgeon, prospective, randomized, subject-masked contralateral eye study with an active comparator and was approved by an appropriate ethics committee. Twenty-five subjects with uncomplicated cataract who were scheduled for cataract surgery were enrolled. If surgery was uneventful, subjects received either an injection in that eye or followed a minimum drop postoperative pharmaceutical regimen. The second eye surgery was performed with the opposite treatment. Subjects were followed for 1 month. Measures of interest were the changes in intraocular pressure (IOP) from baseline and the changes in corneal and macular thickness. Subjects were also asked to evaluate pain perception, visual quality, and overall satisfaction with surgery. They were also asked which regimen they preferred. Results IOP was not statistically significantly different between the groups (P=0.81); there was also no statistically significant difference in IOP over time (P=0.74). There was no statistically significant difference in central macular thickness at 1 week and 1 month between the groups (P=0.18). The central corneal thickness was significantly greater 1 day postoperatively relative to baseline, but there was no statistically significant difference between the groups at any time point (P=0.92). The difference in reported pain was also not statistically significantly different between the groups (P=0.67). Satisfaction with surgery was similar for both groups, but significantly more subjects preferred the injection for overall experience (P<0.01). Conclusion Cataract surgery completed with the two pharmaceutical regimens was similar in outcome. Significantly more

  16. Tuberculosis--advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.

    PubMed

    Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin

    2016-04-01

    Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480,000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to

  17. Treatment Outcomes with Fluoroquinolone-Containing Regimens for Isoniazid-Resistant Pulmonary Tuberculosis

    PubMed Central

    Lee, Hyun; Jeong, Byeong-Ho; Park, Hye Yun; Jeon, Kyeongman; Huh, Hee Jae; Lee, Nam Yong

    2015-01-01

    Resistance to isoniazid (INH) is the most common form of drug resistance in pulmonary tuberculosis (TB). Although fluoroquinolones (FQs) are recommended to strengthen treatment regimens for INH-resistant pulmonary TB, few studies have evaluated the clinical efficacy of FQ-containing regimens in patients with INH-resistant pulmonary TB. A retrospective cohort study of 140 patients with INH-resistant pulmonary TB was performed between 2005 and 2012. We evaluated whether FQ-containing regimens yielded improved treatment outcomes for patients with INH-resistant pulmonary TB. Overall, favorable outcomes were achieved in 128 (91.4%) patients. Unfavorable outcomes occurred in 12 patients (8.6%), including 7 with treatment failure (5.0%) and 5 with relapse after initial treatment completion (3.6%). FQs, such as levofloxacin and moxifloxacin, were given to 75 (53.6%) patients. Favorable treatment outcomes were more frequent for patients who received FQs (97.3% [73/75 patients]) than for those who did not receive FQs (84.6% [55/65 patients]) (P = 0.007). Patients who did not receive FQs were more likely to develop treatment failure (9.2% [6/65 patients] versus 1.3% [1/75 patients]) (P = 0.049) than patients who received FQs. The adjusted proportion of unfavorable outcomes was significantly higher among patients who did not receive FQs (8.8%; 95% confidence interval [CI], 3.3 to 21.5%) than among those who did receive FQs (1.5%; 95% CI, 0.3 to 7.7%) (P = 0.037). These results suggest that the addition of FQs can improve treatment outcomes for patients with INH-resistant pulmonary TB. PMID:26525801

  18. Central nervous system HIV infection in "less-drug regimen" antiretroviral therapy simplification strategies.

    PubMed

    Ferretti, Francesca; Gianotti, Nicola; Lazzarin, Adriano; Cinque, Paola

    2014-02-01

    Less-drug regimens (LDR) refer to combinations of either two antiretroviral drugs or ritonavir-boosted protease inhibitor (PI) monotherapy. They may represent a simplification strategy in patients with persistently suppressed human immunodeficiency virus (HIV) viremia, with the main benefits of reducing drug-related toxicities and costs. Systemic virological efficacy of LDR is slightly lower as compared with combined antiretroviral therapy (cART), but patients with failure do not usually develop drug resistance and resuppress HIV replication after reintensification. A major concern of LDR is the lower efficacy in the virus reservoirs, especially in the central nervous system (CNS), where viral compartmentalization and independent evolution of infection may lead to CNS viral escape, often associated with neurologic symptoms. The authors reviewed studies of virological and functional CNS efficacy of LDR, particularly of boosted PI monotherapy regimens, for which more information is available. Symptomatic viral CSF escape was observed mainly in PI/r monotherapy patients with plasma failure and low nadir CD4+ cell counts, and resolved upon reintroduction of triple drug cART, whereas asymptomatic viral failure in CSF was not significantly more frequent in patients on PI/r monotherapy compared with patients on standard cART. In addition, there was no difference in functional outcomes between PI monotherapy and cART patients, irrespective of CSF viral escape. More data are needed on the CNS effect of dual ART regimens and, in general, on long-term efficacy of LDR. Simplification with LDR may be an attractive option in patients with suppressed viral load, if they are well selected and monitored for potential CNS complications.

  19. In vivo biofilm formation on stainless steel bonded retainers during different oral health-care regimens

    PubMed Central

    Jongsma, Marije A; van der Mei, Henny C; Atema-Smit, Jelly; Busscher, Henk J; Ren, Yijin

    2015-01-01

    Retention wires permanently bonded to the anterior teeth are used after orthodontic treatment to prevent the teeth from relapsing to pre-treatment positions. A disadvantage of bonded retainers is biofilm accumulation on the wires, which produces a higher incidence of gingival recession, increased pocket depth and bleeding on probing. This study compares in vivo biofilm formation on single-strand and multi-strand retention wires with different oral health-care regimens. Two-centimetre wires were placed in brackets that were bonded to the buccal side of the first molars and second premolars in the upper arches of 22 volunteers. Volunteers used a selected toothpaste with or without the additional use of a mouthrinse containing essential oils. Brushing was performed manually. Regimens were maintained for 1 week, after which the wires were removed and the oral biofilm was collected to quantify the number of organisms and their viability, determine the microbial composition and visualize the bacteria by electron microscopy. A 6-week washout period was employed between regimens. Biofilm formation was reduced on single-strand wires compared with multi-strand wires; bacteria were observed to adhere between the strands. The use of antibacterial toothpastes marginally reduced the amount of biofilm on both wire types, but significantly reduced the viability of the biofilm organisms. Additional use of the mouthrinse did not result in significant changes in biofilm amount or viability. However, major shifts in biofilm composition were induced by combining a stannous fluoride- or triclosan-containing toothpaste with the mouthrinse. These shifts can be tentatively attributed to small changes in bacterial cell surface hydrophobicity after the adsorption of the toothpaste components, which stimulate bacterial adhesion to the hydrophobic oil, as illustrated for a Streptococcus mutans strain. PMID:25572920

  20. Virologic response and haematologic toxicity of boceprevir- and telaprevir-containing regimens in actual clinical settings

    PubMed Central

    Butt, A. A.; Yan, P.; Shaikh, O. S.; Freiberg, M. S.; Re, V. Lo; Justice, A. C.; Sherman, K. E.

    2016-01-01

    SUMMARY Effectiveness, safety and tolerability of boceprevir (BOC) and telaprevir (TPV) in actual clinical settings remain unknown. We determined rates of sustained virologic response (SVR) and haematologic adverse effects among persons treated with BOC- or TPV-containing regimens, compared with pegylated interferon/ribavirin (PEG/RBV). Using an established cohort of hepatitis C virus (HCV)-infected persons, Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), we identified those treated with a BOC- or TPV-containing regimen and HCV genotype 1-infected controls treated with PEG/RBV. We excluded those with HIV co-infection and missing HCV RNA values to determine SVR. Primary endpoints were SVR (undetectable HCV RNA ≥12 weeks after treatment completion) and haematologic toxicity (grade 3/4 anaemia, neutropenia and thrombocytopenia). We evaluated 2288 persons on BOC-, 409 on TPV-containing regimen and 6308 on PEG/RBV. Among these groups, respectively, 31%, 43% and 9% were treatment-experienced; 17%, 37% and 14% had baseline cirrhosis; 63%, 54% and 48% were genotype 1a. SVR rates among noncirrhotics were as follows: treatment naïve: 65% (BOC), 67% (TPV) and 31% (PEG/RBV); treatment experienced: 57% (BOC), 54% (TPV) and 13% (PEG/RBV); (P-value not significant for BOC vs TPV; P < 0.0001 for BOC or TPV vs PEG/RBV). Haematologic toxicities among BOC-, TPV- and PEG/RBV-treated groups were as follows: grade 3/4 anaemia 7%, 11% and 3%; grade 4 thrombocytopenia 2.2%, 5.4% and 1.7%; grade 4 neutropenia 8.2%, 5.6% and 3.4%. SVR rates are higher and closer to those reported in pivotal clinical trials among BOC- and TPV-treated persons compared with PEG/RBV-treated persons. Haematologic adverse events are frequent, but severe toxicity is uncommon. PMID:25524834

  1. High dietary protein regimens provide significant protection from mercury nephrotoxicity in rats

    SciTech Connect

    Andrews, P.M.; Chung, E.M. )

    1990-09-01

    The effects of high protein dietary regimens prior to the administration of inorganic mercury were investigated. Male Sprague-Dawley rats were pair-fed on purified test diets containing either normal (20%) or high (60%) concentrations of protein. Mercury was administered as a single intravenous injection of mercuric chloride (1 mg/kg). All rats maintained on normal dietary protein prior to and following mercury injection exhibited severe kidney dysfunction, extensive necrosis of both second (S2) and third (S3) segments of the kidney proximal tubules, and 100% mortality. In contrast, rats maintained on high dietary protein for 48 hr or longer just prior to mercury injection and returned to normal dietary protein immediately following mercury administration all survived and exhibited normal serum creatinine and BUN values within 4 days following mercury administration. The kidneys of this latter group took up significantly less radiolabeled mercury during the first 12 hr following mercury injection, and exhibited relatively little damage to the second segments (S2) of the proximal tubules. The third segments (S3) of the proximal tubules, however, exhibited the same degree of necrosis as that observed in the control group. Maintaining rats on high dietary protein regimens for shorter periods of time prior to mercury infusion (i.e., 12 or 24 hr) also dramatically reduced subsequent acute renal failure and improved survival, although not to the extent noted following 48 hr or longer on these diets. These observations suggested that high dietary protein regimens may protect from mercury nephrotoxicity by reducing mercury uptake to the second segments (S2) of the proximal tubules during the initial period of exposure to intravenously administered mercury.

  2. In vivo biofilm formation on stainless steel bonded retainers during different oral health-care regimens.

    PubMed

    Jongsma, Marije A; van der Mei, Henny C; Atema-Smit, Jelly; Busscher, Henk J; Ren, Yijin

    2015-03-23

    Retention wires permanently bonded to the anterior teeth are used after orthodontic treatment to prevent the teeth from relapsing to pre-treatment positions. A disadvantage of bonded retainers is biofilm accumulation on the wires, which produces a higher incidence of gingival recession, increased pocket depth and bleeding on probing. This study compares in vivo biofilm formation on single-strand and multi-strand retention wires with different oral health-care regimens. Two-centimetre wires were placed in brackets that were bonded to the buccal side of the first molars and second premolars in the upper arches of 22 volunteers. Volunteers used a selected toothpaste with or without the additional use of a mouthrinse containing essential oils. Brushing was performed manually. Regimens were maintained for 1 week, after which the wires were removed and the oral biofilm was collected to quantify the number of organisms and their viability, determine the microbial composition and visualize the bacteria by electron microscopy. A 6-week washout period was employed between regimens. Biofilm formation was reduced on single-strand wires compared with multi-strand wires; bacteria were observed to adhere between the strands. The use of antibacterial toothpastes marginally reduced the amount of biofilm on both wire types, but significantly reduced the viability of the biofilm organisms. Additional use of the mouthrinse did not result in significant changes in biofilm amount or viability. However, major shifts in biofilm composition were induced by combining a stannous fluoride- or triclosan-containing toothpaste with the mouthrinse. These shifts can be tentatively attributed to small changes in bacterial cell surface hydrophobicity after the adsorption of the toothpaste components, which stimulate bacterial adhesion to the hydrophobic oil, as illustrated for a Streptococcus mutans strain.

  3. Genetics-Based Pediatric Warfarin Dosage Regimen Derived Using Pharmacometric Bridging

    PubMed Central

    Lala, Mallika; Burckart, Gilbert J.; Takao, Cheryl M.; Pravica, Vera; Momper, Jeremiah D.; Gobburu, Jogarao V.S.

    2013-01-01

    BACKGROUND Warfarin dosage regimens using CYP2C9 and VKORC1 polymorphisms have been extensively studied in adults and is included in US Food and Drug Administration-approved warfarin labeling. However, no dosage algorithm is available for pediatric patients. OBJECTIVE To derive a genetics-based pediatric dosge regimen for warfarin, including starting dose and titration scheme. METHODS A model-based approach was developed based on a previously validated warfarin dosage model in adults, with subsequent comparison to pediatric data from pediatric warfarin dose, genotyping, and international normalized ratio (INR) results. The adult model was based on a previously established model from the CROWN (CReating an Optimal Warfarin dosing Nomogram) trial. Pediatric warfarin data were obtained from a study conducted at the Children’s Hospital of Los Angeles with 26 subjects. Variant alleles of CYP2C9 (rs1799853 or *2, and rs1057910 or *3) and the VKORC1 single nucleotide polymorphism (SNP) rs9923231 (−1639 G>A) were assessed, where the rs numbers are reference SNP identification tags assigned by the National Center for Biotechnology Information. RESULTS A pediatric warfarin model was derived using the previously validated model and clinical pharmacology considerations. The model was validated, and clinical trial simulation and stochastic modeling were used to optimize pediatric dosage and titration. The final dosage regimen was optimized based on simulations targeting a high (≥60%) proportion of INRs within the therapeutic range by week 2 of warfarin therapy while minimizing INRs >3.5 or <2. CONCLUSIONS The proposed pediatric warfarin dosage scheme based on individual CYP2C9 (alleles *1,*2,*3) and VKORC1 rs9923231 (-1639 G>A) genotypes may offer improved dosage compared to current treatment strategies, especially in patients with variant CYP2C9 and VKORC1 alleles. This pilot study provides the foundation for a larger prospective evaluation of genetics-based warfarin

  4. Cancer detection rates of different prostate biopsy regimens in patients with renal failure.

    PubMed

    Hoşcan, Mustafa Burak; Özorak, Alper; Oksay, Taylan; Perk, Hakkı; Armağan, Abdullah; Soyupek, Sedat; Serel, Tekin Ahmet; Koşar, Alim

    2014-07-01

    We aimed to evaluate the cancer detection rates of 6-, 10-, 12-core biopsy regimens and the optimal biopsy protocol for prostate cancer diagnosis in patients with renal failure. A total of 122 consecutive patients with renal failure underwent biopsy with age-specific prostate-specific antigen (PSA) levels up to 20 ng/mL. The 12-core biopsy technique (sextant biopsy + lateral base, lateral mid-zone, lateral apex, bilaterally) performed to all patients. Pathology results were examined separately for each sextant, 10-core that exclude parasagittal mid-zones from 12-cores (10a), 10-core that exclude apex zones from 12-cores (10b) and 12-core biopsy regimens. Of 122 patients, 37 (30.3%) were positive for prostate cancer. The cancer detection rates for sextant, 10a, 10b and 12 cores were 17.2%, 29%, 23.7% and 30.7%, respectively. Biopsy techniques of 10a, 10b and 12 cores increased the cancer detection rates by 40%, 27.5% and 43.2% among the sextant technique, respectively. Biopsy techniques of 10a and 12 cores increased the cancer detection rates by 17.1% and 21.6% among 10b biopsy technique, respectively. There were no statistical differences between 12 core and 10a core about cancer detection rate. Adding lateral cores to sextant biopsy improves the cancer detection rates. In our study, 12-core biopsy technique increases the cancer detection rate by 5.4% among 10a core but that was not statistically different. On the other hand, 12-core biopsy technique includes all biopsy regimens. We therefore suggest 12-core biopsy or minimum 10-core strategy incorporating six peripheral biopsies with elevated age- specific PSA levels up to 20 ng/mL in patients with renal failure.

  5. The Relationship between Grade of Ischemia, Success of Reperfusion, and Type of Thrombolytic Regimen

    PubMed Central

    Ayça, Burak; Conkbayır, Cenk; Katkat, Fahrettin; Gulsen, Kamil; Akin, Fatih; Okuyan, Ertuğrul; Baskurt, Murat; Okcun, Barıs

    2015-01-01

    Background This study was aimed to determine whether the grade of ischemia can predict the success of reperfusion in patients treated with thrombolytic therapy (TT) for ST elevation myocardial infarction (STEMI). Material/Methods We enrolled 229 consecutive patients with diagnosis of STEMI and receiving TT. Patients were divided into 2 groups – grade 2 ischemia (GI2) and grade 3 ischemia (GI3) – according to initial electrocardiogram (ECG). As TT, fibrin-specific (tissue plasminogen activator (t-PA)) or non-fibrin-specific (streptokinase (SKZ)) regimens were used. Successful reperfusion was defined as >50% resolution of the maximal ST segment on 90-min ECG. We tried to evaluate whether the grade of ischemia could predict the success of reperfusion and if there were any differences in terms of successful reperfusion between different thrombolytic regimens. Results The successful reperfusion rate was significantly higher in GI2 than GI3 (82.4% vs. 64.4% respectively, p=0.002). The success rate was lowest at anterior GI3 (55.8%). Although there was no significant difference between thrombolytic regimens in all groups (p=0.77), t-Pa was superior to SKZ in anterior GI3 (63,6% vs. 30%, p=0.061). In addition, in multivariate analysis, GI and infarct localization were found as independent predictors for successful reperfusion with TT (p=0.006 and p=0.042, respectively). Conclusions In the current study, we found that GI2 is an independent predictor for successful reperfusion in STEMI treated with TT. Fibrin specific regime should be preferred in anterior GI3. PMID:25746841

  6. Comparisons of memory for nonverbal auditory and visual sequential stimuli.

    PubMed

    McFarland, D J; Cacace, A T

    1995-01-01

    Properties of auditory and visual sensory memory were compared by examining subjects' recognition performance of randomly generated binary auditory sequential frequency patterns and binary visual sequential color patterns within a forced-choice paradigm. Experiment 1 demonstrated serial-position effects in auditory and visual modalities consisting of both primacy and recency effects. Experiment 2 found that retention of auditory and visual information was remarkably similar when assessed across a 10s interval. Experiments 3 and 4, taken together, showed that the recency effect in sensory memory is affected more by the type of response required (recognition vs. reproduction) than by the sensory modality employed. These studies suggest that auditory and visual sensory memory stores for nonverbal stimuli share similar properties with respect to serial-position effects and persistence over time.

  7. Multiple fault condition recognition of gearbox with sequential hypothesis test

    NASA Astrophysics Data System (ADS)

    Chen, Hanxin; Shang, Yunfei; Sun, Kui

    2013-11-01

    A novel method for the fault condition recognition in which the recognition system interrogates a propagation channel adaptively and intelligently by using the available data is proposed based on sequential hypothesis testing. The waveform of the data in the propagation channel for the fault condition recognition is designed with the kurtosis of the measured data in time domain. The sequential hypothesis testing framework is proposed when hard decisions are made with adequate confidence. The distinguished characteristic of the channel recognition is that it operates in a closed loop and makes constant optimization in response to its changing understanding of the channel. The fault condition recognition of the gearbox is to update the multiple target hypothesis/class based on the measured data, customize waveform as the class probabilities changes, and make conclusion when the sufficient understanding of the propagation channel is achieved.

  8. 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.

  9. Sequential Folding using Light-activated Polystyrene Sheet

    PubMed Central

    Lee, Yonghee; Lee, Hyeok; Hwang, Taesoon; Lee, Jong-Gu; Cho, Maenghyo

    2015-01-01

    A pre-strained polystyrene (PS) polymer sheet is deformed when it approaches the glass transition state as a result of light absorption. By controlling the light absorption of the polymer sheet, non-contact sequential folding can be accomplished. Line patterns of different transparencies and shapes are used to control the light absorption. The line pattern shape is closely related to the folding angle and folding start time. The relation between the line pattern design and folding performance was evaluated experimentally to develop a technique for folding PS sheets. The results show that sequential folding of PS sheets can be accomplished by changing the degree of transparency of the line pattern. Using the technique developed in this study, self-folding origami structures with complicated shapes can be designed and manufactured. PMID:26559611

  10. 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. PMID:23505831

  11. 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.

  12. 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.

  13. Sequential filtering applied to the determination of tracking station locations

    NASA Technical Reports Server (NTRS)

    Schutz, B. E.; Condon, S. P.; Tapley, B. D.

    1975-01-01

    The extended sequential filter has been applied to the problem of dynamically determining the geocentric coordinates of two laser satellite tracking stations. This filter provides significant advantages over the classical batch methods through (1) fewer iterations required for convergence, (2) wider radius of convergence, and (3) availability of the parameter estimate evolution. Processing the data sequentially readily identifies the data arcs required to minimize the effects of geopotential model errors. By means of the Smithsonian standard earth 2 and the Goddard earth model 1 geopotentials to reduce laser range observations of the Beacon Explorer-C satellite, it is demonstrated that a two-pass arc is optimal for estimating the height of one station and all coordinates of the second station while minimizing the effect of geopotential model error. These two-pass estimates are in good agreement with other determinations that utilize considerably more data as well as different satellites.

  14. 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.

  15. The use of sequential probabilities in the segmentation of speech.

    PubMed

    van der Lugt, A H

    2001-07-01

    The present investigation addresses the possible utility of sequential probabilities in the segmentation of spoken language. In a series of five word- spotting and two control lexical decision experiments, high- versus low-probability consonant-vowel (Experiments 1, 2, 5, and 7) and vowel-consonant (Experiments 1, 3, 4, and 6) strings were presented either in the nonsense contexts of target words (Experiments 1-3) or within the target words themselves (Experiments 4-7). The results suggest that listeners, at least for sequences in the onset position, indeed use sequential probabilities as cues for segmentation. The probability of a sound sequence influenced segmentation more when the sequence occurred within the target words (Experiments 4-7 vs. Experiments 1-3). Furthermore, the effects were reliable only when the sequences occurred in the onset position (Experiments 1, 2, 5, and 7 vs. Experiments 1, 3, 4, and 6). PMID:11521849

  16. 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.

  17. 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.

  18. Plasmon-driven sequential chemical reactions in an aqueous environment

    PubMed Central

    Zhang, Xin; Wang, Peijie; Zhang, Zhenglong; Fang, Yurui; Sun, Mengtao

    2014-01-01

    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. PMID:24958029

  19. 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.

  20. A Minimax Procedure in the Context of Sequential Mastery Testing. Research Report 99-04.

    ERIC Educational Resources Information Center

    Vos, Hans J.

    The purpose of this paper is to derive optimal rules for sequential mastery tests. In a sequential mastery test, the decision is to classify a subject as a master or a nonmaster, or to continue sampling and administering another random test item. The framework of minimax sequential decision theory (minimum information approach) is used; that is,…

  1. 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)

  2. 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…

  3. Comparative Impact of Suppressive Antiretroviral Regimens on the CD4/CD8 T-Cell Ratio: A Cohort Study.

    PubMed

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

    2016-03-01

    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 CD4/CD8 increase in the

  4. Acid demineralization susceptibility of dental enamel submitted to different bleaching techniques and fluoridation regimens.

    PubMed

    Salomão, Dlf; Santos, Dm; Nogueira, Rd; Palma-Dibb, Rg; Geraldo-Martins, Vr

    2014-01-01

    The aim of the current study was to assess the acid demineralization susceptibility of bleached dental enamel submitted to different fluoride regimens. One hundred bovine enamel blocks (6×6×3 mm) were randomly divided into 10 groups (n=10). Groups 1 and 2 received no bleaching. Groups 3 to 6 were submitted to an at-home bleaching technique using 6% hydrogen peroxide (HP; G3 and G4) or 10% carbamide peroxide (CP; G5 and G6). Groups 7 to 10 were submitted to an in-office bleaching technique using 35% HP (G7 and G8) or 35% CP (G9 and G10). During bleaching, a daily fluoridation regimen of 0.05% sodium fluoride (NaF) solution was performed on groups 3, 5, 7, and 9, while weekly fluoridation with a 2% NaF gel was performed on groups 4, 6, 8, and 10. The samples in groups 2 to 10 were pH cycled for 14 consecutive days. The samples from all groups were then assessed by cross-sectional Knoop microhardness at different depths from the outer enamel surface. The average Knoop hardness numbers (KHNs) were compared using one-way analysis of variance and Tukey tests (α=0.05). The comparison between groups 1 and 2 showed that the demineralization method was effective. The comparison among groups 2 to 6 showed the same susceptibility to acid demineralization, regardless of the fluoridation method used. However, the samples from groups 8 and 10 showed more susceptibility to acid demineralization when compared with group 2 (p<0.05). Groups 7 and 9 provided similar results to group 2, but the results of those groups were different when compared with groups 8 and 10. The use of 6% HP and 10% CP associated with daily or weekly fluoridation regimens did not increase the susceptibility of enamel to acid demineralization. However, the use of 35% HP and 35% CP must be associated with a daily fluoridation regimen, otherwise the in-office bleaching makes the bleached enamel more susceptible to acid demineralization.

  5. Hepatitis C treatment in the elderly: New possibilities and controversies towards interferon-free regimens.

    PubMed

    Vespasiani-Gentilucci, Umberto; Galati, Giovanni; Gallo, Paolo; De Vincentis, Antonio; Riva, Elisabetta; Picardi, Antonio

    2015-06-28

    Due to the progressive aging of the hepatitis C virus (HCV) population which have acquired the infection during its maximum spread after the Second World War, the management of the elderly HCV-infected patient is emerging as a hot topic. Unfortunately, although it is recognized that the progression of HCV-related liver disease gets faster with aging, and that even extra-hepatic manifestations of HCV infection are probably worse in the elderly, till now, treatment attempts in this population have been significantly limited by the well-known contraindications and side effects of interferon (IFN). The arrival of several new anti-HCV drugs, and the possibility to combine them in safe and effective anti-viral regimens, is relighting the hope of a cure for many elderly patients who had been cut out of IFN-based treatments. However, although these new regimens will be certainly more manageable, it should be underscored that IFN-free doesn't mean free from any contraindication or side-effect. Moreover, one issue which promises to become central is that of the possible interactions between antiviral therapy and the multiple drugs frequently assumed by elderly patients because of comorbidities. In this review, we will revise the epidemiology pointing to HCV as an infection of the elderly, the evidences that HCV harms the health of the aged patient more than that of the young one, and the available experiences of HCV treatment in the elderly with the "old" IFN-based regimens and with the newer drugs. We will conclude that the availability of IFN-free regimens should prompt us to change our mind and consider a significantly larger number of possible candidates among elderly patients, who would take significant advantage from viral eradication. Rather than the anagraphic age, drug-drug interactions and, mainly in case of economic restrictions, an evaluation of life expectancy dependent on liver disease with respect to that dependent on comorbidities, are likely to be the key

  6. Hepatitis C treatment in the elderly: New possibilities and controversies towards interferon-free regimens

    PubMed Central

    Vespasiani-Gentilucci, Umberto; Galati, Giovanni; Gallo, Paolo; De Vincentis, Antonio; Riva, Elisabetta; Picardi, Antonio

    2015-01-01

    Due to the progressive aging of the hepatitis C virus (HCV) population which have acquired the infection during its maximum spread after the Second World War, the management of the elderly HCV-infected patient is emerging as a hot topic. Unfortunately, although it is recognized that the progression of HCV-related liver disease gets faster with aging, and that even extra-hepatic manifestations of HCV infection are probably worse in the elderly, till now, treatment attempts in this population have been significantly limited by the well-known contraindications and side effects of interferon (IFN). The arrival of several new anti-HCV drugs, and the possibility to combine them in safe and effective anti-viral regimens, is relighting the hope of a cure for many elderly patients who had been cut out of IFN-based treatments. However, although these new regimens will be certainly more manageable, it should be underscored that IFN-free doesn’t mean free from any contraindication or side-effect. Moreover, one issue which promises to become central is that of the possible interactions between antiviral therapy and the multiple drugs frequently assumed by elderly patients because of comorbidities. In this review, we will revise the epidemiology pointing to HCV as an infection of the elderly, the evidences that HCV harms the health of the aged patient more than that of the young one, and the available experiences of HCV treatment in the elderly with the “old” IFN-based regimens and with the newer drugs. We will conclude that the availability of IFN-free regimens should prompt us to change our mind and consider a significantly larger number of possible candidates among elderly patients, who would take significant advantage from viral eradication. Rather than the anagraphic age, drug-drug interactions and, mainly in case of economic restrictions, an evaluation of life expectancy dependent on liver disease with respect to that dependent on comorbidities, are likely to be the

  7. Influence of daily regimen calcium and vitamin D supplementation on parathyroid hormone secretion.

    PubMed

    Reginster, J-Y; Zegels, B; Lejeune, E; Micheletti, M C; Kvsaz, A; Seidel, L; Sarlet, N

    2002-02-01

    Calcium and vitamin D supplementation has been shown to reduce secondary hyperparathyroidism and play a role in the management of senile osteoporosis. In order to define the optimal regimen of calcium and vitamin D supplementation to produce the maximal inhibition of parathyroid hormone secretion, we have compared the administration of a similar amount of Ca and vitamin D, either as a single morning dose or split in two doses, taken 6 hours apart. Twelve healthy volunteers were assigned to three investigational procedures, at weekly intervals. After a blank control procedure, when they were not exposed to any drug intake, they received two calcium-vitamin D supplement regimens including either two doses of Orocal D3 (500 mg Ca and 400 IU vitamin D) 6 hours apart or one water-soluble effervescent powder pack of Cacit D3 in a single morning dose (1000 mg Ca and 880 IU vitamin D). During the three procedures (control and the two calcium-vitamin D supplementations), venous blood was drawn every 60 minutes for up to 9 hours, for serum Ca and serum PTH measurements. The order of administration of the two Ca and vitamin D supplementation sequences was allocated by randomization. No significant changes in serum Ca were observed during the study. During the 6 hours following Ca and vitamin D supplementation, a statistically significant decrease in serum PTH was observed with both regimens, compared with baseline and with the control procedure. Over this period of time, no differences were observed between the two treatment regimens. However, between the sixth and the ninth hour, serum PTH levels were still significantly decreased compared with baseline with split dose Orocal D3 administration, while they returned to baseline value with the Cacit D3 preparation. During this period, the percentage decrease in serum PTH compared with baseline was significantly more pronounced with Orocal D3 than with Cacit D3 (P = 0.0021). We therefore conclude that the administration of two

  8. [A case of malignant pheochromocytoma treated with 131I-metaiodobenzylguanidine and CVD regimen].

    PubMed

    Ukimura, O; Kojima, M; Hosoi, S; Itoh, H; Watanabe, H; Minamikawa, T

    1994-05-01

    A 44-year-old male had multiple metastasis to the lung, liver, kidney and paraaortic lymph node from primary adrenal malignant pheochromocytoma. Radiation therapy with 131I-metaiodobenzylguanidine (131I-MIBG), was first performed, which was followed by chemotherapy with cyclophosphamide, vincristine and dacarbazine (CVD). A total amount of 4810 MBq of 131I-MIBG was administered then 7 cycles of CVD regimen were added. He was survived for sixteen months with tumor response in primary tumor, paraaortic lymph node and liver metastasis tumors, in addition to hormonal response. It was considered that the survival was prolonged in spite of advanced case with inoperative primary tumor.

  9. Rethinking Dosing Regimen Selection of Piperaquine for Malaria Chemoprevention: A Simulation Study

    PubMed Central

    Sambol, Nancy C.; Tappero, Jordan W.; Arinaitwe, Emmanuel; Parikh, Sunil

    2016-01-01

    Background The combination of short-acting dihydroartemisinin and long-acting piperaquine (DP) is among the first-line therapies for the treatment of uncomplicated Plasmodium falciparum malaria. Population pharmacokinetic models of piperaquine (PQ) based on data from acute treatment of young children can be used to predict exposure profiles of piperaquine under different DP chemoprevention regimens. The purpose of our study was to make such predictions in young children. Methods Based on a prior population pharmacokinetic model of PQ in young Ugandan children, we simulated capillary plasma concentration-time profiles (including their variability) of candidate chemoprevention regimens for a reference population of 1–2 year olds weighing at least 11 kg. Candidate regimens that were tested included monthly administration of standard therapeutic doses, bimonthly dosing, and weekly dosing (with and without a loading dose). Results Once daily doses of 320 mg for three days (960 mg total) at the beginning of each month are predicted to achieve an average steady-state trough capillary piperaquine concentration of 35 ng/mL, with 60% achieving a level of 30 ng/mL or higher. In contrast, weekly dosing of 320 mg (i.e., 33% higher amount per month) is predicted to approximately double the average steady-state trough concentration, increase the percent of children predicted to achieve 30 ng/mL or higher (94%), while at the same time lowering peak concentrations. Exposure at steady-state, reached at approximately 3 months of multiple dosing, is expected to be approximately 2-fold higher than exposure following initial dosing, due to accumulation. A loading dose improves early exposure, thereby reducing the risk of breakthrough infections at the initiation of chemoprevention. Conclusions Once weekly chemoprevention of DP predicts favourable exposures with respect to both trough and peak concentrations. These predictions need to be verified, as well as safety evaluated, in field

  10. 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

  11. 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.

  12. Reservoir characterization with sequential Gaussian simulation constrained by diffraction tomography

    SciTech Connect

    Lo, T.W.; Bermawi, A.

    1994-12-31

    A geostatistical approach for reservoir characterization that honors both surface seismic data and wireline data is described. It first computes a velocity profiles with seismic diffraction tomography, then, performs kriging with an external drift and sequential Gaussian simulation using the velocity profiles as soft data and the sonic logs as hard data. The product is a velocity profile with a resolution as high as that of the smoothed sonic logs, showing lateral velocity variations constrained by surface seismic data.

  13. Effect of sequential isoproturon pulse exposure on Scenedesmus vacuolatus.

    PubMed

    Vallotton, Nathalie; Eggen, Rik Ilda Lambertus; Chèvre, Nathalie

    2009-04-01

    Aquatic organisms are typically exposed to fluctuating concentrations of herbicides in streams. To assess the effects on algae of repeated peak exposure to the herbicide isoproturon, we subjected the alga Scenedesmus vacuolatus to two sequential pulse exposure scenarios. Effects on growth and on the inhibition of the effective quantum yield of photosystem II (PSII) were measured. In the first scenario, algae were exposed to short, 5-h pulses at high isoproturon concentrations (400 and 1000 microg/l), each followed by a recovery period of 18 h, while the second scenario consisted of 22.5-h pulses at lower concentrations (60 and 120 microg/l), alternating with short recovery periods (1.5 h). In addition, any changes in the sensitivity of the algae to isoproturon following sequential pulses were examined by determining the growth rate-EC(50) prior to and following exposure. In both exposure scenarios, we found that algal growth and its effective quantum yield were systematically inhibited during the exposures and that these effects were reversible. Sequential pulses to isoproturon could be considered a sequence of independent events. Nevertheless, a consequence of inhibited growth during the repeated exposures is the cumulative decrease in biomass production. Furthermore, in the second scenario, when the sequence of long pulses began to approach a scenario of continuous exposure, a slight increase in the tolerance of the algae to isoproturon was observed. These findings indicated that sequential pulses do affect algae during each pulse exposure, even if algae recover between the exposures. These observations could support an improved risk assessment of fluctuating exposures to reversibly acting herbicides. PMID:18709397

  14. 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

  15. Automatic sequential fluid handling with multilayer microfluidic sample isolated pumping.

    PubMed

    Liu, Jixiao; Fu, Hai; Yang, Tianhang; Li, Songjing

    2015-09-01

    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 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.

  17. Forced guidance and distribution of practice in sequential information processing.

    NASA Technical Reports Server (NTRS)

    Decker, L. R.; Rogers, C. A., Jr.

    1973-01-01

    Distribution of practice and forced guidance were used in a sequential information-processing task in an attempt to increase the capacity of human information-processing mechanisms. A reaction time index of the psychological refractory period was used as the response measure. Massing of practice lengthened response times while forced guidance shortened them. Interpretation was in terms of load reduction upon the response-selection stage of the information-processing system.-

  18. 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.

  19. Bioerodible System for Sequential Release of Multiple Drugs

    PubMed Central

    Sundararaj, Sharath C.; Thomas, Mark V.; Dziubla, Thomas D.; Puleo, David A.

    2013-01-01

    Because many complex physiological processes are controlled by multiple biomolecules, comprehensive treatment of certain disease conditions may be more effectively achieved by administration of more than one type of drug. Thus, the objective of the present research was to develop a multilayered, polymer-based system for sequential delivery of multiple drugs. The polymers used were cellulose acetate phthalate (CAP) complexed with Pluronic F-127 (P). After evaluating morphology of the resulting CAPP system, in vitro release of small molecule drugs and a model protein was studied from both single and multilayered devices. Drug release from single-layered CAPP films followed zero-order kinetics related to surface erosion of the association polymer. Release studies from multilayered CAPP devices showed the possibility of achieving intermittent release of one type of drug as well as sequential release of more than one type of drug. Mathematical modeling accurately predicted the release profiles for both single layer and multilayered devices. The present CAPP association polymer-based multilayer devices can be used for localized, sequential delivery of multiple drugs for the possible treatment of complex disease conditions, and perhaps for tissue engineering applications, that require delivery of more than one type of biomolecule. PMID:24096151

  20. Effectiveness of sequential automatic-manual home respiratory polygraphy scoring.

    PubMed

    Masa, Juan F; Corral, Jaime; Pereira, Ricardo; Duran-Cantolla, Joaquin; Cabello, Marta; Hernández-Blasco, Luis; Monasterio, Carmen; Alonso-Fernandez, Alberto; Chiner, Eusebi; Vázquez-Polo, Francisco-José; Montserrat, Jose M

    2013-04-01

    Automatic home respiratory polygraphy (HRP) scoring functions can potentially confirm the diagnosis of sleep apnoea-hypopnoea syndrome (SAHS) (obviating technician scoring) in a substantial number of patients. The result would have important management and cost implications. The aim of this study was to determine the diagnostic cost-effectiveness of a sequential HRP scoring protocol (automatic and then manual for residual cases) compared with manual HRP scoring, and with in-hospital polysomnography. We included suspected SAHS patients in a multicentre study and assigned them to home and hospital protocols at random. We constructed receiver operating characteristic (ROC) curves for manual and automatic scoring. Diagnostic agreement for several cut-off points was explored and costs for two equally effective alternatives were calculated. Of 366 randomised patients, 348 completed the protocol. Manual scoring produced better ROC curves than automatic scoring. There was no sensitive automatic or subsequent manual HRP apnoea-hypopnoea index (AHI) cut-off point. The specific cut-off points for automatic and subsequent manual HRP scorings (AHI >25 and >20, respectively) had a specificity of 93% for automatic and 94% for manual scorings. The costs of manual protocol were 9% higher than sequential HRP protocol; these were 69% and 64%, respectively, of the cost of the polysomnography. A sequential HRP scoring protocol is a cost-effective alternative to polysomnography, although with limited cost savings compared to HRP manual scoring.