The Study of Productivity Measurement and Incentive Methodology (Phase III - Paper Test). Volume 1
1986-03-14
possible to measure explicitly, in terms of dollars the profit impacts of these uncontrollable as well as controllable factors and to de - termine and...the rate of engineering changes increases. • Production processes arc be- coming less reliant on direct la - bor as the primary factor in pro...MFPMM makes it •: —.sibie to measure explicitly, in terms of dollars the profit impacts of these uncontrollable as well as controllable factors and to de
Cheung, Deanna G; Aizenberg, Diego; Gorbunov, Vladimir; Hafeez, Kudsia; Chen, Chien-Wei; Zhang, Jack
2018-01-01
A majority of patients with hypertension fail to achieve blood pressure (BP) control despite treatment with commonly prescribed drugs. This randomized, double-blind phase III trial assessed the superiority of sacubitril/valsartan 200 mg (97/103 mg) to continued olmesartan 20 mg in reducing ambulatory systolic BP after 8-week treatment in patients with mild to moderate essential hypertension uncontrolled with olmesartan 20 mg alone. A total of 376 patients were randomized to receive either sacubitril/valsartan (n = 188) or olmesartan (n = 188). Superior reductions in 24-hour mean ambulatory systolic BP were observed in the sacubitril/valsartan group vs the olmesartan group (-4.3 mm Hg vs -1.1 mm Hg, P < .001). Reductions in 24-hour mean ambulatory diastolic BP and pulse pressure and office systolic BP and diastolic BP were significantly greater with sacubitril/valsartan vs olmesartan (P < .014). A greater proportion of patients achieved BP control with sacubitril/valsartan vs olmesartan. The overall incidence of adverse events was comparable between the groups. Compared with continued olmesartan, sacubitril/valsartan was more effective and generally safe in patients with hypertension uncontrolled with olmesartan 20 mg. ©2018 Wiley Periodicals, Inc.
Burke, Thomas F; Danso-Bamfo, Sandra; Guha, Moytrayee; Oguttu, Monica; Tarimo, Vincent; Nelson, Brett D
2017-10-01
To examine the outcomes of women in advanced shock from uncontrolled postpartum hemorrhage (PPH) who underwent placement of an Every Second Matters for Mothers and Babies Uterine Balloon Tamponade (ESM-UBT) device. In a prospective case series, data were collected for women who received an ESM-UBT device at healthcare facilities in Kenya, Senegal, Sierra Leone, and Tanzania between September 1, 2012, and September 30, 2016. Shock class was assigned on the basis of recorded blood pressures and mental status at the time of UBT placement. Data for 306 women with uncontrolled PPH from uterine atony across 117 facilities were analyzed. Normal vital signs or class I/II shock were reported for 166 (54.2%). In this group, one death occurred and was attributed to PPH (survival rate 99.4%). There were no cases of shock progression. One hundred and eleven (36.3%) were in class III shock and 29 (9.5%) in class IV shock; the respective survival rates were 97.3% (n=108) and 86.2% (n=25). The ESM-UBT device arrests hemorrhage, prevents shock progression, and is associated with high survival rates among women with uncontrolled PPH from uterine atony. © 2017 International Federation of Gynecology and Obstetrics.
Stern, S A; Jwayyed, S; Dronen, S C; Wang, X
2000-08-01
Resuscitation studies of hypertonic saline using controlled and uncontrolled hemorrhage models yield conflicting results with regard to efficacy. These disparate results reflect the use of models and resuscitation regimens that are not comparable between studies. This study evaluated the effects of comparable and clinically relevant resuscitation regimens of 7.5% sodium chloride/6% dextran 70 (HSD) and 0.9% sodium chloride (NS) in a near-fatal uncontrolled hemorrhage model. Thirty-six swine (14.2 to 21.4 kg) with 4-mm aortic tears were bled to a pulse pressure of 5 mm Hg (40-45 mL/kg). The animals were resuscitated with either NS or HSD administered in volumes that provided equivalent sodium loads at similar rates. Group II (n = 12) was resuscitated with 80 mL/kg of NS at a rate of 4 mL/kg/min. Group III (n = 12) received 9.6 mL/kg of HSD at a rate of 0.48 mL/kg/min. In both groups, crystalloid resuscitation was followed by shed blood infusion (30 mL/kg) at a rate of 2 mL/kg/min. Group I (controls; n = 12) were not resuscitated. One-hour mortality was significantly greater in group I (92%) as compared with group II (33%) and group III (33%) (Fisher's exact test; p = 0.004). Intraperitoneal hemorrhage was significantly greater in group II (34 +/- 20 mL/kg) and group III (31 +/- 13 mL/ kg) as compared with group I (5 +/- 2 mL/kg) (ANOVA; p < 0.05). There was no significant difference in hemodynamic parameters between groups II and III. In this model of severe uncontrolled hemorrhage, resuscitation with HSD or NS, administered in volumes that provided equivalent sodium loads at similar rates, had similar effects on mortality, hemodynamic parameters, and hemorrhage from the injury site.
Lacosamide: in partial-onset seizures.
Cross, Sarah A; Curran, Monique P
2009-01-01
Lacosamide is a functionalized amino acid, the antiepileptic effects of which appear to be due to a novel mode of action, namely the selective enhancement of slow inactivation of voltage-gated sodium channels. Lacosamide is available as oral or intravenous formulations. Bioequivalence between the oral tablet and the oral syrup of lacosamide has been established. The bioavailability of the oral lacosamide tablet was similar to that of a 30- or 60-minute intravenous infusion of lacosamide administered at the same dosage. Oral lacosamide when added concomitantly with between one and three antiepileptic drugs was effective in adult patients with uncontrolled partial-onset seizures with or without secondary generalization, according to pooled data (n = 1308) from three phase II/III studies that had a 12-week maintenance phase. The percentage of patients with a >or=50% reduction from baseline to the maintenance phase in seizure frequency was significantly greater with oral lacosamide 200 or 400 mg/day (34% and 40%) than with placebo (23%). The median percentage reduction in seizure frequency per 28 days from baseline to the maintenance phase was significantly greater with lacosamide 400 mg/day than with placebo in each of the three phase II/III studies. Lacosamide was generally well tolerated in adult patients with partial-onset seizures, with most treatment-emergent adverse events being of mild or moderate severity. Dizziness was the most common treatment-related adverse event. When used as short-term replacement for oral lacosamide, intravenous lacosamide was well tolerated when administered as a 15-, 30- or 60-minute infusion.
Targeted therapy for localized non-small-cell lung cancer: a review
Paleiron, Nicolas; Bylicki, Olivier; André, Michel; Rivière, Emilie; Grassin, Frederic; Robinet, Gilles; Chouaïd, Christos
2016-01-01
Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC), but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations) is a major challenge. PMID:27462164
Masab, Muhammad; Saif, Muhammad Wasif
2017-12-01
Metastatic neuroendocrine tumors (NETs) are associated with carcinoid syndrome that is typically characterized by diarrhea, cutaneous flushing and bronchospasm. Treatment with somatostatin analogues (SSA) improves the symptom burden but a significant proportion of patients stop responding to SSA therapy eventually. Novel agents with the potential to effectively control the symptoms are urgently needed. This article reviews an in-depth analysis of the phase I-III clinical trials determining the clinical rationale for the use of tryptophan hydroxylase inhibitor, telotristat ethyl in patients with well-differentiated metastatic NETs and uncontrolled carcinoid syndrome. Telotristat ethyl has already been approved for the treatment of inadequately controlled carcinoid syndrome symptoms in metastatic NET patients on SSA therapy. Results from multiple phase I-III clinical studies of telotristat ethyl therapy have reported a significant decrease in the daily bowel movement frequency, increase in quality of life and the subsequent decrease in annual health costs related to carcinoid syndrome symptoms in NET patients. The associated decrease in urinary 5-hydroxyindoleacetic acid (u5-HIAA) provides evidence that telotristat ethyl effectively decreases serotonin production, and therefore, offers a rationale to investigate this agent to mitigate serotonin-mediated complications in this patient population, especially cardiac valvular disease or mesenteric fibrosis.
2005-07-01
drugs are used to reduce surgical bleeding. This series of studies tested whether these drugs (aprotinin, desmopressin, tranexamic acid , e- aminocaproic ...desmopressin, tranexamic acid , 8- aminocaproic acid ) could reduce bleeding due to traumatic injuries in two models of uncontrolled hemorrhage in rats... acid ) could reduce bleeding due to traumatic injuries in two models of uncontrolled hemorrhage in rats. In the first phase of each study, a lethal
Sperling, Michael R; Abou-Khalil, Bassel; Harvey, Jay; Rogin, Joanne B; Biraben, Arnaud; Galimberti, Carlo A; Kowacs, Pedro A; Hong, Seung Bong; Cheng, Hailong; Blum, David; Nunes, Teresa; Soares-da-Silva, Patrício
2015-02-01
To evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial-onset seizures. This randomized, placebo-controlled, double-blind, parallel-group, phase III study was conducted at 173 centers in 19 countries, including the United States and Canada. Eligible patients were aged ≥16 years and had uncontrolled partial-onset seizures despite treatment with 1-2 antiepileptic drugs (AEDs). After an 8-week baseline period, patients were randomized to once-daily placebo (n = 226), ESL 800 mg (n = 216), or ESL 1,200 mg (n = 211). Following a 2-week titration period, patients received ESL 800 or 1,200 mg once-daily for 12 weeks. Seizure data were captured and documented using event-entry or daily entry diaries. Standardized seizure frequency (SSF) during the maintenance period (primary end point) was reduced with ESL 1,200 mg (p = 0.004), and there was a trend toward improvement with ESL 800 mg (p = 0.06), compared with placebo. When data for titration and maintenance periods were combined, ESL 800 mg (p = 0.001) and 1,200 mg (p < 0.001) both reduced SSF. There were no statistically significant interactions between treatment response and geographical region (p = 0.38) or diary version (p = 0.76). Responder rate (≥50% reduction in SSF) was significantly higher with ESL 1,200 mg (42.6%, p < 0.001) but not ESL 800 mg (30.5%, p = 0.07) than placebo (23.1%). Incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation increased with ESL dose. The most common TEAEs were dizziness, somnolence, nausea, headache, and diplopia. Adjunctive ESL 1,200 mg once-daily was more efficacious than placebo in adult patients with refractory partial-onset seizures. The once-daily 800 mg dose showed a marginal effect on SSF, but did not reach statistical significance. Both doses were well tolerated. Efficacy assessment was not affected by diary format used. © 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.
Xiao, Jing; Hua, Tianqi; Shen, Huan; Zhang, Min; Wang, Xiao-Jian; Gao, Yue-Xia; Lu, Qinyun; Wu, Chuanli
2017-04-07
We evaluated how metabolic disorders affected antihypertension therapy. 2,912 rural Chinese patients with hypertension who provided blood samples, demographic and clinical data at baseline and after 1 year of antihypertension therapy were evaluated. At baseline, 1,515 patients (52.0%) were already receiving drug therapy and 11.4% of them had controlled blood pressure (BP). After 1 year, all 2,912 patients were receiving antihypertension therapy that was administered by community physicians, and 59.42% of them had controlled BP. Central obesity and abnormal triglyceride, high-density lipoprotein cholesterol, and glucose were associated with 15-70% higher risks of uncontrolled hypertension. Metabolic syndrome using the JIS criteria was associated with poor BP control (odds ratio: 1.71 and 1.54 for the baseline and follow-up datasets, respectively). The risk of uncontrolled hypertension increased with the number of metabolic disorders (p for trend <0.01). The presence of ≥3 metabolic disorder factors was associated with higher risks of poor BP control. The associations of metabolic factors and uncontrolled hypertension were stronger for the standard and modified ATP III criteria, compared to the IDF and JIS criteria. Metabolic factors were associated with less effective antihypertension therapy, and all definitions of metabolic syndrome helped identify patients with elevated risks of uncontrolled hypertension.
Risk Assessment During the Final Phase of an Uncontrolled Re-Entry
NASA Astrophysics Data System (ADS)
Gaudel, A.; Hourtolle, C.; Goester, J. F.; Fuentes, N.
2013-09-01
As French National Space Agency, CNES is empowered to monitor compliance with technical regulations of the French Space Operation Act, FSOA, and to take all necessary measures to ensure the safety of people, property, public health and environment for all space operations involving French responsibility at international level.Therefore, CNES developed ELECTRA that calculates the risk for ground population involved in three types of events: rocket launching, controlled re-entry and uncontrolled re-entry. For the first two cases, ELECTRA takes into account degraded cases due to a premature stop of propulsion.Major evolutions were implemented recently on ELECTRA to meet new users' requirements, like the risk assessment during the final phase of uncontrolled re-entry, that can be combined with the computed risk for each country involved by impacts.The purpose of this paper is to provide an overview of the ELECTRA method and main functionalities, and then to highlight these recent improvements.
26 CFR 1.482-0 - Outline of regulations under section 482.
Code of Federal Regulations, 2011 CFR
2011-04-01
... transfer pricing rules for other transactions. (1) Services transactions that include other types of.... (iii) Subleases. (d) Transfer of property. (e) [Reserved] For further guidance, see § 1.482-0T, the... in connection with a transfer of tangible property. (a) In general. (b) Comparable uncontrolled price...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-06-04
... or refer to air-fuel ratio controls. iii. The initials BART mean or refer to Best Available Retrofit... install BART controls for the purpose of eliminating or reducing visibility impairment. The specific... retrofit controls at certain larger, often uncontrolled, older stationary sources in order to address...
40 CFR 63.498 - Back-end process provisions-recordkeeping.
Code of Federal Regulations, 2011 CFR
2011-07-01
... be the crumb rubber dry weight of the rubber leaving the stripper. (iv) The organic HAP content of... be the crumb rubber dry weight of the crumb rubber leaving the stripper. (iii) The hourly average of... test runs. (1) The uncontrolled residual organic HAP content in the latex or dry crumb rubber, as...
40 CFR 63.498 - Back-end process provisions-recordkeeping.
Code of Federal Regulations, 2012 CFR
2012-07-01
... be the crumb rubber dry weight of the rubber leaving the stripper. (iv) The organic HAP content of... be the crumb rubber dry weight of the crumb rubber leaving the stripper. (iii) The hourly average of... test runs. (1) The uncontrolled residual organic HAP content in the latex or dry crumb rubber, as...
40 CFR 63.498 - Back-end process provisions-recordkeeping.
Code of Federal Regulations, 2014 CFR
2014-07-01
... be the crumb rubber dry weight of the rubber leaving the stripper. (iv) The organic HAP content of... be the crumb rubber dry weight of the crumb rubber leaving the stripper. (iii) The hourly average of... test runs. (1) The uncontrolled residual organic HAP content in the latex or dry crumb rubber, as...
40 CFR 63.498 - Back-end process provisions-recordkeeping.
Code of Federal Regulations, 2013 CFR
2013-07-01
... be the crumb rubber dry weight of the rubber leaving the stripper. (iv) The organic HAP content of... be the crumb rubber dry weight of the crumb rubber leaving the stripper. (iii) The hourly average of... test runs. (1) The uncontrolled residual organic HAP content in the latex or dry crumb rubber, as...
Sperling, Michael R; Abou-Khalil, Bassel; Harvey, Jay; Rogin, Joanne B; Biraben, Arnaud; Galimberti, Carlo A; Kowacs, Pedro A; Hong, Seung Bong; Cheng, Hailong; Blum, David; Nunes, Teresa; Soares-da-Silva, Patrício
2015-01-01
Objective To evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial-onset seizures. Methods This randomized, placebo-controlled, double-blind, parallel-group, phase III study was conducted at 173 centers in 19 countries, including the United States and Canada. Eligible patients were aged ≥16 years and had uncontrolled partial-onset seizures despite treatment with 1–2 antiepileptic drugs (AEDs). After an 8-week baseline period, patients were randomized to once-daily placebo (n = 226), ESL 800 mg (n = 216), or ESL 1,200 mg (n = 211). Following a 2-week titration period, patients received ESL 800 or 1,200 mg once-daily for 12 weeks. Seizure data were captured and documented using event-entry or daily entry diaries. Results Standardized seizure frequency (SSF) during the maintenance period (primary end point) was reduced with ESL 1,200 mg (p = 0.004), and there was a trend toward improvement with ESL 800 mg (p = 0.06), compared with placebo. When data for titration and maintenance periods were combined, ESL 800 mg (p = 0.001) and 1,200 mg (p < 0.001) both reduced SSF. There were no statistically significant interactions between treatment response and geographical region (p = 0.38) or diary version (p = 0.76). Responder rate (≥50% reduction in SSF) was significantly higher with ESL 1,200 mg (42.6%, p < 0.001) but not ESL 800 mg (30.5%, p = 0.07) than placebo (23.1%). Incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation increased with ESL dose. The most common TEAEs were dizziness, somnolence, nausea, headache, and diplopia. Significance Adjunctive ESL 1,200 mg once-daily was more efficacious than placebo in adult patients with refractory partial-onset seizures. The once-daily 800 mg dose showed a marginal effect on SSF, but did not reach statistical significance. Both doses were well tolerated. Efficacy assessment was not affected by diary format used. PMID:25528898
Translation failure and medical reversal: Two sides to the same coin.
Prasad, Vinay
2016-01-01
Translation failure occurs when the results of preclinical, observational and/or early phase studies fail to predict the results of well done (i.e. appropriately controlled, adequately powered, and properly conducted) phase III or randomised clinical trials. Some failures occur when promising basic science findings fail to replicate in human studies, while others happen when promising uncontrolled trial data show an exaggerated effect that vanishes in the setting of a randomised trial. Medical reversals occur when the results of preclinical, observational and/or early phase studies fail to predict the results of subsequent randomized clinical trials, but the practice has already gained widespread acceptance. Oncologic examples include bevacizumab and the use of autologous stem cell transplant in metastatic breast cancer. In a well-intentioned effort to reduce the rate of translation failure, oncologists must be careful that changes to regulatory processes and clinical trial design do not actually work to increase the approval of ineffective compounds. By trying to cure translation failure, we should be careful to avoid medical reversal. The rise of surrogate end-points and role of hard-wired bias in oncology trials suggest that we may be currently ignoring the simple fact that translation failure and medical reversal are two sides to the same coin. Published by Elsevier Ltd.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gritti, Fabrice; Guiochon, Georges A
2009-01-01
The single-component equilibrium adsorption of the tripeptide Leucyl-Leucyl-Leucine (LLL) on a high-efficiency Jupiter Proteo column (C{sub 12}) was investigated experimentally and modeled theoretically. The experimental equilibrium isotherms of LLL for adsorption on a C{sub 12} packing material from an aqueous solution of methanol (48%) and trifluoroacetic acid (0.1%) were measured by frontal analysis (FA). The FA measurements were done with two solutions, one in which the pH was controlled, the other in which it was not. Two solutions of LLL in the mobile phase were prepared (4.3 and 5.4 g/L) and their pH measured (2.94 and 2.88), respectively. The firstmore » solution was titrated with TFA to match the pH of the mobile phase (2.03), so its pH was controlled. The pH of the other solution was left uncontrolled. In both cases the isotherms could be modeled by a bi-Langmuir equation, a choice consistent with the bimodal affinity energy distribution (AED) obtained for LLL. The isotherm parameters derived from the inverse method (IM) of isotherm determination under controlled pH conditions (by fitting calculated profiles to experimental breakthrough profiles) are in a good agreement with those derived from the FA data. Under uncontrolled pH conditions, the application of IM suggests the coexistence of two different adsorption mechanisms. According to the isotherm parameters found by these three methods (FA, AED and IM), the C{sub 12}-bonded silica can adsorb around 500 and 70 g/L of LLL under controlled and uncontrolled pH conditions, respectively. The adsorption of LLL on the C{sub 12} material strongly depends on the pH of the mobile phase and on the quantity of TFA added, which plays the role of an ion-pairing agent.« less
NASA Astrophysics Data System (ADS)
Berton, Mariana Piatto; de Cássia Dourado, Rita; de Lima, Flávia Biondi Fernandes; Rodrigues, Ana Beatriz Bertoncello; Ferrari, Fábio Borba; do Carmo Vieira, Leonardo Dimas; de Souza, Pedro Alves; Borba, Hirasilva
2015-08-01
The objective of this study was to evaluate the effect of temperature on the performance and carcass yield of pigs housed in different environments. Twenty castrated male pigs of the Topigs line were assigned to two treatments: T1, controlled environment, and T2, uncontrolled environment containing a shallow pool. A completely randomized design consisting of two treatments and ten repetitions each was used. The data were submitted to analysis of variance, and means were compared by the Tukey test at a level of significance of 5 % using the SAS 9.2 program (SAS Institute, Inc., NC, USA). The results showed that rearing pigs in an uncontrolled environment during the growing and finishing phases reduced daily feed intake (1.722 and 3.164 kg, respectively) and improved feed conversion (2.15 and 2.70 kg, respectively), but did not influence the carcass yield of the animals. In conclusion, rearing pigs under different environmental conditions during the growing and finishing phases influenced animal performance without interfering with carcass yield.
Berton, Mariana Piatto; de Cássia Dourado, Rita; de Lima, Flávia Biondi Fernandes; Rodrigues, Ana Beatriz Bertoncello; Ferrari, Fábio Borba; do Carmo Vieira, Leonardo Dimas; de Souza, Pedro Alves; Borba, Hirasilva
2015-08-01
The objective of this study was to evaluate the effect of temperature on the performance and carcass yield of pigs housed in different environments. Twenty castrated male pigs of the Topigs line were assigned to two treatments: T1, controlled environment, and T2, uncontrolled environment containing a shallow pool. A completely randomized design consisting of two treatments and ten repetitions each was used. The data were submitted to analysis of variance, and means were compared by the Tukey test at a level of significance of 5 % using the SAS 9.2 program (SAS Institute, Inc., NC, USA). The results showed that rearing pigs in an uncontrolled environment during the growing and finishing phases reduced daily feed intake (1.722 and 3.164 kg, respectively) and improved feed conversion (2.15 and 2.70 kg, respectively), but did not influence the carcass yield of the animals. In conclusion, rearing pigs under different environmental conditions during the growing and finishing phases influenced animal performance without interfering with carcass yield.
Studies of uncontrolled air traffic patterns, phase 1
NASA Technical Reports Server (NTRS)
Baxa, E. G., Jr.; Scharf, L. L.; Ruedger, W. H.; Modi, J. A.; Wheelock, S. L.; Davis, C. M.
1975-01-01
The general aviation air traffic flow patterns at uncontrolled airports are investigated and analyzed and traffic pattern concepts are developed to minimize the midair collision hazard in uncontrolled airspace. An analytical approach to evaluate midair collision hazard probability as a function of traffic densities is established which is basically independent of path structure. Two methods of generating space-time interrelationships between terminal area aircraft are presented; one is a deterministic model to generate pseudorandom aircraft tracks, the other is a statistical model in preliminary form. Some hazard measures are presented for selected traffic densities. It is concluded that the probability of encountering a hazard should be minimized independently of any other considerations and that the number of encounters involving visible-avoidable aircraft should be maximized at the expense of encounters in other categories.
Simulation Tools for Power Electronics Courses Based on Java Technologies
ERIC Educational Resources Information Center
Canesin, Carlos A.; Goncalves, Flavio A. S.; Sampaio, Leonardo P.
2010-01-01
This paper presents interactive power electronics educational tools. These interactive tools make use of the benefits of Java language to provide a dynamic and interactive approach to simulating steady-state ideal rectifiers (uncontrolled and controlled; single-phase and three-phase). Additionally, this paper discusses the development and use of…
Bateman, Eric D; Guerreros, Alfredo G; Brockhaus, Florian; Holzhauer, Björn; Pethe, Abhijit; Kay, Richard A; Townley, Robert G
2017-08-01
Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP 2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS).Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d ) or twice-daily (2, 25, 75 or 150 mg b.i.d ) fevipiprant (n=782), montelukast 10 mg q.d (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg b.i.d Fevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg q.d and 75 mg b.i.d groups, with no clinically meaningful differences between q.d and b.i.d Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments.Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted. Copyright ©ERS 2017.
Guerreros, Alfredo G.; Brockhaus, Florian; Pethe, Abhijit; Kay, Richard A.; Townley, Robert G.
2017-01-01
Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS). Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d.) or twice-daily (2, 25, 75 or 150 mg b.i.d.) fevipiprant (n=782), montelukast 10 mg q.d. (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg b.i.d. Fevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg q.d. and 75 mg b.i.d. groups, with no clinically meaningful differences between q.d. and b.i.d. Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments. Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted. PMID:28838980
One year in review 2016: Behçet's syndrome.
Hatemi, Gulen; Seyahi, Emire; Fresko, Izzet; Talarico, Rosaria; Hamuryudan, Vedat
2016-01-01
Several articles highlighting the epidemiology, pathogenesis, clinical features, treatment modalities and disease assessment of Behçet's syndrome (BS) have been published during the last year. Clinical and radiological features of lower extremity deep vein thrombosis due to BS can be quite different than those found in thrombosis due to other causes; additionally, frequency of post-thrombotic syndrome is significantly increased in BS. Some clinical and colonoscopic features are useful in differentiating BS from Crohn's disease. Barkhof criteria may be helpful in differentiating neurologic involvement due to BS from multiple sclerosis. Anatomical localization of papulopustular lesions but not histology has been found to be helpful in differentiating papulopustular lesions of BS from those found in acne vulgaris. Several studies looked at the ovarian reserve with contradicting results. A population-based cohort study found higher risk of hematological malignancies only among female BS patients living in Taiwan. The role of genetic factors and environment is discussed and both autoimmune and autoinflammatory features are underlined in the pathogenesis of BS. New data on the epistatic interactions between ERAP and HLA B51 is available and information on the microbiome have started to appear. New uncontrolled data suggest beneficial effects of anti-TNFs for refractory extra-ocular complications of BS such as pulmonary artery, gastrointestinal and central nervous system involvement. Uncontrolled studies suggest promising results with interleukin-1 inhibition but gevokizumab, a humanised anti IL-1β antibody, failed to meet the primary endpoint of time to first ocular exacerbation in a phase III trial. The debate on anticoagulation continues with new observational data.
Yu, Qi; Huang, Zirong; Ren, Mulan; Chang, Qing; Zhang, Zhongqi; Parke, Susanne
2018-01-01
To investigate the efficacy and safety of a combined oral contraceptive containing estradiol valerate and dienogest (EV/DNG) in healthy Asian women. In this multicenter Phase III study, women received oral EV/DNG in a 28-day regimen for 13 cycles. The primary efficacy endpoint was the number of unintended pregnancies, measured by the Pearl Index (PI); secondary efficacy endpoints included bleeding pattern and cycle control parameters. Adverse events were monitored during the study and overall satisfaction with treatment was determined on completion of the study. A total of 954 Asian women (97.7% of subjects assigned to study medication; mean age 33.4 years) were treated. Five pregnancies were reported during EV/DNG treatment over 796.34 relevant woman-years of exposure, giving an unadjusted PI of 0.63 and a cumulative failure rate of 0.0049; 3 pregnancies during EV/DNG treatment over 760.35 relevant woman-years of exposure gave an adjusted PI of 0.39. The bleeding pattern improved during the reporting periods within the study. The proportion of women who experienced withdrawal bleeding decreased with treatment (84.9% of women during Cycle 1 vs 79.3% in Cycle 13), and the mean length of withdrawal bleeding decreased with treatment (4.2 vs 3.4 days). The number and maximum length of intracyclic bleeding/spotting episodes also decreased with EV/DNG. EV/DNG was well tolerated, and 92% of women included in the study were very satisfied or somewhat satisfied with EV/DNG. EV/DNG showed high contraceptive efficacy, was well tolerated in Asian women, and may be effectively used in this population. ClinicalTrials.gov identifier: NCT01638910.
Treating cancer with selective CDK4/6 inhibitors.
O'Leary, Ben; Finn, Richard S; Turner, Nicholas C
2016-07-01
Uncontrolled cellular proliferation, mediated by dysregulation of the cell-cycle machinery and activation of cyclin-dependent kinases (CDKs) to promote cell-cycle progression, lies at the heart of cancer as a pathological process. Clinical implementation of first-generation, nonselective CDK inhibitors, designed to inhibit this proliferation, was originally hampered by the high risk of toxicity and lack of efficacy noted with these agents. The emergence of a new generation of selective CDK4/6 inhibitors, including ribociclib, abemaciclib and palbociclib, has enabled tumour types in which CDK4/6 has a pivotal role in the G1-to-S-phase cell-cycle transition to be targeted with improved effectiveness, and fewer adverse effects. Results of pivotal phase III trials investigating palbociclib in patients with advanced-stage oestrogen receptor (ER)-positive breast cancer have demonstrated a substantial improvement in progression-free survival, with a well-tolerated toxicity profile. Mechanisms of acquired resistance to CDK4/6 inhibitors are beginning to emerge that, although unwelcome, might enable rational post-CDK4/6 inhibitor therapeutic strategies to be identified. Extending the use of CDK4/6 inhibitors beyond ER-positive breast cancer is challenging, and will likely require biomarkers that are predictive of a response, and the use of combination therapies in order to optimize CDK4/6 targeting.
Ethical, legal, and societal issues and recommendations for controlled and uncontrolled DCD.
Haase, Bernadette; Bos, Michael; Boffa, Catherine; Lewis, Penney; Rudge, Chris; Valero, Ricard; Wind, Tineke; Wright, Linda
2016-07-01
This report deals with organ retrieval procedures in both controlled and uncontrolled DCD, looking at the ethical, legal, and psychosocial aspects during the different phases of the process. A recently published report by the UK Donation Ethics Committee (UKDEC) has served as an important reference document to outline the steps in the controlled DCD patient-donor pathway (Academy of Medical Royal Colleges. UK Donation Ethics Committee. An ethical framework for controlled donation after circulatory death. December 2011). For uncontrolled DCD, the UKDEC pathway description was adapted. At the 6th International Conference in Organ Donation held in Paris in 2013, an established expert European Working Group reviewed the UKDEC reports, which were then considered along with the available published literature. Along this pathway, the crucial ethical, legal, and psychosocial aspects have been flagged, and relevant recommendations have been formulated based on a consensus of the working group. © 2015 Steunstichting ESOT.
Niess, Hanno; von Einem, Jobst C; Thomas, Michael N; Michl, Marlies; Angele, Martin K; Huss, Ralf; Günther, Christine; Nelson, Peter J; Bruns, Christiane J; Heinemann, Volker
2015-04-08
Adenocarcinoma originating from the digestive system is a major contributor to cancer-related deaths worldwide. Tumor recurrence, advanced local growth and metastasis are key factors that frequently prevent these tumors from curative surgical treatment. Preclinical research has demonstrated that the dependency of these tumors on supporting mesenchymal stroma results in susceptibility to cell-based therapies targeting this stroma. TREAT-ME1 is a prospective, uncontrolled, single-arm phase I/II study assessing the safety and efficacy of genetically modified autologous mesenchymal stromal cells (MSC) as delivery vehicles for a cell-based gene therapy for advanced, recurrent or metastatic gastrointestinal or hepatopancreatobiliary adenocarcinoma. Autologous bone marrow will be drawn from each eligible patient after consent for bone marrow donation has been obtained (under a separate EC-approved protocol). In the following ~10 weeks the investigational medicinal product (IMP) is developed for each patient. To this end, the patient's MSCs are stably transfected with a gamma-retroviral, replication-incompetent and self-inactivating (SIN) vector system containing a therapeutic promoter - gene construct that allows for tumor-specific expression of the therapeutic gene. After release of the IMP the patients are enrolled after given informed consent for participation in the TREAT-ME 1 trial. In the phase I part of the study, the safety of the IMP is tested in six patients by three treatment cycles consisting of re-transfusion of MSCs at different concentrations followed by administration of the prodrug Ganciclovir. In the phase II part of the study, sixteen patients will be enrolled receiving IMP treatment. A subgroup of patients that qualifies for surgery will be treated preoperatively with the IMP to verify homing of the MSCs to tumors as to be confirmed in the surgical specimen. The TREAT-ME1 clinical study involves a highly innovative therapeutic strategy combining cell and gene therapy and is conducted at a high level of pharmaceutical quality ensuring patient safety. This patient-tailored approach represents the first clinical study worldwide utilizing genetically engineered MSCs in humans. EU Clinical Trials Register/European Union Drug Regulating Authorities Clinical Trials Database number: 2012-003741-15.
Chan, John K; Ueda, Stefanie M; Sugiyama, Valerie E; Stave, Christopher D; Shin, Jacob Y; Monk, Bradley J; Sikic, Branimir I; Osann, Kathryn; Kapp, Daniel S
2008-03-20
To identify the characteristics of phase II studies that predict for subsequent "positive" phase III trials (those that reached the proposed primary end points of study or those wherein the study drug was superior to the standard regimen investigating targeted agents in advanced tumors. We identified all phase III clinical trials of targeted therapies against advanced cancers published from 1985 to 2005. Characteristics of the preceding phase II studies were reviewed to identify predictive factors for success of the subsequent phase III trial. Data were analyzed using the chi(2) test and logistic regression models. Of 351 phase II studies, 167 (47.6%) subsequent phase III trials were positive and 184 (52.4%) negative. Phase II studies from multiple rather than single institutions were more likely to precede a successful trial (60.4% v 39.4%; P < .001). Positive phase II results were more likely to lead to a successful phase III trial (50.8% v 22.5%; P = .003). The percentage of successful trials from pharmaceutical companies was significantly higher compared with academic, cooperative groups, and research institutes (89.5% v 44.2%, 45.2%, and 46.3%, respectively; P = .002). On multivariate analysis, these factors and shorter time interval between publication of phase II results and III study publication were independent predictive factors for a positive phase III trial. In phase II studies of targeted agents, multiple- versus single-institution participation, positive phase II trial, pharmaceutical company-based trials, and shorter time period between publication of phase II to phase III trial were independent predictive factors of success in a phase III trial. Investigators should be cognizant of these factors in phase II studies before designing phase III trials.
Nb-doped SrTiO3 glass-ceramics as high temperature stable n-type oxide thermoelectrics
NASA Astrophysics Data System (ADS)
Lingner, Julian; Jakob, Gerhard; Letz, Martin
2012-06-01
Niobium doped SrTiO3 is known for its high potential as an oxide thermoelectric material and is one of the possible candidates for the n-type site in an oxidic thermoelectric module. The high thermal conductivity [1] and the lack of high-temperature stability of the oxygen vacancies [2] limit its properties in the ceramic systems. Glass-ceramics are intrinsic nano-structured systems and provide crystal phases densely embedded in a glass matrix which prevents the material from detoriation at high temperatures. In particular, the glass-matrix prevents an uncontrolled reoxidization as well as an uncontrolled grain growth therefore retaining the nano-structure even at high temperatures. Here, measurements and results of first glass-ceramic systems are presented, which show a low thermal conductivity due to the residue glass phase. Furthermore a stable thermal cycling up to 650 °C is demonstrated.
Conversion to eslicarbazepine acetate monotherapy: A pooled analysis of 2 phase III studies.
Sperling, Michael R; French, Jacqueline; Jacobson, Mercedes P; Pazdera, Ladislav; Gough, Mallory; Cheng, Hailong; Grinnell, Todd; Blum, David
2016-03-22
To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy. This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical control threshold (65.3%). Pooled exit rates were as follows: ESL 1,600 mg = 20.6% (95% confidence interval: 15.6%-26.8%); ESL 1,200 mg = 30.8% (23.0%-40.5%). Use of 2 baseline AEDs or rescue medication, US location, epilepsy duration ≥20 years, and higher maximum baseline seizure frequency were associated with higher exit risks. Median percent reductions in standardized seizure frequency between baseline and the 18-week double-blind period were as follows: ESL 1,600 mg = 43.2%; ESL 1,200 mg = 35.7%; baseline carbamazepine use was associated with smaller reductions. Safety profiles were similar between ESL doses. Exit rates for ESL monotherapy (1,600 mg and 1,200 mg once daily) were lower than the historical control threshold, irrespective of baseline AED use and region, with no additional safety concerns identified. Clinical factors and location clearly influence treatment responses in conversion-to-monotherapy trials. This pooled analysis provides Class IV evidence that for adults with medically uncontrolled partial-onset seizures, ESL monotherapy is well tolerated and effective. © 2016 American Academy of Neurology.
Meneilly, Graydon S; Roy-Duval, Christine; Alawi, Hasan; Dailey, George; Bellido, Diego; Trescoli, Carlos; Manrique Hurtado, Helard; Guo, Hailing; Pilorget, Valerie; Perfetti, Riccardo; Simpson, Hamish
2017-04-01
To evaluate the efficacy and safety of lixisenatide versus placebo on glycemic control in older patients with type 2 diabetes uncontrolled on their current antidiabetic treatment. In this phase III, double-blind, randomized, placebo-controlled, two-arm, parallel-group, multicenter trial, patients aged ≥70 years were randomized to receive once-daily lixisenatide 20 μg or placebo before breakfast concomitantly with their existing antidiabetic therapy (including insulin) for 24 weeks. Patients at risk for malnutrition or with moderate to severe cognitive impairment were excluded. The primary end point was absolute change in HbA 1c from baseline to week 24. Secondary end points included change from baseline to week 24 in 2-h postprandial plasma glucose (PPG) and body weight. A total of 350 patients were randomized. HbA 1c decreased substantially with lixisenatide (-0.57% [6.2 mmol/mol]) compared with placebo (+0.06% [0.7 mmol/mol]) from baseline to week 24 ( P < 0.0001). Mean reduction in 2-h PPG was significantly greater with lixisenatide (-5.12 mmol/L) than with placebo (-0.07 mmol/L; P < 0.0001). A greater decrease in body weight was observed with lixisenatide (-1.47 kg) versus placebo (-0.16 kg; P < 0.0001). The safety profile of lixisenatide in this older population, including rates of nausea and vomiting, was consistent with that observed in other lixisenatide studies. Hypoglycemia was reported in 17.6% of patients with lixisenatide versus 10.3% with placebo. In nonfrail older patients uncontrolled on their current antidiabetic treatment, lixisenatide was superior to placebo in HbA 1c reduction and in targeting postprandial hyperglycemia, with no unexpected safety findings. © 2017 by the American Diabetes Association.
Phase III of Early Restoration | NOAA Gulf Spill Restoration
information about this phase of Early Restoration, including fact sheets on each project. The final Phase III 44 projects are documented in a final Record of Decision. Information about Phase III of Early Archive Home Phase III of Early Restoration Phase III of Early Restoration Beach habitat would be restored
Honkoop, Persijn J; Simpson, Andrew; Bonini, Matteo; Snoeck-Stroband, Jiska B; Meah, Sally; Fan Chung, Kian; Usmani, Omar S; Fowler, Stephen; Sont, Jacob K
2017-01-01
Introduction Asthma is a variable lung condition whereby patients experience periods of controlled and uncontrolled asthma symptoms. Patients who experience prolonged periods of uncontrolled asthma have a higher incidence of exacerbations and increased morbidity and mortality rates. The ability to determine and to predict levels of asthma control and the occurrence of exacerbations is crucial in asthma management. Therefore, we aimed to determine to what extent physiological, behavioural and environmental data, obtained by mobile healthcare (mHealth) and home-monitoring sensors, as well as patient characteristics, can be used to predict episodes of uncontrolled asthma and the onset of asthma exacerbations. Methods and analysis In an 1-year observational study, patients will be provided with mHealth and home-monitoring systems to record daily measurements for the first-month (phase I) and weekly measurements during a follow-up period of 11 months (phase II). Our study population consists of 150 patients, aged ≥18 years, with a clinician's diagnosis of asthma, currently on controller medication, with uncontrolled asthma and/or minimally one exacerbation in the past 12 months. They will be enrolled over three participating centres, including Leiden, London and Manchester. Our main outcomes are the association between physiological, behavioural and environmental data and (1) the loss of asthma control and (2) the occurrence of asthma exacerbations. Ethics This study was approved by the Medical Ethics Committee of the Leiden University Medical Center in the Netherlands and by the NHS ethics service in the UK. Trial registration number NCT02774772. PMID:28119390
Honkoop, Persijn J; Simpson, Andrew; Bonini, Matteo; Snoeck-Stroband, Jiska B; Meah, Sally; Fan Chung, Kian; Usmani, Omar S; Fowler, Stephen; Sont, Jacob K
2017-01-24
Asthma is a variable lung condition whereby patients experience periods of controlled and uncontrolled asthma symptoms. Patients who experience prolonged periods of uncontrolled asthma have a higher incidence of exacerbations and increased morbidity and mortality rates. The ability to determine and to predict levels of asthma control and the occurrence of exacerbations is crucial in asthma management. Therefore, we aimed to determine to what extent physiological, behavioural and environmental data, obtained by mobile healthcare (mHealth) and home-monitoring sensors, as well as patient characteristics, can be used to predict episodes of uncontrolled asthma and the onset of asthma exacerbations. In an 1-year observational study, patients will be provided with mHealth and home-monitoring systems to record daily measurements for the first-month (phase I) and weekly measurements during a follow-up period of 11 months (phase II). Our study population consists of 150 patients, aged ≥18 years, with a clinician's diagnosis of asthma, currently on controller medication, with uncontrolled asthma and/or minimally one exacerbation in the past 12 months. They will be enrolled over three participating centres, including Leiden, London and Manchester. Our main outcomes are the association between physiological, behavioural and environmental data and (1) the loss of asthma control and (2) the occurrence of asthma exacerbations. This study was approved by the Medical Ethics Committee of the Leiden University Medical Center in the Netherlands and by the NHS ethics service in the UK. NCT02774772. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Therapeutic use of dextromethorphan: key learnings from treatment of pseudobulbar affect.
Miller, Ariel; Panitch, Hillel
2007-08-15
A variety of neurological conditions and disease states are accompanied by pseudobulbar affect (PBA), an emotional disorder characterized by uncontrollable outbursts of laughing and crying. The causes of PBA are unclear but may involve lesions in neural circuits regulating the motor output of emotional expression. Several agents used in treating other psychiatric disorders have been applied in the treatment of PBA with some success but data are limited and these agents are associated with unpleasant side effects due to nonspecific activity in diffuse neural networks. Dextromethorphan (DM), a widely used cough suppressant, acts at receptors in the brainstem and cerebellum, brain regions implicated in the regulation of emotional output. The combination of DM and quinidine (Q), an enzyme inhibitor that blocks DM metabolism, has recently been tested in phase III clinical trials in patients with multiple sclerosis and amyotrophic lateral sclerosis and was both safe and effective in palliating PBA symptoms. In addition, clinical studies pertaining to the safety and efficacy of DM/Q in a variety of neurological disease states are ongoing.
Phase III Early Restoration Public Meetings | NOAA Gulf Spill Restoration
Archive Home Phase III Early Restoration Public Meetings Phase III Early Restoration Public Meetings share Posted on December 6, 2013 | Assessment and Early Restoration Restoration Area Title: Phase III Early on the draft plan for the third phase of Early Restoration, which proposes more than $625 million in
Using phase II data for the analysis of phase III studies: An application in rare diseases.
Wandel, Simon; Neuenschwander, Beat; Röver, Christian; Friede, Tim
2017-06-01
Clinical research and drug development in orphan diseases are challenging, since large-scale randomized studies are difficult to conduct. Formally synthesizing the evidence is therefore of great value, yet this is rarely done in the drug-approval process. Phase III designs that make better use of phase II data can facilitate drug development in orphan diseases. A Bayesian meta-analytic approach is used to inform the phase III study with phase II data. It is particularly attractive, since uncertainty of between-trial heterogeneity can be dealt with probabilistically, which is critical if the number of studies is small. Furthermore, it allows quantifying and discounting the phase II data through the predictive distribution relevant for phase III. A phase III design is proposed which uses the phase II data and considers approval based on a phase III interim analysis. The design is illustrated with a non-inferiority case study from a Food and Drug Administration approval in herpetic keratitis (an orphan disease). Design operating characteristics are compared to those of a traditional design, which ignores the phase II data. An analysis of the phase II data reveals good but insufficient evidence for non-inferiority, highlighting the need for a phase III study. For the phase III study supported by phase II data, the interim analysis is based on half of the patients. For this design, the meta-analytic interim results are conclusive and would justify approval. In contrast, based on the phase III data only, interim results are inconclusive and require further evidence. To accelerate drug development for orphan diseases, innovative study designs and appropriate methodology are needed. Taking advantage of randomized phase II data when analyzing phase III studies looks promising because the evidence from phase II supports informed decision-making. The implementation of the Bayesian design is straightforward with public software such as R.
Pseudo-phase-matched four-wave mixing in soliton wavelength-division multiplexing transmission.
Mamyshev, P V; Mollenauer, L F
1996-03-15
In a soliton transmission system using lumped amplifiers, pseudo phase matching allows four-wave mixing fields from soliton-soliton collisions to grow uncontrollably and inf lict severe penalties. Through numerical simulation, we show that this growth can be eliminated, or at least greatly reduced, through the use of fiber whose dispersion is tapered, either continuously or in steps, in conformity with the fiber loss curve.
Kurata, Takayasu; Nakaya, Aya; Yokoi, Takashi; Niki, Maiko; Kibata, Kayoko; Takeyasu, Yuki; Torii, Yoshitaro; Katashiba, Yuichi; Ogata, Makoto; Miyara, Takayuki; Nomura, Shosaku
2017-01-01
Background Epidermal growth factor receptor tyrosine kinase inhibitors significantly prolong the progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC). However, most patients develop tumor regrowth and their prognosis remains poor. A new treatment strategy for NSCLC harboring EGFR mutation is therefore necessary. Methods In phase I, eligible patients were administered oral erlotinib daily and intravenous pemetrexed, carboplatin, and bevacizumab every 3 weeks for four cycles with maintenance of pemetrexed and bevacizumab until progressive disease was observed. The dose of erlotinib was 100 mg for dose level 1 and 150 mg for dose level 2. The doses of pemetrexed, carboplatin, and bevacizumab were fixed at 500 mg/m2, area under the concentration–time curve of 6 mg/mL · min, and 15 mg/kg, respectively. The dose-limiting toxicities were grade 3/4 neutropenia with fever or infection, grade 4 leukopenia lasting for ≥7 days, grade 4 thrombocytopenia, grade 3/4 uncontrollable nonhematological toxicity, and delayed administration of the subsequent cycle by >2 weeks because of adverse events. Results Six patients were enrolled in phase I (dose level 1, n = 3; dose level 2, n = 3). During the induction phase, grade 3 neutropenia without fever was observed in one patient at dose level 1 and two patients at dose level 2. Grade 3 anemia was reported in one patient at dose level 1 and grade 3 thrombocytopenia was reported in two patients at dose level 1 and dose level 2, respectively. Conclusion Four-drug combination therapy is a feasible and promising. PMID:28740574
Erwin, Kim; Martin, Molly A; Flippin, Tara; Norell, Sarah; Shadlyn, Ariana; Yang, Jie; Falco, Paula; Rivera, Jaime; Ignoffo, Stacy; Kumar, Rajesh; Margellos-Anast, Helen; McDermott, Michael; McMahon, Kate; Mosnaim, Giselle; Nyenhuis, Sharmilee M; Press, Valerie G; Ramsay, Jessica E; Soyemi, Kenneth; Thompson, Trevonne M; Krishnan, Jerry A
2016-01-01
To present the methods and outcomes of stakeholder engagement in the development of interventions for children presenting to the emergency department (ED) for uncontrolled asthma. We engaged stakeholders (caregivers, physicians, nurses, administrators) from six EDs in a three-phase process to: define design requirements; prototype and refine; and evaluate. Interviews among 28 stakeholders yielded themes regarding in-home asthma management practices and ED discharge experiences. Quantitative and qualitative evaluation showed strong preference for the new discharge tool over current tools. Engaging end-users in contextual inquiry resulted in CAPE (CHICAGO Action Plan after ED discharge), a new stakeholder-balanced discharge tool, which is being tested in a multicenter comparative effectiveness trial.
Alternatives to lithium and divalproex in the maintenance treatment of bipolar disorder.
Gnanadesikan, Mukund; Freeman, Marlene P; Gelenberg, Alan J
2003-06-01
The role of lithium carbonate in the maintenance treatment of bipolar disorder is well established. Unfortunately, many patients fail to respond adequately to this agent or are unable to tolerate its adverse effects. Divalproex has become a commonly used alternative to lithium, but it also is ineffective or poorly tolerated in many patients. This article attempts to review the available data on maintenance therapy in bipolar disorder with a variety of anticonvulsants and antipsychotics (both conventional and novel), with reference to relevant studies in acute mania and bipolar depression as well. Evidence on maintenance therapy and relevant acute-phase data were collected using MEDLINE database searches. Data on maintenance therapy with agents other than lithium and divalproex are sparse, and often derived from open, uncontrolled studies. Implications and flaws of available data are discussed. Other than lithium, there are few robust double-blind data to support the use of a variety of agents in the maintenance phase. However, uncontrolled data suggest that a number of agents merit further study.
Suzuki, Kazuyuki; Endo, Ryujin; Takikawa, Yasuhiro; Moriyasu, Fuminori; Aoyagi, Yutaka; Moriwaki, Hisataka; Terai, Shuji; Sakaida, Isao; Sakai, Yoshiyuki; Nishiguchi, Shuhei; Ishikawa, Toru; Takagi, Hitoshi; Naganuma, Atsushi; Genda, Takuya; Ichida, Takafumi; Takaguchi, Koichi; Miyazawa, Katsuhiko; Okita, Kiwamu
2018-05-01
The efficacy and safety of rifaximin in the treatment of hepatic encephalopathy (HE) are widely known, but they have not been confirmed in Japanese patients with HE. Thus, two prospective, randomized studies (a phase II/III study and a phase III study) were carried out. Subjects with grade I or II HE and hyperammonemia were enrolled. The phase II/III study, which was a randomized, evaluator-blinded, active-comparator, parallel-group study, was undertaken at 37 institutions in Japan. Treatment periods were 14 days. Eligible patients were randomized to the rifaximin group (1200 mg/day) or the lactitol group (18-36 g/day). The phase III study was carried out in the same patients previously enrolled in the phase II/III study, and they were all treated with rifaximin (1200 mg/day) for 10 weeks. In the phase II/III study, 172 patients were enrolled. Blood ammonia (B-NH 3 ) concentration was significantly improved in the rifaximin group, but the difference between the two groups was not significant. The portal systemic encephalopathy index (PSE index), including HE grade, was significantly improved in both groups. In the phase III study, 87.3% of enrolled patients completed the treatment. The improved B-NH 3 concentration and PSE index were well maintained from the phase II/III study during the treatment period of the phase III study. Adverse drug reactions (ADRs) were seen in 13.4% of patients who received rifaximin, but there were no severe ADRs leading to death. The efficacy of rifaximin is sufficient and treatment is well tolerated in Japanese patients with HE and hyperammonemia. © 2017 The Japan Society of Hepatology.
Grob, Jean-Jacques; Mortier, Laurent; D'Hondt, Lionel; Grange, Florent; Baurain, Jean Francois; Dréno, Brigitte; Lebbe, Céleste; Robert, Caroline; Dompmartin, Anne; Neyns, Bart; Gillet, Marc; Louahed, Jamila; Jarnjak, Silvija; Lehmann, Frédéric F
2017-01-01
We assessed safety, immunogenicity and clinical activity of recombinant MAGE-A3 antigen combined with AS15 immunostimulant (MAGE-A3 immunotherapeutic) in association with dacarbazine in patients with metastatic melanoma. In this open-label, phase I/II, uncontrolled multicentre trial conducted in Belgium and France, patients with MAGE-A3-positive melanoma received up to 24 doses of MAGE-A3 immunotherapeutic (four cycles) coadministered with eight doses of dacarbazine. Adverse events (AE) were recorded until 31 days postvaccination, and serious AEs (SAE), until 30 days following the last dose. MAGE-A3-specific antibodies were measured by ELISA. Clinical activity of MAGE-A3 immunotherapeutic was assessed in patients positive/negative for previously identified gene signature (GS) associated with clinical outcome. Forty-eight patients were enrolled and treated (32 GS+, 15 GS-, 1 unknown GS status); two patients completed the study. All patients reported AEs, the most common were 'general disorders and administration site conditions' (94%). Treatment-related AEs were reported by 85% of patients; the most common was pain at injection site (38%). Sixteen SAEs were reported by 21% of patients; two were considered as treatment related (neutropenia and thrombocytopenia; grade 4). Postdose 4, all patients were seropositive for MAGE-A3-specific antibodies, with a geometric mean titre of 2778.7 ELISA units (EU)/mL (95% CI 1638.3 to 4712.8). One complete and three partial responses were reported (only in GS+ patients). Median overall survival was 11.4 months for GS+ and 5.3 months for GS- patients. Although this trial shows poor results compared with the new results with checkpoint inhibitors, it gives an interesting insight in rapidly developing fields like combinations of immunotherapy and chemotherapy, new generation vaccines and the use of gene profile as a predictive marker. NCT00849875.
Kawamori, Ryuzo; Kaku, Kohei; Hanafusa, Toshiaki; Oikawa, Tatsuya; Kageyama, Shigeru; Hotta, Nigishi
2014-02-12
We investigated the efficacy and safety of repaglinide as an add-on therapy for Japanese patients with type 2 diabetes mellitus receiving metformin monotherapy (at a dose of 1,500 mg/day, mainly) in addition to diet and exercise. In the 16-week multicenter, placebo-controlled, randomized, double-blind, parallel-group trial (the phase III study), patients with type 2 diabetes mellitus with metformin monotherapy were randomly assigned to the repaglinide or placebo group. Thereafter, a 36-week, multicenter, uncontrolled, dose-titration method study was extended to a total duration of 52 weeks (the long-term study). The primary end-point of each study was a change in glycated hemoglobin (HbA1c) from baseline. After 16 weeks, mean reductions in HbA1c were significantly greater for the repaglinide group than for the placebo group (-0.98 ± 0.72% vs 0.13 ± 0.63%, P < 0.001). In the long-term study, the mean change in HbA1c was -0.76 ± 0.83%. The rate of adverse events was 60.6 and 50.0% in the repaglinide and placebo groups, respectively, in the phase III study, and 78.3% in the long-term study. Hypoglycemia was reported in 11.7, 0 and 13.3% of patients in the repaglinide group, placebo group and long-term study, respectively. Combination therapy with repaglinide and metformin resulted in an approximately 1% reduction in HbA1c at week 16 and in a significant long-term improvement in HbA1c at the end of the study. No safety problems were noted during the concomitant use of repaglinide and metformin. These studies were registered with JapicCTI (nos. JapicCTI-101202 and JapicCTI-101203).
Los Angeles International Airport Runway Incursion Studies: Phase III--Center-Taxiway Simulation
NASA Technical Reports Server (NTRS)
Madson, Michael D.
2004-01-01
Phase III of the Los Angeles International Airport Runway Incursion Studies was conducted, under an agreement with HNTB Corporation, at the NASA Ames FutureFlight Central (FFC) facility in June 2003. The objective of the study was the evaluation of a new center-taxiway concept at LAX. This study is an extension of the Phase I and Phase II studies previously conducted at FFC. This report presents results from Phase III of the study, in which a center-taxiway concept between runways 25L and 25R was simulated and evaluated. Phase III data were compared objectively against the Baseline data. Subjective evaluations by participating LAX controllers were obtained with regard to workload, efficiency, and safety criteria. To facilitate a valid comparison between Baseline and Phase III data, the same scenarios were used for Phase III that were tested during Phases I and II. This required briefing participating controllers on differences in airport and airline operations between 2001 and today.
Erwin, Kim; Martin, Molly A; Flippin, Tara; Norell, Sarah; Shadlyn, Ariana; Yang, Jie; Falco, Paula; Rivera, Jaime; Ignoffo, Stacy; Kumar, Rajesh; Margellos-Anast, Helen; McDermott, Michael; McMahon, Kate; Mosnaim, Giselle; Nyenhuis, Sharmilee M; Press, Valerie G; Ramsay, Jessica E; Soyemi, Kenneth; Thompson, Trevonne M; Krishnan, Jerry A
2016-01-01
Aim: To present the methods and outcomes of stakeholder engagement in the development of interventions for children presenting to the emergency department (ED) for uncontrolled asthma. Methods: We engaged stakeholders (caregivers, physicians, nurses, administrators) from six EDs in a three-phase process to: define design requirements; prototype and refine; and evaluate. Results: Interviews among 28 stakeholders yielded themes regarding in-home asthma management practices and ED discharge experiences. Quantitative and qualitative evaluation showed strong preference for the new discharge tool over current tools. Conclusion: Engaging end-users in contextual inquiry resulted in CAPE (CHICAGO Action Plan after ED discharge), a new stakeholder-balanced discharge tool, which is being tested in a multicenter comparative effectiveness trial. PMID:26690579
Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis
Wex, Eva; Pautsch, Alexander; Schnapp, Gisela; Hostettler, Katrin E.; Stowasser, Susanne; Kolb, Martin
2015-01-01
Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease characterised by fibrosis of the lung parenchyma and loss of lung function. Although the pathogenic pathways involved in IPF have not been fully elucidated, IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair, in which there is uncontrolled proliferation of lung fibroblasts and differentiation of fibroblasts into myofibroblasts, which excessively deposit extracellular matrix (ECM) proteins in the interstitial space. A number of profibrotic mediators including platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and transforming growth factor-β are believed to play important roles in the pathogenesis of IPF. Nintedanib is a potent small molecule inhibitor of the receptor tyrosine kinases PDGF receptor, FGF receptor and vascular endothelial growth factor receptor. Data from in vitro studies have shown that nintedanib interferes with processes active in fibrosis such as fibroblast proliferation, migration and differentiation, and the secretion of ECM. In addition, nintedanib has shown consistent anti-fibrotic and anti-inflammatory activity in animal models of lung fibrosis. These data provide a strong rationale for the clinical efficacy of nintedanib in patients with IPF, which has recently been demonstrated in phase III clinical trials. PMID:25745043
1984-10-01
8 iii "i t-. Table of Contents (cont.) Section Title Page -APPENDIX A Acronyms, Definitions, Nomenclature and Units of Measure B Scope of Work, Task...Identification/Records Search Phase II - Problem Confirmation and Quantification Phase III - Technology Base Development Phase IV - Corrective Action Only...Problem Identification/Records Search Phase II - Problem Confirmation and Quantification Phase III - Technology Base Development Phase IV - Corrective
Motilin-induced gastric contractions signal hunger in man.
Tack, J; Deloose, E; Ang, D; Scarpellini, E; Vanuytsel, T; Van Oudenhove, L; Depoortere, I
2016-02-01
Hunger is controlled by the brain, which receives input from signals of the GI tract (GIT). During fasting, GIT displays a cyclical motor pattern, the migrating motor complex (MMC), regulated by motilin. To study the relationship between hunger and MMC phases (I-III), focusing on spontaneous and pharmacologically induced phase III and the correlation with plasma motilin and ghrelin levels. The role of phase III was also studied in the return of hunger after a meal in healthy individuals and in patients with loss of appetite. In fasting healthy volunteers, mean hunger ratings during a gastric (62.5±7.5) but not a duodenal (40.4±5.4) phase III were higher (p<0.0005) than during phase I (27.4±4.7) and phase II (37±4.5). The motilin agonist erythromycin, but not the cholinesterase inhibitor neostigmine, induced a premature gastric phase III, which coincided with an increase in hunger scores from 29.2±7 to 61.7±8. The somatostatin analogue octreotide induced a premature intestinal phase III without a rise in hunger scores. Hunger ratings significantly correlated (β=0.05; p=0.01) with motilin plasma levels, and this relationship was lost after erythromycin administration. Motilin, but not ghrelin administration, induced a premature gastric phase III and a rise in hunger scores. In contrast to octreotide, postprandial administration of erythromycin induced a premature gastric phase III accompanied by an early rise in hunger ratings. In patients with unexplained loss of appetite, gastric phase III was absent and hunger ratings were lower. Motilin-induced gastric phase III is a hunger signal from GIT in man. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Tohara, K; Uchida, Y; Suzuki, H; Itoh, Z
2000-02-01
Mechanisms of initiation of phase III contractions in the jejunum during the digestive state are not well understood. To test whether phase III can be induced by a local injection of various agents in a jejunal segment, a polyethylene tube was chronically placed in a branch of the jejunal artery, and force transducers were chronically placed in the upper jejunum. Local injection of atropine, hexamethonium and xylocaine induced caudal-migrating phase III in the injected segment only in the digestive state, and simultaneous intra-arterial infusions of L-arginine, an NK-1 antagonist, or 5-hydroxytryptamine (5-HT) 1P and 3 antagonists inhibited the induced phase III. Intravenous atropine and hexamethonium also inhibited xylocaine-induced phase III contractions. Atropine and hexamethonium-induced phase III were brought about by inhibition of neural transmission at nicotinic receptors in the inhibitory pathway to NO neurones. NK-1, 5-HT1P and 5-HT3 receptors are present in the excitatory but not the inhibitory pathway to NO neurones. Xylocaine appears to stop neuronal transmission from mechanoreceptors to NO neurones. Thus, the initiation of spontaneous occurrence of phase III in the digestive jejunum is likely to be brought about by transient cessation of postprandial contractions in a segment of the jejunum.
Psychosocial functioning in adolescents with complex partial seizures.
Elliott, I
1992-03-01
This pilot study examined psychosocial functioning in adolescents (age 12.5-18.5 years) with complex partial seizures. Twenty-five subjects were divided into three groups: Group I (N = 11), medically treated with uncontrolled seizures; Group II (N = 6), medically managed with controlled seizures; and Group III (N = 8), epilepsy refractory to medical management with seizure control following surgery. Psychosocial functioning was measured using the "Adolescent Psychosocial Inventory" of Batzel and Dodrill. Findings revealed significant differences (F 4.80. p less than 0.02) in psychosocial functioning between the three groups. Group I showed the poorest overall adjustment; Group II, the best adjustment; Group III was better adjusted than Group I, but less than Group II. Significant difficulties were evident in the areas of school, interpersonal, emotional, seizure adjustment and overall psychosocial functioning in Group III. No problems were evident in Group II. School, emotional and overall adjustment were moderately problematic in Group III. Analysis of biological and demographic data revealed a significant association between increased numbers of medications and poorer psychosocial functioning (r = 58, p less than 0.02). The study results provide direction for clinic and community nurse specialists to set priorities with regard to assessment and supportive interventions.
2017-06-16
Acoustic Impacts on Marine Mammals and Sea Turtles: Methods and Analytical Approach for Phase III Training and Testing Sarah A. Blackstock Joseph O...December 2017 4. TITLE AND SUBTITLE Quantifying Acoustic Impacts on Marine Mammals and Sea Turtles: Methods and Analytical Approach for Phase III...Navy’s Phase III Study Areas as described in each Environmental Impact Statement/ Overseas Environmental Impact Statement and describes the methods
Multiorgan failure in the serious trauma patient.
Llompart-Pou, J A; Talayero, M; Homar, J; Royo, C
2014-10-01
Multiorgan failure remains one of the leading causes of late morbidity and mortality after severe trauma. In the early phase, it is related with an uncontrolled hyper-inflammation state, whereas in the late phase (>72 h), septic complications play a major role. We review the underlying pathophysiology, the evaluation with different scales and the clinical factors associated with multiorgan failure, as well as potential treatment options. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.
Primary care practice leaders who consider engaging in quality improvement (QI) need to understand the practice level costs incurred when asking staff to take on new tasks. The Heart Healthy Lenoir study is a prospective cohort trial in which QI methods were used to enhance hypertension (HTN) care and reduce racial disparities in blood pressure control in small rural primary care practices in North Carolina. As part of this effort, we performed an activity-based costing analysis to describe the costs incurred to develop, implement, and maintain key tasks.We interviewed 20 practice stakeholders and phone-based health coaches during 2012-2014. We calculated the time invested by individuals to perform each task within each study phase and applied national hourly wages to generate cost estimates. Our descriptive analyses focus on four of the most widely used practices. Activities included time to abstract HTN control data, participate in project meetings, identify patients with uncontrolled HTN, create standardized work, and provide additional health coaching for patients with uncontrolled HTN. Despite practice and staffing differences, the developmental phase costs were similar, ranging from $879 to $1,417. Implementation costs varied more widely as practices took different approaches to identifying patients with uncontrolled HTN. Practice-specific phone health coaching costs ranged from $19,508 to more than $38,000. This study adds to the growing literature regarding practice level costs of engaging in systems change. Understanding these costs and balancing them against practice incentives may be helpful as stakeholders make decisions regarding HTN QI.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-07-11
...: Passport Demand Forecasting Study Phase III ACTION: Notice of request for public comments. SUMMARY: The... of 1995. Title of Information Collection: Passport Demand Forecasting Study Phase III. OMB Control... Consular Affairs/Passport Services (CA/PPT) Form Number: SV-2012-0006. Respondents: A national...
Phenomenology of Polymorphism, III: p, TDiagram and Stability of Piracetam Polymorphs
NASA Astrophysics Data System (ADS)
Céolin, R.; Agafonov, V.; Louër, D.; Dzyabchenko, V. A.; Toscani, S.; Cense, J. M.
1996-02-01
The nootropic drug Piracetam is known to crystallize in three phases. In order to obtain their stability hierarchy from sublimation pressure inequalities, the drawing of a topologicalp,Tdiagram was attempted. For such a purpose and also for quality control, crystallographic and thermodynamic data were required. Powder X-ray diffractometry (XRD) and differential scanning calorimetry (DSC) were used. Molecular energy calculations were performed. Phase I melts at 426 K (ΔfusH(I) = +180 J·g-1). Phase II transforms into Phase I at 399 K (Δ(II→I)H= +24 J·g-1). Phase III transforms into phase I at 392 K (Δ(III→I)H= +28 J·g-1) or melts at 412 K (ΔfusH(III) = +210 J·g-1). Thep,Tdiagram shows that phase I is stable at higher temperature and phase II at lower temperature, like phase III, which is stable under high pressure. At room temperature, phase II is the more stable form, and phase I the less stable one. This agrees with the spontaneous I → II transformation observed at 298 K within a few hours, and with lattice energies, calculated previously. Molecular energy calculations and crystal structure comparison show how intermolecular hydrogen bonds and H-bonded dimers, in phases II and III, may stabilize conformations higher in energy than those of the isolated molecule and of phase I.
Security Quality Requirements Engineering (SQUARE): Case Study Phase III
2006-05-01
Security Quality Requirements Engineering (SQUARE): Case Study Phase III Lydia Chung Frank Hung Eric Hough Don Ojoko-Adams Advisor...Engineering (SQUARE): Case Study Phase III CMU/SEI-2006-SR-003 Lydia Chung Frank Hung Eric Hough Don Ojoko-Adams Advisor Nancy R. Mead...1 1.1 The SQUARE Process ............................................................................... 1 1.2 Case Study Clients
Howard, Randy B; Sayeed, Iqbal; Stein, Donald G
2017-06-01
To date, outcomes for all Phase III clinical trials for traumatic brain injury (TBI) have been negative. The recent disappointing results of the Progesterone for the Treatment of Traumatic Brain Injury (ProTECT) and Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury (SyNAPSe) Phase III trials for progesterone in TBI have triggered considerable speculation about the reasons for the negative outcomes of these two studies in particular and for those of all previous Phase III TBI clinical trials in general. Among the factors proposed to explain the ProTECT III and SyNAPSe results, the investigators themselves and others have cited: 1) the pathophysiological complexity of TBI itself; 2) issues with the quality and clinical relevance of the preclinical animal models; 3) insufficiently sensitive clinical endpoints; and 4) inappropriate clinical trial designs and strategies. This paper highlights three critical trial design factors that may have contributed substantially to the negative outcomes: 1) suboptimal doses and treatment durations in the Phase II studies; 2) the strategic decision not to perform Phase IIB studies to optimize these variables before initiating Phase III; and 3) the lack of incorporation of the preclinical and Chinese Phase II results, as well as allometric scaling principles, into the Phase III designs. Given these circumstances and the exceptional pleiotropic potential of progesterone as a TBI (and stroke) therapeutic, we are advocating a return to Phase IIB testing. We advocate the incorporation of dose and schedule optimization focused on lower doses and a longer duration of treatment, combined with the addressing of other potential trial design problems raised by the authors in the recently published trial results.
Hutton, Brian; Ng, Terry; Shorr, Risa; Clemons, Mark
2015-01-01
Background. Many cancer patients receive supplemental ascorbate (vitamin C) in the belief that it synergizes the anticancer effects of chemotherapy and reduces its toxicity. Methods. A systematic review was performed to evaluate the antitumor effects and toxicity of ascorbate treatment. Medline (1946 to March 2014), EMBASE (1947 to March 2014), and the Cochrane central register (1993 to March 2014) were searched for randomized and observational studies. Results. Of 696 identified records, 61 full-text articles were screened and 34 were included. In total, 5 randomized controlled trials (RCTs) (n = 322), 12 phase I/II trials (n = 287), 6 observational studies (n = 7,599), and 11 case reports (n = 267) were identified. Because of study heterogeneity, no meta-analyses were performed. No RCTs reported any statistically significant improvements in overall or progression-free survival or reduced toxicity with ascorbate relative to control arm. Evidence for ascorbate’s antitumor effects was limited to case reports and observational and uncontrolled studies. Conclusion. There is no high-quality evidence to suggest that ascorbate supplementation in cancer patients either enhances the antitumor effects of chemotherapy or reduces its toxicity. Given the high financial and time costs to patients of this treatment, high-quality placebo-controlled trials are needed. PMID:25601965
NASA Astrophysics Data System (ADS)
Hoffmann, U.; Wilson, B.
The ban on the export of used lead-acid batteries (ULAB) from Annex VII to non-Annex VII countries pursuant to decision III/1 of the Basel Convention reduced the availability of imported scrap feedstock for battery recycling in the Philippines. As ULAB supply from other developing countries becomes scarcer, the ban is likely to encourage and enhance collection and recuperation for domestically generated scrap. From a short-term perspective, this study explores the technological and managerial opportunities for improving the environmental and occupational health performance of the formal battery recycling sector and unregulated reconditioning. From a medium- and long-term point of view, the study investigates restructuring the informal ULAB's collection and recycling sector. The objective has been to make the smaller battery recyclers and reconditioners in the informal sector part of an effective and efficient collection infrastructure that supports an environmentally sound secondary lead sector. This approach gradually phases out uncontrolled, inefficient and environmentally unacceptable methods of secondary lead recovery. Due attention has also been paid to the logistical peculiarities of an archipelago, in particular the regional spread of collection infrastructure, collection and shipment costs as well as the assurance of environmentally safe transport.
New approaches in the treatment of hypertension.
Oparil, Suzanne; Schmieder, Roland E
2015-03-13
Hypertension is the most common modifiable risk factor for cardiovascular disease and death, and lowering blood pressure with antihypertensive drugs reduces target organ damage and prevents cardiovascular disease outcomes. Despite a plethora of available treatment options, a substantial portion of the hypertensive population has uncontrolled blood pressure. The unmet need of controlling blood pressure in this population may be addressed, in part, by developing new drugs and devices/procedures to treat hypertension and its comorbidities. In this Compendium Review, we discuss new drugs and interventional treatments that are undergoing preclinical or clinical testing for hypertension treatment. New drug classes, eg, inhibitors of vasopeptidases, aldosterone synthase and soluble epoxide hydrolase, agonists of natriuretic peptide A and vasoactive intestinal peptide receptor 2, and a novel mineralocorticoid receptor antagonist are in phase II/III of development, while inhibitors of aminopeptidase A, dopamine β-hydroxylase, and the intestinal Na(+)/H(+) exchanger 3, agonists of components of the angiotensin-converting enzyme 2/angiotensin(1-7)/Mas receptor axis and vaccines directed toward angiotensin II and its type 1 receptor are in phase I or preclinical development. The two main interventional approaches, transcatheter renal denervation and baroreflex activation therapy, are used in clinical practice for severe treatment resistant hypertension in some countries. Renal denervation is also being evaluated for treatment of various comorbidities, eg, chronic heart failure, cardiac arrhythmias and chronic renal failure. Novel interventional approaches in early development include carotid body ablation and arteriovenous fistula placement. Importantly, none of these novel drug or device treatments has been shown to prevent cardiovascular disease outcomes or death in hypertensive patients. © 2015 American Heart Association, Inc.
DOT National Transportation Integrated Search
2005-12-01
This volume provides an overview of the six studies that compose Phase II of the Enhanced Night Visibility project and the experimental plan for its third and final portion, Phase III. The Phase II studies evaluated up to 12 vision enhancement system...
Torresi, Joseph; Heron, Leon G; Qiao, Ming; Marjason, Joanne; Chambonneau, Laurent; Bouckenooghe, Alain; Boaz, Mark; van der Vliet, Diane; Wallace, Derek; Hutagalung, Yanee; Nissen, Michael D; Richmond, Peter C
2015-09-22
The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vaccine (CYD-TDV) has undergone extensive clinical trials. Here safety and consistency of immunogenicity of phase III manufacturing lots of CYD-TDV were evaluated and compared with a phase II lot and placebo in a dengue-naïve population. Healthy 18-60 year-olds were randomly assigned in a 3:3:3:3:1 ratio to receive three subcutaneous doses of either CYD-TDV from any one of three phase III lots or a phase II lot, or placebo, respectively in a 0, 6, 12 month dosing schedule. Neutralising antibody geometric mean titres (PRNT50 GMTs) for each of the four dengue serotypes were compared in sera collected 28 days after the third vaccination-equivalence among lots was demonstrated if the lower and upper limits of the two-sided 95% CIs of the GMT ratio were ≥0.5 and ≤2.0, respectively. 712 participants received vaccine or placebo and 614 (86%) completed the study; 17 (2.4%) participants withdrew after adverse events. Equivalence of phase III lots was demonstrated for 11 of 12 pairwise comparisons. One of three comparisons for serotype 2 was not statistically equivalent. GMTs for serotype 2 in phase III lots were close to each other (65.9, 44.1 and 58.1, respectively). Phase III lots can be produced in a consistent manner with predictable immune response and acceptable safety profile similar to previously characterised phase II lots. The phase III lots may be considered as not clinically different as statistical equivalence was shown for serotypes 1, 3 and 4 across the phase III lots. For serotype 2, although equivalence was not shown between two lots, the GMTs observed in the phase III lots were consistently higher than those for the phase II lot. As such, in our view, biological equivalence for all serotypes was demonstrated. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Patil, Sagar; Chakraborty, Saswati
2017-03-21
The effect of step feed strategy and intermittent aeration on removal of chemical oxygen demand (COD) and nitrogen was investigated in a laboratory scale horizontal subsurface flow constructed wetland (HSSFCW). Wetland was divided into four zones along the length (zone I to IV), and influent was introduced into first and third zones by step feeding. Continuous study was carried out in four phases. In phases I to III, 30% of influent was bypassed to zone III for denitrification along with organics removal. Intermittent aeration was provided only in zone II at 2.5 L/min for 4 h/day, during phases II, III and IV. In phase I, 87% COD and 43% NH 4 + -N (ammonia-nitrogen) removal were obtained from influents of 331 and 30 mg/L, respectively. In phase II study, external aeration resulted in 97% COD and 71% NH 4 + -N removal in the wetland. In phase IV, 40% of feed was delivered to zone III. Higher supply of organic in zone III resulted in higher denitrification, and total nitrogen removal rate increased to 70% from 56%. In the final effluent, concentration of NO 3 - -N was 9-11 mg/L in phase I to III and decreased to 4 mg/L in phase IV. Batch study showed that COD and NH 4 + -N removal followed first order kinetics in different zones of wetland.
Gandhi, Sahil Sandesh; Chien, Liang-Chy
2017-12-01
The amorphous blue phase III of cholesteric liquid crystals, also known as the "blue fog," are among the rising stars in materials science that can potentially be used to develop next-generation displays with the ability to compete toe-to-toe with disruptive technologies like organic light-emitting diodes. The structure and properties of the practically unobservable blue phase III have eluded scientists for more than a century since it was discovered. This progress report reviews the developments in this field from both fundamental and applied research perspectives. The first part of this progress report gives an overview of the 130-years-long scientific tour-de-force that very recently resulted in the revelation of the mysterious structure of blue phase III. The second part reviews progress made in the past decade in developing electrooptical, optical, and photonic devices based on blue phase III. The strong and weak aspects of the development of these devices are underlined and criticized, respectively. The third- and-final part proposes ideas for further improvement in blue phase III technology to make it feasible for commercialization and widespread use. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Grob, Jean-Jacques; Mortier, Laurent; D’Hondt, Lionel; Grange, Florent; Baurain, Jean Francois; Dréno, Brigitte; Lebbe, Céleste; Robert, Caroline; Dompmartin, Anne; Neyns, Bart; Gillet, Marc; Louahed, Jamila; Jarnjak, Silvija; Lehmann, Frédéric F
2017-01-01
Background We assessed safety, immunogenicity and clinical activity of recombinant MAGE-A3 antigen combined with AS15 immunostimulant (MAGE-A3 immunotherapeutic) in association with dacarbazine in patients with metastatic melanoma. Methods In this open-label, phase I/II, uncontrolled multicentre trial conducted in Belgium and France, patients with MAGE-A3-positive melanoma received up to 24 doses of MAGE-A3 immunotherapeutic (four cycles) coadministered with eight doses of dacarbazine. Adverse events (AE) were recorded until 31 days postvaccination, and serious AEs (SAE), until 30 days following the last dose. MAGE-A3-specific antibodies were measured by ELISA. Clinical activity of MAGE-A3 immunotherapeutic was assessed in patients positive/negative for previously identified gene signature (GS) associated with clinical outcome. Results Forty-eight patients were enrolled and treated (32 GS+, 15 GS−, 1 unknown GS status); two patients completed the study. All patients reported AEs, the most common were ‘general disorders and administration site conditions’ (94%). Treatment-related AEs were reported by 85% of patients; the most common was pain at injection site (38%). Sixteen SAEs were reported by 21% of patients; two were considered as treatment related (neutropenia and thrombocytopenia; grade 4). Postdose 4, all patients were seropositive for MAGE-A3-specific antibodies, with a geometric mean titre of 2778.7 ELISA units (EU)/mL (95% CI 1638.3 to 4712.8). One complete and three partial responses were reported (only in GS+ patients). Median overall survival was 11.4 months for GS+ and 5.3 months for GS− patients. Conclusion Although this trial shows poor results compared with the new results with checkpoint inhibitors, it gives an interesting insight in rapidly developing fields like combinations of immunotherapy and chemotherapy, new generation vaccines and the use of gene profile as a predictive marker. Trial registration number NCT00849875. PMID:29177094
Failures in Phase III: Causes and Consequences.
Seruga, Bostjan; Ocana, Alberto; Amir, Eitan; Tannock, Ian F
2015-10-15
Phase III randomized controlled trials (RCT) in oncology fail to lead to registration of new therapies more often than RCTs in other medical disciplines. Most RCTs are sponsored by the pharmaceutical industry, which reflects industry's increasing responsibility in cancer drug development. Many preclinical models are unreliable for evaluation of new anticancer agents, and stronger evidence of biologic effect should be required before a new agent enters the clinical development pathway. Whenever possible, early-phase clinical trials should include pharmacodynamic studies to demonstrate that new agents inhibit their molecular targets and demonstrate substantial antitumor activity at tolerated doses in an enriched population of patients. Here, we review recent RCTs and found that these conditions were not met for most of the targeted anticancer agents, which failed in recent RCTs. Many recent phase III RCTs were initiated without sufficient evidence of activity from early-phase clinical trials. Because patients treated within such trials can be harmed, they should not be undertaken. The bar should also be raised when making decisions to proceed from phase II to III and from phase III to marketing approval. Many approved agents showed only better progression-free survival than standard treatment in phase III trials and were not shown to improve survival or its quality. Introduction of value-based pricing of new anticancer agents would dissuade the continued development of agents with borderline activity in early-phase clinical trials. When collaborating with industry, oncologists should be more critical and better advocates for cancer patients. ©2015 American Association for Cancer Research.
Levin, Bruce; Thompson, John L P; Chakraborty, Bibhas; Levy, Gilberto; MacArthur, Robert; Haley, E Clarke
2011-08-01
TNK-S2B, an innovative, randomized, seamless phase II/III trial of tenecteplase versus rt-PA for acute ischemic stroke, terminated for slow enrollment before regulatory approval of use of phase II patients in phase III. (1) To review the trial design and comprehensive type I error rate simulations and (2) to discuss issues raised during regulatory review, to facilitate future approval of similar designs. In phase II, an early (24-h) outcome and adaptive sequential procedure selected one of three tenecteplase doses for phase III comparison with rt-PA. Decision rules comparing this dose to rt-PA would cause stopping for futility at phase II end, or continuation to phase III. Phase III incorporated two co-primary hypotheses, allowing for a treatment effect at either end of the trichotomized Rankin scale. Assuming no early termination, four interim analyses and one final analysis of 1908 patients provided an experiment-wise type I error rate of <0.05. Over 1,000 distribution scenarios, each involving 40,000 replications, the maximum type I error in phase III was 0.038. Inflation from the dose selection was more than offset by the one-half continuity correction in the test statistics. Inflation from repeated interim analyses was more than offset by the reduction from the clinical stopping rules for futility at the first interim analysis. Design complexity and evolving regulatory requirements lengthened the review process. (1) The design was innovative and efficient. Per protocol, type I error was well controlled for the co-primary phase III hypothesis tests, and experiment-wise. (2a) Time must be allowed for communications with regulatory reviewers from first design stages. (2b) Adequate type I error control must be demonstrated. (2c) Greater clarity is needed on (i) whether this includes demonstration of type I error control if the protocol is violated and (ii) whether simulations of type I error control are acceptable. (2d) Regulatory agency concerns that protocols for futility stopping may not be followed may be allayed by submitting interim analysis results to them as these analyses occur.
Stowe, Ashley; Burger, Arnold
2016-05-10
A method for synthesizing I-III-VI.sub.2 compounds, including: melting a Group III element; adding a Group I element to the melted Group III element at a rate that allows the Group I and Group III elements to react thereby providing a single phase I-III compound; and adding a Group VI element to the single phase I-III compound under heat, with mixing, and/or via vapor transport. The Group III element is melted at a temperature of between about 200 degrees C. and about 700 degrees C. Preferably, the Group I element consists of a neutron absorber and the group III element consists of In or Ga. The Group VI element and the single phase I-III compound are heated to a temperature of between about 700 degrees C. and about 1000 degrees C. Preferably, the Group VI element consists of S, Se, or Te. Optionally, the method also includes doping with a Group IV element activator.
Ichikawa, Akio; Ono, Hiroshi; Furuta, Kenjiro; Shiotsuki, Takahiro; Shinoda, Tetsuro
2007-08-17
Juvenile hormone III (JH III) racemate was prepared from methyl (2E,6E)-farnesoate via epoxidation with 3-chloroperbenzoic acid (mCPBA). Enantioselective separation of JH III was conducted using normal-phase high-performance liquid chromatography (HPLC) on a chiral stationary phase. [(2)H(3)]Methyl (2E,6E)-farnesoate was also prepared from (2E,6E)-farnesoic acid and [(2)H(4)]methanol (methanol-d(4)) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 4-dimethylaminopyridine (DMAP); the conjugated double bond underwent isomerization to some degree. Epoxidation of [(2)H(3)]methyl (2E,6E)-farnesoate with mCPBA gave a novel deuterium-substituted internal standard [(2)H(3)]JH III (JH III-d(3)). The standard curve was produced by linear regression using the peak area ratios of JH III and JH III-d(3) in liquid chromatography-mass spectrometry (LC-MS).
Design of an electrostatic phase shifting device for biological transmission electron microscopy.
Koeck, Philip J B
2018-04-01
I suggest an electrostatic phase plate designed to broaden the contrast transfer function of a transmission electron microscope operated close to Scherzer defocus primarily in the low resolution direction. At higher defocus the low frequency behavior is equal to that close to Scherzer defocus, but CTF-correction becomes necessary to extend image interpretation to higher resolution. One simple realization of the phase plate consists of two ring shaped electrodes symmetrically surrounding the central beam. Since no physical components come into contact with the central beam and charge on the electrodes is controlled by an external voltage supply, problems with uncontrolled charging are expected to be reduced. Copyright © 2018 Elsevier B.V. All rights reserved.
Shin, John I; Phan, Kevin; Kothari, Parth; Kim, Jun S; Guzman, Javier Z; Cho, Samuel K
2017-08-01
This is a retrospective analysis of administrative database. To elucidate the effect of glycemic control on surgical outcomes of middle-aged and elderly idiopathic scoliosis patients undergoing spinal fusion surgery. Diabetes mellitus (DM) is a condition thought to adversely affect outcomes of spine surgery. However, no study has stratified glycemic control levels and their impact on outcome for idiopathic scoliosis patients receiving a spinal fusion surgery. Previous studies may have reported higher than true rates of complications for controlled diabetic patients, who are the majority of diabetic patients. The Nationwide Inpatient Sample was queried from years 2002 to 2011. We extracted idiopathic scoliosis patients older than 45 years of age that received spinal fusion and analyzed complications and outcomes variables among 3 cohorts: nondiabetic patients, controlled diabetics, and uncontrolled diabetics. Multivariate analyses were used to assess whether glycemic control was a risk factor for adverse postoperative outcomes. Controlled diabetics had significantly increased rates of acute renal failure (ARF), while uncontrolled diabetics had significantly increased rates of acute postoperative hemorrhage. In multivariate analyses controlling for patient factors and comorbidities, controlled DM was found to be an independent predictor of ARF [odds ratio (OR), 1.863; 95% confidence interval (CI), 1.346-2.579; P=0.0002), and uncontrolled DM was found to be a significant risk factor for acute postoperative hemorrhage (OR, 2.182; 95% CI, 1.192-3.997; P=0.0115), ARF (OR, 4.839; 95% CI, 1.748-13.392; P=0.0024), deep vein thrombosis (OR, 5.825; 95% CI, 1.329-25.522, P=0.0194) and in-patient mortality (OR, 8.889; 95% CI, 1.001-78.945; P=0.0499). Controlled DM was found to be a risk factor for ARF in adult idiopathic scoliosis patients undergoing spinal fusion surgery, while uncontrolled DM was shown to be a risk factor for postoperative hemorrhage, ARF, deep vein thrombosis, and mortality. The present study provides valuable data for better informed consent for patients with diabetes considering surgery for idiopathic scoliosis. Level III.
Rare earth elements as a fingerprint of soil components solubilization
NASA Astrophysics Data System (ADS)
Davranche, M.; Grybos, M.; Gruau, G.; Pédrot, M.; Dia, A.
2009-04-01
The retention of rare earth element (REE) in the soil profile are mainly controlled by three factors, (i) the stability of the primary REE-carrying minerals, (ii) the presence of secondary phases as clays and Fe- and Mn-oxyhydroxides and (ii) the concentration of colloidal organic matter (OM). Considering that each soil phases (mineral or organic) displays (ii) various surface properties, such as specific area, surface sites density and nature and (ii) their own REE distribution inherited from the rock weathering, their mobilization through various chemical reactions (dissolution, colloidal release….) may involve the development of various shaped REE patterns in the soil solutions. REE fractionation from the different soil phases may therefore be used to identify the response of the soil system to a particular chemical process such as reductive and/or acidic dissolution. To test this purpose, an organic-rich wetland soil sample was incubated under anaerobic condition at both pH 5 and uncontrolled pH. The REE patterns developed in the soil solution were then compared to the REE patterns obtained through either aerobic at pH 3 and 7 incubations or a chemical reduction experiment (using hydroxylamine). REE patterns in anaerobic and aerobic at pH 7 experiments exhibited the same middle rare earth element (MREE) downward concavity significant of the complexation of REE with soil OM. By contrast, under acidic condition, the REE pattern exhibited a positive Eu anomaly due to the dissolution of soil feldspar. Finally, REE pattern obtained from the chemical reducing experiment showed an intermediary flat shape corresponding to a mixing between the soil organic and mineral phases dissolution. The comparison of the various REE pattern shapes allowed to conclude that (i) biological reduction of wetland soil involved amorphous Fe(III) colloids linked to OM and, (ii) that the REE mobility was controlled by the dynamic of OM in wetland soil. They also evidence the potential of REE to be use as a tracer of the soil phases involved in the various chemical processes running in soil solutions.
Unusual Enhancement of Magnetization by Pressure in the Antiferro-Quadrupole-Ordered Phase in CeB6
NASA Astrophysics Data System (ADS)
Ikeda, Suguru; Sera, Masafumi; Hane, Shingo; Uwatoko, Yoshiya; Kosaka, Masashi; Kunii, Satoru
2007-06-01
The effect of pressure on CeB6 was investigated by the measurement of the magnetization (M) under pressure, and we obtained the following results. The effect of pressure on M in phase I is very small. By applying pressure, TQ is enhanced, but TN and the critical field from the antiferromagnetic (AFM) phase III to the antiferro-quadrupole (AFQ) phase II (HcIII--II) are suppressed, as previously reported. The magnetization curve in phase III shows the characteristic shoulder at H˜ HcIII--II/2 at ambient pressure. This shoulder becomes much more pronounced by applying pressure. Both HcIII--II and the magnetic field, where a shoulder is seen in the magnetization curve in phase III, are largely suppressed by pressure. In phase II, the M-T curve at a low magnetic field exhibits an unusual concave temperature dependence below TQ down to TN. Thus, we found that the lower the magnetic field, the larger the enhancement of M in both phases III and II. To clarify the origin of the unusual pressure effect of M, we performed a mean-field calculation for the 4-sublattice model using the experimental results of dTQ/dP>0 and dTN/dP<0 and assuming the positive pressure dependence of the Txyz-antiferro-octupole (AFO) interaction. The characteristic features of the pressure effect of M obtained by the experiments could be reproduced well by the mean-field calculation. We found that the origin of the characteristic effect of pressure on CeB6 is the change in the subtle balance between the AFM interaction and the magnetic field-induced-effective FM interaction induced by the coexistence of the Oxy-AFQ and Txyz-AFO interactions under pressure.
Pearce, Carolyn I; Wilkins, Michael J; Zhang, Changyong; Heald, Steve M; Fredrickson, Jim K; Zachara, John M
2012-08-07
Etched silicon microfluidic pore network models (micromodels) with controlled chemical and redox gradients, mineralogy, and microbiology under continuous flow conditions are used for the incremental development of complex microenvironments that simulate subsurface conditions. We demonstrate the colonization of micromodel pore spaces by an anaerobic Fe(III)-reducing bacterial species (Geobacter sulfurreducens) and the enzymatic reduction of a bioavailable Fe(III) phase within this environment. Using both X-ray microprobe and X-ray absorption spectroscopy, we investigate the combined effects of the precipitated Fe(III) phases and the microbial population on uranium biogeochemistry under flow conditions. Precipitated Fe(III) phases within the micromodel were most effectively reduced in the presence of an electron shuttle (AQDS), and Fe(II) ions adsorbed onto the precipitated mineral surface without inducing any structural change. In the absence of Fe(III), U(VI) was effectively reduced by the microbial population to insoluble U(IV), which was precipitated in discrete regions associated with biomass. In the presence of Fe(III) phases, however, both U(IV) and U(VI) could be detected associated with biomass, suggesting reoxidation of U(IV) by localized Fe(III) phases. These results demonstrate the importance of the spatial localization of biomass and redox active metals, and illustrate the key effects of pore-scale processes on contaminant fate and reactive transport.
Safety and tolerability review of lorcaserin in clinical trials.
Greenway, F L; Shanahan, W; Fain, R; Ma, T; Rubino, D
2016-10-01
Lorcaserin is a novel selective serotonin 2C receptor agonist indicated by the US Food and Drug Administration for chronic weight management in adults with obesity or overweight with ≥1 comorbidity. The safety and efficacy of lorcaserin were established during two Phase III clinical trials in patients without diabetes (BLOOM and BLOSSOM) and one Phase III clinical trial in patients with type 2 diabetes (BLOOM-DM). Headache was the most common adverse event experienced by patients during all Phase III trials. Additional adverse events occurring in >5% of patients receiving lorcaserin included dizziness, fatigue, nausea, dry mouth and constipation in patients without diabetes, and hypoglycaemia, back pain, cough and fatigue in patients with diabetes. In a pooled analysis of echocardiographic data collected during the three lorcaserin Phase III trials, the incidence of FDA-defined valvulopathy was similar in patients taking lorcaserin and the placebo. Here, the safety profile of lorcaserin at the FDA-approved dose of 10 mg twice daily is reviewed using data from the lorcaserin Phase III programme, with a focus on theoretical adverse events commonly associated with agonists of the serotonin receptor family. Based on the lorcaserin Phase III clinical trial data, lorcaserin is safe and well tolerated in the indicated patient populations. © 2016 World Obesity.
Deloose, Eveline; Vos, Rita; Janssen, Pieter; Van den Bergh, Omer; Van Oudenhove, Lukas; Depoortere, Inge; Tack, Jan
2016-03-01
Motilin-induced phase III contractions have been identified as a hunger signal. These phase III contractions occur as part of the migrating motor complex (MMC), a contractility pattern of the gastrointestinal tract during fasting. The mechanism involved in this association between subjective hunger feelings and gastrointestinal motility during the MMC is largely unknown, however, as is its ability to stimulate food intake. We sought to 1) investigate the occurrence of hunger peaks and their relation to phase III contractions, 2) evaluate whether this relation was cholinergically driven, and 3) assess the ability of the motilin receptor agonist erythromycin to induce food intake. An algorithm was developed to detect hunger peaks. The association with phase III contractions was studied in 14 healthy volunteers [50% men; mean ± SEM age: 25 ± 2 y; mean ± SEM body mass index (BMI; in kg/m(2)): 23 ± 1]. The impact of pharmacologically induced phase III contractions on the occurrence of hunger peaks and the involvement of a cholinergic pathway were assessed in 14 healthy volunteers (43% men; age: 29 ± 3 y; BMI: 23 ± 1). Last, the effect of erythromycin administration on food intake was examined in 15 healthy volunteers (40% men; age: 28 ± 3 y; BMI: 22 ± 1). The occurrence of hunger peaks and their significant association with phase III contractions was confirmed (P < 0.0001). Pharmacologically induced phase III contractions were also significantly associated with hunger peaks (P < 0.05), and this association involved a cholinergic pathway. Administering erythromycin significantly stimulated food intake compared with placebo (53% ± 13% compared with 10% ± 5%; P < 0.05). Motilin-induced phase III contractions induced hunger feelings through a cholinergic pathway. Moreover, erythromycin stimulated food intake, suggesting a physiologic role of motilin as an orexigenic signal from the gastrointestinal tract. This trial was registered at www.clinicaltrials.gov as NCT02633579. © 2016 American Society for Nutrition.
Monterey-Salinas Transit ITS Augmentation Project : Phase III Evaluation Report
DOT National Transportation Integrated Search
2009-12-01
The purpose of this document is to present the findings from Phase II and Phase III of the Evaluation of the Intelligent Transportation Systems (ITS) Augmentation Project that was implemented at the Monterey-Salinas Transit (MST) in Monterey, Califor...
The Mississippi Catalog of Competencies for Public Elementary and Secondary Physical Education.
ERIC Educational Resources Information Center
Mississippi State Dept. of Education, Jackson.
Phase III of a five-phase project which has implications for the improvement of instructional programs in Mississippi's elementary and secondary schools is described. In phase III, specifically stated objectives or competencies in physical education, designed to accomplish the objectives stated in phase II, are cataloged. The competencies are…
The use of dihexyldithiocarbamate in reverse-phase HPLC of metal chelates
NASA Astrophysics Data System (ADS)
Fatimah, S. S.; Bahti, H. H.; Hastiawan, I.; Permanasari, A.
2018-05-01
Dialkyldithiocarbamates have long been used as chelating agents in reverse-phase HPLC of transition metals. In the previous study, an alkyl homolog of this type of ligand, namely dihexyldithiocarbamate (DHDTC), was synthesized and characterized. The use of this particular ligand in the revese-phase HPLC of some selected transition metal ions is now reported for the first time. The mobile phase comprising of the flow rate and of the detection, in the separation of the metal chelates of Cd (II), Fe (III), Cu (II), and Co (III), were investigated on a C-18 column. The results showed that dihexylditiocarbamate could be used for separating Cd (II), Fe(III), Cu(II), and Co(III). Therefore, it could be used in simultaneous analysis.
Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies
Mameniškienė, Rūta; Quarato, Pier Paolo; Klein, Pavel; Gamage, Jessica; Schiemann, Jimmy; Johnson, Martin E.; Whitesides, John; McDonough, Belinda; Eckhardt, Klaus
2016-01-01
Objective: To assess the efficacy, safety, and tolerability of adjunctive brivaracetam (BRV), a selective, high-affinity ligand for SV2A, for treatment of partial-onset (focal) seizures (POS) in adults. Methods: Data were pooled from patients (aged 16–80 years) with POS uncontrolled by 1 to 2 antiepileptic drugs receiving BRV 50, 100, or 200 mg/d or placebo, without titration, in 3 phase III studies of BRV (NCT00490035, NCT00464269, and NCT01261325, ClinicalTrials.gov, funded by UCB Pharma). The studies had an 8-week baseline and a 12-week treatment period. Patients receiving concomitant levetiracetam were excluded from the efficacy pool. Results: In the efficacy population (n = 1,160), reduction over placebo (95% confidence interval) in baseline-adjusted POS frequency/28 days was 19.5% (8.0%–29.6%) for 50 mg/d (p = 0.0015), 24.4% (16.8%–31.2%) for 100 mg/d (p < 0.00001), and 24.0% (15.3%–31.8%) for 200 mg/d (p < 0.00001). The ≥50% responder rate was 34.2% (50 mg/d, p = 0.0015), 39.5% (100 mg/d, p < 0.00001), and 37.8% (200 mg/d, p = 0.00003) vs 20.3% for placebo (p < 0.01). Across the safety population groups (n = 1,262), 90.0% to 93.9% completed the studies. Treatment-emergent adverse events (TEAEs) were reported by 68.0% BRV overall (n = 803) and 62.1% placebo (n = 459). Serious TEAEs were reported by 3.0% (BRV) and 2.8% (placebo); 3 patients receiving BRV and one patient receiving placebo died. TEAEs in ≥5% patients taking BRV (vs placebo) were somnolence (15.2% vs 8.5%), dizziness (11.2% vs 7.2%), headache (9.6% vs 10.2%), and fatigue (8.7% vs 3.7%). Conclusions: Adjunctive BRV was effective and generally well tolerated in adults with POS. Classification of evidence: This analysis provides Class I evidence that adjunctive BRV is effective in reducing POS frequency in adults with epilepsy and uncontrolled seizures. PMID:27335114
Phillips, Patrick P J; Dooley, Kelly E; Gillespie, Stephen H; Heinrich, Norbert; Stout, Jason E; Nahid, Payam; Diacon, Andreas H; Aarnoutse, Rob E; Kibiki, Gibson S; Boeree, Martin J; Hoelscher, Michael
2016-03-23
The standard 6-month four-drug regimen for the treatment of drug-sensitive tuberculosis has remained unchanged for decades and is inadequate to control the epidemic. Shorter, simpler regimens are urgently needed to defeat what is now the world's greatest infectious disease killer. We describe the Phase IIC Selection Trial with Extended Post-treatment follow-up (STEP) as a novel hybrid phase II/III trial design to accelerate regimen development. In the Phase IIC STEP trial, the experimental regimen is given for the duration for which it will be studied in phase III (presently 3 or 4 months) and patients are followed for clinical outcomes of treatment failure and relapse for a total of 12 months from randomisation. Operating characteristics of the trial design are explored assuming a classical frequentist framework as well as a Bayesian framework with flat and sceptical priors. A simulation study is conducted using data from the RIFAQUIN phase III trial to illustrate how such a design could be used in practice. With 80 patients per arm, and two (2.5 %) unfavourable outcomes in the STEP trial, there is a probability of 0.99 that the proportion of unfavourable outcomes in a potential phase III trial would be less than 12 % and a probability of 0.91 that the proportion of unfavourable outcomes would be less than 8 %. With six (7.5 %) unfavourable outcomes, there is a probability of 0.82 that the proportion of unfavourable outcomes in a potential phase III trial would be less than 12 % and a probability of 0.41 that it would be less than 8 %. Simulations using data from the RIFAQUIN trial show that a STEP trial with 80 patients per arm would have correctly shown that the Inferior Regimen should not proceed to phase III and would have had a high chance (0.88) of either showing that the Successful Regimen could proceed to phase III or that it might require further optimisation. Collection of definitive clinical outcome data in a relatively small number of participants over only 12 months provides valuable information about the likelihood of success in a future phase III trial. We strongly believe that the STEP trial design described herein is an important tool that would allow for more informed decision-making and accelerate regimen development.
Favre-Réguillon, Alain; Draye, Micheline; Lebuzit, Gérard; Thomas, Sylvie; Foos, Jacques; Cote, Gérard; Guy, Alain
2004-06-17
Cloud point extraction (CPE) was used to extract and separate lanthanum(III) and gadolinium(III) nitrate from an aqueous solution. The methodology used is based on the formation of lanthanide(III)-8-hydroxyquinoline (8-HQ) complexes soluble in a micellar phase of non-ionic surfactant. The lanthanide(III) complexes are then extracted into the surfactant-rich phase at a temperature above the cloud point temperature (CPT). The structure of the non-ionic surfactant, and the chelating agent-metal molar ratio are identified as factors determining the extraction efficiency and selectivity. In an aqueous solution containing equimolar concentrations of La(III) and Gd(III), extraction efficiency for Gd(III) can reach 96% with a Gd(III)/La(III) selectivity higher than 30 using Triton X-114. Under those conditions, a Gd(III) decontamination factor of 50 is obtained.
ERIC Educational Resources Information Center
Stringfield, Sam; And Others
Phase III of the Louisiana School Effectiveness Study (LSES-III) was designed in part to obtain rich, qualitative data on the characteristics of more and less effective schools in the Gulf South. Data were gathered on eight matched outlier pairs of schools during the 1984-1985 school year. Of the eight historically ineffective schools in LSES-III,…
Retrograde adsorption isotherms: an impossible fact?
Helfferich, Friedrich G
2005-06-24
"Retrograde" adsorption isotherms have been reported, but seem to violate thermodynamics and would cause concentration steps to migrate against the direction of fluid-phase flow. In general, what appears to be retrograde behavior is caused by one or more additional, uncontrolled variables. This is illustrated with adsorption of sulfonate on a weak-acid ion exchanger, where adsorption is accompanied by partial conversion of the ion exchanger to the sodium form.
Design and experiment of vehicular charger AC/DC system based on predictive control algorithm
NASA Astrophysics Data System (ADS)
He, Guangbi; Quan, Shuhai; Lu, Yuzhang
2018-06-01
For the car charging stage rectifier uncontrollable system, this paper proposes a predictive control algorithm of DC/DC converter based on the prediction model, established by the state space average method and its prediction model, obtained by the optimal mathematical description of mathematical calculation, to analysis prediction algorithm by Simulink simulation. The design of the structure of the car charging, at the request of the rated output power and output voltage adjustable control circuit, the first stage is the three-phase uncontrolled rectifier DC voltage Ud through the filter capacitor, after by using double-phase interleaved buck-boost circuit with wide range output voltage required value, analyzing its working principle and the the parameters for the design and selection of components. The analysis of current ripple shows that the double staggered parallel connection has the advantages of reducing the output current ripple and reducing the loss. The simulation experiment of the whole charging circuit is carried out by software, and the result is in line with the design requirements of the system. Finally combining the soft with hardware circuit to achieve charging of the system according to the requirements, experimental platform proved the feasibility and effectiveness of the proposed predictive control algorithm based on the car charging of the system, which is consistent with the simulation results.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Starcher, Autumn N.; Li, Wei; Kukkadapu, Ravi K.
Fe(II)-Al(III)-LDH (layered double hydroxide) phases have been shown to form from reactions of aqueous Fe(II) with Fe-free Al-bearing minerals (phyllosilicate/clays and Al-oxides). To our knowledge, the effect of small amounts of structural Fe(III) impurities in “neutral” clays on such reactions, however, were not studied. In this study to understand the role of structural Fe(III) impurity in clays, laboratory batch studies with pyrophyllite (10 g/L), an Al-bearing phyllosilicate, containing small amounts of structural Fe(III) impurities and 0.8 mM and 3 mM Fe(II) (both natural and enriched in 57Fe) were carried out at pH 7.5 under anaerobic conditions (4% H2 – 96%more » N2 atmosphere). Samples were taken up to 4 weeks for analysis by Fe-X-ray absorption spectroscopy and 57Fe Mössbauer spectroscopy. In addition to the precipitation of Fe(II)-Al(III)-LDH phases as observed in earlier studies with pure minerals (no Fe(III) impurities in the minerals), the analyses indicated formation of small amounts of Fe(III) containing solid(s), most probably hybrid a Fe(II)-Al(III)/Fe(III)-LDH phase. The mechanism of Fe(II) oxidation was not apparent but most likely was due to interfacial electron transfer from the sorbed Fe(II) to the structural Fe(III) and/or surface-sorption-induced electron-transfer from the sorbed Fe(II) to the clay lattice. Increase in the Fe(II)/Al ratio of the LDH with reaction time further indicated the complex nature of the samples. This research provides evidence for the formation of both Fe(II)-Al(III)-LDH and Fe(II)-Fe(III)/Al(III)-LDH-like phases during reactions of Fe(II) in systems that mimic the natural environments. Better understanding Fe phase formation in complex laboratory studies will improve models of natural redox systems.« less
Iacoboni, G; Zucca, E; Ghielmini, M; Stathis, A
2018-05-01
The first-line treatment of diffuse large B-cell lymphoma (DLBCL) is the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, curing approximately 60% of patients. Many clinical trials have been carried out over the last 10 years trying to improve the results of this treatment, but the appropriateness of their planning strategies could be rediscussed. Reports of phase III trials evaluating the addition of molecularly targeted agents or new monoclonal antibodies to the classic R-CHOP backbone in first-line induction or maintenance treatment were reviewed. The trial design, primary end point, number of patients enrolled, patient selection criteria, treatment schedule and results were registered for each one. In addition, the phases I and II trials which preceded these phase III trials were also reviewed. Among six phase III trials with results, only one trial evaluating lenalidomide maintenance after response to R-CHOP induction was positive and reached its primary end point. The other five trials did not show an improved outcome with the addition of the new agent. The preceding phases I and II trials were very heterogeneous in their end points and design. Even though most of these trials were considered positive, thus encouraging further investigation, so far they failed to predict the results of the subsequent phase III trials. The standard of care for DLBCL is still R-CHOP. Phase I/II trials failed to predict the results of subsequent phase III trials evaluating non-chemotherapeutic agents added to R-CHOP. The methodology of phase II trials evaluating new agents in DLBCL needs to be better defined in the future.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-08-23
... (ADEC) in four phases. Phases I-III have been transferred from the EPA to ADEC. In March 2011, ADEC made a submission for approval for a one year extension of the transfer of Phase IV of the APDES program... facilities not previously transferred in Phases I-III. The EPA approved the one year extension for Phase IV...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pearce, Carolyn I.; Wilkins, Michael J.; Zhang, Changyong
2012-09-17
Etched silicon microfluidic pore network models (micromodels) with controlled chemical and redox gradients, mineralogy, and microbiology under continuous flow conditions are used for the incremental development of complex microenvironments that simulate subsurface conditions. We demonstrate the colonization of micromodel pore spaces by an anaerobic Fe(III)-reducing bacterial species (Geobacter sulfurreducens) and the enzymatic reduction of a bioavailable Fe(III) phase within this environment. Using both X-ray Microprobe and X-ray Absorption Spectroscopy, we investigate the combined effects of the precipitated Fe(III) phases and the microbial population on uranium biogeochemistry under flow conditions. Precipitated Fe(III) phases within the micromodel were most effectively reduced inmore » the presence of an electron shuttle (AQDS), and Fe(II) ions adsorbed onto the precipitated mineral surface without inducing any structural change. In the absence of Fe(III), U(VI) was effectively reduced by the microbial population to insoluble U(IV), which was precipitated in discrete regions associated with biomass. In the presence of Fe(III) phases, however, both U(IV) and U(VI) could be detected associated with biomass, suggesting re-oxidation of U(IV) by localized Fe(III) phases. These results demonstrate the importance of the spatial localization of biomass and redox active metals, and illustrate the key effects of pore-scale processes on contaminant fate and reactive transport.« less
Changing interdigestive migrating motor complex in rats under acute liver injury.
Liu, Mei; Zheng, Su-Jun; Xu, Weihong; Zhang, Jianying; Chen, Yu; Duan, Zhongping
2014-01-01
Gastrointestinal motility disorder is a major clinical manifestation of acute liver injury, and interdigestive migrating motor complex (MMC) is an important indicator. We investigated the changes and characteristics of MMC in rats with acute liver injury. Acute liver injury was created by d-galactosamine, and we recorded the interdigestive MMC using a multichannel physiological recorder and compared the indexes of interdigestive MMC. Compared with normal controls, antral MMC Phase I duration was significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The duodenal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The jejunal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury compared with normal controls. Compared with the normal controls, rats with acute liver injury had a significantly prolonged interdigestive MMC cycle, related mainly to longer MMC Phases I and IV, shortened MMC Phase III, and MMC Phase II characterized by increased migrating clustered contractions, which were probably major contributors to the gastrointestinal motility disorders.
Lee, Chih-Wei; Wang, Ji-Hung; Hsieh, Jen-Che; Hsieh, Tsung-Cheng; Huang, Chien-Hui
2013-01-01
[Purpose] To investigate the effects of cardiac exercise therapy (CET) on exercise capacity and coronary risk factors (CRFs) of patients with acute myocardial infarction (AMI). [Methods] Patients who participated in an 8-week supervised, hospital-based phase II and 6-month home-based phase III CET with monthly telephone and/or home visits were defined as the exercise group (EG) (n=20), while those who did not receive phase II or phase III CET were defined as the no-exercise group (NEG) (n=10). CRFs were evaluated pre- and post-phase II and eight months after discharge. One and two-way repeated measures ANOVA were used to perform intra- and inter-group comparisons. [Results] Thirty men with AMI aged 49.3 ± 8.3 years were studied. EG increased their exercise capacity (METs) (6.8 ± 1.6 vs.10.0 ± 1.9) after phase II CET and was able to maintain it at 8-month follow-up. Both groups had significantly fewer persons who kept on smoking compared to the first examination. High density lipoprotein cholesterol (HDL-C) increased from 38.1 ± 11.0 to 43.7 ± 8.7 mg/dl at follow-up in EG while no significant difference was noted in NEG. [Conclusion] After phase III CET subjects had maintained the therapeutic effects of smoking cessation, and increasing exercise capacity obtained in phase II CET. HDL-C in EG continued to improve during phase III CET. PMID:24396201
Phase III Simplified Integrated Test (SIT) results - Space Station ECLSS testing
NASA Technical Reports Server (NTRS)
Roberts, Barry C.; Carrasquillo, Robyn L.; Dubiel, Melissa Y.; Ogle, Kathryn Y.; Perry, Jay L.; Whitley, Ken M.
1990-01-01
During 1989, phase III testing of Space Station Freedom Environmental Control and Life Support Systems (ECLSS) began at Marshall Space Flight Center (MSFC) with the Simplified Integrated Test. This test, conducted at the MSFC Core Module Integration Facility (CMIF), was the first time the four baseline air revitalization subsystems were integrated together. This paper details the results and lessons learned from the phase III SIT. Future plans for testing at the MSFC CMIF are also discussed.
Review of phase III trial data on IL-23 inhibitors tildrakizumab and guselkumab for psoriasis.
Amin, M; Darji, K; No, D J; Wu, J J
2017-10-01
The development of monoclonal antibodies targeting IL-12 and IL-23 has enhanced the therapeutic options available for psoriasis patients. Recent research suggests that IL-23 alone plays a role in the pathogenesis of psoriasis. The objective was to review the phase III clinical trial data for the anti-IL-23 agents to evaluate the safety and efficacy profile of each agent. We reviewed the results of the phase III clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab. The results of phase III trials on risankizumab have not yet been reported. By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was >60% among the most efficacious dose of each agent. The percentage of patients achieving PASI 90 at week 16 was the primary endpoint for the phase III trials for guselkumab, which was above 70%. The safety profiles of the agents were comparable, with the most commonly reported adverse events of nasopharyngitis and upper respiratory tract infections. The anti-IL-23 agents demonstrated a rapid clinical improvement that is similar or superior to the improvement seen with currently marketed IL-17 inhibitors with a favourable short-term safety profile. The results of the phase III trials support the notion that IL-23 is a potential target in psoriasis treatment. © 2017 European Academy of Dermatology and Venereology.
Kaneko, Masato; Tanigawa, Takahiko; Hashizume, Kensei; Kajikawa, Mariko; Tajiri, Masahiro; Mueck, Wolfgang
2013-01-01
This study was designed to confirm the appropriateness of the dose setting for a Japanese phase III study of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF), which had been based on model simulation employing phase II study data. The previously developed mixed-effects pharmacokinetic/pharmacodynamic (PK-PD) model, which consisted of an oral one-compartment model parameterized in terms of clearance, volume and a first-order absorption rate, was rebuilt and optimized using the data for 597 subjects from the Japanese phase III study, J-ROCKET AF. A mixed-effects modeling technique in NONMEM was used to quantify both unexplained inter-individual variability and inter-occasion variability, which are random effect parameters. The final PK and PK-PD models were evaluated to identify influential covariates. The empirical Bayes estimates of AUC and C(max) from the final PK model were consistent with the simulated results from the Japanese phase II study. There was no clear relationship between individual estimated exposures and safety-related events, and the estimated exposure levels were consistent with the global phase III data. Therefore, it was concluded that the dose selected for the phase III study with Japanese NVAF patients by means of model simulation employing phase II study data had been appropriate from the PK-PD perspective.
Benzocaine polymorphism: pressure-temperature phase diagram involving forms II and III.
Gana, Inès; Barrio, Maria; Do, Bernard; Tamarit, Josep-Lluís; Céolin, René; Rietveld, Ivo B
2013-11-18
Understanding the phase behavior of an active pharmaceutical ingredient in a drug formulation is required to avoid the occurrence of sudden phase changes resulting in decrease of bioavailability in a marketed product. Benzocaine is known to possess three crystalline polymorphs, but their stability hierarchy has so far not been determined. A topological method and direct calorimetric measurements under pressure have been used to construct the topological pressure-temperature diagram of the phase relationships between the solid phases II and III, the liquid, and the vapor phase. In the process, the transition temperature between solid phases III and II and its enthalpy change have been determined. Solid phase II, which has the highest melting point, is the more stable phase under ambient conditions in this phase diagram. Surprisingly, solid phase I has not been observed during the study, even though the scarce literature data on its thermal behavior appear to indicate that it might be the most stable one of the three solid phases. Copyright © 2013 Elsevier B.V. All rights reserved.
1984-09-10
0") AD STUDIES ON THE INHALATION TOXICITY CO• OF DYES PRESENT IN COLORED Ln SMOKE MUNIlIONS U FINAL REPORT FOR PHASE III STUDIES : SFOUR- ELK...3 RECIIEPIT’S CATA6.0G NUMBE.• 4. TITLE (and ,ubiltI.e) S. TYPE OF REPORT & PERIOD COygC r., Studies on the Inhalation Toxicity of Dyes Final: Phase...III Present in Colored Smoke Munitions. Final Report Fh for Phase 111 Studies : FoLr-Week Inhalation G. PERFORMING ORO. REPORT N,’,ER Exposures of Rats
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chesneau, H.L.; Passman, F.J.; Daniels, D.
1995-05-01
Responding to feed-back from its retail outlet network, a major, vertically integrated petroleum company undertook to diagnose and remediate diesel and gasoline performance problems. Analysis of samples from tanks at refinery, distribution terminal and retail outlet sites established that uncontrolled microbial contamination was rampant throughout the distribution system. The company then developed and instituted a two-phase action plan. During Phase I, all tanks received corrective (shock) biocide treatment preceding mechanical tank cleaning and fuel polishing. An ongoing Phase II program currently includes routine sampling and analysis combined with periodic preventive biocide treatment. This paper describes the initial problem diagnosis, correctivemore » action plan and preventive program; recommending the Phase II program as a model for all companies involved with refining, distribution or retailing gasoline.« less
PLCO Ovarian Phase III Validation Study — EDRN Public Portal
Our preliminary data indicate that the performance of CA 125 as a screening test for ovarian cancer can be improved upon by additional biomarkers. With completion of one additional validation step, we will be ready to test the performance of a consensus marker panel in a phase III validation study. Given the original aims of the PLCO trial, we believe that the PLCO represents an ideal longitudinal cohort offering specimens for phase III validation of ovarian cancer biomarkers.
Kika, T M; Lepira, F B; Kayembe, P K; Makulo, J R; Sumaili, E K; Kintoki, E V; M'Buyamba-Kabangu, J R
Uncontrolled hypertension remains an important issue in daily clinical practice worldwide. Although the majority of patients are treated in primary care, most of the data on blood pressure control originate from population-based studies or secondary healthcare. The aim of this study was to evaluate the frequency of uncontrolled hypertension and associated risk factors among hypertensive patients followed at primary care facilities in Kinshasa, the capital city of Democratic Republic of the Congo. A sample of 298 hypertensive patients seen at primary healthcare facilities, 90 men and 208 women, aged ≥ 18 years, were consecutively included in this cross-sectional study. The majority (66%) was receiving monotherapy, and diuretics (43%) were the most used drugs. According to 2007 European Society of Hypertension/European Society of Cardiology hypertension guidelines, uncontrolled hypertension was defined as blood pressure ≥ 140/90 or ≥ 130/80 mmHg (diabetes or chronic kidney disease). Logistic regression analysis was used to identify the determinants of uncontrolled hypertension. Uncontrolled hypertension was observed in 231 patients (77.5%), 72 men and 159 women. Uncontrolled systolic blood pressure (SBP) was more frequent than uncontrolled diastolic blood pressure (DBP) and increased significantly with advancing age (p = 0.002). The proportion of uncontrolled SBP and DBP was significantly higher in patients with renal failure (p = 0.01) and those with high (p = 0.03) to very high (p = 0.02) absolute cardiovascular risk. The metabolic syndrome (OR 2.40; 95% CI 1.01-5.74; p = 0.04) emerged as the main risk factor associated with uncontrolled hypertension. Uncontrolled hypertension was common in this case series and was associated with factors related to lifestyle and diet, which interact with blood pressure control.
Movement - uncontrolled or slow
Dystonia; Involuntary slow and twisting movements; Choreoathetosis; Leg and arm movements - uncontrollable; Arm and leg movements - uncontrollable; Slow involuntary movements of large muscle groups; Athetoid movements
Plasmapheresis in severe septic shock with disseminated intravascular coagulation.
Zilow, E P; Selle, B; Zilow, G
1994-01-01
An 18-year-old female with CNS relapse of acute lymphoblastic leukemia after previous complete remission of the disease underwent chemotherapy. Due to the therapy she suffered from profound suppression of bone marrow with consecutive thrombocytopenia and leukopenia. Despite prophylactic treatment, severe septicemia occurred with septic shock, hemolysis and disseminated intravascular coagulation (DIC). As the clinical course became uncontrollable by means of conventional therapy, including broad-spectrum antibiotics, substitution of fresh frozen plasma, antithrombin III and heparin therapy, plasma exchange was used as a rescue therapy. This method succeeded in effective replacement of clotting factors and normalization of coagulation, in removal of fibrinogen degradation products and probably of toxins and shock mediators. The patient recovered from shock.
Baity-Jesi, Marco; Calore, Enrico; Cruz, Andres; Fernandez, Luis Antonio; Gil-Narvión, José Miguel; Gordillo-Guerrero, Antonio; Iñiguez, David; Maiorano, Andrea; Marinari, Enzo; Martin-Mayor, Victor; Monforte-Garcia, Jorge; Muñoz Sudupe, Antonio; Navarro, Denis; Parisi, Giorgio; Perez-Gaviro, Sergio; Ricci-Tersenghi, Federico; Ruiz-Lorenzo, Juan Jesus; Schifano, Sebastiano Fabio; Tarancón, Alfonso; Tripiccione, Raffaele; Yllanes, David
2017-01-01
We have performed a very accurate computation of the nonequilibrium fluctuation–dissipation ratio for the 3D Edwards–Anderson Ising spin glass, by means of large-scale simulations on the special-purpose computers Janus and Janus II. This ratio (computed for finite times on very large, effectively infinite, systems) is compared with the equilibrium probability distribution of the spin overlap for finite sizes. Our main result is a quantitative statics-dynamics dictionary, which could allow the experimental exploration of important features of the spin-glass phase without requiring uncontrollable extrapolations to infinite times or system sizes. PMID:28174274
Zadoff-Chu sequence-based hitless ranging scheme for OFDMA-PON configured 5G fronthaul uplinks
NASA Astrophysics Data System (ADS)
Reza, Ahmed Galib; Rhee, June-Koo Kevin
2017-05-01
A Zadoff-Chu (ZC) sequence-based low-complexity hitless upstream time synchronization scheme is proposed for an orthogonal frequency division multiple access passive optical network configured cloud radio access network fronthaul. The algorithm is based on gradual loading of the ZC sequences, where the phase discontinuity due to the cyclic prefix is alleviated by a frequency domain phase precoder, eliminating the requirements of guard bands to mitigate intersymbol interference and inter-carrier interference. Simulation results for uncontrolled-wavelength asynchronous transmissions from four concurrent transmitting optical network units are presented to demonstrate the effectiveness of the proposed scheme.
Preparation of cerium halide solvate complexes
Vasudevan, Kalyan V; Smith, Nickolaus A; Gordon, John C; McKigney, Edward A; Muenchaussen, Ross E
2013-08-06
Crystals of a solvated cerium(III) halide solvate complex resulted from a process of forming a paste of a cerium(III) halide in an ionic liquid, adding a solvent to the paste, removing any undissolved solid, and then cooling the liquid phase. Diffusing a solvent vapor into the liquid phase also resulted in crystals of a solvated cerium(III) halide complex.
Effect of amoxicillin/clavulanate on gastrointestinal motility in children.
Gomez, Roberto; Fernandez, Sergio; Aspirot, Ann; Punati, Jaya; Skaggs, Beth; Mousa, Hayat; Di Lorenzo, Carlo
2012-06-01
The aim of the present study was to evaluate the effect of amoxicillin/clavulanate (A/C) on gastrointestinal motility. Twenty consecutive pediatric patients referred for antroduodenal manometry received 20 mg/kg of A/C into the small bowel lumen. In 10 patients (group A), A/C was given 1 hour after and in 10 (group B), 1 hour before ingestion of a meal. Characteristics of the migrating motor complex, including presence, frequency, amplitude, and propagation of duodenal phase III and phase I duration and phase II motility index (MI), were evaluated 30 minutes before and after A/C administration. There were no statistically significant differences in age and sex between the 2 groups. Manometry studies were considered normal in 8 patients in each group. In group A, 2 patients developed duodenal phase III after receiving A/C, and no significant difference was found in the MI before and after the drug administration. In group B, 9 patients developed duodenal phase III (P <0.05 vs group A). All phase III occurred within a few minutes from the medication administration. Most duodenal phase III contractions were preceded by an antral component during fasting but never after the medication was administered in either of the 2 groups (P<0.001 vs fasting). In group B, the duration of duodenal phase I was shorter after drug administration (P<0.05). There was no significant difference in duodenal phase II MI before and after A/C administration for the 2 study groups. In children, administration of A/C directly into the small bowel before a meal induces phase III-type contractions in the duodenum, with characteristics similar to those present in the fasting state. These data suggest the possible use of A/C as a prokinetic agent. Further studies are needed to clarify its specific mechanism of action and the group of patients most likely to benefit from its use.
Neutron imaging systems utilizing lithium-containing semiconductor crystals
Stowe, Ashley C.; Burger, Arnold
2017-04-25
A neutron imaging system, including: a plurality of Li-III-VI.sub.2 semiconductor crystals arranged in an array, wherein III represents a Group III element and VI represents a Group VI element; and electronics operable for detecting and a charge in each of the plurality of crystals in the presence of neutrons and for imaging the neutrons. Each of the crystals is formed by: melting the Group III element; adding the Li to the melted Group III element at a rate that allows the Li and Group III element to react, thereby providing a single phase Li-III compound; and adding the Group VI element to the single phase Li-III compound and heating. Optionally, each of the crystals is also formed by doping with a Group IV element activator.
75 FR 30385 - Defense Transportation Regulation, Part IV
Federal Register 2010, 2011, 2012, 2013, 2014
2010-06-01
... extensions will be considered due to the timelines associated with funding and programming future Phase III... extensions will be considered due to the timelines associated with funding and programming future Phase III...
Individualized Inservice Teacher Education (Project In-Step). Evaluation Report. Phase III.
ERIC Educational Resources Information Center
Thurber, John C.
This is a report on the third phase of Project IN-STEP, which was intended to develop a viable model for individualized, multi-media in-service teacher education programs. (Phase I and II are reported in ED 033 905, and ED 042 709). The rationale for Phase III was to see if the model could be successfully transferred to an area other than teaching…
Rotator Phases of n-Heptane under High Pressure: Raman Scattering and X-ray Diffraction Studies
DOE Office of Scientific and Technical Information (OSTI.GOV)
C Ma; Q Zhou; F Li
2011-12-31
We performed high-pressure Raman scattering and angle-dispersive synchrotron X-ray diffraction measurements on n-heptane at room temperature. It has been found that n-heptane undergoes a liquid to rotator phase III (R{sub III}) transition at 1.2 GPa and then transforms into another rotator phase R{sub IV} at about 3 GPa. As the pressure reaches 7.5 GPa, a transition from an orientationally disordered R{sub IV} phase to an ordered crystalline state starts and is completed around 14.5 GPa. Our results clearly present the high-pressure phase transition sequence (liquid-R{sub III}-R{sub IV}-crystal) of n-heptane, similar to that of normal alkanes.
Phase transformation in the alumina-titania system during flash sintering experiments
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jha, S. K.; Lebrun, J. M.; Raj, R.
2016-02-01
We show that phase transformation in the alumina–titania system, which produces aluminum-titanate, follows an unusual trajectory during flash sintering. The experiments begin with mixed powders of alumina–titania and end in dense microstructures that are transformed into aluminum-titanate. The sintering and the phase transformation are separated in time, with the sintering occurs during Stage II, and phase transformation during Stage III of the flash sintering experiment. Stage III is the steady-state condition of flash activated state that is established under current control, while Stage II is the period of transition from voltage to current control. The extent of phase transformation increasesmore » with the current density and the hold time in Stage III.« less
Sitia, Roberto; Rubartelli, Anna
2018-04-04
Interleukin 1β (IL-1β) is a major mediator of inflammation, with a causative role in many diseases. Unlike most other cytokines, however, it lacks a secretory signal sequence, raising intriguing mechanistic, functional and evolutionary questions. Despite decades of strenuous efforts in many laboratories, how IL-1β is secreted is still a matter of intense debate. Here, we summarize the different mechanisms and pathways that have been proposed for IL-1β secretion. At least two of them, namely the endolysosomal vesicle-based and gasdermin D-dependent pathways (types III and I in the recent Rabouille's classification of unconventional protein secretion), can be triggered in monocytes, the main source of IL-1β in humans, according to the type and strength of the pro-inflammatory stimuli. As during the escalation of human conflicts, monocytes deploy secretory mechanisms of increasing efficiency and dangerousness, shifting from the specific and controlled type III pathway to the much faster release of type I. Thus, the different mechanisms are activated depending on the severity of the conditions, from the self-limiting type III pathways in response of low pathogen load or small trauma, to the uncontrolled responses that underlie autoinflammatory disorders and sepsis. Copyright © 2018 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Patra, Santanu; Roy, Ekta; Madhuri, Rashmi; Sharma, Prashant K.
2017-05-01
The present work represents the preparation of imprinted magnetic reduced graphene oxide and applied it for the selective removal of Eu (III) from local coal mines area. A simple solid phase extraction method was used for this purpose. The material shows a very high adsorption as well as removal efficiency towards Eu (III), which suggest that the material have potential to be used in future for their real time applications in removal of Eu (III) from complex matrices.
ERIC Educational Resources Information Center
Schulz, Russel E.; Farrell, Jean R.
This resource guide for the use of job aids ("how-to-do-it" guidance) for activities identified in the third phase of the Instructional Systems Development Model (ISD) contains an introduction to the use of job aids, as well as descriptive authoring flowcharts for Blocks III.1 through III.5. The introduction includes definitions;…
Sub-micron phase coexistence in small-molecule organic thin films revealed by infrared nano-imaging
Westermeier, Christian; Cernescu, Adrian; Amarie, Sergiu; Liewald, Clemens; Keilmann, Fritz; Nickel, Bert
2014-01-01
Controlling the domain size and degree of crystallization in organic films is highly important for electronic applications such as organic photovoltaics, but suitable nanoscale mapping is very difficult. Here we apply infrared-spectroscopic nano-imaging to directly determine the local crystallinity of organic thin films with 20-nm resolution. We find that state-of-the-art pentacene films (grown on SiO2 at elevated temperature) are structurally not homogeneous but exhibit two interpenetrating phases at sub-micrometre scale, documented by a shifted vibrational resonance. We observe bulk-phase nucleation of distinct ellipsoidal shape within the dominant pentacene thin-film phase and also further growth during storage. A faint topographical contrast as well as X-ray analysis corroborates our interpretation. As bulk-phase nucleation obstructs carrier percolation paths within the thin-film phase, hitherto uncontrolled structural inhomogeneity might have caused conflicting reports about pentacene carrier mobility. Infrared-spectroscopic nano-imaging of nanoscale polymorphism should have many applications ranging from organic nanocomposites to geologic minerals. PMID:24916130
Development and testing of responder : phase III.
DOT National Transportation Integrated Search
2017-06-28
This report documents the research project Development and Testing of Responder Phase III. Under previous research, a Responder system has been developed to provide relevant and timely information to first responders, allow responders to provid...
Phase III Early Restoration Meeting | NOAA Gulf Spill Restoration
Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News Publications Press Releases Story programmatic approach to early restoration planning for Phase III and future early restoration plans. Open
Phase III Early Restoration Meeting - Corpus Christi, TX | NOAA Gulf Spill
Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open
Phase III Early Restoration Meeting - Pensacola, FL (rescheduled) | NOAA
Restoration Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open
Dohnke, Birte; Nowossadeck, Enno; Müller-Fahrnow, Werner
2010-10-01
This longitudinal study extends the previous research on low participation rates and high dropout rates in phase III cardiac rehabilitation (CR) exercise programmes. It examines the correlates of motivation and participation 6 months after inpatient phase II CR (T1) and the predictors of dropout 6 months later (T2) using the health action process approach (HAPA). Risk perception, outcome expectancies, self-efficacy, intention (at T1), and participation (at T1 and T2) in relation to phase III CR programmes was assessed in 456 patients. Based on intention and participation at T1, patients were classified as nonintenders (56%), intenders (13%), or actors (31%). Group differences were confirmed in outcome expectancies and self-efficacy. By T2, 21% of T1 actors had dropped out. Dropouts and maintainers differed in intention and self-efficacy (at T1). Results are in line with the HAPA and suggest a perspective for tailoring motivational counselling to improve participation in phase III CR programmes.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wu, T.; Griffin, A. M.; Gorski, C. A.
Dissimilatory microbial reduction of solid-phase Fe(III)-oxides and Fe(III)-bearing phyllosilicates (Fe(III)-phyllosilicates) is an important process in anoxic soils, sediments, and subsurface materials. Although various studies have documented the relative extent of microbial reduction of single-phase Fe(III)-oxides and Fe(III)-phyllosilicates, detailed information is not available on interaction between these two processes in situations where both phases are available for microbial reduction. The goal of this research was to use the model dissimilatory iron-reducing bacterium (DIRB) Geobacter sulfurreducens to study Fe(III)-oxide vs. Fe(III)-phyllosilicate reduction in a range of subsurface materials and Fe(III)-oxide stripped versions of the materials. Low temperature (12K) Mossbauer spectroscopy was usedmore » to infer changes in the relative abundances of Fe(III)-oxide, Fe(III)-phyllosilicate, and phyllosilicate-associated Fe(II) (Fe(II)-phyllosilicate). A Fe partitioning model was employed to analyze the fate of Fe(II) and assess the potential for abiotic Fe(II)-catalyzed reduction of Fe(III)-phyllosilicates. The results showed that in most cases Fe(III)- oxide utilization dominated (70-100 %) bulk Fe(III) reduction activity, and that electron transfer from oxide-derived Fe(II) played only a minor role (ca. 10-20 %) in Fe partitioning. In addition, the extent of Fe(III)-oxide reduction was positively correlated to surface area-normalized cation exchange capacity and the phyllosilicate-Fe(III)/total Fe(III) ratio, which suggests that the phyllosilicates in the natural sediments promoted Fe(III)-oxide reduction by binding of oxide-derived Fe(II), thereby enhancing Fe(III)-oxide reduction by reducing or delaying the inhibitory effect that Fe(II) accumulation on oxide and DIRB cell surfaces has on Fe(III)-oxide reduction. In general our results suggest that although Fe(III)-oxide reduction is likely to dominate bulk Fe(III) reduction in most subsurface sediments, Fe(II) binding by phyllosilicates is likely to play a key role in controlling the long-term kinetics of Fe(III)-oxide reduction.« less
Installation Restoration Program. Phase II--Confirmation/Quantification. Stage 1.
1985-03-01
four phases. Phase I, Initial Assessment/ Records Search, is designed to identify possible hazardous waste contami- nated sites and potential...7 71 -. - - IL’ -, 1% 33 AihlIII Is 33 n~iL t iiC UII! ii CL C LU 1-3, Phase II, Confirmation and Quantification, is designed to confirm the...additional monitoring data upon which design of mitigative actions are based. In Phase III, Technology Base Development, appropriate technology is selected and
Swoboda, Sandra M; Earsing, Karen; Strauss, Kevin; Lane, Stephen; Lipsett, Pamela A
2004-02-01
To determine whether electronic monitoring of hand hygiene and voice prompts can improve hand hygiene and decrease nosocomial infection rates in a surgical intermediate care unit. Three-phase quasi-experimental design. Phase I was electronic monitoring and direct observation; phase II was electronic monitoring and computerized voice prompts for failure to perform hand hygiene on room exit; and phase III was electronic monitoring only. Nine-room, 14-bed intermediate care unit in a university, tertiary-care institution. All patient rooms, utility room, and staff lavatory were monitored electronically. All healthcare personnel including physicians, nurses, nursing support personnel, ancillary staff, all visitors and family members, and any other personnel interacting with patients on the intermediate care unit. All patients with an intermediate care unit length of stay >48 hrs were followed for nosocomial infection. Electronic monitoring during all phases, computerized voice prompts during phase II only. We evaluated a total of 283,488 electronically monitored entries into a patient room with 251,526 exits for 420 days (10,080 hrs and 3,549 patient days). Compared with phase I, hand hygiene compliance in patient rooms improved 37% during phase II (odds ratio, 1.38; 95% confidence interval, 1.04-1.83) and 41% in phase III (odds ratio, 1.41; 95% confidence interval, 1.07-1.84). When adjusting for patient admissions during each phase, point estimates of nosocomial infections decreased by 22% during phase II and 48% during phase III; when adjusting for patient days, the number of infections decreased by 10% during phase II and 40% during phase III. Although the overall rate of nosocomial infections significantly decreased when combining phases II and III, the association between nosocomial infection and individual phase was not significant. Electronic monitoring provided effective ongoing feedback about hand hygiene compliance. During both the voice prompt phase and post-intervention phase, hand hygiene compliance and nosocomial infection rates improved suggesting that ongoing monitoring and feedback had both a short-term and, perhaps, a longer-term effect.
NASA Astrophysics Data System (ADS)
Liu, Chuanjiang; Zheng, Haifei; Wang, Duojun
2017-10-01
In our study, a series of Raman experiments on the phase transition of calcite at high pressure and high temperature were investigated using a hydrothermal diamond anvil cell and Raman spectroscopy technique. It was found that calcite I transformed to calcite II and calcite III at pressures of 1.62 and 2.12 GPa and room temperature. With increasing temperature, the phase transition of calcite III to aragonite occurred. Aragonite was retained upon slowly cooling of the system, indicating that the transition of calcite III to aragonite was irreversible. Based on the available data, the phase boundary between calcite III and aragonite was determined by the following relation: P(GPa) = 0.013 × T(°C) + 1.22 (100°C ≤ T ≤ 170°C). It showed that the transition pressure linearly rose with increasing temperature. A better understanding of the stability of calcite III and aragonite is of great importance to further explore the thermodynamic behavior of carbonates and carbon cycling in the mantle.
Trends in heteroepitaxy of III-Vs on silicon for photonic and photovoltaic applications
NASA Astrophysics Data System (ADS)
Lourdudoss, Sebastian; Junesand, Carl; Kataria, Himanshu; Metaferia, Wondwosen; Omanakuttan, Giriprasanth; Sun, Yan-Ting; Wang, Zhechao; Olsson, Fredrik
2017-02-01
We present and compare the existing methods of heteroepitaxy of III-Vs on silicon and their trends. We focus on the epitaxial lateral overgrowth (ELOG) method as a means of achieving good quality III-Vs on silicon. Initially conducted primarily by near-equilibrium epitaxial methods such as liquid phase epitaxy and hydride vapour phase epitaxy, nowadays ELOG is being carried out even by non-equilibrium methods such as metal organic vapour phase epitaxy. In the ELOG method, the intermediate defective seed and the mask layers still exist between the laterally grown purer III-V layer and silicon. In a modified ELOG method called corrugated epitaxial lateral overgrowth (CELOG) method, it is possible to obtain direct interface between the III-V layer and silicon. In this presentation we exemplify some recent results obtained by these techniques. We assess the potentials of these methods along with the other existing methods for realizing truly monolithic photonic integration on silicon and III-V/Si heterojunction solar cells.
Effect of 60 degrees head-down tilt on peripheral gas mixing in the human lung.
Olfert, I Mark; Prisk, G Kim
2004-09-01
The phase III slope of sulfur hexafluoride (SF6) in a single-breath washout (SBW) is greater than that of helium (He) under normal gravity (i.e., 1G), thus resulting in a positive SF6-He slope difference. In microgravity (microG), SF6-He slope difference is smaller because of a greater fall in the phase III slope of SF6 than He. We sought to determine whether increasing thoracic fluid volume using 60 degrees head-down tilt (HDT) in 1G would produce a similar effect to microG on phase III slopes of SF6 and He. Single-breath vital capacity (SBW) and multiple-breath washout (MBW) tests were performed before, during, and 60 min after 1 h of HDT. Compared with baseline (SF6 1.050 +/- 0.182%/l, He 0.670 +/- 0.172%/l), the SBW phase III slopes for both SF6 and He tended to decrease during HDT, reaching nadir at 30 min (SF6 0.609 +/- 0.211%/l, He 0.248 +/- 0.138%/l; P = 0.08 and P = 0.06, respectively). In contrast to microG, the magnitude of the phase III slope decrease was similar for both SF6 and He; therefore, no change in SF6-He slope difference was observed. MBW analysis revealed a decrease in normalized phase III slopes at all time points during HDT, for both SF6 (P < 0.01) and He (P < 0.01). This decrease was due to changes in the acinar, and not the conductive, component of the normalized phase III slope. These findings support the notion that changes in thoracic fluid volume alter ventilation distribution in the lung periphery but also demonstrate that the effect during HDT does not wholly mimic that observed in microG.
Healthcare utilization and costs in adults with stable and uncontrolled epilepsy.
Cramer, Joyce A; Wang, Zhixiao J; Chang, Eunice; Powers, Annette; Copher, Ronda; Cherepanov, Dasha; Broder, Michael S
2014-02-01
Despite the availability of numerous antiepileptic drugs (AEDs), some epilepsies remain resistant to treatment. We compared utilization and costs in patients with uncontrolled epilepsy to those with stable epilepsy. Claims data (2007-2009) were used to identify adults with epilepsy requiring additional AED therapy (having uncontrolled epilepsy) and those not requiring additional AED therapy (having stable epilepsy). The date in 2008 on which an additional AED was started was the index date for patients with uncontrolled epilepsy, and a randomly selected date was used for patients with stable epilepsy, whose AED use was unchanged in the preceding year. In the postindex year, all pharmacy and medical claims were used to estimate overall utilization and costs; claims with epilepsy in any diagnosis field were used to estimate epilepsy-related outcomes. Outcomes were adjusted using multivariate analyses. We identified 1536 patients with uncontrolled epilepsy and 8571 patients with stable epilepsy (mean age: 42.8years; female: 48%). Patients with uncontrolled epilepsy had higher comorbidity rates (p<.02). A greater proportion of patients with uncontrolled epilepsy had ≥1 hospitalization or emergency department visit (p<.001). Patients with uncontrolled epilepsy had a greater mean length of hospital stay and more physician office visits (p<.034). After adjustment, the odds of hospitalization (OR: 1.8, any diagnosis; 2.2, epilepsy-related) and emergency department visit (OR: 1.6, any diagnosis; 1.9, epilepsy-related) were greater for patients with uncontrolled epilepsy. Annual overall ($23,238 vs. $13,839) and epilepsy-related ($12,399 vs. $5511) costs were higher in patients with uncontrolled epilepsy and remained higher after adjustment (p<.001). Patients with uncontrolled epilepsy use more services and incur higher costs compared with those with stable epilepsy. Epilepsy-related costs accounted for <50% of the total costs, suggesting that comorbid conditions and/or underidentification of utilization may substantially contribute to costs. © 2013.
Phase III Early Restoration Meeting - Lake Charles, LA | NOAA Gulf Spill
Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News early restoration planning for Phase III and future early restoration plans. Open House: 5:30pm Public
Tsai, Hung-Sheng; Tsai, Teh-Hua
2012-01-04
The extraction equilibrium of indium(III) from a nitric acid solution using di(2-ethylhexyl) phosphoric acid (D2EHPA) as an acidic extractant of organophosphorus compounds dissolved in kerosene was studied. By graphical and numerical analysis, the compositions of indium-D2EHPA complexes in organic phase and stoichiometry of the extraction reaction were examined. Nitric acid solutions with various indium concentrations at 25 °C were used to obtain the equilibrium constant of InR₃ in the organic phase. The experimental results showed that the extraction distribution ratios of indium(III) between the organic phase and the aqueous solution increased when either the pH value of the aqueous solution and/or the concentration of the organic phase extractant increased. Finally, the recovery efficiency of indium(III) in nitric acid was measured.
Hu, Xuewei; Yang, Lei; Lai, Xinke; Yao, Qi; Chen, Kai
2017-10-03
This paper presented the influence of Al(III) on biodegradability, micromorphology, composition and functional groups characteristics of the biofilm extracellular polymeric substances (EPS) during different growth phases. The sequencing batch biofilm reactors were developed to cultivate biofilms under different Al(III) dosages. The results elucidated that Al(III) affected biofilm development adversely at the beginning of biofilm growth, but promoted the biofilm mass and improved the biofilm activity with the growth of the biofilm. The micromorphological observation indicated that Al(III) led to a reduction of the filaments and promotion of the EPS secretion in growth phases of the biofilm, also Al(III) could promote microorganisms to form larger colonies for mature biofilm. Then, the analysis of EPS contents and components suggested that Al(III) could increase the protein (PN) of tightly bound EPS (TB-EPS) which alleviated the metal toxicity inhibition on the biofilm during the initial phases of biofilm growth. The biofilm could gradually adapt to the inhibition caused by Al(III) at the biofilm maturation moment. Finally, through the Fourier transform infrared spectroscopy, it was found that Al(III) was beneficial for the proliferation and secretion of TB-EPS functional groups, especially the functional groups of protein and polysaccharides.
46 CFR 32.63-5 - Barge hull classifications-B/ALL.
Code of Federal Regulations, 2014 CFR
2014-10-01
... the uncontrolled release of the cargo to the waterways and/or atmosphere. (2) Type II barge hull... measures to preclude uncontrolled release to the atmosphere, but whose uncontrolled release to the...
46 CFR 32.63-5 - Barge hull classifications-B/ALL.
Code of Federal Regulations, 2013 CFR
2013-10-01
... the uncontrolled release of the cargo to the waterways and/or atmosphere. (2) Type II barge hull... measures to preclude uncontrolled release to the atmosphere, but whose uncontrolled release to the...
Santos, L A; Oliveira, M A; Faresin, S M; Santoro, I L; Fernandes, A L G
2007-07-01
Asthma is a common chronic illness that imposes a heavy burden on all aspects of the patient's life, including personal and health care cost expenditures. To analyze the direct cost associated to uncontrolled asthma patients, a cross-sectional study was conducted to determine costs related to patients with uncontrolled and controlled asthma. Uncontrolled patient was defined by daytime symptoms more than twice a week or nocturnal symptoms during two consecutive nights or any limitations of activities, or need for relief rescue medication more than twice a week, and an ACQ score less than 2 points. A questionnaire about direct cost stratification in health services, including emergency room visits, hospitalization, ambulatory visits, and asthma medications prescribed, was applied. Ninety asthma patients were enrolled (45 uncontrolled/45 controlled). Uncontrolled asthmatics accounted for higher health care expenditures than controlled patients, US$125.45 and US$15.58, respectively [emergency room visits (US$39.15 vs US$2.70) and hospitalization (US$86.30 vs US$12.88)], per patient over 6 months. The costs with medications in the last month for patients with mild, moderate and severe asthma were US$1.60, 9.60, and 25.00 in the uncontrolled patients, respectively, and US$6.50, 19.00 and 49.00 in the controlled patients. In view of the small proportion of uncontrolled subjects receiving regular maintenance medication (22.2%) and their lack of resources, providing free medication for uncontrolled patients might be a cost-effective strategy for the public health system.
40 CFR 63.163 - Standards: Pumps in light liquid service.
Code of Federal Regulations, 2013 CFR
2013-07-01
... later than 1 year after the compliance date; and (C) Phase III, beginning no later than 21/2 years after... requirements; and (B) Beginning no later than 1 year after initial start-up, comply with the Phase III... parts per million or greater. (ii) For Phase II, an instrument reading of 5,000 parts per million or...
40 CFR 63.163 - Standards: Pumps in light liquid service.
Code of Federal Regulations, 2012 CFR
2012-07-01
... later than 1 year after the compliance date; and (C) Phase III, beginning no later than 21/2 years after... requirements; and (B) Beginning no later than 1 year after initial start-up, comply with the Phase III... parts per million or greater. (ii) For Phase II, an instrument reading of 5,000 parts per million or...
40 CFR 63.163 - Standards: Pumps in light liquid service.
Code of Federal Regulations, 2014 CFR
2014-07-01
... later than 1 year after the compliance date; and (C) Phase III, beginning no later than 21/2 years after... requirements; and (B) Beginning no later than 1 year after initial start-up, comply with the Phase III... parts per million or greater. (ii) For Phase II, an instrument reading of 5,000 parts per million or...
Okada, Kenji; Miyazaki, Chiaki; Kino, Yoichiro; Ozaki, Takao; Hirose, Mizuo; Ueda, Kohji
2013-07-15
Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. DTaP-sIPV was shown to be a safe and immunogenic vaccine. JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).
Małuszyńska, Hanna; Czarnecki, Piotr; Czarnecka, Anna; Pająk, Zdzisław
2012-04-01
Pyridinium chlorochromate, [C(5)H(5)NH](+)[ClCrO(3)](-) (hereafter referred to as PyClCrO(3)), was studied by X-ray diffraction, differential scanning calorimetry (DSC) and dielectric methods. Studies reveal three reversible phase transitions at 346, 316 and 170 K with the following phase sequence: R ̅3m (I) → R3m (II) → Cm (III) → Cc (IV), c' = 2c. PyClCrO(3) is the first pyridinium salt in which all four phases have been successfully characterized by a single-crystal X-ray diffraction method. Structural results together with dielectric and calorimetric studies allow the classification of the two intermediate phases (II) and (III) as ferroelectric with the Curie point at 346 K, and the lowest phase (IV) as most probably ferroelectric. The ferroelectric hysteresis loop was observed only in phase (III). The high ionic conductivity hindered its observation in phase (II).
Sun, Yuankui; Guan, Xiaohong; Wang, Jianmin; Meng, Xiaoguang; Xu, Chunhua; Zhou, Gongming
2014-06-17
In this study, a weak magnetic field (WMF), superimposed with a permanent magnet, was utilized to improve ZVI corrosion and thereby enhance As(V)/As(III) removal by ZVI at pHini 3.0-9.0. The experiment with real arsenic-bearing groundwater revealed that WMF could greatly improve arsenic removal by ZVI even in the presence of various cations and anions. The WMF-induced improvement in As(V)/As(III) removal by ZVI should be primarily associated with accelerated ZVI corrosion, as evidenced by the pH variation, Fe(2+) release, and the formation of corrosion products as characterized with X-ray absorption fine structure spectroscopy. The arsenic species analysis in solution/solid phases at pHini 3.0 revealed that As(III) oxidation to As(V) in aqueous phase preceded its subsequent sequestration by the newly formed iron (hydr)oxides. However, both As(V) adsorption following As(III) oxidation to As(V) in solution and As(III) adsorption preceding its conversion to As(V) in solid phase were observed at pHini 5.0-9.0. The application of WMF accelerated the transformation of As(III) to As(V) in both aqueous and solid phases at pHini 5.0-9.0 and enhanced the oxidation of As(III) to As(V) in solution at pHini 3.0.
ERIC Educational Resources Information Center
Wake Forest Univ., Winston Salem, NC. Bowman Gray School of Medicine.
This publication contains a curriculum developed through functional job analyses for a 24-month physician's assistant training program. Phase 1 of the 3-phase program is a 6-month basic course program in clinical and bioscience principles and is required of all students regardless of their specialty interest. Phase 2 is a 6 to 10 month period of…
Joint probability of statistical success of multiple phase III trials.
Zhang, Jianliang; Zhang, Jenny J
2013-01-01
In drug development, after completion of phase II proof-of-concept trials, the sponsor needs to make a go/no-go decision to start expensive phase III trials. The probability of statistical success (PoSS) of the phase III trials based on data from earlier studies is an important factor in that decision-making process. Instead of statistical power, the predictive power of a phase III trial, which takes into account the uncertainty in the estimation of treatment effect from earlier studies, has been proposed to evaluate the PoSS of a single trial. However, regulatory authorities generally require statistical significance in two (or more) trials for marketing licensure. We show that the predictive statistics of two future trials are statistically correlated through use of the common observed data from earlier studies. Thus, the joint predictive power should not be evaluated as a simplistic product of the predictive powers of the individual trials. We develop the relevant formulae for the appropriate evaluation of the joint predictive power and provide numerical examples. Our methodology is further extended to the more complex phase III development scenario comprising more than two (K > 2) trials, that is, the evaluation of the PoSS of at least k₀ (k₀≤ K) trials from a program of K total trials. Copyright © 2013 John Wiley & Sons, Ltd.
Chattanooga SmartBus Project : phase III evaluation report
DOT National Transportation Integrated Search
2009-12-01
This report presents the results of Phase III of the national evaluation of the Chattanooga Area Regional Transportation Authoritys (CARTA) SmartBus Project. The SmartBus Project is a comprehensive transit ITS program for the city of Chattanooga, ...
Phase III Early Restoration Meeting - Galveston, TX | NOAA Gulf Spill
Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm
Phase III Early Restoration Meeting - Port Arthur, TX | NOAA Gulf Spill
Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm
Phase III Early Restoration Meeting - Panama City, FL | NOAA Gulf Spill
Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm
Tao, Hua; Veetil, Suhas P; Pan, Xingchen; Liu, Cheng; Zhu, Jianqiang
2015-08-01
Air conditioning systems can lead to dynamic phase change in the laser beams of high-power laser facilities for the inertial confinement fusion, and this kind of phase change cannot be measured by most of the commonly employed Hartmann wavefront sensor or interferometry due to some uncontrollable factors, such as too large laser beam diameters and the limited space of the facility. It is demonstrated that this problem can be solved using a scheme based on modulation coherent imaging, and thus the influence of the air conditioning system on the performance of the high-power facility can be evaluated directly.
NASA Technical Reports Server (NTRS)
Andriopoulou, M.; Nakamura, R.; Torkar, K.; Baumjohann, W.; Torbert, R. B.; Lindqvist, P.-A.; Khotyaintsev, Y. V.; Dorelli, John Charles; Burch, J. L.; Russell, C. T.
2016-01-01
Each spacecraft of the recently launched magnetospheric multiscale MMS mission is equipped with Active Spacecraft Potential Control (ASPOC) Instruments, which control the spacecraft potential in order to reduce spacecraft charging effects. ASPOC typically reduces the spacecraft potential to a few volts. On several occasions during the commissioning phase of the mission, the ASPOC instruments were operating only on one spacecraft at a time. Taking advantage of such intervals, we derive photoelectron curves and also perform reconstructions of the uncontrolled spacecraft potential for the spacecraft with active control and estimate the electron plasma density during those periods. We also establish the criteria under which our methods can be applied.
North Carolina "Sealed Corridor" Phase I, II, and III Assessment
DOT National Transportation Integrated Search
2009-10-01
The Federal Railroad Administration (FRA) tasked the John A. Volpe National Transportation Systems Center to document the further success of the North Carolina DOT "Sealed Corridor" project through Phases I, II, and III. The Sealed Corridor is the se...
Phase III gross solids removal devices pilot study, 2002-2005.
DOT National Transportation Integrated Search
2005-12-01
The objective of the Phase III Gross Solids Removal Devices (GSRDs) Pilot study was to : evaluate the performance of non-proprietary devices that can capture gross solids and that can be : incorporated into existing highway drainage systems or implem...
Improvement of conspicuity of trailblazing signs, Phase III : evaluation of fluorescent colors.
DOT National Transportation Integrated Search
2001-01-01
This report represents a Phase III effort to design and evaluate a new sign design for incident route trailblazing. The colors evaluated were fluorescent coral, fluorescent purple, fluorescent yellow-green, and non-fluorescent purple. The results ind...
Clinical Investigation Program Report, RCS MED-300 (R-1).
1985-10-31
Patients with Locally Advanced Gastric Adenocarcinoma, Phase III. (C) 63 1982 SWOG 8006, Preoperative Reductive Chemotherapy for Stage III or IV Operable...Mesothelioma Localized to One Hemithorax, Phase III. (C) 81 1984 SWOG 8104, Treatment of Advanced Seminoma (Stage cII (4) + clII) with Combined...of Locally or Regionally Recurrent but Surgically Resectable Breast Cancer. (C) 99 1984 SWOG 8300, Treatment of Limited Non-Small Cell Lung Cancer
Tchou, Isabelle; Margeli, Alexandra; Tsironi, Maria; Skenderi, Katerina; Barnet, Marc; Kanaka-Gantenbein, Christina; Papassotiriou, Ioannis; Beris, Photis
2009-09-01
We investigated the actions of growth-differentiation factor (GDF)-15, endoglin and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in 15 male athletes who participated in the ultradistance foot race of the 246 km 'Sparthathlon'. Measurements were performed before (phase I), at the end of the race (phase II) and 48 h post-race (phase III). GDF-15 and endoglin serum concentrations were determined with enzyme-linked immunosorbent assay and NT-pro-BNP plasma levels by electrochemiluminescence. GDF-15 levels were increased from phase I (563.9 +/- 57.1 pg ml(-1)) to phase II (2311.1 +/- 462.3 pg ml(-1)) and decreased at phase III (862.0 +/- 158.0 pg ml(-1)) (p < 0.0002). NT-pro-BNP levels followed a similar pattern to that of GDF-15 from 38.1 +/- 4.8 pg ml(-1) at phase I to 1280.6 +/- 259.0 pg ml(-1) at phase II and 89.8 +/- 13.6 pg ml(-1) at phase III (p < 0.0001) and at the same time points, endoglin levels were 4.7 +/- 0.2 ng ml(-1) at phase I, 5.8 +/- 0.2 ng ml(-1) at phase II and 4.3 +/- 0.2 ng ml(-1) at phase III (p < 0.002). These findings indicate that circulating GDF-15, endoglin and NT-pro-BNP levels reflect a transient endothelial dysfunction in these athletes who participated in a foot race consisting of continuous, prolonged and brisk exercise.
Weis, Joachim; Arraras, Juan Ignacio; Conroy, Thierry; Efficace, Fabio; Fleissner, Claudia; Görög, Attila; Hammerlid, Eva; Holzner, Bernhard; Jones, Louise; Lanceley, Anne; Singer, Susanne; Wirtz, Markus; Flechtner, Henning; Bottomley, Andrew
2013-05-01
European Organisation for Research and Treatment of Cancer (EORTC) has developed a new multidimensional instrument measuring cancer-related fatigue that can be used in conjunction with the quality of life core questionnaire, EORTC QLQ-C30. The paper focuses on the development of the phase III module, collaborating with seven European countries, including a patient sample of 318 patients. The methodology followed the EORTC guidelines for developing phase III modules. Patients were assessed by questionnaires (EORTC QLQ-C30 with the EORTC Fatigue Module FA15) followed by an interview, asking for their opinions on the difficulty in understanding, on annoyance and on intrusiveness. The phase II FA15 was revised on the basis of qualitative analyses (comments of the patients), quantitative results (descriptive statistics) as well as the multi-item response theory analyses. The three dimensions (physical, emotional and cognitive) of the scale could be confirmed. As a result, EORTC QLQ-FA13 is now available as a valid phase III module measuring cancer-related fatigue in clinical trials and will be psychometrically improved in the upcoming phase IV. Copyright © 2012 John Wiley & Sons, Ltd.
Cao, Weidan; Qi, Xiaona; Cai, Deborah A; Han, Xuanye
2018-01-01
The purpose of the study was to build a model to explain the relationships between social support, uncontrollability appraisal, adaptive coping, and posttraumatic growth (PTG) among cancer patients in China. The participants who were cancer patients in a cancer hospital in China filled out a survey. The final sample size was 201. Structural equation modeling was used to build a model explaining PTG. Structural equation modeling results indicated that higher levels of social support predicted higher levels of adaptive coping, higher levels of uncontrollability appraisal predicted lower levels of adaptive coping, and higher levels of adaptive coping predicted higher levels of PTG. Moreover, adaptive coping was a mediator between social support and growth, as well as a mediator between uncontrollability and growth. The direct effects of social support and uncontrollability on PTG were insignificant. The model demonstrated the relationships between social support, uncontrollability appraisal, adaptive coping, and PTG. It could be concluded that uncontrollability appraisal was a required but not sufficient condition for PTG. Neither social support nor uncontrollability appraisal had direct influence on PTG. However, social support and uncontrollability might indirectly influence PTG, through adaptive coping. It implies that both internal factors (eg, cognitive appraisal and coping) and external factors (eg, social support) are required in order for growth to happen. Copyright © 2017 John Wiley & Sons, Ltd.
Code of Federal Regulations, 2013 CFR
2013-07-01
... detection for the HPLC analyzer. Sampling systems for all phases shall be identical. (iii) The methanol and... detection for the HPLC analyzer. Sampling systems for all phases shall be identical. (iii) The methanol and...
Code of Federal Regulations, 2012 CFR
2012-07-01
... detection for the HPLC analyzer. Sampling systems for all phases shall be identical. (iii) The methanol and... detection for the HPLC analyzer. Sampling systems for all phases shall be identical. (iii) The methanol and...
Code of Federal Regulations, 2014 CFR
2014-07-01
... detection for the HPLC analyzer. Sampling systems for all phases shall be identical. (iii) The methanol and... detection for the HPLC analyzer. Sampling systems for all phases shall be identical. (iii) The methanol and...
Haron, Md Jelas; Jahangirian, Hossein; Silong, Sidik; Yusof, Nor Azah; Kassim, Anuar; Rafiee-Moghaddam, Roshanak; Mahdavi, Behnam; Peyda, Mazyar; Abdollahi, Yadollah; Amin, Jamileh
2012-01-01
Liquid-liquid iron(III) extraction was investigated using benzyl fatty hydroxamic acids (BFHAs) and methyl fatty hydroxamic acids (MFHAs) as chelating agents through the formation of iron(III) methyl fatty hydroxamate (Fe-MFHs) or iron(III) benzyl fatty hydroxamate (Fe-BFHs) in the organic phase. The results obtained under optimized conditions, showed that the chelating agents in hexane extract iron(III) at pH 1.9 were realized effectively with a high percentage of extraction (97.2% and 98.1% for MFHAs and BFHAs, respectively). The presence of a large amount of Mg(II), Ni(II), Al(III), Mn(II) and Co(II) ions did affect the iron(III) extraction. Finally stripping studies for recovering iron(III) from organic phase (Fe-MFHs or Fe-BFHs dissolved in hexane) were carried out at various concentrations of HCl, HNO3 and H2SO4. The results showed that the desired acid for recovery of iron(III) was 5 M HCl and quantitative recovery of iron(III) was achieved from Fe(III)-MFHs and Fe(III)-BFHs solutions in hexane containing 5 mg/L of Fe(III). PMID:22408444
Secukinumab in the Treatment of Psoriasis and Psoriatic Arthritis: A Review of the Literature.
Abrouk, M; Gandy, J; Nakamura, M; Lee, K; Brodsky, M; Singh, R; Zhu, H; Farahnik, B; Bhutani, T; Koo, J
2017-07-01
While there are several commercially available treatment options for psoriasis and psoriatic arthritis, there remains a large number of individuals who are refractory to current modalities. In the recent past, there has been increasing evidence that interleukin (IL)-17 plays a vital role in the pathophysiology of psoriasis. Preclinical, phase II, and phase III studies of secukinumab (Cosentyx®) targeting IL-17 and its receptor have thus far proved to be promising. We reviewed the results of phase II and phase III clinical trials for secukinumab in the treatment of psoriasis and psoriatic arthritis. Only published studies were considered in the present review. We also performed an English language literature search from January 2003 to September 2015 using PubMed with any of the following key words: (secukinumab OR AIN457) AND (psoriasis OR psoriatic arthritis). In our review of the literature, seven phase III and five phase II clinical trials, as well as open-label extension studies with unpublished findings were found. Results from phase III clinical trials indicated secukinumab to be efficacious and safe for the treatment of psoriasis and psoriatic arthritis according to Psoriasis Area and Severity Index (PASI) and American College of Rheumatology (ACR) scores. The safety profile of this agent was similar across all studies, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction. Secukinumab demonstrates rapid and robust clinical improvement accompanied by a favorable short- term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis and psoriatic arthritis treatment. Additional extension studies of lower level evidence are needed to further understand the safety profile of the drug.
Remedial Action Report for Operable Units 6-05 and 10-04, Phase III
DOE Office of Scientific and Technical Information (OSTI.GOV)
R. P. Wells
2007-08-15
This Phase III remedial action report addresses the remediation of lead-contaminated soils found at the Security Training Facility STF-02 Gun Range at the Idaho National Laboratory Site. Phase I, consisting of developing and implementing institutional controls at Operble Unit 10-04 sites and developing and implementing Idaho National Laboratory Site-wide plans for both institutional controls and ecological monitoring, was addressed in a previous report. Phase II will remediate sites contaminated with trinitrotoluene and Royal Demolition Explosive. Phase IV will remediate hazards from unexploded ordnance.
1979-05-01
Condition of protective coating ; _. inside and out Corrosion ; Damaged parts_; Loose___ Other . .- Concrete : Cracking_/ I Spallingo_; Other...spillways have uncontrolled inlets. The principal - spillway consists of a drop inlet concrete riser which discharges to a 48-inch diameter reinforced... concrete conduit which passes through the dam (see Photos 3 and 5). The concrete conduit discharges to a plunge pool at the pipe outlet. (See Photos 8 and 9
[Griscelli syndrome in a Mexican girl].
Ayala de la Cruz, María del Carmen; Ramírez Campos, Jorge; Govea Sifuentes, Jesús; González Cabello, Diana; Calderón Garcidueñas, Ana Laura; Moreno, Laura; Vargas Almanza, Griselda Nelly
2002-01-01
Griscelli syndrome is an infrequent disease first described in 1978. It is inherited in autosomal recessive form, and is distinguished by partial albinism, pigmentation dilution, cellular immunodeficiency, neurological involvement and uncontrolled phases of macrophage and lymphocyte activation. We report the case of a female child who started with ataxic gait when she was 23 months old. At physical examination a phenotype with brown skin and silvery gray hair, eyebrows and eyelashes was observed. Neurological evolution was with remissions and exacerbations, with cerebellar and, finally, bulbar compromise.
The NCI Division of Cancer Prevention’s Phase 0/I/II Cancer Prevention Clinical Trials Program, also known as the Consortia for Early Phase Prevention Trials, is beginning a new round of studies in the effort toward systematic early clinical development of promising preventive agents for people at increased risk of developing cancer. |
ERIC Educational Resources Information Center
Roberts, Sharon Pol; Heroman, Deborah S.
A 5-year study examined third-graders' perceptions of school climate in 16 Louisiana schools. Part of the Louisiana School Effectiveness Study (LSES), Phase III and IV examined student perceptions in 1984-85 and 1989-90, respectively, and also gathered demographic data and multiple measures of student outcomes through student surveys and classroom…
76 FR 16240 - Mandatory Reliability Standards for Interconnection Reliability Operating Limits
Federal Register 2010, 2011, 2012, 2013, 2014
2011-03-23
... Standards. The Reliability Standards were designed to prevent instability, uncontrolled separation, or... designed to prevent instability, uncontrolled separation, or cascading outages that adversely impact the... instability, uncontrolled separation, or cascading outages. See NERC Glossary, available at http://www.nerc...
Robertson, David S; Prevost, A Toby; Bowden, Jack
2016-09-30
Seamless phase II/III clinical trials offer an efficient way to select an experimental treatment and perform confirmatory analysis within a single trial. However, combining the data from both stages in the final analysis can induce bias into the estimates of treatment effects. Methods for bias adjustment developed thus far have made restrictive assumptions about the design and selection rules followed. In order to address these shortcomings, we apply recent methodological advances to derive the uniformly minimum variance conditionally unbiased estimator for two-stage seamless phase II/III trials. Our framework allows for the precision of the treatment arm estimates to take arbitrary values, can be utilised for all treatments that are taken forward to phase III and is applicable when the decision to select or drop treatment arms is driven by a multiplicity-adjusted hypothesis testing procedure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
Practice versus knowledge when it comes to pressure ulcer prevention.
Provo, B; Piacentine, L; Dean-Baar, S
1997-09-01
This study was completed to determine the current knowledge and documentation patterns of nursing staff in the prevention of pressure ulcers and to identify the prevalence of pressure ulcers. This pre-post intervention study was carried out in three phases. In phase 1, 67 nursing staff members completed a modified version of Bostrom's Patient Skin Integrity Survey. A Braden Scale score, the presence of actual skin breakdown, and the presence of nursing documentation were collected for each patient (n = 43). Phase II consisted of a 20-minute educational session to all staff. In phase III, 51 nursing staff completed a second questionnaire similar to that completed in phase I. Patient data (n = 49) were again collected using the same procedure as phase I. Twenty-seven staff members completed questionnaires in both phase I and phase III of the study. No statistically significant differences were found in the knowledge of the staff before or after the educational session. The number of patients with a documented plan of care showed a statistically significant difference from phase I to phase III. The number of patients with pressure ulcers or at risk for pressure ulcer development (determined by a Braden Scale score of 16 or less) did not differ statistically from phase I to phase III. Knowledge about pressure ulcers in this sample of staff nurses was for the most part current and consistent with the recommendations in the Agency for Health Care Policy and Research guideline. Documentation of pressure ulcer prevention and treatment improved after the educational session. Although a significant change was noted in documentation, it is unclear whether it reflected an actual change in practice.
DOT National Transportation Integrated Search
2009-12-15
This report documents Phase III of the development and operation of a prototype for the Statewide Transportation : Engineering Warehouse for Archived Regional Data (STEWARD). It reflects the progress on the development and : operation of STEWARD sinc...
Application of Δ- and λ-isomerism of octahedral metal complexes for inducing chiral nematic phases.
Sato, Hisako; Yamagishi, Akihiko
2009-11-20
The Delta- and Lambda-isomerism of octahedral metal complexes is employed as a source of chirality for inducing chiral nematic phases. By applying a wide range of chiral metal complexes as a dopant, it has been found that tris(beta-diketonato)metal(III) complexes exhibit an extremely high value of helical twisting power. The mechanism of induction of the chiral nematic phase is postulated on the basis of a surface chirality model. The strategy for designing an efficient dopant is described, together with the results using a number of examples of Co(III), Cr(III) and Ru(III) complexes with C(2) symmetry. The development of photo-responsive dopants to achieve the photo-induced structural change of liquid crystal by use of photo-isomerization of chiral metal complexes is also described.
Application of Δ- and Λ-Isomerism of Octahedral Metal Complexes for Inducing Chiral Nematic Phases
Sato, Hisako; Yamagishi, Akihiko
2009-01-01
The Δ- and Λ-isomerism of octahedral metal complexes is employed as a source of chirality for inducing chiral nematic phases. By applying a wide range of chiral metal complexes as a dopant, it has been found that tris(β-diketonato)metal(III) complexes exhibit an extremely high value of helical twisting power. The mechanism of induction of the chiral nematic phase is postulated on the basis of a surface chirality model. The strategy for designing an efficient dopant is described, together with the results using a number of examples of Co(III), Cr(III) and Ru(III) complexes with C2 symmetry. The development of photo-responsive dopants to achieve the photo-induced structural change of liquid crystal by use of photo-isomerization of chiral metal complexes is also described. PMID:20057959
Jia, Xiaoyu; Gong, Dirong; Zhao, Junyi; Ren, Hongyun; Wang, Jiani; Zhang, Xian
2018-03-19
This paper describes the preparation of zwitterion-functionalized polymer microspheres (ZPMs) and their application to simultaneous enrichment of V(V), Cr(III), As(III), Sn(IV), Sb(III) and Hg(II) from environmental water samples. The ZPMs were prepared by emulsion copolymerization of ethyl methacrylate, 2-diethylaminoethyl methacrylate and triethylene glycol dimethyl acrylate followed by modification with 1,3-propanesultone. The components were analyzed by elemental analyses as well as Fourier transform infrared spectroscopy, and the structures were characterized by scanning electron microscopy and transmission electron microscopy. The ZPMs were packed into a mini-column for on-line solid-phase extraction (SPE) of the above metal ions. Following extraction with 40 mM NH 4 NO 3 and 0.5 M HNO 3 solution, the ions were quantified by ICP-MS. Under the optimized conditions, the enrichment factors (from a 40 mL sample) are up to 60 for the ions V(V), As(III), Sb(III) and Hg(II), and 55 for Cr(III) and Sn(IV). The detection limits are 1.2, 3.4, 1.0, 3.7, 2.1 and 1.6 ng L -1 for V(V), Cr(III), As(III), Sn(IV), Sb(III) and Hg(II), respectively, and the relative standard deviations (RSDs) are below 5.2%. The feasibility and accuracy of the method were validated by successfully analyzing six certified reference materials as well as lake, well and river waters. Graphical abstract Zwitterion-functionalized polymer microspheres (ZPMs) were prepared and packed into a mini-column for on-line solid-phase extraction (SPE) via pump 1. Then V(V), Cr(III), As(III), Sn(IV), Sb(III) and Hg(II) ions in environmental waters were eluted and submitted to ICP-MS via pump 2.
Sperling, Michael R; Harvey, Jay; Grinnell, Todd; Cheng, Hailong; Blum, David
2015-04-01
To assess the efficacy and safety of eslicarbazepine acetate (ESL) as monotherapy in North American patients with partial-onset seizures (POS). This multicenter, randomized, double-blind "withdrawal to monotherapy" study used historical control data as the comparator. Adults with POS medically uncontrolled by one to two antiepileptic drugs gradually converted to ESL monotherapy. Following an 8-week baseline period, patients were randomized 2:1 to receive ESL 1,600 mg (n = 128) or 1,200 mg QD (n = 65) for 18 weeks. The primary end point was the proportion of patients meeting predefined exit criteria (signifying worsening seizure control). Treatment was considered effective if the 95% upper confidence limit (UCL) for the Kaplan-Meier estimated exit rate was lower than the exit rate threshold calculated from the historical control (65.3%). Kaplan-Meier estimated exit rates were: ESL 1,600 mg, 28.7% (95% CI 21.2-38.1%) and 1,200 mg, 44.4% (32.5-58.3%). The difference between doses was not significant (p = 0.07). For both doses, the 95% UCLs for the exit rate were ˂ 65.3%; ESL monotherapy was considered superior to the historical control. There was no statistically significant increase in the risk of study exit related to carbamazepine use. Nine (7.6%) and five patients (8.3%) remained seizure-free during the 10-week monotherapy period, while taking ESL 1,600 and 1,200 mg, respectively. The reductions in median standardized seizure frequency (seizures per 28 days) between baseline and the 18-week treatment period were: ESL 1,600 mg, 42% and 1,200 mg, 31%. Treatment-emergent adverse events (TEAEs) occurring in ≥ 10% of patients were dizziness, headache, fatigue, somnolence, nausea, and nasopharyngitis. The TEAE most frequently leading to discontinuation was hyponatremia (2.1%). ESL was efficacious and well tolerated as monotherapy in North American patients, and led to a reduction in seizure frequency. Exit rates for ESL 1,600 and 1,200 mg QD were superior to the historical control; the difference in exit rates between doses was not statistically significant. © 2015 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.
Letoublon, Christian; Morra, Irene; Chen, Yao; Monnin, Valerie; Voirin, David; Arvieux, Catherine
2011-05-01
The objective was to clarify the role of hepatic arterial embolization (AE) in the management of blunt hepatic trauma. Retrospective observational study of 183 patients with blunt hepatic trauma admitted to a trauma referral center over a 9-year period. The charts of 29 patients (16%) who underwent hepatic angiography were reviewed for demographics, injury specific data, management strategy, angiographic indication, efficacy and complications of embolization, and outcome. AE was performed in 23 (79%) of the patients requiring angiography. Thirteen patients managed conservatively underwent emergency embolization after preliminary computed tomography scan. Six had postoperative embolization after damage control laparotomy and four had delayed embolization. Arterial bleeding was controlled in all the cases. Sixteen patients (70%) had one or more liver-related complications; temporary biliary leak (n=11), intra-abdominal hypertension (n=14), inflammatory peritonitis (n=3), hepatic necrosis (n=3), gallbladder infarction (n=2), and compressive subcapsular hematoma (n=1). Unrecognized hepatic necrosis could have contributed to the late posttraumatic death of one patient. AE is a key element in modern management of high-grade liver injuries. Two principal indications exist in the acute postinjury phase: primary hemostatic control in hemodynamically stable or stabilized patients with radiologic computed tomography evidence of active arterial bleeding and adjunctive hemostatic control in patients with uncontrolled suspected arterial bleeding despite emergency laparotomy. Successful management of injuries of grade III upward often entails a combined angiographic and surgical approach. Awareness of the ischemic complications due to angioembolization is important.
De Luca, Chiara; Raskovic, Desanka; Pacifico, Valeria; Thai, Jeffrey Chung Sheun; Korkina, Liudmila
2011-01-01
Whilst facing a worldwide fast increase of food and environmental allergies, the medical community is also confronted with another inhomogeneous group of environment-associated disabling conditions, including multiple chemical sensitivity (MCS), fibromyalgia, chronic fatigue syndrome, electric hypersensitivity, amalgam disease and others. These share the features of poly-symptomatic multi-organ cutaneous and systemic manifestations, with postulated inherited/acquired impaired metabolism of chemical/physical/nutritional xenobiotics, triggering adverse reactions at exposure levels far below toxicologically-relevant values, often in the absence of clear-cut allergologic and/or immunologic involvement. Due to the lack of proven pathogenic mechanisms generating measurable disease biomarkers, these environmental hypersensitivities are generally ignored by sanitary and social systems, as psychogenic or “medically unexplained symptoms”. The uncontrolled application of diagnostic and treatment protocols not corresponding to acceptable levels of validation, safety, and clinical efficacy, to a steadily increasing number of patients demanding assistance, occurs in many countries in the absence of evidence-based guidelines. Here we revise available information supporting the organic nature of these clinical conditions. Following intense research on gene polymorphisms of phase I/II detoxification enzyme genes, so far statistically inconclusive, epigenetic and metabolic factors are under investigation, in particular free radical/antioxidant homeostasis disturbances. The finding of relevant alterations of catalase, glutathione-transferase and peroxidase detoxifying activities significantly correlating with clinical manifestations of MCS, has recently registered some progress towards the identification of reliable biomarkers of disease onset, progression, and treatment outcomes. PMID:21845158
Phase I/II adaptive design for drug combination oncology trials
Wages, Nolan A.; Conaway, Mark R.
2014-01-01
Existing statistical methodology on dose finding for combination chemotherapies has focused on toxicity considerations alone in finding a maximum tolerated dose combination to recommend for further testing of efficacy in a phase II setting. Recently, there has been increasing interest in integrating phase I and phase II trials in order to facilitate drug development. In this article, we propose a new adaptive phase I/II method for dual-agent combinations that takes into account both toxicity and efficacy after each cohort inclusion. The primary objective, both within and at the conclusion of the trial, becomes finding a single dose combination with an acceptable level of toxicity that maximizes efficacious response. We assume that there exist monotone dose–toxicity and dose–efficacy relationships among doses of one agent when the dose of other agent is fixed. We perform extensive simulation studies that demonstrate the operating characteristics of our proposed approach, and we compare simulated results to existing methodology in phase I/II design for combinations of agents. PMID:24470329
Hexafluorobenzene under Extreme Conditions.
Pravica, Michael; Sneed, Daniel; Wang, Yonggang; Smith, Quinlan; White, Melanie
2016-03-17
We report the results from three high pressure experiments on hexafluorobenzene (C6F6). In the first experiment, Raman spectra were recorded up to 34.4 GPa. A phase transition from I → II was observed near 2 GPa. Near 8.8 GPa, a phase transition to an unreported phase (III) commenced. Above 20.6 GPa, yet another phase was observed (IV). Pressure cycling was employed to determine that, below 25.6 GPa, all pressure-induced alterations were reversible. However, at pressures above 20 GPa, dramatic spectral changes and broadening were observed at 25.6 and 34.4 GPa. The sample irreversibly changed into a soft solid with waxlike consistency when pressure was reduced to ambient and was recoverable. In the second experiment, IR spectra were collected up to 14.6 GPa. The phase transition (II → III) near 8.8 GPa was confirmed. An angular dispersive X-ray diffraction experiment was conducted to 25.6 GPa. Phase transitions above 1.4 GPa (I → II), above 5.5 GPa (II → III), above 10 GPa (III → IV), and above 15.5 GPa (IV → V) were observed. Near 25.6 GPa, long-range crystalline order was lost as the X-ray diffraction spectrum presented evidence of an amorphous solid.
Bystricka, Judita; Musilova, Janette; Tomas, Jan; Vollmannova, Alena; Lachman, Jaromir; Kavalcova, Petra
2014-01-01
In this study the changes of total polyphenolics in different anatomical parts (stems, leaves, flowers and seeds) of common buckwheat (Fagopyrum esculentum Moench.) during vegetation period were analysed. The content of total polyphenolics was evaluated in growth phase I (formation of buds), phase II (at the beginning of flowering), phase III (full blossoming) and phase IV (full ripeness). In all growth phases (GP) the stems and leaves were evaluated and statistically significant differences in polyphenolics content between the two parts were confirmed. Statistically significant differences (p < 0.01) in polyphenolics content (in GP II and III) between stems and leaves; and between stems and flowers were found. In flowers an average of 13.8 times higher and in leaves 6 times higher concentration of polyphenolics in comparison with stems was measured. In GP III the content of polyphenolics in common buckwheat was following: flowers > leaves > achene > stems. In flowers an average of 11.9 times higher, in leaves 8.3 times higher and in achenes 5.9 times higher contents of polyphenolics compared with stems were found. In GP III and IV (leaves, achenes, stems) the leaves contained in average 20 times higher and achenes 5.6 times higher polyphenolics than stems. PMID:28234337
Van Bambeke, Françoise
2014-11-01
Lipoglycopeptide, ketolide, and quinolone antibiotics are currently in clinical development, with specific advantages over available molecules within their respective classes. The lipoglycopeptide oritavancin is bactericidal against MRSA, vancomycin-resistant enterococci, and multiresistant Streptococcus pneumoniae, and proved effective and safe for the treatment of acute bacterial skin and skin structure infection (ABSSSI) upon administration of a single 1200 mg dose (two completed phase III trials). The ketolide solithromycin (two phase III studies recruiting for community-acquired pneumonia) shows a profile of activity similar to that of telithromycin, but in vitro data suggest a lower risk of hepatotoxicity, visual disturbance, and aggravation of myasthenia gravis due to reduced affinity for nicotinic receptors. Among quinolones, finafloxacin and delafloxacin share the unique property of an improved activity in acidic environments (found in many infection sites). Finafloxacin (phase II completed; activity profile similar to that of ciprofloxacin) is evaluated for complicated urinary tract and Helicobacter pylori infections. The other quinolones (directed towards Gram-positive pathogens) show improved activity on MRSA and multiresistant S. pneumoniae compared to current molecules. They are in clinical evaluation for ABSSSI (avarofloxacin (phase II completed), nemonoxacin and delafloxacin (ongoing phase III)), respiratory tract infections (zabofloxacin and nemonoxacin (ongoing phase III)), or gonorrhea (delafloxacin).
A mobile phone based alarm system for supervising vital parameters in free moving rats.
Kellermann, Kristine; Kreuzer, Matthias; Omerovich, Adem; Hoetzinger, Franziska; Kochs, Eberhard F; Jungwirth, Bettina
2012-02-23
Study protocols involving experimental animals often require the monitoring of different parameters not only in anesthetized, but also in free moving animals. Most animal research involves small rodents, in which continuously monitoring parameters such as temperature and heart rate is very stressful for the awake animals or simply not possible. Aim of the underlying study was to monitor heart rate, temperature and activity and to assess inflammation in the heart, lungs, liver and kidney in the early postoperative phase after experimental cardiopulmonary bypass involving 45 min of deep hypothermic circulatory arrest in rats. Besides continuous monitoring of heart rate, temperature and behavioural activity, the main focus was on avoiding uncontrolled death of an animal in the early postoperative phase in order to harvest relevant organs before autolysis would render them unsuitable for the assessment of inflammation. We therefore set up a telemetry-based system (Data Science International, DSI™) that continuously monitored the rat's temperature, heart rate and activity in their cages. The data collection using telemetry was combined with an analysis software (Microsoft excel™), a webmail application (GMX) and a text message-service. Whenever an animal's heart rate dropped below the pre-defined threshold of 150 beats per minute (bpm), a notification in the form of a text message was automatically sent to the experimenter's mobile phone. With a positive predictive value of 93.1% and a negative predictive value of 90.5%, the designed surveillance and alarm system proved a reliable and inexpensive tool to avoid uncontrolled death in order to minimize suffering and harvest relevant organs before autolysis would set in. This combination of a telemetry-based system and software tools provided us with a reliable notification system of imminent death. The system's high positive predictive value helped to avoid uncontrolled death and facilitated timely organ harvesting. Additionally we were able to markedly reduce the drop out rate of experimental animals, and therefore the total number of animals used in our study. This system can be easily adapted to different study designs and prove a helpful tool to relieve stress and more importantly help to reduce animal numbers.
Wang, F; Leung, A O W; Wu, S C; Yang, M S; Wong, M H
2009-07-01
A multi-trophic, multi-exposure phase assessment approach was applied to characterize the toxicity of sediments collected from two rivers in Guiyu, China, an e-waste recycling centre. Elutriate toxicity tests (bacterium Vibrio fischeri and microalga Selenastrum capricornutum) and whole sediment toxicity test (crustacean Heterocypris incongruens) showed that most sediments exhibited acute toxicity, due to elevated heavy metals and PAHs levels, and low pH caused by uncontrolled acid discharge. The survival rates of crustaceans were negatively (p < 0.05) correlated with total PAHs in sediments (411-1755 mg kg(-1)); EC50s of V. fischeri on the elutriates were significantly correlated with elutriate pH (p < 0.01). Significant (p < 0.05) correlations between the induction of hepatic metallothionein in tilapia (Oreochromis mossambicus) and metal concentrations (Cu, Zn, Pb) in sediments were also observed, when fish were fed with diets containing sediment. The results showed that uncontrolled e-waste recycling activities may bring adverse effects to local aquatic ecosystem.
75 FR 14575 - Voting Equipment Evaluations Phase III
Federal Register 2010, 2011, 2012, 2013, 2014
2010-03-26
..., Human Performance-Based Standards and Usability Testing. NIST Phase III research is designed to: (1... vendor equipment will not be released. Comparative information may be released in a blind manner... electronic poll book systems as well as software used for ballot design and creation. Dated: March 23, 2010...
78 FR 18325 - Defense Transportation Regulation, Part IV
Federal Register 2010, 2011, 2012, 2013, 2014
2013-03-26
... received in connection with the Defense Personal Property Program (DP3) Phase III Direct Procurement Method... at http://www.transcom.mil/dtr/part-iv/phaseiii.cfm (DPM SECTION). All identified changes will be... Defense Personal Property System (DPS) Phase III programming projected for FY17. FOR FURTHER INFORMATION...
76 FR 36095 - Defense Transportation Regulation, Part IV
Federal Register 2010, 2011, 2012, 2013, 2014
2011-06-21
... with the Defense Personal Property Program (DP3) Phase III Domestic Small Shipments (dS2) and... Regulation, Part IV Web site at http://www.transcom.mil/dtr/part-iv/phaseiii.cfm . All identified changes... based on completion of Defense Personal Property System (DPS) Phase III programming projected for FY15...
DOE Office of Scientific and Technical Information (OSTI.GOV)
O'Neil, Lori Ross; Conway, T. J.; Tobey, D. H.
The Secure Power Systems Professional Phase III final report was released last year which an appendix of Job Profiles. This new report is that appendix broken out as a standalone document to assist utilities in recruiting and developing Secure Power Systems Professionals at their site.
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2011-08-29
...: Passport Demand Forecasting Study Phase III, OMB Number 1405-0177 ACTION: Notice of request for public... approval in accordance with the Paperwork Reduction Act of 1995. Title of Information Collection: Passport... Passport Services CA/PPT. Form Number: SV2011-0010. [[Page 53705
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78 FR 68345 - Airworthiness Directives; The Boeing Company Airplanes
Federal Register 2010, 2011, 2012, 2013, 2014
2013-11-14
... of the outboard actuator load path, could result in uncontrolled retraction of the outboard flap... outboard actuator load path, if not corrected, could result in uncontrolled retraction of the outboard flap..., combined with loss of the outboard actuator load path, could result in uncontrolled retraction of the...
Yoneyama, Koichiro; Schmitt, Christophe; Kotani, Naoki; Levy, Gallia G; Kasai, Ryu; Iida, Satofumi; Shima, Midori; Kawanishi, Takehiko
2017-12-06
Emicizumab (ACE910) is a bispecific antibody mimicking the cofactor function of activated coagulation factor VIII. In phase I-I/II studies, emicizumab reduced the bleeding frequency in patients with severe hemophilia A, regardless of the presence of factor VIII inhibitors, at once-weekly subcutaneous doses of 0.3, 1, and 3 mg/kg. Using the phase I-I/II study data, population pharmacokinetic and repeated time-to-event (RTTE) modeling were performed to quantitatively characterize the relationship between the pharmacokinetics of emicizumab and reduction in bleeding frequency. Simulations were then performed to identify the minimal exposure expected to achieve zero bleeding events for 1 year in at least 50% of patients and to select the dosing regimens to be tested in phase III studies. The RTTE model adequately predicted the bleeding onset over time as a function of plasma emicizumab concentration. Simulations suggested that plasma emicizumab concentrations of ≥ 45 μg/mL should result in zero bleeding events for 1 year in at least 50% of patients. This efficacious exposure provided the basis for selecting previously untested dosing regimens of 1.5 mg/kg once weekly, 3 mg/kg every 2 weeks, and 6 mg/kg every 4 weeks for phase III studies. A pharmacometric approach guided the phase III dose selection of emicizumab in hemophilia A, without conducting a conventional dose-finding study. Phase III studies with the selected dosing regimens are currently ongoing. This case study indicates that a pharmacometric approach can substitute for a conventional dose-finding study in rare diseases and will streamline the drug development process.
Toscani, Siro; Céolin, René; Minassian, Léon Ter; Barrio, Maria; Veglio, Nestor; Tamarit, Josep-Lluis; Louër, Daniel; Rietveld, Ivo B
2016-01-30
The trimorphism of the active pharmaceutical ingredient piracetam is a famous case of polymorphism that has been frequently revisited by many researchers. The phase relationships between forms I, II, and III were ambiguous because they seemed to depend on the heating rate of the DSC and on the history of the samples or they have not been observed at all (equilibrium II-III). In the present paper, piezo-thermal analysis and high-pressure differential thermal analysis have been used to elucidate the positions of the different solid-solid and solid-liquid equilibria. The phase diagram, involving the three solid phases, the liquid phase and the vapor phase, has been constructed. It has been shown that form III is the high-pressure, low-temperature form and the stable form at room temperature. Form II is stable under intermediary conditions and form I is the low pressure, high temperature form, which possesses a stable melting point. The present paper demonstrates the strength of the topological approach based on the Clapeyron equation and the alternation rule when combined with high-pressure measurements. Copyright © 2015 Elsevier B.V. All rights reserved.
NASA Technical Reports Server (NTRS)
Criswell, C. William
1987-01-01
The eruption of Mount St. Helens on May 18, 1980 can be subdivided into six phases: the paroxysmal phase I, the early Plinian phase II, the early ash flow phase III, the climactic phase IV, the late ash flow phase V, and phase VI, the activity of which consisted of a low-energy ash plume. These phases are correlated with stratigraphic subunits of ash-fall tephra and pyroclastic flow deposits. Sustained vertical discharge of phase II produced evolved dacite with high S/Cl ratios. Ash flow activity of phase III is attributed to decreases in gas content, indicated by reduced S/Cl ratios and increased clast density of the less evolved gray pumice. Climactic events are attributed to vent clearing and exhaustion of the evolved dacite.
Design of Phase II Non-inferiority Trials.
Jung, Sin-Ho
2017-09-01
With the development of inexpensive treatment regimens and less invasive surgical procedures, we are confronted with non-inferiority study objectives. A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial. Furthermore, due to lack of phase II non-inferiority trial design methods, we do not have an opportunity to investigate the efficacy of the experimental therapy through a phase II trial. As a result, we often fail to open a non-inferiority phase III trial and a large number of non-inferiority clinical questions still remain unanswered. In this paper, we want to develop some designs for non-inferiority randomized phase II trials with feasible sample sizes. At first, we review a design method for non-inferiority phase III trials. Subsequently, we propose three different designs for non-inferiority phase II trials that can be used under different settings. Each method is demonstrated with examples. Each of the proposed design methods is shown to require a reasonable sample size for non-inferiority phase II trials. The three different non-inferiority phase II trial designs are used under different settings, but require similar sample sizes that are typical for phase II trials.
Li, Weiying; Wang, Feng; Zhang, Junpeng; Qiao, Yu; Xu, Chen; Liu, Yao; Qian, Lin; Li, Wenming; Dong, Bingzhi
2016-02-15
The bacterial community of biofilms in drinking water distribution systems (DWDS) with various water sources has been rarely reported. In this research, biofilms were sampled at three points (A, B, and C) during the river water source phase (phase I), the interim period (phase II) and the reservoir water source phase (phase III), and the biofilm community was determined using the 454-pyrosequencing method. Results showed that microbial diversity declined in phase II but increased in phase III. The primary phylum was Proteobacteria during three phases, while the dominant class at points A and B was Betaproteobacteria (>49%) during all phases, but that changed to Holophagae in phase II (62.7%) and Actinobacteria in phase III (35.6%) for point C, which was closely related to its water quality. More remarkable community shift was found at the genus level. In addition, analysis results showed that water quality could significantly affect microbial diversity together, while the nutrient composition (e.g. C/N ration) of the water environment might determine the microbial community. Furthermore, Mycobacterium spp. and Pseudomonas spp. were detected in the biofilm, which should give rise to attention. This study revealed that water source switching produced substantial impact on the biofilm community. Copyright © 2015 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Nonoda, Ryohei; Shojiki, Kanako; Tanikawa, Tomoyuki; Kuboya, Shigeyuki; Katayama, Ryuji; Matsuoka, Takashi
2016-05-01
The effects of growth conditions such as Mg/Ga and V/III ratios on the properties of N-polar (000\\bar{1}) p-type GaN grown by metalorganic vapor phase epitaxy were studied. Photoluminescence spectra from Mg-doped GaN depended on Mg/Ga and V/III ratios. For the lightly doped samples, the band-to-acceptor emission was observed at 3.3 eV and its relative intensity decreased with increasing V/III ratio. For the heavily doped samples, the donor-acceptor pair emission was observed at 2.8 eV and its peak intensity monotonically decreased with V/III ratio. The hole concentration was maximum for the Mg/Ga ratio. This is the same tendency as in group-III polar (0001) growth. The V/III ratio also reduced the hole concentration. The higher V/III ratio reduced the concentration of residual donors such as oxygen by substituting nitrogen atoms. The surface became rougher with increasing V/III ratio and the hillock density increased.
Probability of success for phase III after exploratory biomarker analysis in phase II.
Götte, Heiko; Kirchner, Marietta; Sailer, Martin Oliver
2017-05-01
The probability of success or average power describes the potential of a future trial by weighting the power with a probability distribution of the treatment effect. The treatment effect estimate from a previous trial can be used to define such a distribution. During the development of targeted therapies, it is common practice to look for predictive biomarkers. The consequence is that the trial population for phase III is often selected on the basis of the most extreme result from phase II biomarker subgroup analyses. In such a case, there is a tendency to overestimate the treatment effect. We investigate whether the overestimation of the treatment effect estimate from phase II is transformed into a positive bias for the probability of success for phase III. We simulate a phase II/III development program for targeted therapies. This simulation allows to investigate selection probabilities and allows to compare the estimated with the true probability of success. We consider the estimated probability of success with and without subgroup selection. Depending on the true treatment effects, there is a negative bias without selection because of the weighting by the phase II distribution. In comparison, selection increases the estimated probability of success. Thus, selection does not lead to a bias in probability of success if underestimation due to the phase II distribution and overestimation due to selection cancel each other out. We recommend to perform similar simulations in practice to get the necessary information about the risk and chances associated with such subgroup selection designs. Copyright © 2017 John Wiley & Sons, Ltd.
Maximizing return on socioeconomic investment in phase II proof-of-concept trials.
Chen, Cong; Beckman, Robert A
2014-04-01
Phase II proof-of-concept (POC) trials play a key role in oncology drug development, determining which therapeutic hypotheses will undergo definitive phase III testing according to predefined Go-No Go (GNG) criteria. The number of possible POC hypotheses likely far exceeds available public or private resources. We propose a design strategy for maximizing return on socioeconomic investment in phase II trials that obtains the greatest knowledge with the minimum patient exposure. We compare efficiency using the benefit-cost ratio, defined to be the risk-adjusted number of truly active drugs correctly identified for phase III development divided by the risk-adjusted total sample size in phase II and III development, for different POC trial sizes, powering schemes, and associated GNG criteria. It is most cost-effective to conduct small POC trials and set the corresponding GNG bars high, so that more POC trials can be conducted under socioeconomic constraints. If δ is the minimum treatment effect size of clinical interest in phase II, the study design with the highest benefit-cost ratio has approximately 5% type I error rate and approximately 20% type II error rate (80% power) for detecting an effect size of approximately 1.5δ. A Go decision to phase III is made when the observed effect size is close to δ. With the phenomenal expansion of our knowledge in molecular biology leading to an unprecedented number of new oncology drug targets, conducting more small POC trials and setting high GNG bars maximize the return on socioeconomic investment in phase II POC trials. ©2014 AACR.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bezryadin, N. N.; Kotov, G. I., E-mail: giktv@mail.ru; Kuzubov, S. V., E-mail: kuzub@land.ru
2015-03-15
Surfaces of GaAs(100), InAs(100), and GaP(100) substrates thermally treated in selenium vapor have been investigated by transmission electron microscopy and electron probe X-ray microanalysis. Some specific features and regularities of the formation of A{sub 3}{sup III}B{sub 4}{sup VI} (100)c(2 × 2) surface phases and thin layers of gallium or indium selenides A{sub 2}{sup III}B{sub 3}{sup VI} (100) on surfaces of different A{sup III}B{sup V}(100) semiconductors are discussed within the vacancy model of surface atomic structure.
Adeniyi, Oladele Vincent; Yogeswaran, Parimalaranie; Longo-Mbenza, Benjamin; Ter Goon, Daniel
2016-01-01
Paucity of data on the prevalence, treatment and control of hypertension in individuals living with type 2 diabetes mellitus (T2DM) in the rural communities of South Africa may undermine efforts to reduce the morbidity and mortality associated with cardiovascular diseases. This study examines the socio-demographic and clinical determinants of uncontrolled hypertension among individuals living with T2DM in the rural communities of Mthatha, South Africa. This cross-sectional study involved a serially selected sample of 265 individuals living with T2DM and hypertension at Mthatha General Hospital, Mthatha. Uncontrolled hypertension was defined as systolic blood pressure greater than or equal to 140 mmHg and diastolic blood pressure greater than or equal to 90mmHg in accordance with the Eight Joint National Committee Report (JNC 8) (2014). We performed univariate and multivariate logistic regression analyses to identify the significant determinants of uncontrolled hypertension. Of the total participants (n = 265), the prevalence of uncontrolled hypertension was 75.5% (n = 200). In univariate analysis of all participants, male gender (p = 0.029), age≥65 years (p = 0.016), unemployed status (p<0.0001), excessive alcohol intake (p = 0.005) and consumption of western-type diet (p<0.0001) were positively associated with uncontrolled hypertension. In multivariate logistic regression (LR method) analysis, unemployed status (p<0.0001), excessive alcohol intake (p = 0.007) and consumption of western-type diet (p<0.0001) were independently and significantly associated with uncontrolled hypertension. There is significant association between increasing number and classes of anti-hypertensive drugs and uncontrolled hypertension (p = 0.05 and 0.02, respectively). Prevalence of uncontrolled hypertension was high in individuals with concomitant hypertension and T2DM in the study population. Male sex, aging, clinic inertia, unemployed status and nutritional transitions are the most important determinants of uncontrolled hypertension in T2DM in Mthatha, South Africa. Treatment to blood pressure targets, though feasible in our setting, would require concerted efforts by addressing these determinants and clinic inertia.
Comparison of the Intensity of Ventilation at Windows Exchange in the Room - Case Study
NASA Astrophysics Data System (ADS)
Kapalo, Peter; Voznyak, Orest
2017-06-01
Doing the replacement of old wooden windows in a new plastic windows, in the old buildings, we get the great reducing of the building heat loss. Simpler maintenance and attendance of window is the next advantage. New windows are characterized by better tightness. The aim of the article is determination due to the performed experimental measurements, how much more are reduce the uncontrolled ventilation that is caused of the infiltration windows. In the article there is presented the experimental measurement of indoor air quality in the room in two phases. In the first phase there is the room installed by 55 year old wood window. In the second phase there is the same room installed by new plastic window. Due to the experimental measurement of indoor air quality it is calculated intensity of ventilation - infiltration. These results of ventilation intensity are reciprocally compared.
The history of couple therapy: a millennial review.
Gurman, Alan S; Fraenkel, Peter
2002-01-01
In this article, we review the major conceptual and clinical influences and trends in the history of couple therapy to date, and also chronicle the history of research on couple therapy. The evolving patterns in theory and practice are reviewed as having progressed through four distinctive phases: Phase I--Atheoretical Marriage Counseling Formation (1930-1963); Phase II--Psychoanalytic Experimentation (1931-1966); Phase III--Family Therapy Incorporation (1963-1985); and Phase IV--Refinement, Extension, Diversification, and Integration (1986-present). The history of research in the field is described as having passed through three phases: Phase I--A Technique in Search of Some Data (1930-1974), Phase II--Irrational(?) Exuberance (1975-1992), and Phase III--Caution and Extension (1993-present). The article concludes with the identification of Four Great Historical Ironies in the History of Couple Therapy.
Bush, Karen; Heep, Markus; Macielag, Mark J; Noel, Gary J
2007-04-01
Ceftobiprole is the first of the investigational beta-lactam antibiotics with in vitro activity against methicillin-resistant staphylococci to reach and complete Phase III therapeutic trials. Its antibacterial spectrum includes methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, penicillin-resistant streptococci and many Gram-negative pathogens. It has demonstrated in vivo activity against many experimental infections caused by these pathogens. Ceftobiprole has completed Phase III clinical trials for complicated skin and skin structure infections, is being studied in Phase III pneumonia trials and has demonstrated non-inferiority compared with vancomycin in a Phase III complicated skin and skin structure infections trial, resulting in > 90% clinical cures of infections caused by MRSA. Other anti-MRSA beta-lactams in therapeutic clinical trials include the carbapenem CS-023/RO-4908463 and the cephalosporin ceftaroline (PPI-0903). The future of all of these agents will depend on their clinical efficacy, safety and their ability to be accepted as beta-lactams for the reliable treatment of a broad spectrum of infections, including those caused by MRSA.
HST/COS Far-ultraviolet Spectroscopic Analysis of U Geminorum Following a Wide Outburst
NASA Astrophysics Data System (ADS)
Godon, Patrick; Shara, Michael M.; Sion, Edward M.; Zurek, David
2017-12-01
We used the Cosmic Origins Spectrograph (COS) on the Hubble Space Telescope (HST) to obtain a series of four far-ultraviolet (FUV; 915-2148 Å) spectroscopic observations of the prototypical dwarf nova U Geminorum during its cooling following a two-week outburst. Our FUV spectral analysis of the data indicates that the white dwarf (WD) cools from a temperature of ˜41,500 K, 15 days after the peak of the outburst, to ˜36,250 K, 56 days after the peak of the outburst, assuming a massive WD (log(g) = 8.8) and a distance of 100.4 ± 3.7 pc. These results are self-consistent with a ˜1.1 M ⊙ WD with a 5000 ± 200 km radius. The spectra show absorption lines of H I, He II, C II III IV, N III IV, O VI, S IV, Si II III IV, Al III, Ar III, and Fe II, but no emission features. We find suprasolar abundances of nitrogen, confirming the anomalous high N/C ratio. The FUV light curve reveals a ±5% modulation with the orbital phase, showing dips near phases 0.25 and ˜0.75, where the spectra exhibit an increase in the depth of some absorption lines and in particular strong absorption lines from Si II, Al III, and Ar III. The phase dependence we observe is consistent with material overflowing the disk rim at the hot spot, reaching a maximum elevation near phase 0.75, falling back at smaller radii near phase 0.5 where it bounces off the disk surface, and again rising above the disk near phase ˜0.25. There is a large scatter in the absorption lines’ velocities, especially for the silicon lines, while the carbon lines seem to match more closely the orbital velocity of the WD. This indicates that many absorption lines are affected by—or form in—the overflowing stream material veiling the WD, making the analysis of the WD spectra more difficult. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by AURA, Inc., under NASA contract NAS 5-26555.
Microbial exudate promoted dissolution and transformation of chromium containing minerals
NASA Astrophysics Data System (ADS)
Saad, E. M.; Sun, J.; Tang, Y.
2015-12-01
Because of its utility in many industrial processes, chromium has become the second most common metal contaminant in the United States. The two most common oxidation states of chromium in nature are Cr(III), which is highly immobile, and Cr(VI), which is highly mobile and toxic. In both natural and engineered environments, the most common remediation of Cr(VI) is through reduction, which results in chromium sequestration in the low solubility mixed Cr(III)-Fe(III) (oxy)hydroxide phases. Consequently, the stability of these minerals must be examined to assess the fate of chromium in the subsurface. We examined the dissolution of mixed Cr(III)-Fe(III) (oxy)hydroxides in the presence of common microbial exudates, including the siderophore desferrioxamine B (DFOB; a common organic ligand secreted by most microbes with high affinity for ferric iron and other trivalent metal ions) and oxalate (a common organic acid produced by microbes). The solids exhibited incongruent dissolution with preferential leaching of Fe from the solid phase. Over time, this leads to a more Cr rich mineral, which is known to be more soluble than the corresponding mixed mineral phase. We are currently investigating the structure of the reacted mineral phases and soluble Cr(III) species, as well as the potential oxidation and remobilization of the soluble Cr species. Results from this study will provide insights regarding the long term transport and fate of chromium in the natural environment in the presence of microbial activities.
Cañadillas-Delgado, Laura; Fabelo, Oscar; Rodríguez-Velamazán, J Alberto; Lemée-Cailleau, Marie-Hélène; Mason, Sax A; Pardo, Emilio; Lloret, Francesc; Zhao, Jiong-Peng; Bu, Xian-He; Simonet, Virginie; Colin, Claire V; Rodríguez-Carvajal, Juan
2012-12-05
Neutron diffraction studies have been carried out to shed light on the unprecedented order-disorder phase transition (ca. 155 K) observed in the mixed-valence iron(II)-iron(III) formate framework compound [NH(2)(CH(3))(2)](n)[Fe(III)Fe(II)(HCOO)(6)](n). The crystal structure at 220 K was first determined from Laue diffraction data, then a second refinement at 175 K and the crystal structure determination in the low temperature phase at 45 K were done with data from the monochromatic high resolution single crystal diffractometer D19. The 45 K nuclear structure reveals that the phase transition is associated with the order-disorder of the dimethylammonium counterion that is weakly anchored in the cavities of the [Fe(III)Fe(II)(HCOO)(6)](n) framework. In the low-temperature phase, a change in space group from P31c to R3c occurs, involving a tripling of the c-axis due to the ordering of the dimethylammonium counterion. The occurrence of this nuclear phase transition is associated with an electric transition, from paraelectric to antiferroelectric. A combination of powder and single crystal neutron diffraction measurements below the magnetic order transition (ca. 37 K) has been used to determine unequivocally the magnetic structure of this Néel N-Type ferrimagnet, proving that the ferrimagnetic behavior is due to a noncompensation of the different Fe(II) and Fe(III) magnetic moments.
NASA Astrophysics Data System (ADS)
Takemura, T.; Chin, M.
2014-12-01
It is important to understand relative contributions of each regional and sector emission of aerosols and their precursor gases to the regional and global mean radiative forcing of aerosol-radiation and aerosol-cloud interactions. This is because it is useful for international cooperation on controls of air pollution and anthropogenic climate change along most suitable reduction path of their emissions from each region and sector. The Task Force on Hemispheric Transport of Air Pollution (TF HTAP) under the United Nations researches the intercontinental transport of air pollutants including aerosols with strong support of the Aerosol Comparisons between Observations and Models (AeroCOM). The ongoing AeroCOM Phase III/HTAP2 experiment assesses relative contributions of regional and sector sources of aerosols and their precursor gases to the air quality using global aerosol transport models with latest emission inventories. In this study, the extended analyses on the relative contributions of each regional and sector emission to the radiative forcing of aerosol-radiation and aerosol-cloud interactions are done from the AeroCOM Phase III/HTAP2 experiment. Simulated results from MIROC-SPRINTARS and other some global aerosol models participating in the the AeroCOM Phase III/HTAP2 experiment are assessed. Acknowledgements: This study is based on the AeroCOM Phase III/HTAP2 experiment and partly supported by the Environment Research and Technology Development Fund (S-12-3) of the Ministry of the Environment, Japan.
2012-01-01
Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery) may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH) are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10), and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC)-controlled Phase I/II study (N = 7) in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10): All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min) of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7): Hemostatic success at 10 min (primary endpoint) was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial hemorrhage as a replacement for sutures. The study was suspended after 7/30 planned subjects were enrolled. Conclusions The first-in-man trial of fibrin pad demonstrated its safety and efficacy as an adjunctive hemostatic technique for mild-to-moderate bleeding in partial nephrectomy. The study also suggested that the product should not replace sutures or meticulous surgical techniques for the treatment of severe arterial hemorrhage. Trial registration Phase I/II trial, NCT00598130 PMID:23137020
NASA Astrophysics Data System (ADS)
Ning, Guo
1995-06-01
The solid-phase behavior of [n-C9H19NH3]2CuCl4 was investigated by infrared spectroscopy. The nature of the three solid phases (phase I, phase II, and phase III) is discussed. A temperature-dependent study of infrared spectra provides evidence for the occurrence of structural phase transitions related to the dynamics of the alkyl chains and -NH3 polar heads. The phase transition at Tc1 (22°C) arises from variation in the interaction and packing structure of the chain. The phase transition at Tc2 (34°C) is related to variation in partial conformational order-disorder at the intramolecular level. The GTG or GTG‧ and small concentration of TG structures near the CH3 group are generated in phase III (above 38°C).
Li, Zhenhua; Chang, Xijun; Zou, Xiaojun; Zhu, Xiangbing; Nie, Rong; Hu, Zheng; Li, Ruijun
2009-01-26
A new method that utilizes ethylenediamine-modified activated carbon (AC-EDA) as a solid-phase extractant has been developed for simultaneous preconcentration of trace Cr(III), Fe(III), Hg(II) and Pb(II) prior to the measurement by inductively coupled plasma optical emission spectrometry (ICP-OES). The new sorbent was prepared by oxidative surface modification. Experimental conditions for effective adsorption of trace levels of Cr(III), Fe(III), Hg(II) and Pb(II) were optimized with respect to different experimental parameters using batch and column procedures in detail. The optimum pH value for the separation of metal ions simultaneously on the new sorbent was 4.0. Complete elution of absorbed metal ions from the sorbent surface was carried out using 3.0 mL of 2% (%w/w) thiourea and 0.5 mol L(-1) HCl solution. Common coexisting ions did not interfere with the separation and determination of target metal ions. The maximum static adsorption capacity of the sorbent at optimum conditions was found to be 39.4, 28.9, 60.5 and 49.9 mg g(-1) for Cr(III), Fe(III), Hg(II) and Pb(II), respectively. The time for 94% adsorption of target metal ions was less than 2 min. The detection limits of the method was found to be 0.28, 0.22, 0.09 and 0.17 ng mL(-1) for Cr(III), Fe(III), Hg(II) and Pb(II), respectively. The precision (R.S.D.) of the method was lower 4.0% (n=8). The prepared sorbent as solid-phase extractant was successfully applied for the preconcentration of trace Cr(III), Fe(III), Hg(II) and Pb(II) in natural and certified samples with satisfactory results.
Uncontrollable Stress, Coping, and Subjective Well-Being in Urban Adolescents
ERIC Educational Resources Information Center
Coyle, Laura D.; Vera, Elizabeth M.
2013-01-01
The purpose of this study was to determine whether uncontrollable stress related to levels of subjective well-being (SWB) in a group of ethnically diverse urban adolescents. Additionally, the researchers examined what types of coping skills were utilized in the face of high levels of uncontrollable stress. Finally, a moderation model was proposed,…
Thayabaranathan, Tharshanah; Cadilhac, Dominique A; Srikanth, Velandai K; Fitzgerald, Sharyn M; Evans, Roger G; Kim, Joosup; Gerraty, Richard P; Phan, Thanh G; Bladin, Christopher F; Nelson, Mark R; Frayne, Judith H; Thrift, Amanda G
2016-06-01
Recruitment and retention of patients in a clinical trial is important for generalizability and robustness of findings. We aimed to investigate features of a study design that were associated with recruitment and retention in a Phase II and Phase III trial of a secondary prevention program for stroke. Following informed consent in hospital, Phase II participants were randomized to intervention or usual care. Baseline clinical assessments were conducted at home approximately 3 months after discharge. In Phase III study, informed consent was obtained at home. We compared the characteristics of participants recruited and retained to 12 months for both phases. Interviews with study nurses were undertaken in order to ascertain their opinions of features of study design. Triangulation was used to identify the features of study design that nurses thought had improved recruitment and retention. All 24 eligible participants were recruited to the Phase II pilot study (100% recruitment), with 67% retention at 12 months. In Phase III study, 570 participants were recruited, and 93% of these participants had reached their 12-month assessment (n = 532) and were still participating. Consistent with the greater patient retention in Phase III study, nurses reported that patients' willingness to participate was greater when consent was obtained at home. Following a change in the consent process from hospital to home, more participants continued participation to 12 months. Pilot studies can provide important data to improve study design and better understand potential barriers to recruitment and retention. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
2013-01-01
Background Expression of miR-17-92 enhances T-cell survival and interferon (IFN)-γ production. We previously reported that miR-17-92 is down-regulated in T-cells derived from glioblastoma (GBM) patients. We hypothesized that transgene-derived co-expression of miR17-92 and chimeric antigen receptor (CAR) in T-cells would improve the efficacy of adoptive transfer therapy against GBM. Methods We constructed novel lentiviral vectors for miR-17-92 (FG12-EF1a-miR-17/92) and a CAR consisting of an epidermal growth factor receptor variant III (EGFRvIII)-specific, single-chain variable fragment (scFv) coupled to the T-cell receptor CD3ζ chain signaling module and co-stimulatory motifs of CD137 (4-1BB) and CD28 in tandem (pELNS-3C10-CAR). Human T-cells were transduced with these lentiviral vectors, and their anti-tumor effects were evaluated both in vitro and in vivo. Results CAR-transduced T-cells (CAR-T-cells) exhibited potent, antigen-specific, cytotoxic activity against U87 GBM cells that stably express EGFRvIII (U87-EGFRvIII) and, when co-transduced with miR-17-92, exhibited improved survival in the presence of temozolomide (TMZ) compared with CAR-T-cells without miR-17-92 co-transduction. In mice bearing intracranial U87-EGFRvIII xenografts, CAR-T-cells with or without transgene-derived miR-17-92 expression demonstrated similar levels of therapeutic effect without demonstrating any uncontrolled growth of CAR-T-cells. However, when these mice were re-challenged with U87-EGFRvIII cells in their brains, mice receiving co-transduced CAR-T-cells exhibited improved protection compared with mice treated with CAR-T-cells without miR-17-92 co-transduction. Conclusion These results warrant the development of novel CAR-T-cell strategies that incorporate miR-17-92 to improve therapeutic potency, especially in patients with GBM. PMID:24829757
Ohno, Masasuke; Ohkuri, Takayuki; Kosaka, Akemi; Tanahashi, Kuniaki; June, Carl H; Natsume, Atsushi; Okada, Hideho
2013-01-01
Expression of miR-17-92 enhances T-cell survival and interferon (IFN)-γ production. We previously reported that miR-17-92 is down-regulated in T-cells derived from glioblastoma (GBM) patients. We hypothesized that transgene-derived co-expression of miR17-92 and chimeric antigen receptor (CAR) in T-cells would improve the efficacy of adoptive transfer therapy against GBM. We constructed novel lentiviral vectors for miR-17-92 (FG12-EF1a-miR-17/92) and a CAR consisting of an epidermal growth factor receptor variant III (EGFRvIII)-specific, single-chain variable fragment (scFv) coupled to the T-cell receptor CD3ζ chain signaling module and co-stimulatory motifs of CD137 (4-1BB) and CD28 in tandem (pELNS-3C10-CAR). Human T-cells were transduced with these lentiviral vectors, and their anti-tumor effects were evaluated both in vitro and in vivo. CAR-transduced T-cells (CAR-T-cells) exhibited potent, antigen-specific, cytotoxic activity against U87 GBM cells that stably express EGFRvIII (U87-EGFRvIII) and, when co-transduced with miR-17-92, exhibited improved survival in the presence of temozolomide (TMZ) compared with CAR-T-cells without miR-17-92 co-transduction. In mice bearing intracranial U87-EGFRvIII xenografts, CAR-T-cells with or without transgene-derived miR-17-92 expression demonstrated similar levels of therapeutic effect without demonstrating any uncontrolled growth of CAR-T-cells. However, when these mice were re-challenged with U87-EGFRvIII cells in their brains, mice receiving co-transduced CAR-T-cells exhibited improved protection compared with mice treated with CAR-T-cells without miR-17-92 co-transduction. These results warrant the development of novel CAR-T-cell strategies that incorporate miR-17-92 to improve therapeutic potency, especially in patients with GBM.
Vanstone, Meredith; Rewegan, Alex; Brundisini, Francesca; Dejean, Deirdre; Giacomini, Mita
2015-01-01
Patients with uncontrolled type 1 diabetes mellitus may be candidates for pancreatic islet cell transplantation. This report synthesizes qualitative research on how patients with uncontrolled type 1 diabetes perceive their quality of life. The objective of this analysis was to examine the perceptions of patients with uncontrolled type 1 diabetes on how it affects their lived experience and quality of life. This report synthesizes 31 primary qualitative studies to examine quality of life from the perspectives of adult patients with type 1 diabetes mellitus and their families or partners. We performed a qualitative meta-synthesis to integrate findings across primary research studies. Long- and short-term negative consequences of uncontrolled type 1 diabetes affect all aspects of patients' lives: physical, emotional, practical, and social. The effect on each domain is far-reaching, and effects interact across domains. Uncontrolled blood sugar levels lead to substantial psychological distress, negative moods, cognitive difficulties, irritable or aggressive behaviour, and closely associated problems with relationships, self-image, and confidence. Emotional distress is pervasive and under-addressed by health care providers. Patients live in fear of complications from diabetes over the long term. In the shorter term, they are anxious about the personal, social, and professional consequences of hypoglycemic episodes (e.g., injury, humiliation), and may curtail normal activities such as driving or socializing because they are worried about having an episode. The quality of life for patients' family members is also negatively impacted by uncontrolled type 1 diabetes. Uncontrolled type 1 diabetes has significant negative impacts on the quality of life of both people with the disease and their families.
Reasons for uncontrolled seizures in children: the impact of pseudointractability.
Asadi-Pooya, Ali A; Emami, Mehrdad
2012-11-01
We investigated the various possible reasons for uncontrolled seizures in patients under 18 years of age to determine the impact of pseudointractability. We also investigated the various forms of pseudointractability in children with uncontrolled seizures. In this cross-sectional retrospective chart review study, all patients under 18 years of age with their first seizure occurring at least 6 months prior to the referral date, taking at least one antiepileptic drug (AED), and having at least one seizure in the past 3 months were studied. The presumed reason for uncontrolled seizures was arbitrarily considered to be one of these five categories: poor adherence; wrong medication; wrong dose of the correct medication; diagnosis other than epilepsy; and finally, medically refractory epilepsy. Statistical analyses were performed using Chi-square and Fisher's Exact tests to determine potentially significant differences, and a P value less than 0.05 was considered significant. During the study period, 198 patients were referred to us due to uncontrolled seizures. Ninety patients (45%) were taking one AED, 55 (28%) were taking two AEDs, and 53 (27%) patients were taking more than two AEDs at the time of referral. Four percent of these patients did not have epilepsy. Forty-seven percent of the children with uncontrolled seizures had medically refractory epilepsy; 37% were taking the wrong AEDs; 10% were taking suboptimal doses of AEDs; and 2% had poor drug adherence. Uncontrolled seizures in children are a commonly encountered problem, particularly at epilepsy clinics. One should consider all possible reasons for these uncontrolled seizures, including non-epileptic seizures, pseudointractability, and medically refractory epilepsy. The mainstay for making a correct diagnosis is a detailed clinical history. Copyright © 2012 Elsevier Inc. All rights reserved.
Anal Cancer: An Examination of Radiotherapy Strategies
DOE Office of Scientific and Technical Information (OSTI.GOV)
Glynne-Jones, Rob; Lim, Faye
2011-04-01
The Radiation Therapy Oncology Group 9811, ACCORD-03, and ACT II Phase III trials in anal cancer showed no benefit for cisplatin-based induction and maintenance chemotherapy, or radiation dose-escalation >59 Gy. This review examines the efficacy and toxicity of chemoradiation (CRT) in anal cancer, and discusses potential alternative radiotherapy strategies. The evidence for the review was compiled from randomized and nonrandomized trials of radiation therapy and CRT. A total of 103 retrospective/observational studies, 4 Phase I/II studies, 16 Phase II prospective studies, 2 randomized Phase II studies, and 6 Phase III trials of radiotherapy or chemoradiation were identified. There are nomore » meta-analyses based on individual patient data. A 'one-size-fits-all' approach for all stages of anal cancer is inappropriate. Early T1 tumors are probably currently overtreated, whereas T3/T4 lesions might merit escalation of treatment. Intensity-modulated radiotherapy or the integration of biological therapy may play a role in future.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Belles, F.E.
1993-01-01
Uncontrolled NOx emissions from a variety of pulse combustors were measured. The implementation of flue-gas recirculation to reduce NOx was studied. A flexible workstation for parametric testing was built and used to study the phasing between pressure and heat release, and effects of fuel/air mixing on performance. Exhaust-pipe heat transfer was analyzed. An acoustic model of pulse combustion was developed. Technical support was provided to manufacturers on noise, ignition and condensation. A computerized bibliographic database on pulse combustion was created.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Noel, Donna
This project integrated state-of-the-art exploration technologies with a geologic framework and reservoir modeling to ultimately determine the efficacy of future geothermal production within the PLPT reservation. The information gained during this study should help the PLPT to make informed decisions regarding construction of a geothermal power plant. Additional benefits included the transfer of new technologies and geothermal data to the geothermal industry and it created and/or preserved nearly three dozen jobs accordance with the American Recovery and Reinvestment Act of 2009. A variety of tasks were conducted to achieve the above stated objectives. The following are the tasks completed withinmore » the project: 1. Permitting 2. Shallow temperature survey 3. Seismic data collection and analysis 4. Fracture stress analysis 5. Phase I reporting Permitting 7. Shallow temperature survey 8. Seismic data collection and analysis 9. Fracture stress analysis 10. Phase I reporting 11. Drilling two new wells 12. Borehole geophysics 13. Phase II reporting 14. Well testing and geochemical analysis 15. Three-dimensional geologic model 16. Three-dimensional reservoir analysis 17. Reservation wide geothermal potential analysis 18. Phase III reporting Phase I consisted of tasks 1 – 5, Phase II tasks 6 – 8, and Phase III tasks 9 – 13. This report details the results of Phase III tasks. Reports are available for Phase I, and II as separate documents.« less
Sexual murderers' implicit theories.
Beech, Anthony; Fisher, Dawn; Ward, Tony
2005-11-01
Interviews with 28 sexual murderers were subjected to grounded theory analysis. Five implicit theories (ITs) were identified: dangerous world, male sex drive is uncontrollable, entitlement, women as sexual objects, and women as unknowable. These ITs were found to be identical to those identified in the literature as being present in rapists. The presence of dangerous world and male sex drive is uncontrollable were present, or absent, such that three groups could be identified: (a) dangerous world plus male sex drive is uncontrollable; (b) dangerous world, in the absence of male sex drive is uncontrollable; (c) male sex drive is uncontrollable in the absence of dangerous world. These three groups were found to differ in motivation: (a) were motivated by urges to rape and murder; (b) were motivated by grievance, resentment and/or anger toward women; (c) were motivated to sexually offend but were prepared to kill to avoid detection, or secure compliance.
Silva, Cínthia R B; Putarov, Thaila C; Fruhvald, Erika; Destro, Flavia C; Marques Filho, Wolff C; Thomazini, Camila M; Barbosa, Tatiana S; Orsi, Ricardo O; Siqueira, Edson R
2014-07-01
The present study aimed to evaluate the effect of propolis use on hematological and serum biochemical parameters in Blue-fronted Amazons (Amazona aestiva). For this, 12 adult birds were distributed randomly into individual cages, divided into treatments with different propolis levels (A = 0.0%; B = 0.5%; and C = 1.0%), in 3 distinct phases (I, II, and III), with 15-d duration for phases I and III and 30 d for phase II, totaling 60 d. In phases I and III, all birds received treatment A ration, and in phase II received A, B, or C (4 birds per treatment). At the end of each phase, blood was collected for biochemical and hematological evaluations. The variables were analyzed by ANOVA (P < 0.05). Results suggest that 0.5% propolis reduced lactate dehydrogenase levels, whereas treatment B augmented hemoglobin concentrations and eosinophil count. It is concluded that 0.5% propolis improves levels of lactate dehydrogenase, hemoglobin, and eosinophils. © 2014 Poultry Science Association Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mączka, Mirosław, E-mail: m.maczka@int.pan.wroc.pl; Gągor, Anna; Hermanowicz, Krzysztof
2016-05-15
We have incorporated Cr(III) into [(CH{sub 3}){sub 2}NH{sub 2}][Mn(HCOO){sub 3}] (DMMn) multiferroic metal organic framework (MOF). The highest concentration of Cr(III) in the synthesized samples reached 15.9 mol%. The obtained samples were characterized by powder and single-crystal X-ray diffraction, DSC, magnetic susceptibility, dielectric, EPR, Raman and IR methods. These methods and the performed chemical analysis revealed that electrical charge neutrality after substitution of Cr(III) for Mn(II) is maintained by partial replacement of dimethylammonium (DMA{sup +}) cations by neutral HCOOH molecules. These changes in the chemical composition are responsible for weakening of the hydrogen bonds and decreased flexibility of the framework.more » This in turn leads to lowering of the ferroelectric phase transition temperature, observed around 185 K for undoped DMMn and around 155 K for the sample containing 3.1 mol% of Cr(III), and lack of macroscopic phase transition for the samples with Cr(III) content of 8.2 and 15.9 mol %. Another interesting effect observed for the studied samples is pronounced strengthening of the weak ferromagnetism of in Cr(III)-doped samples, associated with slight decrease of the ferromagnetic ordering temperature from 8.5 K for DMMn to 7.0 K for the sample with 15.9 mol % Cr(III) content. - Graphical abstract: Incorporation of Cr(III) into [(CH3)2NH2[Mn(HCOO)3] framework increases the magnetization. - Highlights: • Chromium(III) substitutes for Mn(II) in the studied MOF. • Charge neutrality is maintained by replacing DMA{sup +} cations by neutral HCOOH molecules. • Compounds with 8.2 and 15.9% of Cr(III) show no phase transition above 100 K. • Doping with Cr(III) increases magnetization.« less
Chen, Yuehua; Wang, Huiyong; Pei, Yuanchao; Wang, Jianji
2018-05-15
It is significant to develop sustainable strategies for the selective separation of rare earth from transition metals from fundamental and practical viewpoint. In this work, an environmentally friendly solvent extraction approach has been developed to selectively separate neodymium (III) from cobalt (II) and nickel (II) by using an ionic liquid-based aqueous two phase system (IL-ATPS). For this purpose, a hydrophilic ionic liquid (IL) tetrabutylphosphonate nitrate ([P 4444 ][NO 3 ]) was prepared and used for the formation of an ATPS with NaNO 3 . Binodal curves of the ATPSs have been determined for the design of extraction process. The extraction parameters such as contact time, aqueous phase pH, content of phase-formation components of NaNO 3 and the ionic liquid have been investigated systematically. It is shown that under optimal conditions, the extraction efficiency of neodymium (III) is as high as 99.7%, and neodymium (III) can be selectively separated from cobalt (II) and nickel (II) with a separation factor of 10 3 . After extraction, neodymium (III) can be stripped from the IL-rich phase by using dilute aqueous sodium oxalate, and the ILs can be quantitatively recovered and reused in the next extraction process. Since [P 4444 ][NO 3 ] works as one of the components of the ATPS and the extractant for the neodymium, no organic diluent, extra etractant and fluorinated ILs are used in the separation process. Thus, the strategy described here shows potential in green separation of neodymium from cobalt and nickel by using simple IL-based aqueous two-phase system. Copyright © 2018 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Shen, Guofeng; Ren, Guoxin; Guo, Wei; Chen, Yazhu
2012-11-01
The principle of a ultrasound thermo-chemotherapy instrument and the clinical phase I/II research on short-term and long-term therapeutic effect and main side-effect of ultrasound hyperthermia combined with chemotherapy in oral and maxillofacial-head & neck carcinoma by the instrument will be presented in this paper.
DOE Office of Scientific and Technical Information (OSTI.GOV)
O'Neil, Lori Ross; Conway, T. J.; Tobey, D. H.
The Secure Power Systems Professional Phase III final report was released last year which an appendix of Behavioral Interview Guidelines by Job Roles. This new report is that appendix broken out as a standalone document to assist utilities in recruiting and developing Secure Power Systems Professionals at their site.
DOE Office of Scientific and Technical Information (OSTI.GOV)
O'Neil, Lori Ross; Conway, T. J.; Tobey, D. H.
The Secure Power Systems Professional Phase III final report was released last year which an appendix of Individual and Team Performance Guidelines. This new report is that appendix broken out as a standalone document to assist utilities in recruiting and developing Secure Power Systems Professionals at their site.
Metallography and microstructure interpretation of some archaeological tin bronze vessels from Iran
DOE Office of Scientific and Technical Information (OSTI.GOV)
Oudbashi, Omid, E-mail: o.oudbashi@aui.ac.ir; Davami, Parviz, E-mail: pdavami@razi-foundation.com
2014-11-15
Archaeological excavations in western Iran have recently revealed a significant Luristan Bronzes collection from Sangtarashan archaeological site. The site and its bronze collection are dated to Iron Age II/III of western Iran (10th–7th century BC) according to archaeological research. Alloy composition, microstructure and manufacturing technique of some sheet metal vessels are determined to reveal metallurgical processes in western Iran in the first millennium BC. Experimental analyses were carried out using Scanning Electron Microscopy–Energy Dispersive X-ray Spectroscopy and Optical Microscopy/Metallography methods. The results allowed reconstructing the manufacturing process of bronze vessels in Luristan. It proved that the samples have been manufacturedmore » with a binary copper–tin alloy with a variable tin content that may relates to the application of an uncontrolled procedure to make bronze alloy (e.g. co-smelting or cementation). The presence of elongated copper sulphide inclusions showed probable use of copper sulphide ores for metal production and smelting. Based on metallographic studies, a cycle of cold working and annealing was used to shape the bronze vessels. - Highlights: • Sangtarashan vessels are made by variable Cu-Sn alloys with some impurities. • Various compositions occurred due to applying uncontrolled smelting methods. • The microstructure represents thermo-mechanical process to shape bronze vessels. • In one case, the annealing didn’t remove the eutectoid remaining from casting. • The characteristics of the bronzes are similar to other Iron Age Luristan Bronzes.« less
NASA Astrophysics Data System (ADS)
Allaf, Abdul. W.; Kassem, M.; Alibrahim, M.; Boustani, Ihsan
1999-03-01
An attempt was made to observe the gas-phase infrared spectrum of Phosphorus (III) oxycyanide, OPCN for the first time. This molecule was produced by an on-line process using phosphorus (III) oxychloride, OPCl as precursor passed over heated AgCN. The products were characterised by the infrared spectra of their vapours. The low resolution gas-phase Fourier transform infrared spectrum shows two bands centered at 2165 and 1385 cm -1. These bands are assigned to, ν1 (CN stretch) and ν2 (OP stretch), respectively. Ab initio self-consistent-field (SCF) molecular orbital (MO) and Møller-Plesset second order perturbation theory (MP2) calculations were performed to determine the geometry, total energy and vibrational frequencies of OPCN.
Biogeochemical transformation of Fe minerals in a petroleum-contaminated aquifer
Zachara, John M.; Kukkadapu, Ravi K.; Glassman, Paul L.; Dohnalkova, Alice; Fredrickson, Jim K.; Anderson, Todd
2004-01-01
The Bemidji aquifer in Minnesota, USA is a well-studied site of subsurface petroleum contamination. The site contains an anoxic groundwater plume where soluble petroleum constituents serve as an energy source for a region of methanogenesis near the source and bacterial Fe(III) reduction further down gradient. Methanogenesis apparently begins when bioavailable Fe(III) is exhausted within the sediment. Past studies indicate that Geobacter species and Geothrix fermentens-like organisms are the primary dissimilatory Fe-reducing bacteria at this site. The Fe mineralogy of the pristine aquifer sediments and samples from the methanogenic (source) and Fe(III) reducing zones were characterized in this study to identify microbiologic changes to Fe valence and mineral distribution, and to identify whether new biogenic mineral phases had formed. Methods applied included X-ray diffraction; X-ray fluorescence (XRF); and chemical extraction; optical, transmission, and scanning electron microscopy; and Mössbauer spectroscopy.All of the sediments were low in total Fe content (≈ 1%) and exhibited complex Fe-mineralogy. The bulk pristine sediment and its sand, silt, and clay-sized fractions were studied in detail. The pristine sediments contained Fe(II) and Fe(III) mineral phases. Ferrous iron represented approximately 50% of FeTOT. The relative Fe(II) concentration increased in the sand fraction, and its primary mineralogic residence was clinochlore with minor concentrations found as a ferroan calcite grain cement in carbonate lithic fragments. Fe(III) existed in silicates (epidote, clinochlore, muscovite) and Fe(III) oxides of detrital and authigenic origin. The detrital Fe(III) oxides included hematite and goethite in the form of mm-sized nodular concretions and smaller-sized dispersed crystallites, and euhedral magnetite grains. Authigenic Fe(III) oxides increased in concentration with decreasing particle size through the silt and clay fraction. Chemical extraction and Mössbauer analysis indicated that this was a ferrihydrite like-phase. Quantitative mineralogic and Fe(II/III) ratio comparisons between the pristine and contaminated sediments were not possible because of textural differences. However, comparisons between the texturally-similar source (where bioavailable Fe(III) had been exhausted) and Fe(III) reducing zone sediments (where bioavailable Fe(III) remained) indicated that dispersed detrital, crystalline Fe(III) oxides and a portion of the authigenic, poorly crystalline Fe(III) oxide fraction had been depleted from the source zone sediment by microbiologic activity. Little or no effect of microbiologic activity was observed on silicate Fe(III). The presence of residual “ferrihydrite” in the most bioreduced, anoxic plume sediment (source) implied that a portion of the authigenic Fe(III) oxides were biologically inaccessible in weathered, lithic fragment interiors. Little evidence was found for the modern biogenesis of authigenic ferrous-containing mineral phases, perhaps with the exception of thin siderite or ferroan calcite surface precipitates on carbonate lithic fragments within source zone sediments.
Steinhoff, Bernhard J; Somerville, Ernest R; Van Paesschen, Wim; Ryvlin, Philippe; Schelstraete, Isabelle
2007-08-01
The Safety of Keppra as Adjunctive Therapy in Epilepsy (SKATE) study aimed to evaluate the safety and efficacy of levetiracetam (Keppra, LEV) as add-on therapy for refractory partial seizures in clinical practice. This Phase IV, 16-week, open-label study recruited patients > or =16-year old with treatment-resistant partial seizures. LEV (1000 mg/day) was added to a stable concomitant antiepileptic drug regimen. LEV dosage was adjusted based on seizure control and tolerability to a maximum of 3000 mg/day. 1541 patients (intent-to-treat population) were recruited including 1346 (87.3%) who completed the study and 77.0% who declared further continuing on LEV after the trial. Overall, 50.5% of patients reported at least one adverse event that was considered related to LEV treatment. The most frequently reported drug-related adverse events were mild-to-moderate somnolence, fatigue, dizziness and headache. Serious adverse events considered related to LEV occurred in 1.0% of patients. 7.5% of patients reported adverse events as the most important reason for study drug discontinuation. The median reduction from baseline in the frequency of all seizures was 50.2%; 15.8% of patients were seizure free; 50.1% had seizure frequency reduction of > or =50%. At the end of the study, 60.4% of patients were considered by the investigator to show marked or moderate improvement. There was a significant improvement in health-related quality of life as assessed with the QOLIE-10-P (total score increasing from 55.6 to 61.6; p<0.001). This community-based study suggests that LEV is well tolerated and effective as add-on therapy for refractory partial seizures in adults. These data provide supportive evidence for the safety and efficacy of LEV demonstrated in the pivotal Phase III placebo-controlled studies.
Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse
2015-01-01
In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4(+) T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158.
Thermal neutron detector and gamma-ray spectrometer utilizing a single material
Stowe, Ashley; Burger, Arnold; Lukosi, Eric
2017-05-02
A combined thermal neutron detector and gamma-ray spectrometer system, including: a detection medium including a lithium chalcopyrite crystal operable for detecting thermal neutrons in a semiconductor mode and gamma-rays in a scintillator mode; and a photodetector coupled to the detection medium also operable for detecting the gamma rays. Optionally, the detection medium includes a .sup.6LiInSe.sub.2 crystal. Optionally, the detection medium comprises a compound formed by the process of: melting a Group III element; adding a Group I element to the melted Group III element at a rate that allows the Group I and Group III elements to react thereby providing a single phase I-III compound; and adding a Group VI element to the single phase I-III compound and heating; wherein the Group I element includes lithium.
NASA Astrophysics Data System (ADS)
Muehe, E. M.; Adaktylou, I. J.; Obst, M.; Schröder, C.; Behrens, S.; Hitchcock, A. P.; Tylsizczak, T.; Michel, F. M.; Krämer, U.; Kappler, A.
2014-12-01
Agricultural soils are increasingly burdened with heavy metals such as Cd from industrial sources and impure fertilizers. Metal contaminants enter the food chain via plant uptake from soil and negatively affect human and environmental health. New remediation approaches are needed to lower soil metal contents. To apply these remediation techniques successfully, it is necessary to understand how soil microbes and minerals interact with toxic metals. Here we show that microbial Fe(III) reduction initially mobilizes Cd before its immobilization under anoxic conditions. To study how microbial Fe(III) reduction influences Cd mobility, we isolated a new Cd-tolerant, Fe(III)-reducing Geobacter sp. from a heavily Cd-contaminated soil. In lab experiments, this Geobacter strain first mobilized Cd from Cd-loaded Fe(III) hydroxides followed by precipitation of Cd-bearing mineral phases. Using Mössbauer spectroscopy and scanning electron microscopy, the original and newly formed Cd-containing Fe(II) and Fe(III) mineral phases, including Cd-Fe-carbonates, Fe-phosphates and Fe-(oxyhydr)oxides, were identified and characterized. Using energy-dispersive X-ray spectroscopy and synchrotron-based scanning transmission X-ray microscopy, Cd was mapped in the Fe(II) mineral aggregates formed during microbial Fe(III) reduction. Microbial Fe(III) reduction mobilizes Cd prior to its precipitation in Cd-bearing mineral phases. The mobilized Cd could be taken up by phytoremediating plants, resulting in a net removal of Cd from contaminated sites. Alternatively, Cd precipitation could reduce Cd bioavailability in the environment, causing less toxic effects to crops and soil microbiota. However, the stability and thus bioavailability of these newly formed Fe-Cd mineral phases needs to be assessed thoroughly. Whether phytoremediation or immobilization of Cd in a mineral with reduced Cd bioavailability are feasible mechanisms to reduce toxic effects of Cd in the environment remains to be determined.
Chronic Health Outcomes and Prescription Drug Copayments in Medicaid.
Kostova, Deliana; Fox, Jared
2017-05-01
Prescription drug copayments and cost-sharing have been linked to reductions in prescription drug use and expenditures. However, little is known about their effect on specific health outcomes. To evaluate the association between prescription drug copayments and uncontrolled hypertension, uncontrolled hypercholesterolemia, and prescription drug utilization among Medicaid beneficiaries with these conditions. Select adults aged 20-64 from NHANES 1999-2012 in 18 states. Uncontrolled hypertension, uncontrolled hypercholesterolemia, and taking medication for each of these conditions. A differencing regression model was used to evaluate health outcomes among Medicaid beneficiaries in 4 states that introduced copayments during the study period, relative to 2 comparison groups-Medicaid beneficiaries in 14 states unaffected by shifts in copayment policy, and a within-state counterfactual group of low-income adults not on Medicaid, while controlling for individual demographic factors and unobserved state-level characteristics. Although uncontrolled hypertension and hypercholesterolemia declined among all low-income persons during the study period, the trend was less pronounced in Medicaid beneficiaries affected by copayments. After netting out concurrent trends in health outcomes of low-income persons unaffected by Medicaid copayment changes, we estimated that introduction of drug copayments in Medicaid was associated with an average rise in uncontrolled hypertension and uncontrolled hypercholesterolemia of 7.7 and 13.2 percentage points, respectively, and with reduced drug utilization for hypercholesterolemia. As Medicaid programs change in the years following the Affordable Care Act, prescription drug copayments may play a role as a lever for controlling hypertension and hypercholesterolemia at the population level.
Bellmunt, J; Kerst, J M; Vázquez, F; Morales-Barrera, R; Grande, E; Medina, A; González Graguera, M B; Rubio, G; Anido, U; Fernández Calvo, O; González-Billalabeitia, E; Van den Eertwegh, A J M; Pujol, E; Perez-Gracia, J L; González Larriba, J L; Collado, R; Los, M; Maciá, S; De Wit, R
2017-07-01
Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second lines. Vinflunine is the only treatment approved in this setting by the European Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy versus vinflunine. This is a multicenter, randomized, open-label, phase II/III study, following a Simon's optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II. ECOG Performance Status, anaemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and overall survival for the phase III. Seventy patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and six patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median progression-free survival for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P = 0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found favouring vinflunine (median 7.6 versus 5.5 months). Grade 3- to 4-related adverse events were seen in 41% patients with no difference between the two arms. This phase II/III second line bladder study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those known previously. NCT01830231. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Hu, Qiufen; Chen, Xiubin; Yang, Xiangjun; Huang, Zhangjie; Chen, Jing; Yang, Guangyu
2006-04-01
A new chromogenic reagent, 5-(2-hydroxy-5-nitrophenylazo)thiorhodanine (HNATR) was synthesized. A highly sensitive, selective and rapid method for the determination microg l(-1) level of Au(III) based on the rapid reaction of Au(III) with HNATR and the solid phase extraction of the colored complex with a reversed phase polymer-based C(18) cartridge have been developed. The HNATR reacted with Au(III) to form a red complex of a molar ratio 1:2 (Au(III) to HNATR) in the presence of 0.05 - 0.5 mol l(-1) of phosphoric acid solution and emulsifier-OP medium. This complex was enriched by the solid phase extraction with a polymer-based C(18) cartridge. The enrichment factor of 100 was achieved. The molar absorptivity of the complex is 1.37 x 10(5) l mol(-1) cm(-1) at 520 nm in the measured solution. The system obeys Beer's law in the range of 0.01 - 3 microg ml(-1). The relative standard deviation for eleven replicates sample of 0.5 microg l(-1) level is 2.18%. The detection limit, based on the three times of standard deviation is 0.02 microg l(-1) in the original sample. This method was applied to the determination of gold in water and ore with good results.
Preparation of III-V semiconductor nanocrystals
Alivisatos, A. Paul; Olshavsky, Michael A.
1996-01-01
Nanometer-scale crystals of III-V semiconductors are disclosed, They are prepared by reacting a group III metal source with a group V anion source in a liquid phase at elevated temperature in the presence of a crystallite growth terminator such as pyridine or quinoline.
... strengthening exercise"). Resume low-impact aerobic training; maintain general fitness. III Phase III treatment focuses on restoring ankle proprioception (balance and position awareness) as well as agility and ...
Deloose, E; Janssen, P; Lannoo, M; Van der Schueren, B; Depoortere, I; Tack, J
2016-07-01
Motilin-induced phase III contractions of the migrating motor complex (MMC) signal hunger in healthy volunteers. The current aim was to study the role of motilin as a hunger-inducing factor in obese patients and to evaluate the effect of Roux-en-Y gastric bypass (RYGB) surgery on plasma motilin levels and hunger scores. Motilin and ghrelin plasma levels were determined during a complete MMC cycle in controls and obese patients selected for RYGB before, 6 months and 1 year after surgery. 20 min after the end of the second phase III, obese patients received an intravenous infusion of 40 mg erythromycin. Hunger was scored every 5 min. Hedonic hunger was assessed in obese patients with the Power of Food Scale questionnaire. Obesity caused a switch in the origin of phase III from antrum to duodenum. Obese patients had significantly higher motilin levels compared with controls during the MMC but tended to lack the motilin peak prior to phase III necessary to trigger hunger. Hunger scores during phase III were significantly lower in obese patients, but could be restored to control levels through the administration of a low dose of the motilin agonist, erythromycin. After RYGB surgery motilin, but not ghrelin, levels decreased in parallel with hedonic hunger scores. Motilin may be an important regulator involved in the pathogenesis of obesity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Rojas-Anaya, Hector; Skogen, Karoline; Miles, Kenneth Alan
2012-06-01
To identify factors that influence the use of PET in phase III oncology trials in the UK by evaluating stakeholder perspectives. A wide range of UK PET research stakeholders with a potential interest in the use of PET in phase III trials were identified and invited to participate. These UK PET research stakeholders were consulted using a semistructured questionnaire on their personal experience with and involvement in PET research, the role of PET in phase III oncology clinical trials and on the promotion of UK PET research and unmet clinical needs in oncology. Responses were analysed quantitatively and by qualitative content analysis of free-text responses. A total of 118 responses were received from a wide range of stakeholders representing several professional groups and working environments. Of these respondents, 49 (42%) were using PET in their research. There was the general perception that using PET in clinical research is beneficial in oncology. The two major barriers identified were poor availability of PET and perceived difficulties in funding of excess treatment costs (75% of respondents). Other factors included limited coverage of PET in training, uncertainty about developing imaging protocols or the status of tracers other than 18F-fluorodeoxyglucose, and low awareness of the role of PET in patient selection for therapeutic trials. Patient concerns about radiation were not perceived as a research barrier. Interventions that improve the availability and funding pathways for PET research scans and that increase researcher awareness could help promote the use of PET for phase III oncology trials in the UK.
Objectives and methodology of BIOBADASER phase iii.
Sanchez-Piedra, Carlos; Hernández Miguel, M Victoria; Manero, Javier; Roselló, Rosa; Sánchez-Costa, Jesús Tomás; Rodríguez-Lozano, Carlos; Campos, Cristina; Cuende, Eduardo; Fernández-Lopez, Jesús Carlos; Bustabad, Sagrario; Martín Domenech, Raquel; Pérez-Pampín, Eva; Del Pino-Montes, Javier; Millan-Arcineas, Ana Milena; Díaz-González, Federico; Gómez-Reino, Juan Jesús
2017-09-18
Describe the objectives, methods and results of the first year of the new version of the Spanish registry of adverse events involving biological therapies and synthetic drugs with an identifiable target in rheumatic diseases (BIOBADASER III). Multicenter prospective registry of patients with rheumatic inflammatory diseases being treated with biological drugs or synthetic drugs with an identifiable target in rheumatology departments in Spain. The main objective of BIOBADASER Phase III is the registry and analysis of adverse events; moreover, a secondary objective was added consisting of assessing the effectiveness by means of the registry of activity indexes. Patients in the registry are evaluated at least once every year and whenever they experience an adverse event or a change in treatment. The collection of data for phase iii began on 17 December 2015. During the first year, 35 centers participated. The number of patients included in this new phase in December 2016 was 2,664. The mean age was 53.7 years and the median duration of treatment was 8.1 years. In all, 40.4% of the patients were diagnosed with rheumatoid arthritis. The most frequent adverse events were infections and infestations. BIOBADASER Phase III has been launched to adapt to a changing pharmacological environment, with the introduction of biosimilars and small molecules in the treatment of rheumatic diseases. This new stage is adapted to the changes in the reporting of adverse events and now includes information related to activity scores. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.
Assessment of asthma control: the SERENA study.
Corrado, Antonio; Renda, Teresa; Polese, Guido; Rossi, Andrea
2013-11-01
Several studies suggest that many asthmatic subjects have uncontrolled asthma. The control of asthma is now considered the major goal of therapy. to ascertain the level of asthma control, by Asthma Control Test (ACT), in "real-life" clinical practice and the potential risk factors for uncontrolled disease in patients treated with inhaled corticosteroids (ICS) and long-acting beta-adrenergic agonists (LABA). SERENA is a multi-centre, cross-sectional, 6-month observational, non-interventional study carried out in 16 Pulmonary Units in Italy. Asthmatic outpatients aged over 18, undergoing treatment with ICS at medium-high daily doses associated with LABA, were enrolled. The patients were divided in 3 subgroups according to the level of asthma control by ACT score (25:controlled; 20-24:partly controlled; <20: uncontrolled). Out of a total of 548 patients, 396 met the inclusion criteria. Only 9.1% of patients had asthma controlled, while partly controlled and uncontrolled asthma accounted for 39.6% and 51.3% respectively. The mean age was 54.5 ± 15.8 and the mean duration of asthma was 16.1 ± 14.1 years. There were more females than males (63% vs 37%) and females had highest prevalence of uncontrolled asthma (63.1%). The mean values of FEV1% predicted were lower in the uncontrolled group (p < 0.001). The percentage of patients with at least 1 exacerbation, unscheduled visit and/or admissions was lower in controlled (22.2%, 8.3%, 8.3%) than in partly controlled (50%, 38.6%, 9.2%) and uncontrolled (83.2%, 66.2%, 27.8%) groups (p < 0.0001). The multivariate ordinal logistic regression analysis identified female sex, FEV1 and exacerbations as the strongest independent factors associated with the uncontrolled disease. This study highlights the importance in clinical practice of a periodic assessment by a validated asthma control instrument and exacerbations/health care contacts during previous year. Clinicians should be aware that a significant proportion of patients can have uncontrolled asthma, despite regular pharmacological treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.
ERIC Educational Resources Information Center
Carr, Dorothy B.; Avance, Lyonel D.
Presented is a sequenced instructional program in physical education which constitutes the third of a three-phase, 4-year project, funded by Title III, for handicapped children, preschool through high school levels, in the Los Angeles Unified School District. Described are the project setting and the following accomplishments: a curriculum guide…
Effects of PECS Phase III Application Training on Independent Mands in Young Children with Autism
ERIC Educational Resources Information Center
Love, Jessica June
2013-01-01
The purpose of this study was to examine the effects of PECS phase III application training on independent mands in young children with autism. Participants were five children with autism ranging from ages 2 to 4 years old. A multiple baseline across participants was used to evaluate acquisition of independent correct mands across baseline and…
About the Lung and Upper Aerodigestive Cancer Research Group | Division of Cancer Prevention
The Lung and Upper Aerodigestive Cancer Research Group conducts and supports research on the prevention and early detection of lung and head and neck cancers, as well as new approaches to clinical prevention studies including cancer immunoprevention.Phase 0/I/II Cancer Prevention Clinical Trials ProgramThe group jointly administers the Phase 0/I/II Cancer Prevention Clinical
Pressure effect on the long-range order in CeB6
NASA Astrophysics Data System (ADS)
Sera, M.; Ikeda, S.; Iwakubo, H.; Uwatoko, Y.; Hane, S.; Kosaka, M.; Kunii, S.
2006-08-01
The pressure effect of CeB6 was investigated. The pressure dependence of the Néel temperature, TN and the critical field from the antiferro-magnetic phase III to antiferro-quadrupolar phase II, HcIII-II of CeB6 exhibits the unusual pressure dependence that the suppression rate of HcIII-II is much larger than that of TN. In order to explain this unusual result, we have performed the mean field calculation for the 4-sublattice model assuming that the pressure dependence of TN, the antiferro-octupolar and quadrupolar temperatures, Toct and TQ as follows; dTN/dP<0, dToct/dP>dTQ/dP>0 and could explain the unusual pressure dependence of TN and HcIII-II.
Preparation of III-V semiconductor nanocrystals
Alivisatos, A.P.; Olshavsky, M.A.
1996-04-09
Nanometer-scale crystals of III-V semiconductors are disclosed. They are prepared by reacting a group III metal source with a group V anion source in a liquid phase at elevated temperature in the presence of a crystallite growth terminator such as pyridine or quinoline. 4 figs.
Zhang, Liuyang; Luo, Jinju; Shen, Xinyu; Li, Chunya; Wang, Xian; Nie, Bei; Fang, Huaifang
2018-05-10
Direct detecting of trace amount Al(III) in aqueous solution by stripping voltammetry is often frustrated by its irreversible reduction, resided at −1.75 V (vs. Ag/AgCl reference), which is in a proximal potential of proton reduction. Here, we described an electroanalytical approach, combined with liquid phase microextraction (LPME) using ionic liquid (IL), to quantitatively assess trace amount aluminum in environmental samples. The Al(III) was caged by 8-hydroxyquinoline, forming a superb hydrophobic metal⁻chelate, which sequentially transfers and concentrates in the bottom layer of IL-phase during LPME. The preconcentrated Al(III) was further analyzed by a square-wave anodic stripping voltammetry (SW-ASV). The resulting Al-deposited electrodes were characterized by scanning electron microscopy and powder X-ray diffraction, showing the intriguing amorphous nanostructures. The method developed provides a linear calibration ranging from 0.1 to 1.2 ng L −1 with a correlation coefficient of 0.9978. The LOD attains as low as 1 pmol L −1 , which reaches the lowest report for Al(III) detection using electroanalytical techniques. The applicable methodology was implemented for monitoring Al(III) in commercial distilled water.
NASA Astrophysics Data System (ADS)
Kim, Jeomoh; Ji, Mi-Hee; Detchprohm, Theeradetch; Dupuis, Russell D.; Fischer, Alec M.; Ponce, Fernando A.; Ryou, Jae-Hyun
2015-09-01
Unintentional incorporation of gallium (Ga) in InAlN layers grown with different molar flow rates of Group-III precursors by metalorganic chemical vapor deposition has been experimentally investigated. The Ga mole fraction in the InAl(Ga)N layer was increased significantly with the trimethylindium (TMIn) flow rate, while the trimethylaluminum flow rate controls the Al mole fraction. The evaporation of metallic Ga from the liquid phase eutectic system between the pyrolized In from injected TMIn and pre-deposited metallic Ga was responsible for the Ga auto-incorporation into the InAl(Ga)N layer. The theoretical calculation on the equilibrium vapor pressure of liquid phase Ga and the effective partial pressure of Group-III precursors based on growth parameters used in this study confirms the influence of Group-III precursors on Ga auto-incorporation. More Ga atoms can be evaporated from the liquid phase Ga on the surrounding surfaces in the growth chamber and then significant Ga auto-incorporation can occur due to the high equilibrium vapor pressure of Ga comparable to effective partial pressure of input Group-III precursors during the growth of InAl(Ga)N layer.
Exploring the Photoreduction of Au(III) Complexes in the Gas-Phase
NASA Astrophysics Data System (ADS)
Marcum, Jesse C.; Kaufman, Sydney H.; Weber, J. Mathias
2010-06-01
We have used photodissociation spectroscopy to probe the electronic structure and photoreduction of Au(III) in gas-phase complexes containing Cl- and OH-. The gas-phase electronic spectrum of [AuCl_4]- closely resembles the aqueous solution spectrum, showing a lack of strong solvatochromic shifts. Substitution of Cl- ligands with OH- results in a strong blue shift, in agreement with ligand-field theory. Upon excitation, [AuCl_4]- can dissociate by loss of either one or two neutral Cl atoms, resulting in the reduction of gold from Au(III) to Au(II) and Au(I) respectively. The hydroxide substituted complex, [AuCl_2(OH)_2]-, demonstrates similar behavior but the only observable fragment channel is the loss of two neutral OH ligands, leading only to Au(I).
NASA Astrophysics Data System (ADS)
Ariga, Katsuhiko; Aono, Masakazu
2016-11-01
The construction of functional systems with nanosized parts would not possible by simple technology (nanotechnology). It can be handled by certain kinds of more sophisticated carpenter work or artistic architectonics (nanoarchitectonics). However, architecting materials in the nanoscale is not very simple because of various unexpected and uncontrollable thermal/statistical fluctuations and mutual interactions. The latter factors inevitably disturb the interactions between component building blocks. Therefore, several techniques and actions, including the regulation of atomic/molecular manipulation, molecular modification by organic chemistry, control of physicochemical interactions, self-assembly/organization, and application of external physical stimuli, must be well combined. This short review describes the historical backgrounds and essences of nanoarchitectonics, followed by a brief introduction of recent examples related to nanoarchitectonics. These examples are categorized in accordance with their physical usages: (i) atom/molecule control; (ii) devices and sensors; (iii) the other applications based on interfacial nanoarchitectonics.
Polymerase III transcription factor B activity is reduced in extracts of growth-restricted cells.
Tower, J; Sollner-Webb, B
1988-01-01
Extracts of cells that are down-regulated for transcription by RNA polymerase I and RNA polymerase III exhibit a reduced in vitro transcriptional capacity. We have recently demonstrated that the down-regulation of polymerase I transcription in extracts of cycloheximide-treated and stationary-phase cells results from a lack of an activated subform of RNA polymerase I which is essential for rDNA transcription. To examine whether polymerase III transcriptional down-regulation occurs by a similar mechanism, the polymerase III transcription factors were isolated and added singly and in pairs to control cell extracts and to extracts of cells that had reduced polymerase III transcriptional activity due to cycloheximide treatment or growth into stationary phase. These down-regulations result from a specific reduction in TFIIIB; TFIIIC and polymerase III activities remain relatively constant. Thus, although transcription by both polymerase III and polymerase I is substantially decreased in extracts of growth-arrested cells, this regulation is brought about by reduction of different kinds of activities: a component of the polymerase III stable transcription complex in the former case and the activated subform of RNA polymerase I in the latter. Images PMID:3352599
NASA Astrophysics Data System (ADS)
Zhang, Li; Chang, Xijun; Li, Zhenhua; He, Qun
2010-02-01
A new selective solid-phase extractant using activated carbon as matrix which was purified, oxidized and modified by triethylenetetramine (AC-TETA) was prepared and characterized by FT-IR spectroscopy. At pH 4, quantitative extraction of trace Cr(III), Fe(III) and Pb(II) was obtained and determined by inductively coupled plasma optical emission spectrometry (ICP-OES). Complete elution of the adsorbed metal ions from the sorbent surface was carried out using 0.5 mol L -1 HCl. The maximum static adsorption capacity of sorbent for Cr(III), Fe(III) and Pb(II) was 34.6, 36.5 and 51.9 mg g -1, respectively. The time of quantitative adsorption was less than 2 min. The detection limits of the method was found to be 0.71, 0.35 and 0.45 ng mL -1 for Cr(III), Fe(III) and Pb(II), and the relative standard deviation (RSD) was 3.7%, 2.2% and 2.5%, respectively. Moreover, the method was free from interference with common coexiting ions. The method was also successfully applied to the preconcentration of trace Cr(III), Fe(III) and Pb(II) in synthetic samples and a real sample with satisfactory results.
Saladino, Jessica; Liu, Mian; Live, David; Sharp, Joshua S.
2009-01-01
Hydroxyl radical footprinting is a technique for studying protein structure and binding that entails oxidizing a protein system of interest with diffusing hydroxyl radicals, and then measuring the amount of oxidation of each amino acid. One important issue in hydroxyl radical footprinting is limiting amino acid oxidation by secondary oxidants to prevent uncontrolled oxidation which can cause amino acids to appear more solvent accessible than they really are. Previous work suggested that hydrogen peroxide was the major secondary oxidant of concern in hydroxyl radical footprinting experiments; however, even after elimination of all hydrogen peroxide, some secondary oxidation was still detected. Evidence is presented for the formation of peptidyl hydroperoxides as the most abundant product upon oxidation of aliphatic amino acids. Both reverse phase liquid chromatography and catalase treatment were shown to be ineffective at eliminating peptidyl hydroperoxides. The ability of these peptidyl hydroperoxides to directly oxidize methionine is demonstrated, suggesting the value of methionine amide as an in situ protectant. Hydroxyl radical footprinting protocols require the use of an organic sulfide or similar peroxide scavenger in addition to removal of hydrogen peroxide in order to successfully eradicate all secondary oxidizing species and prevent uncontrolled oxidation of sulfur-containing residues. PMID:19278868
A study of solar preflare activity using two-dimensional radio and SMM-XRP observations
NASA Technical Reports Server (NTRS)
Kundu, M. R.; Gopalswamy, N.; Saba, J. L. R.; Schmelz, J. T. S.; Strong, K. T.
1987-01-01
A study of type III activity at meter-decameter wavelengths in the preflare phase of the February 3, 1986 flare is presented, using data obtained with the Clark Lake Multifrequency Radioheliograph. This activity is compared with similar type III burst activity during the impulsive phase, and it is found that there is a displacement of burst sources between the onset and end times of the activity. A comparison of this displacement at three frequencies suggests that the type III emitting electrons gain access progressively to diverging and different field lines relative to the initial field lines. The energetics of the type III emitting electrons are inferred from observations and compared with those of the associated hard X-ray emitting electrons. The soft X-ray data from SMM-XRP show enhanced emission measure, density, and temperature in the region associated with the preflare type III activity.
A study of solar preflare activity using two-dimensional radio and SMM-XRP observations
NASA Astrophysics Data System (ADS)
Kundu, M. R.; Gopalswamy, N.; Saba, J. L. R.; Schmelz, J. T. S.; Strong, K. T.
1987-09-01
The authors present a study of type III activity at meter-decameter wavelengths in the preflare phase of the 1986 February 3 flare using data obtained with the Clark Lake Multifrequency Radioheliograph. They compare this activity with similar type III burst activity during the impulsive phase and find that there is a displacement of burst sources between the onset and end times of the activity. A comparison of this displacement at three frequencies suggests that the type III emitting electrons gain access progressively to diverging and different field lines relative to the initial field lines. The energetics of the type III emitting electrons are inferred from observations and compared with those of the associated hard X-ray emitting electrons. The soft X-ray data from SMM-XRP shows enhanced emission measure, density and temperature in the region associated with the preflare type III activity.
DOT National Transportation Integrated Search
1966-12-01
This report describes a laboratory research program on the durability of lightweight concrete. Two phases of a three phase study are covered by this report, while the remaining phase is still under study. The two phases being reported are Phase II - ...
Loss of bladder control; Uncontrollable urination; Urination - uncontrollable; Incontinence - urinary ... have diabetes, keep your blood sugar under good control. For urine leaks, wear absorbent pads or undergarments. ...
... movements; Body movements - uncontrollable; Dyskinesia; Athetosis; Myoclonus; Ballismus Images Central nervous system and peripheral nervous system References Jankovic J, Lang AE. Diagnosis and assessment of Parkinson disease ...
Orbital phase dependent IUE spectra of the nova like binary II Arietis
NASA Technical Reports Server (NTRS)
Guinan, E. F.; Sion, E. M.
1981-01-01
Nine low dispersion IUE spectra of the nova like binary TT Ari over its 3h17m orbital period were obtained. Four short wave spectra and five long wave spectra exhibit marked changes in line strength and continuum shape with orbital phase. The short wave spectra show the presence in absorption of C III, Lyman alpha, SiIII, NV, SiIV, CIV, HeII, AlIII, and NIV. The CIV shows a P Cygni profile on two of the spectra. Implications of these spectra for the nature of nova like variables are discussed.
Uncontrolled eating in adolescents: The role of impulsivity and automatic approach bias for food.
Booth, Charlotte; Spronk, Desiree; Grol, Maud; Fox, Elaine
2018-01-01
Obesity is a global problem reaching epidemic proportions and can be explained by unhealthy eating and sedentary lifestyles. Understanding the psychological processes underlying unhealthy eating behaviour is crucial for the development of effective obesity prevention programmes. Dual-process models implicate the interplay between impaired cognitive control and enhanced automatic responsivity to rewarding food cues as key risk factors. The current study assessed the influence of four different components of trait impulsivity (reflecting impaired cognitive control) and automatic approach bias for food (reflecting automatic responsivity to food) on uncontrolled eating in a large sample (N = 504) of young adolescents. Of the four impulsivity factors, negative urgency was found to be the strongest predictor of uncontrolled eating. Interestingly, we found that lack of premeditation was a key risk factor for uncontrolled eating, but only when approach bias for food was high, supporting a dual-process model. Lack of perseverance showed a similar interactive pattern to a lesser degree and sensation-seeking did not predict uncontrolled eating. Together, our results show that distinct components of trait impulsivity are differentially associated with uncontrolled eating behaviour in adolescents, and that automatic processing of food cues may be an important factor in modulating this relationship. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Turner, Sally Ann; Luszczynska, Aleksandra; Warner, Lisa; Schwarzer, Ralf
2010-02-01
The study tested the effects of positive mood enhancement on chocolate chip cookie consumption in the context of emotional and uncontrolled eating styles. The relationship between emotional eating style and chocolate chip cookie intake was assumed to be mediated by uncontrolled eating style. Further, it was hypothesized that the effectiveness of the positive mood enhancement may be more salient among those who have effective control of their eating. In this experimental study, respondents (N=106, 70% women, aged 16-45 years old) were assigned by means of cluster randomization to the control or positive mood enhancement condition (a comedy movie clip). Compared to the control condition, positive mood enhancement resulted in consuming on average 53.86 kcal less. Relationships between emotional eating style and cookie intake were mediated by uncontrolled eating. Moderated mediation analysis indicated that the effect of a mediator (uncontrolled eating) on cookie intake was moderated by the group assignment. Positive mood enhancement resulted in eating on average 3.3 cookies less among individuals with a more controlled eating style. By contrast, among those who presented uncontrolled eating, positive mood enhancement led to consuming an average of 1.7 cookies more. 2009 Elsevier Ltd. All rights reserved.
Mirrione, Martine M; Schulz, Daniela; Lapidus, Kyle A B; Zhang, Samuel; Goodman, Wayne; Henn, Fritz A
2014-01-01
Uncontrollable stress can have a profound effect on an organism's ability to respond effectively to future stressful situations. Behavior subsequent to uncontrollable stress can vary greatly between individuals, falling on a spectrum between healthy resilience and maladaptive learned helplessness. It is unclear whether dysfunctional brain activity during uncontrollable stress is associated with vulnerability to learned helplessness; therefore, we measured metabolic activity during uncontrollable stress that correlated with ensuing inability to escape future stressors. We took advantage of small animal positron emission tomography (PET) and 2-deoxy-2[(18)F]fluoro-D-glucose ((18)FDG) to probe in vivo metabolic activity in wild type Sprague Dawley rats during uncontrollable, inescapable, unpredictable foot-shock stress, and subsequently tested the animals response to controllable, escapable, predictable foot-shock stress. When we correlated metabolic activity during the uncontrollable stress with consequent behavioral outcomes, we found that the degree to which animals failed to escape the foot-shock correlated with increased metabolic activity in the lateral septum and habenula. When used a seed region, metabolic activity in the habenula correlated with activity in the lateral septum, hypothalamus, medial thalamus, mammillary nuclei, ventral tegmental area, central gray, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and rostromedial tegmental nucleus, caudal linear raphe, and subiculum transition area. Furthermore, the lateral septum correlated with metabolic activity in the preoptic area, medial thalamus, habenula, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and caudal linear raphe. Together, our data suggest a group of brain regions involved in sensitivity to uncontrollable stress involving the lateral septum and habenula.
Mirrione, Martine M.; Schulz, Daniela; Lapidus, Kyle A. B.; Zhang, Samuel; Goodman, Wayne; Henn, Fritz A.
2013-01-01
Uncontrollable stress can have a profound effect on an organism's ability to respond effectively to future stressful situations. Behavior subsequent to uncontrollable stress can vary greatly between individuals, falling on a spectrum between healthy resilience and maladaptive learned helplessness. It is unclear whether dysfunctional brain activity during uncontrollable stress is associated with vulnerability to learned helplessness; therefore, we measured metabolic activity during uncontrollable stress that correlated with ensuing inability to escape future stressors. We took advantage of small animal positron emission tomography (PET) and 2-deoxy-2[18F]fluoro-D-glucose (18FDG) to probe in vivo metabolic activity in wild type Sprague Dawley rats during uncontrollable, inescapable, unpredictable foot-shock stress, and subsequently tested the animals response to controllable, escapable, predictable foot-shock stress. When we correlated metabolic activity during the uncontrollable stress with consequent behavioral outcomes, we found that the degree to which animals failed to escape the foot-shock correlated with increased metabolic activity in the lateral septum and habenula. When used a seed region, metabolic activity in the habenula correlated with activity in the lateral septum, hypothalamus, medial thalamus, mammillary nuclei, ventral tegmental area, central gray, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and rostromedial tegmental nucleus, caudal linear raphe, and subiculum transition area. Furthermore, the lateral septum correlated with metabolic activity in the preoptic area, medial thalamus, habenula, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and caudal linear raphe. Together, our data suggest a group of brain regions involved in sensitivity to uncontrollable stress involving the lateral septum and habenula. PMID:24550809
Bilastine: in allergic rhinitis and urticaria.
Carter, Natalie J
2012-06-18
Bilastine is an orally administered, second-generation antihistamine used in the symptomatic treatment of seasonal or perennial allergic rhinoconjunctivitis and urticaria. In two well designed phase III trials, 14 days' treatment with bilastine was associated with a significantly lower area under the effect curve (AUEC) for the reflective total symptom score (TSS) than placebo in patients with symptomatic seasonal allergic rhinitis. Additionally, reflective nasal symptom scores were significantly lower in bilastine than placebo recipients in patients with a history of seasonal allergic rhinitis who were challenged with grass pollen allergen in a single-centre, phase II study. Neither bilastine nor cetirizine was effective in the treatment of perennial allergic rhinitis with regard to the mean AUEC for reflective TSS in another well designed phase III trial. However, results may have been altered by differences in some baseline characteristics and placebo responses between study countries. In another well designed phase III trial, compared with placebo, bilastine was associated with a significantly greater change from baseline to day 28 in the mean reflective daily urticaria symptom score in patients with chronic urticaria. There were no significant differences in primary endpoint results between bilastine and any of the active comparators used in these trials (i.e. cetirizine, levocetirizine and desloratadine). Bilastine was generally well tolerated, with a tolerability profile that was generally similar to that of the other second-generation antihistamines included in phase III clinical trials.
Studies of phase transitions in the aripiprazole solid dosage form.
Łaszcz, Marta; Witkowska, Anna
2016-01-05
Studies of the phase transitions in an active substance contained in a solid dosage form are very complicated but essential, especially if an active substance is classified as a BCS Class IV drug. The purpose of this work was the development of sensitive methods for the detection of the phase transitions in the aripiprazole tablets containing initially its form III. Aripiprazole exhibits polymorphism and pseudopolymorphism. Powder diffraction, Raman spectroscopy and differential scanning calorimetry methods were developed for the detection of the polymorphic transition between forms III and I as well as the phase transition of form III into aripiprazole monohydrate in tablets. The study involved the initial 10 mg and 30 mg tablets, as well as those stored in Al/Al blisters, a triplex blister pack and HDPE bottles (with and without desiccant) under accelerated and long term conditions. The polymorphic transition was not observed in the initial and stored tablets but it was visible on the DSC curve of the Abilify(®) 10 mg reference tablets. The formation of the monohydrate was observed in the diffractograms and Raman spectra in the tablets stored under accelerated conditions. The monohydrate phase was not detected in the tablets stored in the Al/Al blisters under long term conditions. The results showed that the Al/Al blisters can be recommended as the packaging of the aripiprazole tablets containing form III. Copyright © 2015 Elsevier B.V. All rights reserved.
Lubiprostone: in constipation-predominant irritable bowel syndrome.
Carter, Natalie J; Scott, Lesley J
2009-06-18
Lubiprostone is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of human gastrointestinal epithelial cells, thereby increasing chloride-rich fluid secretion. Although the mechanism is unclear, this may then decrease intestinal transit time, allowing the passage of stool and alleviating symptoms of constipation. Oral lubiprostone was effective in the treatment of patients with constipation-predominant irritable bowel syndrome (IBS-C) in large (n = 193-583) phase II (dose-finding) and phase III randomized, double-blind, placebo-controlled, multicentre trials. The number of patients with IBS-C demonstrating an overall response to treatment (primary endpoint) in the two phase III trials was significantly greater in patients receiving lubiprostone 8 microg twice daily for 3 months than in those receiving placebo. In addition, a randomized, 4-week withdrawal period at the end of one of the phase III trials demonstrated that discontinuation of lubiprostone was not associated with rebound of IBS symptoms. Lubiprostone was generally well tolerated in clinical trials, with the majority of adverse events being of mild to moderate severity. In patients with IBS-C who received lubiprostone 8 microg twice daily, nausea was the most frequently occurring adverse event that was considered possibly or probably treatment related. No serious treatment-related adverse events were reported in a 36-week open-label extension to the phase III trials.
76 FR 33589 - Standards Improvement Project-Phase III
Federal Register 2010, 2011, 2012, 2013, 2014
2011-06-08
... rule: I. Background A. Introduction B. Regulatory History II. Legal Considerations III. Summary and... without diminishing worker protections. B. Regulatory History The Standards Improvement Project (SIP...
Graham, Mark J; Lee, Richard G; Bell, Thomas A; Fu, Wuxia; Mullick, Adam E; Alexander, Veronica J; Singleton, Walter; Viney, Nick; Geary, Richard; Su, John; Baker, Brenda F; Burkey, Jennifer; Crooke, Stanley T; Crooke, Rosanne M
2013-05-24
Elevated plasma triglyceride levels have been recognized as a risk factor for the development of coronary heart disease. Apolipoprotein C-III (apoC-III) represents both an independent risk factor and a key regulatory factor of plasma triglyceride concentrations. Furthermore, elevated apoC-III levels have been associated with metabolic syndrome and type 2 diabetes mellitus. To date, no selective apoC-III therapeutic agent has been evaluated in the clinic. To test the hypothesis that selective inhibition of apoC-III with antisense drugs in preclinical models and in healthy volunteers would reduce plasma apoC-III and triglyceride levels. Rodent- and human-specific second-generation antisense oligonucleotides were identified and evaluated in preclinical models, including rats, mice, human apoC-III transgenic mice, and nonhuman primates. We demonstrated the selective reduction of both apoC-III and triglyceride in all preclinical pharmacological evaluations. We also showed that inhibition of apoC-III was well tolerated and not associated with increased liver triglyceride deposition or hepatotoxicity. A double-blind, placebo-controlled, phase I clinical study was performed in healthy subjects. Administration of the human apoC-III antisense drug resulted in dose-dependent reductions in plasma apoC-III, concomitant lowering of triglyceride levels, and produced no clinically meaningful signals in the safety evaluations. Antisense inhibition of apoC-III in preclinical models and in a phase I clinical trial with healthy subjects produced potent, selective reductions in plasma apoC-III and triglyceride, 2 known risk factors for cardiovascular disease. This compelling pharmacological profile supports further clinical investigations in hypertriglyceridemic subjects.
Brush Day & Night Phase III to Phase IV: ensuring that good oral health habits are sustainable.
Melo, Paulo; Fine, Charlotte; Malone, Sinead; Horn, Virginie
2018-05-01
Over the past 10 years, the FDI-Unilever Brush Day & Night partnership has significantly influenced the life of children worldwide through the implementation of school programmes for oral health education and prevention. This article reports the key facts and outcomes of Phase III of the partnership, and announces the launch of Phase IV. During Phase III, the expert advisors of the Brush Day & Night partnership conducted a longitudinal study to evaluate the impact of the '21 Day' programme in almost 8,000 children in 10 countries. Analysis revealed the effectiveness of the 21 Day programme in sustainably educating children to brush their teeth twice a day, with the greatest impact observed in children aged 7-9 years. With the launch of Phase IV, the Brush Day & Night partnership will continue to deliver its oral health school programme for 7-9 year-old children with a strengthened methodology, including randomized sampling and control groups. The scope of the evaluation will be broadened to include oral health-related quality of life indicators, and monitoring of the oral health knowledge of children's parents/carers. © 2018 FDI World Dental Federation.
Phase I and II feasibility study report for the 300-FF-5 operable unit
DOE Office of Scientific and Technical Information (OSTI.GOV)
NONE
1993-12-31
The purpose of this Phase I/II feasibility study is to assemble and screen a list of alternatives for remediation of the 300-FF-5 operable site on the Hanford Reservation. This screening is based on information gathered in the Phase I Remedial Investigation (RI) and on currently available information on remediation technologies. The alternatives remaining after screening provide a range of response actions for remediation. In addition, key data needs are identified for collection during a Phase II RI (if necessary). This Phase I/II FS represents a primary document as defined by the Tri-Party Agreement, but will be followed by a Phasemore » III FS that will further develop the alternatives and provide a detailed evaluation of them. The following remedial action objectives were identified for the 300-FF-5 operable unit: Limit current human exposure to contaminated groundwater in the unit; Limit discharge of contaminated groundwater to the Columbia River; Reduce contaminant concentrations in groundwater below acceptable levels by the year 2018.« less
Luo, Xiaoping; Hou, Ling; Liang, Li; Dong, Guanping; Shen, Shuixian; Zhao, Zhuhui; Gong, Chun Xiu; Li, Yuchuan; Du, Min-Lian; Su, Zhe; Du, Hongwei; Yan, Chaoying
2017-08-01
We assessed the efficacy and safety of a weekly pegylated human growth hormone (PEG-rhGH) (Jintrolong) vs daily rhGH for children with growth hormone deficiency (GHD). Phase II and III, multicenter, open-label, randomized controlled trials. 108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively. Patients in the phase II study were randomized 1:1:1 to weekly Jintrolong (0.1 mg/kg/week PEG-rhGH complex), weekly Jintrolong (0.2 mg/kg/week PEG-rhGH complex) or daily rhGH (0.25 mg/kg/week) for 25 weeks. Patients in the phase III study were randomized in a 2:1 ratio to weekly Jintrolong (0.2 mg/kg/week) or daily rhGH (0.25 mg/kg/week) for 25 weeks. The primary endpoint for both studies was height velocity (HV) increase at the end of treatment. Other growth-related parameters, safety and compliance were also monitored. The phase II study established the preliminary efficacy, safety and recommended dose of Jintrolong PEG-rhGH. In the phase III study, we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment (from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year) vs daily rhGH (from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year) at the end of treatment ( P < 0.05). Additionally, significantly greater improvement in the height standard deviation scores was associated with Jintrolong throughout the treatment ( P < 0.05). Adverse event rates and treatment compliance were comparable between the two groups. Jintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH. © 2017 The authors.
Hou, Ling; Liang, Li; Dong, Guanping; Shen, Shuixian; Zhao, Zhuhui; Gong, Chun Xiu; Li, Yuchuan; Du, Min-lian; Su, Zhe; Du, Hongwei; Yan, Chaoying
2017-01-01
Objective We assessed the efficacy and safety of a weekly pegylated human growth hormone (PEG-rhGH) (Jintrolong) vs daily rhGH for children with growth hormone deficiency (GHD). Design Phase II and III, multicenter, open-label, randomized controlled trials. Methods 108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively. Patients in the phase II study were randomized 1:1:1 to weekly Jintrolong (0.1 mg/kg/week PEG-rhGH complex), weekly Jintrolong (0.2 mg/kg/week PEG-rhGH complex) or daily rhGH (0.25 mg/kg/week) for 25 weeks. Patients in the phase III study were randomized in a 2:1 ratio to weekly Jintrolong (0.2 mg/kg/week) or daily rhGH (0.25 mg/kg/week) for 25 weeks. The primary endpoint for both studies was height velocity (HV) increase at the end of treatment. Other growth-related parameters, safety and compliance were also monitored. Results The phase II study established the preliminary efficacy, safety and recommended dose of Jintrolong PEG-rhGH. In the phase III study, we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment (from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year) vs daily rhGH (from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year) at the end of treatment (P < 0.05). Additionally, significantly greater improvement in the height standard deviation scores was associated with Jintrolong throughout the treatment (P < 0.05). Adverse event rates and treatment compliance were comparable between the two groups. Conclusion Jintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH. PMID:28566441
Prevention of Posttraumatic Contractures with Ketotifen (PERK)
2017-10-01
opportunity to design a Phase III RCT on the use of ketotifen in post -traumatic joint contractures. The goal is to design and develop the infrastructure to...Research (CIHR) for the Phase III RCT. 2. KEYWORDS Post -traumatic contractures, elbow fractures, randomized clinical trial, multicenter, ketotifen...application to use ketotifen in post -traumatic joint contracture prevention was submitted to the Division of Pulmonary, Allergy, and Rheumatology
ERIC Educational Resources Information Center
Marzano Research Laboratory, 2011
2011-01-01
This document contains the Phase III report from the "What Works in Oklahoma Schools" study. As opposed to describing the findings from the study that was conducted, it provides a tool-kit that can be used by Oklahoma principals and teachers to determine the best courses of action for their schools and classrooms. The tools provided in…
Army Enlisted Personnel Competency Assessment Program: Phase III Pilot Tests
2007-03-01
Officer’s Representatives and Subject Matter POCs: Tonia Heffner and Peter Greenston Contract for Manpower, Personnel, Leader Development, and Training ...3926 March 2007 Army Project Number Personnel Performance 622785A790 and Training Technology Approved for public release; distribution is unlimited. 111...8217 ARMY ENLISTED PERSONNEL COMPETENCY ASSESSMENT PROGRAM: PHASE III PILOT TESTS EXECUTIVE SUMMARY Research Requirement: The Army Training and Leader
Fernandez, Jose R; Allison, David B
2004-04-01
Rimonabant, an antagonist of central cannabinoid type 1 (CB1) receptors, is being developed by Sanofi-Synthélabo for the potential treatment of obesity and as a potential smoking cessation agent. Phase III trials were initiated for obesity in August 2001 and were ongoing in September 2003. By September 2002, the compound had entered phase III trials for smoking cessation, and these trials were ongoing in September 2003.
Ultracompact electro-optic phase modulator based on III-V-on-silicon microdisk resonator.
Lloret, J; Kumar, R; Sales, S; Ramos, F; Morthier, G; Mechet, P; Spuesens, T; Van Thourhout, D; Olivier, N; Fédéli, J-M; Capmany, J
2012-06-15
A novel ultracompact electro-optic phase modulator based on a single 9 μm-diameter III-V microdisk resonator heterogeneously integrated on and coupled to a nanophotonic waveguide is presented. Modulation is enabled by effective index modification through carrier injection. Proof-of-concept implementation involving binary phase shift keying modulation format is assembled. A power imbalance of ∼0.6 dB between both symbols and a modulation rate up to 1.8 Gbps are demonstrated without using any special driving technique.
US-UK Collaboration on Fossil Energy Advanced Materials: Task 1—Steam Oxidation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Holcomb, Gordon R.; Tylczak, Joseph; Carney, Casey
This presentation goes over the following from the US-UK collaboration on Fossil Energy Advanced Materials: Task 1, Steam Oxidation: US-led or co-led deliverables, Phase II products (US), 2011-present, Phase III products, Phase III Plan, an explanation of sCO 2 compared with sH 2O, an explanation of Ni-base Alloys, an explanation of 300 Series (18Cr-8Ni)/E-Brite, an explanation of the typical Microchannel HX Fabrication process, and an explanation of diffusion bonded Ni-base superalloys.
Manufacturing Technology for Apparel Automation. Phase 1, 2 and 3 Activity.
1987-10-15
A189 129 MANUFACTURING TECHNOLOGY FOR APPAREL AUTOMATION PHASE I t/l 2 AND I ACTIVITY(U) NORTH CAROLINA STATE UNIV ATRALEIGH SCHOOL OF TEXTILES E M...34III 1.8 - iai T ON HART St 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 MTC FILE coax Report: NCSU/DLA-87/2 CDRL A004 MANUFACTURING TECHNOLOGY FOR APPAREL...I Report: NCSU/DLA-87/2 CDRL A004 MANUFACTURING TECHNOLOGY FOR APPAREL AUTOMATION Phase I, II and III Activity Edwin M. McPherson North Carolina
Raman spectra of solid benzene under high pressure
NASA Technical Reports Server (NTRS)
Thiery, M.-M.; Kobashi, K.; Spain, I. L.
1985-01-01
Raman spectra of solid benzene have been measured at room temperature up to about 140 kbar, using the diamond anvil cell. Effort has been focused upon the lattice vibration spectra at pressures above that of phase II. It is found that a change in slopes occurs in the frequency-pressure curves at about 40 kbar. Furthermore, a new band appears above 90 kbar. These features probably correspond respectively to the II-III phase transition, which has been reported previously, and a III-IV phase transition, reported here for the first time.
NASA Astrophysics Data System (ADS)
Zhou, S.; Collier, S.; Hee, J.; Wigder, N. L.; Jaffe, D. A.; Zhang, Q.
2014-12-01
This study investigates the physical and chemical characteristics and atmospheric processing of aerosols from uncontrolled forest fires across the Pacific Northwest. The measurements were made at the Mt. Bachelor Observatory (MBO) located at the summit of Mt. Bachelor in central Oregon (43.9794° N, 121.6885° W, 2,763 m asl) in summer 2013 during the DOE sponsored Biomass Burning Observation Project (BBOP) field campaign. We utilized an Aerodyne High Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) coupled with a thermodenuder. Observations during periods affected by biomass burning (BB) pollution showed elevated non-refractory submicron aerosol (NR-PM1) concentration up to 140 μg/m3. NR-PM1 correlated well with PM light scattering (up to ~ 600 Mm-1 at 550 nm) and gas phase CO (up to ~0.4 ppmv). The AMS BB tracer, f60, i.e., fraction of organic signals at m/z = 60, was also enhanced with a maximum of ~ 2%. Organic aerosol (OA) dominated the PM composition in BB plumes (94.1% of the NR-PM1 mass) with an average concentration of 13.9 μg/m3. Three distinctive BBOA factors were identified by Positive Matrix Factorization (PMF): a fresh BBOA-I factor (O/C=0.27, H/C=1.52, f60 = 2.26%) that correlates well with ammonium nitrate; an intermediately oxidized BBOA-II (O/C=0.52, H/C=1.47, f60 = 1.05%), and a highly oxidized BBOA-III (O/C=0.95, H/C=1.02) with a low f60 (< 0.01%) and enhanced tracer ions for carboxylic acids (e.g., CHO2+). During persistent BB plume events from fixed fire sources, fresh BBOA-I initially dominated the OA composition, but decreased as the more oxidized BBOA-II increased while BBOA-III remained unchanged. These events shed light on the chemical transformation of BB aerosol during atmospheric aging. We will examine the enhancement of different BBOA factors relative to CO to investigate secondary organic aerosol (SOA) formation processes in BB plumes.
NASA Astrophysics Data System (ADS)
Zhang, Yan; Chen, Hua-Xin; Duan, Li; Fan, Ji-Bin; Ni, Lei; Ji, Vincent
2018-07-01
Using density-functional perturbation theory, we systematically investigate the Born effective charges and dielectric properties of cubic, tetragonal, monoclinic, ortho-I (Pbca), ortho-II (Pnma) and ortho-III (Pca21) phases of ZrO2. The magnitudes of the Born effective charges of the Zr and oxygen atoms are greater than their nominal ionic valences (+4 for Zr and -2 for oxygen), indicating a strong dynamic charge transfer from Zr atoms to O atoms and a mixed covalent-ionic bonding in six phases of ZrO2. For all six phases of ZrO2, the electronic contributions εij∞ to the static dielectric constant are rather small (range from 5 to 6.5) and neither strongly anisotropic nor strongly dependent on the structural phase, while the ionic contributions εijion to the static dielectric constant are large and not only anisotropic but also dependent on the structural phase. The average dielectric constant εbar0 of the six ZrO2 phases decreases in the sequence of tetragonal, cubic, ortho-II (Pnma), ortho-I (Pbca), ortho-III (Pca21) and monoclinic. So among six phases of ZrO2, the tetragonal and cubic phases are two suitable phases to replace SiO2 as the gate dielectric material in modern integrated-circuit technology. Furthermore, for the tetragonal ZrO2 the best orientation is [100].
Lloret, Juan; Morthier, Geert; Ramos, Francisco; Sales, Salvador; Van Thourhout, Dries; Spuesens, Thijs; Olivier, Nicolas; Fédéli, Jean-Marc; Capmany, José
2012-05-07
A broadband microwave photonic phase shifter based on a single III-V microdisk resonator heterogeneously integrated on and coupled to a nanophotonic silicon-on-insulator waveguide is reported. The phase shift tunability is accomplished by modifying the effective index through carrier injection. A comprehensive semi-analytical model aiming at predicting its behavior is formulated and confirmed by measurements. Quasi-linear and continuously tunable 2π phase shifts at radiofrequencies greater than 18 GHz are experimentally demonstrated. The phase shifter performance is also evaluated when used as a key element in tunable filtering schemes. Distortion-free and wideband filtering responses with a tuning range of ~100% over the free spectral range are obtained.
Martin-Bastida, A; Lao-Kaim, N P; Loane, C; Politis, M; Roussakis, A A; Valle-Guzman, N; Kefalopoulou, Z; Paul-Visse, G; Widner, H; Xing, Y; Schwarz, S T; Auer, D P; Foltynie, T; Barker, R A; Piccini, P
2017-02-01
To determine whether iron deposition in deep brain nuclei assessed using high-pass filtered phase imaging plays a role in motor disease severity in Parkinson's disease (PD). Seventy patients with mild to moderate PD and 20 age- and gender-matched healthy volunteers (HVs) underwent susceptibility-weighted imaging on a 3 T magnetic resonance imaging scanner. Phase shifts (radians) in deep brain nuclei were derived from high-pass filtered phase images and compared between groups. Analysis of clinical laterality and correlations with motor severity (Unified Parkinson's Disease Rating Scale, Part III, UPDRS-III) were performed. Phase shifts (in radians) were compared between HVs and three PD subgroups divided according to UPDRS-III scores using analysis of covariance, adjusting for age and regional area. Parkinson's disease patients had significantly (P < 0.001) higher radians than HVs bilaterally in the putamen, globus pallidus and substantia nigra (SN). The SN contralateral to the most affected side showed higher radians (P < 0.001) compared to the less affected side. SN radians positively correlated with UPDRS-III and bradykinesia-rigidity subscores, but not with tremor subscores. ancova followed by post hoc Bonferroni-adjusted pairwise comparisons revealed that SN radians were significantly greater in the PD subgroup with higher UPDRS-III scores compared to both lowest UPDRS-III PD and HV groups (P < 0.001). Increased nigral iron accumulation in PD appears to be stratified according to disease motor severity and correlates with symptoms related to dopaminergic neurodegeneration. This semi-quantitative in vivo iron assessment could prove useful for objectively monitoring PD progression, especially in clinical trials concerning iron chelation therapies. © 2016 EAN.
Method for the determination of chromium in feed matrix by HPLC.
Umesh, Balakrishnan; Rajendran, Rajendra Moorthy; Manoharan, Muthu Tamizh
2015-11-01
An improved method for the chromatographic separation and determination of chromium (III) and (VI) [ CRIII AND CRVI: ] in mineral mixtures and feed samples has been developed. The method uses precolumn derivatization using ammonium pyrrolidinedithiocarbamate ( APD: ) followed by reversed-phase liquid chromatography to separate the chromium ions. Both Cr(III) and Cr(VI) species are chelated with ammonium pyrrolidinedithiocarbamate prior to separation by mixing with acetonitrile and 0.5 mmol acetate buffer (pH 4.5). Optimum chromatographic separations were obtained with a polymer-based reversed-phase column (Kinetex, 5 μ, 250 × 4.5 mm, Phenomenex, Torrance, CA) and a mobile phase containing acetonitrile and water (7:3). Both Cr(III) and Cr(VI) ion concentrations were directly determined from the corresponding areas in the chromatogram. The effect of analytical parameters, including pH, concentration of ligand, incubation temperature, and mobile phase, was optimized for both chromium complexes. The range of the procedure was found to be linear for Cr(III) and Cr(VI) concentrations between 0.125 and 4 μg/mL (r² = 0.9926) and 0.1 and 3.0 μg/mL (r² = 0.9983), respectively. Precision was evaluated by replicate analysis in which the percentage relative standard deviation values for chromium complex were found to be below 4.0. The recoveries obtained (85-115%) for both Cr(III) and Cr(VI) complexes indicated the accuracy of the developed method. The degradation products, as well as the excipients, were well resolved from the chromium complex peak in the chromatogram. Finally, the new method proved to be suitable for routine analysis of Cr(III) and Cr(VI) species in raw materials, mineral mixtures, and feed samples. © 2015 Poultry Science Association Inc.
Urban adolescent stress and hopelessness.
Landis, Dana; Gaylord-Harden, Noni K; Malinowski, Sara L; Grant, Kathryn E; Carleton, Russell A; Ford, Rebecca E
2007-12-01
This study sought to explore potential mechanisms through which uncontrollable, chronic stressors may lead to hopelessness in low-income, urban adolescents. In particular, the roles of specific coping strategies as moderators and/or mediators of the association between stressors and hopelessness were examined. Results suggest that chronic, uncontrollable stressors were significantly and positively related to hopelessness in this sample. Active coping, distraction coping, and social-support-seeking coping emerged as moderators for males, such that uncontrollable stressors were more highly associated with hopelessness for those boys who reported using more active, distraction, and social-support-seeking coping strategies. An analogous moderating effect was found for ruminative coping for girls. Ruminative coping also emerged as a mediator of the relation between uncontrollable stressors and hopelessness for girls.
Walker, Tilman; Heinemann, Pascal; Bruckner, Thomas; Streit, Marcus R; Kinkel, Stefan; Gotterbarm, Tobias
2017-07-01
The Oxford unicompartmental knee arthroplasty (OUKA) has been proven to be an effective treatment for anteromedial osteoarthritis of the knee joint. New instrumentation has been introduced to improve the reproducibility of implant positioning and to minimize bone loss during tibial resection (Oxford Microplasty; Zimmer Biomet, Warsaw, Indiana, USA). To assess the effect of the new instrumentation, we retrospectively evaluated the postoperative radiographs and surgical records of 300 OUKAs in three consecutive cohorts of patients. The first cohort consists of the first 100 minimal invasive implantations of the OUKA using the conventional phase III instrumentation, the second cohort consists of the 100 most recent minimal invasive OUKA with the conventional phase III instrumentation and the third cohort consists of the first 100 minimal invasive OUKA using the new Oxford Microplasty instrumentation. Mean bearing thickness was statistically significant and lower in OUKA with use of the updated instrumentation than with the conventional instrumentation (p = 0.01 and p = 0.04). Additionally, statistically significant and more femoral components were aligned within the accepted range of tolerance in both the coronal and the sagittal plane with use of the updated instrumentation compared to the conventional phase III instrumentation in group A (p = 0.029 and p = 0.038) and in the sagittal plane with use of the updated instrumentation compared to the conventional phase III instrumentation in group B (p = 0.002). The new modified instrumentation seems to be an effective tool to reduce the risk of malalignment of the femoral component in the coronal and in the sagittal plane compared to the conventional phase III instrumentation. Furthermore, the instrumentation is also effective in determining an adequate level of tibial resection and thus avoiding unnecessary bone loss.
Shirshekanb, Mahsa; Rezadoost, Hassan; Javanbakht, Mehran; Ghassempour, Ali Reza
2017-01-01
There is no other naturally occurring defense agent against cancer that has a stronger effect than paclitaxel, commonly known under the brand name of Taxol ® . The major drawback for the more widespread use of paclitaxel and its precious precursor, 10-deacetylbaccatin III (10-DAB III), is that they require large-scale extraction from different parts of yew trees ( Taxus species), cell cultures, taxane-producing endophytic fungi, and Corylus species. In our previous work, a novel online two-dimensional heart-cut liquid chromatography process using hydrophilic interaction/ reversed-phase chromatography was used to introduce a semi-preparative treatment for the separation of polar (10-deacetylbaccatin III) and non-polar (paclitaxel) taxanes from Taxus baccata L. In this work, a combination of the absorbent (Diaion ® HP-20) and a silica based solid phase extraction is utilized as a new, efficient, and cost effective method for large-scale production of taxanes. This process avoids the technical problem of two-dimensional preparative liquid chromatography. The first stage of the process involves discarding co-extractive polar compounds including chlorophylls and pigments using a non-polar synthetic hydrophobic absorbent, Diaion ® HP-20. Extract was then loaded on to a silica based hydrophilic interaction solid phase extraction (silica 40-60 micron). Taxanes was eluted using a mixture of water and methanol at the optimized ratio of 70:30. Finally, the fraction containing taxanes was applied to semi-preparative reversed phase HPLC. The results revealed that using this procedure, paclitaxel and 10-DAB III could be obtained at 8 and 3 times more, respectively than by the traditional method of extraction.
Zhang, Sheng; Liang, Fei; Li, Wenfeng
2017-11-01
The decision to make protocols of phase III randomized controlled trials (RCTs) publicly accessible by leading journals was a landmark event in clinical trial reporting. Here, we compared primary outcomes defined in protocols with those in publications describing the trials and in trial registration. We identified phase III RCTs published between January 1, 2012, and June 30, 2015, in The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The BMJ with available protocols. Consistency in primary outcomes between protocols and registries (articles) was evaluated. We identified 299 phase III RCTs with available protocols in this analysis. Out of them, 25 trials (8.4%) had some discrepancy for primary outcomes between publications and protocols. Types of discrepancies included protocol-defined primary outcome reported as nonprimary outcome in publication (11 trials, 3.7%), protocol-defined primary outcome omitted in publication (10 trials, 3.3%), new primary outcome introduced in publication (8 trials, 2.7%), protocol-defined nonprimary outcome reported as primary outcome in publication (4 trials, 1.3%), and different timing of assessment of primary outcome (4 trials, 1.3%). Out of trials with discrepancies in primary outcome, 15 trials (60.0%) had discrepancies that favored statistically significant results. Registration could be seen as a valid surrogate of protocol in 237 of 299 trials (79.3%) with regard to primary outcome. Despite unrestricted public access to protocols, selective outcome reporting persists in a small fraction of phase III RCTs. Only studies from four leading journals were included, which may cause selection bias and limit the generalizability of this finding. Copyright © 2017 Elsevier Inc. All rights reserved.
Lorcaserin: an investigational serotonin 2C agonist for weight loss.
Hurren, Kathryn M; Berlie, Helen D
2011-11-01
The pharmacology, pharmacokinetics, and adverse effects of the selective serotonin (5-HT) agonist lorcaserin are reviewed, with an emphasis on efficacy and safety data from Phase III clinical trials. Lorcaserin is highly selective for a subtype of 5-HT receptors important in appetite regulation, with low affinity for other 5-HT-receptor subtypes whose activation is thought to underlie serious cardiovascular adverse effects; such effects have been seen with nonselective serotonergic agents for weight loss (e.g., fenfluramine). In two Phase III trials of lorcaserin, the cumulative proportion of patients who achieved weight loss of ≥5% over 12 months was about 47% with lorcaserin use versus 20-25% among placebo users (p < 0.0001 for both trials). Lorcaserin was generally well tolerated in the clinical trials to date; nausea and vomiting, headache, and dizziness were the most commonly reported adverse effects. In two of the three Phase III trials to date, lorcaserin use was not found to increase the risk of cardiac valvulopathy; however, in the other Phase III trial, which focused on patients with diabetes, lorcaserin use was associated with an increased rate of new valvulopathy. In a carcinogenicity evaluation involving laboratory rats, lorcaserin was linked to the development of various malignancies, a finding with uncertain implications for its potential future use in humans. Lorcaserin, a 5-HT(2C) agonist, has demonstrated efficacy in patients who are obese or are overweight with associated comorbidities. Phase III trials have found that more than 35% of patients lost greater than 5% of their baseline weight. The maker of lorcaserin has indicated it will continue to seek U.S. marketing approval of the drug for the indications of long-term weight loss and weight-loss maintenance in specific patient populations.
Sphingosine 1-phosphate receptor modulators in multiple sclerosis.
Subei, Adnan M; Cohen, Jeffrey A
2015-07-01
Sphingosine 1-phosphate (S1P) receptor modulators possess a unique mechanism of action as disease-modifying therapy for multiple sclerosis (MS). Subtype 1 S1P receptors are expressed on the surfaces of lymphocytes and are important in regulating egression from lymph nodes. The S1P receptor modulators indirectly antagonize the receptor's function and sequester lymphocytes in lymph nodes. Fingolimod was the first S1P agent approved in the USA in 2010 for relapsing MS after two phase III trials (FREEDOMS and TRANSFORMS) demonstrated potent efficacy, and good safety and tolerability. Post-marketing experience, as well as a third phase III trial (FREEDOMS II), also showed favorable results. More selective S1P receptor agents-ponesimod (ACT128800), siponimod (BAF312), ozanimod (RPC1063), ceralifimod (ONO-4641), GSK2018682, and MT-1303-are still in relatively early stages of development, but phase I and II trials showed promising efficacy and safety. However, these observations have yet to be reproduced in phase III clinical trials.
Chubar, Natalia; Gerda, Vasyl; Szlachta, Małgorzata
2014-11-18
Selenium cycling in the environment is greatly controlled by various minerals, including Mn and Fe hydrous oxides. At the same time, such hydrous oxides are the main inorganic ion exchangers suitable (on the basis of their chemical nature) to sorb (toxic) anions, separating them from water solutions. The mechanism of selenite adsorption by the new mixed adsorbent composed of a few (amorphous and crystalline) phases [maghemite, MnCO3, and X-ray amorphous Fe(III) and Mn(III) hydrous oxides] was studied by extended X-ray absorption fine structure (EXAFS) spectroscopy [supported by Fourier transform infrared (FTIR) and X-ray diffraction (XRD) data]. The complexity of the porous adsorbent, especially the presence of the amorphous phases of Fe(III) and Mn(III) hydrous oxides, is the main reason for its high selenite removal performance demonstrated by batch and column adsorption studies shown in the previous work. Selenite was bound to the material via inner-sphere complexation (via oxygen) to the adsorption sites of the amorphous Fe(III) and Mn(III) oxides. This anion was attracted via bidentate binuclear corner-sharing coordination between SeO3(2-) trigonal pyramids and both FeO6 and MnO6 octahedra; however, the adsorption sites of Fe(III) hydrous oxides played a leading role in selenite removal. The contribution of the adsorption sites of Mn(III) oxide increased as the pH decreased from 8 to 6. Because most minerals have a complex structure (they are seldom based on individual substances) of various crystallinity, this work is equally relevant to environmental science and environmental technology because it shows how various solid phases control cycling of chemical elements in the environment.
Furtado, Jeremy D; Wedel, Mark K; Sacks, Frank M
2012-04-01
Mipomersen, an antisense oligonucleotide that reduces hepatic production of apoB, has been shown in phase 2 studies to decrease plasma apoB, LDL cholesterol (LDL-C), and triglycerides. ApoC-III inhibits VLDL and LDL clearance, and it stimulates inflammatory responses in vascular cells. Concentrations of VLDL or LDL with apoC-III independently predict cardiovascular disease. We performed an exploratory posthoc analysis on a subset of hypercholesterolemic subjects obtained from a randomized controlled dose-ranging phase 2 study of mipomersen receiving 100, 200, or 300 mg/wk, or placebo for 13 wk (n = 8 each). ApoC-III-containing lipoproteins were isolated by immuno-affinity chromatography and ultracentrifugation. Mipomersen 200 and 300 mg/wk reduced total apoC-III from baseline by 6 mg/dl (38-42%) compared with placebo group (P < 0.01), and it reduced apoC-III in both apoB lipoproteins and HDL. Mipomersen 100, 200, and 300 mg doses reduced apoB concentration of LDL with apoC-III (27%, 38%, and 46%; P < 0.05). Mipomersen reduced apoC-III concentration in HDL. The drug had no effect on apoE concentration in total plasma and in apoB lipoproteins. In summary, antisense inhibition of apoB synthesis reduced plasma concentrations of apoC-III and apoC-III-containing lipoproteins. Lower concentrations of apoC-III and LDL with apoC-III are associated with reduced risk of coronary heart disease (CHD) in epidemiologic studies independent of traditional risk factors.
Phase II trial of CoQ10 for ALS finds insufficient evidence to justify Phase III
Kaufmann, Petra; Thompson, John L.P.; Levy, Gilberto; Buchsbaum, Richard; Shefner, Jeremy; Krivickas, Lisa S.; Katz, Jonathan; Rollins, Yvonne; Barohn, Richard J.; Jackson, Carlayne E.; Tiryaki, Ezgi; Lomen-Hoerth, Catherine; Armon, Carmel; Tandan, Rup; Rudnicki, Stacy A.; Rezania, Kourosh; Sufit, Robert; Pestronk, Alan; Novella, Steven P.; Heiman-Patterson, Terry; Kasarskis, Edward J.; Pioro, Erik P.; Montes, Jacqueline; Arbing, Rachel; Vecchio, Darleen; Barsdorf, Alexandra; Mitsumoto, Hiroshi; Levin, Bruce
2010-01-01
Objective Amyotrophic lateral sclerosis (ALS) is a devastating, and currently incurable, neuromuscular disease in which oxidative stress and mitochondrial impairment are contributing to neuronal loss. Coenzyme Q10 (CoQ10), an antioxidant and mitochondrial cofactor, has shown promise in ALS transgenic mice, and in clinical trials for neurodegenerative diseases other than ALS. Our aims were to choose between two high doses of CoQ10 for ALS, and to determine if it merits testing in a Phase III clinical trial. Methods We designed and implemented a multi-center trial with an adaptive, two-stage, bias-adjusted, randomized, placebo-controlled, double-blind, Phase II design (n=185). The primary outcome in both stages was decline in the ALS Functional Rating Scale-revised (ALSFRSr) score over 9 months. Stage 1 (dose selection, 35 participants per group) compared CoQ10 doses of 1,800 and 2,700 mg/day. Stage 2 (futility test, 75 patients per group) compared the dose selected in Stage 1 against placebo. Results Stage 1 selected the 2,700 mg dose. In Stage 2, the pre-specified primary null hypothesis that this dose is superior to placebo was not rejected. It was rejected, however, in an accompanying pre-specified sensitivity test, and further supplementary analyses. Pre-specified secondary analyses showed no significant differences between CoQ10 at 2,700 mg/day and placebo. There were no safety concerns. Interpretation CoQ10 at 2,700 mg daily for 9 months shows insufficient promise to warrant Phase III testing. Given this outcome, the adaptive Phase II design incorporating a dose selection and a futility test avoided the need for a much larger conventional Phase III trial. PMID:19743457
Galileo Parachute System modification program
NASA Technical Reports Server (NTRS)
Mcmenamin, H. J.; Pochettino, L. R.
1984-01-01
This paper discusses the development program conducted on the Galileo Parachute System following the slow opening performance of the main parachute during the first system drop test. The parachute system is part of the Galileo entry probe that will descend through the Jupiter atmosphere. The uncontrolled parachute opening experienced in this test was not acceptable for the probe system. Therefore, the main parachute design was modified and the system sequence was changed to prevent a recurrence. These alterations and their system effects were evaluated analytically, and in a ground test program. At the conclusion of this phase, the system drop test was successfully repeated.
Yang, Haichen; Laurenza, Antonio; Williams, Betsy; Patten, Anna; Hussein, Ziad; Ferry, Jim
2015-08-01
Perampanel is a selective, noncompetitive AMPA receptor antagonist approved as adjunctive treatment for partial seizures. To assess potential for delayed cardiac repolarization, a Phase I thorough QT study was performed, supplemented by plasma concentration-QT data modeled from 3 pooled Phase III studies. The Phase I thorough QT study (double-blind, combined fixed-sequence, parallel-group) quantified the effect of perampanel (6 mg once daily for 7 days, followed by dose escalation to a single 8-mg dose, a single 10-mg dose, then 12 mg once daily for 7 days), moxifloxacin positive control (single 400-mg dose on Day 16), and placebo on QT interval duration in healthy subjects (N = 261). Electrocardiograms were recorded at baseline, Day 7 (post 6 mg dose), and Day 16 (post 12 mg dose). Statistical comparisons were between the highest approved perampanel dose (12 mg) versus placebo, a "mid-therapeutic" dose (6 mg) versus placebo, and moxifloxacin versus placebo. Acknowledging that the Phase I thorough QT study could not incorporate a true "supratherapeutic" dose due to length of titration and tolerability concerns in healthy subjects, Phase III studies of perampanel included expanded electrocardiogram safety evaluations specifically intended to support concentration-QT response modeling. The lack of effect of perampanel on the QT interval is shown from pooled analysis of 3 double-blind, placebo-controlled, 19-week, Phase III studies with perampanel doses ≤ 12 mg (N = 1038, total perampanel; and N=442, placebo) in patients with partial seizures. QT measures were corrected for heart rate using Fridericia's (QTcF; the primary endpoint) and Bazett's (QTcB) formulas. In the Phase I thorough QT study, the positive control moxifloxacin caused peak time-matched, baseline-adjusted, placebo-corrected (ΔΔ) QTcF of 12.15 ms at 4h postdose, confirming a drug effect on QTc interval and study assessment sensitivity. Mean baseline-adjusted (Δ) QTcF versus nominal time curves were comparable between perampanel 12 mg and placebo, with most ΔQTcF values being slightly negative. Healthy subjects receiving perampanel 6 and 12 mg doses for 7 days showed no evidence of effects on cardiac repolarization. Peak ΔΔQTcF was 2.34 ms at 1.5h postdose for perampanel 6 mg and 3.92 ms at 0.5h postdose for perampanel 12 mg. At every time point, the upper 95% confidence limit of ΔΔQTcF for perampanel 6 and 12 mg was <10 ms. Phase III studies revealed no clinically significant difference between patients with partial seizures treated with perampanel or placebo in QTcF and QTcB values >450 ms, with no dose-dependent increases or large incremental changes from baseline of >60 ms. Regression analysis of individual plasma perampanel concentrations versus corresponding QTc interval values in Phase I thorough QT and Phase III studies demonstrated no relationship between perampanel concentrations and QT interval duration. Treatment with perampanel 6 mg and 12 mg for 7 days did not delay cardiac repolarization in healthy volunteers. In a population analysis of 1480 patients with partial seizures treated with perampanel doses ≤ 12 mg or placebo, no clinically significant trends in QT interval data were noted. Based on the thorough QT study and evaluations from pooled Phase III studies, there is no evidence of prolonged QT interval duration with perampanel treatment. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Weinstein, B. A.; Lindberg, G. P.
Pressure-Raman spectroscopy in ZnSe and ZnTe single crystals reveals that Se and Te nano-crystals (NCs) precipitate in these II-VI hosts for pressures far below their I-II phase transitions. The inclusions are evident from the appearance and negative pressure-shift of the A1 Raman peaks of Se and Te (trigonal phase). The Se and Te NCs nucleate at dislocations and grain boundaries that arise from pressure-induced plastic flow. This produces chemical and structural inhomogeneities in the zincblende phase of the host. At substantially higher pressures, the I-II transition proceeds in the presence of these inhomogenities. This can affect the transition's onset pressure Pt and width ΔPt, and the occurrence of metastable phases along the transition path. Precipitation models in metals show that nucleation of inclusions depends on the Peierls stress τp and a parameter α related to the net free energy gained on nucleation. For favorable values of τp and α, NC precipitation at pressures below the I-II transition could occur in other compounds. We propose criteria to judge whether this is likely based on the observed ranges of τp in the hosts, and estimates of α derived from the cohesive energy densities of the NC materials. One finds trends that can serve as a useful guide, both to test the proposed criteria, and to decide when closer scrutiny of phase transition experiments is warranted, e.g., in powders where high dislocation densities are initially created
ERIC Educational Resources Information Center
Lane Community Coll., Eugene, OR.
A final report and final evaluation report of Phase III are provided for a project to establish a national clearinghouse for apprenticeship-related instructional materials. The final report provides a summary and a narrative account of these project activities: identification of materials; identification of apprenticeship curriculum needs;…
ERIC Educational Resources Information Center
Carr, Deborah; Felce, Janet
2007-01-01
The study investigated the impact of mastery of the Picture Exchange Communication System (PECS) to Phase III, on the communications of children with autism. Children aged between 3 and 7 years, formed a PECS intervention group and a non-intervention control group. The intervention group received 15 h of PECS teaching over 5 weeks. Three 2-h…
Phase 2 Site Investigations Report. Volume 3 of 3: Appendices
1994-09-01
Phase II Site Investigations Ee Report Cn Volume III of III Appendices Fort Devens Sudbury Training Annex, Massachusetts September 1994 Contract No...laboratory quality control (QC) samples collected during field investigations at the Sudbury Training Annex of Fort Devens , Massachusetts. The QC...returned to its original condition. E & E performed this procedure for each monitoring well tested during the 1993 slug testing activities at Fort Devens
Kim, Michelle M; Parmar, Hemant; Cao, Yue; Pramanik, Priyanka; Schipper, Matthew; Hayman, James; Junck, Larry; Mammoser, Aaron; Heth, Jason; Carter, Corey A; Oronsky, Arnold; Knox, Susan J; Caroen, Scott; Oronsky, Bryan; Scicinski, Jan; Lawrence, Theodore S; Lao, Christopher D
2016-04-01
Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial. Published by Elsevier Inc.
Jafar, Tazeen H; Gandhi, Mihir; Jehan, Imtiaz; Naheed, Aliya; de Silva, H Asita; Shahab, Hunaina; Alam, Dewan; Luke, Nathasha; Lim, Ching Wee
2018-04-26
Uncontrolled blood pressure (BP) is a leading risk factor for death and disability in South Asia. We aimed to determine the cross-country variation, and the factors associated with uncontrolled BP among adults treated for hypertension in rural South Asia. We enrolled 1718 individuals aged ≥40 years treated for hypertension in a cross-sectional study from rural communities in Bangladesh, Pakistan, and Sri Lanka. Multivariable logistic regression model was used to determine the factors associated with uncontrolled BP (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg). Among hypertensive individuals, 58.0% (95% confidence interval 55.7, 60.4) had uncontrolled BP: 52.8% (49.0, 56.6) in Bangladesh, 70.6% (65.7, 75.1) in Pakistan, and 56.5% (52.7, 60.1) in Sri Lanka. The odds (odds ratio (95% confidence interval)) of uncontrolled BP were significantly higher in individuals with lower wealth index (1.17 (1.02, 1.35)); single vs married (1.46 (1.10, 1.93)); higher log urine albumin-to-creatinine ratio (1.41 (1.24, 1.60)); lower estimated glomerular filtration rate (1.23 (1.01, 1.49)); low vs high adherence to antihypertensive medication (1.50 (1.16, 1.94)); and Pakistan (2.91 (1.60, 5.28)) vs Sri Lanka. However, the odds were lower in those with vs without self-reported kidney disease (0.51 (0.28, 0.91)); and receiving vs not receiving statins (0.62 (0.44, 0.87)). The majority of individuals with treated hypertension have uncontrolled BP in rural Bangladesh, Pakistan, and Sri Lanka with significant disparities among and within countries. Urgent public health efforts are needed to improve access and adherence to antihypertensive medications in disadvantaged populations in rural South Asia.
Reasons for uncontrolled seizures in adults; the impact of pseudointractability.
Asadi-Pooya, Ali A; Emami, Mehrdad; Ashjazadeh, Nahid; Nikseresht, Alireza; Shariat, Abdolhamid; Petramfar, Peyman; Yousefipour, Gholamali; Borhani-Haghighi, Afshin; Izadi, Sadegh; Rahimi-Jaberi, Abbas
2013-05-01
We investigated the various possible reasons for uncontrolled seizures in patients 18 years of age and older to determine the impact of pseudointractability. We also tried to investigate the various forms of pseudointractability. In this cross-sectional study, all patients 18 years of age and older with their first seizure occurring at least six months prior to the referral date, taking at least one antiepileptic drug (AED) and having at least one seizure in the past three months were studied. The presumed reason for uncontrolled seizures was arbitrarily considered to be one of these five categories: Poor compliance; Wrong medication (misclassification); Wrong dose of the correct medication; Diagnosis other than epilepsy; and finally, Medically-refractory epilepsy. Statistical analyses were performed using Chi-square and Fisher's exact tests, and a P value less than 0.05 was considered significant. 350 patients were referred to us due to uncontrolled seizures. One hundred ninety-one (55%) were male and 159 (45%) were female. Twelve percent of the patients had diagnoses other than epilepsy, 40% had indeed medically-refractory epilepsy; 29% were taking the wrong AEDs (misclassified epilepsy); 18% were taking suboptimal doses of AEDs; and 1% had poor drug compliance. The most common reason for uncontrolled seizures among patients with idiopathic generalized epilepsy was taking the wrong AED. However, among patients with focal epilepsy, true medically-refractory epilepsy was the most common reason. Uncontrolled seizures are a commonly encountered problem, especially at epilepsy clinics and one should consider all possible reasons for these uncontrolled seizures. The mainstay for making a correct diagnosis is a detailed clinical history. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Lee, Ki Hyeong; Kim, Ji-Yeon; Lee, Moon Hee; Han, Hye Sook; Lim, Joo Han; Park, Keon Uk; Park, In Hae; Cho, Eun Kyung; Yoon, So Young; Kim, Jee Hyun; Choi, In Sil; Park, Jae Hoo; Choi, Young Jin; Kim, Hee-Jun; Jung, Kyung Hae; Kim, Si-Young; Oh, Do-Youn; Im, Seock-Ah
2016-04-01
Pegylated granulocyte-colony-stimulating factor (G-CSF) is frequently used to prevent febrile neutropenia (FN) in patients undergoing chemotherapy with a high risk of myelosuppression. This phase II/III study was conducted to determine the adequate dose of pegteograstim, a new formulation of pegylated G-CSF, and to evaluate the efficacy and safety of pegteograstim compared to pegfilgrastim. In the phase II part, 60 breast cancer patients who were undergoing DA (docetaxel and doxorubicin) or TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy were randomly selected to receive a single subcutaneous injection of 3.6 or 6.0 mg pegteograstim on day 2 of each chemotherapy cycle. The phase III part was seamlessly started to compare the dose of pegteograstim at selected in phase II with 6.0 mg pegfilgrastim in 117 breast cancer patients. The primary endpoint of both the phase II and III parts was the duration of grade 4 neutropenia in the chemotherapy cycle 1. The mean duration of grade 4 neutropenia for the 3.6 mg pegteograstim (n = 33) was similar to that for the 6.0 mg pegteograstim (n = 26) (1.97 ± 1.79 days vs. 1.54 ± 0.95 days, p = 0.33). The 6.0 mg pegteograstim was selected to be compared with the 6.0 mg pegfilgrastim in the phase III part. In the phase III part, the primary analysis revealed that the efficacy of pegteograstim (n = 56) was non-inferior to that of pegfilgrastim (n = 59) [duration of grade 4 neutropenia, 1.64 ± 1.18 days vs. 1.80 ± 1.05 days; difference, -0.15 ± 1.11 (p = 0.36, 97.5 % confidence intervals = 0.57 and 0.26)]. The time to the absolute neutrophil count (ANC) recovery of pegteograstim (≥2000/μL) was significantly shorter than that of pegfilgrastim (8.85 ± 1.45 days vs. 9.83 ± 1.20 days, p < 0.0001). Other secondary endpoints showed no significant difference between the two groups. The safety profiles of the two groups did not differ significantly. Pegteograstim was shown to be as effective as pegfilgrastim in the reduction of chemotherapy-induced neutropenia in the breast cancer patients who were undergoing chemotherapy with a high risk of myelosuppression.
The role of the opioid system in binge eating disorder.
Giuliano, Chiara; Cottone, Pietro
2015-12-01
Binge eating disorder is characterized by excessive, uncontrollable consumption of palatable food within brief periods of time. Excessive intake of palatable food is thought to be driven by hedonic, rather than energy homeostatic, mechanisms. However, reward processing does not only comprise consummatory actions; a key component is represented by the anticipatory phase directed at procuring the reward. This phase is highly influenced by environmental food-associated stimuli, which can robustly enhance the desire to eat even in the absence of physiological needs. The opioid system (endogenous peptides and their receptors) has been strongly linked to the rewarding aspects of palatable food intake, and perhaps represents the key system involved in hedonic overeating. Here we review evidence suggesting that the opioid system can also be regarded as one of the systems that regulates the anticipatory incentive processes preceding binge eating hedonic episodes.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brown, Lewis R.; Byrnes, Martin J.; Stephens, James O.
This project was designed to demonstrate that a microbially enhanced oil recovery process (MEOR), developed in part under DOE Contract No. DE-AC22-90BC14665, will increase oil recovery from fluvial dominated deltaic oil reservoirs. The process involves stimulating the in-situ indigenous microbial population in the reservoir to grow in the more permeable zones, thus diverting flow to other areas of the reservoir, thereby increasing the effectiveness of the waterflood. This five and a half year project is divided into three phases, Phase I, Planning and Analysis (9 months), Phase II, Implementation (45 months), and Phase III, Technology Transfer (12 months). Phase Imore » was completed and reported in the first annual report. This fifth annual report covers the completion of Phase II and the first six months of Phase III.« less
Moreno, Beatriz; de Faria, Ana Paula; Ritter, Alessandra Mileni Versuti; Yugar, Lara Buonalumi Tacito; Ferreira-Melo, Silvia Elaine; Amorim, Rivadavio; Modolo, Rodrigo; Fattori, André; Yugar-Toledo, Juan Carlos; Coca, Antonio; Moreno, Heitor
2018-05-01
This study aimed to evaluate the effects of glycated hemoglobin (HbA 1c ) on flow-mediated dilation, intima-media thickness, pulse wave velocity, and left ventricular mass index in patients with resistant hypertension (RHTN) comparing RHTN-controlled diabetes mellitus and RHTN-uncontrolled type 2 diabetes mellitus. Two groups were formed: HbA 1c <7.0% (RHTN-controlled diabetes mellitus: n = 98) and HbA 1c ≥7.0% (RHTN-uncontrolled diabetes mellitus: n = 122). Intima-media thickness and flow-mediated dilation were measured by high-resolution ultrasound, left ventricular mass index by echocardiography, and arterial stiffness by carotid-femoral pulse wave velocity. No differences in blood pressure levels were found between the groups but body mass index was higher in patients with RHTN-uncontrolled diabetes mellitus. Endothelial dysfunction and arterial stiffness were worse in patients with RHTN-uncontrolled diabetes mellitus. Intima-media thickness and left ventricular mass index measurements were similar between the groups. After adjustments, multiple linear regression analyses showed that HbA 1c was an independent predictor of flow-mediated dilation and pulse wave velocity in all patients with RHTN. In conclusion, HbA 1c may predict the grade of arterial stiffness and endothelial dysfunction in patients with RHTN, and superimposed uncontrolled diabetes mellitus implicates further impairment of vascular function. ©2018 Wiley Periodicals, Inc.
Fox, Robert V.; Zhang, Fengyan; Rodriguez, Rene G.; Pak, Joshua J.; Sun, Chivin
2016-06-21
Single source precursors or pre-copolymers of single source precursors are subjected to microwave radiation to form particles of a I-III-VI.sub.2 material. Such particles may be formed in a wurtzite phase and may be converted to a chalcopyrite phase by, for example, exposure to heat. The particles in the wurtzite phase may have a substantially hexagonal shape that enables stacking into ordered layers. The particles in the wurtzite phase may be mixed with particles in the chalcopyrite phase (i.e., chalcopyrite nanoparticles) that may fill voids within the ordered layers of the particles in the wurtzite phase thus produce films with good coverage. In some embodiments, the methods are used to form layers of semiconductor materials comprising a I-III-VI.sub.2 material. Devices such as, for example, thin-film solar cells may be fabricated using such methods.
Prevalence of pseudoresistant hypertension due to inaccurate blood pressure measurement
Bhatt, Hemal; Siddiqui, Mohammed; Judd, Eric; Oparil, Suzanne; Calhoun, David
2016-01-01
Background The prevalence of pseudoresistant hypertension (HTN) due to inaccurate BP measurement remains unknown. Methods Triage BP measurements and measurements obtained at the same clinic visit by trained physicians were compared in consecutive adult patients referred for uncontrolled resistant HTN (RHTN). Triage BP measurements were taken by the clinic staff during normal intake procedures. BP measurements were obtained by trained physicians using the BpTRU device. The prevalence of uncontrolled RHTN and differences in BP measurements were compared. Results Of 130 patients with uncontrolled RHTN, 33.1% (n=43) were falsely identified as having uncontrolled RHTN based on triage BP measurements. The median (IQR) of differences in systolic BP between pseudoresistant and true resistant groups were 23 (17 – 33) mm Hg and 13 (6 – 21) mm Hg, respectively (P=0.0001). The median (IQR) of differences in diastolic BP between the two groups were 12 (7 – 18) mm Hg and 8 (4 – 11) mm Hg, respectively (P=0.001). Conclusion Triage BP technique overestimated the prevalence of uncontrolled RHTN in approximately 33% of the patients emphasizing the importance of obtaining accurate BP measurements. PMID:27129931
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Jeomoh, E-mail: jkim610@gatech.edu; Ji, Mi-Hee; Detchprohm, Theeradetch
2015-09-28
Unintentional incorporation of gallium (Ga) in InAlN layers grown with different molar flow rates of Group-III precursors by metalorganic chemical vapor deposition has been experimentally investigated. The Ga mole fraction in the InAl(Ga)N layer was increased significantly with the trimethylindium (TMIn) flow rate, while the trimethylaluminum flow rate controls the Al mole fraction. The evaporation of metallic Ga from the liquid phase eutectic system between the pyrolized In from injected TMIn and pre-deposited metallic Ga was responsible for the Ga auto-incorporation into the InAl(Ga)N layer. The theoretical calculation on the equilibrium vapor pressure of liquid phase Ga and the effectivemore » partial pressure of Group-III precursors based on growth parameters used in this study confirms the influence of Group-III precursors on Ga auto-incorporation. More Ga atoms can be evaporated from the liquid phase Ga on the surrounding surfaces in the growth chamber and then significant Ga auto-incorporation can occur due to the high equilibrium vapor pressure of Ga comparable to effective partial pressure of input Group-III precursors during the growth of InAl(Ga)N layer.« less
Kang, Youngjea; Kampf, Jeff W; Meyerhoff, Mark E
2007-08-29
A fluoride-selective optical sensor based on scandium(III)-octaethylporphyrin (Sc(III)OEP) as an ionophore within a plasticized PVC film is described. The presence of fluoride ion in the aqueous sample phase increases the formation of a difluoro-bridged Sc(III)OEP dimer species in the polymer film. The ability of the Sc(III) porphyrin to form the dimeric structure in the presence of fluoride is confirmed by UV-vis spectroscopy and X-ray crystallography. For more practical sensing applications, a pH chromoionophore (ETH 7075) is added to the plasticized PVC film along with Sc(III)OEP and the observed optical response is based on coextraction of protons with sample phase fluoride to create the dimeric porphyrin and a protonated chromoionophore species. The selectivity pattern observed is F- > ClO4(-), SCN-, NO3(-) > Br-, Cl-. Only organic salicylate is a significant interferent. Fast and reversible fluoride response is observed over the range of 10(-4) to 10(-2) M fluoride, allowing use of the sensing film in a waveguide configuration for flow-injection measurements.
Kang, Youngjea; Kampf, Jeff W.; Meyerhoff, Mark E.
2007-01-01
A fluoride-selective optical sensor based on scandium(III) octaethylporphyrin (Sc(III)OEP) as an ionophore within a plasticized PVC film is described. The presence of fluoride ion in the aqueous sample phase increases the formation of a difluoro-bridged Sc(III)OEP dimer species in the polymer film. The ability of the Sc(III) porphyrin to form the dimeric structure in the presence of fluoride is confirmed by UV-Vis spectroscopy and X-ray crystallography. For more practical sensing applications, a pH chromoionophore (ETH 7075) is added to the plasticized PVC film along with Sc(III)OEP and the observed optical response is based on co-extraction of protons with sample phase fluoride to create the dimeric porphyrin and a protonated chromoionophore species. The selectivity pattern observed is F-≫ClO4-, SCN-, NO3->Br-, Cl-. Only organic salicylate is a significant interferent. Fast and reversible fluoride response is observed over the range of 10-4 ~10-2 M fluoride, allowing use of the sensing film in a waveguide configuration for flow-injection measurements. PMID:17719905
NASA Astrophysics Data System (ADS)
Dresvyannikov, A. F.; Kolpakov, M. E.
2018-05-01
X-ray fluorescence, X-ray phase analysis, and transmission Mössbauer and NGR spectrometry are used to study the formation, phase, and elemental composition of Fe-Ti particles. The interaction between Fe(III) ions and dispersed titanium in an aqueous solution containing chloride ions and HF is studied. It is shown that the resulting Fe-Ti samples are a set of core-shell microparticles with titanium cores coated with micro- and nanosized α-Fe nucleation centers with the thinness outer layer of iron(III) oxide characterized by a developed surface.
Lee, Cindy; Vather, Ryash; O'Callaghan, Anne; Robinson, Jackie; McLeod, Briar; Findlay, Michael; Bissett, Ian
2013-12-01
Malignant bowel obstruction (MBO) is common in patients with advanced cancer. To perform a phase II study to assess the feasibility of conducting a phase III trial investigating the therapeutic value of gastrografin in MBO. Randomized double-blinded placebo-controlled feasibility study. Participants received 100 mL of either gastrografin or placebo. Over 8 months, 57 patients were screened and 9 enrolled (15.8% recruitment rate). Of the 9 enrolled, 4 received gastrografin (with 2 completing assessment) and 5 received placebo (with 4 completing assessment). It is not feasible to conduct a phase III trial using the same study protocol. This study validates the use of the phase II feasibility study to assess protocol viability in a palliative population prior to embarking on a larger trial.
The emplacement of long lava flows in Mare Imbrium, the Moon
NASA Astrophysics Data System (ADS)
Garry, W. B.
2012-12-01
Lava flow margins are scarce on the lunar surface. The best developed lava flows on the Moon occur in Mare Imbrium where flow margins are traceable nearly their entire flow length. The flow field originates in the southwest part of the basin from a fissure or series of fissures and cones located in the vicinity of Euler crater and erupted in three phases (Phases I, II, III) over a period of 0.5 Billion years (3.0 - 2.5 Ga). The flow field was originally mapped with Apollo and Lunar Orbiter data by Schaber (1973) and shows the flow field extends 200 to 1200 km from the presumed source area and covers an area of 2.0 x 10^5 km^2 with an estimated eruptive volume of 4 x 10^4 km^3. Phase I flows extend 1200 km and have the largest flow volume, but interestingly do not exhibit visible topography and are instead defined by difference in color from the surrounding mare flows. Phases II and III flows have well-defined flow margins (10 - 65 m thick) and channels (0.4 - 2.0 km wide, 40 - 70 m deep), but shorter flow lengths, 600 km and 400 km respectively. Recent missions, including Lunar Reconnaissance Orbiter (LRO), Kaguya (Selene), and Clementine, provide high resolution data sets of these lava flows. Using a combination of data sets including images from LRO Wide-Angle-Camera (WAC)(50-100 m/pixel) and Narrow-Angle-Camera (NAC) (up to 0.5m/pixel), Kaguya Terrain Camera (TC) (10 m/pixel), and topography from LRO Lunar Orbiter Laser Altimeter (LOLA), the morphology has been remapped and topographic measurements of the flow features have been made in an effort to reevaluate the emplacement of the flow field. Morphologic mapping reveals a different flow path for Phase I compared to the original mapping completed by Schaber (1973). The boundaries of the Phase I flow field have been revised based on Moon Mineralogy Mapper color ratio images (Staid et al., 2011). This has implications for the area covered and volume erupted during this stage, as well as, the age of Phase I. Flow features and margins have been identified in the Phase I flow within the LROC WAC mosaic and in Narrow Angle Camera (NAC) images. These areas have a mottled appearance. LOLA profiles over the more prominent flow lobes in Phase I reveal these margins are less 10 m thick. Phase II and III morphology maps are similar to previous flow maps. Phase III lobes near Euler are 10-12 km wide and 20-30 m thick based on measurements of the LOLA 1024ppd Elevation Digital Terrain Model (DTM) in JMoon. One of the longer Phase III lobes varies between 15 to 50 km wide and 25 to 60 m thick, with the thickest section at the distal end of the lobe. The Phase II lobe is 15 to 25 m thick and up to 35 km wide. The eruptive volume of the Mare Imbrium lava flows has been compared to terrestrial flood basalts. The morphology of the lobes in Phase II and III, which includes levees, thick flow fronts, and lobate margins suggests these could be similar to terrestrial aa-style flows. The Phase I flows might be more representative of sheet flows, pahoehoe-style flows, or inflated flows. Morphologic comparisons will be made with terrestrial flows at Askja volcano in Iceland, a potential analog to compare different styles of emplacement for the flows in Mare Imbrium.
2011-01-01
effects of stressors on excessive and uncontrolled drinking and relapse-like drinking. We proposed to use foot-shock as the stressor to elicit increase...did significantly increase deprivation-induced relapse-like drinking, and that this effect was more robust in mutant mice lacking the NPY Y1R. Thus...ethanol consumption using a models of excessive uncontrolled drinking, and mutant mice lacking NPY or the Y1R were more sensitive to the effects of
Attitude control concepts for precision-pointing nonrigid spacecraft
NASA Technical Reports Server (NTRS)
Likins, P. W.
1974-01-01
Literal criteria are developed for the controllability and observability of general models of flexible spacecraft. Results are interpreted in special cases and in physical terms, permitting in some cases the identification of uncontrollable and unobservable states simply by examination of scalars composed of modal parameters and location matrices for sensors and actuators. A procedure is established for isolation of uncontrollable states, whereby sensor and actuator configurations assure that uncontrollable flexible mode states are also unobservable; in many applications such states can then be removed by coordinate truncation.
NASA Astrophysics Data System (ADS)
Sekiguchi, Kazuki; Shirakawa, Hiroki; Chokawa, Kenta; Araidai, Masaaki; Kangawa, Yoshihiro; Kakimoto, Koichi; Shiraishi, Kenji
2017-04-01
We analyzed the metal organic vapor phase epitaxial growth mechanism of the III-nitride semiconductors GaN, AlN, and InN by first-principles calculations and thermodynamic analyses. In these analyses, we investigated the decomposition processes of the group III source gases X(CH3)3 (X = Ga, Al, In) at finite temperatures and determined whether the (CH3)2GaNH2 adduct can be formed or not. The results of our calculations show that the (CH3)2GaNH2 adduct cannot be formed in the gas phase in GaN metal organic vapor phase epitaxy (MOVPE), whereas, in AlN MOVPE, the formation of the (CH3)2AlNH2 adduct in the gas phase is exclusive. In the case of GaN MOVPE, trimethylgallium (TMG, [Ga(CH3)3]) decomposition into Ga gas on the growth surface with the assistance of H2 carrier gas, instead of the formation of the (CH3)2GaNH2 adduct, occurs almost exclusively. Moreover, in the case of InN MOVPE, the formation of the (CH3)2InNH2 adduct does not occur and it is relatively easy to produce In gas even without H2 in the carrier gas.
Takahashi, Fumihiro; Morita, Satoshi
2018-02-08
Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.
Metalloporphyrin Co(III)TMPyP ameliorates acute, sublethal cyanide toxicity in mice.
Benz, Oscar S; Yuan, Quan; Amoscato, Andrew A; Pearce, Linda L; Peterson, Jim
2012-12-17
The formation of Co(III)TMPyP(CN)(2) at pH 7.4 has been shown to be completely cooperative (α(H) = 2) with an association constant of 2.1 (±0.2) × 10(11). The kinetics were investigated by stopped-flow spectrophotometry and revealed a complicated net reaction exhibiting 4 phases at pH 7.4 under conditions where cyanide was in excess. The data suggest molecular HCN (rather than CN(-)) to be the attacking nucleophile around neutrality. The two slower phases do not seem to be present when cyanide is not in excess, and the other two phases have rates comparable to that observed for cobalamin, a known effective cyanide scavenger. Addition of bovine serum albumin (BSA) did not affect the cooperativity of cyanide binding to Co(III)TMPyP, only lowered the equilibrium constant slightly to 1.2 (±0.2) × 10(11) and had an insignificant effect on the observed rate. A sublethal mouse model was used to assess the effectiveness of Co(III)TMPyP as a potential cyanide antidote. The administration of Co(III)TMPyP to sodium cyanide intoxicated mice resulted in the time required for the surviving mice to right themselves from a supine position being significantly decreased (9 ± 2 min) compared to that of the controls (33 ± 2 min). All observations were consistent with the demonstrated antidotal activity of Co(III)TMPyP operating through a cyanide-binding (i.e., scavenging) mechanism.
The GKSS beamlines at PETRA III and DORIS III
NASA Astrophysics Data System (ADS)
Haibel, A.; Beckmann, F.; Dose, T.; Herzen, J.; Utcke, S.; Lippmann, T.; Schell, N.; Schreyer, A.
2008-08-01
Due to the high brilliance of the new storage ring PETRA III at DESY in Hamburg, the low emittance of 1 nmrad and the high fraction of coherent photons also in the hard X-ray range extremely intense and sharply focused X-ray light will be provided. These advantages of the beam fulfill excellently the qualifications for the planned Imaging BeamLine IBL and the High Energy Materials Science Beamline (HEMS) at PETRA III, i.e. for absorption tomography, phase enhanced and phase contrast experiments, for diffraction, for nano focusing, for nano tomography, and for high speed or in-situ experiments with highest spatial resolution. The existing HARWI II beamline at the DORIS III storage ring at DESY completes the GKSS beamline concept with setups for high energy tomography (16-150 keV) and diffraction (16-250 keV), characterized by a large field of view and an excellent absorption contrast with spatial resolutions down to 2 μm.
ERIC Educational Resources Information Center
Brookland-Cayce Schools, West Columbia, SC.
An evaluation of the second phase of a projected 3-year Title III inservice reading instruction program for teaching personnel is presented after one and one-half years of operation in 16 Cayce-West Columbia, South Carolina, schools. Included is an evaluation prepared by each of the 11 elementary supervisors which includes objectives and how they…
Installation Restoration Program Records Search for Westover Air Force Base, Massachusetts.
1982-04-01
Phase III (not part of this contract) consists of a technology base development study to support the development of project plans for controlling...determine the extent and magnitude of the contaminant migration. Phase III (not part of this contract) consists of a technology base development study to...number of vegetation studies have attempted to classify the potential climax vegetation within the region of Westover AFB (Braun, 1972; Kuchler, 1975
Kaufman, Howard L; Bines, Steven D
2010-06-01
There are few effective treatment options available for patients with advanced melanoma. An oncolytic herpes simplex virus type 1 encoding granulocyte macrophage colony-stimulating factor (GM-CSF; Oncovex(GM-CSF)) for direct injection into accessible melanoma lesions resulted in a 28% objective response rate in a Phase II clinical trial. Responding patients demonstrated regression of both injected and noninjected lesions highlighting the dual mechanism of action of Oncovex(GM-CSF) that includes both a direct oncolytic effect in injected tumors and a secondary immune-mediated anti-tumor effect on noninjected tumors. Based on these preliminary results a prospective, randomized Phase III clinical trial in patients with unresectable Stage IIIb or c and Stage IV melanoma has been initiated. The rationale, study design, end points and future development of the Oncovex(GM-CSF) Pivotal Trial in Melanoma (OPTIM) trial are discussed in this article.
Burden of uncontrolled epilepsy in patients requiring an emergency room visit or hospitalization.
Manjunath, Ranjani; Paradis, Pierre Emmanuel; Parisé, Hélène; Lafeuille, Marie-Hélène; Bowers, Brian; Duh, Mei Sheng; Lefebvre, Patrick; Faught, Edward
2012-10-30
To quantify the clinical and economic burden of uncontrolled epilepsy in patients requiring emergency department (ED) visit or hospitalization. Health insurance claims from a 5-state Medicaid database (1997Q1-2009Q2) and 55 self-insured US companies ("employer," 1999Q1 and 2008Q4) were analyzed. Adult patients with epilepsy receiving antiepileptic drugs (AED) were selected. Using a retrospective matched-cohort design, patients were categorized into cohorts of "uncontrolled" (≥ 2 changes in AED therapy, then ≥ 1 epilepsy-related ED visit/hospitalization within 1 year) and "well-controlled" (no AED change, no epilepsy-related ED visit/hospitalization) epilepsy. Matched cohorts were compared for health care resource utilization and costs using multivariate conditional regression models and nonparametric methods. From 110,312 (Medicaid) and 36,529 (employer) eligible patients, 3,454 and 602 with uncontrolled epilepsy were matched 1:1 to patients with well-controlled epilepsy, respectively. In both populations, uncontrolled epilepsy cohorts presented about 2 times more fractures and head injuries (all p values < 0.0001) and higher health care resource utilization (ranges of adjusted incidence rate ratios [IRRs] [all-cause utilization]: AEDs = 1.8-1.9, non-AEDs = 1.3-1.5, hospitalizations = 5.4-6.7, length of hospital stays = 7.3-7.7, ED visits = 3.7-5.0, outpatient visits = 1.4-1.7, neurologist visits = 2.3-3.1; all p values < 0.0001) than well-controlled groups. Total direct health care costs were higher in patients with uncontrolled epilepsy (adjusted cost difference [95% confidence interval (CI)] Medicaid = $12,258 [$10,482-$14,083]; employer = $14,582 [$12,019-$17,097]) vs well-controlled patients. Privately insured employees with uncontrolled epilepsy lost 2.5 times more work days, with associated indirect costs of $2,857 (95% CI $1,042-$4,581). Uncontrolled epilepsy in patients requiring ED visit or hospitalization was associated with significantly greater health care resource utilization and increased direct and indirect costs compared to well-controlled epilepsy in both publicly and privately insured settings.
Reyna-Bensusan, Natalia; Wilson, David C; Smith, Stephen R
2018-05-01
Uncontrolled burning of municipal solid waste (MSW) is an important source of air pollution and is wide spread in many developing countries, but only limited data quantify the extent of domestic open burning of household waste. Here, we present some of the first field data to be reported on the uncontrolled domestic burning of waste. A representative community of Mexico (Huejutla de Reyes Municipality) was investigated and household surveys, interviews with waste operators and a waste characterisation analysis were completed to assess the extent of, and factors controlling, the open burning of waste. Waste collection provision to rural communities was very limited and, consequently 92% of households in rural areas reported that they disposed of waste by uncontrolled burning in backyards or unofficial dumps. Overall, 24% of the total MSW generated in the Municipality was disposed by uncontrolled burning. Urban and periurban areas received twice-weekly collections and the rate of uncontrolled burning was considerably smaller compared to rural households, corresponding to approximately 2% of total waste generation. Carbon equivalency calculations showed that burning waste in backyards represented approximately 6% of the total and 8.5% of fuel related CO 2 Eq emissions by the municipality. Moreover, the equivalent carbon dioxide (CO 2 Eq) from black carbon (BC) emitted by uncontrolled burning in backyards was over fifteen times larger compared to methane (CH 4 ) potentially released from equivalent amounts of combustible biodegradable waste disposal at the official dumpsite. An assessment of local respiratory health data showed the incidence of disease was higher in rural than in urban areas, when the opposite trend is typically observed in the international literature; given the high rate of burning activity found in rural areas we suggest that open burning of waste could be a major reason for the apparent poorer respiratory health status of the rural population and requires further investigation. The results emphasise the importance of including BC from uncontrolled burning of waste in international emission inventories of greenhouse gases and in the assessment of the health status of local communities in developing countries where this practice is prevalent. Copyright © 2018 Elsevier Inc. All rights reserved.
Brod, Meryl; Pfeiffer, Kathryn M; Barnett, Anthony H; Berntorp, Kerstin; Vilsbøll, Tina; Weissenberger, Benno
2016-07-11
To investigate perceptions of control among people with uncontrolled and well controlled type 2 diabetes (T2D) treated with basal insulin, as well as differences in perceptions and diabetes management practices between the two groups. Web surveys of 1012 people with uncontrolled T2D (HbA 1c >8.0% or 64 mmol/mol) on basal insulin in Sweden, Switzerland, and the UK and 295 people with well controlled T2D (HbA 1c <7.5% or 58 mmol/mol) on basal insulin in the UK were conducted. People with uncontrolled T2D perceived a wide range of factors as very/extremely important for deciding whether they are well controlled, including diet (80.7%), HbA 1c value (78.9%), times per day insulin taken (78.8%), insulin units taken per day (77.6%), and energy levels (74.5%). Fifty-one percent of uncontrolled respondents considered the past week or more recently when thinking about control. Perceived major obstacles to control included stress (75.4%), other health issues (70.8%), medicine side effects (69.9%), food cravings (69.8%), doctor not understanding individual situation (67.6%), and life crises (66.9%). Many uncontrolled respondents reported that diabetes was very/extremely interfering with their lives, including energy level (71.0%), performance at work (70.0%), general health (69.9%), and doing what one wants (69.3%). Analyses showed significant differences between well controlled and uncontrolled UK respondents. Compared to the uncontrolled, people with well controlled T2D were significantly more likely to consider the last 24 hours/current time when thinking about control (50% vs. 21%, p < 0.001) and reported greater healthcare contact related to diabetes and more frequent glucose measurement. Study limits include potential selection bias of web surveys and possible recall bias in patient-reported data. The results illuminate how people with T2D treated with basal insulin perceive control and show important differences between the well controlled and uncontrolled. Findings may have implications for improving patient and physician education and diabetes management.
Tóth, Júlia; Bollins, Jack; Szczelkun, Mark D.
2015-01-01
DNA cleavage by the Type III restriction enzymes requires long-range protein communication between recognition sites facilitated by thermally-driven 1D diffusion. This ‘DNA sliding’ is initiated by hydrolysis of multiple ATPs catalysed by a helicase-like domain. Two distinct ATPase phases were observed using short oligoduplex substrates; the rapid consumption of ∼10 ATPs coupled to a protein conformation switch followed by a slower phase, the duration of which was dictated by the rate of dissociation from the recognition site. Here, we show that the second ATPase phase is both variable and only observable when DNA ends are proximal to the recognition site. On DNA with sites more distant from the ends, a single ATPase phase coupled to the conformation switch was observed and subsequent site dissociation required little or no further ATP hydrolysis. The overall DNA dissociation kinetics (encompassing site release, DNA sliding and escape via a DNA end) were not influenced by the second phase. Although the data simplifies the ATP hydrolysis scheme for Type III restriction enzymes, questions remain as to why multiple ATPs are hydrolysed to prepare for DNA sliding. PMID:26538601
Servagi-Vernat, Stéphanie; Créhange, Gilles; Bonnetain, Franck; Mertens, Cécile; Brain, Etienne; Bosset, Jean François
2017-07-13
The management of elderly patients with cancer is a therapeutic challenge and a public health problem. Definitive chemoradiotherapy (CRT) is an accepted standard treatment for patients with locally advanced esophageal cancer who cannot undergo surgery. However, there are few reports regarding tolerance to CRT in elderly patients. We previously reported results for CRT in patients aged ≥75 years. Following this first phase II trial, we propose to conduct a phase I/II study to evaluate the combination of carboplatin and paclitaxel, with concurrent RT in unresectable esophageal cancer patients aged 75 years or older. This prospective multicenter phase I/II study will include esophageal cancer in patients aged 75 years or older. Study procedures will consist to determinate the tolerated dose of chemotherapy (Carboplatin, paclitaxel) and of radiotherapy (41.4-45 and 50.4 Gy) in the phase I. Efficacy will be assessed using a co-primary endpoint encompassing health related quality of life and the progression-free survival in the phase II with the dose recommended of CRT in the phase I. This geriatric evaluation was defined by the French geriatric oncology group (GERICO). This trial has been designed to assess the tolerated dose of CRT in selected patient aged 75 years or older. Clinicaltrials.gov ID: NCT02735057 . Registered on 18 March 2016.
Gielkens, H A; van den Biggelaar, A; Vecht, J; Onkenhout, W; Lamers, C B; Masclee, A A
1999-02-01
Patients on total parenteral nutrition have an increased risk of developing gallstones because of gall bladder hypomotility. High dose amino acids may prevent biliary stasis by stimulating gall bladder emptying. To investigate whether intravenous amino acids also influence antroduodenal motility. Eight healthy volunteers received, on three separate occasions, intravenous saline (control), low dose amino acids (LDA), or high dose amino acids (HDA). Antroduodenal motility was recorded by perfusion manometry and duodenocaecal transit time (DCTT) using the lactulose breath hydrogen test. DCTT was significantly prolonged during LDA and HDA treatment compared with control. The interdigestive motor pattern was maintained and migrating motor complex (MMC) cycle length was significantly reduced during HDA compared with control and LDA due to a significant reduction in phase II duration. Significantly fewer phase IIIs originated in the gastric antrum during LDA and HDA compared with control. Duodenal phase II motility index was significantly reduced during HDA, but not during LDA, compared with control. Separate intravenous infusion of high doses of amino acids in healthy volunteers: (1) modulates interdigestive antroduodenal motility; (2) shortens MMC cycle length due to a reduced duration of phase II with a lower contractile incidence both in the antrum and duodenum (phase I remains unchanged whereas the effect on phase III is diverse: in the antrum phase III is suppressed and in the duodenum the frequency is increased); and (3) prolongs interdigestive DCTT.
Klinck, Mary P; Monteiro, Beatriz P; Lussier, Bertrand; Guillot, Martin; Moreau, Maxim; Otis, Colombe; Steagall, Paulo Vm; Frank, Diane; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Del Castillo, Jérôme Re; Troncy, Eric
2017-09-01
Objectives Feline osteoarthritis causes pain and disability. Detection and measurement is challenging, relying heavily on owner report. This study describes refinement of the Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians. Methods A video analysis of osteoarthritic (n = 6) and non-osteoarthritic (n = 4) cats facilitated expansion of scale items. Three successive therapeutic trials (using gabapentin, tramadol and oral transmucosal meloxicam spray) in laboratory cats with and without natural osteoarthritis (n = 12-20), permitted construct validation (assessments of disease status sensitivity and therapeutic responsiveness) and further scale refinements based on performance. Results Scale osteoarthritic sensitivity improved from phase I to phase III; phase III scale total score ( P = 0.0001) and 4/5 subcategories - body posture ( P = 0.0006), gait ( P = 0.0031), jumping (0.0824) and global distance examination ( P = 0.0001) - detected osteoarthritic cats. Total score inter-rater (intra-class correlation coefficients [ICC] = 0.64-0.75), intra-rater (ICC = 0.90-0.91) and overall internal consistency (Cronbach's alpha = 0.85) reliability were good to excellent. von Frey anesthesiometer-induced paw withdrawal threshold increased with gabapentin in phase I, in osteoarthritic cats ( P <0.001) but not in non-osteoarthritic cats ( P = 0.075). Night-time activity increased during gabapentin treatment. Objective measures also detected tramadol and/or meloxicam treatment effects in osteoarthritic cats in phases II and III. There was some treatment responsiveness: in phase I, 3/10 subcategory scores improved ( P <0.09) in treated osteoarthritic cats; in phase II, 3/8 subcategories; and in phase III, 1/5 subcategories improved ( P <0.096). Conclusions and relevance The revised scale detected naturally occurring osteoarthritis, but not treatment effects, in laboratory cats, suggesting future potential for screening of at-risk cats. Further study is needed to confirm reliability, validity (disease sensitivity and treatment responsiveness) and clinical feasibility, as well as cut-off scores for osteoarthritic vs non-osteoarthritic status, in client-owned cats.
Quan, Huibiao; Zhang, Huachuan; Wei, Weiping; Fang, Tuanyu; Chen, Daoxiong; Chen, Kaining
2017-01-01
The aim of the present study was to explore the effects of various combinations of exenatide, metformin (MET) and biphasic insulin aspart 30 (BIA30) on type 2 diabetes mellitus (T2DM). Two hundred overweight or obese patients newly diagnosed with T2DM were evenly randomized into two groups: A (twice daily for all: Phase I, 5 µg exenatide + 0.5 g MET for 4 weeks, then 10 µg exenatide + 0.5 g MET for 8 weeks; Phase II, 0.5 g MET for 12 weeks; Phase III, 0.3–0.4 U/kg/day BIA30 + 0.5 g MET for 12 weeks) and B (Phases I, II, III matched the phases III, II and I in group A). In groups A and B a significant decrease and increase, respectively, in glycated hemoglobin (HbAlc) and body mass index (BMI) was noted during Phase I. A 3.2±0.4-kg decrease in body weight in group A and a 2.6±0.3-kg increase in group B was observed. In Phase II, HbAlc was significantly increased in both groups (P<0.05). In Phase III, the BMI was increased in group A and reduced in group B (P<0.05). There was a 3.8±0.4-kg weight decrease in group B and 4.2±0.5-kg increase in group A (P<0.05). The combination of exenatide and MET promoted weight loss, glycemic control, β-cell function index, C peptide and adiponectin levels. These results suggested that the combination of exenatide and MET is better than the combination of BIA and MET for the therapy of overweight or obese patients newly diagnosed with T2DM. PMID:28912879
Guideline-based intervention to reduce telemetry rates in a large tertiary centre.
Ramkumar, Satish; Tsoi, Edward H; Raghunath, Ajay; Dias, Floyd F; Li Wai Suen, Christopher; Tsoi, Andrew H; Mansfield, Darren R
2017-07-01
Inappropriate cardiac telemetry use is associated with reduced patient flow and increased healthcare costs. To evaluate the outcomes of guideline-based application of cardiac telemetry. Phase I involved a prospective audit (March to August 2011) of telemetry use at a tertiary hospital. Data were collected on indication for telemetry and clinical outcomes. Phase II prospectively included patients more than 18 years under general medicine requiring ward-based telemetry. As phase II occurred at a time remotely from phase I, an audit similar to phase I (phase II - baseline) was completed prior to a 3-month intervention (May to August 2015). The intervention consisted of a daily telemetry ward round and an admission form based on the American Heart Association guidelines (class I, telemetry indicated; class II, telemetry maybe indicated; class III, telemetry not indicated). Patient demographics, telemetry data, and clinical outcomes were studied. Primary endpoint was the percentage reduction of class III indications, while secondary endpoint included telemetry duration. In phase I (n = 200), 38% were admitted with a class III indication resulting in no change in clinical management. A total of 74 patients was included in phase II baseline (mean ± standard deviation (SD) age 73 years ± 14.9, 57% male), whilst 65 patients were included in the intervention (mean ± SD age 71 years ± 18.4, 35% male). Both groups had similar baseline characteristics. There was a reduction in class III admissions post-intervention from 38% to 11%, P < 0.001. Intervention was associated with a reduction in median telemetry duration (1.8 ± 1.8 vs 2.4 ± 2.5 days, P = 0.047); however, length of stay was similar in both groups (P > 0.05). Guideline-based telemetry admissions and a regular telemetry ward round are associated with a reduction in inappropriate telemetry use. © 2017 Royal Australasian College of Physicians.
NASA Astrophysics Data System (ADS)
Heinzmann, U.; Helmstedt, A.; Dohmeier, N.; Müller, N.; Gryzia, A.; Brechling, A.; Hoeke, V.; Krickemeyer, E.; Glaser, T.; Fonin, M.; Bouvron, S.; Leicht, P.; Tietze, T.; Goering, E.; Kuepper, K.
2014-04-01
It is demonstrated that local magnetic moments of single molecule magnets (SMM) normally studied by XMCD at very low temperatures and high magnetic fields can be measured by means of spin-resolved electron emission in the paramagnetic phase at room temperature by use of circularly polarized radiation.
Pilot preference and procedures at uncontrolled airports
NASA Technical Reports Server (NTRS)
Parker, L. C.
1975-01-01
The report presents the results of a pilot questionnaire utilized at the 1974 Reading, Pennsylvania Air Show to obtain data on pilot procedures and preference in the terminal airspace of uncontrolled airports.
High-pressure phase transitions, amorphization, and crystallization behaviors in Bi2Se3.
Zhao, Jinggeng; Liu, Haozhe; Ehm, Lars; Dong, Dawei; Chen, Zhiqiang; Gu, Genda
2013-03-27
The phase transition, amorphization, and crystallization behaviors of the topological insulator bismuth selenide (Bi2Se3) were discovered by performing in situ high-pressure angle-dispersive x-ray diffraction experiments during an increasing, decreasing, and recycling pressure process. In the compression process, Bi2Se3 transforms from the original rhombohedral structure (phase I(A)) to a monoclinic structure (phase II) at about 10.4 GPa, and further to a body-centered tetragonal structure (phase III) at about 24.5 GPa. When releasing pressure to ambient conditions after the complete transformation from phase II to III, Bi2Se3 becomes an amorphous solid (AM). In the relaxation process from this amorphous state, Bi2Se3 starts crystallizing into an orthorhombic structure (phase I(B)) about five hours after releasing the pressure to ambient. A review of the pressure-induced phase transition behaviors of A2B3-type materials composed from the V and VI group elements is presented.
Furtado, Jeremy D.; Wedel, Mark K.; Sacks, Frank M.
2012-01-01
Mipomersen, an antisense oligonucleotide that reduces hepatic production of apoB, has been shown in phase 2 studies to decrease plasma apoB, LDL cholesterol (LDL-C), and triglycerides. ApoC-III inhibits VLDL and LDL clearance, and it stimulates inflammatory responses in vascular cells. Concentrations of VLDL or LDL with apoC-III independently predict cardiovascular disease. We performed an exploratory posthoc analysis on a subset of hypercholesterolemic subjects obtained from a randomized controlled dose-ranging phase 2 study of mipomersen receiving 100, 200, or 300 mg/wk, or placebo for 13 wk (n = 8 each). ApoC-III–containing lipoproteins were isolated by immuno-affinity chromatography and ultracentrifugation. Mipomersen 200 and 300 mg/wk reduced total apoC-III from baseline by 6 mg/dl (38–42%) compared with placebo group (P < 0.01), and it reduced apoC-III in both apoB lipoproteins and HDL. Mipomersen 100, 200, and 300 mg doses reduced apoB concentration of LDL with apoC-III (27%, 38%, and 46%; P < 0.05). Mipomersen reduced apoC-III concentration in HDL. The drug had no effect on apoE concentration in total plasma and in apoB lipoproteins. In summary, antisense inhibition of apoB synthesis reduced plasma concentrations of apoC-III and apoC-III–containing lipoproteins. Lower concentrations of apoC-III and LDL with apoC-III are associated with reduced risk of coronary heart disease (CHD) in epidemiologic studies independent of traditional risk factors. PMID:22301884
Method for Improving Mg Doping During Group-III Nitride MOCVD
Creighton, J. Randall; Wang, George T.
2008-11-11
A method for improving Mg doping of Group III-N materials grown by MOCVD preventing condensation in the gas phase or on reactor surfaces of adducts of magnesocene and ammonia by suitably heating reactor surfaces between the location of mixing of the magnesocene and ammonia reactants and the Group III-nitride surface whereon growth is to occur.
Impact of Availability of Companion Diagnostics on the Clinical Development of Anticancer Drugs.
Tibau, Ariadna; Díez-González, Laura; Navarro, Beatriz; Galán-Moya, Eva M; Templeton, Arnoud J; Seruga, Bostjan; Pandiella, Atanasio; Amir, Eitan; Ocana, Alberto
2017-06-01
Companion diagnostics permit the selection of patients likely to respond to targeted anticancer drugs; however, it is unclear if the drug development process differs between drugs developed with or without companion diagnostics. Identification of differences in study design could help future clinical development. Anticancer drugs approved for use in solid tumors between 28 September 2000 and 4 January 2014 were identified using a search of the US FDA website. Phase III trials supporting registration were extracted from the drug label. Each published study was reviewed to obtain information about the phase I and II trials used for the development of the respective drug. We identified 35 drugs and 59 phase III randomized trials supporting regulatory approval. Fifty-three phase I trials and 47 phase II trials were cited in the studies and were used to support the design of these phase III trials. The approval of drugs using a companion diagnostic has increased over time (p for trend 0.01). Expansion cohorts were more frequently observed with drugs developed with a companion diagnostic (62 vs. 20%; p = 0.005). No differences between drugs developed with or without a companion diagnostic were observed for the design of phase I and II studies. The approval of drugs developed with a companion diagnostic has increased over time. The availability of a companion diagnostic was associated with more frequent use of phase I expansion cohorts comprising patients selected by the companion diagnostic.
Reznik, Samantha J; Nusslock, Robin; Pornpattananangkul, Narun; Abramson, Lyn Y; Coan, James A; Harmon-Jones, Eddie
2017-08-01
Research suggests that midline posterior versus frontal electroencephalographic (EEG) theta activity (PFTA) may reflect a novel neurophysiological index of approach motivation. Elevated PFTA has been associated with approach-related tendencies both at rest and during laboratory tasks designed to enhance approach motivation. PFTA is sensitive to changes in dopamine signaling within the fronto-striatal neural circuit, which is centrally involved in approach motivation, reward processing, and goal-directed behavior. To date, however, no studies have examined PFTA during a laboratory task designed to reduce approach motivation or goal-directed behavior. Considerable animal and human research supports the hypothesis put forth by the learned helplessness theory that exposure to uncontrollable aversive stimuli decreases approach motivation by inducing a state of perceived uncontrollability. Accordingly, the present study examined the effect of perceived uncontrollability (i.e., learned helplessness) on PFTA. EEG data were collected from 74 participants (mean age = 19.21 years; 40 females) exposed to either Controllable (n = 26) or Uncontrollable (n = 25) aversive noise bursts, or a No-Noise Condition (n = 23). In line with prediction, individuals exposed to uncontrollable aversive noise bursts displayed a significant decrease in PFTA, reflecting reduced approach motivation, relative to both individuals exposed to controllable noise bursts or the No-Noise Condition. There was no relationship between perceived uncontrollability and frontal EEG alpha asymmetry, another commonly used neurophysiological index of approach motivation. Results have implications for understanding the neurophysiology of approach motivation and establishing PFTA as a neurophysiological index of approach-related tendencies.
2011-01-01
Background Uncontrollable aversive events are associated with feelings of helplessness and cortisol elevation and are suitable as a model of depression. The high comorbidity of depression and pain symptoms and the importance of controllability in both conditions are clinically well-known but empirical studies are scarce. The study investigated the relationship of pain experience, helplessness, and cortisol secretion after controllable vs. uncontrollable electric skin stimulation in healthy male individuals. Methods Sixty-four male volunteers were randomly assigned to receive 30 controllable (self-administered) or uncontrollable (experimenter-administered) painful electric skin stimuli. Perceived pain intensity (PPI), subjective helplessness ratings, and salivary cortisol concentrations were assessed. PPI was assessed after stress exposure. For salivary cortisol concentrations and subjective helplessness ratings, areas under the response curve (AUC) were calculated. Results After uncontrollable vs. controllable stress exposure significantly higher PPI ratings (P = 0.023), higher subjective helplessness AUC (P < 0.0005) and higher salivary cortisol AUC (P = 0.004, t-tests) were found. Correlation analyses revealed a significant correlation between subjective helplessness AUC and PPI (r = 0.500, P < 0.0005), subjective helplessness AUC and salivary cortisol AUC (r = 0.304, P = 0.015) and between PPI and salivary cortisol AUC (r = 0.298, P = 0.017). Conclusions The results confirm the impact of uncontrollability on stress responses in humans; the relationship of PPI with subjective helplessness and salivary cortisol suggests a cognitive-affective sensitization of pain perception, particularly under uncontrollable conditions. PMID:21718526
Sorption of Ferrioxime B to Synthetic and Biogenic layer type Mn Oxides
NASA Astrophysics Data System (ADS)
Duckworth, O. W.; Bargar, J. R.; Sposito, G.
2005-12-01
Siderophores are biogenic chelating agents produced in terrestrial and marine environments to increase the bioavailablity of ferric iron. Recent work has suggested that both aqueous and solid-phase Mn(III) may affect siderophore-mediated iron transport, but no information appears to be available about the effect of solid-phase Mn(IV). To probe the effect of solid-phase Mn(IV), we studied the sorption reaction of ferrioxamine B [principally the species, Fe(III)HDFOB+, an Fe(III) chelate of the trihydroxamate siderophore, desferrioxamine B (DFOB)] with two synthetic birnessites [layer type Mn(IV) oxides] and a biogenic birnessite produced by Pseudomonas putida MnB1. We found that all of these predominantly Mn(IV) oxides greatly reduced the aqueous concentration of Fe(III)HDFOB+ over the pH range between 5 and 9. After 72 h equilibration time at pH 8, the sorption behavior for the synthetic birnessites could be accurately described by a Langmuir isotherm; for the biogenic oxide, a Freundlich isotherm was best utilized to model the sorption data. To study the molecular nature of the interaction between the Fe(III)HDFOB+ complex and the oxide surface, Fe K-edge extended X-Ray absorption fine structure (EXAFS) spectroscopy was employed. Analysis of the X-ray absorption spectra indicated that Fe(III) associated with the Mn(IV) oxides is not complexed with DFOB, but instead is incorporated into the mineral structure, thus implying that the Mn(IV) oxides displaced Fe(III) from the siderophore complex. These results indicate that manganese oxides, including biominerals, may strongly sequester iron from soluble ferric complexes and thus may play a significant role in the biogeochemical cycling of iron.
NASA Astrophysics Data System (ADS)
Jew, A. D.; Dustin, M. K.; Harrison, A. L.; Joe-Wong, C. M.; Thomas, D.; Maher, K.; Brown, G. E.; Bargar, J.
2016-12-01
Due to the rapid growth of hydraulic fracturing in the United States, understanding the cause for the rapid production drop off of new wells over the initial months of production is paramount. One possibility for the production decrease is pore occlusion caused by the oxidation of Fe(II)-bearing phases resulting in Fe(III) precipitates. To understand the release and fate of Fe in the shale systems, we reacted synthesized fracture fluid at 80oC with shale from four different geological localities (Marcellus Fm., Barnett Fm., Eagle Ford Fm., and Green River Fm.). A variety of wet chemical and synchrotron-based techniques (XRF mapping and x-ray absorption spectroscopy) were used to understand Fe release and solid phase Fe speciation. Solution pH was found to be the greatest factor for Fe release. Carbonate-poor Barnett and Marcellus shale showed rapid Fe release into solution followed by a plateau or significant drop in Fe concentrations indicating mineral precipitation. Conversely, in high carbonate shales, Eagle Ford and Green River, no Fe was detected in solution indicating fast Fe oxidation and precipitation. For all shale samples, bulk Fe EXAFS data show that a significant amount of Fe in the shales is bound directly to organic carbon. Throughout the course of the experiments inorganic Fe(II) phases (primarily pyrite) reacted while Fe(II) bound to C showed no indication of reaction. On the micron scale, XRF mapping coupled with μ-XANES spectroscopy showed that at pH < 4.0, Fe(III) bearing phases precipitated as diffuse surface precipitates of ferrihydrite, goethite, and magnetite away from Fe(II) point sources. In near circum-neutral pH systems, Fe(III)-bearing phases (goethite and hematite) form large particles 10's of μm's in diameter near Fe(II) point sources. Idealized systems containing synthesized fracturing fluid, dissolved ferrous chloride, and bitumen showed that bitumen released during reaction with fracturing fluids is capable of oxidizing Fe(II) to Fe(III) at pH's 2.0 and 7.0. This indicates that bitumen can play a large role in Fe oxidation and speciation in the subsurface. This work shows that shale mineralogy has a significant impact on the morphology and phases of Fe(III) precipitates in the subsurface which in turn can significantly impact subsurface solution flow.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Goldman, N; Leforestier, C; Saykally, R J
We present results of gas phase cluster and liquid water simulations from the recently determined VRT(ASP-W)III water dimer potential energy surface. VRT(ASP-W)III is shown to not only be a model of high ''spectroscopic'' accuracy for the water dimer, but also makes accurate predictions of vibrational ground-state properties for clusters up through the hexamer. Results of ambient liquid water simulations from VRT(ASP-W)III are compared to those from ab initio Molecular Dynamics, other potentials of ''spectroscopic'' accuracy, and to experiment. The results herein represent the first time that a ''spectroscopic'' potential surface is able to correctly model condensed phase properties of water.
School Emergencies--Preparation Not Panic.
ERIC Educational Resources Information Center
Sousa, Barbara
1982-01-01
A three-phase emergency recognition course was designed to train 26 faculty and staff members to recognize and respond to emergency school medical situations. Phase I included comprehensive first aid, cardiopulmonary resuscitation (CPR), and injections. Phase II dealt with recognition of medical emergencies, and Phase III recertified those who had…
NASA Astrophysics Data System (ADS)
Pippinger, T.; Miletich, R.; Merlini, M.; Lotti, P.; Schouwink, P.; Yagi, T.; Crichton, W. A.; Hanfland, M.
2015-01-01
High-pressure phase transformations between the polymorphic forms I, II, III, and IIIb of CaCO3 were investigated by analytical in situ high-pressure high-temperature experiments on oriented single-crystal samples. All experiments at non-ambient conditions were carried out by means of Raman scattering, X-ray, and synchrotron diffraction techniques using diamond-anvil cells in the pressure range up to 6.5 GPa. The composite-gasket resistive heating technique was applied for all high-pressure investigations at temperatures up to 550 K. High-pressure Raman spectra reveal distinguishable characteristic spectral differences located in the wave number range of external modes with the occurrence of band splitting and shoulders due to subtle symmetry changes. Constraints from in situ observations suggest a stability field of CaCO3-IIIb at relatively low temperatures adjacent to the calcite-II field. Isothermal compression of calcite provides the sequence from I to II, IIIb, and finally, III, with all transformations showing volume discontinuities. Re-transformation at decreasing pressure from III oversteps the stability field of IIIb and demonstrates the pathway of pressure changes to determine the transition sequence. Clausius-Clapeyron slopes of the phase boundary lines were determined as: Δ P/Δ T = -2.79 ± 0.28 × 10-3 GPa K-1 (I-II); +1.87 ± 0.31 × 10-3 GPa K-1 (II/III); +4.01 ± 0.5 × 10-3 GPa K-1 (II/IIIb); -33.9 ± 0.4 × 10-3 GPa K-1 (IIIb/III). The triple point between phases II, IIIb, and III was determined by intersection and is located at 2.01(7) GPa/338(5) K. The pathway of transition from I over II to IIIb can be interpreted by displacement with small shear involved (by 2.9° on I/II and by 8.2° on II/IIIb). The former triad of calcite-I corresponds to the [20-1] direction in the P21/ c unit cell of phase II and to [101] in the pseudomonoclinic C setting of phase IIIb. Crystal structure investigations of triclinic CaCO3-III at non-ambient pressure-temperature conditions confirm the reported structure, and the small changes associated with the variation in P and T explain the broad stability of this structure with respect to variations in P and T. PVT equation of state parameters was determined from experimental data points in the range of 2.20-6.50 GPa at 298-405 K providing = 87.5(5.1) GPa, ( δK T/ δT) P = -0.21(0.23) GPa K-1, α 0 = 0.8(21.4) × 10-5 K-1, and α 1 = 1.0(3.7) × 10-7 K-1 using a second-order Birch-Murnaghan equation of state formalism.
Fujita, Yasuki; Shimizu, Tomoaki; Matsumoto, Atsuhiro; Aoki, Motoaki
2008-09-01
Thyroid storm, sudden onset of life-threatening manifestations of hyperthyroidism, often appears during and after surgery in patients with uncontrolled hyperthyroidism. We report perioperative and postoperative management of two such cases with uncontrolled hyperthyroidism. The first patient is a 41-year-old man with a past history of uncontrolled Graves disease, and was scheduled for emergency video-assisted thoracoscopic surgery for spontaneous pneumothorax. The second patient is a 25-year-old man with a past history of hypertension, and was scheduled for open reduction and internal fixation for mandibular fracture. In both patients, tachycardia and hypertension were observed at admission to the operating room. Therapy included the use of landiolol infusion, a short acting beta blocker, for control of tachycardia. Heart rate was controlled around 90 beats x min(-1) using landiolol during surgery. In each case, landiolol was administered until they can take long acting beta blocker and antithyroid drug orally. In the postoperative period, delirium appeared for a few hours in the first case, but no severe complications were observed in each case. Short acting beta blocker was useful for control of tachycardia in the perioperative and postoperative management of the patient with uncontrolled hyperthyroidism.
Kim, Jin Yong; Yang, Soo Hyun; Kwon, Jihyun; Lee, Hyun Woo; Kim, Hyun
2017-03-30
The unpredictable and inescapable electric shock-induced "learned helplessness" paradigm has long been used to produce an animal model of depression to identify the molecules associated with depressive symptoms or to assess the efficacy of pharmacological treatments for depression. After exposure to unpredictable and inescapable shocks (uncontrollable stress), most of mice showed defect in escape behavior in active avoidance test (learned helplessness, LH), while others did not (non-learned helplessness, NLH). Here, we investigated whether mice with LH or NLH exhibited depressive symptoms, including anhedonia, anxiety, and despair. We found that compared with control naïve mice, both uncontrollable shocks-induced LH and NLH mice showed increased anhedonia- and anxiety- but not despair-like behaviors. Notably, mice subjected to uncontrollable shocks showed similar behaviors, irrespective of whether they also showed LH or NLH. Furthermore, since both LH and NLH mice showed only anhedonia- and anxiety- but not despair-like behaviors, this model may be generally inadequate for classic depression-like behavior assessment. In conclusion, uncontrollable electric shock induces depression-like behavior, irrespective of the state of helplessness. Copyright © 2017 Elsevier B.V. All rights reserved.
2011-04-01
a ‘strategy as process’ manner to develop capabilities that are flexible, adaptable and robust. 3.4 Future structures The need for agile...to develop models of the future security environment 3.4.10 Planning Under Deep Uncertainty Future structures The need for agile, flexible and... Organisation NEC Network Enabled Capability NGO Non Government Organisation NII Networking and Information Infrastructure PVO Private Voluntary
NASA Technical Reports Server (NTRS)
Berman, A. L.
1977-01-01
An algorithm was developed for the continuous and automatic computation of Doppler noise concurrently at four sample rate intervals, evenly spanning three orders of magnitude. Average temporal Doppler phase fluctuation spectra will be routinely available in the DSN tracking system Mark III-77 and require little additional processing. The basic (noise) data will be extracted from the archival tracking data file (ATDF) of the tracking data management system.
Vithanage, Meththika; Wijesekara, Hasintha; Mayakaduwa, S S
2017-07-01
Extract and analysis of the Dissolved Organic Carbon (DOC) fractions were analyzed from the leachate of an uncontrolled dumpsite at Gohagoda, Sri Lanka. DOC fractions, humic acid (HA), fulvic acid (FA) and the hydrophilic (Hyd) fractions were isolated and purified with the resin techniques. Spectroscopic techniques and elemental analysis were performed to characterize DOCs. Maximum TOC and DOC values recorded were 56,955 and 28,493 mg/L, respectively. Based on the total amount of DOC fractionation, Hyd dominated accounting for ∼60%, and HA and FA constituted ∼22% and ∼17%, respectively, exhibiting the mature phase of the dumpsite. The elemental analysis of DOCs revealed carbon variation following HA > FA > Hyd, while hydrogen and nitrogen were similar in each fraction. The N/C ratio for HA was recorded as 0.18, following a similar trend in old dumpsite leachate elsewhere. The O/C ratios for HA and FA were recorded higher as much as 1.0 and 9.3, respectively, indicating high degree of carbon mineralization in the leachates. High content of carboxylic, phenolic and lactone groups in all DOCs was observed disclosing their potential for toxic substances transportation. The results strongly suggest the risk associated with DOCs in dumpsite leachate to the aquatic and terrestrial environment.
Plaza, V; Quirce, S; Delgado, J; Martinez Moragón, E; Pérez de Llano, L
2016-11-21
Background. Numerous studies conclude that about half of the asthmatic population is not well controlled. The aim of this study was to discuss causes, consequences and possible solutions of uncontrolled asthma (UCA). Methods. Discussion amongst asthma experts from the fields of Pneumology, Allergy and Primary Care, structured in three phases: 1) survey to get the opinion of participants involved in different areas of UCA; 2) expert meeting, in which the results of the survey were discussed, and the diagnosis, treatment and monitoring of UCA were presented and discussed; and, 3) with the main findings, 83 items were formulated and subjected to consensus among all participants through the Delphi method. Results. There was consensus on 86.7% of the items in the Delphi questionnaire, mostly in terms of agreement. Conclusions. The UCA analysis results show the need for future improvement in the following areas: to incorporate clinical performance protocols into asthma CPG to identify aggravating factors and comorbidities; to develop an inexpensive and easy-to-use tool to identify adherence; to establish patient phenotype; to analyse treatment side effects and to provide personalized treatment, especially assessing its efficacy and safety (symptom control and future risks). It is necessary to generate new evidence to determine additional tests to be used to monitor these patients.
Lee, Sin-Ae; Lee, Sung-Yul; Cho, Ik-Hyun; Oh, Min-A; Kang, Eun-Sil; Kim, Yong-Bae; Seo, Woo Duck; Choi, Suyong; Nam, Ju-Ock; Tamamori-Adachi, Mimi; Kitajima, Shigetaka; Ye, Sang-Kyu; Kim, Semi; Hwang, Yoon-Jin; Kim, In-San; Park, Ki Hun; Lee, Jung Weon
2008-01-01
The growth of normal cells is arrested when they come in contact with each other, a process known as contact inhibition. Contact inhibition is lost during tumorigenesis, resulting in uncontrolled cell growth. Here, we investigated the role of the tetraspanin transmembrane 4 superfamily member 5 (TM4SF5) in contact inhibition and tumorigenesis. We found that TM4SF5 was overexpressed in human hepatocarcinoma tissue. TM4SF5 expression in clinical samples and in human hepatocellular carcinoma cell lines correlated with enhanced p27Kip1 expression and cytosolic stabilization as well as morphological elongation mediated by RhoA inactivation. These TM4SF5-mediated effects resulted in epithelial-mesenchymal transition (EMT) via loss of E-cadherin expression. The consequence of this was aberrant cell growth, as assessed by S-phase transition in confluent conditions, anchorage-independent growth, and tumor formation in nude mice. The TM4SF5-mediated effects were abolished by suppressing the expression of either TM4SF5 or cytosolic p27Kip1, as well as by reconstituting the expression of E-cadherin. Our observations have revealed a role for TM4SF5 in causing uncontrolled growth of human hepatocarcinoma cells through EMT. PMID:18357344
Phase III Archives | NOAA Gulf Spill Restoration
III Early Restoration Plan and Draft Early Restoration PEIS Executive Summary (pdf, 3.4 MB) Project Summary Table (pdf, 80 KB) Public Repositories (pdf, 113 KB) Press Release (pdf, 501 KB) Press Release
Zhang, Li; Li, Zhenhua; Hu, Zheng; Chang, Xijun
2011-09-01
The first study on the high efficiency of triocarbohydrazide modified attapulgite as solid-phase extractant for preconcentration of trace Au(III) prior to the measurement by inductively coupled plasma optical emission spectrometry (ICP-OES) has been reported. Experimental conditions for effective adsorption of trace levels of Au(III) were optimized with respect to different experimental parameters using batch and column procedures in detail. At pH 3, Au(III) could be quantitatively adsorbed on the new sorbent, and the adsorbed Au(III) could be completely eluted from the sorbent surface by 2.0mL 1.0molL(-1) of HCl+2% CS(NH(2))(2) solution. An enrichment factor of 150 was accomplished. Moreover, common interfering ions did not interfere in both separation and determination. The maximum adsorption capacity of the sorbent for Au(III) was found to be 66.7mgg(-1). The detection limit (3σ) of this method was 0.32μgL(-1) and the relative standard deviation (RSD) was 3.3% (n=8). The method, with high selectivity, sensitivity and reproducibility, was validated using certified reference materials, and had been applied for the determination of trace Au(III) with satisfactory results. Copyright © 2011 Elsevier B.V. All rights reserved.
Chromium(iii) oxidation by biogenic manganese oxides with varying structural ripening.
Tang, Yuanzhi; Webb, Samuel M; Estes, Emily R; Hansel, Colleen M
2014-09-20
Manganese (Mn) oxides, which are generally considered biogenic in origin within natural systems, are the only oxidants of Cr(iii) under typical environmental conditions. Yet the influence of Mn biooxide mineral structural evolution on Cr(iii) oxidation under varying geochemical conditions is unknown. In this study we examined the role of light, organic carbon, pH, and the structure of biogenic Mn oxides on Cr(iii) oxidation. Aging of Mn oxides produced by a marine bacterium within the widespread Roseobacter clade resulted in structural ripening from a colloidal hexagonal to a particulate triclinic birnessite phase. The structurally diverse Mn oxides were then reacted with aqueous Cr(iii) within artificial seawater in the presence or absence of carbon and light. Here we found that Cr(iii) oxidation capacity was highest at near neutral pH and in the combined presence of carbon and light. Mn oxide ripening from a hexagonal to a triclinic birnessite phase led to decreased Cr(iii) oxidation in the presence of carbon and light, whereas no change in reactivity was observed in the absence of carbon and/or in the dark. As only minimal Cr(iii) oxidation was observed in the absence of Mn oxides, these results strongly point to coupled Mn oxide- and photo-induced generation of organic and/or oxygen radicals involved in Cr(iii) oxidation. Based on Mn oxide concentration and structural trends, we postulate that Mn(ii) produced from the oxidation of Cr(iii) by the primary Mn oxide is recycled in the presence of organics and light conditions, (re)generating secondary hexagonal birnessite and thereby allowing for continuous oxidation of Cr(iii). In the absence of this Mn oxide regeneration, Cr(iii) induced structural ripening of the hexagonal birnessite precludes further Cr(iii) oxidation. These results highlight the complexity of reactions involved in Mn oxide mediated Cr(iii) oxidation and suggest that photochemical carbon reactions are requisite for sustained Cr(iii) oxidation and persistence of reactive Mn oxides.
Kobalava, Z D; Villevalde, S V; Kulakov, V V
2017-11-01
To study effects of a fixed azilsartan medoxomil/chlorthalidone combination (Edarbi Clo) on clinical, ambulatory and central blood pressure (BP) in patients with uncontrolled arterial hypertension (AH)). Patients (n=25) with uncontrolled AH were given fixed azilsartan medoxomil/chlorthalidone combination (40 / 12.5 mg / day) for 4 weeks. After 4 weeks, in patients who did not achieve target BP levels the dose was increased up to 40 / 25 mg / day. Duration of the study was 12 weeks. After 12 weeks of treatment 88 % of patients achieved target clinical BP (.
Complexation Enhancement Drives Water-to-Oil Ion Transport: A Simulation Study
DOE Office of Scientific and Technical Information (OSTI.GOV)
Qiao, Baofu; Ferru, Geoffroy; Ellis, Ross J.
We address the structures and energetics of ion solvation in aqueous and organic solutions to understand liquid-liquid ion transport. Atomistic molecular dynamics (MD) simulations with polarizable force field are performed to study the coordination transformations driving lanthanide (Ln(III)) and nitrate ion transport between aqueous and an alkylamide-oil solution. An enhancement of the coordination behavior in the organic phase is achieved in contrast with the aqueous solution. In particular, the coordination number of Ce3+ increases from 8.9 in the aqueous to 9.9 in the organic solutions (from 8 in the aqueous to 8.8 in the organic systems for Yb3+). Moreover, themore » local coordination environ ment changes dramatically. Potential of mean force calculations show that the Ln(III)-ligand coordination interaction strengths follow the order of Ln(III-)nitrate> Ln(III)-water>Ln(III)-DMDBTDMA. They increase 2-fold in the lipophilic environment in comparison to the aqueous phase, and we attribute this to the shedding of the outer solvation shell. Our findings highlight the importance of outer sphere interactions on the competitive solvation energetics that cause ions to migrate between immiscible phases; an essential ingredient for advancing important applications such as rare earth metal separations. Some open questions in simulating the coordination behavior of heavy metals are also addressed.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hawkins, Cory A.; Bustillos, Christian G.; May, Iain
Conventional solvent extraction of selected f-element cations by bis(2-ethylhexyl)phosphoric acid (HDEHP) yields increased extraction from aqueous to organic solution along the series Np(V) < Cm(III) < Eu(III) < U(VI), with distribution ratios all within two orders of magnitude. However, in the presence of the water-soluble tetradentate Schiff base (N,N'-bis(5-sulfonatosalicylidene)-ethylenediamine or H 2salenSO 3), selective complexation of the two actinyl cations (Np(V) and U(VI)) resulted in an extraction order of Np(V) < U(VI) << Eu(III) < Cm(III). The extraction of neither Cm(III) or Eu(III) by HDEHP are significantly impacted by the presence of the aqueous phase Schiff base. Despite observed hydrolyticmore » decomposition of H 2salenSO 3 in aqueous solutions, the calculated high conditional stability constant (β 11 = 26) for the complex [UO 2(salenSO 3)] 2- demonstrates its capacity for aqueous hold-back of U(VI). UV-visible-NIR spectroscopy of solutions prepared with a Np(VI) stock and H 2salenSO 3 suggest that reduction of Np(VI) to Np(V) by the ligand was rapid, resulting in a pentavalent Np complex that was substantially retained in the aqueous phase. Lastly, results from 1H NMR of aqueous solutions of H 2salenSO 3 with U(VI) and La(III), Eu(III), and Lu(III) provides additional evidence that the ligand readily chelates U(VI), but has only weak interactions with trivalent lanthanide ions.« less
ELM suppression in helium plasmas with 3D magnetic fields
Evans, T. E.; Loarte, A.; Orlov, D. M.; ...
2017-06-21
Experiments in DIII-D, using non-axisymmetric magnetic perturbation fields in high-purity low toroidal rotation, 4He plasmas have resulted in Type-I edge localized mode (ELM) suppression and mitigation. Suppression is obtained in plasmas with zero net input torque near the L–H power threshold using either electron cyclotron resonant heating (ECRH) or balanced co- and counter-I p neutral beam injection (NBI) resulting in conditions equivalent to those expected in ITER's non-active operating phase. In low-power ECRH H-modes, periods with uncontrolled density and impurity radiation excursions are prevented by applying n = 3 non-axisymmetric magnetic perturbation fields. ELM suppression results from a reduction andmore » an outward shift of the electron pressure gradient peak compared to that in the high-power ELMing phase. Here, the change in the electron pressure gradient peak is primarily due to a drop in the pedestal temperature rather than the pedestal density.« less
ELM suppression in helium plasmas with 3D magnetic fields
NASA Astrophysics Data System (ADS)
Evans, T. E.; Loarte, A.; Orlov, D. M.; Grierson, B. A.; Knölker, M. M.; Lyons, B. C.; Cui, L.; Gohil, P.; Groebner, R. J.; Moyer, R. A.; Nazikian, R.; Osborne, T. H.; Unterberg, E. A.
2017-08-01
Experiments in DIII-D, using non-axisymmetric magnetic perturbation fields in high-purity low toroidal rotation, 4He plasmas have resulted in Type-I edge localized mode (ELM) suppression and mitigation. Suppression is obtained in plasmas with zero net input torque near the L-H power threshold using either electron cyclotron resonant heating (ECRH) or balanced co- and counter-I p neutral beam injection (NBI) resulting in conditions equivalent to those expected in ITER’s non-active operating phase. In low-power ECRH H-modes, periods with uncontrolled density and impurity radiation excursions are prevented by applying n = 3 non-axisymmetric magnetic perturbation fields. ELM suppression results from a reduction and an outward shift of the electron pressure gradient peak compared to that in the high-power ELMing phase. The change in the electron pressure gradient peak is primarily due to a drop in the pedestal temperature rather than the pedestal density.
Phase Transformations During Cooling of Automotive Steels
NASA Astrophysics Data System (ADS)
Padgett, Matthew C.
This thesis explores the effect of cooling rate on the microstructure and phases in advanced high strength steels (AHSS). In the manufacturing of automobiles, the primary joining mechanism for steel is resistance spot welding (RSW), a process that produces a high heat input and rapid cooling in the welded metal. The effect of RSW on the microstructure of these material systems is critical to understanding their mechanical properties. A dual phase steel, DP-600, and a transformation induced plasticity bainitic-ferritic steel, TBF-1180, were studied to assess the changes to their microstructure that take place in controlled cooling environments and in uncontrolled cooling environments, i.e. resistance spot welding. Continuous cooling transformation (CCT) diagrams were developed using strip specimens of DP-600 and TBF-1180 to determine the phase transformations that occur as a function of cooling rate. The resulting phases were determined using a thermal-mechanical simulator and dilatometry, combined with light optical microscopy and hardness measurements. The resulting phases were compared with RSW specimens where cooling rate was controlled by varying the welding time for two-plate welds. Comparisons were drawn between experimental welds of DP-600 and simulations performed using a commercial welding software. The type and quantity of phases present after RSW were examined using a variety of techniques, including light optical microscopy using several etchants, hardness measurements, and x-ray diffraction (XRD).
Ohyama, Kunio; Akaike, Takenori; Hirobe, Chieko; Yamakawa, Toshio
2003-01-01
A crude extract was prepared with ethanol from dried ripened Vitex agnus-castus fruits growing in Israel (Vitex extract). Cytotoxicity of the extract against human uterine cervical canal fibroblast (HCF), human embryo fibroblast (HE-21), ovarian cancer (MCF-7), cervical carcinoma (SKG-3a), breast carcinoma (SKOV-3), gastric signet ring carcinoma (KATO-III), colon carcinoma (COLO 201), and small cell lung carcinoma (Lu-134-A-H) cells was examined. After culture for 24 h (logarithmic growth phase) or 72 h (stationary growth phase), the cells were treated with various concentrations of Vitex extract. In both growth phases, higher growth activity of cells and more cytotoxic activity of Vitex extract were seen. The cytotoxic activity against stationary growth-phase cells was less than that against logarithmic growth-phase cells. DNA fragmentation of Vitex extract-treated cells was seen in SKOV-3, KATO-III, COLO 201, and Lu-134-A-H cells. The DNA fragmentation in Vitex extract-treated KATO-III cells was inhibited by the presence of the antioxidative reagent pyrrolidine dithiocarbamate or N-acetyl-L-cysteine (NAC). Western blotting analysis showed that in Vitex extract-treated KATO-III cells, the presence of NAC also inhibited the expression of heme oxygenase-1 and the active forms of caspases-3, -8 and -9. It is concluded that the cytotoxic activity of Vitex extract may be attributed to the effect on cell growth, that cell death occurs through apoptosis, and that this apoptotic cell death may be attributed to increased intracellular oxidation by Vitex extract treatment.
Slade, Alexander N; Stanic, Sinisa
2016-03-01
Two recent clinical trials, phase III RTOG 0614 and phase II RTOG 0933, showed some effectiveness of Memantine and IMRT planning for hippocampus sparing, among patients receiving whole brain radiotherapy (WBRT) for brain metastases; however, their use in routine clinical practice is unknown. A survey was sent to 1933 radiation oncologists in the US. Data collected included utilization of Memantine and hippocampus sparing, reasons for adoption and non-adoption, and demographic variables. A total of 196 radiation oncologists responded to the survey, with 64% reporting using Memantine in almost none of the patients receiving WBRT for brain metastases, and only 11% considering Memantine for <10% of their patients. The most common reason for not using Memantine was a poor patient performance status, and limited life expectancy. Likewise, 56% of radiation oncologists would not change their clinical practice to include hippocampus sparing IMRT in patients receiving WBRT based on the results of RTOG 0933. Further validation of hippocampus sparing in a phase III trial was supported by 71% of radiation oncologists, whereas further exploration of Memantine for this purpose in a phase III trial was supported by 42%. At this time, the majority of surveyed radiation oncologists in the US do not use Memantine, or IMRT planning for hippocampus sparing in patients receiving WBRT. Further validation of the hippocampus sparing concept in a phase III trial was supported, before adopting it in routine clinical practice. Copyright © 2015 Elsevier Inc. All rights reserved.
Grzelak, Adam; Gawraczyński, Jakub; Jaroń, Tomasz; Somayazulu, Maddury; Derzsi, Mariana; Struzhkin, Viktor; Grochala, Wojciech
2017-05-15
The X-ray diffraction data collected up to ca. 56 GPa and the Raman spectra measured up to 74.8 GPa for AgO, or Ag I Ag III O 2 , which is a prototypical mixed valence (disproportionated) oxide, indicate that two consecutive phase transitions occur: the first-order phase transition occurs between 16.1 GPa and 19.7 GPa, and a second-order phase transition occurs at ca. 40 GPa. All polymorphic forms host the square planar [Ag III O 4 ] units typical of low-spin Ag III . The disproportionated Imma form persists at least up to 74.8 GPa, as indicated by Raman spectra. Theoretical hybrid density functional theory (DFT) calculations show that the first-order transition is phonon-driven. AgO stubbornly remains disproportionated up to at least 100 GPa-in striking contrast to its copper analogue-and the fundamental band gap of AgO is ∼0.3 eV at this pressure and is weakly pressure-dependent. Metallization of AgO is yet to be achieved.
Evidence to Support Peer Tutoring Programs at the Undergraduate Level
ERIC Educational Resources Information Center
Colver, Mitchell; Fry, Trevor
2016-01-01
The present study examined undergraduate peer tutoring in three phases. Phase I qualitatively surveyed students' perceptions about the effectiveness of tutoring. Phase II examined the usefulness of promoting regular use of services through a tutoring contract. Phase III utilized an archival, quasi-experimental approach to estimate the effect of…
40 CFR 72.92 - Phase I unit allowance surrender.
Code of Federal Regulations, 2010 CFR
2010-07-01
... chapter) for all Phase I units in the dispatch system. (iii) Calculating percentage change in dispatch... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Phase I unit allowance surrender. 72... (CONTINUED) PERMITS REGULATION Compliance Certification § 72.92 Phase I unit allowance surrender. (a) Annual...
40 CFR 72.92 - Phase I unit allowance surrender.
Code of Federal Regulations, 2011 CFR
2011-07-01
... chapter) for all Phase I units in the dispatch system. (iii) Calculating percentage change in dispatch... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Phase I unit allowance surrender. 72... (CONTINUED) PERMITS REGULATION Compliance Certification § 72.92 Phase I unit allowance surrender. (a) Annual...
Seeking the Profile of an Elementary Educator: Phase III.
ERIC Educational Resources Information Center
Arth, Alfred A.; And Others
This paper presents the third phase of a student-faculty investigation seeking the profile of the elementary school teacher. Phase I discovered an indication of different personality traits in elementary and secondary teachers. Phase II redesigned the original questionnaire and supported the findings with additional research. This third phase…
Dean, Bonnie B; Calimlim, Brian C; Sacco, Patricia; Aguilar, Daniel; Maykut, Robert; Tinkelman, David
2010-09-08
Results of a national survey of asthmatic children that evaluated management goals established in 2004 by the National Asthma Education and Prevention Program (NAEPP) indicated that asthma symptom control fell short on nearly every goal. An Internet-based survey was administered to adult caregivers of children aged 6-12 years with moderate to severe asthma. Asthma was categorized as uncontrolled when the caregiver reported pre-specified criteria for daytime symptoms, nighttime awakening, activity limitation, or rescue medication based on the NAEPP guidelines. Children's health-related quality of life (HRQOL) and caregivers' quality of life (QOL) were assessed using the Child Health Questionnaire Parent Form 28 (CHQ-PF28) and caregiver's work productivity using a modified Work Productivity and Activity Impairment Questionnaire. Children with uncontrolled vs. controlled asthma were compared. 360 caregivers of children with uncontrolled asthma and 113 of children with controlled asthma completed the survey. Children with uncontrolled asthma had significantly lower CHQ-PF28 physical (mean 38.1 vs 49.8, uncontrolled vs controlled, respectively) and psychosocial (48.2 vs 53.8) summary measure scores. They were more likely to miss school (5.5 vs 2.2 days), arrive late or leave early (26.7 vs 7.1%), miss school-related activities (40.6 vs 6.2%), use a rescue inhaler at school (64.2 vs 31.0%), and visit the health office or school nurse (22.5 vs 8.8%). Caregivers of children with uncontrolled asthma reported significantly greater work and activity impairment and lower QOL for emotional, time-related and family activities. Poorly controlled asthma symptoms impair HRQOL of children, QOL of their caregivers, and productivity of both. Proper treatment and management to improve symptom control may reduce humanistic and economic burdens on asthmatic children and their caregivers.
Feng, Yan-Ru; Zhu, Yuan; Liu, Lu-Ying; Wang, Wei-Hu; Wang, Shu-Lian; Song, Yong-Wen; Wang, Xin; Tang, Yuan; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Zhang, Shi-Ping; Liu, Xin-Fan; Yu, Zi-Hao; Li, Ye-Xiong; Jin, Jing
2016-05-03
The aim of this study is to present an interim analysis of a phase III trial (NCT00714077) of postoperative concurrent capecitabine and radiotherapy with or without oxaliplatin for pathological stage II and III rectal cancer. Patients with pathologically confirmed stage II and III rectal cancer were randomized to either radiotherapy with concurrent capecitabine (Cap-RT group) or with capecitabine and oxaliplatin (Capox-RT group). The primary endpoint was 3-year disease-free survival rate (DFS). The 3-year DFS rate was 73.9% in the Capox-RT group and 71.6% in the Cap-RT group (HR 0.92, p = 0.647), respectively. No significant difference was observed in overall survival, cumulative incidence of local recurrence and distant metastasis between the two groups (p > 0.05). More grade 3-4 acute toxicity was observed in the Capox-RT group than in the Cap-RT group (38.1% vs. 29.2%, p = 0.041). Inclusion of oxaliplatin in the capecitabine-based postoperative regimen did not improve DFS but increased toxicities for pathological stage II and III rectal cancer in this interim analysis.
Tu, Zhifeng; He, Qun; Chang, Xijun; Hu, Zheng; Gao, Ru; Zhang, Lina; Li, Zhenhua
2009-09-07
A novel method that utilizes 1-(2-formamidoethyl)-3-phenylurea-modified activated carbon (AC-1-(2-formamidoethyl)-3-phenylurea) as a solid-phase extractant has been developed for simultaneous preconcentration of trace Cr(III), Cu(II), Fe(III) and Pb(II) prior to the measurement by inductively coupled plasma atomic emission spectrometry (ICP-AES). Experimental conditions for effective adsorption of trace levels of Cr(III), Cu(II), Fe(III) and Pb(II) were optimized using batch and column procedures in detail. The optimum pH value for the separation of metal ions simultaneously on the new sorbent was 4. And the adsorbed metal ions could be completely eluted by using 2.0 mL 2.0 mol L(-1) HCl solution. Common coexisting ions did not interfere with the separation and determination of target metal ions. The maximum static adsorption capacity of the sorbent at optimum conditions was found to be 39.8, 39.9, 77.8 and 17.3 mg g(-1) for Cr(III), Cu(II), Fe(III) and Pb(II), respectively. The detection limits of the method were found to be 0.15, 0.41, 0.27 and 0.36 ng mL(-1) for Cr(III), Cu(II), Fe(III) and Pb(II), respectively. The relative standard deviation (RSD) of the method was lower than 4.0% (n=8). The method was successfully applied for the preconcentration of trace Cr(III), Cu(II), Fe(III) and Pb(II) in natural and certified samples with satisfactory results.
NASA Astrophysics Data System (ADS)
Liang, Liyuan; McCarthy, John F.; Jolley, Louwanda W.; McNabb, J. Andrew; Mehlhorn, Tonia L.
1993-05-01
The dynamics of dissolved, colloidal, and deposited iron phases were examined during a forced-gradient field experiment. The experiment involved the injection of oxygenated water containing high levels of natural organic matter (NOM) into a sandy aquifer. The initial redox potential of the aquifer favored Fe(II) in the groundwater. The changes in the concentrations of Fe(II) and Fe(III) were observed in sampling wells. Under the increased dissolved oxygen (DO) conditions, Fe(II) oxygenation was rapid, resulting in the formation of Fe(III) (hydr) oxide colloids. The oxidation follows the rate law as given in STUMM and MORGAN (1981): d[ Fe(II)] /dt = - k obs[ O2( aq)] /[ H+] 2[ Fe(II)] , with a rate constant, kobs to be 1.9 × 10 -12 M min -1. For an averaged pH and DO of the groundwater, the half time of Fe(II) oxidation is 49 h. The NOM was postulated to stabilize the newly formed colloids, thereby increasing the turbidity in the groundwater. The additional increase in the colloidal fraction of Fe(III) oxide suggested that transport of the colloidal particles was occurring. At those locations where DO remained constantly low, the turbidity increase was moderate, and up to 80% of Fe(III) was in the dissolved phase (< 3000 mol. wt). The latter observation was attributed to the presence of NOM, forming Fe(III)-organic complexes. In addition, NOM may play a role in the oxygen consumption through a Fe(II)/Fe(III) catalyzed oxidation of organic matter as outlined by STUMM and MORGAN (1981, p. 469). In this mechanism, Fe(II) oxidation is slow, maintaining a near constant Fe(II) concentration, in agreement with field data. The overall increase in Fe(III) under low DO conditions was postulated to be a combination of (1) slow oxidation, (2) ligand-promoted and catalytic dissolution of deposited iron phases, and (3) the transport of newly formed iron oxide colloids along flow paths.
Fiteni, Frédéric; Anota, Amélie; Westeel, Virginie; Bonnetain, Franck
2016-02-18
Health-related quality of life (HRQoL) is recognized as a component endpoint for cancer therapy approvals. The aim of this review was to evaluate the methodology of HRQoL analysis and reporting in phase III clinical trials of first-line chemotherapy in advanced non-small cell lung cancers (NSCLC). A search in MEDLINE databases identified phase III clinical trials in first-line chemotherapy for advanced NSCLC, published between January 2008 to December 2014. Two authors independently extracted information using predefined data abstraction forms. A total of 55 phase III advanced NSCLC trials were identified. HRQoL was declared as an endpoint in 27 studies (49%). Among these 27 studies, The EORTC questionnaire Quality of Life Questionnaire C30 was used in 13 (48%) of the studies and The Functional Assessment of Cancer Therapy-General was used in 12 (44%) trials. The targeted dimensions of HRQoL, the minimal clinically important difference and the statistical approaches for dealing with missing data were clearly specified in 13 (48.1%), 9 (33.3%) and 5 (18.5%) studies, respectively. The most frequent statistical methods for HRQoL analysis were: the mean change from baseline (33.3%), the linear mixed model for repeated measures (22.2%) and time to HRQoL score deterioration (18.5%). For each targeted dimension, the results for each group, the estimated effect size and its precision were clearly reported in 4 studies (14.8%), not clearly reported in 11 studies (40.7%) and not reported at all in 12 studies (44.4%). This review demonstrated the weakness and the heterogeneity of the measurement, analysis, and reporting of HRQoL in phase III advanced NSCLC trials. Precise and uniform recommendations are needed to compare HRQoL results across publications and to provide understandable messages for patients and clinicians.
AIR EMISSIONS FROM SCRAP TIRE COMBUSTION
The report discusses air emissions from two types of scrap tire combustion: uncontrolled and controlled. Uncontrolled sources are open tire fires, which produce many unhealthful products of incomplete combustion and release them directly into the atmosphere. Controlled combustion...
EMISSIONS OF PCDD/F FROM UNCONTROLLED, DOMESTIC WASTE BURNING
Emissions of polychlorinated bibenzodioxin and dibenzofuran (PCDD/F) result from inefficiencies of combustion processes, most typically waste combustion. Uncontrolled combustion, such as occurs during so-called "backyard burning" of domestic waste, may therefore produce optimal ...
Young-age gender differences in mathematics mediated by independent control or uncontrollability.
Zirk-Sadowski, Jan; Lamptey, Charlotte; Devine, Amy; Haggard, Mark; Szűcs, Dénes
2014-05-01
We studied whether the origins of math anxiety can be related to a biologically supported framework of stress induction: (un)controllability perception, here indicated by self-reported independent efforts in mathematics. Math anxiety was tested in 182 children (8- to 11-year-olds). Latent factor modeling was used to test hypotheses on plausible causal processes and mediations within competing models in quasi-experimental contrasts. Uncontrollability perception in mathematics, or (in)dependence of efforts, best fit the data as an antecedent of math anxiety. In addition, the relationship of math anxiety with gender was fully mediated by adaptive perception of control (i.e. controllability). That is, young boys differ from girls in terms of their experience of control in mathematics learning. These differences influence math anxiety. Our findings are consistent with recent suggestions in clinical literature according to which uncontrollability makes women more susceptible to fear and anxiety disorders. © 2014 John Wiley & Sons Ltd.
Oki, E; Murata, A; Yoshida, K; Maeda, K; Ikejiri, K; Munemoto, Y; Sasaki, K; Matsuda, C; Kotake, M; Suenaga, T; Matsuda, H; Emi, Y; Kakeji, Y; Baba, H; Hamada, C; Saji, S; Maehara, Y
2016-07-01
Preventing distant recurrence and achieving local control are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur-uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer. The ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20-80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500-600 mg/day on days 1-5, followed by 2 days rest) or S-1 (80-120 mg/day on days 1-28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events. In total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61.7% [95% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63-0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm. One-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
Hayes, Douglas G.; Gomez del Rio, Javier A.; Ye, Ran; ...
2015-01-20
Small-angle neutron scattering (SANS) analysis using the Teubner₋Strey model has been employed to evaluate the effect of protein incorporation into the middle, bicontinuous microemulsion (BμE) phase of Winsor-III (W III) systems formed by an aerosol-OT (AOT)/alkyl ethoxylate mixed surfactant system to understand better the extraction of proteins into and out of BμEs and to study the effect of proteins on a system that serves as a biomimetic analog of cell membranes. Under conditions of high salinity, the incorporation of positively charged proteins cytochrome c, lysozyme, and α-chymotrypsin, near their solubilization limit in the BμEs promoted the release of water andmore » oil from the BμEs, a decrease in the quasi-periodic repeat distance (d), an increase in ordering (a decrease in the amphiphilicity factor, f a) for the surfactant monolayers, and a decrease in the surface area per surfactant headgroup, suggesting that the proteins affected the self-assembly of components in the BμE phase and produced Debye shielding of AOTs sulfonate headgroup. For W III systems possessing lower salinity, cytochrome c reduced the efficiency of surfactant in the BμE phase, noted by increases in d and f a, suggesting that the enzyme and AOT underwent ion pairing. We find that the results of this study demonstrate the importance of ionic strength to modulate proteinsurfactant interactions, which in turn will control the release of proteins encapsulated in the BμEs, relevant to W III-based protein extraction and controlled release from BμE delivery systems, and demonstrate the utility of BμEs as a model system to understand the effect of proteins on biomembranes.« less
Organic and Aqueous Redox Speciation of Cu(III) Periodate Oxidized Transuranium Actinides
DOE Office of Scientific and Technical Information (OSTI.GOV)
McCann, Kevin; Sinkov, Sergey I.; Lumetta, Gregg J.
A hexavalent group actinide separation process could streamline used nuclear fuel recycle and waste management. The limiting factor to such a process compatible with current fuel dissolution practices is obtaining and maintaining hexavalent Am, in molar nitric acid due to the high reduction potential of the Am(VI)/Am(III) couple (1.68 V vs SCE). Two strong oxidants, sodium bismuthate and Cu(III) periodate, have demonstrated quantitative oxidation of Am under molar acid conditions and better than 50% recovery by diamyl amylphosphonate (DAAP) is possible under these same conditions. This work considers the use of Cu(III) periodate to oxidize Np(V) to Np(VI) and Pu(IV)more » to Pu(VI) and recover these elements by extraction with DAAP. A metal:oxidant ratio of 1:1.2 and 1:3 was necessary to quantitatively oxidize Np(V) and Pu(IV), respectively, to the hexavalent state. Extraction of hexavalent Np, Pu, and Am by 1 M DAAP in n-dodecane was measured using UV-Vis [Pu(VI), Am (VI)] and NIR [Np(VI)]. Distribution values of Am(VI) were found to match previous tracer level studies. The organic phase spectra of Np, Pu, and Am are presented and molar absorptivities are calculated for characteristic peaks. Hexavalent Pu was found to be stable in the organic phase while Np(VI) showed some reduction to Np(V) and Am was present as Am(III), Am(V), and Am(VI) species in aqueous and organic phases during the extraction experiments. These results demonstrate, for the first time, the ability to recover macroscopic amounts of americium that would be present during fuel reprocessing and are the first characterization of Am organic phase oxidation state speciation relevant to a hexavalent group actinide separation process under acidic conditions.« less
New treatments for the motor symptoms of Parkinson's disease.
Vijverman, Anne-Catherine; Fox, Susan H
2014-11-01
Levodopa remains the most potent drug to treat motor symptoms in Parkinson's disease (PD); however, motor fluctuations and levodopa-induced dyskinesia that occur with long-term use restrict some of its therapeutic value. Despite these limitations, the medical treatment of PD strives for continuous relief of symptoms using different strategies throughout the course of the illness: increasing the half-life of levodopa, using 'levodopa-sparing agents' and adding non-dopaminergic drugs. New options to 'improve' delivery of levodopa are under investigation, including long-acting levodopa, nasal inhalation and continuous subcutaneous or intrajejunal administration of levodopa. Long-acting dopamine agonists were recently developed and are undergoing further comparative studies to investigate potential superiority over the immediate-release formulations. Non-dopaminergic drugs acting on adenosine receptors, cholinergic, adrenergic, serotoninergic and glutamatergic pathways are newly developed and many are being evaluated in Phase II and Phase III trials. This article focuses on promising novel therapeutic approaches for the management of PD motor symptoms and motor complications. We will provide an update since 2011 on new formulations of current drugs, new drugs with promising results in Phase II and Phase III clinical trials, old drugs with new possibilities and some new potential strategies that are currently in Phase I and II of development (study start date may precede 2011 but are included as study is still ongoing or full data have not yet been published). Negative Phase II and Phase III clinical trials published since 2011 will also be briefly mentioned.
Hee, Siew Wan; Parsons, Nicholas; Stallard, Nigel
2018-03-01
The motivation for the work in this article is the setting in which a number of treatments are available for evaluation in phase II clinical trials and where it may be infeasible to try them concurrently because the intended population is small. This paper introduces an extension of previous work on decision-theoretic designs for a series of phase II trials. The program encompasses a series of sequential phase II trials with interim decision making and a single two-arm phase III trial. The design is based on a hybrid approach where the final analysis of the phase III data is based on a classical frequentist hypothesis test, whereas the trials are designed using a Bayesian decision-theoretic approach in which the unknown treatment effect is assumed to follow a known prior distribution. In addition, as treatments are intended for the same population it is not unrealistic to consider treatment effects to be correlated. Thus, the prior distribution will reflect this. Data from a randomized trial of severe arthritis of the hip are used to test the application of the design. We show that the design on average requires fewer patients in phase II than when the correlation is ignored. Correspondingly, the time required to recommend an efficacious treatment for phase III is quicker. © 2017 The Author. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Use of column V alkyls in organometallic vapor phase epitaxy (OMVPE)
NASA Technical Reports Server (NTRS)
Ludowise, M. J.; Cooper, C. B., III
1982-01-01
The use of the column V-trialkyls trimethylarsenic (TMAs) and trimethylantimony (TMSb) for the organometallic vapor phase epitaxy (OM-VPE) of III-V compound semiconductors is reviewed. A general discussion of the interaction chemistry of common Group III and Group V reactants is presented. The practical application of TMSb and TMAs for OM-VPE is demonstrated using the growth of GaSb, GaAs(1-y)Sb(y), Al(x)Ga(1-x)Sb, and Ga(1-x)In(x)As as examples.
Eating traits questionnaires as a continuum of a single concept. Uncontrolled eating.
Vainik, Uku; Neseliler, Selin; Konstabel, Kenn; Fellows, Lesley K; Dagher, Alain
2015-07-01
Research on eating behaviour has identified several potentially relevant eating-related traits captured by different questionnaires. Often, these questionnaires predict Body Mass Index (BMI), but the relationship between them has not been explicitly studied. We studied the unity and diversity of questionnaires capturing five common eating-related traits: Power of Food, Eating Impulsivity, emotional eating, Disinhibition, and binge eating in women from Estonia (n = 740) and Canada (n = 456). Using bifactor analysis, we showed that a) these questionnaires are largely explained by a single factor, and b) relative to this shared factor, only some questionnaires offered additional variance in predicting BMI. Hence, these questionnaires seemed to characterise a common factor, which we label Uncontrolled Eating. Item Response Theory techniques were then applied to demonstrate that c) within this common factor, the questionnaires could be placed on a continuum of Uncontrolled Eating. That is, Eating Impulsivity focused on the milder degree, Power of Food Scale, emotional eating scales, and Disinhibition on intermediate degrees, and the Binge Eating Scale on the most severe degrees of Uncontrolled Eating. In sum, evidence from two samples showed that questionnaires capturing five common BMI-related traits largely reflected the same underlying latent trait - Uncontrolled Eating. In Estonia, some questionnaires focused on different severities of this common construct, supporting a continuum model of Uncontrolled Eating. These findings provide a starting point for developing better questionnaires of the neurobehavioural correlates of obesity, and provide a unifying perspective from which to view the existing literature. R scripts and data used for the analysis are provided. Copyright © 2015 Elsevier Ltd. All rights reserved.
Deficits in episodic memory are related to uncontrolled eating in a sample of healthy adults.
Martin, A A; Davidson, T L; McCrory, M A
2018-05-01
Despite a substantial amount of animal data linking deficits in memory inhibition to the development of overeating and obesity, few studies have investigated the relevance of memory inhibition to uncontrolled eating in humans. Further, although memory for recent eating has been implicated as an important contributor to satiety and energy intake, the possibility that variations in episodic memory relate to individual differences in food intake control has been largely neglected. To examine these relationships, we recruited ninety-three adult subjects to attend a single lab session where we assessed body composition, dietary intake, memory performance, and eating behaviors (Three Factor Eating Questionnaire). Episodic recall and memory inhibition were assessed using a well-established measure of memory interference (Retrieval Practice Paradigm). Hierarchical regression analyses indicated that memory inhibition was largely unrelated to participants' eating behaviors; however, episodic recall was reliably predicted by restrained vs. uncontrolled eating: recall was positively associated with strategic dieting (β = 2.45, p = 0.02), avoidance of fatty foods (β = 3.41, p = 0.004), and cognitive restraint (β = 1.55, p = 0.04). In contrast, recall was negatively associated with uncontrolled eating (β = -1.15, p = 0.03) and emotional eating (β = -2.46, p = 0.04). These findings suggest that episodic memory processing is related to uncontrolled eating in humans. The possibility that deficits in episodic memory may contribute to uncontrolled eating by disrupting memory for recent eating is discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.
A seamless phase IIB/III adaptive outcome trial: design rationale and implementation challenges.
Chen, Y H Joshua; Gesser, Richard; Luxembourg, Alain
2015-02-01
The licensed four-valent prophylactic human papillomavirus vaccine is highly efficacious in preventing cervical, vulvar, vaginal, and anal cancers and related precancers caused by human papillomavirus types 6, 11, 16, and 18. These four types account for approximately 70% of cervical cancers. A nine-valent human papillomavirus vaccine, including the four original types (6, 11, 16, and 18) plus the next five most prevalent types in cervical cancer (31, 33, 45, 52, and 58) could provide approximately 90% overall cervical cancer coverage. To expedite the nine-valent human papillomavirus vaccine clinical development, an adaptive, seamless Phase IIB/III outcome trial with ∼ 15,000 subjects was conducted to facilitate dose formulation selection and provide pivotal evidence of safety and efficacy for regulatory registrations. We discuss the design rationale and implementation challenges of the outcome trial, focusing on the adaptive feature of the seamless Phase IIB/III design. Subjects were enrolled in two parts (Part A and Part B). Approximately 1240 women, 16-26 years of age, were enrolled in Part A for Phase IIB evaluation and equally randomized to one of three dose formulations of the nine-valent human papillomavirus vaccine or the four-valent human papillomavirus vaccine (active control). Based on an interim analysis of immunogenicity and safety, one dose formulation of the nine-valent human papillomavirus vaccine was selected for evaluation in the Phase III part of the study. Subjects enrolled in Part A who received the selected dose formulation of the nine-valent human papillomavirus vaccine or four-valent human papillomavirus vaccine continued to be followed up and contributed to the final efficacy and safety analyses. In addition, ∼ 13,400 women 16-26 years of age were enrolled in Part B, randomized to nine-valent human papillomavirus vaccine at the selected dose formulation or four-valent human papillomavirus vaccine, and followed for immunogenicity, efficacy, and safety. A seamless Phase IIB/III design was justified by the extensive pre-existing knowledge of the licensed four-valent human papillomavirus vaccine and the development objectives for the nine-valent human papillomavirus vaccine. Subjects enrolled in Part A who received either the selected nine-valent human papillomavirus formulation or four-valent human papillomavirus vaccine contributed ∼ 10% of person-years of follow-up due to its earlier start-thereby maximizing the overall efficiency of the trial. Some of the challenges encountered in the implementation of the adaptive design included practical considerations during Phase IIB formulation selection by internal and external committees, End-of-Phase II discussion with health authorities and managing changes in the assay for immunological endpoints. Application of the experience and lesson learned from this seamless adaptive design to other clinical programs may depend on case-by-case consideration. A seamless Phase IIB/III adaptive design was successfully implemented in this large outcome study. The development time of the second-generation nine-valent human papillomavirus vaccine was shortened due to improved statistical efficiency. © The Author(s) 2014.
Olney, Nicholas; Rosen, Howard
2010-04-01
AVANIR Pharmaceuticals Inc, under license from Irisys Research & Development, is developing AVP-923 (Zenvia, Neurodex) for the treatment of pseudobulbar affect (PBA; in collaboration with Medison Pharma Ltd) and neuropathic pain associated with diabetic peripheral neuropathy. PBA, the main indication of AVP-923, is a neurological disorder characterized by uncontrollable and unpredictable episodes of laughing and/or crying. AVP-923 consists of a combination of the NMDA antagonist/sigma1 receptor agonist dextromethorphan hydrobromide (DM) and the cytochrome P450 2D6 (CYP2D6) enzyme inhibitor quinidine sulfate (Q). DM has been under investigation for several years as a neuroprotective agent in stroke, neurosurgery and amyotrophic lateral sclerosis (ALS); however, it is rapidly metabolized by CYP2D6, reducing the drug's bioavailability at neuronal targets. The inclusion of Q inhibits the rapid first-pass metabolism of DM to increase systemic concentrations of the drug in the plasma and, in theory, increase the potential efficacy. The initial clinical data for AVP-923 in the treatment of PBA demonstrated the combination was effective, but exhibited significant side effects. Of particular concern to the FDA were increased QTc intervals reported in patients dosed with a 30-/30-mg dose of DM/Q. A subsequent phase III clinical trial assessing a lower dose of AVP-923 (20 or 30 mg DM/10 mg Q) for the treatment of PBA in patients with ALS or multiple sclerosis was implemented by AVANIR and demonstrated a favorable safety profile of AVP-923 while maintaining efficacy. Pending approval of the data from the FDA, AVP-923 would be the first FDA-approved treatment for PBA.
Effect of a Low-Dose Contraceptive Patch on Efficacy, Bleeding Pattern, and Safety
Wiegratz, Inka; Bassol, Susana; Weisberg, Edith; Mellinger, Uwe
2014-01-01
This Phase III, uncontrolled, open-label, multicenter study was conducted to investigate the contraceptive efficacy, bleeding pattern, and cycle control of a novel once-a-week contraceptive patch, delivering low-dose ethinyl estradiol (EE) and gestodene (GSD) at the same systemic exposure seen after oral administration of a combined oral contraceptive containing 0.02 mg EE/0.06 mg GSD. Participants were women aged 18 to 35 years, all of whom received the EE/GSD patch for 13 cycles each of 21 treatment days (one patch per week for 3 weeks) followed by a 7-day, patch-free interval. The primary efficacy variable was the occurrence of unintended pregnancies during the study period as assessed by life table analysis and the Pearl Index. Secondary efficacy variables were days with bleeding during four 90-day reference periods and during 1 treatment year, bleeding pattern, and cycle control. The Kaplan-Meier probability of contraceptive protection after 364 treatment days was 98.8% and the adjusted Pearl Index was 0.81. The percentage of participants with intracyclic bleeding/spotting decreased over time, from 11.4% to 6.8% in cycles 1 and 12, respectively. Almost all participants (range: 90.8%-97.6%) experienced withdrawal bleeding across the study period. Compliance was very high (mean: 97.9%; median: 100%). The most frequent adverse events were headache (9.5%) and application site reaction (8.5%); no clinically significant safety concerns were observed. Results suggest the EE/GSD patch is highly effective in preventing pregnancy. Menstrual bleeding pattern was favorable and within the ranges expected of a healthy female population. The patch was well tolerated and treatment compliance was high. PMID:24784719
Quantifying Uncontrolled Air Emissions from Two Florida Landfills
Landfill gas emissions, if left uncontrolled, contribute to air toxics, climate change, trospospheric ozone, and urban smog. Measuring emissions from landfills presents unique challenges due to the large and variable source area, spatial and temporal variability of emissions, and...
Establishing procedures and guidelines for pedestrian treatments at uncontrolled locations
DOT National Transportation Integrated Search
2017-08-01
Pedestrians are the most vulnerable road users. The risks to pedestrians crossing at uncontrolled locations are much higher than at signalized intersections. There has been an increasing trend in pedestrian deaths during the past decade. Specifically...
G2 accumulation and melanin overproduction in malignant melanocytes treated with a new nitrosourea.
Buchdahl, C; Papon, J; Communal, Y; Bourges, M; Madelmont, J C
1998-12-01
Cystemustine (N'-(2-chloroethyl)-N-(2-(methylsulphonyl)ethyl)-N'-nitrosourea), a new anticancer chloroethylnitrosourea (CENU) is being tested in a phase II clinical trial of disseminated melanoma. The antitumour effect of this drug is mainly due to DNA damage in malignant melanocytes. Recently, we have shown that this damage can induce apoptosis in some melanoma cell lines. In others, apoptosis is not clearly observed, although there is a strong cytostatic effect. In this paper, we have characterized the cytological effect of cystemustine on murine malignant melanocytes (B16 cell line) which are resistant to apoptosis induced by this CENU. The results show that 3 days after cystemustine treatment, these melanocytes had accumulated in phase G2 of the cell cycle. There was then a strong morphological modification during a long cytostatic phase up to 30 days after treatment. During this cytostatic phase, there was uncontrolled DNA synthesis and marked swelling. Also, tyrosinase activity, melanin content and the number of mature melanosomes were greatly increased. These results suggest that when malignant melanocytes are not able to undergo apoptosis after treatment with CENU, they accumulate in G2 and this is followed by enhancement of melanogenesis.
Towards a drift-free multi-level Phase Change Memory
NASA Astrophysics Data System (ADS)
Cinar, Ibrahim; Ozdemir, Servet; Cogulu, Egecan; Gokce, Aisha; Stipe, Barry; Katine, Jordan; Aktas, Gulen; Ozatay, Ozhan
For ultra-high density data storage applications, Phase Change Memory (PCM) is considered a potentially disruptive technology. Yet, the long-term reliability of the logic levels corresponding to the resistance states of a PCM device is an important issue for a stable device operation since the resistance levels drift uncontrollably in time. The underlying mechanism for the resistance drift is considered as the structural relaxation and spontaneous crystallization at elevated temperatures. We fabricated a nanoscale single active layer-phase change memory cell with three resistance levels corresponding to crystalline, amorphous and intermediate states by controlling the current injection site geometry. For the intermediate state and the reset state, the activation energies and the trap distances have been found to be 0.021 eV and 0.235 eV, 1.31 nm and 7.56 nm, respectively. We attribute the ultra-low and weakly temperature dependent drift coefficient of the intermediate state (ν = 0.0016) as opposed to that of the reset state (ν = 0.077) as being due to the dominant contribution of the interfacial defects in electrical transport in the case of the mixed phase. Our results indicate that the engineering of interfacial defects will enable a drift-free multi-level PCM device design.
Ge, Hao; Qian, Hong
2011-01-01
A theory for an non-equilibrium phase transition in a driven biochemical network is presented. The theory is based on the chemical master equation (CME) formulation of mesoscopic biochemical reactions and the mathematical method of large deviations. The large deviations theory provides an analytical tool connecting the macroscopic multi-stability of an open chemical system with the multi-scale dynamics of its mesoscopic counterpart. It shows a corresponding non-equilibrium phase transition among multiple stochastic attractors. As an example, in the canonical phosphorylation–dephosphorylation system with feedback that exhibits bistability, we show that the non-equilibrium steady-state (NESS) phase transition has all the characteristics of classic equilibrium phase transition: Maxwell construction, a discontinuous first-derivative of the ‘free energy function’, Lee–Yang's zero for a generating function and a critical point that matches the cusp in nonlinear bifurcation theory. To the biochemical system, the mathematical analysis suggests three distinct timescales and needed levels of description. They are (i) molecular signalling, (ii) biochemical network nonlinear dynamics, and (iii) cellular evolution. For finite mesoscopic systems such as a cell, motions associated with (i) and (iii) are stochastic while that with (ii) is deterministic. Both (ii) and (iii) are emergent properties of a dynamic biochemical network. PMID:20466813
Fazio, N; Scarpa, A; Falconi, M
2014-01-01
Advanced enteropancreatic (EP) neuroendocrine tumors (NETs) can be treated with several different therapies, including chemotherapy, biotherapy, and locoregional treatments. Over the last few decades, impressive progress has been made in the biotherapy field. Three main druggable molecular targets have been studied and developed in terms of therapy: somatostatin receptor (sstr), mammalian target of rapamycin (mTOR), and angiogenic factors. In particular, research has moved from the old somatostatin analogs (SSAs), such as octreotide (OCT) and lanreotide (LAN), specifically binding to the sstr-2, to the newer pasireotide (PAS), which presents a wider sstr spectrum. Over the last ten years, several molecular targeted agents (MTAs) have been studied in phase II trials, and very few of them have reached phase III. The mTOR inhibitor everolimus and the multitargeted inhibitor sunitinib have been approved for clinical use by the FDA and EMA in advanced well/moderately-differentiated (WD, MD) progressive pancreatic neuroendocrine tumors (PNETs), on the basis of the positive results of two international large randomized phase III trials vs. placebo. Bevacizumab has been studied in a large US phase III trial vs. interferon (IFN)-alfa2b, and results are pending. In this review, the biological and clinical aspects of MTAs introduced into clinical practice or which are currently in an advanced phase of clinical investigation are addressed.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Beeston, Michael Philip; University of Exeter in Cornwall; Tuen van Elteren, Johannes
A methodology is presented to study the physico-chemical processes in old tailings ponds using an array of analytical-physical chemistry approaches. A case study was conducted on the sorption/desorption behaviour of arsenic in tailings pond 2406, at the King Edward Mine (KEM) in Cornwall, UK. The tailings pond was in operation from approximately 1907 to 1921. The methodology involves two principal stages: (1) sequential extraction followed by subsequent arsenic species determination to characterise the material with regards to the association of arsenic with soil phases and identification of As (III/V) in the easily accessible soil phase; (2) batch contacting/equilibrating the tailingsmore » pond material with As(III/V), followed by a similar procedure as in stage 1 to establish the material's As(III/V) phase distribution kinetics/thermodynamics. By extrapolating the data from present day samples we infer past and future elemental mobility. From this study it is concluded that adsorption and desorption from tailings material is a rapid process for the most unstable soil phases (non-specific and specific) and a slow process for the more stable phases (poorly crystalline and well crystalline). The hypothetical application of this conclusion to the tailings from dam 2406 is that, during the initial phases of the dam's creation (ca. 100 years ago), when arsenic was both in solution and bound to mineralogical components, arsenic must have dispersed into the environment as a result of slow As(V) adsorption/phase distribution processes. Aging of the tailings material sees the movement of the arsenic to the more stable soil phases, producing a situation that is seen at present day.« less
Estreet, Anthony; Apata, Jummai; Kamangar, Farin; Schutzman, Christine; Buccheri, Jane; O'Keefe, Anne-Marie; Wagner, Fernando; Sheikhattari, Payam
2017-01-01
This study compares participant' sretention in three phases of smoking cessation interventions, one provided in a health clinic and the subsequent two in community-based settings. Smoking cessation interventions were conducted in three phases from 2008 to 2015 in two underserved urban communities with low socioeconomic profiles and high rates of smoking ( n = 951). Phase I was conducted in a clinic; Phases II and III were conducted in community venues. In Phases II and III, incremental changes were made based on lessons learned from the previous phases. Retention (attending six or more sessions) was the primary predictor of cessation and was analyzed while controlling for associated factors including age, gender, race, employment, education, and nicotine dependence. Retention increased substantially over the three phases, with rates for attending six or more sessions of 13.8%, 51.9%, and 67.9% in Phases I, II, and III, respectively. Retention was significantly higher in community settings than in the clinic setting (adjusted odds ratio [OR] = 6.7; 95% confidence intervals [CI] = 4.6, 9.8). In addition to the intervention in community venues, predictors of retention included age and unemployment. Higher retention was significantly associated with higher quit rates (adjusted OR = 2.4; 95% CI = 1.5, 3.8). Conducting the intervention in community settings using trained peer motivators rather than health-care providers resulted in significantly higher retention and smoking cessation rates. This was due in part to the ability to tailor cessation classes in the community for specific populations and improving the quality of the intervention based on feedback from participants and community partners.
Zadeh, Wendy Waldman; Escartin, Antonio; Byrnes, William; Tennigkeit, Frank; Borghs, Simon; Li, Ting; Dedeken, Peter; De Backer, Marc
2015-09-01
To evaluate the efficacy and safety of lacosamide administered as either first add-on or later add-on antiepileptic drug (AED) therapy for patients with uncontrolled partial-onset seizures (POS). In this open-label, multicentre trial, patients with POS initiated oral lacosamide (titrated to 400 mg/day) either as add-on to first AED monotherapy, or as later add-on to 1-3 concomitant AEDs after ≥ 2 previous AEDs. The primary efficacy variable was the proportion of patients achieving seizure freedom for the first 12 weeks of the 24-week Maintenance Phase. 456 patients received ≥ 1 dose of lacosamide (96 as first add-on, 360 as later add-on). In the first add-on cohort, 27/72 (37.5%) patients completed 12 weeks treatment and remained seizure-free; 18/68 (26.5%) remained seizure-free after 24 weeks. 64/91 (70.3%) patients achieved ≥ 50% reduction in seizure frequency during maintenance treatment. This was accompanied by a mean 7.1 ± 16.00 point improvement from Baseline in the Quality of Life Inventory in Epilepsy (QOLIE-31-P) total score for 24-week completers, with improvement reported in all subscales. Most common treatment-emergent adverse events (TEAEs) were dizziness (31.3%) and headache (13.5%). In the later add-on cohort, 39/261 (14.9%) and 29/249 (11.6%) patients remained seizure-free after completing 12 and 24 weeks' treatment, respectively. 178/353 (50.4%) patients achieved ≥ 50% reduction in seizure frequency during maintenance treatment. Mean change in QOLIE-31-P total score was 4.8 ± 14.74 points among 24-week completers. Common TEAEs were dizziness (33.6%), somnolence (15.0%) and headache (11.4%). Lacosamide initiated as first add-on treatment was efficacious and well tolerated in patients with uncontrolled POS. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
NASA Astrophysics Data System (ADS)
Amin, Alaa S.; El-Sharjawy, Abdel-Azeem M.; Kassem, Mohammed A.
2013-06-01
A new simple, very sensitive, selective and accurate procedure for the determination of trace amounts of thallium(III) by solid-phase spectrophotometry (SPS) has been developed. The procedure is based on fixation of Tl(III) as quinalizarin ion associate on a styrene-divinylbenzene anion-exchange resin. The absorbance of resin sorbed Tl(III) ion associate is measured directly at 636 and 830 nm. Thallium(I) was determined by difference measurements after oxidation of Tl(I) to Tl(III) with bromine. Calibration is linear over the range 0.5-12.0 μg L-1 of Tl(III) with relative standard deviation (RSD) of 1.40% (n = 10). The detection and quantification limits are 150 and 495 ng L-1 using 0.6 g of the exchanger. The molar absorptivity and Sandell sensitivity are also calculated and found to be 1.31 × 107 L mol-1 cm-1 and 0.00156 ng cm-2, respectively. The proposed procedure has been successfully applied to determine thallium in water, urine and serum samples.
Amin, Alaa S; El-Sharjawy, Abdel-Azeem M; Kassem, Mohammed A
2013-06-01
A new simple, very sensitive, selective and accurate procedure for the determination of trace amounts of thallium(III) by solid-phase spectrophotometry (SPS) has been developed. The procedure is based on fixation of Tl(III) as quinalizarin ion associate on a styrene-divinylbenzene anion-exchange resin. The absorbance of resin sorbed Tl(III) ion associate is measured directly at 636 and 830 nm. Thallium(I) was determined by difference measurements after oxidation of Tl(I) to Tl(III) with bromine. Calibration is linear over the range 0.5-12.0 μg L(-1) of Tl(III) with relative standard deviation (RSD) of 1.40% (n=10). The detection and quantification limits are 150 and 495 ng L(-1) using 0.6 g of the exchanger. The molar absorptivity and Sandell sensitivity are also calculated and found to be 1.31×10(7) L mol(-1)cm(-1) and 0.00156 ng cm(-2), respectively. The proposed procedure has been successfully applied to determine thallium in water, urine and serum samples. Copyright © 2013 Elsevier B.V. All rights reserved.
Analysis of Wake VAS Benefits Using ACES Build 3.2.1: VAMS Type 1 Assessment
NASA Technical Reports Server (NTRS)
Smith, Jeremy C.
2005-01-01
The FAA and NASA are currently engaged in a Wake Turbulence Research Program to revise wake turbulence separation standards, procedures, and criteria to increase airport capacity while maintaining or increasing safety. The research program is divided into three phases: Phase I near term procedural enhancements; Phase II wind dependent Wake Vortex Advisory System (WakeVAS) Concepts of Operations (ConOps); and Phase III farther term ConOps based on wake prediction and sensing. The Phase III Wake VAS ConOps is one element of the Virtual Airspace Modelling and Simulation (VAMS) program blended concepts for enhancing the total system wide capacity of the National Airspace System (NAS). This report contains a VAMS Program Type 1 (stand-alone) assessment of the expected capacity benefits of Wake VAS at the 35 FAA Benchmark Airports and determines the consequent reduction in delay using the Airspace Concepts Evaluation System (ACES) Build 3.2.1 simulator.
Phases of Feminist Re-Vision in the Psychology of Personality.
ERIC Educational Resources Information Center
Torrey, Jane W.
1987-01-01
Reviews McIntosh's 1983 theory on the five-phase evolution of scholarship required by increasing feminism. Documents the sequence of the five phases using references to scholarly literature on the psychology of personality. Elaborates on Phase III in which investigators study women as inherently different from men and urges further study and…
Early Restoration | NOAA Gulf Spill Restoration
Early Restoration Plan. On April 20, 2011 we reached an agreement with BP to start restoration planning draft plan for the third phase of early restoration in December 2013. We are considering your comments : All Phase III information and documents Phase II Useful Links: Phase II Early Restoration Plan &
NASA Astrophysics Data System (ADS)
Zhuo, Yi; Chen, Zimin; Tu, Wenbin; Ma, Xuejin; Pei, Yanli; Wang, Gang
2017-10-01
Gallium oxide thin films of β and ε phase were grown on c-plane sapphire using metal-organic chemical vapor deposition and the phase compositions were analyzed using X-ray diffraction. The epitaxial phase diagram was constructed as a function of the growth temperature and VI/III ratio. A low growth temperature and low VI/III ratio were beneficial for the formation of hexagonal-type ε-Ga2O3. Further structure analysis revealed that the epitaxial relationship between ε-Ga2O3 and c-plane sapphire is ε-Ga2O3 (0001) || Al2O3 (0001) and ε-Ga2O3 || Al2O3 . The structural evolution of the mixed-phase sample during film thickening was investigated. By reducing the growth rate, the film evolved from a mixed phase to the energetically favored ε phase. Based on these results, a Ga2O3 thin film with a phase-pure ε-Ga2O3 upper layer was successfully obtained.
X-ray Raman spectroscopic study of benzene at high pressure.
Pravica, Michael; Grubor-Urosevic, Ognjen; Hu, Michael; Chow, Paul; Yulga, Brian; Liermann, Peter
2007-10-11
We have used X-ray Raman spectroscopy (XRS) to study benzene up to approximately 20 GPa in a diamond anvil cell at ambient temperature. The experiments were performed at the High-Pressure Collaborative Access Team's 16 ID-D undulator beamline at the Advanced Photon Source. Scanned monochromatic X-rays near 10 keV were used to probe the carbon X-ray edge near 284 eV via inelastic scattering. The diamond cell axis was oriented perpendicular to the X-ray beam axis to prevent carbon signal contamination from the diamonds. Beryllium gaskets confined the sample because of their high transmission throughput in this geometry. Spectral alterations with pressure indicate bonding changes that occur with pressure because of phase changes (liquid: phase I, II, III, and III') and possibly due to changes in the hybridization of the bonds. Changes in the XRS spectra were especially evident in the data taken when the sample was in phase III', which may be related to a rate process observed in earlier shock wave studies.
NASA Astrophysics Data System (ADS)
Dubrovskii, V. G.
2015-05-01
We present a refined model for the vapor-liquid-solid growth and crystal structure of Au-catalyzed III-V nanowires, which revisits several assumptions used so far and is capable of describing the transition from mononuclear to polynuclear regime and ultimately to regular atomistic growth. We construct the crystal phase diagrams and calculate the wurtzite percentages, elongation rates, critical sizes, and polynucleation thresholds of Au-catalyzed GaAs nanowires depending on the As flow. We find a non-monotonic dependence of the crystal phase on the group V flow, with the zincblende structure being preferred at low and high group V flows and the wurtzite structure forming at intermediate group V flows. This correlates with most of the available experimental data. Finally, we discuss the atomistic growth picture which yields zincblende crystal structure and should be very advantageous for fabrication of ternary III-V nanowires with well-controlled composition and heterointerfaces.
Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis.
Mills, Edward; Wilson, Kumanan; Clarke, Mike; Foster, Brian; Walker, Scott; Rachlis, Beth; DeGroot, Nick; Montori, Victor M; Gold, Wayne; Phillips, Elizabeth; Myers, Stephen; Gallicano, Keith
2005-03-01
To determine whether ingestion of milk thistle affects the pharmacokinetics of indinavir. We conducted a three-period, randomized controlled trial with 16 healthy participants. We randomized participants to milk thistle or control. All participants received initial dosing of indinavir, and baseline indinavir levels were obtained (AUC(0-8)) (phase I). The active group were then given 450 mg milk-thistle extract capsules to be taken t.i.d. from day 2 to day 30. The control group received no plant extract. On day 29 and day 30, indinavir dosing and sampling was repeated in both groups as before (phase II). After a wash-out period of 7 days, indinavir dosing and sampling were repeated as before (phase III). All participants completed the trial, but two were excluded from analysis due to protocol violation. There were no significant between-group differences. Active group mean AUC(0-8) indinavir decreased by 4.4% (90% CI, -27.5% to -26%, P=0.78) from phase I to phase II in the active group, and by 17.3% (90% CI, -37.3% to +9%, P=0.25) in phase III. Control group mean AUC(0-8) decreased by 21.5% (90% CI, -43% to +8%, P=0.2) from phase I to phase II and by 38.5% (90% CI, -55.3% to -15.3%, P=0.01) of baseline at phase III. To place our findings in context, milk thistle-indinavir trials were identified through systematic searches of the literature. A meta-analysis of three milk thistle-indinavir trials revealed a non-significant pooled mean difference of 1% in AUC(0-8) (95% CI, -53% to 55%, P=0.97). Indinavir levels were not reduced significantly in the presence of milk thistle.
NASA Astrophysics Data System (ADS)
Erkişi, Aytaç
2018-06-01
The quaternary full Heusler alloys FeMnCrSn and FeMnCrSb, which have face-centred cubic (FCC) crystal structure and conform to ? space group with 216 space number, have been investigated using Generalised Gradient Approximation (GGA) in the Density Functional Theory (DFT) as implemented in VASP (Vienna Ab initio Simulation Package) software. These alloys are considered in ferromagnetic (FM) order. After the investigation of structural stability of these alloys, their mechanical and thermal properties and also electronic band structures have been examined. The calculated spin-polarised electronic band structures and total electronic density of states (DOS) within GGA approximation show that these alloys can exhibit both metallic and half-metallic characters in different structural phases. The calculated formation enthalpies and the plotted energy-volume graphs show that Type-III phase is most stable structural phase for these materials. Also, FeMnCrSb alloy in Type-I/Type-III phases and FeMnCrSn alloy in Type-III phase show half-metallic behaviour with integer total magnetic moments almost 2 and 1 μB per formula unit, respectively, since there are band gaps observed in spin-down states, whereas they have metallic behaviour in majority bands. Other structural phases of both systems are also metallic. Moreover, the calculated elastic constants and the estimated anisotropy shear factors indicate that these materials are stable mechanically in all of three phases except FeMnCrSn in Type-I phase that does not satisfy Born stability criteria in this phase and have high anisotropic behaviour.
EMISIONES AL AIRE DE LA COMBUSTION DE LLANTAS USADAS (SPANISH VERSION)
The report discusses air emissions from two types of scrap tire combustion: uncontrolled and controlled. Uncontrolled sources are open tire fires, which produce many unhealthful products of incomplete combustion and release them directly into the atmosphere. Controlled combustion...
26 CFR 1.482-6 - Profit split method.
Code of Federal Regulations, 2012 CFR
2012-04-01
... consistency between the controlled and uncontrolled taxpayers in accounting practices that materially affect... result. Thus, for example, if differences in inventory and other cost accounting practices would... between the controlled and uncontrolled transactions increases, the relative weight accorded the analysis...
26 CFR 1.482-6 - Profit split method.
Code of Federal Regulations, 2013 CFR
2013-04-01
... consistency between the controlled and uncontrolled taxpayers in accounting practices that materially affect... result. Thus, for example, if differences in inventory and other cost accounting practices would... between the controlled and uncontrolled transactions increases, the relative weight accorded the analysis...
26 CFR 1.482-6 - Profit split method.
Code of Federal Regulations, 2014 CFR
2014-04-01
... consistency between the controlled and uncontrolled taxpayers in accounting practices that materially affect... result. Thus, for example, if differences in inventory and other cost accounting practices would... between the controlled and uncontrolled transactions increases, the relative weight accorded the analysis...
26 CFR 1.482-6 - Profit split method.
Code of Federal Regulations, 2011 CFR
2011-04-01
... consistency between the controlled and uncontrolled taxpayers in accounting practices that materially affect... result. Thus, for example, if differences in inventory and other cost accounting practices would... between the controlled and uncontrolled transactions increases, the relative weight accorded the analysis...
Fleischman, David; Kim, Bryan
2017-01-01
Surgical management of elevated intraocular pressure (IOP) in an eye with scarred conjunctiva, an encircling band, and silicone oil has limited options. By combining the flow restrictor of the Ahmed Glaucoma Valve (New World Medical, Rancho Cucamonga, California) and the capsule of the encircling band as a conduit for aqueous flow, immediate pressure reduction could theoretically be achieved in eyes with limited conjunctival mobilization. This is a description of a surgical technique in a case of a patient with multiple ocular surgeries with uncontrolled multimechanism glaucoma despite using all available topical and oral glaucoma medications. A combination of the Ahmed valve with a modification of the Schocket shunt technique was used in this case of an encircling band and poor conjunctiva. At 10-month follow-up, the patient maintains controlled pressures on dorzolamide-timolol drops. The combined Ahmed-Schocket (or Schockmed) technique may be another surgical option for management of uncontrolled IOP in cases of scarred conjunctiva and encircling bands needing immediate pressure reduction. A novel surgical option for uncontrolled glaucoma in eyes with poor conjunctiva and encircling bands. How to cite this article: Fleischman D, Kim B. Schockmed Valve: A Novel Surgical Option for Uncontrolled Glaucoma in Eyes with Poor Conjunctiva and Encircling Bands. J Curr Glaucoma Pract 2017;11(3):120-124.
Richell, Rebecca A; Deakin, J F William; Anderson, Ian M
2005-02-01
Previous research provides evidence linking serotonin (5-hydroxytryptamine, 5-HT) with stress and depression. The controllable/uncontrollable (C/UC) stress paradigm aims to generate a state/condition, namely a feeling of lack of control in the context of a stressor, which might be an important factor in precipitating a negative mood state. Acute tryptophan depletion (ATD) is a technique that produces a decrease in central 5-HT levels in vivo. This study investigated the role of 5-HT in the behavioral response to a C/UC stress paradigm with ATD. Healthy adult volunteers were randomly assigned to receive either a TRP-supplemented (n = 15) or TRP-deficient (n = 13) amino acid drink. At 5 hours postdrink, volunteers were subjected to sessions of controllable and uncontrollable noise stress (100-dB white noise). Subjective ratings of mood were obtained before and after the interventions. Participants who received the tryptophan-depleting drink had greater self-report ratings of negative mood on visual analogue scales and the Profile of Mood States after the uncontrollable stress than did participants who received the balanced drink. The results suggest that 5-HT might play a role in providing resilience to uncontrollable stress. Additional studies with specific 5-HT pharmacologic probes will further clarify the results.
Mahieu, Julien; Rinieri, Philippe; Bubenheim, Michael; Calenda, Emile; Melki, Jean; Peillon, Christophe; Baste, Jean-Marc
2016-06-01
Background Minimally invasive surgery has been recently recommended for treatment of early-stage non-small cell lung cancer. Despite the recent increase of robotic surgery, the place and potential advantages of the robot in thoracic surgery has not been well defined until now. Methods We reviewed our prospective database for retrospective comparison of our first 28 video-assisted thoracoscopic surgery lobectomies (V group) and our first 28 robotic lobectomies (R group). Results No significant difference was shown in median operative time between the two groups (185 vs. 190 minutes, p = 0.56). Median preincision time was significantly longer in the R group (80 vs. 60 minutes, P < 0.0001). The rate of emergency conversion for uncontrolled bleeding was lower in the R group (one vs. four). Median length of stay was comparable (6 days in the R group vs. 7 days in the V group, p = 0.4) with no significant difference in the rate of postoperative complications (eight Grade I in both groups, four Grade III or IV in the V group vs. six in the R group, according to the Clavien-Dindo classification, p = 0.93). No postoperative cardiac morbidity was observed in the R group. Median drainage time was similar (5 days, p = 0.78), with a rate of prolonged air leak slightly higher in the R group (25 vs. 17.8%, p = 0.74). Conclusion Perioperative outcomes are similar even in the learning period but robotic approach seems to offer more operative safety with fewer conversions for uncontrolled bleeding. Georg Thieme Verlag KG Stuttgart · New York.
High Trait Impulsivity Predicts Food Addiction-Like Behavior in the Rat
Velázquez-Sánchez, Clara; Ferragud, Antonio; Moore, Catherine F; Everitt, Barry J; Sabino, Valentina; Cottone, Pietro
2014-01-01
Impulsivity is a behavioral trait frequently seen not only in drug-addicted individuals but also in individuals who pathologically overeat. However, whether impulsivity predates the development of uncontrollable feeding is unknown. In this study, we hypothesized that a high impulsivity trait precedes and confers vulnerability for food addiction-like behavior. For this purpose, we trained ad libitum-fed male Wistar rats in a differential reinforcement of low rates of responding (DRL) task to select Low- and High-impulsive rats. Then, we allowed Low- and High-impulsive rats to self-administer a highly palatable diet (Palatable group) or a regular chow diet (Chow group) in 1-h daily sessions, under fixed ratio (FR) 1, FR3, FR5, and under a progressive ratio (PR) schedules of reinforcement. In addition, we tested the compulsiveness for food in Low- and High-impulsive rats by measuring the food eaten in the aversive, open compartment of a light/dark conflict test. Finally, we measured the expression of the transcription factor ΔFosB in the shell and the core of the nucleus accumbens, which is a marker for neuroadaptive changes following addictive drug exposure. The data we obtained demonstrate that impulsivity is a trait that predicts the development of food addiction-like behaviors, including: (i) excessive intake, (ii) heightened motivation for food, and (iii) compulsive-like eating, when rats are given access to highly palatable food. In addition, we show that the food addiction phenotype in high impulsive subjects is characterized by an increased expression of the transcription factor ΔFosB in the nucleus accumbens shell. These results reveal that impulsivity confers an increased propensity to develop uncontrollable overeating of palatable food. PMID:24776685
High trait impulsivity predicts food addiction-like behavior in the rat.
Velázquez-Sánchez, Clara; Ferragud, Antonio; Moore, Catherine F; Everitt, Barry J; Sabino, Valentina; Cottone, Pietro
2014-09-01
Impulsivity is a behavioral trait frequently seen not only in drug-addicted individuals but also in individuals who pathologically overeat. However, whether impulsivity predates the development of uncontrollable feeding is unknown. In this study, we hypothesized that a high impulsivity trait precedes and confers vulnerability for food addiction-like behavior. For this purpose, we trained ad libitum-fed male Wistar rats in a differential reinforcement of low rates of responding (DRL) task to select Low- and High-impulsive rats. Then, we allowed Low- and High-impulsive rats to self-administer a highly palatable diet (Palatable group) or a regular chow diet (Chow group) in 1-h daily sessions, under fixed ratio (FR) 1, FR3, FR5, and under a progressive ratio (PR) schedules of reinforcement. In addition, we tested the compulsiveness for food in Low- and High-impulsive rats by measuring the food eaten in the aversive, open compartment of a light/dark conflict test. Finally, we measured the expression of the transcription factor ΔFosB in the shell and the core of the nucleus accumbens, which is a marker for neuroadaptive changes following addictive drug exposure. The data we obtained demonstrate that impulsivity is a trait that predicts the development of food addiction-like behaviors, including: (i) excessive intake, (ii) heightened motivation for food, and (iii) compulsive-like eating, when rats are given access to highly palatable food. In addition, we show that the food addiction phenotype in high impulsive subjects is characterized by an increased expression of the transcription factor ΔFosB in the nucleus accumbens shell. These results reveal that impulsivity confers an increased propensity to develop uncontrollable overeating of palatable food.
Zanin, Esther; Desai, Arshad; Poser, Ina; Toyoda, Yusuke; Andree, Cordula; Moebius, Claudia; Bickle, Marc; Conradt, Barbara; Piekny, Alisa; Oegema, Karen
2014-01-01
SUMMARY During animal cell cytokinesis, the spindle directs contractile ring assembly by activating RhoA in a narrow equatorial zone. Rapid GTPase activating protein (GAP)-mediated inactivation (RhoA flux) is proposed to limit RhoA zone dimensions. Testing the significance of RhoA flux has been hampered by the fact that the GAP targeting RhoA is not known. Here, we identify M-phase GAP (MP-GAP) as the primary GAP targeting RhoA during mitosis/cytokinesis. MP-GAP inhibition caused excessive RhoA activation in M-phase leading to the uncontrolled formation of large cortical protrusions and late cytokinesis failure. RhoA zone width was broadened by attenuation of the centrosomal asters but was not affected by MP-GAP inhibition alone. Simultaneous aster attenuation and MP-GAP inhibition led to RhoA accumulation around the entire cell periphery. These results identify the major GAP restraining RhoA during cell division and delineate the relative contributions of RhoA flux and centrosomal asters in controlling RhoA zone dimensions. PMID:24012485
Kunoh, Tatsuki; Matsumoto, Syuji; Nagaoka, Noriyuki; Kanashima, Shoko; Hino, Katsuhiko; Uchida, Tetsuya; Tamura, Katsunori; Kunoh, Hitoshi; Takada, Jun
2017-07-26
Leptothrix species produce microtubular organic-inorganic materials that encase the bacterial cells. The skeleton of an immature sheath, consisting of organic exopolymer fibrils of bacterial origin, is formed first, then the sheath becomes encrusted with inorganic material. Functional carboxyl groups of polysaccharides in these fibrils are considered to attract and bind metal cations, including Fe(III) and Fe(III)-mineral phases onto the fibrils, but the detailed mechanism remains elusive. Here we show that NH 2 of the amino-sugar-enriched exopolymer fibrils is involved in interactions with abiotically generated Fe(III) minerals. NH 2 -specific staining of L. cholodnii OUMS1 detected a terminal NH 2 on its sheath skeleton. Masking NH 2 with specific reagents abrogated deposition of Fe(III) minerals onto fibrils. Fe(III) minerals were adsorbed on chitosan and NH 2 -coated polystyrene beads but not on cellulose and beads coated with an acetamide group. X-ray photoelectron spectroscopy at the N1s edge revealed that the terminal NH 2 of OUMS1 sheaths, chitosan and NH 2 -coated beads binds to Fe(III)-mineral phases, indicating interaction between the Fe(III) minerals and terminal NH 2 . Thus, the terminal NH 2 in the exopolymer fibrils seems critical for Fe encrustation of Leptothrix sheaths. These insights should inform artificial synthesis of highly reactive NH 2 -rich polymers for use as absorbents, catalysts and so on.
2017-10-01
Following the first phase III study of edaravone for amyotrophic lateral sclerosis (ALS), this extension study was performed to evaluate longer-term efficacy and safety. Patients given edaravone in the first 24-week phase III study (Cycles 1-6) were randomised to edaravone (E-E) or placebo (E-P) in the subsequent 24-week double-blind period (Cycles 7-12). Patients given placebo in phase III were switched to edaravone (P-E). Subsequently, all patients received edaravone for 12 weeks (Cycles 13-15). Efficacy endpoints included revised ALS Functional Rating Scale (ALSFRS-R) score. Analysis populations were the full analysis set (FAS) and the efficacy-expected subpopulation (EESP) defined by post-hoc analysis of the first phase III study. The least-squares mean and standard error of the intergroup difference (E-E vs. E-P) of change in the ALSFRS-R score from Cycles 7-12 was 1.16 ± 0.93 (p = 0.2176) in the FAS, and 1.85 ± 1.14 (p = 0.1127) in the EESP. The ALSFRS-R score changed almost linearly in the E-E group throughout Cycles 1-15 (60 weeks). The incidence of serious adverse events associated with ALS progression was higher in E-E than in E-P. Edaravone might have potential efficacy for up to 15 cycles when used to treat patients in the EESP with careful safety monitoring.
Water-soluble Schiff base-actinyl complexes and their effect on the solvent extraction of f-elements
Hawkins, Cory A.; Bustillos, Christian G.; May, Iain; ...
2016-09-07
Conventional solvent extraction of selected f-element cations by bis(2-ethylhexyl)phosphoric acid (HDEHP) yields increased extraction from aqueous to organic solution along the series Np(V) < Cm(III) < Eu(III) < U(VI), with distribution ratios all within two orders of magnitude. However, in the presence of the water-soluble tetradentate Schiff base (N,N'-bis(5-sulfonatosalicylidene)-ethylenediamine or H 2salenSO 3), selective complexation of the two actinyl cations (Np(V) and U(VI)) resulted in an extraction order of Np(V) < U(VI) << Eu(III) < Cm(III). The extraction of neither Cm(III) or Eu(III) by HDEHP are significantly impacted by the presence of the aqueous phase Schiff base. Despite observed hydrolyticmore » decomposition of H 2salenSO 3 in aqueous solutions, the calculated high conditional stability constant (β 11 = 26) for the complex [UO 2(salenSO 3)] 2- demonstrates its capacity for aqueous hold-back of U(VI). UV-visible-NIR spectroscopy of solutions prepared with a Np(VI) stock and H 2salenSO 3 suggest that reduction of Np(VI) to Np(V) by the ligand was rapid, resulting in a pentavalent Np complex that was substantially retained in the aqueous phase. Lastly, results from 1H NMR of aqueous solutions of H 2salenSO 3 with U(VI) and La(III), Eu(III), and Lu(III) provides additional evidence that the ligand readily chelates U(VI), but has only weak interactions with trivalent lanthanide ions.« less
Effect of Laughter Yoga on Psychological Well-being and Physiological Measures.
Miles, Cindy; Tait, Elizabeth; Schure, Marc B; Hollis, Marianne
2016-01-01
In 2014, laughter yoga (LY) achieved the intermediate level, tier 2, under the Title III-D Evidence-based Disease Prevention and Health Promotion Program through the Administration on Aging (AOA). Further research is needed to qualify LY under the criteria for the highest tier, tier 3, to assure continued funding for LY classes at senior centers. The study intended to demonstrate further the benefits of LY and to qualify LY as tier 3 under Title III-D. Using a quasi-experimental design, the research team conducted a preintervention/postintervention study in 3 phases. The study was done in a variety of community centers. Phase 1, a pilot phase, was limited to North Carolina, and phase 2 was conducted in multiple states. Phase 3 was held at the North Carolina Area Agency on Aging's annual Volunteer Appreciation meeting. Participants in phases 1 (n = 109) and 2 (n = 247) enrolled in LY classes. Classes were advertised by fliers posted in community and in retirement centers. The ability of participants to participate in a class was based solely on their desire to participate, regardless of age, ability, health status, or physical impairment. Phase 3 (n = 23) was a convenience sample only. All phases were voluntary. The pre- and posttests for all 3 phases were Likert-scale surveys, 10 questions on the Psychological Outcomes of Well-being (POWB) survey. Pulse and other physiological measurements were also assessed pre- and postintervention. Analysis included a t test on each of the 10 POWB and physiological measures for all phases. All 10 POWB measures for phases 1 and 2 showed significant improvements between the pre- and postintervention testing (P < .001). Phase 3, the control, showed no significant improvement. The initial study demonstrated that LY meets the criteria to qualify for tier 3 under the Title III-D Evidence-based Disease Prevention and Health Promotion Program and that a large number of Americans, regardless of age and physical ability, could benefit from LY.
McLaughlin, Vallerie V; Jansa, Pavel; Nielsen-Kudsk, Jens E; Halank, Michael; Simonneau, Gérald; Grünig, Ekkehard; Ulrich, Silvia; Rosenkranz, Stephan; Gómez Sánchez, Miguel A; Pulido, Tomás; Pepke-Zaba, Joanna; Barberá, Joan Albert; Hoeper, Marius M; Vachiéry, Jean-Luc; Lang, Irene; Carvalho, Francine; Meier, Christian; Mueller, Katharina; Nikkho, Sylvia; D'Armini, Andrea M
2017-12-28
Following positive results from the Phase III CHEST-1 study in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), the Phase IIIb CTEPH early access study (EAS) was designed to assess the safety and tolerability of riociguat in real-world clinical practice, as well as to provide patients with early access to riociguat before launch. Riociguat is approved for the treatment of inoperable and persistent/recurrent CTEPH. We performed an open-label, uncontrolled, single-arm, early access study in which 300 adult patients with inoperable or persistent/recurrent CTEPH received riociguat adjusted from 1 mg three times daily (tid) to a maximum of 2.5 mg tid. Patients switching from unsatisfactory prior pulmonary arterial hypertension (PAH)-targeted therapy (n = 84) underwent a washout period of at least 3 days before initiating riociguat. The primary aim was to assess the safety and tolerability of riociguat, with World Health Organization functional class and 6-min walking distance (6MWD) as exploratory efficacy endpoints. In total, 262 patients (87%) completed study treatment and entered the safety follow-up (median treatment duration 47 weeks). Adverse events were reported in 273 patients (91%). The most frequently reported serious adverse events were syncope (6%), right ventricular failure (3%), and pneumonia (2%). There were five deaths, none of which was considered related to study medication. The safety and tolerability of riociguat was similar in patients switched from other PAH-targeted therapies and those who were treatment naïve. In patients with data available, mean ± standard deviation 6MWD had increased by 33 ± 42 m at Week 12 with no clinically relevant differences between the switched and treatment-naïve subgroups. Riociguat was well tolerated in patients with CTEPH who were treatment naïve, and in those who were switched from other PAH-targeted therapies. No new safety signals were observed. ClinicalTrials.org NCT01784562 . Registered February 4, 2013.
NASA Astrophysics Data System (ADS)
Jelenković, Emil V.; To, Suet
2017-09-01
In this paper the effect of hydrogen implantation in silicon on nanoindentation-induced phase transformation is investigated. Hydrogen ions were implanted in silicon through 300 nm thick oxide with double energy implantation (75 and 40 keV). For both energies implantation dose was 4 × 1016 cm-2. Some samples were thermally annealed at 400 °C. The micro-Raman spectroscopy was applied on nanoindentation imprints and the obtained results were related to the pop out/elbow appearances in nanoindentatioin unloading-displacement curves. The Raman spectroscopy revealed a suppression of Si-XII and Si-III phases and formation of a-Si in the indents of hydrogen implanted Si. The high-resolution x-ray diffraction measurements were taken to support the analysis of silicon phase formation during nanoindentation. Implantation induced strain, high hydrogen concentration, and platelets generation were found to be the factors that control suppression of c-Si phases Si-XII and Si-III, as well as a-Si phase enhancement during nanoindentation. [Figure not available: see fulltext.
Yao, Liang-Zi; Crisostomo, Christian P.; Yeh, Chun-Chen; ...
2015-11-05
We have carried out systematic first-principles electronic structure computations of growth of ultrathin films of compounds of group III (B, Al, In, Ga, and Tl) with group V (N, P, As, Sb, and Bi) elements on Si(111) substrate, including effects of hydrogenation. Two bilayers (BLs) of AlBi, InBi, GaBi, TlAs, and TlSb are found to support a topological phase over a wide range of strains, in addition to BBi, TlN, and TlBi which can be driven into the nontrivial phase via strain. A large band gap of 134 meV is identified in hydrogenated 2 BL film of InBi. One andmore » two BL films of GaBi and 2 BL films of InBi and TlAs on Si(111) surface possess nontrivial phases with a band gap as large as 121 meV in the case of 2 BL film of GaBi. Persistence of the nontrivial phase upon hydrogenations in the III-V thin films suggests that these films are suitable for growing on various substrates.« less
Trobaugh-Lotrario, Angela D; Meyers, Rebecka L; Feusner, James H
2016-04-01
Data are limited regarding outcomes of patients treated for relapsed hepatoblastoma. We reviewed enrollment patterns and outcomes of patients with hepatoblastoma on Children's Oncology Group (COG) phase I/II studies. The medical literature was searched for reports of COG phase I/II studies using PUBMED as well as an inventory from the COG publications office searching manuscripts published from 2000 to 2014. Seventy-one patients with relapsed hepatoblastoma were enrolled on 23 separate COG phase I/II studies. Four studies collected α-fetoprotein (AFP) data, but none utilized AFP decline in assessing response. Most studies enrolled few patients with relapsed hepatoblastoma: 7 studies enrolled 1 patient, and another 7 studies enrolled 2 patients each. Only 9 studies enrolled 3 or more patients with relapsed hepatoblastoma. Four responses were reported. Dedicated strata and/or focus on 1 or 2 studies with compelling biological or clinical rationale for hepatoblastoma may improve accrual (and statistical significance of response data) of patients with relapsed hepatoblastoma. Prospective study of AFP decline versus RECIST response could help determine the optimal method of assessing response to identify potentially beneficial treatments in hepatoblastoma.
NASA Astrophysics Data System (ADS)
Menegário, Amauri A.; Silva, Ariovaldo José; Pozzi, Eloísa; Durrant, Steven F.; Abreu, Cassio H.
2006-09-01
The yeast Saccharomyces cerevisiae was immobilized in cubes of polyurethane foam and the ability of this immobilized material to separate Sb(III) and Sb(V) was investigated. A method based on sequential determination of total Sb (after on-line reduction of Sb(V) to Sb(III) with thiourea) and Sb(III) (after on-line solid-liquid phase extraction) by hydride generation inductively coupled plasma optical emission spectrometry is proposed. A flow system assembled with solenoid valves was used to manage all stages of the process. The effects of pH, sample loading and elution flow rates on solid-liquid phase extraction of Sb(III) were evaluated. Also, the parameters related to on-line pre-reduction (reaction coil and flow rates) were optimized. Detection limits of 0.8 and 0.15 μg L - 1 were obtained for total Sb and Sb(III), respectively. The proposed method was applied to the analysis of river water and effluent samples. The results obtained for the determination of total Sb were in agreement with expected values, including the river water Standard Reference Material 1640 certified by the National Institute of Standards and Technology (NIST). Recoveries of Sb(III) and Sb(V) in spiked samples were between 81 ± 19 and 111 ±15% when 120 s of sample loading were used.
Liu, F; Bagley, W P; Carroll, R C
2000-09-01
SR-90107 is a synthetic pentasaccharide heparinoid Factor Xa antagonist and thrombokinase inhibitor in joint development by Sanofi-Synthelabo (formerly Sanofi) and Organon as a potential treatment and prophylaxis for deep vein thrombosis (DVT) and symptomatic pulmonary embolism following hip or knee surgery and as a potential treatment for coronary artery diseases [330073,359231]. The compound is in phase III clinical trials for the prevention of DVT and pulmonary embolism; phase III trials for the treatment of DVT and pulmonary embolism were expected to start in the first quarter of 2000 and phase IIb trials in cardiology indications are also underway. NDAs are planned to be submitted in Europe and the US in the third quarter of 2000 for the prevention of DVT and symptomatic pulmonary embolism, in 2002 for the treatment of DVT and pulmonary embolism and in 2004 for the treatment of coronary artery diseases [359231]. DVT AND PULMONARY EMBOLISM: The compound had entered phase III clinical trials by December 1998 for the prevention of thrombosis [320585]. By February 2000, four phase III trials in the prevention of DVT and pulmonary embolism following orthopaedic surgery were underway: the European PENTHIFRA trial, which involves 1707 patients with hip fracture; the US PENTATHLON trial, which involves 2200 patients undergoing hip replacements; the European EPHESUS trial, which involves 2200 patients undergoing hip replacements; and the US PENTAMAKS trial, which involves 1000 patients undergoing major knee surgery [359231]. Clinical data from these trials are expected to be available by June 2000 [359793]. By February 2000, preparations were also being made for two phase III trials of SR-90107 for the treatment of DVT and pulmonary embolism, both expected to be initiated in the first quarter of 2000; the MATISSE DVT trial, a double-blind trial of SR-90107 versus enoxaparin sodium in 2200 patients; and the MATISSE PE trial, an open study of SR-90107 versus unfractionated heparin in 2200 patients [359231]. CORONARY ARTERY DISEASES: By February 2000, SR-90107 was also under development for unstable angina, percutaneous transluminal coronary angioplasty, and acute myocardial infarction. At this time, the phase IIb PENTALYSE trial in thrombolyzed acute myocardial infarction patients had been completed, demonstrating a good safety/efficacy ratio, and the phase IIb PENTUA trial in unstable angina was ongoing [359231]. In October 1999, Merrill Lynch forecast sales of EUR 180 million in 2003, planning a review of this figure once clinical data were available [346209]. Also in October 1999, Lehman Brothers predicted that the product had a 70% chance of reaching the market with potential peak sales of US 700 million dollars in 2008 [346267].
Qi, Pengfei; Pichler, Thomas
2016-02-01
Antimony (Sb) is a naturally occurring element of growing environmental concern whose toxicity, adsorption behavior and other chemical properties are similar to that of arsenic (As). However, less is known about Sb compared to As. Individual and simultaneous adsorption experiments with Sb(III) and Sb(V) were conducted in batch mode with focus on the Sb speciation of the remaining liquid phase during individual Sb(III) adsorption experiments. The simultaneous adsorption and oxidation of Sb(III) was confirmed by the appearance of Sb(V) in the solution at varying Fe/Sb ratios (500, 100 and 8) and varying pH values (3.8, 7 and 9). This newly formed Sb(V) was subsequently removed from solution at a Fe/Sb ratio of 500 or at a pH of 3.8. However, more or less only Sb(V) was observed in the liquid phase at the end of the experiments at lower Fe/Sb ratios and higher pH, indicating that competition took place between the newly formed Sb(V) and Sb(III), and that Sb(III) outcompeted Sb(V). This was independently confirmed by simultaneous adsorption experiments of Sb(III) and Sb(V) in binary systems. Under such conditions, the presence of Sb(V) had no influence on the adsorption of Sb(III) while Sb(V) adsorption was significantly inhibited by Sb(III) over a wide pH range (4-10). Thus, in the presence of ferrihydrite and under redox conditions, which allow the presence of both Sb species, Sb(V) should be the dominant species in aquatic environments, since Sb(III) is adsorbed preferentially and at the same time oxidized to Sb(V). Copyright © 2015 Elsevier Ltd. All rights reserved.
Richert, Laura; Doussau, Adélaïde; Lelièvre, Jean-Daniel; Arnold, Vincent; Rieux, Véronique; Bouakane, Amel; Lévy, Yves; Chêne, Geneviève; Thiébaut, Rodolphe
2014-02-26
Many candidate vaccine strategies against human immunodeficiency virus (HIV) infection are under study, but their clinical development is lengthy and iterative. To accelerate HIV vaccine development optimised trial designs are needed. We propose a randomised multi-arm phase I/II design for early stage development of several vaccine strategies, aiming at rapidly discarding those that are unsafe or non-immunogenic. We explored early stage designs to evaluate both the safety and the immunogenicity of four heterologous prime-boost HIV vaccine strategies in parallel. One of the vaccines used as a prime and boost in the different strategies (vaccine 1) has yet to be tested in humans, thus requiring a phase I safety evaluation. However, its toxicity risk is considered minimal based on data from similar vaccines. We newly adapted a randomised phase II trial by integrating an early safety decision rule, emulating that of a phase I study. We evaluated the operating characteristics of the proposed design in simulation studies with either a fixed-sample frequentist or a continuous Bayesian safety decision rule and projected timelines for the trial. We propose a randomised four-arm phase I/II design with two independent binary endpoints for safety and immunogenicity. Immunogenicity evaluation at trial end is based on a single-stage Fleming design per arm, comparing the observed proportion of responders in an immunogenicity screening assay to an unacceptably low proportion, without direct comparisons between arms. Randomisation limits heterogeneity in volunteer characteristics between arms. To avoid exposure of additional participants to an unsafe vaccine during the vaccine boost phase, an early safety decision rule is imposed on the arm starting with vaccine 1 injections. In simulations of the design with either decision rule, the risks of erroneous conclusions were controlled <15%. Flexibility in trial conduct is greater with the continuous Bayesian rule. A 12-month gain in timelines is expected by this optimised design. Other existing designs such as bivariate or seamless phase I/II designs did not offer a clear-cut alternative. By combining phase I and phase II evaluations in a multi-arm trial, the proposed optimised design allows for accelerating early stage clinical development of HIV vaccine strategies.
DIOXIN EMISSIONS FROM OPEN AND UNCONTROLLED BURNING OF BIOMASS AND WASTE
Emissions of polychlorinated dibenzodioxins and dibenszofurans (PCDD/PCDF) from uncontrolled burring of biomass and waste are responsible for a significant, if not major, portion of the global releases. Limited testing for emissions, coupled with activity factors, shows that som...
Penny, Melissa A; Galactionova, Katya; Tarantino, Michael; Tanner, Marcel; Smith, Thomas A
2015-07-29
The RTS,S/AS01 malaria vaccine candidate recently completed Phase III trials in 11 African sites. Recommendations for its deployment will partly depend on predictions of public health impact in endemic countries. Previous predictions of these used only limited information on underlying vaccine properties and have not considered country-specific contextual data. Each Phase III trial cohort was simulated explicitly using an ensemble of individual-based stochastic models, and many hypothetical vaccine profiles. The true profile was estimated by Bayesian fitting of these models to the site- and time-specific incidence of clinical malaria in both trial arms over 18 months of follow-up. Health impacts of implementation via two vaccine schedules in 43 endemic sub-Saharan African countries, using country-specific prevalence, access to care, immunisation coverage and demography data, were predicted via weighted averaging over many simulations. The efficacy against infection of three doses of vaccine was initially approximately 65 % (when immunising 6-12 week old infants) and 80 % (children 5-17 months old), with a 1 year half-life (exponential decay). Either schedule will avert substantial disease, but predicted impact strongly depends on the decay rate of vaccine effects and average transmission intensity. For the first time Phase III site- and time-specific data were available to estimate both the underlying profile of RTS,S/AS01 and likely country-specific health impacts. Initial efficacy will probably be high, but decay rapidly. Adding RTS,S to existing control programs, assuming continuation of current levels of malaria exposure and of health system performance, will potentially avert 100-580 malaria deaths and 45,000 to 80,000 clinical episodes per 100,000 fully vaccinated children over an initial 10-year phase.
Lee, Su Hyun; Lee, Dong Hoon; Ha, Dong Hoon; Oh, Young Jun
2015-10-08
Little is known about the changes in autonomic function during spinal anaesthesia in type 2 diabetic patients. The purpose of the study was to assess the influence of spinal anaesthesia on the heart rate variability in type 2 diabetic patients according to the glycated hemoglobin (HbA1c) level. Sixty-six patients who were scheduled for elective orthostatic lower limb surgery were assigned to three groups (n = 22, each) according to HbA1c; controlled diabetes mellitus (HbA1c < 7 %), uncontrolled diabetes mellitus (HbA1c > 7 %) and the control group. The heart rate variability was measured 10 min before (T0), and at10 min (T1), 20 min (T2) and 30 min (T3) after spinal anaesthesia. Before spinal anaesthesia, total, low-and high-frequency power were significantly lower in the uncontrolled diabetec group than in other group (p < 0.05). During spinal anaesthesia, total, low- and high-frequency powers were did not change in the uncontrolled diabetec group while the low-frequency power in the controlled diabetec group was significantly depressed (p < 0.05). The ratio of low-to high-frequency was comparable among the groups, while it was reduced at T1-2 than at T0 in all the groups. The blood pressures were higher in the uncontrolled diabetec group than in the other groups. Spinal anaesthesia had an influence on the cardiac autonomic modulation in controlled diabetec patients, but not in uncontrolled diabetec patients. There were no differences in all haemodynamic variables during an adequate level of spinal anaesthesia in controlled and uncontrolled type 2 DM. ClinicalTrials.gov NCT02137057.
Impact of Behavioral Control on the Processing of Nociceptive Stimulation
Grau, James W.; Huie, J. Russell; Garraway, Sandra M.; Hook, Michelle A.; Crown, Eric D.; Baumbauer, Kyle M.; Lee, Kuan H.; Hoy, Kevin C.; Ferguson, Adam R.
2012-01-01
How nociceptive signals are processed within the spinal cord, and whether these signals lead to behavioral signs of neuropathic pain, depends upon their relation to other events and behavior. Our work shows that these relations can have a lasting effect on spinal plasticity, inducing a form of learning that alters the effect of subsequent nociceptive stimuli. The capacity of lower spinal systems to adapt, in the absence of brain input, is examined in spinally transected rats that receive a nociceptive shock to the tibialis anterior muscle of one hind leg. If shock is delivered whenever the leg is extended (controllable stimulation), it induces an increase in flexion duration that minimizes net shock exposure. This learning is not observed in subjects that receive the same amount of shock independent of leg position (uncontrollable stimulation). These two forms of stimulation have a lasting, and divergent, effect on subsequent learning: controllable stimulation enables learning whereas uncontrollable stimulation disables it (learning deficit). Uncontrollable stimulation also enhances mechanical reactivity. We review evidence that training with controllable stimulation engages a brain-derived neurotrophic factor (BDNF)-dependent process that can both prevent and reverse the consequences of uncontrollable shock. We relate these effects to changes in BDNF protein and TrkB signaling. Controllable stimulation is also shown to counter the effects of peripheral inflammation (from intradermal capsaicin). A model is proposed that assumes nociceptive input is gated at an early sensory stage. This gate is sensitive to current environmental relations (between proprioceptive and nociceptive input), allowing stimulation to be classified as controllable or uncontrollable. We further propose that the status of this gate is affected by past experience and that a history of uncontrollable stimulation will promote the development of neuropathic pain. PMID:22934018
Asthma control in Saudi Arabia: Gender implications.
Torchyan, Armen A
2017-05-01
Gender-related factors in asthma control should be considered in clinical consultations to substantially improve asthma control in women. Meanwhile, a limited number of studies have been reported on gender differences in factors related to asthma control, especially in Saudi Arabia. To study the potential gender differences in factors associated with asthma control among adult patients with physician-diagnosed asthma. A cross-sectional study was conducted in adult patients with asthma who attended primary care clinics at three major hospitals in Riyadh, Saudi Arabia. Asthma control was measured by using the Asthma Control Test. Asthma control status was classified as either controlled (Asthma Control Test score of >19) or uncontrolled (Asthma Control Test score of ≤19). Multiple logistic regression analysis was performed. In this study, 58.9% of men and 77.0% of women had uncontrolled asthma (p = 0.002). Factors associated with uncontrolled asthma were different between men and women, except for household income. Reporting higher levels of stress (odds ratio [OR] 4.3 [95% confidence interval {CI}, 1.7-11.1]), daily tobacco smoking (OR 5.8 [95% CI, 1.5-23.5]), and a monthly household income of <15,000 Saudi Arabian Riyals (OR 4.5 [95% CI, 1.9-10.5]) were associated with uncontrolled asthma in men. Being unemployed (OR 3.4 [95% CI, 1.3-9.4]), being obese (OR 3.2 [95% CI, 1.1-9.2]), or having a monthly household income of <15,000 Saudi Arabian Riyals (OR 3.1 [95% CI, 1.2-8.0]) were associated with uncontrolled asthma in women. This study demonstrated that many factors, such as stress, occupation, and obesity, had a differential relationship with uncontrolled asthma among men and women in Saudi Arabia that could provide more insight into methods of improving asthma control, especially in women.
Dau, Phuong D.; Shuh, David K.; Sturzbecher-Hoehne, Manuel; ...
2016-07-07
The divalent oxidation state is increasingly stable relative to the trivalent state for the later actinide elements, with californium the first actinide to exhibit divalent chemistry under moderate conditions. Although there is evidence for divalent Cf in solution and solid compounds, there are no reports of discrete complexes in which Cf II is coordinated by anionic ligands. Described here is the divalent Cf methanesulfinate coordination complex, Cf II(CH 3SO 2) 3-, prepared in the gas phase by reductive elimination of CH 3SO 2 from Cf III(CH 3SO 2) 4-. Comparison with synthesis of the corresponding Sm and Cm complexes revealsmore » reduction of CfIII and SmIII, and no evidence for reduction of Cm III. This reflects the comparative 3+/2+ reduction potentials: Cf 3+ (-1.60 V) ≈ Sm 3+ (-1.55 V) >> Cm 3+ (-3.7 V). Association of O 2 to the divalent complexes is attributed to formation of superoxides, with recovery of the trivalent oxidation state. Lastly, the new gas-phase chemistry of californium, now the heaviest element to have been studied in this manner, provides evidence for Cf II coordination complexes and similar chemistry of Cf and Sm.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dau, Phuong D.; Shuh, David K.; Sturzbecher-Hoehne, Manuel
The divalent oxidation state is increasingly stable relative to the trivalent state for the later actinide elements, with californium the first actinide to exhibit divalent chemistry under moderate conditions. Although there is evidence for divalent Cf in solution and solid compounds, there are no reports of discrete complexes in which Cf II is coordinated by anionic ligands. Described here is the divalent Cf methanesulfinate coordination complex, Cf II(CH 3SO 2) 3-, prepared in the gas phase by reductive elimination of CH 3SO 2 from Cf III(CH 3SO 2) 4-. Comparison with synthesis of the corresponding Sm and Cm complexes revealsmore » reduction of CfIII and SmIII, and no evidence for reduction of Cm III. This reflects the comparative 3+/2+ reduction potentials: Cf 3+ (-1.60 V) ≈ Sm 3+ (-1.55 V) >> Cm 3+ (-3.7 V). Association of O 2 to the divalent complexes is attributed to formation of superoxides, with recovery of the trivalent oxidation state. Lastly, the new gas-phase chemistry of californium, now the heaviest element to have been studied in this manner, provides evidence for Cf II coordination complexes and similar chemistry of Cf and Sm.« less
DOT National Transportation Integrated Search
2015-08-01
This report provides the findings from the third phase of a three-part study about the influences of neighborhood crimes on travel : mode choice. While previous phases found evidence that high levels of neighborhood crime discourage people from choos...
APPROACHES FOR REMEDIATION OF UNCONTROLLED WOOD PRESERVING SITES
This document provides an overview of remediation of uncontrolled wood preserving sites. It is, in part, a distillation of discussions that took place at a Forum on Wood Preserving Waste that was held in San Francisco, California, in October 1988. Information from this workshop h...
36 CFR 228.108 - Surface use requirements.
Code of Federal Regulations, 2013 CFR
2013-07-01
... authorized in an approved surface use plan of operations, protect such resources. (e) Fire prevention and control. To the extent practicable, the operator shall take measures to prevent uncontrolled fires on the area of operation and to suppress uncontrolled fires resulting from the operations. (f) Fisheries...
36 CFR 228.108 - Surface use requirements.
Code of Federal Regulations, 2012 CFR
2012-07-01
... authorized in an approved surface use plan of operations, protect such resources. (e) Fire prevention and control. To the extent practicable, the operator shall take measures to prevent uncontrolled fires on the area of operation and to suppress uncontrolled fires resulting from the operations. (f) Fisheries...
36 CFR 228.108 - Surface use requirements.
Code of Federal Regulations, 2014 CFR
2014-07-01
... authorized in an approved surface use plan of operations, protect such resources. (e) Fire prevention and control. To the extent practicable, the operator shall take measures to prevent uncontrolled fires on the area of operation and to suppress uncontrolled fires resulting from the operations. (f) Fisheries...
The report summarizes the results of a four-phase program to demonstrate that fuel cell energy recovery using a commercial phosphoric acid fuel cell is both environmentally sound and commercially feasible. Phase I, a conceptual design and evaluation study, addressed the technical...
The report summarizes the results of a four-phase program to demonstrate that fuel cell energy recovery using a commercial phosphoric acid fuel cell is both environmentally sound and commercially feasible. Phase I, a conceptual design and evaluation study, addressed the technical...
1978-08-01
12°±30’ 1180±2° OPTIONAL .0005 IN./IN. BACK TAPER 015 RAD LIPS TO BE WITHIN .002 OF TRUE ANGULAR POSITION NOTES: 1. LAND WIDTH: 28% ± .005... horoscope and dye-penetrant requirements. 79 PHASE 1 PHASE II PHASE III PHASE IV CUTTING DRILLING MACHINING NONDESTRUCTIVE EVALUATION METHOD MATERIAL
NASA Astrophysics Data System (ADS)
Jin, Cheng-Jie; Wang, Wei; Jiang, Rui
2016-08-01
The proper setting of traffic signals at signalized intersections is one of the most important tasks in traffic control and management. This paper has evaluated the four-phase traffic signal plans at a four-leg intersection via cellular automaton simulations. Each leg consists of three lanes, an exclusive left-turn lane, a through lane, and a through/right-turn lane. For a comparison, we also evaluate the two-phase signal plan. The diagram of the intersection states in the space of inflow rate versus turning ratio has been presented, which exhibits four regions: In region I/II/III, congestion will propagate upstream and laterally and result in queue spillover with both signal plans/two-phase signal plan/four-phase signal plan, respectively. Therefore, neither signal plan works in region I, and only the four-phase signal plan/two-phase signal plan works in region II/III. In region IV, both signal plans work, but two-phase signal plan performs better in terms of average delays of vehicles. Finally, we study the diagram of the intersection states and average delays in the asymmetrical configurations.
40 CFR 76.12 - Phase I NOX compliance extension.
Code of Federal Regulations, 2011 CFR
2011-07-01
... (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.12 Phase I NOX compliance extension. (a... outage. (iii) Fuel and energy balance summaries and power and other consumption requirements (including...
40 CFR 76.12 - Phase I NOX compliance extension.
Code of Federal Regulations, 2013 CFR
2013-07-01
... (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.12 Phase I NOX compliance extension. (a... outage. (iii) Fuel and energy balance summaries and power and other consumption requirements (including...
40 CFR 76.12 - Phase I NOX compliance extension.
Code of Federal Regulations, 2014 CFR
2014-07-01
... (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.12 Phase I NOX compliance extension. (a... outage. (iii) Fuel and energy balance summaries and power and other consumption requirements (including...
40 CFR 76.12 - Phase I NOX compliance extension.
Code of Federal Regulations, 2012 CFR
2012-07-01
... (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.12 Phase I NOX compliance extension. (a... outage. (iii) Fuel and energy balance summaries and power and other consumption requirements (including...
40 CFR 76.12 - Phase I NOX compliance extension.
Code of Federal Regulations, 2010 CFR
2010-07-01
... (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.12 Phase I NOX compliance extension. (a... outage. (iii) Fuel and energy balance summaries and power and other consumption requirements (including...
The NATO III 5 MHz Distribution System
NASA Technical Reports Server (NTRS)
Vulcan, A.; Bloch, M.
1981-01-01
A high performance 5 MHz distribution system is described which has extremely low phase noise and jitter characteristics and provides multiple buffered outputs. The system is completely redundant with automatic switchover and is self-testing. Since the 5 MHz reference signals distributed by the NATO III distribution system are used for up-conversion and multiplicative functions, a high degree of phase stability and isolation between outputs is necessary. Unique circuit design and packaging concepts insure that the isolation between outputs is sufficient to quarantee a phase perturbation of less than 0.0016 deg when other outputs are open circuited, short circuited or terminated in 50 ohms. Circuit design techniques include high isolation cascode amplifiers. Negative feedback stabilizes system gain and minimizes circuit phase noise contributions. Balanced lines, in lieu of single ended coaxial transmission media, minimize pickup.
The role of technology in reducing health care costs. Phase II and phase III.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cilke, John F.; Parks, Raymond C.; Funkhouser, Donald Ray
2004-04-01
In Phase I of this project, reported in SAND97-1922, Sandia National Laboratories applied a systems approach to identifying innovative biomedical technologies with the potential to reduce U.S. health care delivery costs while maintaining care quality. The effort provided roadmaps for the development and integration of technology to meet perceived care delivery requirements and an economic analysis model for development of care pathway costs for two conditions: coronary artery disease (CAD) and benign prostatic hypertrophy (BPH). Phases II and III of this project, which are presented in this report, were directed at detailing the parameters of telemedicine that influence care deliverymore » costs and quality. These results were used to identify and field test the communication, interoperability, and security capabilities needed for cost-effective, secure, and reliable health care via telemedicine.« less
Brunoni, Andre Russowsky; Nitsche, Michael A.; Bolognini, Nadia; Bikson, Marom; Wagner, Tim; Merabet, Lotfi; Edwards, Dylan J.; Valero-Cabre, Antoni; Rotenberg, Alexander; Pascual-Leone, Alvaro; Ferrucci, Roberta; Priori, Alberto; Boggio, Paulo; Fregni, Felipe
2011-01-01
Background Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past ten years, tDCS physiological mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodological, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. Methods We convened a workgroup of researchers in the field to review, discuss and provide updates and key challenges of neuromodulation use for clinical research. Main Findings/Discussion We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (i) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (ii) methodological aspects related to the clinical research of tDCS as divided according to study phase (i.e., preclinical, phase I, phase II and phase III studies); (iii) ethical and regulatory concerns; (iv) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS. PMID:22037126
Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders
2017-11-15
Hurler Syndrome (MPS I); Hurler-Scheie Syndrome; Hunter Syndrome (MPS II); Sanfilippo Syndrome (MPS III); Krabbe Disease (Globoid Leukodystrophy); Metachromatic Leukodystrophy (MLD); Adrenoleukodystrophy (ALD and AMN); Sandhoff Disease; Tay Sachs Disease; Pelizaeus Merzbacher (PMD); Niemann-Pick Disease; Alpha-mannosidosis
LABORATORY STUDY ON THE OXIDATION OF ARSENIC III TO ARSENIC V
A one-year laboratory study was performed to determine the ability of seven oxidants to oxidize As(III) to As(V). These included chlorine, permanganate, ozone, chlorine dioxide, monochloramine, a solid-phase oxidizing media, and 254 nm ultraviolet light. Chlorine and permanganate...
Phase 2 Sequential and Concurrent Chemoradiation for Advanced Nasopharyngeal Carcinoma (NPC)
2016-12-09
Stage II Lymphoepithelioma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx
1987-04-30
1.5 ZrO2 * 0.3 As203, 0.024 Cr203, melted under various conditions. Parallel measurements of X-ray diffraction, optical and EPR spectra reveal the...optical and EPR spectra reveal the different formation of gahnite from precursor glass or petalite-like phase. Introduction In a number of recent...conditions on optical and EPR spectra of Cr(III). Further on the parallel changes of spectra and x-ray diffraction patterns are indica- ted. The gahnite
Analysis of WakeVAS Benefits Using ACES Build 3.2.1
NASA Technical Reports Server (NTRS)
Smith, Jeremy C.
2005-01-01
The FAA and NASA are currently engaged in a Wake Turbulence Research Program to revise wake turbulence separation standards, procedures, and criteria to increase airport capacity while maintaining or increasing safety. The research program is divided into three phases: Phase I near term procedural enhancements; Phase II wind dependent Wake Vortex Advisory System (WakeVAS) Concepts of Operations (ConOps); and Phase III farther term ConOps based on wake prediction and sensing. This report contains an analysis that evaluates the benefits of a closely spaced parallel runway (CSPR) Phase I ConOps, a single runway and CSPR Phase II ConOps and a single runway Phase III ConOps. A series of simulation runs were performed using the Airspace Concepts Evaluation System (ACES) Build 3.21 air traffic simulator to provide an initial assessment of the reduction in delay and cost savings obtained by the use of a WakeVAS at selected U.S. airports. The ACES simulator is being developed by NASA Ames Research Center as part of the Virtual Airspace Modelling and Simulation (VAMS) program.
Prasad, Vinay; Goldstein, Jeffery A.
2015-01-01
Background Although participation in cancer clinical trials is low, little is known about the number of available clinical trials, and open spots for patients. Moreover, it is unclear what the relationship is between clinical trial openings and the incidence and mortality of cancer subtypes. Methodology We identified the number of phase I, phase II, and phase III registered at clinicaltrials.gov by cancer (tumor) type. All counts were over the preceding 5 years (2008 to 2013). We compared these counts against the incidence and prevalence of disease reported by Surveillance, Epidemiology, and End Results (SEER) database for 32 common cancers Results From 2008 to 2013, 3879 phase I trials, 4982 phase II trials and 1379 phase III trials concerning a cancer subtype were registered in clinicaltrials.gov. These trials had a cumulative proposed recruitment of 203396, 421502, and 697787 patients, respectively. Trial enrollment varied by tumor type, with both over and under-representation occurring. Conclusion Opportunities to enroll in clinical trials vary by phase and tumor type. Oncologists must remain committed to clinical trials. PMID:26321010
Prasad, Vinay; Goldstein, Jeffery A
2015-11-01
Although participation in cancer clinical trials is low, little is known about the number of available clinical trials, and open spots for patients. Moreover, it is unclear what the relationship is between clinical trial openings and the incidence and mortality of cancer subtypes. We identified the number of phase I, phase II and phase III registered at clinicaltrials.gov by cancer (tumour) type. All counts were over the preceding 5 years (2008-2013). We compared these counts against the incidence and prevalence of disease reported by Surveillance, Epidemiology and End Results (SEER) database for 32 common cancers. From 2008 to 2013, 3879 phase I trials, 4982 phase II trials and 1379 phase III trials concerning a cancer subtype were registered in clinicaltrials.gov. These trials had a cumulative proposed recruitment of 203,396, 421,502 and 697,787 patients, respectively. Trial enrollment varied by tumour type, with both over and under-representation occurring. Opportunities to enroll in clinical trials vary by phase and tumour type. Oncologists must remain committed to clinical trials. Published by Elsevier Ltd.
Shock, release and Taylor impact of the semicrystalline thermoplastic polytetrafluoroethylene
NASA Astrophysics Data System (ADS)
Bourne, N. K.; Brown, E. N.; Millett, J. C. F.; Gray, G. T.
2008-04-01
The high strain-rate response of polymers is a subject that has gathered interest over recent years due to their increasing engineering importance, particularly in load bearing applications subject to extremes of pressure and strain rate. The current work presents two specific sets of experiments interrogating the effect of dynamic, high-pressure loading in the regime of the phase II to phase III pressure-induced crystalline phase transition in polytetrafluoroethylene (PTFE). These are gas-gun driven plate- and Taylor impact. Together these experiments highlight several effects associated with the dynamic, pressure-induced phase transitions in PTFE. An elevated release wave speed shows evidence of a pressure-induced phase change at a stress commensurate with that observed statically. It is shown that convergence between analytic derivations of release wave speed and the data requires the phase II to III transition to occur. Taylor impact is an integrated test that highlights continuum behavior that has origin in mesoscale response. There is a rapid transition from ductile to brittle behavior observed that occurs at a pressure consistent with this phase transition.
Demmer, Ryan T; Holtfreter, Birte; Desvarieux, Moïse; Jacobs, David R; Kerner, Wolfgang; Nauck, Matthias; Völzke, Henry; Kocher, Thomas
2012-10-01
To explore associations between diabetes etiology (type 1 diabetes mellitus [T1DM] vs. T2DM) and glycemic control in the prediction of 5-year periodontal status change. The Study of Health in Pomerania (SHIP) is a population-based stratified sample of German men and women. Healthy participants and those determined to have T2DM arose from the SHIP cohort, and T1DM participants were recruited from diabetes clinics in the catchment area that gave rise to SHIP. Dentate participants (n = 2,626; 53% women; 20-81 years of age) were included. Diabetes was determined via physician diagnosis and/or HbA(1c) ≥6.5% (uncontrolled diabetes >7.0%). Examiners blinded to diabetes status performed random half-mouth periodontal examinations, assessing probing depth (PD) and attachment loss (AL) (four sites/tooth) at baseline and follow-up. Participants were categorized into six groups as follows: 1) diabetes free (n = 2,280), 2) incident T2DM (n = 79), 3) controlled T2DM (n = 80), 4) uncontrolled T2DM (n = 72), 5) controlled T1DM (n = 43), and 6) uncontrolled T1DM (n = 72). In multivariable regressions, mean PD change (ΔMPD), mean AL change (ΔMAL), or incident tooth-loss values were regressed across the aforementioned diabetes categories. Mean (SD) ΔMPD and ΔMAL values among all participants were -0.08 ± 0.5 mm and 0.08 ± 1.03 mm, respectively, and 34% lost one or more teeth. Relative to diabetes-free participants, those with uncontrolled T2DM experienced greater ΔMPD ± SE (P < 0.05), whereas participants with either uncontrolled T1DM or uncontrolled T2DM realized greater ΔMAL (P < 0.05). Uncontrolled T1DM and T2DM were both associated with an increased risk of future tooth loss (P < 0.05). Diabetes control, but not etiology, was associated with future tooth loss and accelerated AL progression.
NASA Astrophysics Data System (ADS)
Gunnars, Anneli; Blomqvist, Sven; Johansson, Peter; Andersson, Christian
2002-03-01
The formation of Fe(III) oxyhydroxide colloids by oxidation of Fe(II) and their subsequent aggregation to larger particles were studied in laboratory experiments with natural water from a freshwater lake and a brackish coastal sea. Phosphate was incorporated in the solid phase during the course of hydrolysis of iron. The resulting precipitated amorphous Fe(III) oxyhydroxide phases were of varying composition, depending primarily on the initial dissolved Fe/P molar ratio, but with little influence by salinity or concentration of calcium ions. The lower limiting Fe/P ratio found for the solid phase suggests the formation of a basic Fe(III) phosphate compound with a stoichiometric Fe/P ratio of close to two. This implies that an Fe/P stoichiometry of ≈2 ultimately limits the capacity of precipitating Fe(III) to fix dissolved phosphate at oxic/anoxic boundaries in natural waters. In contrast to phosphorus, the uptake of calcium seemed to be controlled by sorption processes at the surface of the iron-rich particles formed. This uptake was more efficient in freshwater than in brackish water, suggesting that salinity restrains the uptake of calcium by newly formed Fe(III) oxyhydroxides in natural waters. Moreover, salinity enhanced the aggregation rate of the colloids formed. The suspensions were stabilised by the presence of organic matter, although this effect was less pronounced in seawater than in freshwater. Thus, in seawater of 6 to 33 ‰S, the removal of particles was fast (removal half time < 200 h), whereas the colloidal suspensions formed in freshwater were stable (removal half time > 900 h). Overall, oxidation of Fe(II) and removal of Fe(III) oxyhydroxide particles were much faster in seawater than in freshwater. This more rapid turnover results in lower iron availability in coastal seawater than in freshwater, making iron more likely to become a limiting element for chemical scavenging and biologic production.
Investor Outlook: Focus on Upcoming LCA2 Gene Therapy Phase III Results.
Schimmer, Joshua; Breazzano, Steven
2015-09-01
Investor interest in gene therapy has increased substantially over the past few years, and the next major catalyst for the field is likely to be Spark Therapeutics's phase III trial for the treatment of visual impairment caused by RPE65 gene mutations (often referred to as Leber congenital amaurosis type 2, or LCA2, but may include other retinal disorders). Analysis of the approach from the basic genetics, underlying visual mechanisms, clinical data, and commercialization considerations helps frame investor expectations and the potential implications for the broader field.
Estreet, Anthony; Apata, Jummai; Kamangar, Farin; Schutzman, Christine; Buccheri, Jane; O’Keefe, Anne-Marie; Wagner, Fernando; Sheikhattari, Payam
2017-01-01
Background: This study compares participant’ sretention in three phases of smoking cessation interventions, one provided in a health clinic and the subsequent two in community-based settings. Methods: Smoking cessation interventions were conducted in three phases from 2008 to 2015 in two underserved urban communities with low socioeconomic profiles and high rates of smoking (n = 951). Phase I was conducted in a clinic; Phases II and III were conducted in community venues. In Phases II and III, incremental changes were made based on lessons learned from the previous phases. Retention (attending six or more sessions) was the primary predictor of cessation and was analyzed while controlling for associated factors including age, gender, race, employment, education, and nicotine dependence. Results: Retention increased substantially over the three phases, with rates for attending six or more sessions of 13.8%, 51.9%, and 67.9% in Phases I, II, and III, respectively. Retention was significantly higher in community settings than in the clinic setting (adjusted odds ratio [OR] = 6.7; 95% confidence intervals [CI] = 4.6, 9.8). In addition to the intervention in community venues, predictors of retention included age and unemployment. Higher retention was significantly associated with higher quit rates (adjusted OR = 2.4; 95% CI = 1.5, 3.8). Conclusions: Conducting the intervention in community settings using trained peer motivators rather than health-care providers resulted in significantly higher retention and smoking cessation rates. This was due in part to the ability to tailor cessation classes in the community for specific populations and improving the quality of the intervention based on feedback from participants and community partners. PMID:29416835
Oguni, M; Tanaka, O; Shinohara, H; Yoshioka, T; Setogawa, T
1991-01-01
The development of the retinal pigment epithelium (RPE) was studied ultrastructurally, using 13 externally normal human embryos, Carnegie stages ranging from 13 to 23 (4-8 week of gestation). Melanosomes in the peripheral and posterior RPE were classified according to Fitzpatrick et al. The melanosome of phase I is formed from the Golgi complex and parcelled off into small vesicles. The vesicle enlarges and elongates to form an oval organelle with membranous structures in it (phase II melanosome). Subsequently, melanin deposits on the membranous structures of the melanosomes (phase III melanosomes), and the completion of this process produces a uniformly electrondense granule without discernible internal structures (phase IV melanosome). Melanosomes of phases III and IV appeared in the RPE at stage 15. As the embryonic stage advanced, the ratio of phase II melanosomes decreased and that of phase IV melanosomes increased. The number of phase III melanosomes reached a peak in the peripheral and posterior RPE at stages 15 and 18, respectively. After stage 17, the increase in melanosomes and intracellular organelles was more prominent in the posterior than in the peripheral RPE. During stages 13 and 15, gap junctions were present not only in the apical but also basal plasma membranes of the RPE. At stage 20, gap junctions in the basal plasma membrane disappeared except for the transitional areas from the RPE to the neural retina (NR). In addition, gap junctions were observed between NR and RPE only in the peripheral region at stage 20. The morphological and quantitative differences in the peripheral and posterior RPE in the embryonic period are discussed.
Rodent models of depression: learned helplessness induced in mice.
Anisman, H; Merali, Z
2001-05-01
Uncontrollable stressors induce a variety of behavioral disturbances that are in many ways reminiscent of the symptoms that characterize clinical depression. These deficits are evident across a range of species, including mice. Given the increasing focus on genetic techniques involving mice to identify the mechanisms subserving these behavioral disturbances (e.g., recombinant, knockout, and transgenic strains), it is of particular interest to provide a detailed description of the method to induce behavioral deficits in response to uncontrollable stressors. This unit describes the procedure used to assess the effects of controllable and uncontrollable shock on subsequent shock escape performance in mice using an escape-delay procedure.
The radio frequency (RF) heating process can be used to volumetrically heat and thus decontaminate uncontrolled landfills and hazardous substances from spills. After the landfills are heated, decontamination of the hazardous substances occurs due to thermal decomposition, vaporiz...
26 CFR 1.482-5 - Comparable profits method.
Code of Federal Regulations, 2010 CFR
2010-04-01
... operating profit represents a return for the investment of resources and assumption of risks. Therefore... from a sufficient number of years of data to reasonably measure returns that accrue to uncontrolled... party and uncontrolled comparables include the following— (i) Rate of return on capital employed. The...
Effects of Prolonged Deprivation on Learned Helplessness.
ERIC Educational Resources Information Center
Mal, Suraj; And Others
1990-01-01
Investigated influence of prolonged deprivation on responses to uncontrollable outcome among 104 Indian students in the tenth grade. Finds high-deprived and female students displayed greater helplessness than did their low-deprived and male counterparts. Females and high-deprives students attributed uncontrollable outcome more to internal, stable,…
Deleanu, Oana-Claudia; Mălăuţ, Andra Elena; Nebunoiu, Ana Maria; Micheu, Miruna Mihaela; Mihălţan, Florin Dumitru
2014-01-01
Arterial hypertension (HT) and obstructive sleep apnea syndrome (OSAS) are associated through cause-effect relationship. We aimed to study the effect of medication controlled hypertension on OSAS patients. From 483 followed patients with OSAS, 252 associating HT; 142 patients of them (56.34%) received antihypertensive medication, 59 patients (41.54%) had controlled HT, 83 patients (58.46%) had uncontrolled HT. Demographic and anthropometric data, OSAS symptoms, comorbidities, apnea index (IA), apnea-hypopnea index (IAH), desaturation index, CPAP titration, CPAP failure rate were studiated regarding differences between patients with controlled and uncontrolled HT. Fifty nine patients with controlled HT were: 20 women (33.9%), 39 men (66.1%), with mean age of 56.08 years +/- 11.33, with an average AHI of 53.61 +/- 34.42/hour, an average of CPAP pressure prediction of 10.15 +/- 243 cm H2O. Eighty three patients with uncontrolled HT were: 18 women (21.7%), 65 men (78.3%), with mean age 55 +/- 9.06 years, with an average AHl of 61.91 +/- 43.61/hour, an average of CPAP pressure prediction of 10.47 +/- 2cm H2O. Comparing with the controlled HT group, patients with uncontrolled HT reported morning headaches, morning fatigue and impotency in a higher rate (p = 0.020, 0.018, 0.011 respectively); Epworth Sleepiness Scale was under 10 (cut-off for daytime sleepiness) in patients with controlled HT(p = 0.001) and higher in those with uncontrolled HT. Patients with uncontrolled HT were diagnosed with HT for a longer period (p = 0.006), had higher values of systolic and diastolic blood pressure at the time of the presentation. Statistically significant differences were found only for AHI post-CPAP (11.89/h vs. 22.30/h, p = 0.013) and nocturnal desaturation index post-CPAP (6.03/h vs. 16.55/h, p = 0.017), both higher in patients with uncontrolled HT. The hypothesis regarding existing differences related to the cardiovascular comorbidities was not supported. Controlled blood pressure deletes sleepiness, a defining symptom for OSAS and reduces remaining symptoms (headaches, impotency and morning fatigue). Presence of OSAS symptoms is less common in the controlled HT group, making the OSAS more difficult to suspect. These patients may have a grater benefit from CPAP therapy--they have AHI post-CPAP and desaturations post-CPAP significantly lower than patients with uncontrolled HT.
Deloose, Eveline; Tack, Jan
2016-02-15
During the fasting state the upper gastrointestinal tract exhibits a specific periodic migrating contraction pattern that is known as the migrating motor complex (MMC). Three different phases can be distinguished during the MMC. Phase III of the MMC is the most active of the three and can start either in the stomach or small intestine. Historically this pattern was designated to be the housekeeper of the gut since disturbances in the pattern were associated with small intestinal bacterial overgrowth; however, its role in the involvement of hunger sensations was already hinted in the beginning of the 20th century by both Cannon (Cannon W, Washburn A. Am J Physiol 29: 441-454, 1912) and Carlson (Carlson A. The Control of Hunger in Health and Disease. Chicago, IL: Univ. of Chicago Press, 1916). The discovery of motilin in 1973 shed more light on the control mechanisms of the MMC. Motilin plasma levels fluctuate together with the phases of the MMC and induce phase III contractions with a gastric onset. Recent research suggests that these motilin-induced phase III contractions signal hunger in healthy subjects and that this system is disturbed in morbidly obese patients. This minireview describes the functions of the MMC in the gut and its regulatory role in controlling hunger sensations. Copyright © 2016 the American Physiological Society.
A Methodology for Phased Array Radar Threshold Modeling Using the Advanced Propagation Model (APM)
2017-10-01
TECHNICAL REPORT 3079 October 2017 A Methodology for Phased Array Radar Threshold Modeling Using the Advanced Propagation Model (APM...Head 55190 Networks Division iii EXECUTIVE SUMMARY This report summarizes the methodology developed to improve the radar threshold modeling...PHASED ARRAY RADAR CONFIGURATION ..................................................................... 1 3. METHODOLOGY
Central State University: Phase III Report
ERIC Educational Resources Information Center
Ohio Board of Regents, 2013
2013-01-01
This document is the final report on Central State University's implementation of Section 371 of Ohio Amended Substitute House Bill 153. Implementation of Phase I action items required that deliverables and timelines be shifted to give Central State the best opportunity for early success. In Phase II, Central State responded aggressively to a…
Kerley, C P; Dolan, E; Cormican, L
2017-11-01
Dietary nitrate has been shown to increase nitrate/nitrite levels in multiple populations, with potential blood pressure lowering effects. However, there are few reports among hypertensives. We aimed to assess the effect of daily nitrate in subjects with controlled hypertension vs. uncontrolled hypertension. On day 0, hypertensives wore an ambulatory BP monitor (ABPM) for 24 h and fasting blood was taken. Subjects then consumed concentrated beetroot juice (12.9 mmol nitrate) for 14 consecutive days. On day 14 subjects consumed their last nitrate dose after fasting blood was drawn and again had an ABPM for 24 h. According to baseline ABPM, 11 subjects had controlled BP while 8 had uncontrolled BP. There were similar, significant increases in serum nitrate/nitrite in both groups. We observed little change in BP variables among controlled hypertensives. However, there were reductions in BP variables in uncontrolled hypertensives where decreases in nighttime DBP (-6 ± 4.8 mmHg), arterial stiffness (-0.08 ± 0.03 ambulatory arterial stiffness index) and LDL (-0.36 ± 0.42 mmol/L) reached significance (p = 003, 0.05 and 0.046, respectively). Our results support the existing data suggesting an anti-hypertensive effect of nitrate-containing beetroot juice, but only among those with uncontrolled hypertension.
Kubo, Mary N.; Kayima, Joshua K.; Were, Anthony J.; McLigeyo, Seth O.; Ogola, Elijah N.
2015-01-01
Objective. To determine the factors associated with poor blood pressure control among renal transplant recipients in a resource-limited setting. Methods. A cross-sectional study was carried out on renal transplant recipients at the Kenyatta National Hospital. Sociodemographic details, blood pressure, urine albumin : creatinine ratio, and adherence using the MMAS-8 questionnaire were noted. Independent factors associated with uncontrolled hypertension were determined using logistic regression analysis. Results. 85 subjects were evaluated. Mean age was 42.4 (SD ± 12.2) years, with a male : female ratio of 1.9 : 1. Fifty-five patients (64.7%) had uncontrolled hypertension (BP ≥ 130/80 mmHg). On univariate analysis, male sex (OR 3.7, 95% CI 1.4–9.5, p = 0.006), higher levels of proteinuria (p = 0.042), and nonadherence to antihypertensives (OR 18, 95% CI 5.2–65.7, p < 0.001) were associated with uncontrolled hypertension. On logistic regression analysis, male sex (adjusted OR 4.6, 95% CI 1.1–19.0, p = 0.034) and nonadherence (adjusted OR 33.8, 95% CI 8.6–73.0, p < 0.001) were independently associated with uncontrolled hypertension. Conclusion. Factors associated with poor blood pressure control in this cohort were male sex and nonadherence to antihypertensives. Emphasis on adherence to antihypertensive therapy must be pursued within this population. PMID:26257920
NASA Astrophysics Data System (ADS)
de Mello, Juliana Lolli Malagoli; Berton, Mariana Piatto; de Cassia Dourado, Rita; Giampietro-Ganeco, Aline; de Souza, Rodrigo Alves; Ferrari, Fábio Borba; de Souza, Pedro Alves; Borba, Hirasilva
2017-10-01
The aim of this study was to evaluate the effect of ambient temperature on the physical and chemical characteristics of the longissimus dorsi muscle by comparing the quality of meat from pigs reared in a controlled and in an uncontrolled environment, the latter provided with a shallow pool. Twenty castrated male pigs of the Topigs line were randomly allotted to two treatments: a controlled environment, with constant temperature (22 °C) and relative humidity (70%); and an uncontrolled environment in a conventional shed for rearing pigs equipped with a shallow pool, where pigs were subject to climatic variations. Meat from pigs kept in the controlled environment showed a greater capacity to retain intracellular water, higher tenderness, and lower cholesterol levels than meat from pigs reared in the uncontrolled environment, but displayed higher lipid oxidation and a lower concentration of DHA. Treatments had no effect on color, pH, chemical composition, or fatty acid profile (except DHA concentration). Rearing pigs in sheds equipped with a shallow pool minimizes the effects of environmental heat on meat quality, allowing the production of high-quality meat in warm climate regions without expensive investments. Animals reared in an uncontrolled environment equipped with a shallow pool are able to produce meat with characteristics within the quality standards and with similar quality to that of meat from animals raised in controlled environment.
Zarei, Mahnaz; Farahnak, Zahra; Hosseinzadeh-Attar, Mohammad Javad; Javanbakht, Mohammad Hassan; Hosseinzadeh, Payam; Derakhshanian, Hoda; Farahbakhsh-Farsi, Payam; Djalali, Mahmoud
2016-05-01
This study was designed to compare lipid peroxidation and antioxidant enzymes activity in Type 2 diabetes patients with good or weak glycemic control. In this case-control study, 62 Type 2 diabetic patients with glycated hemoglobin (HbA1c) between 6 and 8 were enrolled as the controlled group and 55 patients with HbA1c > 8 were selected as an uncontrolled group. Patients were all referred to Iranian Diabetes Association in Tehran, Iran, from 2010 onward. Groups were chosen by convenience sampling and were matched based on age, sex and duration of disease. Demographic questionnaire, two 24-hour food recall, HbA1c, insulin, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase were measured in blood samples. Data were analyzed by Food Processor II and SPSS software. A mean daily consumption of energy, carbohydrate, protein, and fat was not significantly different between two groups. MDA in the uncontrolled group was significantly higher than controlled group (2.03 ± 0.88 vs. 1.65 ± 1.01 nmol/ml; P = 0.030). A mean SOD was slightly higher in the uncontrolled group comparing to the control group (843.3 ± 101.9 vs. 828.0 ± 127.3 U/g Hb; P = 0.400). These data suggest that MDA as a lipid peroxidation indicator is higher in uncontrolled diabetes probably due to chronic high blood sugar followed by higher oxidative stress.
de Mello, Juliana Lolli Malagoli; Berton, Mariana Piatto; de Cassia Dourado, Rita; Giampietro-Ganeco, Aline; de Souza, Rodrigo Alves; Ferrari, Fábio Borba; de Souza, Pedro Alves; Borba, Hirasilva
2017-10-01
The aim of this study was to evaluate the effect of ambient temperature on the physical and chemical characteristics of the longissimus dorsi muscle by comparing the quality of meat from pigs reared in a controlled and in an uncontrolled environment, the latter provided with a shallow pool. Twenty castrated male pigs of the Topigs line were randomly allotted to two treatments: a controlled environment, with constant temperature (22 °C) and relative humidity (70%); and an uncontrolled environment in a conventional shed for rearing pigs equipped with a shallow pool, where pigs were subject to climatic variations. Meat from pigs kept in the controlled environment showed a greater capacity to retain intracellular water, higher tenderness, and lower cholesterol levels than meat from pigs reared in the uncontrolled environment, but displayed higher lipid oxidation and a lower concentration of DHA. Treatments had no effect on color, pH, chemical composition, or fatty acid profile (except DHA concentration). Rearing pigs in sheds equipped with a shallow pool minimizes the effects of environmental heat on meat quality, allowing the production of high-quality meat in warm climate regions without expensive investments. Animals reared in an uncontrolled environment equipped with a shallow pool are able to produce meat with characteristics within the quality standards and with similar quality to that of meat from animals raised in controlled environment.
NASA Astrophysics Data System (ADS)
Inskeep, William P.; Macur, Richard E.; Harrison, Gregory; Bostick, Benjamin C.; Fendorf, Scott
2004-08-01
Acid-sulfate-chloride (pH˜3) geothermal springs in Yellowstone National Park (YNP) often contain Fe(II), As(III), and S(-II) at discharge, providing several electron donors for chemolithotrophic metabolism. The microbial populations inhabiting these environments are inextricably linked with geochemical processes controlling the behavior of As and Fe. Consequently, the objectives of the current study were to (i) characterize Fe-rich microbial mats of an ASC thermal spring, (ii) evaluate the composition and structure of As-rich hydrous ferric oxides (HFO) associated with these mats, and (iii) identify microorganisms that are potentially responsible for mat formation via the oxidation of Fe(II) and or As(III). Aqueous and solid phase mat samples obtained from a spring in Norris Basin, YNP (YNP Thermal Inventory NHSP35) were analyzed using a complement of chemical, microscopic and spectroscopic techniques. In addition, molecular analysis (16S rDNA) was used to identify potentially dominant microbial populations within different mat locations. The biomineralization of As-rich HFO occurs in the presence of nearly equimolar aqueous As(III) and As(V) (˜12 μM), and ˜ 48 μM Fe(II), forming sheaths external to microbial cell walls. These solid phases were found to be poorly ordered nanocrystalline HFO containing mole ratios of As(V):Fe(III) of 0.62 ± 0.02. The bonding environment of As(V) and Fe(III) is consistent with adsorption of arsenate on edge and corner positions of Fe(III)-OH octahedra. Numerous archaeal and bacterial sequences were identified (with no closely related cultured relatives), along with several 16S sequences that are closely related to Acidimicrobium, Thiomonas, Metallosphaera and Marinithermus isolates. Several of these cultured relatives have been implicated in Fe(II) and or As(III) oxidation in other low pH, high Fe, and high As environments (e.g. acid-mine drainage). The unique composition and morphologies of the biomineralized phases may be useful as modern-day analogs for identifying microbial life in past Fe-As rich environments.
NASA Technical Reports Server (NTRS)
Farley, David R.
1987-01-01
The Cal Poly Space Project is an effort on the part of several highly motivated students to deploy a space canister which will examine the effects of microgravity on electroplating and immiscible metals. The experiments will be controlled and monitored by a specialized triple redundancy system developed to defer the possible electronic errors due to uncontrollable factors such as photons from the Sun. With the finalization of the payload design and the near completion of the data control system, the integration phase of the project is anticipated to be completed and the project ready for launching by early 1987. It is hoped that the experiments will lead to new insights in space research and also prove profitable to industry.
Autoimmune control of lesion growth in CNS with minimal damage
NASA Astrophysics Data System (ADS)
Mathankumar, R.; Mohan, T. R. Krishna
2013-07-01
Lesions in central nervous system (CNS) and their growth leads to debilitating diseases like Multiple Sclerosis (MS), Alzheimer's etc. We developed a model earlier [1, 2] which shows how the lesion growth can be arrested through a beneficial auto-immune mechanism. We compared some of the dynamical patterns in the model with different facets of MS. The success of the approach depends on a set of control parameters and their phase space was shown to have a smooth manifold separating the uncontrolled lesion growth region from the controlled. Here we show that an optimal set of parameter values exist in the model which minimizes system damage while, at once, achieving control of lesion growth.
Kim, Jung Ha; Park, Jong-Jae; Lee, Beom Jae; Joo, Moon Kyung; Chun, Hoon Jai; Lee, Sang Woo; Bak, Young-Tae
2016-05-23
Astaxanthin is a carotenoid pigment that has antioxidant, antitumoral, and anti-inflammatory properties. In this in vitro study, we investigated the mechanism of anticancer effects of astaxanthin in gastric carcinoma cell lines. The human gastric adenocarcinoma cell lines AGS, KATO-III, MKN-45, and SNU-1 were treated with various concentrations of astaxanthin. A cell viability test, cell cycle analysis, and immunoblotting were performed. The viability of each cancer cell line was suppressed by astaxanthin in a dose-dependent manner with significantly decreased proliferation in KATO-III and SNU-1 cells. Astaxanthin increased the number of cells in the G0/G1 phase but reduced the proportion of S phase KATO-III and SNU-1 cells. Phosphorylated extracellular signal-regulated kinase (ERK) was decreased in an inverse dose-dependent correlation with astaxanthin concentration, and the expression of p27(kip-1) increased the KATO-III and SNU-1 cell lines in an astaxanthin dose-dependent manner. Astaxanthin inhibits proliferation by interrupting cell cycle progression in KATO-III and SNU-1 gastric cancer cells. This may be caused by the inhibition of the phosphorylation of ERK and the enhanced expression of p27(kip-1).
Maxillary canine-first premolar bilateral transposition in a Class III patient: A case report.
Potrubacz, Maciej Iancu; Tepedino, Michele; Chimenti, Claudio
2016-05-01
Tooth transposition is a rare dental anomaly that often represents a challenge for the clinician. The case of a girl with skeletal Class III malocclusion and concomitant maxillary canine-first premolar bilateral transposition, followed from 7 to 17 years of age, is presented. After a first phase of treatment aimed at resolving the Class III malocclusion, the transposition was maintained and the case finalized with a multibracket appliance.
Sorption of Ferric Iron from Ferrioxamine B to Synthetic and Biogenic Layer Type Manganese Oxides
NASA Astrophysics Data System (ADS)
Duckworth, O.; John, B.; Sposito, G.
2006-12-01
Siderophores are biogenic chelating agents produced in terrestrial and marine environments to increase the bioavailablity of ferric iron. Recent work has suggested that both aqueous and solid-phase Mn(III) may affect siderophore-mediated iron transport, but no information appears to be available about the effect of solid-phase Mn(IV). To probe the effects of predominantly Mn(IV) oxides, we studied the sorption reaction of ferrioxamine B [Fe(III)HDFOB+, an Fe(III) chelate of the trihydroxamate siderophore desferrioxamine B (DFOB)] with two synthetic birnessites [layer type Mn(III, IV) oxides] and a biogenic birnessite produced by Pseudomonas putida MnB1. We found that all of these predominantly Mn(IV) oxides greatly reduced the aqueous concentration of Fe(III)HDFOB+ over at pH 8. After 72 hours equilibration time, the sorption behavior for the synthetic birnessites could be accurately described by a Langmuir isotherm; for the biogenic oxide, a Freundlich isotherm was best utilized to model the sorption data. To study the molecular nature of the interaction between the Fe(III)HDFOB+ complex and the oxide surface, Fe K-edge extended X-ray absorption fine structure (EXAFS) spectroscopy was employed. Analysis of the EXAFS spectra indicated that Fe(III) associated with the Mn(IV) oxides is not complexed by DFOB as in solution, but instead Fe(III) is specifically adsorbed to into the mineral structure at multiple sites with no evidence of DFOB complexation, thus indicating that the Mn(IV) oxides displaced Fe(III) from the siderophore complex. These results indicate that manganese oxides, including biominerals, may strongly sequester iron from soluble ferric complexes and thus may play a significant role in the biogeochemical cycling of iron in marine and terrestrial environments.
Dynamic properties of III-V polytypes from density-functional theory
NASA Astrophysics Data System (ADS)
Benyahia, N.; Zaoui, A.; Madouri, D.; Ferhat, M.
2017-03-01
The recently discovered hexagonal wurtzite phase of several III-V nanowires opens up strong opportunity to engineer optoelectronic and transport properties of III-V materials. Herein, we explore the dynamical and dielectric properties of cubic (3C) and wurtzite (2H) III-V compounds (AlP, AlAs, AlSb, GaP, GaAs, GaSb, InP, InAs, and InSb). For cubic III-V compounds, our calculated phonon frequencies agree well with neutron diffraction and Raman-scattering measurements. In the case of 2H III-V materials, our calculated phonon modes at the zone-center Γ point are in distinguished agreement with available Raman-spectroscopy measurements of wurtzite GaAs, InP, GaP, and InAs nanowires. Particularly, the "fingerprint" of the wurtzite phase, which is our predicted E2(high) phonon mode, at 261 cm-1(GaAs), 308 cm-1(InP), 358 cm-1(GaP), and 214 cm-1(InAs) matches perfectly the respective Raman values of 258 cm-1, 306.4 cm-1, 353 cm-1, and 213.7 cm-1 for GaAs, InP, GaP, and InAs. Moreover, the dynamic charges and high-frequency dielectric constants are predicted for III-V materials in both cubic (3C) and hexagonal (2H) crystal polytypes. It is found that the dielectric properties of InAs and InSb contrast markedly from those of other 2H III-V compounds. Furthermore, InAs and InSb evidence relative strong anisotropy in their dielectric constants and Born effective charges, whereas GaP evinces the higher Born effective charge anisotropy of 2H III-V compounds.
Surface heat loads on the ITER divertor vertical targets
NASA Astrophysics Data System (ADS)
Gunn, J. P.; Carpentier-Chouchana, S.; Escourbiac, F.; Hirai, T.; Panayotis, S.; Pitts, R. A.; Corre, Y.; Dejarnac, R.; Firdaouss, M.; Kočan, M.; Komm, M.; Kukushkin, A.; Languille, P.; Missirlian, M.; Zhao, W.; Zhong, G.
2017-04-01
The heating of tungsten monoblocks at the ITER divertor vertical targets is calculated using the heat flux predicted by three-dimensional ion orbit modelling. The monoblocks are beveled to a depth of 0.5 mm in the toroidal direction to provide magnetic shadowing of the poloidal leading edges within the range of specified assembly tolerances, but this increases the magnetic field incidence angle resulting in a reduction of toroidal wetted fraction and concentration of the local heat flux to the unshadowed surfaces. This shaping solution successfully protects the leading edges from inter-ELM heat loads, but at the expense of (1) temperatures on the main loaded surface that could exceed the tungsten recrystallization temperature in the nominal partially detached regime, and (2) melting and loss of margin against critical heat flux during transient loss of detachment control. During ELMs, the risk of monoblock edge melting is found to be greater than the risk of full surface melting on the plasma-wetted zone. Full surface and edge melting will be triggered by uncontrolled ELMs in the burning plasma phase of ITER operation if current models of the likely ELM ion impact energies at the divertor targets are correct. During uncontrolled ELMs in pre-nuclear deuterium or helium plasmas at half the nominal plasma current and magnetic field, full surface melting should be avoided, but edge melting is predicted.
Homocysteine, Cortisol, Diabetes Mellitus, and Psychopathology
Kontoangelos, K.; Papageorgiou, C. C.; Raptis, A. E.; Tsiotra, P.; Lambadiari, V.; Papadimitriou, G. N.; Rabavilas, A. D.; Dimitriadis, G.; Raptis, S. A.
2015-01-01
Objective. This study investigates the association of homocysteine and cortisol with psychological factors in type 2 diabetic patients. Method. Homocysteine, cortisol, and psychological variables were analyzed from 131 diabetic patients. Psychological factors were assessed with the Eysenck Personality Questionnaire (EPQ), Hostility and Direction of Hostility Questionnaire (HDHQ), the Symptom Checklist 90-R (SCL 90-R), the Zung Self-Rating Depression Scale (ZDRS), and the Maudsley O-C Inventory Questionnaire (MOCI). Blood samples were taken by measuring homocysteine and cortisol in both subgroups during the initial phase of the study (T0). One year later (T1), the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments and with an identical blood analysis. Results. The relation of psychoticism and homocysteine is positive among controlled diabetic patients (P value = 0.006 < 0.05) and negative among uncontrolled ones (P value = 0.137). Higher values of cortisol correspond to lower scores on extraversion subscale (r p = −0.223, P value = 0.010). Controlled diabetic patients showed a statistically significant negative relationship between homocysteine and the act-out hostility subscale (r sp = −0.247, P = 0.023). There is a statistically significant relationship between homocysteine and somatization (r sp = −0.220, P = 0.043). Conclusions. These findings support the notion that homocysteine and cortisol are related to trait and state psychological factors in patients with diabetes mellitus type 2. PMID:25722989
Jenkins, R A; Chinaworapong, S; Morgan, P A; Ruangyuttikarn, C; Sontirat, A; Chiu, J; Michael, R A; Nitayaphan, S; Khamboonruang, C
1998-06-01
Data from recruitment and screening for a phase I/II preventive HIV-1 vaccine trial in Thailand were evaluated with respect to correlates of participation at each phase. Correlates included demographic variables, motivation for interest in the trial, and factors related to communication and contact. Participants were recruited at two sites through varied methods. The majority of prescreenees reported altruistic motives for interest in the trial and blood donors emerged as a group that may have been particularly altruistic. Findings indicated site differences in attrition during recruitment and screening, but not in enrollment into the vaccine trial. Blood donation and willingness to be contacted by phone at home were significantly related to making and keeping screening appointments.
Kässner, Frank; Hodder, Rick; Bateman, Eric D
2004-01-01
Asthma and chronic obstructive pulmonary disease (COPD) can be effectively treated by the use of bronchodilator therapies delivered by inhalation. Berodual is a fixed combination of the anticholinergic agent ipratropium bromide (IB) and the beta2-adrenergic agonist fenoterol hydrobromide (FEN). IB/FEN has been available for the treatment of asthma and COPD in a pressurised metered dose inhaler (MDI) [pMDI] formulation for many years. The pMDI is the most widely used device for the delivery of inhaled medications, such as IB/FEN. However, most conventional pMDIs contain chlorofluorocarbon (CFC) propellants, which are currently being withdrawn because of their detrimental effects on the environment. This has resulted in alternative methods of drug delivery being developed. Respimat Soft Mist Inhaler (SMI) is a new generation, propellant-free inhaler that generates a fine, slow-moving cloud (the Soft Mist) which can be easily inhaled. Scintigraphic studies have shown that this improves deposition of drugs in the lung and results in less oropharyngeal deposition than the CFC-MDI. A clinical development programme has been conducted to compare the efficacy and safety of IB/FEN delivered via Respimat SMI with that of IB/FEN via CFC-MDI in the treatment of patients with asthma or COPD. Five clinical studies (two phase II and three phase III) investigated dosages of IB/FEN 5/12.5 microg to 320/800 microg via Respimat SMI in single and multiple dose administration regimens. Four of the trials were conducted in patients with asthma (three in adults and one in children), while one phase III trial was conducted in patients with COPD. In phase III, 2058 patients participated, with a total of 1112 patients treated with IB/FEN via Respimat SMI. In the phase III studies, each dose from Respimat SMI was given in one actuation compared with two actuations with the CFC-MDI. In the paediatric asthma phase III study, all CFC-MDI doses were delivered via a spacer device. The results of the trials demonstrated that IB/FEN via Respimat SMI allows a reduction in the nominal dose of IB/FEN, while offering similar therapeutic efficacy and safety to a CFC-MDI. In children, Respimat SMI obviates the need for a spacer.
VARIABLES AFFECTING EMISSIONS OF PCDDS/FS FROM UNCONTROLLED COMBUSTION OF HOUSEHOLD WASTE IN BARRELS
The uncontrolled burning of household waste in barrels has recently been implicated as a major source of airborne emissions of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/Fs). Based on the need to generate a more accurate emission factor for burn ba...
40 CFR 63.1386 - Notification, recordkeeping, and reporting requirements.
Code of Federal Regulations, 2012 CFR
2012-07-01
... temperature above the molten glass in an uncontrolled cold top electric furnace, including any period when the... glass surface, the date and time of the exceedance, when corrective actions were initiated, the cause of... was corrected; (iv) Uncontrolled glass-melting furnace (that is not a cold top electric furnace...
40 CFR 63.1386 - Notification, recordkeeping, and reporting requirements.
Code of Federal Regulations, 2013 CFR
2013-07-01
... temperature above the molten glass in an uncontrolled cold top electric furnace, including any period when the... glass surface, the date and time of the exceedance, when corrective actions were initiated, the cause of... was corrected; (iv) Uncontrolled glass-melting furnace (that is not a cold top electric furnace...
40 CFR 63.1386 - Notification, recordkeeping, and reporting requirements.
Code of Federal Regulations, 2011 CFR
2011-07-01
... temperature above the molten glass in an uncontrolled cold top electric furnace, including any period when the... glass surface, the date and time of the exceedance, when corrective actions were initiated, the cause of... was corrected; (iv) Uncontrolled glass-melting furnace (that is not a cold top electric furnace...
40 CFR 63.1386 - Notification, recordkeeping, and reporting requirements.
Code of Federal Regulations, 2014 CFR
2014-07-01
... temperature above the molten glass in an uncontrolled cold top electric furnace, including any period when the... glass surface, the date and time of the exceedance, when corrective actions were initiated, the cause of... was corrected; (iv) Uncontrolled glass-melting furnace (that is not a cold top electric furnace...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhao, Jinggeng; Yu, Zhenhai; Hu, Qingyang
Recently, A 2B 3-type tetradymites have developed into a hot topic in physical and material research fields, where the A and B atoms represent V and VI group elements, respectively. In this study, in situ angle-dispersive X-ray diffraction measurements were performed on Bi 2Te 2Se, BiSbTeSe 2, and Sb 2Te 2Se tetradymites under high pressure. Bi 2Te 2Se transforms from a layered rhombohedral structure (phase I) into 7-fold monoclinic (phase II) and body-centered tetragonal (phase IV) structures at about 8.0 and 14.3 GPa, respectively, without an 8-fold monoclinic structure (phase III) similar to that in Bi 2Te 3. Thus, themore » compression behavior of Bi 2Te 2Se is the same as that of Bi 2Se 3, which could also be obtained from first-principles calculations and in situ high-pressure electrical resistance measurements. Under high pressure, BiSbTeSe 2 and Sb 2Te 2Se undergo similar structural phase transitions to Bi 2Te 2Se, which indicates that the compression process of tellurides can be modulated by doping Se in Te sites. According to these high-pressure investigations of A 2B 3-type tetradymites, the decrease of the B-site atomic radius shrinks the stable pressure range of phase III and expands that of phase II, whereas the decrease of the A-site atomic radius induces a different effect, i.e. expanding the stable pressure range of phase III and shrinking that of phase II. Lastly, the influence of the atomic radius on the compression process of tetradymites is closely related to the chemical composition and the atom arrangement in the quintuple layer.« less
Zhao, Jinggeng; Yu, Zhenhai; Hu, Qingyang; ...
2016-12-14
Recently, A 2B 3-type tetradymites have developed into a hot topic in physical and material research fields, where the A and B atoms represent V and VI group elements, respectively. In this study, in situ angle-dispersive X-ray diffraction measurements were performed on Bi 2Te 2Se, BiSbTeSe 2, and Sb 2Te 2Se tetradymites under high pressure. Bi 2Te 2Se transforms from a layered rhombohedral structure (phase I) into 7-fold monoclinic (phase II) and body-centered tetragonal (phase IV) structures at about 8.0 and 14.3 GPa, respectively, without an 8-fold monoclinic structure (phase III) similar to that in Bi 2Te 3. Thus, themore » compression behavior of Bi 2Te 2Se is the same as that of Bi 2Se 3, which could also be obtained from first-principles calculations and in situ high-pressure electrical resistance measurements. Under high pressure, BiSbTeSe 2 and Sb 2Te 2Se undergo similar structural phase transitions to Bi 2Te 2Se, which indicates that the compression process of tellurides can be modulated by doping Se in Te sites. According to these high-pressure investigations of A 2B 3-type tetradymites, the decrease of the B-site atomic radius shrinks the stable pressure range of phase III and expands that of phase II, whereas the decrease of the A-site atomic radius induces a different effect, i.e. expanding the stable pressure range of phase III and shrinking that of phase II. Lastly, the influence of the atomic radius on the compression process of tetradymites is closely related to the chemical composition and the atom arrangement in the quintuple layer.« less