Individualized homeopathic treatment and fluoxetine for moderate to severe depression in peri- and postmenopausal women (HOMDEP-MENOP study): a randomized, double-dummy, double-blind, placebo-controlled trial.

PubMed

Macías-Cortés, Emma Del Carmen; Llanes-González, Lidia; Aguilar-Faisal, Leopoldo; Asbun-Bojalil, Juan

2015-01-01

Perimenopausal period refers to the interval when women's menstrual cycles become irregular and is characterized by an increased risk of depression. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. The aim of this study was to assess efficacy and safety of individualized homeopathic treatment versus placebo and fluoxetine versus placebo in peri- and postmenopausal women with moderate to severe depression. A randomized, placebo-controlled, double-blind, double-dummy, superiority, three-arm trial with a 6 week follow-up study was conducted. The study was performed in a public research hospital in Mexico City in the outpatient service of homeopathy. One hundred thirty-three peri- and postmenopausal women diagnosed with major depression according to DSM-IV (moderate to severe intensity) were included. The outcomes were: change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression, Beck Depression Inventory and Greene Scale, after 6 weeks of treatment, response and remission rates, and safety. Efficacy data were analyzed in the intention-to-treat population (ANOVA with Bonferroni post-hoc test). After a 6-week treatment, homeopathic group was more effective than placebo by 5 points in Hamilton Scale. Response rate was 54.5% and remission rate, 15.9%. There was a significant difference among groups in response rate definition only, but not in remission rate. Fluoxetine-placebo difference was 3.2 points. No differences were observed among groups in the Beck Depression Inventory. Homeopathic group was superior to placebo in Greene Climacteric Scale (8.6 points). Fluoxetine was not different from placebo in Greene Climacteric Scale. Homeopathy and fluoxetine are effective and safe antidepressants for climacteric women. Homeopathy and fluoxetine were significantly different from placebo in response definition only. Homeopathy, but not fluoxetine, improves menopausal symptoms scored by Greene Climacteric Scale. ClinicalTrials.gov NCT01635218. https://clinicaltrials.gov/ct2/show/NCT01635218 [corrected].

Slow infusion of low{\\hyphen}dose ketamine reduces bothersome side effects compared to IV push: a double{\\hyphen}blind, double dummy, randomized controlled trial.

PubMed

Clattenburg, Eben J; Hailozian, Christian; Haro, Daniel; Yoo, Tina; Flores, Stefan; Louie, Derex; Herring, Andrew A

2018-04-12

We compared the analgesic efficacy and incidence of side effects when low{\\hyphen}dose (0.3 mg{\\sol}kg) ketamine (LDK) is administered as a slow infusion (SI) over 15 minutes versus an intravenous push (IVP) over one minute. This was a prospective, randomized, double blind, double dummy, placebo{\\hyphen}controlled trial of adult ED patients presenting with moderate to severe pain (numerical rating score ≥ 5). Patients received ketamine 0.3mg{\\sol}kg administered either as a SI or IVP. Our primary outcome was the proportion of patients experiencing any psychoperceptual side effect over 60 minutes. A secondary outcome was incidence of moderate or greater psychoperceptual side effects. Additional outcomes included reduction in pain NRS scores at 60 minutes and percent maximum summed pain intensity difference ({\\percnt}SPID). Fifty{\\hyphen}nine participants completed the study. 86.2{\\percnt} of the IVP arm and 70.0{\\percnt} of the SI arm experienced any side effect (difference 16.2{\\percnt}, 95{\\percnt}CI {\\hyphen}5.4 - 37.8). We found a large reduction in moderate or greater psychoperceptual side effects with SI administration-75.9{\\percnt} reported moderate or greater side effects versus 43.4{\\percnt} in the SI arm (difference 32.5{\\percnt}, 95{\\percnt}CI 7.9 - 57.1). Additionally, the IVP arm experienced more hallucinations (n{\\equal}8, 27.6{\\percnt}) than the SI arm (SI n{\\equal}2, 6.7{\\percnt}; difference 20.9{\\percnt}, 95{\\percnt}CI 1.8 - 43.4). We found no significant differences in analgesic efficacy. At 60 minutes, the mean {\\percnt}SPID in the IVP and SI arms was 39.9{\\percnt} and 33.5{\\percnt}, respectively, with a difference of 6.5{\\percnt} (95{\\percnt}CI {\\hyphen}5.8 - 18.7). Most patients who are administered LDK experience a psychoperceptual side effect regardless of administration via SI or IVP. However, patients receiving LDK as a SI reported significantly fewer moderate or greater psychoperceptual side effects and hallucinations with equivalent analgesia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Individualized Homeopathic Treatment and Fluoxetine for Moderate to Severe Depression in Peri- and Postmenopausal Women (HOMDEP-MENOP Study): A Randomized, Double-Dummy, Double-Blind, Placebo-Controlled Trial

PubMed Central

Macías-Cortés, Emma del Carmen; Llanes-González, Lidia; Aguilar-Faisal, Leopoldo; Asbun-Bojalil, Juan

2015-01-01

Background Perimenopausal period refers to the interval when women's menstrual cycles become irregular and is characterized by an increased risk of depression. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. The aim of this study was to assess efficacy and safety of individualized homeopathic treatment versus placebo and fluoxetine versus placebo in peri- and postmenopausal women with moderate to severe depression. Methods/Design A randomized, placebo-controlled, double-blind, double-dummy, superiority, three-arm trial with a 6 week follow-up study was conducted. The study was performed in a public research hospital in Mexico City in the outpatient service of homeopathy. One hundred thirty-three peri- and postmenopausal women diagnosed with major depression according to DSM-IV (moderate to severe intensity) were included. The outcomes were: change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression, Beck Depression Inventory and Greene Scale, after 6 weeks of treatment, response and remission rates, and safety. Efficacy data were analyzed in the intention-to-treat population (ANOVA with Bonferroni post-hoc test). Results After a 6-week treatment, homeopathic group was more effective than placebo by 5 points in Hamilton Scale. Response rate was 54.5% and remission rate, 15.9%. There was a significant difference among groups in response rate definition only, but not in remission rate. Fluoxetine-placebo difference was 3.2 points. No differences were observed among groups in the Beck Depression Inventory. Homeopathic group was superior to placebo in Greene Climacteric Scale (8.6 points). Fluoxetine was not different from placebo in Greene Climacteric Scale. Conclusion Homeopathy and fluoxetine are effective and safe antidepressants for climacteric women. Homeopathy and fluoxetine were significantly different from placebo in response definition only. Homeopathy, but not fluoxetine, improves menopausal symptoms scored by Greene Climacteric Scale. Trial Registration ClinicalTrials.gov NCT01635218 Protocol Publication http://www.trialsjournal.com/content/14/1/105. PMID:25768800

A prospective randomized, double-dummy trial comparing IV push low dose ketamine to short infusion of low dose ketamine for treatment of  pain in the ED.

PubMed

Motov, Sergey; Mai, Mo; Pushkar, Illya; Likourezos, Antonios; Drapkin, Jefferson; Yasavolian, Matthew; Brady, Jason; Homel, Peter; Fromm, Christian

2017-08-01

Compare adverse effects and analgesic efficacy of low-dose ketamine for acute pain in the ED administered either by single intravenous push (IVP) or short infusion (SI). Patients 18-65, presenting to ED with acute abdominal, flank, or musculoskeletal pain with initial pain score≥5, were randomized to ketamine 0.3mg/kg by either IVP or SI with placebo double-dummy. Adverse effects were evaluated by Side Effects Rating Scale for Dissociative Anesthetics (SERSDA) and Richmond Agitation-Sedation Scale (RASS) at 5, 15, 30, 60, 90, and 120min post-administration; analgesic efficacy was evaluated by Numerical Rating Scale (NRS). 48 patients enrolled in the study. IVP group had higher overall rates of feeling of unreality on SERSDA scale: 92% versus 54% (difference 37.5%; p=0.008; 95% CI 9.3-59.5%). At 5min median severity of feeling of unreality was 3.0 for IVP versus 0.0 for SI (p=0.001). IVP also showed greater rates of sedation on RASS scale at 5min: median RASS -2.0 versus 0.0 (p=0.01). Decrease in mean pain scores from baseline to 15min was similar across groups: 5.2±3.53 (95% CI 3.7-6.7) for IVP; 5.75±3.48 (95% CI 4.3-7.2) for SI. There were no statistically significant differences with respect to changes in vital signs and need for rescue medication. Low-dose ketamine given as a short infusion is associated with significantly lower rates of feeling of unreality and sedation with no difference in analgesic efficacy in comparison to intravenous push. Copyright © 2017 Elsevier Inc. All rights reserved.

Improvement of insulin sensitivity and beta-cell function by nateglinide and repaglinide in type 2 diabetic patients - a randomized controlled double-blind and double-dummy multicentre clinical trial.

PubMed

Li, J; Tian, H; Li, Q; Wang, N; Wu, T; Liu, Y; Ni, Z; Yu, H; Liang, J; Luo, R; Li, Y; Huang, L

2007-07-01

To evaluate the efficacy of nateglinide vs. repaglinide in blood glucose (BG) control and the effect on insulin resistance and beta-Cell function in patients with type 2 diabetes. A randomized controlled double-blind and double-dummy multicentre clinical trial was conducted. A total of 230 Chinese patients with type 2 diabetes were enrolled in five clinical centres. The patients were divided randomly into group A [repaglinide 1.0 mg three times daily (t.i.d.), n = 115] or group B (nateglinide 90 mg t.i.d., n = 115). At baseline and end of the 12-week clinical trial, standard mixed meal tolerance tests were performed. A total of 223 patients (96.9%) completed the trial. There was no significant difference between repaglinide and nateglinide groups in the effects of reducing fasting blood glucose (FBG), 30-, 60- and 120-min BG during 12 weeks (p > 0.05). At week 12, no significant difference was shown between the two groups in BG or haemoglobin A(1c) (HbA(1c)) (p > 0.05). However, the effect on HbA(1c) in repaglinide group was stronger than that in nateglinide group (p < 0.05). After 12-week treatment, area under the curve (AUC) of BG decreased (p < 0.05), and AUC of insulin and C-peptide (CP) increased in both groups (p < 0.05). The effects of nateglinide on AUC of BG, insulin and CP were similar to that of repaglinide (p > 0.05). There was no significant difference between the two groups in AUC of BG, insulin or CP in week 12 (p > 0.05). Furthermore, homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function indexes measured by HOMA-beta, DeltaI(30)/DeltaG(30) and (DeltaI(30)/DeltaG(30))/HOMA-IR were improved significantly in both groups during 12 weeks (p < 0.05). The effects of improving HOMA-IR and beta-cell function indexes in nateglinide group were comparable with that of repaglinide group (p > 0.05). The efficacy of repaglinide and nateglinide in FBG, postprandial glucose excursion and early-phase insulin secretion is similar. But the effect of repaglinide 1.0 mg t.i.d. on HbA(1c) is stronger than that of nateglinide 90 mg t.i.d.. This trial had shown that nateglinide and repaglinide could comparably improve insulin sensitivity and beta-cell function.

A Prospective, Randomized, Double-Blinded, Double-Dummy Pilot Study to Assess the Preemptive Effect of Triple Therapy with Aprepitant, Dexamethasone, and Promethazine versus Ondansetron, Dexamethasone and Promethazine on Reducing the Incidence of Postoperative Nausea and Vomiting Experienced by Patients Undergoing Craniotomy Under General Anesthesia.

PubMed

Bergese, Sergio Daniel; Puente, Erika G; Antor, Maria A; Viloria, Adolfo L; Yildiz, Vedat; Kumar, Nicolas Alexander; Uribe, Alberto A

2016-01-01

Postoperative nausea and vomiting (PONV) is among the most common distressing complications of surgery under anesthesia. Previous studies have demonstrated that patients who undergo craniotomy have incidences of nausea and vomiting as high as 50-70%. The main purpose of this pilot study is to assess the incidence of PONV by using two different prophylactic regimens in subjects undergoing a craniotomy. Thus, we designed this study to assess the efficacy and safety of triple therapy with the combination of dexamethasone, promethazine, and aprepitant versus ondansetron to reduce the incidence of PONV in patients undergoing craniotomy. This is a prospective, single center, two-armed, randomized, double-dummy, double-blind, pilot study. Subjects were randomly assigned to one of the two treatment groups. Subjects received 40 mg of aprepitant pill (or matching placebo pill) 30-60 min before induction of anesthesia and 4 mg of ondansetron IV (or 2 ml of placebo saline solution) at induction of anesthesia. In addition, all subjects received 25 mg of promethazine IV and 10 mg of dexamethasone IV at induction of anesthesia. Assessments of PONV commenced for the first 24 h after surgery and were subsequently assessed for up to 5 days. The overall incidence of PONV during the first 24 h after surgery was 31.0% (n = 15) in the aprepitant group and 36.2% (n = 17) for the ondansetron group. The median times to first emetic and significant nausea episodes were 7.6 (2.9, 48.7) and 14.3 (4.4, 30.7) hours, respectively, for the aprepitant group and 6.0 (2.2, 29.5) and 9.6 (0.7, 35.2) hours, respectively, for the ondansetron group. There were no statistically significant differences between these groups. No adverse events directly related to study medications were found. This pilot study showed similar effectiveness when comparing the two PONV prophylaxis regimens. Our data showed that both treatments could be effective regimens to prevent PONV in patients undergoing craniotomy under general anesthesia. Future trials testing new PONV prophylaxis regimens in this surgical population should be performed to gain a better understanding of how to best provide prophylactic treatment.

A spontaneous, double-blind, double-dummy cross-over study on the effects of daily vardenafil on arterial stiffness in patients with vasculogenic erectile dysfunction.

PubMed

Aversa, Antonio; Letizia, Claudio; Francomano, Davide; Bruzziches, Roberto; Natali, Marco; Lenzi, Andrea

2012-10-18

It is known that the incidence of endothelial dysfunction in patients with vascular erectile dysfunction (ED) is increased. The effects of daily vardenafil on endothelial function and arterial stiffness in patients with erectile dysfunction (ED) have never been investigated. 20 men complaining vascular ED (mean IIEF5=12 ± 6 and peak systolic velocity-PSV=24 ± 2 cm/s) were enrolled in a 4-week, randomized, double-blind, double-dummy, crossover study (mean age 59 ± 11) and received either vardenafil 10mg daily or 20mg on-demand with a two-week washout interval. Primary endpoints were variation from baseline of reactive hyperemia (RH) and augmentation index (AI) calculated by fingertip peripheral arterial tonometry (PAT) device. Secondary endpoints were variations of IIEF-5 and SEP3 scores from baseline and plasma surrogate markers of endothelial function, i.e. endothelin-1 (ET-1) and adrenomedullin (ADM). Patients who took daily vardenafil (vs. on-demand) reported significant (P<0.01) improvements in arterial stiffness as evaluated by AI and reduction of plasma ADM levels (p<0.05) but no improvement in average RH. When corrected for heart rate, ADM showed a strong direct relationship with AI (r(2)=0.22; p<0.005). The proportion of patients with an IIEF5 score of ≥ 22 or in SEP3 percentage of success rates were similar. Each treatment resulted in significantly greater IIEF5 scores (p<0.001) and better SEP3 response rates (p<0.0001) compared with baseline. We demonstrated that daily vardenafil improves arterial stiffness and erectile function measurements in men with severe vasculogenic ED. This effect may be mediated, at least in part, by a reduction in ADM circulating levels. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Efficacy of individualized homeopathic treatment and fluoxetine for moderate to severe depression in peri- and postmenopausal women (HOMDEP-MENOP): study protocol for a randomized, double-dummy, double-blind, placebo-controlled trial.

PubMed

Macías-Cortés, Emma del Carmen; Aguilar-Faisal, Leopoldo; Asbun-Bojalil, Juan

2013-04-23

The perimenopausal period refers to the interval when women's menstrual cycles become irregular and is characterized by an increased risk of depressive symptoms. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. Previous trials suggest that individualized homeopathic treatments improve depression. In classical homeopathy, an individually selected homeopathic remedy is prescribed after a complete case history of the patient. The aim of this study is to assess the efficacy and safety of the homeopathic individualized treatment versus placebo or fluoxetine in peri- and postmenopausal women with moderate to severe depression. A randomized, placebo-controlled, double-blind, double-dummy, three-arm trial with a six-week follow-up study was designed. The study will be conducted in a public research hospital in Mexico City (Juárez de México Hospital) in the outpatient service of homeopathy. One hundred eighty nine peri- and postmenopausal women diagnosed with major depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (moderate to severe intensity) will be included. The primary outcome is change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression after the fourth and sixth week of treatment. Secondary outcomes are: Beck Depression Inventory change in mean score, Greene's Scale change in mean score, response and remission rates and safety. Efficacy data will be analyzed in the intention-to-treat population. To determine differences in the primary and secondary outcomes among groups at baseline and weeks four and six, data will be analyzed by analysis of variance for independent measures with the Bonferroni post-hoc test. This study is the first trial of classical homeopathy that will evaluate the efficacy of homeopathic individualized treatment using C-potencies versus placebo or fluoxetine in peri- and postmenopausal women with moderate to severe depression. It is an attempt to deal with the obstacles of homeopathic research due to the need for individual prescriptions in one of the most common psychiatric diseases. ClinicalTrials.gov Identifier: NCT01635218.

Efficacy of individualized homeopathic treatment and fluoxetine for moderate to severe depression in peri- and postmenopausal women (HOMDEP-MENOP): study protocol for a randomized, double-dummy, double-blind, placebo-controlled trial

PubMed Central

2013-01-01

Background The perimenopausal period refers to the interval when women’s menstrual cycles become irregular and is characterized by an increased risk of depressive symptoms. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. Previous trials suggest that individualized homeopathic treatments improve depression. In classical homeopathy, an individually selected homeopathic remedy is prescribed after a complete case history of the patient. The aim of this study is to assess the efficacy and safety of the homeopathic individualized treatment versus placebo or fluoxetine in peri- and postmenopausal women with moderate to severe depression. Methods/design A randomized, placebo-controlled, double-blind, double-dummy, three-arm trial with a six-week follow-up study was designed. The study will be conducted in a public research hospital in Mexico City (Juárez de México Hospital) in the outpatient service of homeopathy. One hundred eighty nine peri- and postmenopausal women diagnosed with major depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (moderate to severe intensity) will be included. The primary outcome is change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression after the fourth and sixth week of treatment. Secondary outcomes are: Beck Depression Inventory change in mean score, Greene’s Scale change in mean score, response and remission rates and safety. Efficacy data will be analyzed in the intention-to-treat population. To determine differences in the primary and secondary outcomes among groups at baseline and weeks four and six, data will be analyzed by analysis of variance for independent measures with the Bonferroni post-hoc test. Discussion This study is the first trial of classical homeopathy that will evaluate the efficacy of homeopathic individualized treatment using C-potencies versus placebo or fluoxetine in peri- and postmenopausal women with moderate to severe depression. It is an attempt to deal with the obstacles of homeopathic research due to the need for individual prescriptions in one of the most common psychiatric diseases. Trial registration ClinicalTrials.gov Identifier: NCT01635218. PMID:23782520

Rationale and design of the Helping Ease Renal failure with Bupi Yishen compared with the Angiotensin II Antagonist Losartan (HERBAAL) trial: a randomized controlled trial in non-diabetes stage 4 chronic kidney disease.

PubMed

Mao, Wei; Zhang, Lei; Zou, Chuan; Li, Chuang; Wu, Yifan; Su, Guobin; Guo, Xinfeng; Wu, Yuchi; Lu, Fuhua; Lin, Qizhan; Wang, Lixin; Bao, Kun; Xu, Peng; Zhao, Daixin; Peng, Yu; Liang, Hui; Lu, Zhaoyu; Gao, Yanxiang; Jie, Xina; Zhang, La; Wen, Zehuai; Liu, Xusheng

2015-09-08

Chronic kidney disease (CKD) is a global public health problem. Currently, as for advanced CKD populations, medication options limited in angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), which were partially effective. A Chinese herbal compound, Bupi Yishen formula, has showed renal protective potential in experiments and retrospective studies. This study will evaluate the efficacy and safety of Bupi Yishen formula (BYF) in patients with CKD stage 4. In this double blind, double dummy, randomized controlled trial (RCT), there will be 554 non-diabetes stage 4 CKD patients from 16 hospitals included and randomized into two groups: Chinese medicine (CM) group or losartan group. All patients will receive basic conventional therapy. Patients in CM group will be treated with BYF daily while patients in control group will receive losartan 100 mg daily for one year. The primary outcome is the change in estimated glomerular filtration rate (eGFR) over 12 months. Secondary outcomes include the incidence of endpoint events, liver and kidney function, urinary protein creatinine ratio, cardiovascular function and quality of life. This study will be the first multi-center, double blind RCT to assess whether BYF, compared with losartan, will have beneficial effects on eGFR for non-diabetes stage 4 CKD patients. The results will help to provide evidence-based recommendations for clinicians. Chinese Clinical Trial Registry Number: ChiCTR-TRC-10001518 .

Prevention of upper gastrointestinal bleeding in critically ill Chinese patients: a randomized, double-blind study evaluating esomeprazole and cimetidine.

PubMed

Lou, Wenhui; Xia, Ying; Xiang, Peng; Zhang, Liangqing; Yu, Xiangyou; Lim, Sam; Xu, Mo; Zhao, Lina; Rydholm, Hans; Traxler, Barry; Qin, Xinyu

2018-04-20

To assess the efficacy and safety of esomeprazole in preventing upper gastrointestinal (GI) bleeding in critically ill Chinese patients, using cimetidine as an active comparator. A pre-specified non-inferiority limit (5%) was used to compare rates of significant upper GI bleeding in this randomized, double-blind, parallel-group, phase 3 study across 27 intensive care units in China. Secondary endpoints included safety and tolerability measures. Patients required mechanical ventilation and had at least one additional risk factor for stress ulcer bleeding. Patients were randomized to receive either active esomeprazole 40 mg, as a 30-min intravenous (IV) infusion twice daily, and an IV placebo cimetidine infusion or active cimetidine 50 mg/h, as a continuous infusion following an initial bolus of 300 mg, and placebo esomeprazole injections, given up to 14 days. Patients were blinded using this double-dummy technique. Of 274 patients, 2.7% with esomeprazole and 4.6% with cimetidine had significant upper GI bleeding (bright red blood in the gastric tube not clearing after lavage or persistent Gastroccult-positive "coffee grounds" material). Non-inferiority of esomeprazole to cimetidine was demonstrated. The safety profiles of both drugs were similar and as expected in critically ill patients. Esomeprazole is effective in preventing upper GI bleeding in critically ill Chinese patients, as demonstrated by the non-inferiority analysis using cimetidine as an active control. ClinicalTrials.gov identifier NCT02157376.

The effect of bupropion XL and escitalopram on memory and functional outcomes in adults with major depressive disorder: results from a randomized controlled trial.

PubMed

Soczynska, Joanna K; Ravindran, Lakshmi N; Styra, Rima; McIntyre, Roger S; Cyriac, Anna; Manierka, Marena S; Kennedy, Sidney H

2014-12-15

Decrements in cognitive function are a common feature of Major Depressive Disorder (MDD), and whether distinct classes of antidepressants differentially affect memory in these individuals has not been sufficiently evaluated. In this study we sought to determine the effect of escitalopram and bupropion XL on memory and psychosocial function. Forty-one individuals (18-50 years) with MDD were enrolled in an 8-week, double-blind, double-dummy, randomized controlled comparative trial of bupropion XL and escitalopram. Thirty-six participants completed pre and post memory assessments. Verbal, non-verbal and working memory were evaluated with a comprehensive neuropsychological battery. Psychosocial function was assessed with the Sheehan Disability Scale and Endicott Work Productivity Scale. Escitalopram and bupropion XL significantly improved immediate as well as delayed verbal and nonverbal memory, global function (all p≤0.001), and work productivity (p=0.045), with no significant between-group differences. Improvement in immediate verbal memory exerted a direct influence on improvement in global function (p=0.006). Treatment with either escitalopram or bupropion XL was associated with improvement in memory and psychosocial function in adults with MDD. Copyright © 2014. Published by Elsevier Ireland Ltd.

Efficacy and safety of extended- versus immediate-release pramipexole in Japanese patients with advanced and L-dopa-undertreated Parkinson disease: a double-blind, randomized trial.

PubMed

Mizuno, Yoshikuni; Yamamoto, Mitsutoshi; Kuno, Sadako; Hasegawa, Kazuko; Hattori, Nobutaka; Kagimura, Tatsuro; Sarashina, Akiko; Rascol, Olivier; Schapira, Anthony H V; Barone, Paolo; Hauser, Robert A; Poewe, Werner

2012-01-01

To compare the efficacy, safety, tolerability, and trough plasma levels of pramipexole extended-release (ER) and pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD). After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to pramipexole ER once daily or pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label pramipexole ER, beginning with a 4-week dose-adjustment phase. Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to pramipexole ER. In L-dopa-treated patients, pramipexole ER and pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from pramipexole IR to pramipexole ER with no impact on efficacy.

Effect of bottles, cups, and dummies on breast feeding in preterm infants: a randomised controlled trial

PubMed Central

Collins, Carmel T; Ryan, Philip; Crowther, Caroline A; McPhee, Andrew J; Paterson, Susan; Hiller, Janet E

2004-01-01

Objective To determine the effect of artificial teats (bottle and dummy) and cups on breast feeding in preterm infants. Design Randomised controlled trial. Setting Two large tertiary hospitals, 54 peripheral hospitals. Participants 319 preterm infants (born at 23-33 weeks' gestation) randomly assigned to one of four groups: cup/no dummy (n = 89), cup/dummy (n = 72), bottle/no dummy (n = 73), bottle/dummy (n = 85). Women with singleton or twin infants < 34 weeks' gestation who wanted to breastfeed were eligible to participate. Interventions Cup or bottle feeding occurred when the mother was unable to be present to breast feed. Infants randomised to the dummy groups received a dummy on entry into the trial. Main outcome measures Full breast feeding (compared with partial and none) and any breast feeding (compared with none) on discharge home. Secondary outcomes: prevalence of breast feeding at three and six months after discharge and length of hospital stay. Results 303 infants (and 278 mothers) were included in the intention to treat analysis. There were no significant differences for any of the study outcomes according to use of a dummy. Infants randomised to cup feeds were more likely to be fully breast fed on discharge home (odds ratio 1.73, 95% confidence interval 1.04 to 2.88, P = 0.03), but had a longer length of stay (hazard ratio 0.71, 0.55 to 0.92, P = 0.01). Conclusions Dummies do not affect breast feeding in preterm infants. Cup feeding significantly increases the likelihood that the baby will be fully breast fed at discharge home, but has no effect on any breast feeding and increases the length of hospital stay. PMID:15208209

Effect of bottles, cups, and dummies on breast feeding in preterm infants: a randomised controlled trial.

PubMed

Collins, Carmel T; Ryan, Philip; Crowther, Caroline A; McPhee, Andrew J; Paterson, Susan; Hiller, Janet E

2004-07-24

To determine the effect of artificial teats (bottle and dummy) and cups on breast feeding in preterm infants. Randomised controlled trial. Two large tertiary hospitals, 54 peripheral hospitals. 319 preterm infants (born at 23-33 weeks' gestation) randomly assigned to one of four groups: cup/no dummy (n = 89), cup/dummy (n = 72), bottle/no dummy (n = 73), bottle/dummy (n = 85). Women with singleton or twin infants < 34 weeks' gestation who wanted to breastfeed were eligible to participate. Cup or bottle feeding occurred when the mother was unable to be present to breast feed. Infants randomised to the dummy groups received a dummy on entry into the trial. Full breast feeding (compared with partial and none) and any breast feeding (compared with none) on discharge home. prevalence of breast feeding at three and six months after discharge and length of hospital stay. 303 infants (and 278 mothers) were included in the intention to treat analysis. There were no significant differences for any of the study outcomes according to use of a dummy. Infants randomised to cup feeds were more likely to be fully breast fed on discharge home (odds ratio 1.73, 95% confidence interval 1.04 to 2.88, P = 0.03), but had a longer length of stay (hazard ratio 0.71, 0.55 to 0.92, P = 0.01). Dummies do not affect breast feeding in preterm infants. Cup feeding significantly increases the likelihood that the baby will be fully breast fed at discharge home, but has no effect on any breast feeding and increases the length of hospital stay.

Refined Dummy Atom Model of Mg(2+) by Simple Parameter Screening Strategy with Revised Experimental Solvation Free Energy.

PubMed

Jiang, Yang; Zhang, Haiyang; Feng, Wei; Tan, Tianwei

2015-12-28

Metal ions play an important role in the catalysis of metalloenzymes. To investigate metalloenzymes via molecular modeling, a set of accurate force field parameters for metal ions is highly imperative. To extend its application range and improve the performance, the dummy atom model of metal ions was refined through a simple parameter screening strategy using the Mg(2+) ion as an example. Using the AMBER ff03 force field with the TIP3P model, the refined model accurately reproduced the experimental geometric and thermodynamic properties of Mg(2+). Compared with point charge models and previous dummy atom models, the refined dummy atom model yields an enhanced performance for producing reliable ATP/GTP-Mg(2+)-protein conformations in three metalloenzyme systems with single or double metal centers. Similar to other unbounded models, the refined model failed to reproduce the Mg-Mg distance and favored a monodentate binding of carboxylate groups, and these drawbacks needed to be considered with care. The outperformance of the refined model is mainly attributed to the use of a revised (more accurate) experimental solvation free energy and a suitable free energy correction protocol. This work provides a parameter screening strategy that can be readily applied to refine the dummy atom models for metal ions.

Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial.

PubMed

Kendler, David L; Marin, Fernando; Zerbini, Cristiano A F; Russo, Luis A; Greenspan, Susan L; Zikan, Vit; Bagur, Alicia; Malouf-Sierra, Jorge; Lakatos, Péter; Fahrleitner-Pammer, Astrid; Lespessailles, Eric; Minisola, Salvatore; Body, Jean Jacques; Geusens, Piet; Möricke, Rüdiger; López-Romero, Pedro

2017-11-09

No clinical trials have compared osteoporosis drugs with incident fractures as the primary outcome. We compared the anti-fracture efficacy of teriparatide with risedronate in patients with severe osteoporosis. In this double-blind, double-dummy trial, we enrolled post-menopausal women with at least two moderate or one severe vertebral fracture and a bone mineral density T score of less than or equal to -1·50. Participants were randomly assigned to receive 20 μg of teriparatide once daily plus oral weekly placebo or 35 mg of oral risedronate once weekly plus daily injections of placebo for 24 months. The primary outcome was new radiographic vertebral fractures. Secondary, gated outcomes included new and worsened radiographic vertebral fractures, clinical fractures (a composite of non-vertebral and symptomatic vertebral), and non-vertebral fractures. This study is registered with ClinicalTrials.gov (NCT01709110) and EudraCT (2012-000123-41). We enrolled 680 patients in each group. At 24 months, new vertebral fractures occurred in 28 (5·4%) of 680 patients in the teriparatide group and 64 (12·0%) of 680 patients in the risedronate group (risk ratio 0·44, 95% CI 0·29-0·68; p<0·0001). Clinical fractures occurred in 30 (4·8%) of 680 patients in the teriparatide group compared with 61 (9·8%) of 680 in the risedronate group (hazard ratio 0·48, 95% CI 0·32-0·74; p=0·0009). Non-vertebral fragility fractures occurred in 25 (4·0%) patients in the teriparatide group and 38 (6·1%) in the risedronate group (hazard ratio 0·66; 95% CI 0·39-1·10; p=0·10). Among post-menopausal women with severe osteoporosis, the risk of new vertebral and clinical fractures is significantly lower in patients receiving teriparatide than in those receiving risedronate. Lilly. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects

PubMed Central

Pantaleon, Carmela; Iverson, Matthew; Smith, Michael D.; Kinzler, Eric R.; Aigner, Stefan

2018-01-01

Objective To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), abuse-deterrent formulation of morphine sulfate after oral and intranasal administration. Methods This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK of morphine and its active metabolite, M6G, from crushed intranasal Morphine ARER and intact oral Morphine ARER compared with crushed intranasal ER morphine following administration to nondependent, recreational opioid users. The correlation between morphine PK and the pharmacodynamic parameter of drug liking, a measure of abuse potential, was also evaluated. Results Mean maximum observed plasma concentration (Cmax) for morphine was lower with crushed intranasal Morphine ARER (26.2 ng/mL) and intact oral Morphine ARER (18.6 ng/mL), compared with crushed intranasal ER morphine (49.5 ng/mL). The time to Cmax (Tmax) was the same for intact oral and crushed intranasal Morphine ARER (1.6 hours) and longer for crushed intranasal morphine ER (1.1 hours). Higher mean maximum morphine Cmax, Tmax, and abuse quotient (Cmax/Tmax) were positively correlated with maximum effect for drug liking (R2 ≥ 0.9795). Conclusion These data suggest that Morphine ARER maintains its ER profile despite physical manipulation and intranasal administration, which may be predictive of a lower intranasal abuse potential compared with ER morphine.

Single and double acquisition strategies for compensation of artifacts from eddy current and transient oscillation in balanced steady-state free precession.

PubMed

Lee, Hyun-Soo; Choi, Seung Hong; Park, Sung-Hong

2017-07-01

To develop single and double acquisition methods to compensate for artifacts from eddy currents and transient oscillations in balanced steady-state free precession (bSSFP) with centric phase-encoding (PE) order for magnetization-prepared bSSFP imaging. A single and four different double acquisition methods were developed and evaluated with Bloch equation simulations, phantom/in vivo experiments, and quantitative analyses. For the single acquisition method, multiple PE groups, each of which was composed of N linearly changing PE lines, were ordered in a pseudocentric manner for optimal contrast and minimal signal fluctuations. Double acquisition methods used complex averaging of two images that had opposite artifact patterns from different acquisition orders or from different numbers of dummy scans. Simulation results showed high sensitivity of eddy-current and transient-oscillation artifacts to off-resonance frequency and PE schemes. The artifacts were reduced with the PE-grouping with N values from 3 to 8, similar to or better than the conventional pairing scheme of N = 2. The proposed double acquisition methods removed the remaining artifacts significantly. The proposed methods conserved detailed structures in magnetization transfer imaging well, compared with the conventional methods. The proposed single and double acquisition methods can be useful for artifact-free magnetization-prepared bSSFP imaging with desired contrast and minimized dummy scans. Magn Reson Med 78:254-263, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term non-steroidal anti-inflammatory drug (NSAID) therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial.

PubMed

Sugano, Kentaro; Kontani, Teiji; Katsuo, Shinichi; Takei, Yoshinori; Sakaki, Nobuhiro; Ashida, Kiyoshi; Mizokami, Yuji; Asaka, Masahiro; Matsui, Shigeyuki; Kanto, Tatsuya; Soen, Satoshi; Takeuchi, Tsutomu; Hiraishi, Hideyuki; Hiramatsu, Naoki

2012-05-01

Low-dose lansoprazole has not been intensively evaluated for its efficacy in the prevention of recurrent gastric or duodenal ulcers in patients receiving long-term non-steroidal anti-inflammatory drug (NSAID) therapy for pain relief in such diseases as rheumatoid arthritis, osteoarthritis, and low back pain. This multi-center, prospective, double-blind, randomized, active-controlled study involving 99 sites in Japan was designed to compare the efficacy of lansoprazole (15 mg daily) with gefarnate (50 mg twice daily). Patients with a history of gastric or duodenal ulcers who required long-term NSAID therapy were randomized to receive lansoprazole 15 mg daily (n = 185) or gefarnate 50 mg twice daily (n = 181) and followed up for 12 months or longer prospectively. The cumulative incidence of gastric or duodenal ulcer at days 91, 181, and 361 from the start of the study was calculated by the Kaplan-Meier method as 3.3, 5.9, and 12.7%, respectively, in the lansoprazole group versus 18.7, 28.5, and 36.9%, respectively, in the gefarnate group. The risk for ulcer development was significantly (log-rank test, P < 0.0001) lower in the lansoprazole group than in the gefarnate group, with the hazard ratio being 0.2510 (95% CI 0.1400-0.4499). A long-term follow-up study showed an acceptable safety profile for low-dose lansoprazole therapy, with diarrhea as the most frequent adverse event. Lansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term NSAID therapy.

Effectiveness and Safety of Transdermal Buprenorphine Versus Sustained-release Tramadol in Patients With Moderate to Severe Musculoskeletal Pain: An 8-Week, Randomized, Double-Blind, Double-Dummy, Multicenter, Active-controlled, Noninferiority Study.

PubMed

Leng, Xiaomei; Li, Zhanguo; Lv, Houshan; Zheng, Yi; Liu, Yi; Dai, Kerong; Yao, Chen; Yan, Xiaoyan; Zeng, Xiaofeng

2015-07-01

The aim of this noninferiority study was to investigate clinical effectiveness and safety of buprenorphine transdermal system (BTDS) in patients with moderate to severe musculoskeletal pain inadequately controlled with nonsteroidal anti-inflammatory drugs, compared with sustained-release tramadol tablets. Eligible patients were randomized (1:1) to receive low-dose 7-day BTDS (5, 10, and 20 μg/h, maximum dosage of 20 μg/h) or sustained-release tramadol tablets (100 mg, maximum dosage of 400 mg/d) over an 8-week double-blind treatment period (3-week titration, 5-week maintenance). The primary endpoint was the difference in the visual analogue scale (VAS) pain scores from baseline to treatment completion. Noninferiority was assumed if the treatment difference on the VAS scale was within ±1.5 cm, this threshold indicating a clinically meaningful result. ClinicalTrials.gov identifier: NCT01476774. Two hundred eighty patients were randomized to BTDS (n=141) or to tramadol (n=139). Both treatments were associated with a significant reduction in pain by the end of the treatment. The least squares mean difference of the change from baseline in VAS scores between the BTDS and tramadol groups were 0.45 (95% confidence interval, -0.02 to 0.91), which was within the ±1.5 cm predefined threshold, indicating that the effectiveness of BTDS was not inferior to the effectiveness of sustained-release tramadol tablets. The incidence of adverse events was comparable between the 2 treatment groups. Our results suggest that BTDS is a good therapeutic option for patients experiencing chronic musculoskeletal pain of moderate to severe intensity that is insufficiently controlled by nonsteroidal anti-inflammatory drugs.

Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine: randomized double-blind phase II evaluation of safety and immunogenicity.

PubMed

Nasveld, Peter E; Marjason, Joanne; Bennett, Sonya; Aaskov, John; Elliott, Suzanne; McCarthy, Karen; Kanesa-Thasan, Niranjan; Feroldi, Emmanuel; Reid, Mark

2010-11-01

A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever vaccine (YF-17D strain; Stamaril®, Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.

Randomized, double-blind study of grepafloxacin versus amoxycillin in patients with acute bacterial exacerbations of chronic bronchitis.

PubMed

Langan, C E; Cranfield, R; Breisch, S; Pettit, R

1997-12-01

This randomized, multicentre, double-blind, double-dummy study compared the efficacy and safety of grepafloxacin and amoxycillin in acute bacterial exacerbations of chronic bronchitis (ABECB). Patients were randomized to receive grepafloxacin 400 mg or 600 mg od, or amoxycillin 500 mg tds, for 7 or 10 days. The trial recruited 656 patients, of whom 566 (86%) completed the study. Clinical success rates at the 2 week follow-up visit for the population evaluable for clinical efficacy were 82% (165/202 patients) in the grepafloxacin 400 mg group, 85% (175/206) in the grepafloxacin 600 mg group and 85% (172/203 patients) in the amoxycillin group. The 95% confidence interval confirmed the equivalence of the two grepafloxacin doses and amoxycillin, with no significant difference between the grepafloxacin groups. The microbiological success rates at follow-up showed equivalence between the grepafloxacin 400 mg and amoxycillin groups: 86% (144/168 isolates) and 83% (162/195), respectively. The grepafloxacin 600 mg group achieved a statistically significantly higher eradication rate (92%, 150/164; 95% CI 2.0%, 16.1%) than the amoxycillin group in the follow-up assessment for microbiological and clinical efficacy (evaluable population). There was no significant difference between the two grepafloxacin treatment groups (95% CI -13.3%, 0.9%; P= 0.087). All three treatment regimens successfully eradicated the pathogens most commonly isolated during the study, including Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae. Grepafloxacin had a good safety profile, comparable to that of amoxycillin, although grepafloxacin 600 mg was associated with a higher incidence of nausea, dyspepsia and taste perversion than amoxycillin. It can be concluded that grepafloxacin 400 mg or 600 mg od is as effective as amoxycillin 500 mg tds in the treatment of ABECB.

The efficacy and resource utilization of remifentanil and fentanyl in fast-track coronary artery bypass graft surgery: a prospective randomized, double-blinded controlled, multi-center trial.

PubMed

Cheng, D C; Newman, M F; Duke, P; Wong, D T; Finegan, B; Howie, M; Fitch, J; Bowdle, T A; Hogue, C; Hillel, Z; Pierce, E; Bukenya, D

2001-05-01

We compared (a) the perioperative complications; (b) times to eligibility for, and actual time of the following: extubation, less intense monitoring, intensive care unit (ICU), and hospital discharge; and (c) resource utilization of nursing ratio for patients receiving either a typical fentanyl/isoflurane/propofol regimen or a remifentanil/isoflurane/propofol regimen for fast-track cardiac anesthesia in 304 adults by using a prospective randomized, double-blinded, double-dummy trial. There were no differences in demographic data, or perioperative mortality and morbidity between the two study groups. The mini-mental status examination at postoperative Days 1 to 3 were similar between the two groups. The eligible and actual times for extubation, less intense monitoring, ICU discharge, and hospital discharge were not significantly different. Further analyses revealed no differences in times for extubation and resource utilization after stratification by preoperative risk scores, age, and country. The nurse/patient ratio was similar between the remifentanil/isoflurane/propofol and fentanyl/isoflu-rane/propofol groups during the initial ICU phase and less intense monitoring phase. Increasing preoperative risk scores and older age (>70 yr) were associated with longer times until extubation (eligible), ICU discharge (eligible and actual), and hospital discharge (eligible and actual). Times until extubation (eligible and actual) and less intense monitoring (eligible) were significantly shorter in Canadian patients than United States' patients. However, there was no difference in hospital length of stay in Canadian and United States' patients. We conclude that both anesthesia techniques permit early and similar times until tracheal extubation, less intense monitoring, ICU and hospital discharge, and reduced resource utilization after coronary artery bypass graft surgery. An ultra-short opioid technique was compared with a standard fast-track small-dose opioid technique in coronary artery bypass graft patients in a prospective randomized, double-blinded controlled study. The postoperative recovery and resource utilization, including stratification of preoperative risk score, age, and country, were analyzed.

Homeopathic Individualized Q-Potencies versus Fluoxetine for Moderate to Severe Depression: Double-Blind, Randomized Non-Inferiority Trial

PubMed Central

Adler, U. C.; Paiva, N. M. P.; Cesar, A. T.; Adler, M. S.; Molina, A.; Padula, A. E.; Calil, H. M.

2011-01-01

Homeopathy is a complementary and integrative medicine used in depression, The aim of this study is to investigate the non-inferiority and tolerability of individualized homeopathic medicines [Quinquagintamillesmial (Q-potencies)] in acute depression, using fluoxetine as active control. Ninety-one outpatients with moderate to severe depression were assigned to receive an individualized homeopathic medicine or fluoxetine 20 mg day−1 (up to 40 mg day−1) in a prospective, randomized, double-blind double-dummy 8-week, single-center trial. Primary efficacy measure was the analysis of the mean change in the Montgomery & Åsberg Depression Rating Scale (MADRS) depression scores, using a non-inferiority test with margin of 1.45. Secondary efficacy outcomes were response and remission rates. Tolerability was assessed with the side effect rating scale of the Scandinavian Society of Psychopharmacology. Mean MADRS scores differences were not significant at the 4th (P = .654) and 8th weeks (P = .965) of treatment. Non-inferiority of homeopathy was indicated because the upper limit of the confidence interval (CI) for mean difference in MADRS change was less than the non-inferiority margin: mean differences (homeopathy-fluoxetine) were −3.04 (95% CI −6.95, 0.86) and −2.4 (95% CI −6.05, 0.77) at 4th and 8th week, respectively. There were no significant differences between the percentages of response or remission rates in both groups. Tolerability: there were no significant differences between the side effects rates, although a higher percentage of patients treated with fluoxetine reported troublesome side effects and there was a trend toward greater treatment interruption for adverse effects in the fluoxetine group. This study illustrates the feasibility of randomized controlled double-blind trials of homeopathy in depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in acute treatment of outpatients with moderate to severe depression. PMID:19687192

Social interactions between live and artificial weakly electric fish: Electrocommunication and locomotor behavior of Mormyrus rume proboscirostris towards a mobile dummy fish

PubMed Central

Kirschbaum, Frank; von der Emde, Gerhard

2017-01-01

Mormyrid weakly electric fish produce short, pulse-type electric organ discharges for actively probing their environment and to communicate with conspecifics. Animals emit sequences of pulse-trains that vary in overall frequency and temporal patterning and can lead to time-locked interactions with the discharge activity of other individuals. Both active electrolocation and electrocommunication are additionally accompanied by stereotypical locomotor patterns. However, the concrete roles of electrical and locomotor patterns during social interactions in mormyrids are not well understood. Here we used a mobile fish dummy that was emitting different types of electrical playback sequences to study following behavior and interaction patterns (electrical and locomotor) between individuals of weakly electric fish. We confronted single individuals of Mormyrus rume proboscirostris with a mobile dummy fish designed to attract fish from a shelter and recruit them into an open area by emitting electrical playbacks of natural discharge sequences. We found that fish were reliably recruited by the mobile dummy if it emitted electrical signals and followed it largely independently of the presented playback patterns. While following the dummy, fish interacted with it spatially by displaying stereotypical motor patterns, as well as electrically, e.g. through discharge regularizations and by synchronizing their own discharge activity to the playback. However, the overall emission frequencies of the dummy were not adopted by the following fish. Instead, social signals based on different temporal patterns were emitted depending on the type of playback. In particular, double pulses were displayed in response to electrical signaling of the dummy and their expression was positively correlated with an animals' rank in the dominance hierarchy. Based on additional analysis of swimming trajectories and stereotypical locomotor behavior patterns, we conclude that the reception and emission of electrical communication signals play a crucial role in mediating social interactions in mormyrid weakly electric fish. PMID:28902915

Psychomotor and subjective effects of bilastine, hydroxyzine, and cetirizine, in combination with alcohol: a randomized, double-blind, crossover, and positive-controlled and placebo-controlled Phase I clinical trials.

PubMed

García-Gea, Consuelo; Martínez, Joan; Ballester, Maria Rosa; Gich, Ignasi; Valiente, Román; Antonijoan, Rosa Maria

2014-03-01

The aim of this study was to compare the effects of concomitant administration of alcohol and bilastine versus alcohol alone on the central nervous system. Twenty-four healthy young volunteers of both sexes participated in a randomized, double-blind, double-dummy, crossover, and positive-controlled and placebo-controlled clinical trials. At 1-week intervals, subjects received six different treatments: (i) placebo; (ii) alcohol 0.8 g/kg alone (ALC); (iii) ALC in combination with: bilastine 20 mg (B20 + A); (iv) bilastine 80 mg (B80 + A); (v) cetirizine 10 mg (CET + A); and (vi) hydroxyzine 25 mg (HYD + A). Psychomotor performance tests (fine motor, finger tapping, nystagmus, critical flicker-fusion frequency, temporal estimation, 'd2' cancellation, and simple reaction time) and subjective self-reports (drunkenness, drowsiness, mental slowness, clumsiness, anger, attentiveness, competence, happiness, hostility, interest, and extroversion) were carried out at baseline and multiple points thereafter. All active treatments induced a significant psychomotor impairment. The greatest and most lasting impairment was observed with HYD + A followed by B80 + A and CET + A. In contrast, objective measures showed less impairment with B20 + A and ALC, both with a similar magnitude. Self-reports showed a subjective perception of performance impairment in all active treatments. Concomitant administration of bilastine (at therapeutic dose) and alcohol does not produce greater central nervous system depressant effects than ACL alone. Copyright © 2014 John Wiley & Sons, Ltd.

Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial.

PubMed

Quintana, Daniel S; Westlye, Lars T; Alnæs, Dag; Rustan, Øyvind G; Kaufmann, Tobias; Smerud, Knut T; Mahmoud, Ramy A; Djupesland, Per G; Andreassen, Ole A

2016-07-01

It is unclear if and how exogenous oxytocin (OT) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response. To better understand the delivery routes of intranasal OT administration to the brain and the dose-response, we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging (fMRI) in four treatment conditions, including two different doses of intranasal OT using a novel Breath Powered device, intravenous (IV) OT, which provided similar concentrations of blood plasma OT, and placebo. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults administering a single-dose of these four treatments. We observed a treatment effect on right amygdala activation during the processing of angry and happy face stimuli, with pairwise comparisons revealing reduced activation after the 8IU low dose intranasal treatment compared to placebo. These data suggest the dampening of amygdala activity in response to emotional stimuli occurs via direct intranasal delivery pathways rather than across the blood-brain barrier via systemically circulating OT. This trial is registered at the U.S. National Institutes of Health clinical trial registry (www.clinicaltrials.gov; NCT01983514) and as EudraCT no. 2013-001608-12. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maternal Opioid Treatment: Human Experimental Research (MOTHER) – Approach, Issues, and Lessons Learned

PubMed Central

Jones, Hendrée E.; Fischer, Gabriele; Heil, Sarah H.; Kaltenbach, Karol; Martin, Peter R.; Coyle, Mara G.; Selby, Peter; Stine, Susan M.; O’Grady, Kevin E.; Arria, Amelia M.

2015-01-01

Aims The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current – and single most comprehensive – research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine. Methods The MOTHER study design is outlined, and its basic features are presented. Conclusions At least seven important lessons have been learned from the MOTHER study: (1) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (2) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment goals, patient populations, and hospital practices that in turn differentially impact recruitment rates, treatment compliance, and attrition; (3) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (4) staff turnover needs to be addressed with a proactive focus on both hiring and training; (5) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (6) timely tracking of data in a multi-site trial is both demanding and unforgiving; and, (7) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results. PMID:23106924

A noninferiority confirmatory trial of prasugrel versus clopidogrel in Japanese patients with non-cardioembolic stroke: rationale and study design for a randomized controlled trial - PRASTRO-I trial.

PubMed

Nagao, Takehiko; Toyoda, Kazunori; Kitagawa, Kazuo; Kitazono, Takanari; Yamagami, Hiroshi; Uchiyama, Shinichiro; Tanahashi, Norio; Matsumoto, Masayasu; Minematsu, Kazuo; Nagata, Izumi; Nishikawa, Masakatsu; Nanto, Shinsuke; Abe, Kenji; Ikeda, Yasuo; Ogawa, Akira

2018-04-01

This comparison of PRAsugrel and clopidogrel in Japanese patients with ischemic STROke (PRASTRO)-I trial investigates the noninferiority of prasugrel to clopidogrel sulfate in the prevention of recurrence of primary events (ischemic stroke, myocardial infarction, and death from other vascular causes), and the long-term safety of prasugrel in Japanese patients with non-cardioembolic stroke. This was an active-controlled, randomized, double-blind, double-dummy, parallel-group study conducted between July 2011 and March 2016 at multiple centers around Japan. Patients had to meet eligibility criteria before receiving 3.75 mg prasugrel or 75 mg clopidogrel orally once daily for a period of 96-104 weeks. A total of 3747 patients were included in this trial; 1598 in the 3.75 mg prasugrel group and 1551 in the 75 mg clopidogrel group completed the study. During the study period, 287 (15.2%) patients in the prasugrel group and 311 (16.7%) in the clopidogrel group discontinued treatment. Baseline characteristics, safety, and efficacy results are forthcoming and will be published separately. This article presents the study design and rationale for a trial investigating the noninferiority of prasugrel to clopidogrel sulfate with regards to the inhibitory effect on primary events in patients with non-cardioembolic stroke.

AVP-825 Breath-Powered Intranasal Delivery System Containing 22 mg Sumatriptan Powder vs 100 mg Oral Sumatriptan in the Acute Treatment of Migraines (The COMPASS Study): A Comparative Randomized Clinical Trial Across Multiple Attacks

PubMed Central

Tepper, Stewart J; Cady, Roger K; Silberstein, Stephen; Messina, John; Mahmoud, Ramy A; Djupesland, Per G; Shin, Paul; Siffert, Joao

2015-01-01

Objective The objective of this study was to compare the efficacy, tolerability, and safety of AVP-825, an investigational bi-directional breath-powered intranasal delivery system containing low-dose (22 mg) sumatriptan powder, vs 100 mg oral sumatriptan for acute treatment of migraine in a double-dummy, randomized comparative efficacy clinical trial allowing treatment across multiple migraine attacks. Background In phases 2 and 3, randomized, placebo-controlled trials, AVP-825 provided early and sustained relief of moderate or severe migraine headache in adults, with a low incidence of triptan-related adverse effects. Methods This was a randomized, active-comparator, double-dummy, cross-over, multi-attack study (COMPASS; NCT01667679) with two ≤12-week double-blind periods. Subjects experiencing 2-8 migraines/month in the past year were randomized 1:1 using computer-generated sequences to AVP-825 plus oral placebo tablet or an identical placebo delivery system plus 100 mg oral sumatriptan tablet for the first period; patients switched treatment for the second period in this controlled comparative design. Subjects treated ≤5 qualifying migraines per period within 1 hour of onset, even if pain was mild. The primary end-point was the mean value of the summed pain intensity differences through 30 minutes post-dose (SPID-30) using Headache Severity scores. Secondary outcomes included pain relief, pain freedom, pain reduction, consistency of response across multiple migraines, migraine-associated symptoms, and atypical sensations. Safety was also assessed. Results A total of 275 adults were randomized, 174 (63.3%) completed the study (ie, completed the second treatment period), and 185 (67.3%) treated at least one migraine in both periods (1531 migraines assessed). There was significantly greater reduction in migraine pain intensity with AVP-825 vs oral sumatriptan in the first 30 minutes post-dose (least squares mean SPID-30 = 10.80 vs 7.41, adjusted mean difference 3.39 [95% confidence interval 1.76, 5.01]; P < .001). At each time point measured between 15 and 90 minutes, significantly greater rates of pain relief and pain freedom occurred with AVP-825 treatment compared with oral sumatriptan. At 2 hours, rates of pain relief and pain freedom became comparable; rates of sustained pain relief and sustained pain freedom from 2 to 48 hours remained comparable. Nasal discomfort and abnormal taste were more common with AVP-825 vs oral sumatriptan (16% vs 1% and 26% vs 4%, respectively), but ∼90% were mild, leading to only one discontinuation. Atypical sensation rates were significantly lower with AVP-825 than with conventional higher dose 100 mg oral sumatriptan. Conclusions AVP-825 (containing 22 mg sumatriptan nasal powder) provided statistically significantly greater reduction of migraine pain intensity over the first 30 minutes following treatment, and greater rates of pain relief and pain freedom within 15 minutes, compared with 100 mg oral sumatriptan. Sustained pain relief and pain freedom through 24 and 48 hours was achieved in a similar percentage of attacks for both treatments, despite substantially lower total systemic drug exposure with AVP-825. Treatment was well tolerated, with statistically significantly fewer atypical sensations with AVP-825. PMID:25941016

AVP-825 breath-powered intranasal delivery system containing 22 mg sumatriptan powder vs 100 mg oral sumatriptan in the acute treatment of migraines (The COMPASS study): a comparative randomized clinical trial across multiple attacks.

PubMed

Tepper, Stewart J; Cady, Roger K; Silberstein, Stephen; Messina, John; Mahmoud, Ramy A; Djupesland, Per G; Shin, Paul; Siffert, Joao

2015-05-01

The objective of this study was to compare the efficacy, tolerability, and safety of AVP-825, an investigational bi-directional breath-powered intranasal delivery system containing low-dose (22 mg) sumatriptan powder, vs 100 mg oral sumatriptan for acute treatment of migraine in a double-dummy, randomized comparative efficacy clinical trial allowing treatment across multiple migraine attacks. In phases 2 and 3, randomized, placebo-controlled trials, AVP-825 provided early and sustained relief of moderate or severe migraine headache in adults, with a low incidence of triptan-related adverse effects. This was a randomized, active-comparator, double-dummy, cross-over, multi-attack study (COMPASS; NCT01667679) with two ≤12-week double-blind periods. Subjects experiencing 2-8 migraines/month in the past year were randomized 1:1 using computer-generated sequences to AVP-825 plus oral placebo tablet or an identical placebo delivery system plus 100 mg oral sumatriptan tablet for the first period; patients switched treatment for the second period in this controlled comparative design. Subjects treated ≤5 qualifying migraines per period within 1 hour of onset, even if pain was mild. The primary end-point was the mean value of the summed pain intensity differences through 30 minutes post-dose (SPID-30) using Headache Severity scores. Secondary outcomes included pain relief, pain freedom, pain reduction, consistency of response across multiple migraines, migraine-associated symptoms, and atypical sensations. Safety was also assessed. A total of 275 adults were randomized, 174 (63.3%) completed the study (ie, completed the second treatment period), and 185 (67.3%) treated at least one migraine in both periods (1531 migraines assessed). There was significantly greater reduction in migraine pain intensity with AVP-825 vs oral sumatriptan in the first 30 minutes post-dose (least squares mean SPID-30 = 10.80 vs 7.41, adjusted mean difference 3.39 [95% confidence interval 1.76, 5.01]; P < .001). At each time point measured between 15 and 90 minutes, significantly greater rates of pain relief and pain freedom occurred with AVP-825 treatment compared with oral sumatriptan. At 2 hours, rates of pain relief and pain freedom became comparable; rates of sustained pain relief and sustained pain freedom from 2 to 48 hours remained comparable. Nasal discomfort and abnormal taste were more common with AVP-825 vs oral sumatriptan (16% vs 1% and 26% vs 4%, respectively), but ∼90% were mild, leading to only one discontinuation. Atypical sensation rates were significantly lower with AVP-825 than with conventional higher dose 100 mg oral sumatriptan. AVP-825 (containing 22 mg sumatriptan nasal powder) provided statistically significantly greater reduction of migraine pain intensity over the first 30 minutes following treatment, and greater rates of pain relief and pain freedom within 15 minutes, compared with 100 mg oral sumatriptan. Sustained pain relief and pain freedom through 24 and 48 hours was achieved in a similar percentage of attacks for both treatments, despite substantially lower total systemic drug exposure with AVP-825. Treatment was well tolerated, with statistically significantly fewer atypical sensations with AVP-825. © 2015 The Authors. Headache: The Journal of Head and Face Pain published. by Wiley Periodicals, Inc. on behalf of American Headache Society.

Abelmoschus manihot - a traditional Chinese medicine versus losartan potassium for treating IgA nephropathy: study protocol for a randomized controlled trial.

PubMed

Li, Ping; Chen, Yi-Zhi; Lin, Hong-Li; Ni, Zhao-Hui; Zhan, Yong-Li; Wang, Rong; Yang, Hong-Tao; Fang, Jing-Ai; Wang, Nian-Song; Li, Wen-Ge; Sun, Xue-Feng; Chen, Xiang-Mei

2017-04-11

IgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide, but effective therapy remains limited and many patients progress to end-stage renal disease (ESRD). Only angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin-receptor blockers (ARB) show a high level of evidence (1B level) of being of value in the treatment for IgAN according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. However, traditional Chinese medicine has raised attention in kidney disease research. Abelmoschus manihot, a single medicament of traditional Chinese medicine has shown therapeutic effects in primary glomerular disease according to the randomized controlled clinical trial that we have completed. Here, we conduct a new study to assess the efficacy and safety of Abelmoschus manihot in IgAN. Also, this study is currently the largest double-blind, randomized controlled registered clinical research for the treatment of IgAN. We will conduct a multicenter, prospective, double-blind, double-dummy randomized controlled study. The study is designed as a noninferiority clinical trial. Approximately 1600 biopsy-proven IgAN patients will be enrolled at 100 centers in China and followed up for as long as 48 weeks. IgAN patients will be randomized assigned to the Abelmoschus manihot group (in the form of a huangkui capsule, 2.5 g, three times per day) and the losartan potassium group (losartan potassium, 100 mg/d). The primary outcome is the change in 24-h proteinuria from baseline after 48 weeks of treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after 48 weeks of treatment, the incidence of endpoint events (proteinuria ≥3.5 g/24 h, the doubling of serum creatinine, or receiving blood purification treatment) are the secondary outcomes. Twenty-four-hour proteinuria and eGFR are measured at 0, 4, 12, 24, 36 and 48 weeks. This study will be of sufficient size and scope to evaluate the efficacy and safety of Abelmoschus manihot compared to losartan potassium in treating patients with IgAN. The results of this study may provide a new, effective and safe treatment strategy for IgAN. ClinicalTrials.gov, identifier: NCT02231125 . Registered on 30 August 2014.

Efficacy and safety of loxoprofen hydrogel patch versus loxoprofen tablet in patients with knee osteoarthritis: a randomized controlled non-inferiority trial.

PubMed

Mu, Rong; Bao, Chun-de; Chen, Zhi-wei; Zheng, Yi; Wang, Guo-chun; Zhao, Dong-bao; Hu, Shao-xian; Li, Yu-jun; Shao, Zeng-wu; Zhang, Zhi-yi; Xiao, Wei-guo; Zhang, Weiya; Li, Zhan-guo

2016-01-01

This study is aimed at comparing the efficacy and safety of loxoprofen sodium hydrogel patch (LX-P) with loxoprofen sodium tablet (LX-T) in patients with knee osteoarthritis (OA). One hundred sixty-nine patients were enrolled in a randomized, controlled, double-blind, double-dummy, multicenter, non-inferiority trial of LX-P. Patients were randomly assigned to either LX-P or LX-T groups for a 4-week treatment. The primary efficacy endpoint was the proportion of patients with an overall improvement of ≥50%, and the secondary efficacy endpoint was the proportion of patients with an improvement of ≥25% from baseline in each of the seven main symptoms. The non-inferiority trial was based on a power of 80% and significance level of 2.5% with a non-inferiority margin of -10%. In both intention-to-treat (ITT) and per-protocol (PP) analyses, LX-P was as effective as LX-T in regard to the primary endpoint. In the ITT analysis, the difference between the two groups was 12.6% [95% confidence interval, -1.7 to 26.9%]. No significant differences were found between the two groups in any of the secondary efficacy outcomes. A lower incidence of adverse events was observed in LX-P group; however, the difference was not statistically significant. No serious adverse events were reported in the LX-P group, whereas one case was reported in LX-T group. Based on the present study, topical loxoprofen patch was non-inferior to oral loxoprofen in patients with knee osteoarthritis.

Simultaneous treatment to attain blood pressure and lipid goals and reduced CV risk burden using amlodipine/atorvastatin single-pill therapy in treated hypertensive participants in a randomized controlled trial

PubMed Central

Grimm, Richard; Malik, Mobin; Yunis, Carla; Sutradhar, Santosh; Kursun, Attila

2010-01-01

TOGETHER investigated whether targeting multiple cardiovascular (CV) risk factors using single-pill amlodipine/atorvastatin (AML/ATO) and therapeutic lifestyle changes (TLC) results in greater blood pressure (BP)/lipid control and additional reduction in estimated cardiovascular disease (CVD) risk compared with blood pressure intervention only using amlodipine (AML) + TLC. TOGETHER was a 6-week, randomized, double-blind, double-dummy trial using hypertensive participants with additional CV risk factors without CVD/diabetes. Participants were randomized to either AML/ATO (5 to 10/20 mg) + TLC or AML (5 to 10 mg) + TLC. The primary end point was the difference in proportion of participants attaining both BP (<140/90 mm Hg) and low-density lipoprotein cholesterol (LDL-C) (<100 mg/dL) goals at week 6. At week 6, 67.8% of participants receiving AML/ATO + TLC attained the combined BP/LDL-C goal versus 9.6% with AML + TLC (RD [A–B]: 58.2; 95% CI [48.1 to 68.4] P < 0.001; OR: 19.0; 95% CI 9.1 to 39.6; P < 0.001). Significant reductions from baseline in LDL-C, total cholesterol and triglycerides and estimated 10-year Framingham risk were also observed. Treatment with AML/ATO was well tolerated. In conclusion, a multifactorial CV management approach is more effective in achieving combined BP/LDL-C targets as well as CV risk reduction compared with BP intervention only in this patient population. PMID:20479948

Evaluation of the feasibility of switching from immediate release quetiapine to extended release quetiapine fumarate in stable outpatients with schizophrenia.

PubMed

Möller, Hans-Jürgen; Johnson, Sunny; Mateva, Temenuzhka; Brecher, Martin; Svensson, Ola; Miller, Frank; Meulien, Didier

2008-03-01

This double-blind, double-dummy study (D1444C00146) evaluated the efficacy and safety of switching patients with clinically stable schizophrenia from quetiapine immediate release (IR) to the same dose of once-daily extended release quetiapine fumarate (quetiapine XR). Patients received quetiapine IR 400-800 mg/day twice daily for 4 weeks, and were then randomized (2 : 1) to a once-daily equivalent dose of quetiapine XR or maintained on IR for 6 weeks. The primary variable was the proportion of patients who discontinued treatment owing to lack of efficacy or whose Positive and Negative Syndrome Scale scores increased by at least 20% from randomization to any visit. In total, 497 patients were randomized to quetiapine XR (n=331) or IR (n=166). Noninferiority (6% margin; one-sided test, 2.5% significance level) was narrowly missed for the primary efficacy variable for the modified intention-to-treat population (9.1%, quetiapine XR; 7.2%, quetiapine IR; difference 1.86%; 95% confidence interval: -3.78, 6.57; P=0.0431), but was shown for the per-protocol population (5.3%, quetiapine XR; 6.2%, quetiapine IR; difference: -0.83%; 95% confidence interval: -6.75, 3.71; P=0.0017). Serious adverse event incidence was low for quetiapine XR and IR; there were no unexpected adverse events. In conclusion, efficacy was maintained without compromising safety/tolerability when switching patients with stable schizophrenia from twice-daily quetiapine IR to once-daily quetiapine XR (400-800 mg/day).

Uteroplacental circulation in early pregnancy complicated by threatened abortion supplemented with vaginal micronized progesterone or oral dydrogesterone.

PubMed

Czajkowski, Krzysztof; Sienko, Jacek; Mogilinski, Mariusz; Bros, Magdalena; Szczecina, Roman; Czajkowska, Anna

2007-03-01

To compare the influence of vaginal micronized progesterone and oral dydrogesterone supplementation on uteroplacental circulation in early pregnancy that is complicated by threatened abortion. Randomized, parallel group, double-blind, double dummy-controlled study. Tertiary care university hospital. Fifty-three patients with threatened abortion and a living embryo. Three hundred milligrams of micronized vaginal progesterone or 30 mg of oral dydrogesterone daily supplementation for 6 weeks, serial transvaginal Doppler ultrasound measurement of pulsatility index, resistance index, and systolic/diastolic ratio of the spiral arteries, the uterine arteries, and the intrachorionic area. Uteroplacental blood flow. The study demonstrated that vaginal progesterone administration, but not oral dydrogesterone treatment, results in the decrease in the spiral artery pulsatility and resistance index and systolic/diastolic ratio. Insignificant decrease in pulsatility index and resistance index of the uterine artery was observed at >9 weeks and was not associated with treatment regimen. Dydrogesterone treatment was only accompanied by the decrease in the uterine artery systolic/diastolic ratio. Vaginal progesterone and oral dydrogesterone supplementation have a different influence on the uteroplacental circulation in early pregnancy that is complicated by threatened abortion.

Dosing adjustments in postpartum patients maintained on buprenorphine or methadone.

PubMed

Jones, Hendrée E; Johnson, Rolley E; O'Grady, Kevin E; Jasinski, Donald R; Tuten, Michelle; Milio, Lorraine

2008-06-01

Scant scientific attention has been given to examining the need for agonist medication dose changes in the postpartum period. Study objectives were: 1) to determine the need for medication dose adjustments in participants stabilized on buprenorphine or methadone 3 weeks before and 4 weeks after delivery, and 2) to evaluate the need for methadone dose adjustments during the first 7 days in participants transferred from buprenorphine to methadone at 5 weeks postpartum. Participants were opioid-dependent pregnant women who had completed a randomized, double-blind, double-dummy, flexible dosing comparison of buprenorphine to methadone. Participants received a stable dose of methadone (N = 10) or buprenorphine (N = 8) before and 4 weeks after delivery. Buprenorphine-maintained participants were transferred to methadone at 5 weeks postpartum. There were no significant differences predelivery and/or postdelivery between the buprenorphine and methadone conditions in the mean ratings of dose adequacy, "liking," "hooked," and "craving" of heroin or cocaine. Patient response to the conversion from buprenorphine to methadone seems variable. Buprenorphine-maintained participants required dose changes postpartum only after they transferred to methadone. Regardless of type of medication, postpartum patients should be monitored for signs of overmedication.

Effects of Two Chinese Herbal Formulae for the Treatment of Moderate to Severe Stable Chronic Obstructive Pulmonary Disease: A Multicenter, Double-Blind, Randomized Controlled Trial

PubMed Central

Cao, Yuxue; Du, Yijie; Zhang, Hongying; Luo, Qingli; Li, Bei; Wu, Jinfeng; Lv, Yubao; Sun, Jing; Jin, Hualiang; Wei, Kai; Zhao, Zhengxiao; Kong, Lingwen; Zhou, Xianmei; Miao, Qing; Wang, Gang; Zhou, Qingwei; Dong, Jingcheng

2014-01-01

Objective The study aims to evaluate the efficacy and safety of two Chinese herbal formulae for the treatment of stable COPD. Methods A multicenter, double-blind, double-dummy, and randomized controlled trial (RCT) was conducted. All groups were treated with additional conventional medicines. There were a 6-month treatment and a 12-month follow-up for 5 times. Primary outcomes included lung function test, exacerbation frequency, score of SGRQ. Second outcomes consisted of 6MWD, BODE index, psychological field score, inflammatory factors and cortisol. Results A total of 331 patients were randomly divided into two active treatment groups (Bushen Yiqi (BY) granule group, n = 109; Bushen Fangchuan (BF) tablet group, n = 109) and a placebo group (n = 113). Finally 262 patients completed the study. BY granule & BF tablet increased the values of VC, FEV1 (%) and FEV1/FVC (%), compared with placebo. BY granule improved PEF. Both treatments reduced acute exacerbation frequency (P = 0.067), BODE index and psychological field score, while improved 6MWD. In terms of descent rang of SGRQ score, both treatments increased (P = 0.01). Both treatments decreased inflammatory cytokines, such as IL-8, and IL-17(P = 0.0219). BY granule obviously descended IL-17(P<0.05), IL-1β (P = 0.05), IL-6, compared with placebo. They improved the level of IL-10 and cortisol. BY granule raised cortisol (P = 0.07) and decreased TNF-α. Both treatments slightly descended TGF-β1. In terms of safety, subject compliance and drug combination, there were no differences (P>0.05) among three groups. Conclusions BY granule and BF tablet were positively effective for the treatment of COPD, and the former performed better in general. Trial Registration Chinese Clinical Trial Register center ChiCTR-TRC-09000530 PMID:25118962

Serenoa repens, lycopene and selenium versus tamsulosin for the treatment of LUTS/BPH. An Italian multicenter double-blinded randomized study between single or combination therapy (PROCOMB trial).

PubMed

Morgia, Giuseppe; Russo, Giorgio I; Voce, Salvatore; Palmieri, Fabiano; Gentile, Marcello; Giannantoni, Antonella; Blefari, Franco; Carini, Marco; Minervini, Andrea; Ginepri, Andrea; Salvia, Giuseppe; Vespasiani, Giuseppe; Santelli, Giorgio; Cimino, Sebastiano; Allegro, Rosalinda; Collura, Zaira; Fragalà, Eugenia; Arnone, Salvatore; Pareo, Rosaria M

2014-11-01

Phytotherapy has been used to treat patients with lower urinary tract symptoms (LUTS). We evaluated the efficacy and tolerability of combination therapy between Serenoa Repens (SeR), Lycopene (Ly), and Selenium (Se) + tamsulosin versus single therapies. PROCOMB trial (ISRCTN78639965) was a randomized double-blinded, double-dummy multicenter study of 225 patients between 55 and 80 years old, PSA ≤ 4 ng/ml, IPSS ≥12, prostate volume ≤60 cc, Qmax ≤15 ml/sec, postvoid residual urine (PVR) <150 ml. Participants were randomized group A (SeR-Se-Ly), group B (tamsulosin 0.4 mg), group C (SeR-Se-Ly + tamsulosin 0.4 mg). The primary endpoints of the study were the reduction of IPSS, PVR, and increase of Qmax in group C versus monotherapy groups. The decrease for combination therapy was significantly greater versus group A (P < 0.05) and group B (P < 0.01) for IPSS and versus group A (P < 0.01) for PVR from baseline to 6 months. A greater decrease in IPSS was observed for Group C versus group A (P < 0.01) and increase in Qmax versus group B (P < 0.01), from 6 months to 12 months. At one year, the changes of IPSS and Qmax were greater for Group C versus monotherapies (each comparison <0.05). The proportions of men with a decrease of at least three points (each comparison P < 0.05) and decrease of 25% for IPSS (each comparison P < 0.01) were greater for Group C. SeR-Se-Ly + tamsulosin therapy is more effective than single therapies in improving IPSS and increasing Qmax in patients with LUTS. © 2014 Wiley Periodicals, Inc.

Efficacy and safety of bilastine in Japanese patients with perennial allergic rhinitis: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study.

PubMed

Okubo, Kimihiro; Gotoh, Minoru; Asako, Mikiya; Nomura, Yasuyuki; Togawa, Michinori; Saito, Akihiro; Honda, Takayuki; Ohashi, Yoshihiro

2017-01-01

Bilastine, a novel non-sedating second-generation H 1 antihistamine, has been approved in most European countries since 2010. This study aimed to evaluate the superiority of bilastine over placebo in Japanese patients with perennial allergic rhinitis (PAR). This randomized, double-blind, placebo-controlled, parallel-group, phase III study (trial registration number JapicCTI-142600) evaluated the effect of a 2-week treatment period with bilastine (20 mg once daily), fexofenadine (60 mg twice daily), or a matched placebo (double dummy) in patients with PAR. All patients were instructed to record individual nasal and ocular symptoms in diaries daily. The primary endpoint was the mean change in total nasal symptom scores (TNSS) from baseline to Week 2 (Days 10-13). A total of 765 patients were randomly allocated to receive bilastine, fexofenadine, or placebo (256, 254, and 255 patients, respectively). The mean change in TNSS from baseline at Week 2 was significantly decreased by bilastine (-0.98) compared to placebo (-0.63, P = 0.023). Bilastine and fexofenadine showed no significant difference in the primary endpoint. However, the mean change in TNSS from baseline on Day 1 was more significantly decreased by bilastine (-0.99) than by placebo (-0.28, P < 0.001) or fexofenadine (-0.62, P = 0.032). The active drugs also improved instantaneous TNSS 1 h after the first and before the second drug administration on Day 1 (P < 0.05). The study drugs were well tolerated. After 2-week treatment period, bilastine 20 mg once daily was effective and tolerable in Japanese patients with PAR, and exhibited a rapid onset of action. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

A prospective, randomized, double-blind trial of intranasal dexmedetomidine and oral chloral hydrate for sedated auditory brainstem response (ABR) testing.

PubMed

Reynolds, Jason; Rogers, Amber; Medellin, Eduardo; Guzman, Jonathan A; Watcha, Mehernoor F

2016-03-01

Dexmedetomidine is increasingly used by various routes for pediatric sedation. However, there are few randomized controlled trials comparing the efficacy of dexmedetomidine to other commonly used sedatives. To compare the efficacy of sedation with intranasal dexmedetomidine to oral chloral hydrate for auditory brainstem response (ABR) testing. In this double-blind, double-dummy study, children undergoing ABR testing were randomized to receive intranasal dexmedetomidine 3 mcg · kg(-1) plus oral placebo (Group IN DEX) or oral chloral hydrate 50 mg · kg(-1) plus intranasal saline placebo (Group CH). We recorded demographic data, times from sedative administration to start and completion of testing, quality of sedation, occurrence of predefined adverse events, discharge times, and return to baseline activity on the day of testing. Testing completion rates with a single dose of medication were higher in the IN DEX group (89% vs 66% for CH, odds ratio with 95% confidence intervals 4.04 [1.3-12.6], P = 0.018). The median [95% CI)] time to successful testing start was shorter (25 [20-29] min vs 30 [20-49] min for IN DEX and CH, respectively, log rank test P = 0.02) and the proportion of children whose parents reported a return to baseline activity on the day of testing was greater for the IN DEX than the CH group (89% vs 64%, OR [95% CI] 4.71 [1.34-16.6], P = 0.02). There were no major adverse events in either group and no significant differences in the incidence of minor events. Intranasal dexmedetomidine is an effective alternative to oral chloral hydrate sedation for ABR testing, with the advantages of a higher incidence of testing completion with a single dose, shorter time to desired sedation level, and with significantly more patients reported to return to baseline activity on the same day. © 2016 John Wiley & Sons Ltd.

Efficacy and safety of rilpivirine (TMC278) versus efavirenz at 48 weeks in treatment-naive HIV-1-infected patients: pooled results from the phase 3 double-blind randomized ECHO and THRIVE Trials.

PubMed

Cohen, Calvin J; Molina, Jean-Michel; Cahn, Pedro; Clotet, Bonaventura; Fourie, Jan; Grinsztejn, Beatriz; Wu, Hao; Johnson, Margaret A; Saag, Michael; Supparatpinyo, Khuanchai; Crauwels, Herta; Lefebvre, Eric; Rimsky, Laurence T; Vanveggel, Simon; Williams, Peter; Boven, Katia

2012-05-01

Pooled analysis of phase 3, double-blind, double-dummy ECHO and THRIVE trials comparing rilpivirine (TMC278) and efavirenz. Treatment-naive HIV-1-infected adults were randomized 1:1 to rilpivirine 25 mg once daily or efavirenz 600 mg once daily, with background tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (ECHO) or TDF/FTC, zidovudine/lamivudine, or abacavir/lamivudine (THRIVE). The primary endpoint was confirmed response [viral load <50 copies per milliliter; intent-to-treat time-to-loss-of-virologic-response (ITT-TLOVR) algorithm] at week 48. The pooled data set enabled analyses of subgroups and predictors of response/virologic failure. Confirmed responses were 84% (rilpivirine) and 82% (efavirenz). The difference in response rates (95% confidence interval) was 2.0% (-2.0% to 6.0%). The incidence of virologic failure was 9% (rilpivirine) versus 5% (efavirenz). Responses in ITT-TLOVR and ITT-snapshot analyses were consistent. Responses were similar for rilpivirine and efavirenz by background regimen, gender, race and clade. Suboptimal adherence and higher baseline viral load resulted in lower responses, higher virologic failure, and development of resistance in both groups; the effects on virologic failure were more apparent with rilpivirine. CD4 cell count increased over time in both groups. Rilpivirine compared with efavirenz gave smaller incidences of adverse events leading to discontinuation (3% vs. 8%, respectively), treatment-related grade 2-4 adverse events (16% vs. 31%), rash (3% vs. 14%), dizziness (8% vs. 26%), abnormal dreams/nightmares (8% vs. 13%), and grade 2-4 lipid abnormalities. At week 48, rilpivirine 25 mg once daily and efavirenz 600 mg once daily had comparable response rates. Rilpivirine had more virologic failures and improved tolerability versus efavirenz.

Randomized double-blind comparison of cognitive and EEG effects of lacosamide and carbamazepine.

PubMed

Meador, Kimford J; Loring, David W; Boyd, Alan; Echauz, Javier; LaRoche, Suzette; Velez-Ruiz, Naymee; Korb, Pearce; Byrnes, William; Dilley, Deanne; Borghs, Simon; De Backer, Marc; Story, Tyler; Dedeken, Peter; Webster, Elizabeth

2016-09-01

Differential effectiveness of antiepileptic drugs (AEDs) is more commonly determined by tolerability than efficacy. Cognitive effects of AEDs can adversely affect tolerability and quality of life. This study evaluated cognitive and EEG effects of lacosamide (LCM) compared with carbamazepine immediate-release (CBZ-IR). A randomized, double-blind, double-dummy, two-period crossover, fixed-dose study in healthy subjects compared neuropsychological and EEG effects of LCM (150mg, b.i.d.) and CBZ-IR (200mg, t.i.d.). Testing was conducted at screening, predrug baseline, the end of each treatment period (3-week titration; 3-week maintenance), and the end of each washout period (4weeks after treatment). A composite Z-score was derived for the primary outcome variable (computerized cognitive tests and traditional neuropsychological measures) and separately for the EEG measures. Other variables included individual computer, neuropsychological, and EEG scores and adverse events (AEs). Subjects included 60 healthy adults (57% female; mean age: 34.4years [SD: 10.5]); 44 completed both treatments; 41 were per protocol subjects. Carbamazepine immediate-release had worse scores compared with LCM for the primary composite neuropsychological outcome (mean difference=0.33 [SD: 1.36], p=0.011) and for the composite EEG score (mean difference=0.92 [SD: 1.77], p=0.003). Secondary analyses across the individual variables revealed that CBZ-IR was statistically worse than LCM on 36% (4/11) of the neuropsychological tests (computerized and noncomputerized) and 0% of the four EEG measures; none favored CBZ-IR. Drug-related AEs occurred more with CBZ-IR (49%) than LCM (22%). Lacosamide had fewer untoward neuropsychological and EEG effects and fewer AEs and AE-related discontinuations than CBZ-IR in healthy subjects. Lacosamide exhibits a favorable cognitive profile. Copyright © 2016 Elsevier Inc. All rights reserved.

L-Acetylcarnitine in dysthymic disorder in elderly patients: a double-blind, multicenter, controlled randomized study vs. fluoxetine.

PubMed

Bersani, Giuseppe; Meco, Giuseppe; Denaro, Alessandro; Liberati, Damien; Colletti, Chiara; Nicolai, Raffaella; Bersani, Francesco Saverio; Koverech, Aleardo

2013-10-01

L-Acetylcarnitine (LAC), the acetyl ester of carnitine naturally present in the central nervous system and involved in several neural pathways, has been demonstrated to be active in various animal experimental models resembling some features of human depression. The aim of the study is to verify whether LAC can have an antidepressant action in a population of elderly patients with dysthymic disorder in comparison with a traditional antidepressant such as fluoxetine. Multicentric, double-blind, double-dummy, controlled, randomized study based on a observation period of 7 weeks. 80 patients with DSM-IV diagnosis of dysthymic disorder were enrolled in the study and subdivided into 2 groups. Group A patients received LAC plus placebo; group B patients received fluoxetine 20 mg/die plus placebo. Clinical assessment was performed through several psychometric scales at 6 different moments. Group A patients showed a statistically significant improvement in the following scales: HAM-D, HAM-A, BDI and Touluse Pieron Test. Comparison between the two groups, A and B, generally showed very similar clinical progression. The results obtained with LAC and fluoxetine were equivalent. As the subjects in this study were of senile age, it is possible to hypothesize that the LAC positive effect on mood could be associated with improvement in subjective cognitive symptomatology. The difference in the latency time of clinical response (1 week of LAC treatment, compared with the 2 weeks' latency time with fluoxetine) suggests the existence of different mechanisms of action possibly in relation to the activation of rapid support processes of neuronal activity. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

Rotigotine vs ropinirole in advanced stage Parkinson's disease: a double-blind study.

PubMed

Mizuno, Yoshikuni; Nomoto, Masahiro; Hasegawa, Kazuko; Hattori, Nobutaka; Kondo, Tomoyoshi; Murata, Miho; Takeuchi, Masahiro; Takahashi, Masayoshi; Tomida, Takayuki

2014-12-01

To confirm the superiority of transdermal rotigotine up to 16 mg/24 h over placebo, and non-inferiority to ropinirole, in Japanese Parkinson's disease (PD) patients on concomitant levodopa therapy. This trial was a randomized, double-blind, double-dummy, three-arm parallel group placebo- and ropinirole-controlled trial. Four-hundred and twenty PD patients whose motor symptoms were not well controlled by levodopa treatment were randomized 2:2:1 to receive rotigotine, ropinirole (up to 15 mg/day) or placebo during a 16-week treatment period followed by a 4-week taper period. The primary variable was change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON state) sum score from baseline to the end of the treatment period. The difference in the change in the UPDRS Part III (ON state) sum score from baseline to the end of treatment between rotigotine and placebo groups was -6.4 ± 1.2 (95% CI: -8.7 to -4.1; p < 0.001), indicating superiority of rotigotine over placebo. The difference between rotigotine and ropinirole groups was -1.4 ± 1.0 (95% CI: -3.2 to 0.5), below the non-inferiority margin, indicating the non-inferiority of rotigotine to ropinirole. Application site reaction was seen in 57.7% of the patients in the rotigotine group and in 18.6% in the ropinirole group (P < 0.001). No other safety issue was noted. Rotigotine was well tolerated at doses up to 16 mg/24 h and showed similar efficacy to ropinirole except that the application site reaction was much higher in the rotigotine group. Copyright © 2014. Published by Elsevier Ltd.

Double-blind comparison of two types of benzocaine lozenges for the treatment of acute pharyngitis.

PubMed

Busch, Regina; Graubaum, Hans-Joachim; Grünwald, Jörg; Schmidt, Mathias

2010-01-01

In a reference-controlled double-blind trial in patients with acute pharyngitis the effects of a newly developed lozenge containing 8 mg of benzocaine (p-aminobenzoic acid ethyl ester, CAS 94-09-7) were compared with those of an identically dosed commercial pastille. 246 patients were randomized to receive either the lozenges (group A, n = 123) or the pastilles (group B, n = 123). Each patient took a total of six doses within 12 h according to the double-dummy principle, with each single dose spaced by 2 h. The primary parameter was the assessment of the responder rate with = 50 % pain relief within 15 min post application. Further parameters included the relative relief of pain in the course of the study and the tolerability of the formulation. After application of the first unit the comparison of groups yielded very similar and statistically not differing results for efficacy in both groups, with responder rates of 25.2 % and 22.0 % in groups A and B, respectively. One adverse drug reaction was observed in group B (burning and tingling feeling on the tongue), which, however, did not lead to discontinuation of study participation. In all other cases tolerability was stated to be "good to very good". The application of the benzocaine lozenges was statistically non-inferior to the use of the pastilles.

Lysine clonixinate in minor dental surgery: double-blind randomized parallel study versus paracetamol.

PubMed

Martí, M L; De los Santos, A R; Di Girolamo, G; Gil, M; Manero, E O; Fraga, C

1993-01-01

Lysine clonixinate (LC), an effective and well tolerated non-morphinic analgesic whose mechanism of action is basically due to the inhibition of cyclo-oxygenase, was assessed with a double-blind randomized dummy design versus paracetamol (P) on 200 patients suffering from pain after minor dental surgery. Patients received according to their needs 1 or 2 tablets of 125 mg lysine clonixinate or 500 mg paracetamol every 8 h during 48 h or until pain relief. Both groups, each composed of 100 patients, were comparable in terms of demographic conditions (t test), initial symptoms (chi-square test), characteristics of the extracted dental pieces, surgical complications and wound treatment (chi-square test). Pain intensity scores and daily average intake of tablets (3.4/day) documented in the patients' diary revealed no statistically significant differences between the two treatments (chi-square test). It was found that spontaneous pain measured using a visual analogue scale (VAS) decreased significantly in both treatment groups at the 24-h control examination. The following values were observed in the LC group: baseline 4.38 +/- 1.7; 24-h * 1.20 +/- 1.4; 48-h * 0.36 +/- 1.2. In the P group the values were: baseline 4.28 +/- 1.6; 24-h * 1.11 +/- 1.4; 48-h * 0.30 +/- 0.7 (*p < 0.05). Other variables like facial swelling and night pain, evaluated on a score from 0 to 4 and symptom presence or absence respectively, showed a similar response.(ABSTRACT TRUNCATED AT 250 WORDS)

Optimized scheduling technique of null subcarriers for peak power control in 3GPP LTE downlink.

PubMed

Cho, Soobum; Park, Sang Kyu

2014-01-01

Orthogonal frequency division multiple access (OFDMA) is a key multiple access technique for the long term evolution (LTE) downlink. However, high peak-to-average power ratio (PAPR) can cause the degradation of power efficiency. The well-known PAPR reduction technique, dummy sequence insertion (DSI), can be a realistic solution because of its structural simplicity. However, the large usage of subcarriers for the dummy sequences may decrease the transmitted data rate in the DSI scheme. In this paper, a novel DSI scheme is applied to the LTE system. Firstly, we obtain the null subcarriers in single-input single-output (SISO) and multiple-input multiple-output (MIMO) systems, respectively; then, optimized dummy sequences are inserted into the obtained null subcarrier. Simulation results show that Walsh-Hadamard transform (WHT) sequence is the best for the dummy sequence and the ratio of 16 to 20 for the WHT and randomly generated sequences has the maximum PAPR reduction performance. The number of near optimal iteration is derived to prevent exhausted iterations. It is also shown that there is no bit error rate (BER) degradation with the proposed technique in LTE downlink system.

Optimized Scheduling Technique of Null Subcarriers for Peak Power Control in 3GPP LTE Downlink

PubMed Central

Park, Sang Kyu

2014-01-01

Orthogonal frequency division multiple access (OFDMA) is a key multiple access technique for the long term evolution (LTE) downlink. However, high peak-to-average power ratio (PAPR) can cause the degradation of power efficiency. The well-known PAPR reduction technique, dummy sequence insertion (DSI), can be a realistic solution because of its structural simplicity. However, the large usage of subcarriers for the dummy sequences may decrease the transmitted data rate in the DSI scheme. In this paper, a novel DSI scheme is applied to the LTE system. Firstly, we obtain the null subcarriers in single-input single-output (SISO) and multiple-input multiple-output (MIMO) systems, respectively; then, optimized dummy sequences are inserted into the obtained null subcarrier. Simulation results show that Walsh-Hadamard transform (WHT) sequence is the best for the dummy sequence and the ratio of 16 to 20 for the WHT and randomly generated sequences has the maximum PAPR reduction performance. The number of near optimal iteration is derived to prevent exhausted iterations. It is also shown that there is no bit error rate (BER) degradation with the proposed technique in LTE downlink system. PMID:24883376

Gastrointestinal safety of celecoxib versus naproxen in patients with cardiothrombotic diseases and arthritis after upper gastrointestinal bleeding (CONCERN): an industry-independent, double-blind, double-dummy, randomised trial.

PubMed

Chan, Francis K L; Ching, Jessica Y L; Tse, Yee Kit; Lam, Kelvin; Wong, Grace L H; Ng, Siew C; Lee, Vivian; Au, Kim W L; Cheong, Pui Kuan; Suen, Bing Y; Chan, Heyson; Kee, Ka Man; Lo, Angeline; Wong, Vincent W S; Wu, Justin C Y; Kyaw, Moe H

2017-06-17

Present guidelines are conflicting for patients at high risk of both cardiovascular and gastrointestinal events who continue to require non-steroidal anti-inflammatory drugs (NSAIDs). We hypothesised that a cyclooxygenase-2-selective NSAID plus proton-pump inhibitor is superior to a non-selective NSAID plus proton-pump inhibitor for prevention of recurrent ulcer bleeding in concomitant users of aspirin with previous ulcer bleeding. For this industry-independent, double-blind, double-dummy, randomised trial done in one academic hospital in Hong Kong, we screened patients with arthritis and cardiothrombotic diseases who were presenting with upper gastrointestinal bleeding, were on NSAIDs, and require concomitant aspirin. After ulcer healing, an independent staff member randomly assigned (1:1) patients who were negative for Helicobacter pylori with a computer-generated list of random numbers to receive oral administrations of either celecoxib 100 mg twice per day plus esomeprazole 20 mg once per day or naproxen 500 mg twice per day plus esomeprazole 20 mg once per day for 18 months. All patients resumed aspirin 80 mg once per day. Both patients and investigators were masked to their treatments. The primary endpoint was recurrent upper gastrointestinal bleeding within 18 months. The primary endpoint and secondary safety endpoints were analysed in the modified intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT00153660. Between May 24, 2005, and Nov 28, 2012, we enrolled 514 patients, assigning 257 patients to each study group, all of whom were included in the intention-to-treat population. Recurrent upper gastrointestinal bleeding occurred in 14 patients in the celecoxib group (nine gastric ulcers and five duodenal ulcers) and 31 patients in the naproxen group (25 gastric ulcers, three duodenal ulcers, one gastric ulcer and duodenal ulcer, and two bleeding erosions). The cumulative incidence of recurrent bleeding in 18 months was 5·6% (95% CI 3·3-9·2) in the celecoxib group and 12·3% (8·8-17·1) in the naproxen group (p=0·008; crude hazard ratio 0·44, 95% CI 0·23-0·82; p=0·010). Excluding patients who reached study endpoints, 21 (8%) patients in the celecoxib group and 17 (7%) patients in the naproxen group had adverse events leading to discontinuation of treatment. No treatment-related deaths occurred during the study. In patients at high risk of both cardiovascular and gastrointestinal events who require concomitant aspirin and NSAID, celecoxib plus proton-pump inhibitor is the preferred treatment to reduce the risk of recurrent upper gastrointestinal bleeding. Naproxen should be avoided despite its perceived cardiovascular safety. The Research Grant Council of Hong Kong. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Randomized Controlled Trial Comparing Intranasal Midazolam and Chloral Hydrate for Procedural Sedation in Children.

PubMed

Stephen, Marie Christy Sharafine; Mathew, John; Varghese, Ajoy Mathew; Kurien, Mary; Mathew, George Ani

2015-12-01

To evaluate the efficacy and safety of intranasal midazolam and chloral hydrate syrup for procedural sedation in children. Prospective randomized placebo-controlled trial (double blind, double dummy). Tertiary care hospital over 18 months. Eighty-two children, 1 to 6 years old, undergoing auditory brainstem response testing were randomized to receive either intranasal midazolam with oral placebo or chloral hydrate syrup with placebo nasal spray. Intranasal midazolam was delivered at 0.5 mg/kg (100 mcg per spray) and oral syrup at 50 mg/kg. Children not sedated at 30 minutes had a second dose at half the initial dose. The primary outcomes measured were safety and efficacy. Secondary outcomes were time to onset of sedation, parental separation, nature of parental separation, parental satisfaction, audiologist's satisfaction, time to recovery, and number of attempts. Forty-one children were in each group, and no major adverse events were noted. The chloral hydrate group showed earlier onset of sedation (66%) compared with the intranasal midazolam group (33%). Significant difference in time to recovery was noted in the chloral hydrate group (78 minutes) versus the intranasal midazolam group (108 minutes). The parents' and audiologist's satisfaction was higher for chloral hydrate (95% and 75%) than for intranasal midazolam (49% and 29%, respectively). Overall, sedation was 95% with chloral hydrate versus 51% with intranasal midazolam. Both drugs maintained sedation. Intranasal midazolam and chloral hydrate are both safe and efficacious for pediatric procedural sedation. Chloral hydrate was superior to intranasal midazolam, with an earlier time to onset of sedation, a faster recovery, better satisfaction among parents and the audiologist, and successful sedation. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

A study to assess COPD Symptom-based Management and to Optimise treatment Strategy in Japan (COSMOS-J) based on GOLD 2011.

PubMed

Betsuyaku, Tomoko; Kato, Motokazu; Fujimoto, Keisaku; Hagan, Gerry; Kobayashi, Akihiro; Hitosugi, Hideki; James, Mark; Jones, Paul W

2013-01-01

The Global initiative for chronic Obstructive Lung Disease (GOLD) Committee has proposed a chronic obstructive pulmonary disease (COPD) assessment framework focused on symptoms and on exacerbation risk. This study will evaluate a symptom and exacerbation risk-based treatment strategy based on GOLD in a real-world setting in Japan. Optimal management of COPD will be determined by assessing symptoms using the COPD Assessment Test (CAT) and by assessing the frequency of exacerbations. This study (ClinicalTrials.gov identifier: NCT01762800) is a 24-week, multicenter, randomized, double-blind, double-dummy, parallel-group study. It aims to recruit 400 patients with moderate-to-severe COPD. Patients will be randomized to receive treatment with either salmeterol/fluticasone propionate (SFC) 50/250 μg twice daily or with tiotropium bromide 18 μg once daily. Optimal management of patients will be assessed at four-weekly intervals and, if patients remain symptomatic, as measured using the CAT, or experience an exacerbation, they have the option to step up to treatment with both drugs, ie, SFC twice daily and tiotropium once daily (TRIPLE therapy). The primary endpoint of the study will be the proportion of patients who are able to remain on the randomized therapy. No data are available. This paper summarizes the methodology of the study in advance of the study starting. The results of this study will help physicians to understand whether TRIPLE therapy is more effective than either treatment strategy alone in controlling symptoms and exacerbations in patients with moderate-to-severe COPD. It will also help physicians to understand the GOLD recommendation work in Japan.

Near-infrared bulk optical properties of goat wound tissue and human serum: consequences for an implantable optical glucose sensor.

PubMed

Aernouts, Ben; Sharma, Sandeep; Gellynck, Karolien; Vlaminck, Lieven; Cornelissen, Maria; Saeys, Wouter

2016-10-01

Near-infrared (NIR) spectroscopy offers a promising technological platform for continuous glucose monitoring in the human body. Moreover, these measurements could be performed in vivo with an implantable single-chip based optical sensor. However, a thin tissue layer may grow in the optical path of the sensor. As most biological tissues are highly scattering, they only allow a small fraction of the collimated light to pass, significantly reducing the light throughput. To quantify the effect of a thin tissue layer in the optical path, the bulk optical properties of serum and tissue samples grown on implanted dummy sensors were characterized using double integrating sphere and unscattered transmittance measurements. The estimated bulk optical properties were then used to calculate the light attenuation through a thin tissue layer. The combination band of glucose was found to be the better option, relative to the first overtone band, as the absorptivity of glucose molecules is higher, while the reduction in unscattered transmittance due to tissue growth is less. Additionally, as the wound tissue was found to be highly scattering, the unscattered transmittance of the tissue layer is expected to be very low. Therefore, a sensor configuration which measures the diffuse transmittance and/or reflectance instead was recommended. (a) Dummy sensor; (b) explanted dummy sensor in tissue lump; (c) removal of dummy sensor from tissue lump; and (d) 900 µm slices of tissue lump. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estimation of the auto frequency response function at unexcited points using dummy masses

NASA Astrophysics Data System (ADS)

Hosoya, Naoki; Yaginuma, Shinji; Onodera, Hiroshi; Yoshimura, Takuya

2015-02-01

If structures with complex shapes have space limitations, vibration tests using an exciter or impact hammer for the excitation are difficult. Although measuring the auto frequency response function at an unexcited point may not be practical via a vibration test, it can be obtained by assuming that the inertia acting on a dummy mass is an external force on the target structure upon exciting a different excitation point. We propose a method to estimate the auto frequency response functions at unexcited points by attaching a small mass (dummy mass), which is comparable to the accelerometer mass. The validity of the proposed method is demonstrated by comparing the auto frequency response functions estimated at unexcited points in a beam structure to those obtained from numerical simulations. We also consider random measurement errors by finite element analysis and vibration tests, but not bias errors. Additionally, the applicability of the proposed method is demonstrated by applying it to estimate the auto frequency response function of the lower arm in a car suspension.

Efficacy and Safety of Indacaterol/Glycopyrronium (IND/GLY) Versus Salmeterol/Fluticasone in Chinese Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease: The Chinese Cohort from the LANTERN Study.

PubMed

Zhong, Nanshan; Wang, Changzheng; Zhou, Xiangdong; Zhang, Nuofu; Humphries, Michael; Wang, Linda; Patalano, Francesco; Banerji, Donald

2016-12-01

Inhaled indacaterol/glycopyrronium fixed-dose combination (IND/GLY) is approved in over 80 countries, including the EU, Japan, Australia and Switzerland and the US. The LANTERN study evaluated the efficacy of IND/GLY compared with inhaled long-acting β 2 -agonist (LABA)/inhaled corticosteroid (ICS) or salmeterol/fluticasone (SFC) in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year. Here we present the efficacy and safety of IND/GLY versus SFC in the Chinese cohort from the LANTERN study. LANTERN was a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group study conducted in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year. The patients were randomized (1:1) to once-daily IND/GLY (110/50 μg) or twice-daily SFC (50/500 μg). The primary endpoint was non-inferiority of IND/GLY versus SFC in terms of trough FEV 1 . Of the total 744 patients randomized in the LANTERN study, 598 (80.4%) were from Mainland China and randomized to IND/GLY (n = 298) or SFC (n = 300), and 553 (92.5%) completed the study. IND/GLY showed superiority over SFC with a statistically significant and clinically meaningful improvement in trough FEV 1 , FEV 1 AUC 0-4h , peak FEV 1 and trough forced vital capacity (FVC) change from the baseline. Annualized rate of moderate or severe COPD exacerbations was significantly lower (43%) with IND/GLY compared with SFC (rate ratio: 0.57, p = 0.015). Overall, adverse events were lower for IND/GLY (34.6%) versus SFC (43.1%). IND/GLY was superior in achieving bronchodilation versus SFC in a Chinese subgroup of patients from this study. Clinicaltrials.gov identifier: NCT01709903.

A randomized trial of the efficacy of a new micronized formulation versus a standard formulation of isotretinoin in patients with severe recalcitrant nodular acne.

PubMed

Strauss, J S; Leyden, J J; Lucky, A W; Lookingbill, D P; Drake, L A; Hanifin, J M; Lowe, N J; Jones, T M; Stewart, D M; Jarratt, M T; Katz, I; Pariser, D M; Pariser, R J; Tschen, E; Chalker, D K; Rafal, E S; Savin, R P; Roth, H L; Chang, L K; Baginski, D J; Kempers, S; McLane, J; Eberhardt, D; Leach, E E; Bryce, G; Hong, J

2001-08-01

Isotretinoin is very frequently the drug of choice for the management of severe recalcitrant nodular acne. Recently, a new micronized and more bioavailable formulation of isotretinoin has been developed that permits once-daily administration in lower doses than usually used with standard isotretinoin (Accutane), regardless of whether it is taken with or without food. Our purpose was to determine whether micronized isotretinoin and standard isotretinoin are clinically equivalent. In this multicenter, double-blind, double-dummy study, 600 patients with severe recalcitrant nodular acne were treated with either 0.4 mg/kg of micronized isotretinoin once daily without food (n = 300) or 1.0 mg/kg per day of standard isotretinoin in two divided doses with food (n = 300). Lesion counts were monitored over 20 weeks. Both treatment groups in this well-controlled clinical trial experienced an equivalent reduction in the number of total nodules (facial plus truncal). In addition, an equivalent proportion of patients achieved 90% clearance of the total number of nodules. Both formulations had similar results for other efficacy variables. Once-daily use of the micronized and more bioavailable formulation of isotretinoin under fasted conditions is clinically equivalent to the standard twice-daily formulation under fed conditions in the treatment of severe recalcitrant nodular acne.

Non-absorbable antibiotics for managing intestinal gas production and gas-related symptoms.

PubMed

Di Stefano, M; Strocchi, A; Malservisi, S; Veneto, G; Ferrieri, A; Corazza, G R

2000-08-01

Simethicone, activated charcoal and antimicrobial drugs have been used to treat gas-related symptoms with conflicting results. To study the relationship between gaseous symptoms and colonic gas production and to test the efficacy of rifaximin, a new non-absorbable antimicrobial agent, on these symptoms. Intestinal gas production was measured by hydrogen (H2) and methane (CH4) breath testing after lactulose in 21 healthy volunteers and 34 functional patients. Only the 34 functional patients took part in a double-blind, double-dummy controlled trial, receiving, at random, rifaximin (400 mg b.d per 7 days), or activated charcoal (400 mg b.d per 7 days). The following parameters were evaluated at the start of the study and 1 and 10 days after therapy: bloating, abdominal pain, number of flatus episodes, abdominal girth, and cumulative breath H2 excretion. Hydrogen excretion was greater in functional patients than in healthy volunteers. Rifaximin, but not activated charcoal, led to a significant reduction in H2 excretion and overall severity of symptoms. In particular, in patients treated with rifaximin, a significant reduction in the mean number of flatus episodes and of mean abdominal girth was evident. In patients with gas-related symptoms the colonic production of H2 is increased. Rifaximin significantly reduces this production and the excessive number of flatus episodes.

Onset of action during on-demand treatment with maalox suspension or low-dose ranitidine for heartburn.

PubMed

Faaij, R A; Van Gerven, J M; Jolivet-Landreau, I; Masclee, A A; Vendrig, E M; Schoemaker, R C; Jacobs, L D; Cohen, A F

1999-12-01

To compare the onset of action of the local antacid Maalox and the systemic H2-antagonist ranitidine, during 'on demand' ambulant treatment of a single heartburn episode, using a randomized, parallel group, double-blind, double-dummy design. Subjects with self-perceived heartburn without known gastrointestinal disease or interfering treatments were selected with questionnaires. The study was performed unsupervised, whenever heartburn required medication. An electronic patient diary gave instructions when to take study medication, and provided visual analogue scales and five-item relief ratings for heartburn, at frequent time intervals activated by an alarm-clock. After a study of the natural history of heartburn and the feasibility of the study procedures in 23 patients, 49 subjects took Maalox and 45 ranitidine. Half of these experienced meaningful heartburn relief within 19 min after Maalox, and within 70 min after ranitidine. One hour after intake, the average heartburn relief score was 3.43 in the Maalox group and 3.04 in the ranitidine group (3 means 'slight improvement' and 4 'strong improvement'). Heartburn was similar in both groups after 3 h. Maalox provides faster relief of heartburn than ranitidine. Heartburn can be assessed frequently and reliably under ambulant conditions using an electronic patient diary.

Randomised double-blind comparison of simethicone with cisapride in functional dyspepsia.

PubMed

Holtmann, G; Gschossmann, J; Karaus, M; Fischer, T; Becker, B; Mayr, P; Gerken, G

1999-11-01

To compare the efficacy of simethicone with cisapride in patients with functional (non-ulcer) dyspepsia. After standardized diagnostic work-up and at least 6-days wash-out of medication, 177 patients with functional dyspepsia were enrolled; 173 of them (age 19-71 years) were randomized and treated using a double-dummy technique with simethicone (84 mg t.d.s.) or cisapride (10 mg t.d.s.). At baseline and after 2 and 4 weeks, the intensity of the symptoms was scored from 0 (absent) to 3 (severe) using a standardized symptom questionnaire. Efficacy of the treatment was judged by the patients as 'very good', 'good', 'moderate' or 'no effect'. A total of 166 patients completed the trial. After 2 and 4 weeks, 34% and 46% (respectively), of the patients treated with simethicone judged the improvement in symptoms to be excellent compared to 13% and 22% (respectively) of patients treated with cisapride (P < 0.01). After 2 weeks the difference in the improvement in the global symptom score was significantly better (Delta30.7%, P < 0.001) for simethicone than for cisapride, while this difference failed statistical significance after 4 weeks (Delta10.2%, P=0.11). In patients with functional dyspepsia, simethicone relieves symptoms during the first 2 weeks of treatment significantly better than cisapride.

Evaluation of the abuse potential of lorcaserin, a serotonin 2C (5-HT2C) receptor agonist, in recreational polydrug users.

PubMed

Shram, M J; Schoedel, K A; Bartlett, C; Shazer, R L; Anderson, C M; Sellers, E M

2011-05-01

Lorcaserin is a selective and potent serotonin 2C receptor subtype (5-HT(2C)) agonist under development for the treatment of obesity. This study assessed the drug's abuse potential on the basis of its pharmacological profile. For this purpose, a double-blind, double-dummy, placebo-controlled, randomized seven-way crossover study with single oral doses of lorcaserin (20, 40, and 60 mg), zolpidem (15 and 30 mg), ketamine (100 mg), and placebo was conducted in recreational polydrug users (N = 35). Subjective and objective measures were assessed up to 24 h after the dose. We found that zolpidem and ketamine had significantly higher peak scores relative to placebo on the primary measures as well as on most of the secondary measures. The subjective effects of a 20-mg dose of lorcaserin were similar to those of placebo, whereas supratherapeutic doses of lorcaserin were associated with significant levels of dislike by users as compared with placebo, zolpidem, and ketamine. Perceptual effects were minimal after administration of lorcaserin and significantly lower than after administration of either ketamine or zolpidem. The findings suggest that, at supratherapeutic doses, lorcaserin is associated with distinct, primarily negative, subjective effects and has low abuse potential.

Randomized, Double-Blinded, Double-Dummy, Active-Controlled, and Multiple-Dose Clinical Study Comparing the Efficacy and Safety of Mulberry Twig (Ramulus Mori, Sangzhi) Alkaloid Tablet and Acarbose in Individuals with Type 2 Diabetes Mellitus

PubMed Central

Chen, Yao

2016-01-01

Aims. To evaluate the efficacy and safety of mulberry twig alkaloid (SZ-A) tablet compared with acarbose in patients with type 2 diabetes. Methods. This clinical trial enrolled 38 patients who were randomized into two groups (SZ-A: 23; acarbose: 15) and were treated for 24 weeks. Patients and clinical trial staffs were masked to treatment assignment throughout the study. The primary outcome measures were glycated hemoglobin (HbA1c) and 1-hour and 2-hour postprandial and fasting plasma glucose levels from baseline to the end of treatment. Analysis included all patients who completed this study. Results. By the end of this study, HbA1c level in SZ-A group was decreased from baseline significantly (P < 0.001). No significant difference was found when compared with acarbose group (P = 0.652). Similarly, 1-hour and 2-hour postprandial plasma glucose levels in SZ-A group were decreased from baseline statistically (P < 0.05), without any significant differences compared with acarbose group (P = 0.748 and 0.558, resp.). The fasting plasma glucose levels were not significantly changed in both groups. One of 23 patients in SZ-A group (4.76%) and 5 of 15 patients in acarbose group (33.33%) suffered from gastrointestinal adverse events. Conclusions. Compared with acarbose, SZ-A tablet was effective and safe in glycemic control in patients with type 2 diabetes. PMID:27547230

A Comparison of Cilostazol and Pentoxifylline for Treating Intermittent Claudication

NASA Technical Reports Server (NTRS)

Dawson, David L.; Cutler, Bruce S.; Hiatt, William R.; Hobson, Robert W., II; Martin, John D.; Bortey, Enoch B.; Forbes, William P.; Strandness, D. Eugene, Jr.; Homick, Jerry L. (Technical Monitor)

1999-01-01

A randomized, double-blind, placebo-controlled, parallel-group, phase III multicenter trial was performed to evaluate the relative efficacy and safety of cilostazol and pentoxifylline. The study included 54 outpatient vascular clinics, including sites at Air Force, Veterans Affairs, tertiary care, and university hospitals in the United States. Of 922 consenting patients, 698 met the inclusion criteria, were randomized, and received treatment with either cilostazol 100 mg P0 twice a day, pentoxifylline 400 mg PO 3 times a day, or placebo. Treatment was double-dummy to ensure study blindness. Efficacy was primarily established by maximal walking distance (MWD), measured with constant-speed, variable-grade treadmill testing, assessed at baseline and at 4, 8, 12, 16, 20, and 24 weeks. Mean MWD of cilostazol-treated patients (n=227) was significantly improved at every visit compared with patients who received pentoxifylline (n=232) or placebo (n=239). After 24 weeks of cilostazol, mean MWD increased 53.9% (107.3 m) from baseline, and the effect had not plateaued. This was better (P < 0.001) than the 30.4% (64.4 m) MWD improvement with pentoxifylline. MWD improvement with pentoxifylline was similar (P = 0.82) to that of placebo (64.7 m). Deaths and serious adverse event rates were similar in each group. Common side effects included headache (27.8% with cilostazol, 11.2% with pentoxifylline, 11.7% with placebo), palpitations (17.2% with cilostazol, 2.2% with pentoxifylllne, 1.3% with placebo), and abnormal stools. Cilostazol was significantly better than pentoxifylline or placebo for increasing walking distances; pentoxifylline was no better than placebo.

Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study

PubMed Central

Sandrini, G; Cerbo, R; Del Bene, E; Ferrari, A; Genco, S; Grazioli, I; Martelletti, P; Nappi, G; Pinessi, L; Sarchielli, P; Tamburro, P; Uslenghi, C; Zanchin, G

2007-01-01

Aims and methods: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. Results: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57–1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82–1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. Conclusion: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf. PMID:17627707

Randomised clinical trial: a herbal preparation of myrrh, chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis--a double-blind, double-dummy study.

PubMed

Langhorst, J; Varnhagen, I; Schneider, S B; Albrecht, U; Rueffer, A; Stange, R; Michalsen, A; Dobos, G J

2013-09-01

The herbal treatment with myrrh, dry extract of chamomile flowers and coffee charcoal has anti-inflammatory and antidiarrhoeal potential and might benefit patients with UC. Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis (UC). To compare the efficacy of the two treatments in maintaining remission in patients with ulcerative colitis. We performed a randomised, double-blind, double-dummy study over a 12-month period in patients with UC. Primary endpoint was non-inferiority of the herbal preparation as defined by mean Clinical Colitis Activity Index (CAI-Rachmilewitz). Secondary endpoints were relapse rates, safety profile, relapse-free times, endoscopic activity and faecal biomarkers. A total of 96 patients (51 female) with inactive UC were included. Mean CAI demonstrated no significant difference between the two treatment groups in the intention-to-treat (P = 0.121) or per-protocol (P = 0.251) analysis. Relapse rates in total were 22/49 patients (45%) in the mesalazine treatment group and 25/47 patients (53%) in the herbal treatment group (P = 0.540). Safety profile and tolerability were good and no significant differences were shown in relapse-free time, endoscopy and faecal biomarkers. The herbal preparation of myrrh, chamomile extract and coffee charcoal is well tolerated and shows a good safety profile. We found first evidence for a potential efficacy non-inferior to the gold standard therapy mesalazine, which merits further study of its clinical usefulness in maintenance therapy of patients with ulcerative colitis. EudraCT-Number 2007-007928-18. © 2013 John Wiley & Sons Ltd.

Intravenous zanamivir or oral oseltamivir for hospitalised patients with influenza: an international, randomised, double-blind, double-dummy, phase 3 trial.

PubMed

Marty, Francisco M; Vidal-Puigserver, Joan; Clark, Carol; Gupta, Sandeep K; Merino, Esperanza; Garot, Denis; Chapman, Marianne J; Jacobs, Frédérique; Rodriguez-Noriega, Eduardo; Husa, Petr; Shortino, Denise; Watson, Helen A; Yates, Phillip J; Peppercorn, Amanda F

2017-02-01

Neuraminidase inhibitors are effective for the treatment of acute uncomplicated influenza. However, there is an unmet need for intravenous treatment for patients admitted to hospital with severe influenza. We studied whether intravenous zanamivir was a suitable treatment in this setting. In this international, randomised, double-blind, double-dummy, phase 3 trial, we recruited patients aged 16 years or older with severe influenza admitted to 97 hospitals from 26 countries. We randomly assigned patients (1:1:1 stratified by symptom onset ≤4 days or 5-6 days) to receive 300 mg or 600 mg intravenous zanamivir, or standard-of-care (75 mg oral oseltamivir) twice a day for 5-10 days; patients were followed up for 28 days. The randomisation schedule, including stratification, was generated using GlaxoSmithKline's RandAll software. Patients, site study staff, and sponsor were masked to study treatment. The primary endpoint was time to clinical response-a composite of vital sign stabilisation and hospital discharge-in the influenza-positive population. The trial was powered to show an improvement of 1·5 days or greater with 600 mg intravenous zanamivir. Pharmacokinetic, safety, and virology endpoints were also assessed. This trial is registered with ClinicalTrials.gov, number NCT01231620. Between Jan 15, 2011, and Feb 12, 2015, 626 patients were randomly assigned to receive 300 mg intravenous zanamivir (n=201), 600 mg intravenous zanamivir (n=209), or 75 mg oral oseltamivir (n=205) twice a day; 11 patients discontinued the study before receiving any study treatment. 488 (78%) of 626 patients had laboratory-confirmed influenza. Compared with a median time to clinical response of 5·14 days in the 600 mg intravenous zanamivir group, the median time to clinical response was 5·87 days (difference of -0·73 days, 95% CI -1·79 to 0·75; p=0·25) in the 300 mg intravenous zanamivir group and 5·63 days (difference of -0·48 days, 95% CI -2·11 to 0·97; p=0·39) in the oseltamivir group. Four patients with influenza A/H1N1pdm09 in the oseltamivir group developed H275Y resistance mutations. Adverse events were reported in 373 (61%) of treated patients and were similar across treatment groups; the most common adverse events (300 mg intravenous zanamivir, 600 mg intravenous zanamivir, oseltamivir) were diarrhoea (10 [5%], 15 [7%], 14 [7%]), respiratory failure (11 [5%], 14 [7%], 11 [5%]), and constipation (7 [3%], 13 [6%], 10 [5%]). 41 (7%) treated patients died during the study (15 [7%], 15 [7%], 11 [5%]); the most common causes of death were respiratory failure and septic shock. Time to clinical response to intravenous zanamivir dosed at 600 mg was not superior to oseltamivir or 300 mg intravenous zanamivir. All treatments had a similar safety profile in hospitalised patients with severe influenza. GlaxoSmithKline. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel Once-Daily Extended-Release Tacrolimus Versus Twice-Daily Tacrolimus in De Novo Kidney Transplant Recipients: Two-Year Results of Phase 3, Double-Blind, Randomized Trial.

PubMed

Rostaing, Lionel; Bunnapradist, Suphamai; Grinyó, Josep M; Ciechanowski, Kazimierz; Denny, Jason E; Silva, Helio Tedesco; Budde, Klemens

2016-04-01

1-year data from this trial showed the noninferiority of a novel once-daily extended-release tacrolimus (LCPT; Envarsus XR) to immediate-release tacrolimus (IR-Tac) twice daily after kidney transplantation. Final 24-month analysis of a 2-armed, parallel-group, randomized, double-blind, double-dummy, multicenter, phase 3 trial. 543 de novo kidney recipients randomly assigned to LCPT (n=268) or IR-Tac (n=275); 507 (93.4%) completed the 24-month study. LCPT tablets once daily at 0.17 mg/kg/d or IR-Tac twice daily at 0.1 mg/kg/d; subsequent doses were adjusted to maintain target trough ranges (first 30 days, 6-11 ng/mL; thereafter, 4-11 ng/mL). The intervention was 24 months; the study was double blinded for the entirety. Treatment failure (death, transplant failure, biopsy-proven acute rejection, or loss to follow up) within 24 months. Safety end points included adverse events, serious adverse events, new-onset diabetes, kidney function, opportunistic infections, and malignancies. Pharmacokinetic measures included total daily dose (TDD) of study drugs and tacrolimus trough levels. 24-month treatment failure was LCPT, 23.1%; IR-Tac, 27.3% (treatment difference, -4.14% [95% CI, -11.38% to +3.17%], well below the +10% noninferiority criterion defined for the primary 12-month end point). Subgroup analyses showed fewer treatment failures for LCPT versus IR-Tac among black, older, and female recipients. Safety was similar between groups. From month 1, TDD was lower for LCPT; the difference increased over time. At month 24, mean TDD for LCPT was 24% lower than for the IR-Tac group (P<0.001), but troughs were similar (means at 24 months: LCPT, 5.47 ± 0.17 ng/mL; IR-Tac, 5.8 ± 0.30 ng/mL; P=0.4). Trial participant eligibility criteria may limit the generalizability of results to the global population of de novo kidney transplant recipients. Results suggest that once-daily LCPT in de novo kidney transplantation has comparable efficacy and safety profile to that of IR-Tac. Lower TDD reflects LCPT's improved bioavailability and absorption. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Phase Diagram in a Random Mixture of Two Antiferromagnets with Competing Spin Anisotropies. I

NASA Astrophysics Data System (ADS)

Someya, Yoshiko

1981-12-01

The phase diagram of a random mixture of two antiferromagnets with competing spin anisotropies (A1-xBx) has been analyzed by extending the theory of Matsubara and Inawashiro, and Oguchi and Ishikawa. In the model assumed, the anisotropy energies are expressed by the anisotropic exchange interactions. According to this formulation, it has been shown that the concentration dependence of TN becomes a function of \\includegraphics{dummy.eps}, where P, Q=A, B; SP is a magnitude of P-spin, and JPQη is a η component of exchange integral between P- and Q-spin). Further, the phase boundary between an AF phase and an OAF (oblique antiferromagnetic) phase at T{=}0 K has been shown to be determined by α({\\equiv}SB/SA), if \\includegraphics{dummy.eps} are given. The obtained phase diagrams for Fe1-xCoxCl2, K2Mn1-xFexF4 and Fe1-xCoxCl2\\cdot2H2O are compared with the experimental ones.

A randomized, double-blind study of hydromorphone hydrochloride extended-release tablets versus oxycodone hydrochloride extended-release tablets for cancer pain: efficacy and safety in Japanese cancer patients (EXHEAL: a Phase III study of EXtended-release HydromorphonE for cAncer pain reLief).

PubMed

Inoue, Satoshi; Saito, Yoji; Tsuneto, Satoru; Aruga, Etsuko; Ide, Azusa; Kakurai, Yasuyuki

2017-01-01

In Japan, there are limited options for switching opioid analgesics. Hydromorphone is an opioid analgesic that is routinely used instead of morphine for cancer pain; however, it is not yet available in Japan. The aim of this study was to assess the efficacy and safety of hydromorphone (DS-7113b) extended-release tablets in opioid-naïve patients with cancer pain not relieved by non-opioid analgesics. This was a multicenter, randomized, double-blind, parallel-group trial. A double-dummy method was used for blinding. Each randomized subject received either hydromorphone extended-release tablets plus placebo oxycodone hydrochloride extended-release tablets 4 mg/day (n=88) or placebo hydromorphone extended-release tablets plus oxycodone hydrochloride extended-release tablets 10 mg/day (n=93) orally for 7 days (once-daily dosing for hydromorphone and twice-daily dosing for oxycodone). The doses were adjusted as necessary. Efficacy was evaluated by change in visual analog scale (VAS) score from baseline to completion of treatment. The between-group difference in least squares mean changes in VAS score from baseline to completion or discontinuation of treatment was -0.4 mm (95% CI -5.9 to 5 mm) by analysis of covariance where the baseline VAS score was used as a covariate. The upper limit of the 95% CI was below 10 mm, which was predefined as the noninferiority limit. This verified the noninferiority of hydromorphone tablets relative to oxycodone tablets. The incidence of adverse events was 80.7% (71 of 88) in the hydromorphone group and 83.7% (77 of 93) in the oxycodone group. The most common adverse events were nausea, vomiting, somnolence, diarrhea, and constipation, most of which are commonly observed with opioid analgesics. The efficacy and safety of hydromorphone extended-release tablets were equivalent to those of the oxycodone extended-release formulation.

The effect of systemic lipoic acid on hearing preservation after cochlear implantation via the round window approach: A guinea pig model.

PubMed

Chang, Mun Young; Gwon, Tae Mok; Lee, Ho Sun; Lee, Jun Ho; Oh, Seung Ha; Kim, Sung June; Park, Min-Hyun

2017-03-15

The present study aimed to evaluate the effects of systemic lipoic acid on hearing preservation after cochlear implantation. Twelve Dunkin-Hartley guinea pigs were randomly divided into two groups: the control group and the lipoic acid group. Animals in the lipoic acid group received lipoic acid intraperitoneally for 4 weeks. A sterilised silicone electrode-dummy was inserted through the round window to a depth of approximately 5 mm. The hearing level was measured using auditory brainstem responses (ABRs) prior to electrode-dummy insertion, and at 4 days and 1, 2, 3 and 4 weeks after electrode-dummy insertion. The threshold shift was defined as the difference between the pre-operative threshold and each of the post-operative thresholds. The cochleae were examined histologically 4 weeks after electrode-dummy insertion. Threshold shifts changed with frequency but not time. At 2kHz, ABR threshold shifts were statistically significantly lower in the lipoic acid group than the control group. At 8, 16 and 32kHz, there was no significant difference in the ABR threshold shift between the two groups. Histologic review revealed less intracochlear fibrosis along the electrode-dummy insertion site in the lipoic acid group than in the control group. The spiral ganglion cell densities of the basal, middle and apical turns were significantly higher in the lipoic acid group compared with the control group. Therefore, systemic lipoic acid administration appears to effectively preserve hearing at low frequencies in patients undergoing cochlear implantation. These effects may be attributed to the protection of spiral ganglion cells and prevention of intracochlear fibrosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Ex vivo optical characterization of in vivo grown tissues on dummy sensor implants using double integrating spheres measurement

NASA Astrophysics Data System (ADS)

Sharma, Sandeep; Goodarzi, Mohammad; Aernouts, Ben; Gellynck, Karolien; Vlaminck, Lieven; Bockstaele, Ronny; Cornelissen, Maria; Ramon, Herman; Saeys, Wouter

2014-05-01

Near infrared spectroscopy offers a promising technological platform for continuous glucose monitoring in the human body. NIR measurements can be performed in vivo with an implantable single-chip based optical NIR sensor. However, the application of NIR spectroscopy for accurate estimation of the analyte concentration in highly scattering biological systems still remains a challenge. For instance, a thin tissue layer may grow in the optical path of the sensor. As most biological tissues allow only a small fraction of the collimated light to pass, this might result in a large reduction of the light throughput. To quantify the effect of presence of a thin tissue layer in the optical path, the bulk optical properties of tissue samples grown on sensor dummies which had been implanted for several months in goats were characterized using Double Integrating Spheres and unscattered transmittance measurements. The measured values of diffuse reflectance, diffuse transmittance and collimated transmittance were used as input to Inverse Adding-Doubling algorithm to estimate the bulk optical properties of the samples. The estimates of absorption and scattering coefficients were then used to calculate the light attenuation through a thin tissue layer. Based on the lower reduction in unscattered transmittance and higher absorptivity of glucose molecules, the measurement in the combination band was found to be the better option for the implantable sensor. As the tissues were found to be highly forward scattering with very low unscattered transmittance, the diffuse transmittance measurement based sensor configuration was recommended for the implantable glucose sensor.

76 FR 31860 - Anthropomorphic Test Devices; Hybrid III Test Dummy, ES-2re Side Impact Crash Test Dummy

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-02

... [Docket No. NHTSA-2010-0146] RIN 2127-AK64 Anthropomorphic Test Devices; Hybrid III Test Dummy, ES-2re Side Impact Crash Test Dummy AGENCY: National Highway Traffic Safety Administration (NHTSA), Department..., 2008, concerning a 50th percentile adult male side crash test dummy called the ``ES-2re'' test dummy...

Pharmacodynamic interactions of a solid formulation of sodium oxybate and ethanol in healthy volunteers

PubMed Central

Pross, Nathalie; Patat, Alain; Vivet, Philippe; Bidaut, Michelle; Fauchoux, Nicolas

2015-01-01

Aim The pharmacologic effects of sodium oxybate (SO) have a number of similarities with those of alcohol. This study evaluated the pharmacodynamic interaction of SMO.IR (a solid immediate release formulation of SO) and alcohol (0.7 (males) or 0.57 (females) g kg–1 alcohol using 40% vodka). Methods In a randomized, double-blind, double-dummy, crossover trial, 24 healthy volunteers received randomly a) 2.25 g SMO.IR and placebo alcohol preparation, b) 2.25 g f SMO.IR and alcohol, c) 2.25 g SMO.IR matching placebo and alcohol and d) 2.25 g of SMO.IR matching placebo and placebo alcohol preparation. Objective and subjective cognitive parameters, adverse events and vital signs were assessed before, 15 and 165 min after treatment administration. Results Alcohol produced the expected cognitive impairment and the expected subjective sedation rapidly after intake (from 15 min). The objective effects of SMO.IR were much less pronounced than those of alcohol. The reverse was observed for subjective complaints, which were related to lesser stimulation and greater sedation. Nevertheless, 165 min after administration this sedation feeling was less with SMO.IR than with alcohol. There was a significant interaction between SMO.IR and alcohol at 15 min (i.e. increase in alertness and stimulation and decrease in sedation). In addition, an isolated mild decrease in digit vigilance accuracy occurred at 165 min post-dose after the combination. The co-administration of SMO.IR and alcohol was safe and well-tolerated. Conclusion SMO.IR and alcohol have distinct adverse effect profiles. The objective effects of SMO.IR are much less marked than those of alcohol. No deleterious interaction was observed. PMID:25782469

Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment

PubMed Central

Quintana, D S; Westlye, L T; Rustan, Ø G; Tesli, N; Poppy, C L; Smevik, H; Tesli, M; Røine, M; Mahmoud, R A; Smerud, K T; Djupesland, P G; Andreassen, O A

2015-01-01

Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ‘Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device. PMID:26171983

Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment.

PubMed

Quintana, D S; Westlye, L T; Rustan, Ø G; Tesli, N; Poppy, C L; Smevik, H; Tesli, M; Røine, M; Mahmoud, R A; Smerud, K T; Djupesland, P G; Andreassen, O A

2015-07-14

Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel 'Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.

Comparison of a step-down dose of once-daily ciclesonide with a continued dose of twice-daily fluticasone propionate in maintaining control of asthma.

PubMed

Knox, A; Langan, J; Martinot, J-B; Gruss, C; Häfner, D

2007-10-01

To compare a step-down approach in well-controlled asthma patients, as recommended by treatment guidelines, from fluticasone propionate 250 microg twice daily (FP250 BID), or equivalent, to ciclesonide 160 microg once daily (CIC160 OD) with continued FP250 BID treatment. Patients with well-controlled asthma prior to study entry were included in two identical, randomized, double-blind, double-dummy, parallel-group studies. After a 2-week run-in period with FP250 BID, patients were randomized to CIC160 OD (n = 58) or FP250 BID (n = 53) for 12 weeks. Primary endpoints were percentage of days with asthma control, asthma symptom-free days, rescue medication-free days and nocturnal awakening-free days. Secondary endpoints included lung function variables, asthma symptom scores, rescue medication use and asthma exacerbations. Safety variables were also recorded. Patients had >or= 97% of days with asthma control, 98% asthma symptom-free days and 100% of days free from rescue medication use and nocturnal awakenings in both treatment groups (median values). There were no significant between-treatment differences for any of the primary or secondary efficacy variables. Overall, 42 treatment-emergent adverse events (TEAEs) were reported in the CIC160 OD group and 49 TEAEs were reported in the FP250 BID group. There were no clinically relevant changes from baseline in the safety variables in either treatment group. Patients well controlled on FP250 BID, or equivalent, who were stepped down to CIC160 OD, maintained similar asthma control compared with patients who received continued treatment standardized to FP250 BID.

Beneficial Effects of Adjuvant Melatonin in Minimizing Oral Mucositis Complications in Head and Neck Cancer Patients Receiving Concurrent Chemoradiation.

PubMed

Onseng, Kittipong; Johns, Nutjaree Pratheepawanit; Khuayjarernpanishk, Thanut; Subongkot, Suphat; Priprem, Aroonsri; Hurst, Cameron; Johns, Jeffrey

2017-12-01

Oral mucositis is a major cause of pain and delayed cancer treatment leading to poor survival in head and neck cancer patients receiving concurrent chemoradiation. The study evaluated the effect of adjuvant melatonin on minimizing oral mucositis complications to reduce these treatment delays and interruptions. A randomized, double-blind, double dummy, placebo-controlled clinical trial. Ubon Ratchathani Cancer Hospital, Thailand. Thirty-nine head and neck cancer patients receiving concurrent chemoradiation (5 days/week of radiation plus chemotherapy three or six cycles). Patients were randomized to receive 20 mg melatonin gargle (or matched placebo) before each irradiation, and 20 mg melatonin capsules (or matched placebo) taken nightly during 7 weeks of concurrent chemoradiation. Endpoints were oral mucositis events (incidence and time to grade 3 mucositis or grade 2 xerostomia), pain medication consumption and quality of life (QOL). Melatonin group reported lower incidence of grade 3 oral mucositis (42% vs. 55%) and grade 2 xerostomia (20% vs. 21%); no statistical significance was detected. Melatonin regimen delayed onset of grade 3 mucositis (median 34 days vs. 50 days; p = 0.0318), allowing median time of 16 more patient visits before its onset and fewer interrupted treatments due to oral mucositis were reported (n = 1 vs. n = 5). There was no difference of grade 2 xerostomia (median 32 days vs. 50 days; p = 0.624). Morphine consumption was also reduced (median 57 mg vs. 0 mg; p = 0.0342), while QOL was comparable during the study period. Adjuvant melatonin delayed the onset of oral mucositis, which enables uninterrupted cancer treatment and reduced the amount of morphine used for pain treatment.

Intranasal abuse potential of an abuse-deterrent oxycodone formulation compared to oxycodone immediate release and placebo in nondependent, recreational opioid users.

PubMed

Setnik, Beatrice; Schoedel, Kerri; Bartlett, Cindy; Dick, Chris; Hakim, Nasrat; Geoffroy, Pierre

To assess the intranasal (IN) human abuse potential of ELI-200, a novel immediate-release (IR) oxycodone formulation containing sequestered naltrexone. Randomized, double-blind, double-dummy, active and placebo-controlled, five-way crossover study. Pharmacodynamics, safety, and pharmacokinetics (PKs) were evaluated for up to 36 hours postdose. Single site in Canada (INC Research Toronto). Healthy male and female nondependent recreational opioid users underwent a naloxone challenge and drug discrimination qualification test. Single IN dose of ground ELI-200 (30-mg oxycodone hydrochloride [HCl]/3-mg naltrexone HCl), crushed 30-mg oxycodone HCl IR (Roxicodone®), placebo, fixed placebo, and single oral dose of intact ELI-200 (30mg/3mg). Peak effect (E max ) for bipolar Drug Liking (0-100 point visual analog scale). Of the 44 randomized subjects, 37 completed all five treatment periods. All active treatments showed significantly higher (p<0.001) median Drug Liking E max relative to placebo. Significant reductions (p<0.001) in median Drug Liking [E max ] were observed for IN ELI-200 [56.0] compared to IN oxycodone IR [100.0]. Secondary positive or objective measures (High, Good Drug Effects, Overall Drug Liking, Take Drug Again, and maximum pupil constriction) showed significantly lower E max for IN ELI-200 (p<0.001) compared to IN oxycodone IR. IN administration of ELI-200 demonstrated significantly decreased effects on subjective and physiologic measures, and greater nasal irritation, compared to IN oxycodone IR. These findings, along with the PK profile of naltrexone, demonstrated that when ELI-200 capsules were ground and administered intranasally, the naltrexone component was rapidly released and conferred meaningful abuse-deterrent properties.

Concomitant or sequential administration of live attenuated japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine

PubMed Central

Nasveld, Peter E; Marjason, Joanne; Bennett, Sonya; Aaskov, John; Elliott, Suzanne; McCarthy, Karen; Kanesa-thasan, Niranjan; Feroldi, Emmanuel

2010-01-01

A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever (YF) vaccine (YF-17D strain; Stamaril®, Sanofi Pasteur) or administered sequentially. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE virus strains was determined using a 50% serum-dilution plaque reduction neutralization test (PRNT50). Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82–100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart. PMID:20864814

Bleeding pattern and cycle control of a low-dose transdermal contraceptive patch compared with a combined oral contraceptive: a randomized study.

PubMed

Merz, M; Kroll, R; Lynen, R; Bangerter, K

2015-02-01

The aim of this study was to investigate the bleeding pattern and cycle control of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a combined oral contraceptive (COC) containing 0.02 mg EE and 0.1 mg levonorgestrel (LNG). In this phase III, randomized, controlled, double-blind, double-dummy, multicenter trial, healthy women aged 18-45 years (smokers aged 18-35 years) received either the EE/GSD patch and a placebo tablet (n=171), or a placebo patch and the COC (n=175) for seven 28-day cycles. Bleeding control was assessed in two 90-day reference periods. Mean number of bleeding/spotting days was comparable across treatment groups in both reference periods (p>.05). Mean number of bleeding/spotting episodes was also comparable in reference period 1; however, there were fewer bleeding/spotting episodes for COC in reference period 2 (3.4 versus 3.1; p=.01). Mean length of bleeding/spotting episodes was comparable across treatment groups for both reference periods (p>.05). Withdrawal bleeding occurred consistently in both groups over the entire treatment period, but its absence was more common in the COC group in cycles 4 and 6 of reference period 2 (p<.01). Intracyclic bleeding was comparable between groups. Bleeding pattern and cycle control with the EE/GSD patch was comparable to an EE/LNG-containing COC. The findings suggest that bleeding patterns with the EE/GSD patch are similar to an EE/LNG-containing COC, except for absence of withdrawal bleeding, which was less common in patch users. The EE/GSD patch may constitute an additional contraceptive option for women. Copyright © 2015 Elsevier Inc. All rights reserved.

Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg.

PubMed

Wark, J D; Bensen, W; Recknor, C; Ryabitseva, O; Chiodo, J; Mesenbrink, P; de Villiers, T J

2012-02-01

Patients treated with intravenous zoledronic acid 5 mg for osteoporosis may experience post-dose influenza-like symptoms. Oral acetaminophen/paracetamol or ibuprofen administered 4 h post-infusion reduced the proportion of patients with increased oral temperature and worsening post-infusion symptom scores vs. placebo, thus providing an effective strategy for the treatment of such symptoms. Once-yearly intravenous zoledronic acid 5 mg is a safe and effective treatment for postmenopausal osteoporosis. This study assessed whether transient influenza-like post-dose symptoms associated with intravenous infusion of zoledronic acid can be reduced by post-dose administration of acetaminophen/paracetamol or ibuprofen. In an international, multicenter, randomized, double-blind, double-dummy parallel-group study, bisphosphonate-naïve postmenopausal women with osteopenia (n = 481) were randomized to receive zoledronic acid 5 mg + acetaminophen/paracetamol (n = 135), ibuprofen (n = 137) or placebo (n = 137), or placebo + placebo (n = 72). Acetaminophen/paracetamol and ibuprofen were administered every 6 h for 3 days beginning 4 h post-infusion. The proportion of patients with increased oral temperature (≥1°C above 37.5°C) and with worsening post-infusion symptom scores over 3 days was significantly lower in patients receiving ibuprofen (36.8% and 48.5%) or acetaminophen/paracetamol (37.3% and 46.3%) vs. those receiving placebo (63.5% and 75.9%, respectively; all p < 0.0001) compared with background rates of 11.1% and 16.7%, respectively, in the absence of any active treatment. Overall incidence of adverse events was comparable for patients receiving acetaminophen/paracetamol or ibuprofen. Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg.

Effect of gender and race on the week 48 findings in treatment-naïve, HIV-1-infected patients enrolled in the randomized, phase III trials ECHO and THRIVE.

PubMed

Hodder, S; Arasteh, K; De Wet, J; Gathe, J; Gold, J; Kumar, P; Mohapi, L; Short, W; Crauwels, H; Vanveggel, S; Boven, K

2012-08-01

A week 48 efficacy and safety analysis with respect to gender and race was conducted using pooled data from the phase III, double-blind, double-dummy efficacy comparison in treatment-naïve, HIV-infected subjects of TMC278 and efavirenz (ECHO) and TMC278 against HIV, in a once-daily regimen versus efavirenz (THRIVE) trials. Treatment-naïve, HIV-1-infected adults were randomized to receive rilpivirine (RPV; TMC278) 25 mg once a day (qd), or efavirenz (EFV) 600 mg qd, plus tenofovir/emtricitabine (ECHO) or tenofovir/emtricitabine, zidovudine/lamivudine or abacavir/lamivudine (THRIVE). A total of 1368 participants (76% male and 61% White, of those with available race data) were randomized and treated. No gender-related differences in response rate (percentage of patients with HIV-1 viral load < 50 HIV-1 RNA copies/mL, using an intent-to-treat, time-to-loss-of-virological-response algorithm) were observed (RPV: men, 85%; women, 83%; EFV: men, 82%; women, 83%). Response rates were lower in Black compared with Asian and White participants (RPV: 75% vs. 95% and 85%, respectively; EFV: 74% vs. 93% and 83%, respectively); this finding was mostly a result of higher discontinuation and virological failure rates in Black patients. Safety findings were generally similar across race and gender subgroups. However, nausea occurred more commonly in women than in men in both treatment groups. In men, diarrhoea was more frequent in the EFV group, and abnormal dreams/nightmares were more frequent in men in both the EFV and RPV groups. Overall response rates were high for both RPV and EFV. No gender differences were observed. However, response rates were lower among Black patients, regardless of treatment group. Gender appeared to influence the incidence of gastrointestinal adverse events and abnormal dreams/nightmares for both treatments. © 2012 British HIV Association.

Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel.

PubMed

Ahrendt, Hans-Joachim; Makalová, Dagmar; Parke, Susanne; Mellinger, Uwe; Mansour, Diana

2009-11-01

This study compared the bleeding pattern, cycle control and safety of an oral contraceptive (OC) comprising estradiol valerate/dienogest (E2V/DNG; administered using a dynamic dosing regimen) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG). E2V releases estradiol (E2), which is identical to endogenously produced 17beta-estradiol. This was a randomized, multicenter, double-blind, double-dummy trial lasting seven cycles in healthy women aged 18-50 years. Overall, 798 women were randomized and received allocated treatment (399 per group). There were significantly fewer bleeding/spotting days reported by women who received E2V/DNG than those who received EE/LNG [17.3+/-10.4 vs. 21.5+/-8.6, respectively, p<.0001, Reference Period 1 (Days 1-90); and 13.4+/-9.vs. 15.9+/-7.1, respectively, p<.0001, Reference Period 2 (Days 91-180)]. Through Cycles 1-7, the occurrence of scheduled withdrawal bleeding per cycle was 77.7-83.2% with E2V/DNG and 89.5-93.8% with EE/LNG (p<.0001 per cycle). The duration and intensity of scheduled withdrawal bleeding were reduced with E2V/DNG vs. EE/LNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5%-18.6%) and EE/LNG (9.9%-17.1%) (p>.05 per cycle). No unintended pregnancies occurred with E2V/DNG, but there was one unintended pregnancy with EE/LNG. Adverse drug reactions occurred in 10.0% and 8.5% of women taking E2V/DNG and EE/LNG, respectively. Overall, 79.4% of women were satisfied with E2V/DNG and 79.9% with EE/LNG. A novel OC composed of E2V/DNG is associated with an acceptable bleeding profile that is comparable to that of an EE-containing OC.

Mixed models approaches for joint modeling of different types of responses.

PubMed

Ivanova, Anna; Molenberghs, Geert; Verbeke, Geert

2016-01-01

In many biomedical studies, one jointly collects longitudinal continuous, binary, and survival outcomes, possibly with some observations missing. Random-effects models, sometimes called shared-parameter models or frailty models, received a lot of attention. In such models, the corresponding variance components can be employed to capture the association between the various sequences. In some cases, random effects are considered common to various sequences, perhaps up to a scaling factor; in others, there are different but correlated random effects. Even though a variety of data types has been considered in the literature, less attention has been devoted to ordinal data. For univariate longitudinal or hierarchical data, the proportional odds mixed model (POMM) is an instance of the generalized linear mixed model (GLMM; Breslow and Clayton, 1993). Ordinal data are conveniently replaced by a parsimonious set of dummies, which in the longitudinal setting leads to a repeated set of dummies. When ordinal longitudinal data are part of a joint model, the complexity increases further. This is the setting considered in this paper. We formulate a random-effects based model that, in addition, allows for overdispersion. Using two case studies, it is shown that the combination of random effects to capture association with further correction for overdispersion can improve the model's fit considerably and that the resulting models allow to answer research questions that could not be addressed otherwise. Parameters can be estimated in a fairly straightforward way, using the SAS procedure NLMIXED.

Reconstituting factor concentrates: Defining Evidence of Coaching Non-Experts (DEVICE) in haemophilia--a prospective randomized feasibility study.

PubMed

Bidlingmaier, C; Kurnik, K; Hölscher, G; Kappler, M

2007-09-01

The introduction of new needleless devices as demanded by the US Department of Labor Occupational Safety and Health Administration (OSHA) has caused problems with the reconstitution of antihaemophilic factor in emergency situations. Our aim therefore was to evaluate the feasibility of a needleless device for reconstitution of antihaemophilic factor for non-haemophilia experts and to define evidence of the need for coaching these physicians via providing two additional photographs illustrating the two key points of the factor reconstitution process. Twenty-eight physicians of a tertiary care university children's hospital were randomized into two groups, either with no further explanation of the reconstitution device or with two additional photographs, showing the two key steps of the procedure. Reconstitution of dummy-factor concentrate was video-taped and evaluated by a blinded helper. Main outcome measure was the successful reconstitution of dummy-factor concentrate and procedure failure respectively. Of the group without explanation of the reconstitution device, only two of 14 physicians were able to reconstitute the dummy-factor concentrate. Of the group receiving two photographs, nine of 14 completed the task successfully (P = 0.0068). The needleless device is not self explaining to non-haemophilia physicians involved in emergency services. Coaching via short to the point instructions as provided by simple visual educational material therefore is crucial to enable these physicians to resolve the expensive emergency drug quickly and correctly. Companies concerned with the production of any devices to dissolve drugs, especially for treatment of rare diseases as haemophilia, therefore should take measures to simplify therapy.

Robust boundary treatment for open-channel flows in divergence-free incompressible SPH

NASA Astrophysics Data System (ADS)

Pahar, Gourabananda; Dhar, Anirban

2017-03-01

A robust Incompressible Smoothed Particle Hydrodynamics (ISPH) framework is developed to simulate specified inflow and outflow boundary conditions for open-channel flow. Being purely divergence-free, the framework offers smoothed and structured pressure distribution. An implicit treatment of Pressure Poison Equation and Dirichlet boundary condition is applied on free-surface to minimize error in velocity-divergence. Beyond inflow and outflow threshold, multiple layers of dummy particles are created according to specified boundary condition. Inflow boundary acts as a soluble wave-maker. Fluid particles beyond outflow threshold are removed and replaced with dummy particles with specified boundary velocity. The framework is validated against different cases of open channel flow with different boundary conditions. The model can efficiently capture flow evolution and vortex generation for random geometry and variable boundary conditions.

Blocking and reversing hepatic fibrosis in patients with chronic hepatitis B treated by traditional Chinese medicine (tablets of biejia ruangan or RGT): study protocol for a randomized controlled trial.

PubMed

Qu, Jianhui; Yu, Zujiang; Li, Qin; Chen, Yongping; Xiang, Dedong; Tan, Lin; Lei, Chunliang; Bai, Wenlin; Li, Hongyan; Shang, Qinghua; Chen, Liang; Hu, Xiaoyu; Lu, Wei; Li, Zhiqin; Chen, Da; Wang, Xiaodong; Zhang, Changjiang; Xiao, Guangming; Qi, Xun; Chen, Jing; Zhou, Li; Chen, Guofeng; Li, Yonggang; Zeng, Zhen; Rong, Guanghua; Dong, Zheng; Chen, Yan; Lou, Min; Wang, Chunping; Lu, Yinying; Zhang, Cuihong; Yang, Yongping

2014-11-10

Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC) and ultimately liver-related death. Although oral antiviral therapy for patients with CHB reduces the risk of such complications, once cirrhosis is established, the benefits of antiviral therapy are not robustly demonstrated. According to traditional Chinese medicine (TCM), some Chinese herbal medicines promote blood circulation and soften hard masses, and therefore they may block and reverse hepatic fibrosis. The aim of this study is to evaluate the effects of TCM tablets of the compound biejia ruangan (RGT) administered for fibrosis, and entecavir (ETV), on the development of HCC in patients with CHB or hepatitis B virus (HBV)-related compensated cirrhosis. This multicenter, centrally randomized, double-blind, placebo-controlled, parallel-group study is planned to complete within 5 years. For the study, 1,000 with CHB or HBV-related compensated cirrhosis are randomly assigned in a 1:1 ratio to a treatment group (0.5 mg ETV once daily; 2 g RGT three times daily) or a control group (0.5 mg ETV once daily; 2 g RGT dummy agent three times daily). The primary end points are the development of HCC and liver-related death. Secondary end points include disease progression and overall survival. Although antiviral therapy can achieve sustained suppression of HBV replication, thereby preventing cirrhosis, patients with CHB treated with nucleos(t)ide analogs (NUCs) retain a higher risk for HCC compared with patients with inactive disease. Although previous clinical trials with RGT have confirmed the efficacy of blocking and reversing hepatic fibrosis in patients with CHB or compensated cirrhosis, the long-term risk for HCC or disease progression in these patients treated with combination of RGT and NUCs compared with NUCs alone is unclear. Therefore, it is necessary to investigate the effects of the RGT blockade and reversal of hepatic fibrosis on the development of HCC in patients with CHB or HBV-related compensated cirrhosis in large, prospective, multicenter, double-blind, randomized, controlled trials in China. ClinicalTrials.gov Identifier: NCT01965418. Date registered: 17 October 2013.

Challenges of correlating pH change with relief of clinical symptoms in gastro esophageal reflux disease: a phase III, randomized study of Zegerid versus Losec.

PubMed

Walker, Dave; Ng Kwet Shing, Richard; Jones, Deborah; Gruss, Hans-Jurgen; Reguła, Jarosław

2015-01-01

Zegerid (on demand immediate-release omeprazole and sodium bicarbonate combination therapy) has demonstrated earlier absorption and more rapid pH change compared with Losec (standard enteric coated omeprazole), suggesting more rapid clinical relief of heartburn. This Phase III, multicenter, double-blind, double-dummy, randomized study assessed the clinical superiority of Zegerid versus Losec for rapid relief of heartburn associated with gastro-esophageal reflux disease (GERD). Patients with a history of frequent (2 3 days/week) uncomplicated GERD, were randomized to receive Zegerid (20 mg) or Losec (20 mg) with corresponding placebo. Study medication was self-administered on the first episode of heartburn, and could be taken for up to 3 days within a 14 day study period. Heartburn severity was self assessed up to 180 minutes post dose (9 point Likert scale). Primary endpoint was median time to sustained response (≥3 point reduction in heartburn severity for ≥45 minutes). Of patients randomized to Zegerid (N=122) or Losec (N=117), 228/239 had recorded ≥1 evaluable heartburn episodes and were included in the modified intent-to-treat population. No significant between-group differences were observed for median time to sustained response (60.0 vs. 52.2 minutes, Zegerid [N=117] and Losec [N=111], respectively), sustained partial response (both, 37.5 minutes) and sustained total relief (both, 105 minutes). Significantly more patients treated with Zegerid reached sustained total relief within 0-30 minutes post dose in all analysis sets (p<0.05). Both treatments were well tolerated and did not raise any safety concerns. Superiority of Zegerid over Losec for rapid heartburn relief was not demonstrated; both treatments were equally effective however the rapid onset of action of Losec was unexpected. Factors, including aspects of study design may have contributed to this. This study supports previously reported difficulty in correlating intra-gastric pH change with clinical effect in GERD therapy, highlighting the significance of several technical considerations for studies of this type. ClinicalTrials.gov NCT01493089.

A randomized trial of the efficacy and safety of sequential intravenous/oral moxifloxacin monotherapy versus intravenous piperacillin/tazobactam followed by oral amoxicillin/clavulanate for complicated skin and skin structure infections.

PubMed

Gyssens, Inge C; Dryden, Matthew; Kujath, Peter; Nathwani, Dilip; Schaper, Nicolaas; Hampel, Barbara; Reimnitz, Peter; Alder, Jeff; Arvis, Pierre

2011-11-01

The primary aim of the RELIEF study was to evaluate the efficacy and safety of two sequential intravenous (iv)/oral regimens: moxifloxacin iv/oral versus piperacillin/tazobactam (TZP) iv followed by oral amoxicillin/clavulanate (AMC). The study had a prospective, randomized, double-dummy, double-blind, multicentre design. Patients ≥18 years were prospectively stratified according to complicated skin and skin structure infection (cSSSI) subtype/diagnosis (major abscess, diabetic foot infection, wound infection or infected ischaemic ulcer), surgical intervention and severity of illness. Diagnoses and disease severity were based on predetermined criteria, documented by repeated photographs, and confirmed by an independent data review committee. Patients were randomized to receive either 400 mg of moxifloxacin iv once daily followed by 400 mg of moxifloxacin orally once daily or 4.0/0.5 g of TZP iv thrice daily followed by 875/125 mg of AMC orally twice daily for 7-21 days. The primary efficacy variable was clinical response at test of cure (TOC) for the per-protocol (PP) population. Clinical efficacy was assessed by the data review committee based on repeated photographs and case descriptions. Clinical trials registry number: NCT 00402727. A total of 813 patients were randomized. Clinical success rates at TOC were similar for moxifloxacin and TZP-AMC in the PP [320/361 (88.6%) versus 275/307 (89.6%), respectively; P = 0.758] and intent-to-treat (ITT) [350/426 (82.2%) versus 305/377 (80.9%), respectively; P = 0.632] populations. Thus, moxifloxacin was non-inferior to TZP-AMC. Bacteriological success rates were high in both treatment arms [moxifloxacin: 432/497 (86.9%) versus TZP-AMC: 370/429 (86.2%), microbiologically valid (MBV) population]. Moxifloxacin was non-inferior to TZP-AMC at TOC in both the MBV and the ITT populations. Both treatments were well tolerated. Once-daily iv/oral moxifloxacin monotherapy was clinically and bacteriologically non-inferior to iv TZP thrice daily followed by oral AMC twice daily in patients with cSSSIs.

A randomized trial of the efficacy and safety of sequential intravenous/oral moxifloxacin monotherapy versus intravenous piperacillin/tazobactam followed by oral amoxicillin/clavulanate for complicated skin and skin structure infections

PubMed Central

Gyssens, Inge C.; Dryden, Matthew; Kujath, Peter; Nathwani, Dilip; Schaper, Nicolaas; Hampel, Barbara; Reimnitz, Peter; Alder, Jeff; Arvis, Pierre

2011-01-01

Objectives The primary aim of the RELIEF study was to evaluate the efficacy and safety of two sequential intravenous (iv)/oral regimens: moxifloxacin iv/oral versus piperacillin/tazobactam (TZP) iv followed by oral amoxicillin/clavulanate (AMC). Patients and methods The study had a prospective, randomized, double-dummy, double-blind, multicentre design. Patients ≥18 years were prospectively stratified according to complicated skin and skin structure infection (cSSSI) subtype/diagnosis (major abscess, diabetic foot infection, wound infection or infected ischaemic ulcer), surgical intervention and severity of illness. Diagnoses and disease severity were based on predetermined criteria, documented by repeated photographs, and confirmed by an independent data review committee. Patients were randomized to receive either 400 mg of moxifloxacin iv once daily followed by 400 mg of moxifloxacin orally once daily or 4.0/0.5 g of TZP iv thrice daily followed by 875/125 mg of AMC orally twice daily for 7–21 days. The primary efficacy variable was clinical response at test of cure (TOC) for the per-protocol (PP) population. Clinical efficacy was assessed by the data review committee based on repeated photographs and case descriptions. Clinical trials registry number: NCT 00402727. Results A total of 813 patients were randomized. Clinical success rates at TOC were similar for moxifloxacin and TZP–AMC in the PP [320/361 (88.6%) versus 275/307 (89.6%), respectively; P = 0.758] and intent-to-treat (ITT) [350/426 (82.2%) versus 305/377 (80.9%), respectively; P = 0.632] populations. Thus, moxifloxacin was non-inferior to TZP–AMC. Bacteriological success rates were high in both treatment arms [moxifloxacin: 432/497 (86.9%) versus TZP–AMC: 370/429 (86.2%), microbiologically valid (MBV) population]. Moxifloxacin was non-inferior to TZP–AMC at TOC in both the MBV and the ITT populations. Both treatments were well tolerated. Conclusions Once-daily iv/oral moxifloxacin monotherapy was clinically and bacteriologically non-inferior to iv TZP thrice daily followed by oral AMC twice daily in patients with cSSSIs. PMID:21896561

A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: the Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) trial.

PubMed

Binkley, Neil; Bolognese, Michael; Sidorowicz-Bialynicka, Anna; Vally, Tasneem; Trout, Richard; Miller, Colin; Buben, Christine E; Gilligan, James P; Krause, David S

2012-08-01

The Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) study was a randomized, double-blind, double-dummy, active- and placebo-controlled, multiple-dose, phase 3 study to assess the efficacy and safety of oral recombinant calcitonin for treatment of postmenopausal osteoporosis. A total of 565 women age 46 to 86 (mean 66.5) years were randomized (4:3:2) to receive oral recombinant salmon calcitonin (rsCT) tablets (0.2  mg/d) plus placebo nasal spray, synthetic salmon calcitonin (ssCT) nasal spray (200 IU/d) plus placebo tablets, or placebo (placebo tablets plus placebo nasal spray), respectively for 48 weeks. All women received calcium (≥1000  mg/d) and vitamin D (800 IU/d). Women randomized to oral rsCT had a mean ± SD percent increase from baseline in lumbar spine bone mineral density (BMD) (1.5% ± 3.2%) that was greater than those randomized to ssCT nasal spray (0.78% ± 2.9%) or placebo (0.5% ± 3.2%). Lumbar spine BMD change in those receiving nasal calcitonin did not differ from placebo. Oral rsCT treatment also resulted in greater improvements in trochanteric and total proximal femur BMD than ssCT nasal spray. Reductions in bone resorption markers with oral rsCT were greater than those observed in ssCT nasal spray or placebo recipients. Approximately 80% of subjects in each treatment group experienced an adverse event, the majority of which were mild or moderate in intensity. Gastrointestinal system adverse events were reported by nearly one-half of women in all treatment groups and were the principal reason for premature withdrawals. Less than 10% of women experienced a serious adverse event and no deaths occurred. Overall, oral rsCT was superior to nasal ssCT and placebo for increasing BMD and reducing bone turnover. Oral rsCT was safe and as well tolerated as ssCT nasal spray or placebo. Oral calcitonin may provide an additional treatment alternative for women with postmenopausal osteoporosis. Copyright © 2012 American Society for Bone and Mineral Research.

Challenges of Correlating pH Change with Relief of Clinical Symptoms in Gastro Esophageal Reflux Disease: A Phase III, Randomized Study of Zegerid versus Losec

PubMed Central

Walker, Dave; Ng Kwet Shing, Richard; Jones, Deborah; Gruss, Hans-Jurgen; Reguła, Jarosław

2015-01-01

Background Zegerid (on demand immediate-release omeprazole and sodium bicarbonate combination therapy) has demonstrated earlier absorption and more rapid pH change compared with Losec (standard enteric coated omeprazole), suggesting more rapid clinical relief of heartburn. This Phase III, multicenter, double-blind, double-dummy, randomized study assessed the clinical superiority of Zegerid versus Losec for rapid relief of heartburn associated with gastro-esophageal reflux disease (GERD). Methods Patients with a history of frequent (2 3 days/week) uncomplicated GERD, were randomized to receive Zegerid (20mg) or Losec (20mg) with corresponding placebo. Study medication was self-administered on the first episode of heartburn, and could be taken for up to 3 days within a 14 day study period. Heartburn severity was self assessed up to 180 minutes post dose (9 point Likert scale). Primary endpoint was median time to sustained response (≥3 point reduction in heartburn severity for ≥45 minutes). Results Of patients randomized to Zegerid (N=122) or Losec (N=117), 228/239 had recorded ≥1 evaluable heartburn episodes and were included in the modified intent-to-treat population. No significant between-group differences were observed for median time to sustained response (60.0 vs. 52.2 minutes, Zegerid [N=117] and Losec [N=111], respectively), sustained partial response (both, 37.5 minutes) and sustained total relief (both, 105 minutes). Significantly more patients treated with Zegerid reached sustained total relief within 0–30 minutes post dose in all analysis sets (p<0.05). Both treatments were well tolerated and did not raise any safety concerns. Conclusions Superiority of Zegerid over Losec for rapid heartburn relief was not demonstrated; both treatments were equally effective however the rapid onset of action of Losec was unexpected. Factors, including aspects of study design may have contributed to this. This study supports previously reported difficulty in correlating intra-gastric pH change with clinical effect in GERD therapy, highlighting the significance of several technical considerations for studies of this type. Trial registration ClinicalTrials.gov NCT01493089 PMID:25706883

3g mesalazine granules are superior to 9mg budesonide for achieving remission in active ulcerative colitis: a double-blind, double-dummy, randomised trial.

PubMed

Gross, Volker; Bunganic, Ivan; Belousova, Elena A; Mikhailova, Tatyana L; Kupcinskas, Limas; Kiudelis, Gediminas; Tulassay, Zsolt; Gabalec, Libor; Dorofeyev, Andrey E; Derova, Jelena; Dilger, Karin; Greinwald, Roland; Mueller, Ralph

2011-04-01

Budesonide may be an effective therapy for mild-to-moderately active ulcerative colitis (UC). This study aimed to demonstrate non-inferiority for oral 9mg budesonide once daily (OD) versus 3g mesalazine granules OD. This was an eight-week randomised, double-blind, double-dummy, multicentre study in which patients with mild-to-moderately active UC, defined as Clinical Activity Index (CAI) ≥6 and Endoscopic Index (EI) ≥4, received budesonide (Budenofalk® 3mg capsules×3) or mesalazine (Salofalk® 1000mg granules×3). The primary endpoint was clinical remission at week 8 (CAI ≤4 with stool frequency and rectal bleeding subscores of "0"). 343 patients were randomised (177 budesonide, 166 mesalazine). Fewer patients achieved the primary endpoint with budesonide versus mesalazine (70/177 [39.5%] versus 91/166 [54.8%]) with a difference in proportions of -15.3% (95% CI [-25.7%, -4.8%]; p=0.520 for non-inferiority). The median time to first resolution of symptoms was 14.0 days (budesonide) and 11.0 days (mesalazine) (hazard ratio 1.19; 95% CI [0.94, 1.51]). Mucosal healing was observed in 54/177 (30.5%) budesonide patients versus 65/166 (39.2%) mesalazine patients, a difference of -8.6% (95% CI [-18.7%, 1.4%]; p=0.093). The incidences of adverse events (budesonide 26.6%, mesalazine 25.3%) and serious adverse events (budesonide 1.7%, mesalazine 1.2%) were similar. Once-daily 3g mesalazine administered as granules is superior to 9mg budesonide OD administered as capsules for achieving remission in mild-to-moderately active UC. However, it is noteworthy that remission of UC was attained in about 40% of budesonide-treated patients with a rapid onset of resolution. Copyright © 2010. Published by Elsevier B.V.

75 FR 5931 - Anthropomorphic Test Devices; Hybrid III Test Dummy, ES-2re Side Impact Crash Test Dummy

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-05

... [Docket No. NHTSA-2009-0194] RIN 2127-AK64 Anthropomorphic Test Devices; Hybrid III Test Dummy, ES-2re Side Impact Crash Test Dummy AGENCY: National Highway Traffic Safety Administration (NHTSA), Department... adopted specifications and qualification requirements for a new crash test dummy called the ``ES- 2re...

Effects of Tadalafil Once-Daily or On-Demand vs Placebo on Return to Baseline Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy--Results from a Randomized Controlled Trial (REACTT).

PubMed

Mulhall, John P; Brock, Gerald; Oelke, Matthias; Fode, Mikkel; Probst, Kai A; Henneges, Carsten; d'Anzeo, Gianluca; Rossi, Andrea; Büttner, Hartwig

2016-04-01

The multicenter, randomized, double-blind, double-dummy, placebo-controlled REACTT trial suggested that treatment with tadalafil once daily (OaD) started early after bilateral nerve-sparing radical prostatectomy (nsRP) for prostate cancer may contribute to erectile function (EF)-recovery, which was predefined as achieving an International Index of Erectile Function (IIEF)-EF score ≥22. Here, we report descriptive post-hoc analyses, using the more strict definition for EF-recovery of returning back to the pre-surgery IIEF-EF-level ("back-to-baseline analysis"). REACTT included 422 men <68 years with adenocarcinoma of the prostate and preoperative IIEF-EF ≥22 who underwent nsRP at 50 centers from 9 European countries and Canada. Patients were randomized post-nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil 5 mg OaD (n = 139), tadalafil 20 mg on-demand (pro-re-nata, PRN; n = 142), or placebo (n = 141), followed by 6-week drug-free washout (DFW) and 3-month open-label tadalafil OaD treatment (OLT). Proportion of patients returning to their preoperative IIEF-EF category (22-25 or ≥26) at the end of DBT, DFW, and OLT. Overall, 92.4% of patients had pre-surgery (baseline) IIEF-EF scores ≥26 (tadalafil OaD 94.2%, PRN 91.6%, placebo 91.5%), 7.4% had IIEF-EF 22-25. At the end of DBT, 22.3% of patients on tadalafil OaD had achieved "back-to-baseline" IIEF-EF, compared with 11.3% on tadalafil PRN and 7.8% on placebo. Of all 58 patients "back-to-baseline" at the end of DBT, only 1 PRN-group patient had started from a baseline IIEF-EF <26. The treatment-group difference at the end of DBT was not maintained after DFW. After 3 months of OLT with tadalafil OaD, the proportion of patients with "back-to-baseline" IIEF-EF had almost doubled in all 3 groups. Changing the definition for EF-recovery from IIEF-EF ≥22 to the more strict definition of "returning back-to-baseline IIEF-EF" had no major impact. Tadalafil OaD started early after nsRP improved drug-assisted EF, but had no effect on unassisted EF following treatment cessation after 9 months. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

A randomized placebo-controlled trial of simethicone and cisapride for the treatment of patients with functional dyspepsia.

PubMed

Holtmann, G; Gschossmann, J; Mayr, P; Talley, N J

2002-09-01

To compare the efficacy of simethicone with placebo and the prokinetic cisapride in patients with functional dyspepsia. One hundred and eighty-five patients with functional dyspepsia were randomized and treated in a double-dummy technique with simethicone (105 mg t.d.s.), cisapride (10 mg t.d.s.) or placebo (t.d.s.). The primary outcome measure was the O'Brien global measure of the patients' rating of 10 upper gastrointestinal symptoms (graded as absent = 0, moderate = 1, severe = 2 or very severe = 3). Outcome measures were assessed at baseline and after 2, 4 and 8 weeks of treatment (intention-to-treat). At 2, 4 and 8 weeks, treatment with simethicone and cisapride yielded significantly (all P values < 0.0001) better improvement of symptoms compared to placebo. Simethicone was significantly better than cisapride after 2 weeks (P = 0.0007), but the differences were not statistically significant after 4 and 8 weeks. Patients treated with simethicone judged the efficacy of their treatment as very good in 46% of cases, compared to 15% and 16% receiving cisapride and placebo, respectively. Simethicone and cisapride were significantly better than placebo for symptom control in patients with functional dyspepsia after 2, 4 and 8 weeks of treatment. Simethicone was also superior to the prokinetic cisapride in the first 2 weeks of treatment.

Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball'-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers

PubMed Central

Greenwald, Mark K; Lundahl, Leslie H; Steinmiller, Caren L

2010-01-01

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball'-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); ‘speedball' (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy. PMID:20881947

Oral paracetamol and/or ibuprofen for treating pain after soft tissue injuries: Single centre double-blind, randomised controlled clinical trial

PubMed Central

Lo, Ronson S. L.; Leung, Yuk Ki; Leung, Ling Yan; Man, S. Y.; Woo, W. K.; Cattermole, Giles N.; Rainer, Timothy H.

2018-01-01

Background Soft tissue injuries commonly present to the emergency department (ED), often with acute pain. They cause significant suffering and morbidity if not adequately treated. Paracetamol and ibuprofen are commonly used analgesics, but it remains unknown if either one or the combination of both is superior for pain control. Objectives To investigate the analgesic effect of paracetamol, ibuprofen and the combination of both in the treatment of soft tissue injury in an ED, and the side effect profile of these drugs. Methods Double-blind, double dummy, placebo-controlled randomised controlled trial. 782 adult patients presenting with soft tissue injury without obvious fractures attending the ED of a university hospital in the New Territories of Hong Kong were recruited. Patients were randomised using a random number table into three parallel arms of paracetamol only, ibuprofen only and a combination of paracetamol and ibuprofen in a 1:1:1 ratio. The primary outcome measure was pain score at rest and on activity in the first 2 hours and first 3 days. Data was analysed on an intention to treat basis. Results There was no statistically significant difference in pain score in the initial two hours between the three groups, and no clinically significant difference in pain score in the first three days. Conclusion There was no difference in analgesic effects or side effects observed using oral paracetamol, ibuprofen or a combination of both in patients with mild to moderate pain after soft tissue injuries attending the ED. Trial registration The study is registered with ClinicalTrials.gov (no. NCT00528658). PMID:29408866

Comparison of efficacy between buprenorphine and tramadol in the detoxification of opioid (heroin)-dependent subjects.

PubMed

Chawla, Jatinder Mohan; Pal, Hemraj; Lal, Rakesh; Jain, Raka; Schooler, Nina; Balhara, Yatan Pal Singh

2013-01-01

Tramadol is a synthetic opiate and a centrally acting weak m-opioid receptor agonist. The potential advantages of tramadol include ease of administration, low abuse potential, and being nonscheduled. This study compared tramadol and buprenorphine for controlling withdrawal symptoms in patients with opioid dependence syndrome. Consenting male subjects between 20 and 45 years of age who fulfilled the ICD-10-DCR criteria for opiate dependence syndrome were randomly assigned in a double-blind, double-dummy placebo-controlled trial for detoxification. Those with multiple drug dependence, abnormal cardiac, renal and hepatic functions, psychosis, or organic mental illness were excluded. Assessments included Subjective Opiate Withdrawal Scale (SOWS), Objective Opiate Withdrawal Scale (OOWS), Visual Analog Scale (VAS), and Side Effect Check List. Subjects were evaluated daily and study duration was 10 days. Sixty two subjects were enrolled. The mean SOWS and OOWS and VAS were significantly lower in the buprenorphine group on second and third day of detoxification as compared to the tramadol group. Although the retention rate was higher for buprenorphine group throughout the study, when compared with tramadol the difference was not significant on any day. Three subjects in the tramadol group had seizures. Tramadol was found to have limited detoxification efficacy in moderate to severe opioid withdrawal and substantial risk of seizures as compared to buprenorphine. Further studies are warranted to examine its efficacy in mild opioid withdrawal symptoms and its potential use in outpatient settings where its administration advantages may be valuable.

Factors in Variability of Serial Gabapentin Concentrations in Elderly Patients with Epilepsy.

PubMed

Conway, Jeannine M; Eberly, Lynn E; Collins, Joseph F; Macias, Flavia M; Ramsay, R Eugene; Leppik, Ilo E; Birnbaum, Angela K

2017-10-01

To characterize and quantify the variability of serial gabapentin concentrations in elderly patients with epilepsy. This study included 83 patients (age ≥ 60 yrs) from an 18-center randomized double-blind double-dummy parallel study from the Veterans Affairs Cooperative 428 Study. All patients were taking 1500 mg/day gabapentin. Within-person coefficient of variation (CV) in gabapentin concentrations, measured weekly to bimonthly for up to 52 weeks, then quarterly, was computed. Impact of patient characteristics on gabapentin concentrations (linear mixed model) and CV (linear regression) were estimated. A total of 482 gabapentin concentration measurements were available for analysis. Gabapentin concentrations and intrapatient CVs ranged from 0.5 to 22.6 μg/ml (mean 7.9 μg/ml, standard deviation [SD] 4.1 μg/ml) and 2% to 79% (mean 27.9%, SD 15.3%), respectively, across all visits. Intrapatient CV was higher by 7.3% for those with a body mass index of ≥ 30 kg/m 2 (coefficient = 7.3, p=0.04). CVs were on average 0.5% higher for each 1-unit higher CV in creatinine clearance (coefficient = 0.5, p=0.03) and 1.2% higher for each 1-hour longer mean time after dose (coefficient = 1.2, p=0.04). Substantial intrapatient variability in serial gabapentin concentration was noted in elderly patients with epilepsy. Creatinine clearance, time of sampling relative to dose, and obesity were found to be positively associated with variability. © 2017 Pharmacotherapy Publications, Inc.

Single therapeutic and supratherapeutic doses of corifollitropin alfa, a sustained follicle stimulant, do not prolong the QTcF-interval in healthy postmenopausal volunteers.

PubMed

de Kam, Pieter-Jan; van Kuijk, Jacqueline H M; Zandvliet, Anthe S; Thomsen, Torben

2015-09-01

Corifollitropin alfa (Elonva®) is the first hybrid follicle-stimulating hormone molecule with demonstrated sustained follicle-stimulating activity after a single subcutaneous injection. This trial evaluated if corifollitropin alfa is associated with QT/QTc prolongation and/ or proarrhythmic potential as compared to placebo in healthy post-menopausal women. Participants were healthy, postmenopausal women. Study treatments were corifollitropin alfa 150 μg, corifollitropin alfa 240 μg, and moxifloxacin 400 mg with placebo. This randomized, double blind, double-dummy, 4-period crossover trial compared single doses of corifollitropin alfa 150 μg (therapeutic dose), corifollitropin alfa 240 μg (supratherapeutic dose), and moxifloxacin 400 mg (positive control) with placebo. Corifollitropin alfa was administered on day 1 and moxifloxacin on day 2. The largest time-matched mean QTcF difference versus placebo for the therapeutic dose of corifollitropin alfa was 1.4 ms (upper limit of 1-sided 95% confidence interval (UL 95% CI) = 3.4 ms), and for the supratherapeutic dose was 1.2 ms (UL 95% CI = 3.6 ms). For both the therapeutic and the supratherapeutic dose of corifollitropin alfa and at all time points, the UL 95% CI for the time matched QTcF differences compared with placebo was below 10 ms, the threshold of relevance defined by the ICH E14 guideline. Single therapeutic and supratherapeutic doses of corifollitropin alfa are not associated with clinically relevant QT/QTc-interval prolongation in healthy post-menopausal women.

Randomized, double-blind, comparative study of levofloxacin and ofloxacin in the treatment of complicated urinary tract infections.

PubMed

Peng, M Y

1999-03-01

Levofloxacin, the optical S-(-) isomer of ofloxacin, was compared with ofloxacin in the treatment of complicated urinary tract infections (UTIs). Patients eligible for the trial were randomly assigned to either a daily 300 mg of levofloxacin or 600 mg of ofloxacin for 10 consecutive days. The double blind design was achieved by a double-dummy technique utilizing placebo of both test drugs. Efficacy variables measured were: urine white blood cell counts for the effects on pyuria, urine cultures for effects on bacteriuria, subjective symptoms, and overall clinical efficacy which combined results from effects on bacteriuria, pyuria and subjective symptoms. Safety endpoints were the incidence of adverse events and laboratory test monitoring after a 10-day treatment. A total of 104 patients were enrolled into this trial and 46 patients were evaluable for efficacy endpoints. Most patients with culture-negative (48 cases), mixed flora (5 cases), and less than 10,000 colony forming units/mL of bacteria (3 cases) were excluded from analyses. None of the demographic and baseline characteristics were significantly different between treatments (p > 0.05). Therapeutic effects upon bacteriuria for both treatment groups were similar with a response rate of 90.0% for levofloacin and 88.5% for ofloxacin. Efficacy on the subjective symptoms revealed response rates of 90.0% in the levofloxacin group and 80.7% in the ofloxacin group, with the overall clinical efficacy of 90% in the levofloxacin and 84.6% in the ofloxacin groups. All the efficacy variables measured between treatments were not statistically different which indicated an equivalent efficacy in the treatment of complicated UTIs (p > 0.05). Of the 104 patients exposed to the test medications, only three having adverse effects. One developed epigastralgia in the levofloxacin group, and 2 developed a headache in the ofloxacin treatment. All events were moderate in severity and were resolved quickly after medication. Four laboratory data abnormalities were observed (defined by 25% as exceeding the normal range), and were considered to not be related to the test medications. Both antibiotics were efficacious in the treatment of complicated UTIs (response rates ranging from 80 to 90%) and were well tolerated. Levofloxacin demonstrated comparable antibacterial effects and safety profiles with double potency dosage, compared to the ofloxacin.

Randomized controlled trial of the efficacy and safety of self-adhesive low-level light therapy in women with primary dysmenorrhea.

PubMed

Hong, Gi-Youn; Shin, Byung-Cheul; Park, Seong-Nam; Gu, Yun-Hee; Kim, Nam-Gyun; Park, Kyoung-Jun; Kim, Soo-Yeon; Shin, Yong-Il

2016-04-01

To evaluate the efficacy and safety of low-level light therapy in women with primary dysmenorrhea. A multicenter prospective, randomized, double-blind, placebo-controlled clinical trial including patients 18-35 years of age with primary dysmenorrhea was undertaken at two university hospitals in South Korea between October 2011 and September 2012. Patients were randomized using a computer-generated sequence to receive low-level light therapy using the Color DNA-WSF device or to receive placebo treatment with a dummy device. The severity of menstrual pain, assessed using a visual analog scale, was the primary outcome and was evaluated at baseline and during every menstrual cycle for 3 months following treatment. Patients who received more than one application of treatment (with a Color DNA-WSF or placebo device) were included in analyses. Patients and investigators were masked to the treatment assignments. Overall, 44 patients were assigned to each group. At the final study visit, the reduction in scores using a visual analog scale was significantly greater in patients who received low-level light therapy (n=41; 4.34±2.22) than among those in the control group (n=38; 1.79±1.73; P<0.001 when adjusted for age) No serious adverse events occurred. Low-level light therapy could be an effective, safe treatment modality for women with primary dysmenorrhea. Clinical Trials.gov: NCT02026206. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

SEMICONDUCTOR TECHNOLOGY Dummy fill effect on CMP planarity

NASA Astrophysics Data System (ADS)

Junxiong, Zhou; Lan, Chen; Wenbiao, Ruan; Zhigang, Li; Weixiang, Shen; Tianchun, Ye

2010-10-01

With the use of a chemical-mechanical polishing (CMP) simulator verified by testing data from a foundry, the effect of dummy fill characteristics, such as fill size, fill density and fill shape, on CMP planarity is analyzed. The results indicate that dummy density has a significant impact on oxide erosion, and copper dishing is in proportion to dummy size. We also demonstrate that cross shape dummy fill can have the best dishing performance at the same density.

Comprehensive comparison of liquid chromatography selectivity as provided by two types of liquid chromatography detectors (high resolution mass spectrometry and tandem mass spectrometry): "where is the crossover point?".

PubMed

Kaufmann, A; Butcher, P; Maden, K; Walker, S; Widmer, M

2010-07-12

The selectivity of mass traces obtained by monitoring liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was compared. A number of blank extracts (fish, pork kidney, pork liver and honey) were separated by ultra performance liquid chromatography (UPLC). Detected were some 100 dummy transitions respectively dummy exact masses (traces). These dummy masses were the product of a random generator. The range of the permitted masses corresponded to those which are typical for analytes (e.g. veterinary drugs). The large number of monitored dummy traces ensured that endogenous compounds present in the matrix extract, produced a significant number of detectable chromatographic peaks. All obtained chromatographic peaks were integrated and standardized. Standardisation was done by dividing these absolute peak areas by the average response of a set of 7 different veterinary drugs. This permitted a direct comparison between the LC-HRMS and LC-MS/MS data. The data indicated that the selectivity of LC-HRMS exceeds LC-MS/MS, if high resolution mass spectrometry (HRMS) data is recorded with a resolution of 50,000 full width at half maximum (FWHM) and a corresponding mass window. This conclusion was further supported by experimental data (MS/MS based trace analysis), where a false positive finding was observed. An endogenous matrix compound present in honey matrix behaved like a banned nitroimidazole drug. This included identical retention time and two MRM traces, producing an MRM ratio between them, which perfectly matched the ratio observed in the external standard. HRMS measurement clearly resolved the interfering matrix compound and unmasked the false positive MS/MS finding. Copyright 2010 Elsevier B.V. All rights reserved.

Effect of budesonide/formoterol pressurized metered-dose inhaler on exacerbations versus formoterol in chronic obstructive pulmonary disease: The 6-month, randomized RISE (Revealing the Impact of Symbicort in reducing Exacerbations in COPD) study.

PubMed

Ferguson, Gary T; Tashkin, Donald P; Skärby, Tor; Jorup, Carin; Sandin, Kristina; Greenwood, Michael; Pemberton, Kristine; Trudo, Frank

2017-11-01

Prevention of exacerbations is a primary goal for chronic obstructive pulmonary disease (COPD) therapy. This randomized, double-blind, double-dummy, parallel-group, multicenter study evaluated the effect of budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus formoterol dry powder inhaler (DPI) on reducing COPD exacerbations. 1219 patients aged ≥40 years with moderate-to-very-severe COPD (per lung function) and a history of ≥1 COPD exacerbation received budesonide/formoterol pMDI 320/9 μg twice daily (BID) during a 4-week run-in. Patients were then randomized 1:1 to receive budesonide/formoterol pMDI 320/9 μg BID (n = 606) or formoterol DPI 9 μg BID (n = 613) for 26 weeks. Exacerbations were identified using predefined criteria for symptom worsening and treatment with systemic corticosteroids and/or antibiotics and/or hospitalization. The primary endpoint was annual rate of exacerbations. Budesonide/formoterol pMDI resulted in a 24% reduction in annual rate of exacerbations (0.85 vs 1.12; rate ratio: 0.76 [95% CI: 0.62, 0.92]; P = 0.006), and a significant risk reduction for time to first exacerbation (hazard ratio: 0.78 [95% CI: 0.64, 0.96]; P = 0.016) versus formoterol DPI. The most commonly reported adverse events (AEs; ≥3%) in budesonide/formoterol and formoterol groups were COPD (4.5% vs 8.6%) and nasopharyngitis (5.0% vs 5.2%). Pneumonia AEs were reported in 0.5% and 1.0% of budesonide/formoterol-treated and formoterol-treated patients, respectively. Budesonide/formoterol pMDI is an effective treatment option for reducing exacerbation rates in COPD patients with moderate-to-very-severe airflow limitation and history of exacerbations. No increase in pneumonia was observed with budesonide/formoterol; safety data were consistent with its established profile. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy.

PubMed

Montorsi, Francesco; Oelke, Matthias; Henneges, Carsten; Brock, Gerald; Salonia, Andrea; d'Anzeo, Gianluca; Rossi, Andrea; Mulhall, John P; Büttner, Hartwig

2016-09-01

Understanding predictors for the recovery of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) might help clinicians and patients in preoperative counseling and expectation management of EF rehabilitation strategies. To describe the effect of potential predictors on EF recovery after nsRP by post hoc decision-tree modeling of data from A Study of Tadalafil After Radical Prostatectomy (REACTT). Randomized double-blind double-dummy placebo-controlled trial in 423 men aged <68 yr with adenocarcinoma of the prostate (Gleason ≤7, normal preoperative EF) who underwent nsRP at 50 centers from nine European countries and Canada. Postsurgery 1:1:1 randomization to 9-mo double-blind treatment with tadalafil 5mg once a day (OaD), tadalafil 20mg on demand, or placebo, followed by a 6-wk drug-free-washout, and a 3-mo open-label tadalafil OaD treatment. Three decision-tree models, using the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score at the end of double-blind treatment, washout, and open-label treatment as response variable. Each model evaluated the association between potential predictors: presurgery IIEF domain and IIEF single-item scores, surgical approach, nerve-sparing score (NSS), and postsurgery randomized treatment group. The first decision-tree model (n=422, intention-to-treat population) identified high presurgery sexual desire (IIEF item 12: ≥3.5 and <3.5) as the key predictor for IIEF-EF at the end of double-blind treatment (mean IIEF-EF: 14.9 and 11.1), followed by high confidence to get and maintain an erection (IIEF item 15: ≥3.5 and <3.5; IIEF-EF: 15.4 and 7.1). For patients meeting these criteria, additional non-IIEF-related predictors included robot-assisted laparoscopic surgery (yes or no; IIEF-EF: 19.3 and 12.6), quality of nerve sparing (NSS: <2.5 and ≥2.5; IIEF-EF: 14.3 and 10.5), and treatment with tadalafil OaD (yes and no; IIEF-EF: 17.6 and 14.3). Additional analyses after washout and open-label treatment identified high presurgery intercourse satisfaction as the key predictor. Exploratory decision-tree analyses identified high presurgery sexual desire, confidence, and intercourse satisfaction as key predictors for EF recovery. Patients meeting these criteria might benefit the most from conserving surgery and early postsurgery EF rehabilitation. Strategies for improving EF after surgery should be discussed preoperatively with all patients; this information may support expectation management for functional recovery on an individual patient level. Understanding how patient characteristics and different treatment options affect the recovery of erectile function (EF) after radical surgery for prostate cancer might help physicians select the optimal treatment for their patients. This analysis of data from a clinical trial suggested that high presurgery sexual desire, sexual confidence, and intercourse satisfaction are key factors predicting EF recovery. Patients meeting these criteria might benefit the most from conserving surgery (robot-assisted surgery, perfect nerve sparing) and postsurgery medical rehabilitation of EF. ClinicalTrials.gov, NCT01026818. Copyright © 2016. Published by Elsevier B.V.

A survey of the dummy face and human face stimuli used in BCI paradigm.

PubMed

Chen, Long; Jin, Jing; Zhang, Yu; Wang, Xingyu; Cichocki, Andrzej

2015-01-15

It was proved that the human face stimulus were superior to the flash only stimulus in BCI system. However, human face stimulus may lead to copyright infringement problems and was hard to be edited according to the requirement of the BCI study. Recently, it was reported that facial expression changes could be done by changing a curve in a dummy face which could obtain good performance when it was applied to visual-based P300 BCI systems. In this paper, four different paradigms were presented, which were called dummy face pattern, human face pattern, inverted dummy face pattern and inverted human face pattern, to evaluate the performance of the dummy faces stimuli compared with the human faces stimuli. The key point that determined the value of dummy faces in BCI systems were whether dummy faces stimuli could obtain as good performance as human faces stimuli. Online and offline results of four different paradigms would have been obtained and comparatively analyzed. Online and offline results showed that there was no significant difference among dummy faces and human faces in ERPs, classification accuracy and information transfer rate when they were applied in BCI systems. Dummy faces stimuli could evoke large ERPs and obtain as high classification accuracy and information transfer rate as the human faces stimuli. Since dummy faces were easy to be edited and had no copyright infringement problems, it would be a good choice for optimizing the stimuli of BCI systems. Copyright © 2014 Elsevier B.V. All rights reserved.

Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study.

PubMed

Balasubramaniam, Gowrie; Parker, Trisha; Turner, David; Parker, Mike; Scales, Jonathan; Harnett, Patrick; Harrison, Michael; Ahmed, Khalid; Bhagat, Sweta; Marianayagam, Thiraupathy; Pitzalis, Costantino; Mallen, Christian; Roddy, Edward; Almond, Mike; Dasgupta, Bhaskar

2017-09-05

Acute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD). ASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies. The London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences. EudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No. NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614-34090. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Once versus three times daily dosing of oral budesonide for active Crohn's disease: a double-blind, double-dummy, randomised trial.

PubMed

Dignass, Axel; Stoynov, Simeon; Dorofeyev, Andrey E; Grigorieva, Galina A; Tomsová, Eva; Altorjay, István; Tuculanu, Daniel; Bunganič, Ivan; Pokrotnieks, Juris; Kupčinskas, Limas; Dilger, Karin; Greinwald, Roland; Mueller, Ralph

2014-09-01

Oral budesonide 9 mg/day represents first-line treatment of mild-to-moderately active ileocolonic Crohn's disease. However, there is no precise recommendation for budesonide dosing due to lack of comparative data. A once-daily (OD) 9 mg dose may improve adherence and thereby efficacy. An eight-week, double-blind, double-dummy randomised trial compared budesonide 9 mg OD versus 3mg three-times daily (TID) in patients with mild-to-moderately active ileocolonic Crohn's disease. Primary endpoint was clinical remission defined as CDAI <150 at week 8 (last observation carried forward). The final intent-to-treat population comprised 471 patients (238 [9 mg OD], 233 [3 mg TID]). The confirmatory population for the primary endpoint analysis was the interim per protocol population (n=377; 188 [9 mg OD], 189 [3mg TID]), in which the primary endpoint was statistically non-inferior with budesonide 9 mg OD versus 3 mg TID. Clinical remission was achieved in 71.3% versus 75.1%, a difference of -3.9% (95% CI [-14.6%; 6.4%]; p=0.020 for non-inferiority). The mean (SD) time to remission was 21.9 (13.8) days versus 21.4 (14.6) days with budesonide 9 mg OD versus 3 mg TID, respectively. In a subpopulation of 122 patients with baseline SES-CD ulcer score ≥1, complete mucosal healing occurred in 32.8% (21/64) on 9 mg OD and 41.4% (24/58) on 3mg TID; deep remission (mucosal healing and clinical remission) was observed in 26.6% (17/64) and 32.8% (19/58) of patients, respectively. Treatment-emergent suspected adverse drug reactions were reported in 4.6% of 9 mg OD and 4.7% of 3 mg TID patients. Budesonide at the recommended dose of 9 mg/day can be administered OD without impaired efficacy and safety compared to 3mg TID dosing in mild-to-moderately active Crohn's disease. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) vs Extended-Release Morphine Administered Intranasally in Nondependent Recreational Opioid Users

PubMed Central

Webster, Lynn R.; Smith, Michael D.; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M.

2017-01-01

Abstract Objective. To compare the relative human abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets. Methods. A randomized, double-blind, double-dummy, active- and placebo-controlled five-way crossover study was performed with adult volunteers who were experienced, nondependent, recreational opioid users. After intranasal (IN) administration of manipulated high-volume (HV) morphine-ADER-IMT (60 mg), participants were randomized (1:1:1:1) to receive IN manipulated low-volume (LV) morphine ER (60 mg), IN manipulated LV morphine-ADER-IMT, intact oral morphine-ADER-IMT (60 mg), and placebo in crossover fashion. Pharmacodynamic and pharmacokinetic assessments included peak effect of drug liking (Emax; primary endpoint) using drug liking visual analog scale (VAS) score, Emax using overall drug liking, and take drug again (TDA) VASs scores, and mean abuse quotient (AQ), a pharmacokinetic parameter associated with drug liking. Results. Forty-six participants completed the study. After insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT, drug liking Emax was significantly lower (P < 0.0001) compared with IN morphine ER. Overall drug liking and TDA Emax values were significantly lower (P < 0.0001) after insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT compared with IN morphine ER. Mean AQ was lower after insufflation of HV (9.2) and LV (2.3) morphine-ADER-IMT or ingestion of oral morphine-ADER-IMT (5.5) compared with insufflation of LV morphine ER (37.2). Conclusions. All drug liking, take drug again, and abuse quotient endpoints support a significantly lower abuse potential with insufflation of manipulated morphine-ADER-IMT compared with manipulated and insufflated non-AD ER morphine. PMID:27651510

Week 96 efficacy and safety of rilpivirine in treatment-naive, HIV-1 patients in two Phase III randomized trials.

PubMed

Cohen, Calvin J; Molina, Jean-Michel; Cassetti, Isabel; Chetchotisakd, Ploenchan; Lazzarin, Adriano; Orkin, Chloe; Rhame, Frank; Stellbrink, Hans-Jürgen; Li, Taisheng; Crauwels, Herta; Rimsky, Laurence; Vanveggel, Simon; Williams, Peter; Boven, Katia

2013-03-27

In the week 48 primary analysis of ECHO and THRIVE, rilpivirine demonstrated noninferior efficacy and more favourable tolerability versus efavirenz in treatment-naive, HIV-1-infected adults. Pooled 96-week results are presented. Patients (N = 1368) received rilpivirine 25 mg once-daily (q.d.) or efavirenz 600 mg q.d., with two background nucleoside/nucleotide reverse transcriptase inhibitors, in two randomized, double-blind, double-dummy Phase III trials. At week 96, response rate (% confirmed viral load <50 copies/ml; intent-to-treat, time-to-loss-of-virologic response) was 78% in both groups. Responses were similar for both treatments by background regimen, sex, race, and in patients with more than 95% adherence (M-MASRI) or baseline viral load 100,000 copies/ml or less. Responses were lower and virologic failure higher for rilpivirine versus efavirenz in patients with 95% or less adherence or baseline viral load more than 100,000 copies/ml. Beyond week 48, the incidence of virologic failure was comparable (3 versus 2%) between treatment groups, rilpivirine resistance-associated mutations were consistent with those observed in year 1, there were few adverse events in both groups and no new safety concerns. Over 96 weeks, discontinuations due to adverse events (4 versus 9%), treatment-related grade 2-4 adverse events (17 versus 33%), rash (4 versus 15%), dizziness (8 versus 27%) and abnormal dreams/nightmares (8 versus 13%), and grade 2-4 lipid abnormalities were lower with rilpivirine than efavirenz. Only 2 and 4% of patients in the rilpivirine and efavirenz treatment groups, respectively, reported at least possibly treatment-related grade 2-4 adverse events during the second year of treatment. Rilpivirine 25 mg q.d. and efavirenz 600 mg q.d. had comparable responses at week 96. Rilpivirine had more virologic failures but improved tolerability versus efavirenz. The majority of virologic failures occurred in the first 48 weeks.

Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale.

PubMed

Lopes, Renato D; Alexander, John H; Al-Khatib, Sana M; Ansell, Jack; Diaz, Raphael; Easton, J Donald; Gersh, Bernard J; Granger, Christopher B; Hanna, Michael; Horowitz, John; Hylek, Elaine M; McMurray, John J V; Verheugt, Freek W A; Wallentin, Lars

2010-03-01

Atrial fibrillation (AF) is associated with increased risk of stroke that can be attenuated with vitamin K antagonists (VKAs). Vitamin K antagonist use is limited, in part, by the high incidence of complications when patients' international normalized ratios (INRs) deviate from the target range. The primary objective of ARISTOTLE is to determine if the factor Xa inhibitor, apixaban, is noninferior to warfarin at reducing the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism in patients with AF and at least 1 additional risk factor for stroke. We have randomized 18,206 patients from over 1,000 centers in 40 countries. Patients were randomly assigned in a 1:1 ratio to receive apixaban or warfarin using a double-blind, double-dummy design. International normalized ratios are monitored and warfarin (or placebo) is adjusted aiming for a target INR range of 2 to 3 using a blinded, encrypted point-of-care device. Minimum treatment is 12 months, and maximum expected exposure is 4 years. Time to accrual of at least 448 primary efficacy events will determine treatment duration. The key secondary objectives are to determine if apixaban is superior to warfarin for the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism, and for all-cause death. These will be tested after the primary objective using a closed test procedure. The noninferiority boundary is 1.38; apixaban will be declared noninferior if the 95% CI excludes the possibility that the primary outcome rate with apixaban is >1.38 times higher than with warfarin. ARISTOTLE will determine whether apixaban is noninferior or superior to warfarin in preventing stroke and systemic embolism; whether apixaban has particular benefits in the warfarin-naïve population; whether it reduces the combined rate of stroke, systemic embolism, and death; and whether it impacts bleeding.

Novel Δ9-tetrahydrocannabinol formulation Namisol® has beneficial pharmacokinetics and promising pharmacodynamic effects

PubMed Central

Klumpers, Linda E; Beumer, Tim L; van Hasselt, Johan G C; Lipplaa, Astrid; Karger, Lennard B; Kleinloog, H Daniël; Freijer, Jan I; de Kam, Marieke L; van Gerven, Joop M A

2012-01-01

AIMS Among the main disadvantages of currently available Δ9-tetrahydrocannabinol (THC) formulations are dosing difficulties due to poor pharmacokinetic characteristics. Namisol® is a novel THC formulation, designed to improve THC absorption. The study objectives were to investigate the optimal administration route, pharmacokinetics (PK), pharmacodynamics (PD) and tolerability of Namisol®. METHODS This first in human study consisted of two parts. Panel I included healthy males and females (n = 6/6) in a double-blind, double-dummy, randomized, crossover study with sublingual (crushed tablet) and oral administration of Namisol® (5 mg THC). Based on these results, male and female (n = 4/5) participants from panel I received oral THC 6.5 and 8.0 mg or matching placebo in a randomized, crossover, rising dose study during panel II. PD measurements were body sway; visual analogue scales (VAS) mood, psychedelic and heart rate. THC and 11-OH-THC population PK analysis was performed. RESULTS Sublingual administration showed a flat concentration profile compared with oral administration. Oral THC apparent t1/2 was 72–80 min, tmax was 39–56 min and Cmax 2.92–4.69 ng ml−1. THC affected body sway (60.8%, 95% CI 29.5, 99.8), external perception (0.078 log mm, 95% CI 0.019, 0.137), alertness (−2.7 mm, 95% CI −4.5, −0.9) feeling high (0.256 log mm, 95% CI 0.093, 0.418) and heart rate (5.6 beats min–1, 95% CI 2.7, 6.5). Namisol® was well tolerated. CONCLUSIONS Oral Namisol® showed promising PK and PD characteristics. Variability and tmax of THC plasma concentrations were smaller for Namisol® than reported for studies using oral dronabinol and nabilone. This study was performed in a limited number of healthy volunteers. Therefore, future research on Namisol® should study clinical effects in patient populations. PMID:22680341

Efficacy and Safety of Gabapentin in Comparison to Solifenacin Succinate in Adult Overactive Bladder Treatment.

PubMed

Chua, Michael E; See, Manuel C; Esmeňa, Ednalyn B; Balingit, Jaime C; Morales, Marcelino L

2018-05-01

To evaluate the efficacy and safety of gabapentin in comparison to solifenacin succinate and placebo for the treatment of adult patients with overactive bladder (OAB). A 12-week, randomized, double-blind, double dummy placebo-controlled, clinical trial was conducted between October 2010 and August 2014 at a tertiary medical center. Eligible and consenting patients included were randomized into three treatment groups (placebo, gabapentin and solifenacin). After a 12-week treatment period, an intention to treat analysis was applied to assess between group differences on the micturitions and urgency episodes per 24 h; which were evaluated by 3-day micturition diary mean change from baseline to post treatment. Health related quality of life (HRQOL) domains were likewise assessed by OAB questionnaire (OAB-q). Adverse event were monitored and summarized. Study results were analyzed at statistical significance of 0.05. (ClinicalTrials.gov ID NCT01486706) RESULT: A total of 94 participants were included for end-study efficacy and safety analysis. Compared to placebo, gabapentin and solifenacin have statistically significant improvement in mean number of micturitions per 24 h (adjusted mean difference [AMD] -1.179, 95%CI -1.98, -0.38; P < 0.001; -1.706, 95%CI -2.52, -0.09; P < 0.001; respectively), and in mean number of urgency episodes per 24 h (AMD -0.903, 95%CI -1.44, -0.37; P < 0.001; -0.896, 95%CI -1.44, -0.35; P < 0.001). Gabapentin also demonstrated significant improvement over the solifenacin in the mean number of nocturia episodes/24 h (AMD -0.607, 95%CI -1.04, -0.18; P < 0.001). Adverse event related to gabapentin treatment was lesser than solifenacin, and comparable to placebo. Gabapentin treatment with acceptable safety profile, improves OAB symptoms and HRQOL domains. © 2017 John Wiley & Sons Australia, Ltd.

Targeting hyperglycaemia with either metformin or repaglinide in non-obese patients with type 2 diabetes: results from a randomized crossover trial.

PubMed

Lund, S S; Tarnow, L; Stehouwer, C D A; Schalkwijk, C G; Frandsen, M; Smidt, U M; Pedersen, O; Parving, H-H; Vaag, A

2007-05-01

Metformin is the 'drug-of-first-choice' in obese patients with type 2 diabetes mellitus (T2DM) due to its antihyperglycaemic and cardiovascular protective potentials. In non-obese patients with T2DM, insulin secretagogues are empirically used as first choice. In this investigator-initiated trial, we evaluated the effect of metformin vs. an insulin secretagogue, repaglinide on glycaemic regulation and markers of inflammation and insulin sensitivity in non-obese patients with T2DM. A single-centre, double-masked, double-dummy, crossover study during 2 x 4 months involved 96 non-obese (body mass index < or = 27 kg/m(2)) insulin-naïve patients with T2DM. At enrolment, previous oral hypoglycaemic agents (OHA) were stopped and patients entered a 1-month run-in on diet-only treatment. Hereafter, patients were randomized to either repaglinide 2 mg thrice daily followed by metformin 1 g twice daily or vice versa each during 4 months with 1-month washout between interventions. End-of-treatment levels of haemoglobin A(1c) (HbA(1c)), fasting plasma glucose, mean of seven-point home-monitored plasma glucose and fasting levels of high-sensitivity C-reactive protein and adiponectin were not significantly different between treatments. However, body weight, waist circumference, fasting serum levels of insulin and C-peptide were lower and less number of patients experienced hypoglycaemia during treatment with metformin vs. repaglinide. Both drugs were well tolerated. In non-obese patients with T2DM, overall glycaemic regulation was equivalent with less hypoglycaemia during metformin vs. repaglinide treatment for 2 x 4 months. Metformin was more effective targeting non-glycaemic cardiovascular risk markers related to total and abdominal body fat stores as well as fasting insulinaemia. These findings may suggest the use of metformin as the preferred OHA also in non-obese patients with T2DM.

Exploiting Data Missingness in Bayesian Network Modeling

NASA Astrophysics Data System (ADS)

Rodrigues de Morais, Sérgio; Aussem, Alex

This paper proposes a framework built on the use of Bayesian networks (BN) for representing statistical dependencies between the existing random variables and additional dummy boolean variables, which represent the presence/absence of the respective random variable value. We show how augmenting the BN with these additional variables helps pinpoint the mechanism through which missing data contributes to the classification task. The missing data mechanism is thus explicitly taken into account to predict the class variable using the data at hand. Extensive experiments on synthetic and real-world incomplete data sets reveals that the missingness information improves classification accuracy.

Radial current high power dummy load for characterizing the high power laser triggered transformer-type accelerator.

PubMed

Yin, Yi; Zhong, Hui-Huang; Liu, Jin-Liang; Ren, He-Ming; Yang, Jian-Hua; Zhang, Xiao-Ping; Hong, Zhi-qiang

2010-09-01

A radial-current aqueous resistive solution load was applied to characterize a laser triggered transformer-type accelerator. The current direction in the dummy load is radial and is different from the traditional load in the axial. Therefore, this type of dummy load has smaller inductance and fast response characteristic. The load was designed to accommodate both the resistance requirement of accelerator and to allow optical access for the laser. Theoretical and numerical calculations of the load's inductance and capacitance are given. The equivalent circuit of the dummy load is calculated in theory and analyzed with a PSPICE code. The simulation results agree well with the theoretical analysis. At last, experiments of the dummy load applied to the high power spiral pulse forming line were performed; a quasisquare pulse voltage is obtained at the dummy load.

Radial current high power dummy load for characterizing the high power laser triggered transformer-type accelerator

NASA Astrophysics Data System (ADS)

Yin, Yi; Zhong, Hui-Huang; Liu, Jin-Liang; Ren, He-Ming; Yang, Jian-Hua; Zhang, Xiao-Ping; Hong, Zhi-qiang

2010-09-01

A radial-current aqueous resistive solution load was applied to characterize a laser triggered transformer-type accelerator. The current direction in the dummy load is radial and is different from the traditional load in the axial. Therefore, this type of dummy load has smaller inductance and fast response characteristic. The load was designed to accommodate both the resistance requirement of accelerator and to allow optical access for the laser. Theoretical and numerical calculations of the load's inductance and capacitance are given. The equivalent circuit of the dummy load is calculated in theory and analyzed with a PSPICE code. The simulation results agree well with the theoretical analysis. At last, experiments of the dummy load applied to the high power spiral pulse forming line were performed; a quasisquare pulse voltage is obtained at the dummy load.

Development and validation of a modified Hybrid-III six-year-old dummy model for simulating submarining in motor-vehicle crashes.

PubMed

Hu, Jingwen; Klinich, Kathleen D; Reed, Matthew P; Kokkolaras, Michael; Rupp, Jonathan D

2012-06-01

In motor-vehicle crashes, young school-aged children restrained by vehicle seat belt systems often suffer from abdominal injuries due to submarining. However, the current anthropomorphic test device, so-called "crash dummy", is not adequate for proper simulation of submarining. In this study, a modified Hybrid-III six-year-old dummy model capable of simulating and predicting submarining was developed using MADYMO (TNO Automotive Safety Solutions). The model incorporated improved pelvis and abdomen geometry and properties previously tested in a modified physical dummy. The model was calibrated and validated against four sled tests under two test conditions with and without submarining using a multi-objective optimization method. A sensitivity analysis using this validated child dummy model showed that dummy knee excursion, torso rotation angle, and the difference between head and knee excursions were good predictors for submarining status. It was also shown that restraint system design variables, such as lap belt angle, D-ring height, and seat coefficient of friction (COF), may have opposite effects on head and abdomen injury risks; therefore child dummies and dummy models capable of simulating submarining are crucial for future restraint system design optimization for young school-aged children. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

Treatment satisfaction in type 2 diabetes patients taking empagliflozin compared with patients taking glimepiride.

PubMed

Chirila, Costel; Zheng, Qingyao; Davenport, Eric; Kaschinski, Dagmar; Pfarr, Egon; Hach, Thomas; Palencia, Roberto

2016-05-01

This exploratory analysis assessed and compared patients' treatment satisfaction with empagliflozin plus metformin versus glimepiride plus metformin, using data obtained from the Diabetes Treatment Satisfaction Questionnaire, status version (DTSQs) collected in a randomized, double-blind, double-dummy clinical trial. Observed values for DTSQs scale score and each of its eight items were summarized by visit and treatment arm. Changes from baseline in these scores were analyzed using linear mixed models for repeated measures. The baseline scale score and item scores were comparable between empagliflozin plus metformin (n = 765) and glimepiride plus metformin (n = 780). Compared with baseline, patients reported significant treatment satisfaction increases and significant decreases in perceived hyperglycemia with both treatments at all visits. Also, compared with baseline, a significant increase in perceived frequency of hypoglycemia was observed in the glimepiride treatment group at all visits. No statistically significant treatment difference was observed in DTSQs scale score and its items at week 104. The difference between the treatment groups was significant and in favor of empagliflozin from week 28 onward for perceived frequency of hyperglycemia (P ≤ 0.006) and perceived frequency of hypoglycemia (P ≤ 0.011). Despite positive trends in favor of empagliflozin, there was no significant difference in DTSQs scale score between empagliflozin and glimepiride at 104 weeks. However, when compared with glimepiride, empagliflozin demonstrated significantly lower perceived frequency of hyperglycemia and hypoglycemia at all visits from week 28 onward. This finding is consistent with the clinical results reported for the EMPA-REG H2H-SU trial.

Single-dose extended-release azithromycin versus a 10-day regimen of amoxicillin/clavulanate for the treatment of children with acute otitis media.

PubMed

Arguedas, Adriano; Soley, Carolina; Kamicker, Barbara J; Jorgensen, Daniel M

2011-04-01

A randomized, double-blind, double-dummy, multicenter international study was conducted to assess the clinical and bacteriologic response, safety, and compliance of a single 60-mg/kg dose of azithromycin extended-release (ER) versus a 10-day regimen of amoxicillin/clavulanate 90/6.4 mg/kg per day in children with acute otitis media at high risk of persistent or recurrent middle ear infection. Children aged 3 to 48 months were enrolled and stratified into two age groups (≤ 24 months and >24 months). Pretreatment tympanocentesis was performed at all sites and was repeated during treatment at selected sites. The primary endpoint, clinical response at the test-of-cure visit in the bacteriologic eligible population, was achieved in 80.5% of children in the azithromycin ER group and 84.5% of children in the amoxicillin/clavulanate group (difference-3.9%; 95% confidence interval-10.4, 2.6). Bacteriologic eradication was 82.6% in the azithromycin ER group and 92% in the amoxicillin/clavulanate group (p=0.050). Children who received amoxicillin/clavulanate had significantly higher rates of dermatitis and diarrhea, a greater burden of adverse events, and a lower rate of compliance to study drug compared to those who received azithromycin ER. A single 60-mg/kg dose of azithromycin ER provides near equivalent effectiveness to a 10-day regimen of amoxicillin/clavulanate 90/6.4 mg/kg per day in the treatment of children with acute otitis media. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Pharmacokinetics and pharmacodynamics of GSK961081, a novel inhaled muscarinic antagonist β2 -agonist, and fluticasone propionate administered alone, concurrently and as a combination blend formulation in healthy volunteers.

PubMed

Norris, Virginia; Ambery, Claire; Riley, Trevor

2014-07-01

To investigate the pharmacokinetics and pharmacodynamics of inhaled GSK961081 and fluticasone propionate (FP) given alone, concurrently and as a combination blend formulation. The study was double-blind, double-dummy, four-way crossover. Twenty-four healthy volunteers took single doses of the following in randomized order: (1) GSK961081 800 µg; (2) FP 500 µg; (3) GSK961081 800 µg and FP 500 µg as a blend formulation; and (4) GSK961081 800 µg and FP 500 µg concurrently via separate inhalers. The eLung breathing simulator was also used for the in vitro characterization of the formulations. There was no pharmacokinetic interaction when GSK961081 and FP were administered concurrently. Mean Cmax and AUC(0-t) of GSK961081 were lower (∼20%) and mean Cmax and AUC(0-t) of FP were higher (two fold) following GSK961081/FP blend formulation compared to concurrent or the individual components alone. There was an increase in the FP in vitro ex-throat dose for the GSK961081/FP blend from the eLung breathing simulator. Serum cortisol suppression was greater with GSK961081/FP blend, with lower (∼10%) cortisol levels than after GSK961081 + FP concurrent or FP alone. GSK961081/FP blend formulation was associated with an increase in FP systemic exposure and greater serum cortisol suppression. © 2014, The American College of Clinical Pharmacology.

The effects of dummy/pacifier use on infant blood pressure and autonomic activity during sleep.

PubMed

Yiallourou, Stephanie R; Poole, Hannah; Prathivadi, Pallavi; Odoi, Alexsandria; Wong, Flora Y; Horne, Rosemary S C

2014-12-01

Dummy/pacifier use is protective for sudden infant death syndrome (SIDS); however, the mechanism/s for this are unknown. As impaired cardiovascular control may be the underlying cause of SIDS, we assessed the effects of dummy/pacifier use on cardiovascular control during sleep within the first 6 months of life. Term infants, divided into dummy/pacifier users and non-dummy/pacifier users, were studied at 2-4 weeks (n = 27), 2-3 months (n = 35) and 5-6 months (n = 31) using daytime polysomnography. Heart rate, blood pressure (BP), heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) were measured in triplicate 1-2-min epochs during quiet and active sleep in the supine and prone positions. Overall, during the non-sucking periods, in the prone position, the BP was higher (10-22 mmHg) in dummy/pacifier users compared to non-users at 2-4 weeks and 5-6 months (p < 0.05 for both). HRV and BRS were higher in dummy/pacifier users compared to non-users at 2-4 weeks (p < 0.05). Active sucking increased HRV and BPV, consistent with increased sympathetic activity in dummy/pacifier users. Higher BP and HRV in dummy/pacifier users indicate increased sympathetic tone, which may serve as a protective mechanism against possible hypotension leading to SIDS; however, these effects were not apparent at 2-3 months, when the risk of SIDS is highest. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial.

PubMed

Rosenthal, Richard N; Lofwall, Michelle R; Kim, Sonnie; Chen, Michael; Beebe, Katherine L; Vocci, Frank J

2016-07-19

The effectiveness of buprenorphine treatment of opioid dependence is limited by suboptimal medication adherence, abuse, and diversion. To determine whether 6-month buprenorphine implants are noninferior to daily sublingual buprenorphine as maintenance treatment for opioid-dependent patients with stable abstinence. Outpatient, randomized, active-controlled, 24-week, double-blind, double-dummy study conducted at 21 US sites from June 26, 2014, through May 18, 2015. Outpatients were prescribed daily sublingual buprenorphine for 6 months or more, were abstinent while taking 8 mg/d or less of sublingual buprenorphine for 90 days or longer, and were determined to be clinically stable by their physician. Participants were randomized to receive sublingual buprenorphine plus 4 placebo implants or sublingual placebo plus four 80-mg buprenorphine hydrochloride implants (expected efficacy, 24 weeks). The primary end point was between-group difference in proportion of responders (≥4 of 6 months without opioid-positive urine test result [monthly and 4 times randomly] and self-report). The noninferiority established for the lower bound of the 95% confidence interval was greater than -0.20 (P < .025). Secondary end points included cumulative percentage of negative opioid urine results, abstinence, and time to first illicit opioid use. Safety was assessed by adverse event reporting. Of 177 participants (mean age, 39 years; 40.9% female), 90 were randomized to sublingual buprenorphine with placebo implants and 87 to buprenorphine implants with sublingual placebo; 165 of 177 (93.2%) completed the trial. Eighty-one of 84 (96.4%) receiving buprenorphine implants and 78 of 89 (87.6%) receiving sublingual buprenorphine were responders, an 8.8% difference (1-sided 97.5% CI, 0.009 to ∞; P < .001 for noninferiority). Over 6 months, 72 of 84 (85.7%) receiving buprenorphine implants and 64 of 89 (71.9%) receiving sublingual buprenorphine maintained opioid abstinence (hazard ratio, 13.8; 95% CI, 0.018-0.258; P = .03). Non-implant-related and implant-related adverse events occurred in 48.3% and 23% of the buprenorphine implant group and in 52.8% and 13.5% of participants in the sublingual buprenorphine group, respectively. Among adults with opioid dependence maintaining abstinence with a stable dose of sublingual buprenorphine, the use of buprenorphine implants compared with continued sublingual buprenorphine did not result in an inferior likelihood of remaining a responder. However, the study population had an exceptionally high response rate in the control group, and further studies are needed in broader populations to assess the efficacy in other settings. clinicaltrials.gov Identifier: NCT02180659.

75 FR 71648 - Federal Motor Vehicle Safety Standards, Child Restraint Systems; Hybrid III 10-Year-Old Child...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-24

...This document proposes to amend Federal Motor Vehicle Safety Standard (FMVSS) No. 213, Child Restraint Systems, regarding a Hybrid III 10-year-old child test dummy that the agency seeks to use in the compliance test procedures of the standard. This document supplements a 2005 notice of proposed rulemaking (NPRM) and a 2008 SNPRM previously published in this rulemaking (RIN 2127-AJ44) regarding this test dummy. In the 2005 NPRM, in response to Anton's Law, NHTSA proposed to adopt the 10-year-old child test dummy into FMVSS No. 213 to test child restraints for older children. Subsequently, to address variation that was found in dummy readings due to chin-to-chest contact, NHTSA published the 2008 SNPRM to propose a NHTSA-developed procedure for positioning the test dummy in belt-positioning seats. Comments on the SNPRM objected to the positioning procedure, and some suggested an alternative procedure developed by the University of Michigan Transportation Research Institute (UMTRI). Today's SNPRM proposes to use the UMTRI procedure to position the test dummy rather than the NHTSA-developed procedure. We note that the 10-year-old child dummy may sometimes experience stiff contact between its chin and upper sternal bib region which may result in an unrealistically high value of the head injury criterion (HIC) \\1\\ referenced in the standard. Accordingly, NHTSA proposes that the dummy's HIC measurement will not be used to assess the compliance of the tested child restraint. This SNPRM also proposes other amendments to FMVSS No. 213, including a proposal to permit NHTSA to use, at the manufacturer's option, the Hybrid II or Hybrid III versions of the 6-year-old test dummy, and a proposal to use the UMTRI procedure to position the Hybrid III 6-year- old and 10-year-old dummies when testing belt-positioning seats. ---------------------------------------------------------------------------

Fire Protection of Weapon Storage and Water Mist Redundancy Philosophies

DTIC Science & Technology

2012-11-01

criteria me system ged system ozzles dummy tor d, insulated titute of Swe stems pedo pipe Date 2012 den Refere -03-31 P90 nce 0038-04...test wit tion test wit ution test wi t system, 10 st system, 5 m, 5 bar, 50 , 10 bar, 50 ummy, free- edo dummy pedo dummy pedo dummy ummy, dren...systems usi lower volum pedo dumm temperature discharge d ion. h Institute ynamics dström Date 2012 den ater mist/wa ests indicate fire

Dummy left behind by Skylab 3 crew for the Skylab 4 crew

NASA Technical Reports Server (NTRS)

1973-01-01

This photograph is an illustration of the humorous side of the Skylab 3 crew. This dummy was left behind in the Skylab space station by the Skylab 3 crew to be found by the Skylab 4 crew. The dummy is dressed in a flight suit and placed in the Lower Body Negative Pressure Device. The name tag indicates that it represents Gerald P. Carr, Skylab 4 commander. In the background is a partial view of the dummy for William R. Pogue, Skylab 4 pilot, propped upon the bicycle ergometer (1586); This dummy is dressed in a flight suit and propped upon the bicycle ergometer. The name tag indicates that it represents William R. Pogue, Skylab 4 pilot (1587).

Development of a finite element model of the Thor crash test dummy

DOT National Transportation Integrated Search

2000-03-06

The paper describes the development of a detailed finite element model of the new advanced frontal crash test dummy, Thor. The Volpe Center is developing the model for LS-DYNA in collaboration with GESAC, the dummy hardware developer, under the direc...

Exploratory Decision-Tree Modeling of Data from the Randomized REACTT Trial of Tadalafil Versus Placebo to Predict Recovery of Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy

PubMed Central

Montorsi, Francesco; Oelke, Matthias; Henneges, Carsten; Brock, Gerald; Salonia, Andrea; d’Anzeo, Gianluca; Rossi, Andrea; Mulhall, John P.; Büttner, Hartwig

2017-01-01

Background Understanding predictors for the recovery of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) might help clinicians and patients in preoperative counseling and expectation management of EF rehabilitation strategies. Objective To describe the effect of potential predictors on EF recovery after nsRP by post hoc decision-tree modeling of data from A Study of Tadalafil After Radical Prostatectomy (REACTT). Design, setting, and participants Randomized double-blind double-dummy placebo-controlled trial in 423 men aged <68 yr with adenocarcinoma of the prostate (Gleason ≤7, normal preoperative EF) who underwent nsRP at 50 centers from nine European countries and Canada. Intervention Postsurgery 1:1:1 randomization to 9-mo double-blind treatment with tadalafil 5 mg once a day (OaD), tadalafil 20 mg on demand, or placebo, followed by a 6-wk drug-free-washout, and a 3-mo open-label tadalafil OaD treatment. Outcome measurements and statistical analysis Three decision-tree models, using the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score at the end of double-blind treatment, washout, and open-label treatment as response variable. Each model evaluated the association between potential predictors: presurgery IIEF domain and IIEF single-item scores, surgical approach, nerve-sparing score (NSS), and postsurgery randomized treatment group. Results and limitations The first decision-tree model (n = 422, intention-to-treat population) identified high presurgery sexual desire (IIEF item 12: ≥3.5 and <3.5) as the key predictor for IIEF-EF at the end of double-blind treatment (mean IIEF-EF: 14.9 and 11.1), followed by high confidence to get and maintain an erection (IIEF item 15: ≥3.5 and <3.5; IIEF-EF: 15.4 and 7.1). For patients meeting these criteria, additional non-IIEF–related predictors included robot-assisted laparoscopic surgery (yes or no; IIEF-EF: 19.3 and 12.6), quality of nerve sparing (NSS: <2.5 and ≥2.5; IIEF-EF: 14.3 and 10.5), and treatment with tadalafil OaD (yes and no; IIEF-EF: 17.6 and 14.3). Additional analyses after washout and open-label treatment identified high presurgery intercourse satisfaction as the key predictor. Conclusions Exploratory decision-tree analyses identified high presurgery sexual desire, confidence, and intercourse satisfaction as key predictors for EF recovery. Patients meeting these criteria might benefit the most from conserving surgery and early postsurgery EF rehabilitation. Strategies for improving EF after surgery should be discussed preoperatively with all patients; this information may support expectation management for functional recovery on an individual patient level. Patient summary Understanding how patient characteristics and different treatment options affect the recovery of erectile function (EF) after radical surgery for prostate cancer might help physicians select the optimal treatment for their patients. This analysis of data from a clinical trial suggested that high presurgery sexual desire, sexual confidence, and intercourse satisfaction are key factors predicting EF recovery. Patients meeting these criteria might benefit the most from conserving surgery (robot-assisted surgery, perfect nerve sparing) and postsurgery medical rehabilitation of EF. Trial registration ClinicalTrials.gov, NCT01026818 PMID:26947602

Tetramorium tsushimae Ants Use Methyl Branched Hydrocarbons of Aphids for Partner Recognition.

PubMed

Sakata, Itaru; Hayashi, Masayuki; Nakamuta, Kiyoshi

2017-10-01

In mutualisms, partner discrimination is often the most important challenge for interacting organisms. The interaction between ants and aphids is a model system for studying mutualisms; ants are provided with honeydew by aphids and, in turn, the ants offer beneficial services to the aphids. To establish and maintain this system, ants must discriminate mutualistic aphid species correctly. Although recent studies have shown that ants recognize aphids as mutualistic partners based on their cuticular hydrocarbons (CHCs), it was unclear which CHCs are involved in recognition. Here, we tested whether the n-alkane or methylalkane fraction, or both, of aphid CHCs were utilized as partner recognition cues by measuring ant aggressiveness toward these fractions. When workers of Tetramorium tsushimae ants were presented with dummies coated with n-alkanes of their mutualistic aphid Aphis craccivora, ants displayed higher levels of aggression than to dummies treated with total CHCs or methyl alkanes of A. craccivora; responses to dummies treated with n-alkanes of A. craccivora were similar to those to control dummies or dummies treated with the CHCs of the non-mutualistic aphid Acyrthosiphon pisum. By contrast, ants exhibited lower aggression to dummies treated with either total CHCs or the methylalkane fraction of the mutualistic aphid than to control dummies or dummies treated with CHCs of the non-mutualistic aphid. These results suggest that T. tsushimae ants use methylalkanes of the mutualistic aphid's CHCs to recognize partners, and that these ants do not recognize aphids as partners on the basis of n-alkanes.

A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis.

PubMed

Miehlke, Stephan; Hruz, Petr; Vieth, Michael; Bussmann, Christian; von Arnim, Ulrike; Bajbouj, Monther; Schlag, Christoph; Madisch, Ahmed; Fibbe, Christiane; Wittenburg, Henning; Allescher, Hans Dieter; Reinshagen, Max; Schubert, Stefan; Tack, Jan; Müller, Michaela; Krummenerl, Patrick; Arts, Joris; Mueller, Ralph; Dilger, Karin; Greinwald, Roland; Straumann, Alex

2016-03-01

To investigate the efficacy and safety of two different budesonide formulations (effervescent tablet for orodispersible use (BET) and viscous suspension (BVS)) with different daily dosages for short-term treatment of eosinophilic oesophagitis (EoE). Adults with active EoE (n=76) randomly received 14 days' treatment with either BET 2×1 mg/day (BET1, n=19) or BET 2×2 mg/day (BET2, n=19), or BVS 2×5 mL (0.4 mg/mL)/day (BVS, n=19) or placebo (n=19) in a double-blind, double-dummy fashion, with a 2-week follow-up. Primary end point was histological remission (mean of <16 eosinophils/mm(2 )hpf). Secondary end points included endoscopy score, dysphagia score, drug safety and patient's preference for drug formulation. Histological remission occurred in 100%, 94.7% and 94.7% of budesonide (BET1, BET2, BVS, respectively) and in 0% of placebo recipients (p<0.0001). The improvement in total endoscopic intensity score was significantly higher in the three budesonide groups compared with placebo. Dysphagia improved in all groups at the end of treatment; however, improvement of dysphagia persisted only in those treated with BET1 (p=0.0196 vs placebo). There were no serious adverse events. Local fungal infection (stained fungi) occurred in two patients of each budesonide group (10.5%). The effervescent tablet was preferred by 80% of patients. BET or BVS was highly effective and safe for short-term treatment of EoE. The 1 mg (twice daily) dosage was equally effective as the 2 mg twice daily dosage. The majority of patients preferred the effervescent tablet formulation. NCT02280616; EudraCT number, 2009-016692-29. 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/

A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis

PubMed Central

Miehlke, Stephan; Hruz, Petr; Vieth, Michael; Bussmann, Christian; von Arnim, Ulrike; Bajbouj, Monther; Schlag, Christoph; Madisch, Ahmed; Fibbe, Christiane; Wittenburg, Henning; Allescher, Hans Dieter; Reinshagen, Max; Schubert, Stefan; Tack, Jan; Müller, Michaela; Krummenerl, Patrick; Arts, Joris; Mueller, Ralph; Dilger, Karin; Greinwald, Roland; Straumann, Alex

2016-01-01

Objective To investigate the efficacy and safety of two different budesonide formulations (effervescent tablet for orodispersible use (BET) and viscous suspension (BVS)) with different daily dosages for short-term treatment of eosinophilic oesophagitis (EoE). Design Adults with active EoE (n=76) randomly received 14 days’ treatment with either BET 2×1 mg/day (BET1, n=19) or BET 2×2 mg/day (BET2, n=19), or BVS 2×5 mL (0.4 mg/mL)/day (BVS, n=19) or placebo (n=19) in a double-blind, double-dummy fashion, with a 2-week follow-up. Primary end point was histological remission (mean of <16 eosinophils/mm2 hpf). Secondary end points included endoscopy score, dysphagia score, drug safety and patient's preference for drug formulation. Results Histological remission occurred in 100%, 94.7% and 94.7% of budesonide (BET1, BET2, BVS, respectively) and in 0% of placebo recipients (p<0.0001). The improvement in total endoscopic intensity score was significantly higher in the three budesonide groups compared with placebo. Dysphagia improved in all groups at the end of treatment; however, improvement of dysphagia persisted only in those treated with BET1 (p=0.0196 vs placebo). There were no serious adverse events. Local fungal infection (stained fungi) occurred in two patients of each budesonide group (10.5%). The effervescent tablet was preferred by 80% of patients. Conclusions BET or BVS was highly effective and safe for short-term treatment of EoE. The 1 mg (twice daily) dosage was equally effective as the 2 mg twice daily dosage. The majority of patients preferred the effervescent tablet formulation. ClinicalTrials.gov number NCT02280616; EudraCT number, 2009-016692-29. PMID:25792708

Treatment of Opioid Dependent Pregnant Women: Clinical and Research Issues

PubMed Central

Jones, H.E.; Martin, P.R.; Heil, S.H.; Stine, S.M.; Kaltenbach, K.; Selby, P.; Coyle, M.G.; O’Grady, K.E.; Arria, A.M.; Fischer, G.

2008-01-01

This paper addresses common questions that clinicians face when treating pregnant women with opioid dependence. Guidance is provided to aid clinical decision-making, based on both research evidence and the collective clinical experience of the authors which include investigators in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) project. MOTHER is a double-blind, double-dummy, flexible–dosing, parallel-group clinical trial examining the comparative safety and efficacy of methadone and buprenorphine for the opioid dependence treatment among pregnant women and their neonates. The paper begins with a discussion of appropriate assessment during pregnancy, and then addresses clinical management stages, including maintenance medication selection, induction and stabilization, opioid agonist medication management before, during and after delivery, pain management, breast-feeding, and transfer to aftercare. Lastly, other important clinical issues including managing co-occurring psychiatric disorders and medication interactions are discussed. PMID:18248941

49 CFR 572.197 - Abdomen.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES IIsD Side Impact Crash Test Dummy... impacted side removed. The dummy is equipped with a lower spine laterally oriented accelerometer as... side of the seated dummy tangent to a vertical plane located within 10 mm of the side edge of the bench...

49 CFR 572.197 - Abdomen.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES IIsD Side Impact Crash Test Dummy... impacted side removed. The dummy is equipped with a lower spine laterally oriented accelerometer as... side of the seated dummy tangent to a vertical plane located within 10 mm of the side edge of the bench...

49 CFR 572.191 - General description.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES IIsD Side Impact Crash Test Dummy, Small Adult Female § 572.191 General description. (a) The SID-IIsD Side Impact Crash Test Dummy... the SID-IIsD Side Impact Crash Test Dummy, 5th percentile adult female, is shown in drawing 180-0000...

49 CFR 572.191 - General description.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES IIsD Side Impact Crash Test Dummy, Small Adult Female § 572.191 General description. (a) The SID-IIsD Side Impact Crash Test Dummy... the SID-IIsD Side Impact Crash Test Dummy, 5th percentile adult female, is shown in drawing 180-0000...

49 CFR 572.197 - Abdomen.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES SID-IIsD Side Impact Crash Test Dummy... impacted side removed. The dummy is equipped with a lower spine laterally oriented accelerometer as... side of the seated dummy tangent to a vertical plane located within 10 mm of the side edge of the bench...

49 CFR 572.199 - Pelvis iliac.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 7 2013-10-01 2013-10-01 false Pelvis iliac. 572.199 Section 572.199... Test Dummy, Small Adult Female § 572.199 Pelvis iliac. (a) The iliac is part of the lower torso... the assembled dummy (drawing 180-0000). The dummy is equipped with a laterally oriented pelvis...

49 CFR 572.199 - Pelvis iliac.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false Pelvis iliac. 572.199 Section 572.199... Dummy, Small Adult Female § 572.199 Pelvis iliac. (a) The iliac is part of the lower torso assembly... assembled dummy (drawing 180-0000). The dummy is equipped with a laterally oriented pelvis accelerometer as...

49 CFR 572.199 - Pelvis iliac.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 false Pelvis iliac. 572.199 Section 572.199... Test Dummy, Small Adult Female § 572.199 Pelvis iliac. (a) The iliac is part of the lower torso... the assembled dummy (drawing 180-0000). The dummy is equipped with a laterally oriented pelvis...

49 CFR 572.198 - Pelvis acetabulum.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Pelvis acetabulum. 572.198 Section 572.198... Dummy, Small Adult Female § 572.198 Pelvis acetabulum. (a) The acetabulum is part of the lower torso... torso of the assembled dummy (drawing 180-0000). The dummy is equipped with a laterally oriented pelvis...

49 CFR 572.199 - Pelvis iliac.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Pelvis iliac. 572.199 Section 572.199... Dummy, Small Adult Female § 572.199 Pelvis iliac. (a) The iliac is part of the lower torso assembly... assembled dummy (drawing 180-0000). The dummy is equipped with a laterally oriented pelvis accelerometer as...

49 CFR 572.199 - Pelvis iliac.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Pelvis iliac. 572.199 Section 572.199... Dummy, Small Adult Female § 572.199 Pelvis iliac. (a) The iliac is part of the lower torso assembly... assembled dummy (drawing 180-0000). The dummy is equipped with a laterally oriented pelvis accelerometer as...

49 CFR 572.198 - Pelvis acetabulum.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false Pelvis acetabulum. 572.198 Section 572.198... Dummy, Small Adult Female § 572.198 Pelvis acetabulum. (a) The acetabulum is part of the lower torso... torso of the assembled dummy (drawing 180-0000). The dummy is equipped with a laterally oriented pelvis...

49 CFR 572.161 - General description.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Weighted Child Test Dummy § 572.161 General description. (a) The Hybrid III Six-Year-Old Weighted Child Test Dummy is defined by drawings and specifications containing the following materials: (1) “Parts List and Drawings, Part 572 Subpart S, Hybrid III Weighted Six-Year Old Child Test Dummy (H-III6CW...

Dummy left behind by Skylab 3 crew for the Skylab 4 crew

NASA Image and Video Library

1973-08-16

SL3-113-1586 (July-September 1973) --- This photograph is an illustration of the humorous side of the Skylab 3 crew. This dummy was left behind in the Skylab space station by the Skylab 3 crew to be found by the Skylab 4 crew. The dummy is dressed in a flight suit and placed in the Lower Body Negative Pressure Device. The name tag indicates that it represents Gerald P. Carr, Skylab 4 commander, in the background is a partial view of the dummy for William R. Pogue, Skylab 4 pilot, propped upon the bicycle ergometer. The dummy representing Edward G. Gibson, Skylab science pilot, was left in the waste compartment. Astronauts Alan L. Bean, Owen K. Garriott and Jack R. Lousma were the Skylab 3 crewmen. Photo credit: NASA

Dummy left behind by Skylab 3 crew for the Skylab 4 crew

NASA Image and Video Library

1973-08-16

SL3-113-1587 (July-September 1973) --- This photograph is an illustration of the humorous side of the Skylab 3 crew. This dummy was left behind in the Skylab space station by the Skylab 3 crew to be found by the Skylab 4 crew. The dummy is dressed in a flight suit and propped upon the bicycle ergometer. The name tag indicated that it represents William R. Pogue, Skylab pilot. The dummy for Gerald P. Carr, Skylab 4 commander, was placed in the Lower Body Negative Pressure Device. The dummy representing Edward G. Gibson was left in the waste compartment. Astronauts Alan L. Bean, Owen K. Garriott and Jack R. Lousma were the Skylab 3 crewmen. Gibson is the Skylab 4 science pilot. Photo credit: NASA

Male and female WorldSID and post mortem human subject responses in full-scale vehicle tests.

PubMed

Yoganandan, Narayan; Humm, John; Pintar, Frank; Rhule, Heather; Moorhouse, Kevin; Suntay, Brian; Stricklin, Jim; Rudd, Rodney; Craig, Matthew

2017-05-29

This study compares the responses of male and female WorldSID dummies with post mortem human subject (PMHS) responses in full-scale vehicle tests. Tests were conducted according to the FMVSS-214 protocols and using the U.S. Side Impact New Car Assessment Program change in velocity to match PMHS experiments, published earlier. Moving deformable barrier (MDB) tests were conducted with the male and female surrogates in the left front and left rear seats. Pole tests were performed with the male surrogate in the left front seat. Three-point belt restraints were used. Sedan-type vehicles were used from the same manufacturer with side airbags. The PMHS head was instrumented with a pyramid-shaped nine-axis accelerometer package, with angular velocity transducers on the head. Accelerometers and angular velocity transducers were secured to T1, T6, and T12 spinous processes and sacrum. Three chest bands were secured around the upper, middle, and lower thoraces. Dummy instrumentation included five infrared telescoping rods for assessment of chest compression (IR-TRACC) and a chest band at the first abdomen rib, head angular velocity transducer, and head, T1, T4, T12, and pelvis accelerometers. Morphological responses of the kinematics of the head, thoracic spine, and pelvis matched in both surrogates for each pair. The peak magnitudes of the torso accelerations were lower for the dummy than for the biological surrogate. The brain rotational injury criterion (BrIC) response was the highest in the male dummy for the MDB test and PMHS. The probability of AIS3+ injuries, based on the head injury criterion, ranged from 3% to 13% for the PMHS and from 3% to 21% for the dummy from all tests. The BrIC-based metrics ranged from 0 to 21% for the biological and 0 to 48% for the dummy surrogates. The deflection profiles from the IR-TRACC sensors were unimodal. The maximum deflections from the chest band placed on the first abdominal rib were 31.7 mm and 25.4 mm for the male and female dummies in the MDB test, and 37.4 mm for the male dummy in the pole test. The maximum deflections computed from the chest band contours at a gauge equivalent to the IR-TRACC location were 25.9 mm and 14.8 mm for the male and female dummies in the MDB test, and 37.4 mm for the male dummy in the pole test. Other data (static vehicle deformation profiles, accelerations histories of different body regions, and chest band contours for the dummy and PMHS) are given in the appendix. This is the first study to compare the responses of PMHS and male and female dummies in MDB and pole tests, done using the same recent model year vehicles with side airbag and head curtain restraints. The differences between the dummy and PMHS torso accelerations suggest the need for design improvements in the WorldSID dummy. The translation-based metrics suggest low probability of head injury. As the dummy internal sensor underrecorded the peak deflection, multipoint displacement measures are therefore needed for a more accurate quantification of deflection to improve the safety assessment of occupants.

Injury risk curves for the WorldSID 50th male dummy.

PubMed

Petitjean, Audrey; Trosseille, Xavier; Petit, Philippe; Irwin, Annette; Hassan, Joe; Praxl, Norbert

2009-11-01

The development of the WorldSID 50th percentile male dummy was initiated in 1997 by the International Organisation for Standardisation (ISO/SC12/TC22/WG5) with the objective of developing a more biofidelic side impact dummy and supporting the adoption of a harmonised dummy into regulations. More than 45 organizations from all around the world have contributed to this effort including governmental agencies, research institutes, car manufacturers and dummy manufacturers. The first production version of the WorldSID 50th male dummy was released in March 2004 and demonstrated an improved biofidelity over existing side impact dummies. Full scale vehicle tests covering a wide range of side impact test procedures were performed worldwide with the WorldSID dummy. However, the vehicle safety performance could not be assessed due to lack of injury risk curves for this dummy. The development of these curves was initiated in 2004 within the framework of ISO/SC12/TC22/WG6 (Injury criteria). In 2008, the ACEA- Dummy Task Force (TFD) decided to contribute to this work and offered resources for a project manager to coordinate of the effort of a group of volunteer biomechanical experts from international institutions (ISO, EEVC, VRTC/NHTSA, JARI, Transport Canada), car manufacturers (ACEA, Ford, General Motors, Honda, Toyota, Chrysler) and universities (Wayne State University, Ohio State University, John Hopkins University, Medical College of Wisconsin) to develop harmonized injury risk curves. An in-depth literature review was conducted. All the available PMHS datasets were identified, the test configurations and the quality of the results were checked. Criteria were developed for inclusion or exclusion of PMHS tests in the development of the injury risk curves. Data were processed to account for differences in mass and age of the subjects. Finally, injury risk curves were developed using the following statistical techniques, the certainty method, the Mertz/Weber method, the logistic regression, the survival analysis and the Consistent Threshold Estimate. The paper presents the methods used to check and process the data, select the PMHS tests, and construct the injury risk curves. The PMHS dataset as well as the injury risk curves are provided.

Analgesic Effect of Maternal Human Milk Odor on Premature Neonates: A Randomized Controlled Trial.

PubMed

Baudesson de Chanville, Audrey; Brevaut-Malaty, Véronique; Garbi, Aurélie; Tosello, Barthelemy; Baumstarck, Karine; Gire, Catherine

2017-05-01

Two studies have demonstrated an analgesic effect of maternal milk odor in preterm neonates, without specifying the method of olfactory stimulation. Research aim: This study aimed to assess the analgesic effect of maternal milk odor in preterm neonates by using a standardized method of olfactory stimulation. This trial was prospective, randomized, controlled, double blinded, and centrally administered. The inclusion criteria for breastfed infants included being born between 30 and 36 weeks + 6 days gestational age and being less than 10 days postnatal age. There were two groups: (a) A maternal milk odor group underwent a venipuncture with a diffuser emitting their own mother's milk odor and (2) a control group underwent a venipuncture with an odorless diffuser. The primary outcome was the Premature Infant Pain Profile (PIPP) score, with secondary outcomes being the French scale of neonatal pain-Douleur Aiguë du Nouveau-né (DAN) scale-and crying duration. All neonates were given a dummy. Our study included 16 neonates in the maternal milk odor group and 17 in the control group. Neonates exposed to their own mother's milk odor had a significantly lower median PIPP score during venipuncture compared with the control group (6.3 [interquartile range (IQR) = 5-10] versus 12.0 [IQR = 7-13], p = .03). There was no significant difference between the DAN scores in the two groups ( p = .06). Maternal milk odor significantly reduced crying duration after venipuncture (0 [IQR = 0-0] versus 0 [IQR = 0-18], p = .04). Maternal milk odor has an analgesic effect on preterm neonates.

49 CFR 572.198 - Pelvis acetabulum.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the dummy is in vertical orientation. (4) Push the dummy at the knees and at mid-sternum of the upper torso with just sufficient horizontally oriented force towards the seat back until the back of the upper torso is in contact with the seat back. (5) While maintaining the dummy's position as specified in...

49 CFR 572.195 - Thorax with arm.

Code of Federal Regulations, 2010 CFR

2010-10-01

... dummy is in vertical orientation. (4) Push the dummy at the knees and at mid-sternum of the upper torso with just sufficient horizontally oriented force towards the seat back until the back of the upper torso is in contact with the seat back. (5) While maintaining the dummy's position as specified in...

How Robust Is Linear Regression with Dummy Variables?

ERIC Educational Resources Information Center

Blankmeyer, Eric

2006-01-01

Researchers in education and the social sciences make extensive use of linear regression models in which the dependent variable is continuous-valued while the explanatory variables are a combination of continuous-valued regressors and dummy variables. The dummies partition the sample into groups, some of which may contain only a few observations.…

Dummy Cup Helps Robot-Welder Programmers

NASA Technical Reports Server (NTRS)

Gordon, Stephen S.

1990-01-01

Dummy gas cup used on torch of robotic welder during programming and practice runs. Made of metal or plastic, dummy cup inexpensive and durable. Withstands bumps caused by programming errors, and is sized for special welding jobs within limited clearances. After robot satisfactorily programmed, replaced by ceramic cup of same dimensions for actual welding.

A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer.

PubMed

Body, Jean-Jacques; Facon, Thierry; Coleman, Robert E; Lipton, Allan; Geurs, Filip; Fan, Michelle; Holloway, Donna; Peterson, Mark C; Bekker, Pirow J

2006-02-15

Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for the differentiation, function, and survival of osteoclasts, which play a key role in establishment and propagation of skeletal disease in patients with multiple myeloma or bone metastases as well as many other skeletal diseases. Denosumab (AMG 162), a fully human monoclonal antibody to RANKL, was developed to treat patients with skeletal diseases. This was a randomized, double-blind, double-dummy, active-controlled, multicenter study to determine the safety and efficacy of denosumab in patients with breast cancer (n = 29) or multiple myeloma (n = 25) with radiologically confirmed bone lesions. Patients received a single dose of either denosumab (0.1, 0.3, 1.0, or 3.0 mg/kg s.c.) or pamidronate (90 mg i.v.). Bone antiresorptive effect was assessed by changes in urinary and serum N-telopeptide levels. Pharmacokinetics of denosumab also were assessed. Following a single s.c. dose of denosumab, levels of urinary and serum N-telopeptide decreased within 1 day, and this decrease lasted through 84 days at the higher denosumab doses. Pamidronate also decreased bone turnover, but the effect diminished progressively through follow-up. Denosumab injections were well tolerated. Mean half-lives of denosumab were 33.3 and 46.3 days for the two highest dosages. A single s.c. dose of denosumab given to patients with multiple myeloma or bone metastases from breast cancer was well tolerated and reduced bone resorption for at least 84 days. The decrease in bone turnover markers was similar in magnitude but more sustained than with i.v. pamidronate.

Efficacy and Safety of Fluticasone Furoate/Vilanterol Compared With Fluticasone Propionate/Salmeterol Combination in Adult and Adolescent Patients With Persistent Asthma

PubMed Central

Bleecker, Eugene R.; Lötvall, Jan; O’Byrne, Paul M.; Bateman, Eric D.; Medley, Hilary; Ellsworth, Anna; Jacques, Loretta; Busse, William W.

2013-01-01

Background: The combination of fluticasone furoate (FF), a novel inhaled corticosteroid (ICS), and vilanterol (VI), a long-acting β2 agonist, is under development as a once-daily treatment of asthma and COPD. The aim of this study was to compare the efficacy of FF/VI with fluticasone propionate (FP)/salmeterol (SAL) in patients with persistent asthma uncontrolled on a medium dose of ICS. Methods: In a randomized, double-blind, double-dummy, parallel group study, 806 patients received FF/VI (100/25 μg, n = 403) once daily in the evening delivered through ELLIPTA (GlaxoSmithKline) dry powder inhaler, or FP/SAL (250/50 μg, n = 403) bid through DISKUS/ACCUHALER (GlaxoSmithKline). The primary efficacy measure was 0- to 24-h serial weighted mean (wm) FEV1 after 24 weeks of treatment. Results: Improvements from baseline in 0- to 24-h wmFEV1 were observed with both FF/VI (341 mL) and FP/SAL (377 mL); the adjusted mean treatment difference was not statistically significant (−37 mL; 95% CI, −88 to 15, P = 0.162). There were no differences between 0- to 4-h serial wmFEV1, trough FEV1, and asthma control and quality-of-life questionnaire scores. There was no difference in reported exacerbations between treatments. Both treatments were well tolerated, with no clinically relevant effect on urinary cortisol excretion or vital signs and no treatment-related serious adverse events. Conclusions: The efficacy of once-daily FF/VI was similar to bid FP/SAL in improving lung function in patients with persistent asthma. No safety issues were identified. Trial registry: ClinicalTrials.gov; No.: NCT01147848; URL: www.clinicaltrials.gov PMID:23846316

Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration.

PubMed

Karschner, Erin L; Darwin, W David; Goodwin, Robert S; Wright, Stephen; Huestis, Marilyn A

2011-01-01

Sativex(®), a cannabis extract oromucosal spray containing Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC's effects, but it is unclear if this is due to a pharmacokinetic and/or pharmacodynamic interaction. Cannabis smokers provided written informed consent to participate in this randomized, controlled, double-blind, double-dummy institutional review board-approved study. Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and 5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over 5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor- 9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS. Lower limits of quantification were ≤0.25 μg/L. Nine cannabis smokers completed all 5 dosing sessions. Significant differences (P < 0.05) in maximum plasma concentrations (C(max)) and areas under the curve from 0-10.5 h postdose (AUC(0→10.5)) for all analytes were found between low and high doses of synthetic THC and Sativex. There were no statistically significant differences in C(max), time to maximum concentration or in the AUC(0→10.5) between similar oral THC and Sativex doses. Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively. These data suggest that CBD modulation of THC's effects is not due to a pharmacokinetic interaction at these therapeutic doses.

Differences in the profile of neonatal abstinence syndrome signs in methadone- versus buprenorphine-exposed neonates

PubMed Central

Gaalema, Diann E.; Scott, Teresa Linares; Heil, Sarah H.; Coyle, Mara G.; Kaltenbach, Karol; Badger, Gary J.; Arria, Amelia M.; Stine, Susan M.; Martin, Peter R.; Jones, Hendrée E.

2014-01-01

Aims To compare the profile of signs of neonatal abstinence syndrome (NAS) in methadone- versus buprenorphine-exposed infants. Design, setting and participants Secondary analysis of NAS data from a multi-site, double-blind, double-dummy, flexible-dosing, randomized clinical trial. Data from a total of 129 neonates born to opioid-dependent women who had been assigned to receive methadone or buprenorphine treatment during pregnancy were examined. Measurements For 10 days after delivery, neonates (methadone = 72, buprenorphine = 57) were assessed regularly using a 19-item modified Finnegan scale. Data from neonates who required pharmacological treatment (methadone = 41, buprenorphine = 27) were included up to the time treatment was initiated. The incidence and mean severity of the total NAS score and each individual sign of NAS were calculated and compared between medication conditions, as was the median time until morphine treatment initiation among treated infants in each condition. Findings Two NAS signs (undisturbed tremors and hyperactive Moro reflex) were observed significantly more frequently in methadone-exposed neonates and three (nasal stuffiness, sneezing, loose stools) were observed more frequently in buprenorphine-exposed neonates. Mean severity scores on the total NAS score and five individual signs (disturbed and undisturbed tremors, hyperactive Moro reflex, excessive irritability, failure to thrive) were significantly higher among methadone-exposed neonates, while sneezing was higher among buprenorphine-exposed neonates. Among treated neonates, methadone-exposed infants required treatment significantly earlier than buprenorphine-exposed infants (36 versus 59 hours postnatal, respectively). Conclusions The profile of neonatal abstinence syndrome differs in methadone- versus buprenorphine-exposed neonates, with significant differences in incidence, severity and treatment initiation time. Overall, methadone-exposed neonates have a more severe neonatal abstinence syndrome. PMID:23106927

Once daily mometasone furoate aqueous nasal spray is as effective as twice daily beclomethasone dipropionate for treating perennial allergic rhinitis patients.

PubMed

Drouin, M; Yang, W H; Bertrand, B; Van Cauwenberge, P; Clement, P; Dalby, K; Darnell, R; Ernst, T M; Hébert, J; Karlsson, G; Luciuk, G; Mazza, J; Roovers, M; Ruoppi, P; Seppey, M; Stern, M; Suonpää, J; Sussman, G; Tan, K Y; Tse, K; Widjaja, P; Jensen, P; Nolop, K; Lutsky, B N

1996-08-01

Perennial allergic rhinitis is chronic and persistent, may lead to a constellation of secondary complaints including sinusitis, mouth-breathing, and some symptoms resembling a permanent cold, and often requires constant medical intervention. Well-tolerated nasal corticosteroids, alone or in combination with antihistamines, have been found to be very effective in treating this condition. To compare the effectiveness and tolerability of mometasone furoate aqueous suspension, a new once daily nasal spray, to placebo vehicle and to beclomethasone dipropionate, administered twice daily, in patients with perennial allergic rhinitis. This was a randomized, double-blind, placebo-controlled, double-dummy, parallel group study, in 427 patients age 12 years and older at 24 centers in Canada and Europe. Patients allergic to at least one perennial allergen, confirmed by medical history, skin testing, and adequate symptomatology were eligible to receive one of the following regimens for 3 months: mometasone furoate, 200 micrograms only daily; beclomethasone dipropionate, 200 micrograms twice daily (400 micrograms total dose); or placebo vehicle control. The primary efficacy variable was the change from baseline in total AM plus PM diary nasal symptom score over the first 15 days of treatment. Three hundred eighty-seven patients were valid for efficacy. For the primary efficacy variable, mometasone furoate was significantly (P < or = .01) more effective than placebo and was indistinguishable from beclomethasone dipropionate. Similar trends were seen among individual symptoms, physician symptom evaluations, and therapeutic response. There was no evidence of tachyphylaxis. All treatments were well tolerated. Mometasone furoate nasal spray adequately controls symptoms of perennial allergic rhinitis, offers the advantage of once daily treatment, and is well tolerated.

Next-day effects of ramelteon (8 mg), zopiclone (7.5 mg), and placebo on highway driving performance, memory functioning, psychomotor performance, and mood in healthy adult subjects.

PubMed

Mets, Monique A J; de Vries, Juna M; de Senerpont Domis, Lieke M; Volkerts, Edmund R; Olivier, Berend; Verster, Joris C

2011-10-01

To evaluate the next-morning residual effects of ramelteon (8 mg), zopiclone (7.5 mg), and placebo on driving performance, memory functioning, psychomotor performance, and mood in healthy adult subjects following bedtime dosing and a middle of the night awakening. Single-center, randomized, double-blind, double-dummy, placebo-controlled, crossover study. Utrecht University, The Netherlands. 30 healthy volunteers (15 males and 15 females). a single dose of ramelteon (8 mg), zopiclone (7.5 mg), and placebo, administered at bedtime. A balance test was performed at night. Other tests were performed the following morning, 8.5 h after administration. Subjects performed a 100-km highway driving test in normal traffic. Primary outcome measure was the standard deviation of the lateral position (SDLP), i.e., the weaving of the car. After driving, cognitive, memory, and psychomotor tests were performed and mood was assessed. SDLP was significantly increased after the intake of ramelteon (+2.2 cm) and zopiclone (+2.9 cm). Ramelteon and zopiclone produced significant impairment on reaction time (P<0.024) in the Sternberg Memory Scanning Test, slow (P<0.007) and fast (P<0.010) tracking, reaction speed (P<0.015) and tracking (P<0.001) in the Divided Attention Test, and delayed recall (P<0.032) in the Word Learning Test. In contrast to ramelteon, zopiclone additionally impaired performance on the Digit Symbol Substitution Test (P<0.001) and the balance test (P<0.001). Ramelteon (8 mg) and zopiclone (7.5 mg) significantly impaired driving performance, cognitive, memory, and psychomotor performance the morning following bedtime administration. In contrast to zopiclone, ramelteon produced no balance impairments. CLINICAL TRIAL IDENTIFIER: NCT00319215 (www.clinicaltrials.gov).

Improved Pharmacokinetic and Pharmacodynamic Profile of Rapid-Acting Insulin Using Needle-Free Jet Injection Technology

PubMed Central

Engwerda, Elsemiek E.C.; Abbink, Evertine J.; Tack, Cees J.; de Galan, Bastiaan E.

2011-01-01

OBJECTIVE Insulin administered by jet injectors is dispensed over a larger subcutaneous area than insulin injected with a syringe, which may facilitate a more rapid absorption. This study compared the pharmacologic profile of administration of insulin aspart by jet injection to that by conventional insulin pen. RESEARCH DESIGN AND METHODS Euglycemic glucose clamp tests were performed in 18 healthy volunteers after subcutaneous administration of 0.2 units/kg body wt of aspart, either administered by jet injection or by conventional pen, using a randomized, double-blind, double-dummy, cross over study design. Pharmacodynamic and pharmacokinetic profiles were derived from the glucose infusion rate (GIR) needed to maintain euglycemia and from plasma insulin levels, respectively. RESULTS The time to maximal GIR was significantly shorter when insulin was injected with the jet injector compared with conventional pen administration (51 ± 3 vs. 105 ± 11 min, P < 0.0001). The time to peak insulin concentration was similarly reduced (31 ± 3 vs. 64 ± 6 min, P < 0.0001) and peak insulin concentrations were increased (108 ± 13 vs. 79 ± 7 mU/L, P = 0.01) when insulin was injected by jet injection compared with conventional pen injection. Jet injector insulin administration reduced the time to 50% glucose disposal by ∼40 min (P < 0.0001). There were no differences in maximal GIR, total insulin absorption, or total insulin action between the two devices. CONCLUSIONS Administration of insulin aspart by jet injection enhances insulin absorption and reduces the duration of glucose-lowering action. This profile resembles more closely the pattern of endogenous insulin secretion and may help to achieve better meal insulin coverage and correction of postprandial glucose excursions. PMID:21715522

Comparison of the Analgesic Effects of Dronabinol and Smoked Marijuana in Daily Marijuana Smokers

PubMed Central

Cooper, Ziva D; Comer, Sandra D; Haney, Margaret

2013-01-01

Recent studies have demonstrated the therapeutic potential of cannabinoids to treat pain, yet none have compared the analgesic effectiveness of smoked marijuana to orally administered Δ9-tetrahydrocannabinol (THC; dronabinol). This randomized, placebo-controlled, double-dummy, double-blind study compared the magnitude and duration of analgesic effects of smoked marijuana and dronabinol under well-controlled conditions using a validated experimental model of pain. Healthy male (N=15) and female (N=15) daily marijuana smokers participated in this outpatient study comparing the analgesic, subjective, and physiological effects of marijuana (0.00, 1.98, or 3.56% THC) to dronabinol (0, 10, or 20 mg). Pain response was assessed using the cold-pressor test (CPT): participants immersed their left hand in cold water (4 °C), and the time to report pain (pain sensitivity) and withdraw the hand from the water (pain tolerance) were recorded. Subjective pain and drug effect ratings were also measured as well as cardiovascular effects. Compared with placebo, marijuana and dronabinol decreased pain sensitivity (3.56% 20 mg), increased pain tolerance (1.98% 20 mg), and decreased subjective ratings of pain intensity (1.98, 3.56% 20 mg). The magnitude of peak change in pain sensitivity and tolerance did not differ between marijuana and dronabinol, although dronabinol produced analgesia that was of a longer duration. Marijuana (1.98, 3.56%) and dronabinol (20 mg) also increased abuse-related subjective ratings relative to placebo; these ratings were greater with marijuana. These data indicate that under controlled conditions, marijuana and dronabinol decreased pain, with dronabinol producing longer-lasting decreases in pain sensitivity and lower ratings of abuse-related subjective effects than marijuana. PMID:23609132

Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials

PubMed Central

Kullberg, Bart Jan; Vasquez, José; Mootsikapun, Piroon; Nucci, Marcio; Paiva, José-Artur; Garbino, Jorge; Yan, Jean Li; Aram, Jalal; Capparella, Maria Rita; Conte, Umberto; Schlamm, Haran; Swanson, Robert; Herbrecht, Raoul

2017-01-01

Abstract Objectives: To evaluate the efficacy of anidulafungin for the treatment of candidaemia and invasive candidiasis in a large dataset, including patients with deep-seated tissue candidiasis, neutropenia and infection due to non-albicans Candida species. Methods: Data were pooled from six prospective, multicentre, multinational studies: four open-label, non-comparative studies of anidulafungin and two double-blind, double-dummy, randomized studies of anidulafungin versus caspofungin (clinical trial registrations: NCT00496197, NCT00548262, NCT00537329, NCT00689338, NCT00806351 and NCT00805740; ClinicalTrials.gov). In all studies, patients with culture-confirmed invasive candidiasis received a single intravenous (iv) loading dose of anidulafungin 200 mg on day 1, followed by 100 mg once-daily. Switch to oral fluconazole or voriconazole was permitted after 5–10 days of iv treatment in all studies except one. Antifungal treatment (iv plus oral therapy if applicable) was maintained for ≥14 days after the last positive Candida culture. The primary endpoint was successful global response at end of iv therapy (EOivT) in the modified ITT (mITT) population. Results: In total, 539 patients were included (mITT population). The most common baseline Candida species were Candida albicans (47.9%), Candida glabrata (21.0%), Candida tropicalis (13.7%), Candida parapsilosis (13.2%) and Candida krusei (3.5%). Median duration of anidulafungin iv treatment was 10.0 days. The global response success rate at EOivT was 76.4% (95% CI 72.9%–80.0%). All-cause mortality was 13.0% on day 14 and 19.1% on day 28. Adverse events (AEs) were consistent with the known AE profile for anidulafungin. Conclusions: These data demonstrate that anidulafungin is effective for treatment of candidaemia and invasive candidiasis in a broad patient population. PMID:28459966

Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial.

PubMed

Genovese, Mark C; Pacheco-Tena, César; Covarrubias, Arturo; Leon, Gustavo; Mysler, Eduardo; Keiserman, Mauro; Valente, Robert M; Nash, Peter; Simon-Campos, J Abraham; Box, Jane; Legerton, Clarence W; Nasonov, Evgeny; Durez, Patrick; Elegbe, Ayanbola; Wong, Robert; Li, Xiaohui; Banerjee, Subhashis; Alten, Rieke

2018-04-15

To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported. Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96-8.58), infection 38.60 (36.24-41.12), serious infection 1.68 (1.35-2.07), malignancies 1.09 (0.84-1.42), and autoimmune disorders 1.33 (1.05-1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study. These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.

Antipyretic and analgesic effects of zaltoprofen for the treatment of acute upper respiratory tract infection: verification of a noninferiority hypothesis using loxoprofen sodium.

PubMed

Azuma, Arata; Kudoh, Shoji; Nakashima, Mitsuyoshi; Nagatake, Tsuyoshi

2011-01-01

A multicenter, placebo-controlled, double-dummy, randomized, parallel-group, double-blind study was conducted to verify the hypothesis of noninferiority for single-dose administration of zaltoprofen 160 mg, a nonsteroidal anti-inflammatory drug, compared with loxoprofen sodium 60 mg (loxoprofen), in terms of antipyretic and analgesic effects in patients with acute upper respiratory tract infection. The eligible 330 patients were assigned to one of 3 groups: zaltoprofen 160 mg, loxoprofen 60 mg and placebo. The analysis set consisted of 322 patients. Antipyretic effects were assessed by measuring body temperature, and analgesic effects were evaluated using a visual analog scale (VAS) for 4 h under the control of study staff. A detection kit for influenza virus A and B antigens was used to determine the presence of influenza virus infection. Compared with immediately before administration and with the placebo group, significant decreases in body temperature and summary VAS pain scores were noted in both the zaltoprofen and loxoprofen groups at 4 h after drug administration. Based on the degree of decrease in body temperature and the summary VAS pain scores up to 4 h after administration, noninferiority in terms of antipyretic and analgesic effects of zaltoprofen compared with those of loxoprofen was confirmed after single administration. Similar antipyretic and analgesic effects were also confirmed in influenza virus antigen-positive patients (73 patients). No clinical concerns were identified regarding safety. Zaltoprofen and loxoprofen are confirmed to be safe and useful for patients with acute upper respiratory tract infection, including those with influenza infection. Copyright © 2011 S. Karger AG, Basel.

Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis

PubMed Central

Stone, John H.; Merkel, Peter A.; Spiera, Robert; Seo, Philip; Langford, Carol A.; Hoffman, Gary S.; Kallenberg, Cees G.M.; St. Clair, E. William; Turkiewicz, Anthony; Tchao, Nadia K.; Webber, Lisa; Ding, Linna; Sejismundo, Lourdes P.; Mieras, Kathleen; Weitzenkamp, David; Ikle, David; Seyfert-Margolis, Vicki; Mueller, Mark; Brunetta, Paul; Allen, Nancy B.; Fervenza, Fernando C.; Geetha, Duvuru; Keogh, Karina A.; Kissin, Eugene Y.; Monach, Paul A.; Peikert, Tobias; Stegeman, Coen; Ytterberg, Steven R.; Specks, Ulrich

2011-01-01

BACKGROUND Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. METHODS We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. RESULTS Nine centers enrolled 197 ANCA-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P = 0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. CONCLUSIONS Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.) PMID:20647199

Secukinumab after anti-tumour necrosis factor-α therapy: a phase III study in active rheumatoid arthritis.

PubMed

Dokoupilová, E; Aelion, J; Takeuchi, T; Malavolta, N; Sfikakis, P P; Wang, Y; Rohrer, S; Richards, H B

2018-02-20

To assess the efficacy and safety of secukinumab in patients with rheumatoid arthritis (RA) who failed to respond to tumour necrosis factor- α (TNF-α) inhibitors. This phase III double-blind, double-dummy, placebo-controlled study (NCT01770379) randomized (1:1:1) patients to subcutaneous secukinumab 150 mg, secukinumab 75 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks. American College of Rheumatology (ACR) 20 response at week 24 was the primary endpoint. Secondary outcomes included the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire Disability Index (HAQ-DI), and ACR50 at week 24. Long-term treatment was planned for 5 years. ACR20 response rates at week 24 for the secukinumab 150 mg and 75 mg groups were not statistically superior to placebo. None of the secondary endpoints was met for either secukinumab dose. Although not statistically significant, compared with placebo, numerically greater differences in least squares mean changes from baseline in HAQ-DI score and numerically higher ACR50 response rates were observed at week 24 in both secukinumab treatment groups. No new or unexpected adverse events were observed in this study compared with the large secukinumab safety database across psoriasis, psoriatic arthritis, ankylosing spondylitis, and other RA studies. Given that other second-line therapies have demonstrated efficacy in RA patients who failed to respond to TNF-α inhibitors, these findings may suggest that interleukin-17A inhibition with secukinumab does not provide additional benefit to these patients. This study further confirms the well-characterized safety profile of secukinumab.

Psychometric validation of the Psoriasis Symptom Diary using Phase III study data from patients with chronic plaque psoriasis.

PubMed

Strober, Bruce; Zhao, Yang; Tran, Mary Helen; Gnanasakthy, Ari; Nyirady, Judit; Papavassilis, Charis; Nelson, Lauren M; McLeod, Lori D; Mordin, Margaret; Gottlieb, Alice B; Elewski, Boni E; Lebwohl, Mark

2016-03-01

This analysis aimed to confirm the reliability, validity, and responsiveness of the Psoriasis Symptom Diary (PSD) using data from two Phase III studies in patients with moderate to severe chronic plaque psoriasis. Data from two randomized, double-blind, double-dummy, placebo-controlled, multicenter Phase III studies (n = 820) assessing the efficacy and safety of secukinumab were used. The PSD (24-h recall; 0-10 numeric rating scale) was electronically administered each evening. Test-retest reliability was determined using intraclass correlations. Construct validity hypotheses were evaluated via correlations with the Psoriasis Area and Severity Index (PASI), Investigator's Global Assessment (IGA), Dermatology Life Quality Index (DLQI), EuroQoL 5-Dimension Health Status Questionnaire, and Patient Global Impression of Change (PGIC). Discriminating ability and responsiveness were evaluated by estimating mean differences and effect sizes between known groups (using the PASI and IGA). Phase II-derived, anchor-based PGIC thresholds and cumulative distribution function (CDF) plots described meaningful change. Items on the PSD yielded high intraclass coefficients (>0.90). Correlations were in the anticipated direction and by week 12 were moderate to strong (0.41-0.73) in magnitude, demonstrating construct validity. Average PSD item scores differed predictably and significantly between known groups. Responsiveness effect size estimates were moderate to large (0.6-1.5), and CDF plots showed the percentage of responders to be consistently higher in treatment than in placebo arms across the range of change in PSD scores. The PSD is reliable, valid, and responsive, and represents a valid tool to enhance treatment decisions in patients with moderate to severe plaque psoriasis. © 2015 The International Society of Dermatology.

Comparison of the analgesic effects of dronabinol and smoked marijuana in daily marijuana smokers.

PubMed

Cooper, Ziva D; Comer, Sandra D; Haney, Margaret

2013-09-01

Recent studies have demonstrated the therapeutic potential of cannabinoids to treat pain, yet none have compared the analgesic effectiveness of smoked marijuana to orally administered Δ(9)-tetrahydrocannabinol (THC; dronabinol). This randomized, placebo-controlled, double-dummy, double-blind study compared the magnitude and duration of analgesic effects of smoked marijuana and dronabinol under well-controlled conditions using a validated experimental model of pain. Healthy male (N=15) and female (N=15) daily marijuana smokers participated in this outpatient study comparing the analgesic, subjective, and physiological effects of marijuana (0.00, 1.98, or 3.56% THC) to dronabinol (0, 10, or 20 mg). Pain response was assessed using the cold-pressor test (CPT): participants immersed their left hand in cold water (4 °C), and the time to report pain (pain sensitivity) and withdraw the hand from the water (pain tolerance) were recorded. Subjective pain and drug effect ratings were also measured as well as cardiovascular effects. Compared with placebo, marijuana and dronabinol decreased pain sensitivity (3.56%; 20 mg), increased pain tolerance (1.98%; 20 mg), and decreased subjective ratings of pain intensity (1.98, 3.56%; 20 mg). The magnitude of peak change in pain sensitivity and tolerance did not differ between marijuana and dronabinol, although dronabinol produced analgesia that was of a longer duration. Marijuana (1.98, 3.56%) and dronabinol (20 mg) also increased abuse-related subjective ratings relative to placebo; these ratings were greater with marijuana. These data indicate that under controlled conditions, marijuana and dronabinol decreased pain, with dronabinol producing longer-lasting decreases in pain sensitivity and lower ratings of abuse-related subjective effects than marijuana.

Relative Bioavailability, Intranasal Abuse Potential, and Safety of Benzhydrocodone/Acetaminophen Compared with Hydrocodone Bitartrate/Acetaminophen in Recreational Drug Abusers.

PubMed

Guenther, Sven M; Mickle, Travis C; Barrett, Andrew C; Roupe, Kathryn Ann; Zhou, Jing; Lam, Vincent

2018-05-01

Benzhydrocodone is a hydrocodone prodrug that has been combined with acetaminophen (APAP) in a novel immediate-release analgesic. This study evaluated the relative bioavailability, intranasal abuse potential, and safety of benzhydrocodone/APAP compared with commercially available hydrocodone bitartrate (HB)/APAP. Single-center, randomized, double-blind, double-dummy, two-part study comprising a Dose Selection (Part A) phase and a Main Study (Part B) phase. Clinical research site. Healthy adult, nondependent, recreational opioid users with a history of intranasal abuse. Subjects (N = 42) in Part B received five in-clinic treatments consisting of intranasal and oral benzhydrocodone/APAP (13.34/650 mg), intranasal and oral hydrocodone/APAP (15/650 mg), and placebo, with four or more days of washout between treatments. Pharmacodynamic assessments included subjective effects of Drug Liking, Overall Drug Liking, and Take Drug Again (assessed on visual analog scale [VAS]), as well as nasal irritation. Pharmacokinetics and safety were also assessed. Hydrocodone Cmax was 11% lower for intranasal benzhydrocodone/APAP vs intranasal HB/APAP (P = 0.0027). Early cumulative hydrocodone exposures for intranasal benzhydrocodone/APAP through 0.5, 1, and 2 hours were reduced by approximately 50%, 29%, and 15%, respectively (P ≤ 0.0024). Correspondingly, Drug Liking VAS values up to two hours postdose were significantly lower for intranasal benzhydrocodone/APAP vs intranasal HB/APAP (P ≤ 0.0079), although peak Drug Liking VAS (Emax) scores were not different (P = 0.2814). Adverse nasal effects were more frequent for intranasal benzhydrocodone/APAP vs intranasal HB/APAP. Reduced hydrocodone exposure and drug liking at early time intervals, coupled with adverse nasal effects, can be expected to provide a level of deterrence to the intranasal route of abuse for benzhydrocodone/APAP.

Plasma Cannabinoid Pharmacokinetics following Controlled Oral Δ9-Tetrahydrocannabinol and Oromucosal Cannabis Extract Administration

PubMed Central

Karschner, Erin L.; Darwin, W. David; Goodwin, Robert S.; Wright, Stephen; Huestis, Marilyn A.

2013-01-01

BACKGROUND Sativex®, a cannabis extract oromucosal spray containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC’s effects, but it is unclear if this is due to a pharmacokinetic and/or pharmacodynamic interaction. METHODS Cannabis smokers provided written informed consent to participate in this randomized, controlled, double-blind, double-dummy institutional review board–approved study. Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and 5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over 5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS. Lower limits of quantification were ≤0.25 μg/L. RESULTS Nine cannabis smokers completed all 5 dosing sessions. Significant differences (P < 0.05) in maximum plasma concentrations (Cmax) and areas under the curve from 0–10.5 h postdose (AUC0→10.5) for all analytes were found between low and high doses of synthetic THC and Sativex. There were no statistically significant differences in Cmax, time to maximum concentration or in the AUC0→10.5 between similar oral THC and Sativex doses. Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively. CONCLUSION These data suggest that CBD modulation of THC’s effects is not due to a pharmacokinetic interaction at these therapeutic doses. PMID:21078841

Efficacy and safety profiles of a new S(-)-amlodipine nicotinate formulation versus racemic amlodipine besylate in adult Korean patients with mild to moderate hypertension: an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group, phase III, noninferiority clinical trial.

PubMed

Kim, Sung Ai; Park, Sungha; Chung, Namsik; Lim, Do-Sun; Yang, Joo-Young; Oh, Byung-Hee; Tahk, Seung-Jea; Ahn, Tae-Hoon

2008-05-01

"Chiral switching" from an existing racemate to a pure enantiomeric compound is a popular theme in drug development, especially when the enantiomer is found to have better efficacy and safety profiles. Amlodipine is a racemic mixture, composed of the S(-)-enantiomer, which is the pharmacologically active isomer, and the R(+)-enantiomer, which is 1000-fold less active. S(-)-amlodipine nicotinate, a chirally switched form of amlodipine nicotinate, has been developed and found to be bioequivalent to amlodipine besylate in Phase I clinical trials in Korea. The aim of this study was to compare the efficacy and safety profiles of S(-)-amlodipine nicotinate with those of amlodipine besylate in adult Korean patients with mild to moderate hypertension (diastolic blood pressure [DBP] >or=90 mm Hg and or=90 and or=90 mm Hg). The primary end point was noninferiority of the difference in mean SiDBP from baseline to week 8 for S(-)-amlodipine nicotinate compared with amlodipine besylate. Secondary end points were as follows: (1) noninferiority of the difference in mean sitting systolic blood pressure (SiSBP) from baseline to week 8 between the study groups; and (2) SiDBP response rate (defined as the proportion of patients whose SiDBP was <90 mm Hg or whose SiDBP reduction was >or=10 mm Hg from baseline) after the 8-week treatment. Also, the incidence and severity of adverse events (AEs) and adverse drug reactions (ADRs) were reported. Severe AEs/ADRs were defined as those associated with any of the following: death; an event associated with a high risk of mortality; an event requiring hospitalization; or development of a permanent disability or congenital malformation. One hundred fifty-seven patients were assessed for inclusion in the study. Of these, 124 patients were randomly allocated to receive S(-)-amlodipine nicotinate (42 men, 21 women; mean [SD] age, 52.4 [10.3] years [range, 23-70 years]; weight, 67.7 [10.8] kg [range, 44-92 kg]) or amlodipine besylate (45 men, 16 women; mean [SD] age, 54.5 [10.0] years [range, 30-73]; weight, 68.9 [9.8] kg [range, 49-95 kg]). One hundred sixteen patients completed the study, but 11 patients (8.9%) were dropped from the per-protocol analysis due to violations; therefore, 105 patients were included in the modified intent-to-treat population analysis (S[-]-amlodipine nicotinate, 55 patients; amlodipine besylate, 50 patients). There were no significant between-group differences in the baseline characteristics. Baseline mean (SD) SiSBP and SiDBP were 142.6 (11.3) and 94.9 (4.8) mm Hg in the S(-)-amlodipine nicotinate group, and 141.8 (8.3) and 96.1 (4.9) mm Hg in the amlodipine besylate group. Mean (SD) changes in SiSBP were 17.6 (11.2) mm Hg in the S(-)-amlodipine nicotinate group and 18.6 (12.3) mm Hg in the amlodipine besylate group. The SiDBP response rates were 92.7% in the S(-)-amlodipine nicotinate group and 88.0% in the amlodipine besylate group. There were no significant between-group differences in the prevalence of AEs and ADRs. In the S(-)-amlodipine nicotinate group, 15 patients (23.8%) reported a total of 28 AEs, and 19 patients (31.1%) reported a total of 27 AEs in the amlodipine besylate group. Six patients (9.5%) in the S(-)-amlodipine nicotinate group and 7 patients (11.4%) in the amlodipine besylate group experienced a total of 19 ADRs (11 and 8, respectively). The most common ADRs were liver enzyme elevation (3/63 [4.8%]) in the S(-)-amlodipine nicotinate group and facial flushing (3/61 [4.9%]) in the amlodipine besylate group. No cases of severe AEs or ADRs were reported in either group. The reduction of SiDBP after 8 weeks of treatment with S(-)-amlodipine nicotinate was noninferior compared with that of racemic amlodipine besylate in these adult Korean patients with mild to moderate hypertension. The SiDBP response rate and the reduction of SiSBP after 8 weeks of treatment with S(-)-amlodipine nicotinate were not significantly different from those with racemic amlodipine besylate. Both treatments were generally well tolerated.

49 CFR 572.140 - Incorporation by reference.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Child Crash Test Dummy, Alpha Version § 572.140 Incorporation by reference. (a) The following materials... entitled, “Parts List and Drawings, Subpart P Hybrid III 3-year-old child crash test dummy, (H-III3C, Alpha..., Disassembly and Inspection (PADI), Subpart P, Hybird III 3-year-old Child Crash Test Dummy, (H-III3C, Alpha...

49 CFR 572.140 - Incorporation by reference.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Child Crash Test Dummy, Alpha Version § 572.140 Incorporation by reference. (a) The following materials... entitled, “Parts List and Drawings, Subpart P Hybrid III 3-year-old child crash test dummy, (H-III3C, Alpha..., Disassembly and Inspection (PADI), Subpart P, Hybird III 3-year-old Child Crash Test Dummy, (H-III3C, Alpha...

49 CFR 572.140 - Incorporation by reference.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Child Crash Test Dummy, Alpha Version § 572.140 Incorporation by reference. (a) The following materials... entitled, “Parts List and Drawings, Subpart P Hybrid III 3-year-old child crash test dummy, (H-III3C, Alpha..., Disassembly and Inspection (PADI), Subpart P, Hybird III 3-year-old Child Crash Test Dummy, (H-III3C, Alpha...

49 CFR 572.140 - Incorporation by reference.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Child Crash Test Dummy, Alpha Version § 572.140 Incorporation by reference. (a) The following materials... entitled, “Parts List and Drawings, Subpart P Hybrid III 3-year-old child crash test dummy, (H-III3C, Alpha..., Disassembly and Inspection (PADI), Subpart P, Hybird III 3-year-old Child Crash Test Dummy, (H-III3C, Alpha...

49 CFR 572.140 - Incorporation by reference.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Child Crash Test Dummy, Alpha Version § 572.140 Incorporation by reference. (a) The following materials... entitled, “Parts List and Drawings, Subpart P Hybrid III 3-year-old child crash test dummy, (H-III3C, Alpha..., Disassembly and Inspection (PADI), Subpart P, Hybird III 3-year-old Child Crash Test Dummy, (H-III3C, Alpha...

49 CFR 572.76 - Limbs assembly and test procedure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... between 1g and 2g. (ii) Place the dummy legs in a plane parallel to the dummy's midsagittal plane with the knee pivot center line perpendicular to the dummy's midsagittal plane, and with the feet flat on the... parallel to the midsagittal plane at the specified velocity. (5) Guide the test probe during impact so that...

Do open label blinded outcome studies of novel anticoagulants versus warfarin have equivalent validity to those carried out under double-blind conditions?

PubMed

O'Neil, William M; Welner, Sharon A; Lip, Gregory Y H

2013-03-01

Recent anticoagulants for stroke prevention in AF have been tested in active comparator controlled studies versus warfarin using two designs: double-blind, double-dummy and prospective randomised, open blinded endpoint (PROBE). The former requires elaborate procedures to maintain blinding, while PROBE does not. Outcomes of double-blind and PROBE designed studies of novel anticoagulants for AF, focusing on warfarin controls, were explored. Major, Phase III warfarin-controlled trials for stroke prevention in AF were identified. Odds ratios (ORs) of key outcomes for active comparators versus VKA and event rates for VKA arms were compared between designs, in context of baseline demographics and inclusion criteria. Identified trials studied five novel anticoagulants in three each of PROBE and double-blind design. For ORs of results across studies and outcomes, there was little pattern differentiating the two designs. Among VKA-control subjects, event rates for the primary outcome (stroke or systemic embolism) in PROBE trials at 1.74 %/year (95% confidence interval: 1.54-1.95) was not significantly different from that in double-blind trials, at 1.88 (1.73-2.03). Among other outcomes, VKA-treated subjects in both trial designs had similar event rates, apart from higher all-cause mortality in ROCKET AF, and lower myocardial infarction rates among the PROBE study patients. Although there are differences in outcome between PROBE and double blind trials, they do not appear to be design-related. The exacting requirements of double-blinding in AF trials may not be necessary.

Laboratory Reconstructions of Real World Frontal Crash Configurations using the Hybrid III and THOR Dummies and PMHS.

PubMed

Petitjean, Audrey; Lebarbe, Matthieu; Potier, Pascal; Trosseille, Xavier; Lassau, Jean-Pierre

2002-11-01

Load-limiting belt restraints have been present in French cars since 1995. An accident study showed the greater effectiveness in thorax injury prevention using a 4 kN load limiter belt with an airbag than using a 6 kN load limiter belt without airbag. The criteria for thoracic tolerance used in regulatory testing is the sternal deflection for all restraint types, belt and/or airbag restraint. This criterion does not assess the effectiveness of the restraint 4 kN load limiter belt with airbag observed in accidentology. To improve the understanding of thoracic tolerance, frontal sled crashes were performed using the Hybrid III and THOR dummies and PMHS. The sled configuration and the deceleration law correspond to those observed in the accident study. Restraint conditions evaluated are the 6 kN load-limiting belt and the 4 kN load-limiting belt with an airbag. Loads between the occupant and the sled environment were recorded. Various measurements (including thoracic deflections and head, thorax and pelvis accelerations and angular velocities on the dummies) characterize the dummy and PMHS behavior. PMHS anthropometry and injuries were noted. This study presents the test methodology and the results used to evaluate dummy ability to discriminate both restraint types and dummy measurement ability to be representative of thoracic injury risk for all restraint types. The injury results of the PMHS tests showed the same tendency as the accident study. Some of the criteria proposed in the literature did not show a better protection of the 4 kN load limiter belt with airbag restraint, in particular thoracic deflection maxima for both dummies. The four thoracic deflections measured on the THOR and Hybrid III dummies may allow more accurate analysis of the loading pattern and therefore of injury risk.

Trauma potential and ballistic parameters of cal. 9 mm P.A. dummy launchers.

PubMed

Frank, Matthias; Bockholdt, Britta; Philipp, Klaus-Peter; Ekkernkamp, Axel

2010-07-15

Blank cartridge actuated dummy launching devices are used by migratory bird hunters to train dogs to retrieve downed birds. The devices create a loud noise while simultaneously propelling a hard foam dummy for retrieval. A newly developed dummy launcher is based on a modified cal. 9 mm P.A. blank handgun with an extension tube pinned and welded to the barrel imitation. Currently, there are no experimental investigations on the ballistic background and trauma potential of these uncommon shooting devices. An experimental test set-up consisting of a photoelectric infrared light barrier was used for measurement of the velocity of hard foam dummies propelled with an automatic dummy launcher. Ballistic parameters of the dummies and an aluminium sleeve as improvised projectile (kinetic energy (E), impulse (p), energy density (E') and threshold velocity (v(tsh)) to cause penetrating wounds as a function of cross-sectional density (S)) were calculated. The average velocity (v) of the dummies was measured 25.71 m/s exerting an average impulse (p) of 3.342 Ns. The average kinetic energy (E) was calculated 43.04 J with an average energy density (E') of 0.069 J/mm(2). The average velocity (v) of the aluminium sleeves as improvised projectiles was measured 79.58 m/s exerting an average impulse (p) of 2.228 Ns. The average kinetic energy (E) of the aluminium sleeves was calculated as 88.70 J with an average energy density (E') of 0.282 J/mm(2). The energy delivered by these shooting devices is high enough to cause relevant injuries. The absence of skin penetration must not mislead the emergency physician or forensic expert into neglecting the potential damage from these devices. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Efficacy of MaZiRenWan, a Chinese Herbal Medicine, in Patients With Functional Constipation in a Randomized Controlled Trial.

PubMed

Zhong, Linda L D; Cheng, Chung-Wah; Kun, Wai; Dai, Liang; Hu, Dong-Dong; Ning, Zi-Wan; Xiao, Hai-Tao; Lin, Cheng-Yuan; Zhao, Ling; Huang, Tao; Tian, Ke; Chan, King-Hong; Lam, Ting-Wa; Chen, Xiao-Rui; Wong, Chi-Tak; Li, Min; Lu, Ai-Ping; Wu, Justin C Y; Bian, Zhao-Xiang

2018-04-12

The Chinese herbal medicine, MaZiRenWan (MZRW), has been used for more than 2000 years to treat constipation, but it has not been tested in a randomized controlled trial. We performed a trial to evaluate the efficacy and safety of MZRW, compared with the stimulant laxative senna or placebo, for patients with functional constipation (FC). We performed a double-blind, double-dummy, trial of 291 patients with FC based on Rome III criteria, seen at 8 clinics in Hong Kong from June 2013 through August 2015. Patients were observed for 2 weeks and then assigned randomly (1:1:1) to groups given MZRW (7.5 g, twice daily), senna (15 mg daily), or placebo for 8 weeks. Patients were then followed for 8 weeks and evaluated at baseline and weeks 4, 8 (end of treatment), and 16 (end of follow up). Participants recorded information on stool form and frequency, feeling of complete evacuation, and research medication taken. Data on individual bowel symptoms, global symptom improvement, and adverse events were collected. A complete response was defined as an increase ≥1 complete spontaneous bowel movement (CSBM)/week from baseline (the primary outcome). Secondary outcomes included response during the follow-up period, colonic transit, individual and global symptom assessments, quality of life measured with 36-item short form Chinese version, and adverse events. Although there was no statistically significant difference in proportions of patients with a complete response to MZRW (68%) vs. senna (57.7%) (P = .14) at week 8, there was a statistically significant difference vs. placebo (33.0%) (P < .005). At the 16-week timepoint (after the 8-week follow-up period), 47.4% of patients had a complete response to MZRW, 20.6% had a complete response to senna, and 17.5% had a complete response to placebo (P < .005 for MZRW vs. placebo). The group that received MZRW group also had significant increases in colonic transit and reduced severity of constipation, straining, incomplete evacuation, and global constipation symptoms compared with the groups that received placebo or senna in (P < .05 for all comparisons). In a randomized controlled trial of 291 patients with FC, we found MZRW to be well-tolerated and effective in increasing CSBM/week. MZRW did not appear to be more effective than senna and might be considered as an alternative to this drug. ClincialTrials.gov no: NCT01695850. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2): study protocol for a randomized controlled trial.

PubMed

Chang, Anne B; Grimwood, Keith; Wilson, Andrew C; van Asperen, Peter P; Byrnes, Catherine A; O'Grady, Kerry-Ann F; Sloots, Theo P; Robertson, Colin F; Torzillo, Paul J; McCallum, Gabrielle B; Masters, Ian B; Buntain, Helen M; Mackay, Ian M; Ungerer, Jacobus; Tuppin, Joanne; Morris, Peter S

2013-02-20

Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. Australia and New Zealand Clinical Trials Register (ANZCTR) number http://ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879.

Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. Methods This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. Discussion Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number http://ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879 PMID:23421781

Influences of pre-crash braking induced dummy - forward displacements on dummy behaviour during EuroNCAP frontal crashtest.

PubMed

Woitsch, Gernot; Sinz, Wolfgang

2014-01-01

Combination of active and passive safety systems is a future key to further improvement in vehicle safety. Autonomous braking systems are able to reduce collision speeds, and therefore severity levels significantly. Passengers change their position due to pre-impact vehicle motion, a fact, which has not yet been considered in common crash tests. For this paper, finite elements simulations of crash tests were performed to show that forward displacements due to pre-crash braking do not necessarily increase dummy load levels. So the influence of different pre-crash scenarios, all leading to equal closing speeds in the crash phase, are considered in terms of vehicle motion (pitching, deceleration) and restraint system configurations (belt load limiter, pretensioner). The influence is evaluated by dummy loads as well as contact risk between the dummy and the interior. Copyright © 2013 Elsevier Ltd. All rights reserved.

Intrathoracic pressure variations in an anthropomorphic dummy exposed to air blast, blunt impact, and missiles.

PubMed

Jönsson, A; Arvebo, E; Schantz, B

1988-01-01

Experiments with an anthropomorphic dummy for blast research demonstrated that pressures recorded in the lung model of the dummy could be correlated to primary air blast effects on the lungs of experimental animals. The results presented here were obtained with a dummy of the type mentioned above, but with the lung model modified to improve geometric similarity to man. Blast experiments were performed in a shock tube, and impact experiments in a special impact machine. Experiments with nonpenetrating missiles were performed with small-caliber firearms and the dummy protected by body armor. Severity indices derived from the blast experiments were related to established criteria for primary lung injury in man. Impacts delivered in the impact machine and by nonpenetrating missiles are compared. Relationships between severity of impact based on experiments with animals and primary lung injury in man are discussed.

75 FR 76636 - Anthropomorphic Test Devices; Hybrid III 6-Year-Old Child Test Dummy, Hybrid III 6-Year-Old...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-09

... test H06120 with the original femurs. Therefore, comparisons were made between pre- and post-test... [Docket No. NHTSA-2010-0147] RIN 2127-AK34 Anthropomorphic Test Devices; Hybrid III 6-Year-Old Child Test Dummy, Hybrid III 6-Year-Old Weighted Child Test Dummy AGENCY: National Highway Traffic Safety...

Tiotropium versus salmeterol for the prevention of exacerbations of COPD.

PubMed

Vogelmeier, Claus; Hederer, Bettina; Glaab, Thomas; Schmidt, Hendrik; Rutten-van Mölken, Maureen P M H; Beeh, Kai M; Rabe, Klaus F; Fabbri, Leonardo M

2011-03-24

Treatment guidelines recommend the use of inhaled long-acting bronchodilators to alleviate symptoms and reduce the risk of exacerbations in patients with moderate-to-very-severe chronic obstructive pulmonary disease (COPD) but do not specify whether a long-acting anticholinergic drug or a β(2)-agonist is the preferred agent. We investigated whether the anticholinergic drug tiotropium is superior to the β(2)-agonist salmeterol in preventing exacerbations of COPD. In a 1-year, randomized, double-blind, double-dummy, parallel-group trial, we compared the effect of treatment with 18 μg of tiotropium once daily with that of 50 μg of salmeterol twice daily on the incidence of moderate or severe exacerbations in patients with moderate-to-very-severe COPD and a history of exacerbations in the preceding year. A total of 7376 patients were randomly assigned to and treated with tiotropium (3707 patients) or salmeterol (3669 patients). Tiotropium, as compared with salmeterol, increased the time to the first exacerbation (187 days vs. 145 days), with a 17% reduction in risk (hazard ratio, 0.83; 95% confidence interval [CI], 0.77 to 0.90; P<0.001). Tiotropium also increased the time to the first severe exacerbation (hazard ratio, 0.72; 95% CI, 0.61 to 0.85; P<0.001), reduced the annual number of moderate or severe exacerbations (0.64 vs. 0.72; rate ratio, 0.89; 95% CI, 0.83 to 0.96; P=0.002), and reduced the annual number of severe exacerbations (0.09 vs. 0.13; rate ratio, 0.73; 95% CI, 0.66 to 0.82; P<0.001). Overall, the incidence of serious adverse events and of adverse events leading to the discontinuation of treatment was similar in the two study groups. There were 64 deaths (1.7%) in the tiotropium group and 78 (2.1%) in the salmeterol group. These results show that, in patients with moderate-to-very-severe COPD, tiotropium is more effective than salmeterol in preventing exacerbations. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov number, NCT00563381.).

[Quadruple regimens using domestically manufactured drugs in gastritis and duodenal ulcer patients for Helicobacter pylori eradication: a perspective, multicenter, randomized controlled trial].

PubMed

Gao, Wen; Hu, Fulian; Cheng, Hong; Wang, Huahong; Yang, Yunsheng; Liang, Hao; Zhang, Shutian; Meng, Fandong; Cui, Meihua; Wei, Hong; Sheng, Jianqiu; An, Hejuan J; Jiang, Bo; Chen, Ye; Li, Yanqing; Zuo, Xiuli; Gong, Jun; Zhao, Ping; Dong, Lei; Wang, Bangmao; Jiang, Kai; Zhang, Guiying; Li, Jiansheng; Zhao, Ye; Gao, Hengjun; Yang, Li

2016-01-26

To observe the effects and safety of quadruple regimens including domestically manufactured rabeprazole used as first line/initial therapy for Helicobacter pylori(H.pylori) eradication in gastritis and duodenal ulcer patients, and to investigate the effects of extended use of bismuth after the quadruple therapy on eradication of H. pylori. From January to August 2013, 430 patients with chronic gastritis or duodenal ulcer who were confirmed as H. pylori positive in gastroscopy for upper gastrointestinal symptoms were enrolled from 12 centers in China for initial treatment using quadruple regimens for H. pylori eradication. The study was a prospective, multicenter, randomized double-blinded double-dummy parallel-controlled clinical trial. The 310 chronic gastritis patients were divided into 2 groups: group A1 was given quadruple regime (rabeprazole+ amoxicillin+ clarithromycin+ bismuth potassium citrate) for 10 days followed by bismuth-placebo for 21 days; group A2 was given the quadruple regimen for 10 days and then bismuth potassium citrate for 21 days. The duodenal ulcer patients were given the quadruple for 10 days, then rabeprazole for 14 days. All the patients took (13)C urea breath test to detect H. pylori 28 days after medicine withdrawal. Altogether 428 cases were enrolled and 404 completed the trial. The total eradication rate in the chronic gastritis patients was 85.1% (262/308, intention-to-treat (ITT)analysis), which was 81.7% (125/153, ITT) in the A1 group and 88.4% (137/155, ITT) in the A2 group; the eradication rate in the duodenal ulcer patients was 85.8% (103/120, ITT). No severe adverse effects were reported. The symptoms (pain, burning sensation, reflux, belching, nausea, and vomiting) improvement status was similar among A1 and A2 groups. The quadruple regimen using rabeprazole manufactured in China and administered for 10 days as first line/initial therapy in chronic gastritis and duodenal ulcer patients could achieve good H. pylori eradication rate. The extended use of bismuth after 10-day quadruple regimen might further improve the eradication rate. The regimens containing proton-pump inhibitor and bismuth may be well tolerated and safe in clinical application.

Relative effectiveness of additive pain interventions during vaccination in infants

PubMed Central

Taddio, Anna; Riddell, Rebecca Pillai; Ipp, Moshe; Moss, Steven; Baker, Stephen; Tolkin, Jonathan; Malini, Dave; Feerasta, Sharmeen; Govan, Preeya; Fletcher, Emma; Wong, Horace; McNair, Caitlin; Mithal, Priyanjali; Stephens, Derek

2017-01-01

BACKGROUND: Vaccine injections can cause acute pain and distress in infants, which can contribute to dissatisfaction with the vaccination experience and vaccine hesitancy. We sought to compare the effectiveness of additive pain interventions administered consistently during vaccine injections in the first year of life. METHODS: We conducted a multicentre, longitudinal, double-blind, add-on, randomized controlled trial. Healthy infants were randomly assigned to 1 of 4 levels of pain management for all vaccine injections at 2, 4, 6 and 12 months: (i) placebo control; (ii) parent-directed video education about infant soothing; (iii) the video plus sucrose administered orally or (iv) the video plus sucrose plus liposomal lidocaine applied topically. All infants benefit from injection techniques that minimize pain. We used a double-dummy design; hence all parents watched a video (active psychological intervention or placebo) and all infants received oral solution (sucrose or placebo) and topical cream (lidocaine or placebo). We assessed infant distress during 3 phases — preinjection (baseline), vaccine injection (needle), and 1 minute postinjection (recovery) — using the Modified Behavioural Pain Scale (range 0–10). We compared scores between groups and across infant ages using a mixed-model repeated-measures analysis. RESULTS: A total of 352 infants participated in the study, from Jan. 17, 2012, to Feb. 2, 2016. Demographics did not differ among intervention groups (p > 0.05). Baseline pain scores did not differ among intervention groups (p = 0.4), but did differ across ages (p < 0.001). Needle pain scores differed among groups (p = 0.003) and across ages (p < 0.001). The mean (± standard deviation) needle score was 6.3 (± 0.8) in the video–sucrose–lidocaine group compared with 6.7 (± 0.8) in each of the other groups. There were no other between-group differences. Recovery scores did not differ among groups (p = 0.98), but did differ across ages (p < 0.001). INTERPRETATION: Only liposomal lidocaine provided consistent analgesia within an additive pain intervention regimen during vaccinations in infants. Trial registration: ClinicalTrials.gov, no. NCT01503060 PMID:27956393

Efficacy of oral palonosetron compared to intravenous palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: a phase 3 trial.

PubMed

Boccia, Ralph; Grunberg, Steven; Franco-Gonzales, Edwin; Rubenstein, Edward; Voisin, Daniel

2013-05-01

Palonosetron (Aloxi(®), Onicit(®)) is a pharmacologically unique 5-HT3 receptor antagonist (RA) approved as a single IV injection for the prevention of nausea and vomiting induced by chemotherapy (CINV) of either moderate or highly emetogenic potential (MEC and HEC, respectively). An oral palonosetron formulation has been developed and compared to the IV formulation. In this multinational, multicenter, double-blind, double-dummy, dose-ranging trial, 651 patients were randomly assigned to receive one of the following as a single dose prior to moderately emetogenic chemotherapy: oral palonosetron 0.25, 0.50, and 0.75 mg or IV palonosetron 0.25 mg. Patients were also randomized (1:1) to receive dexamethasone 8 mg IV or matched placebo on day 1. The primary endpoint was complete response (CR; no emesis, no rescue therapy) during the acute phase (0-24 h). Acute CR rates were 73.5, 76.3, 74.1, and 70.4 % for all patients receiving the palonosetron 0.25, 0.50, and 0.75 mg oral doses, and for IV palonosetron 0.25 mg, respectively; delayed CR (24-120 h) rates were 59.4, 62.5, 60.1, and 65.4 %, and overall CR (0-120 h) rates were 53.5, 58.8, 53.2, and 59.3 %, respectively. The addition of dexamethasone improved emetic control (acute CR rate) by at least 15 % for all groups except oral palonosetron 0.25 mg, where the acute CR improvement was approximately 7 %. Adverse events were similar in nature, incidence, and intensity for all oral and IV palonosetron groups, and were the expected adverse events for 5-HT3 RAs (primarily headache and constipation). Oral palonosetron has a similar efficacy and safety profile as IV palonosetron 0.25 mg and may be the preferred formulation in certain clinical situations. Among the tested oral treatments, a palonosetron 0.50-mg oral dose has been favored for the prevention of CINV in patients receiving moderately emetogenic chemotherapy due to a numerical gain in efficacy without a side effect disadvantage.

A Wearable Proprioceptive Stabilizer (Equistasi®) for Rehabilitation of Postural Instability in Parkinson’s Disease: A Phase II Randomized Double-Blind, Double-Dummy, Controlled Study

PubMed Central

Volpe, Daniele; Giantin, Maria Giulia; Fasano, Alfonso

2014-01-01

Background Muscle spindles endings are extremely sensitive to externally applied vibrations, and under such circumstances they convey proprioceptive inflows to the central nervous system that modulate the spinal reflexes excitability or the muscle responses elicited by postural perturbations. The aim of this pilot study is to test the feasibility and effectiveness of a balance training program in association with a wearable proprioceptive stabilizer (Equistasi) that emits focal mechanical vibrations in patients with PD. Methods Forty patients with PD were randomly divided in two groups wearing an active or inactive device. All the patients received a 2-month intensive program of balance training. Assessments were performed at baseline, after the rehabilitation period (T1), and two more months after (T2). Posturographic measures were used as primary endpoint; secondary measures of outcome included the number of falls and several clinical scales for balance and quality of life. Results Both groups improved at the end of the rehabilitation period and we did not find significant between-group differences in any of the principal posturographic measures with the exception of higher sway area and limit of stability on the instrumental functional reach test during visual deprivation at T1 in the Equistasi group. As for the secondary outcome, we found an overall better outcome in patients enrolled in the Equistasi group: 1) significant improvement at T1 on Berg Balance Scale (+45.0%, p = .026), Activities-specific Balance Confidence (+83.7, p = .004), Falls Efficacy Scale (−33.3%, p = .026) and PDQ-39 (−48.8%, p = .004); 2) sustained improvement at T2 in terms of UPDRS-III, Berg Balance Scales, Time Up and Go and PDQ-39; 3) significant and sustained reduction of the falls rate. Conclusions This pilot trial shows that a physiotherapy program for training balance in association with focal mechanical vibration exerted by a wearable proprioceptive stabilizer might be superior than rehabilitation alone in improving patients’ balance. Trial Registration EudraCT 2013-003020-36 and ClinicalTrials.gov (number not assigned) PMID:25401967

Response to Albuterol MDI Delivered Through an Anti-Static Chamber During Nocturnal Bronchospasm

PubMed Central

Prabhakaran, Sreekala; Shuster, Jonathan; Chesrown, Sarah; Hendeles, Leslie

2013-01-01

BACKGROUND Decreasing electrostatic charge on valved holding chambers increases the amount of drug delivered. However, there are no data demonstrating that this increases bronchodilatation. OBJECTIVE To investigate the influence of reducing electrostatic charge on the bronchodilator response to albuterol inhaler during nocturnal bronchospasm. METHODS This randomized double-blind, double-dummy crossover study included subjects, 18—40 years old, with nocturnal bronchospasm (20% overnight decrease in peak flow on 3 of 7 nights during run-in), FEV1 60–80% predicted during the day, and ≥ 12% increase after albuterol. Subjects slept in the clinical research center up to 3 nights for each treatment. FEV1 and heart rate were measured upon awakening spontaneously or at 4:00 am, and 15 min after each dose of 1, 2, and 4 cumulative puffs of albuterol via metered-dose inhaler. The drug was administered through an anti-static valved holding chamber (AeroChamber Plus Z-Stat) or a conventional valved holding chamber containing a static charge (AeroChamber Plus). RESULTS Of 88 consented subjects, 11 were randomized and 7 completed the study. Most exclusions were due to lack of objective evidence of nocturnal bronchospasm. Upon awakening, FEV1 was 44 ± 9% of predicted before the anti-static chamber and 48 ± 7% of predicted before the static chamber. The mean ± SD percent increase in FEV1 after 1, 2, and 4 cumulative puffs using the anti-static versus the static chamber, respectively, were 52 ± 26% versus 30 ± 19%, 73 ± 28% versus 48 ± 26%, and 90 ± 34% versus 64 ± 35%. The point estimates for the differences (and 95% CIs) between the devices (anti-static vs static) were 21% (4–38%) (P = .03), 23% (6–41%) (P = .02), and 25% (7–42%) (P = .01) for 1, 2, and 4 cumulative puffs, respectively. There was no significant difference in heart rate between treatments. CONCLUSIONS Delivery of albuterol through an anti-static chamber provides a clinically relevant improvement in bronchodilator response during acute, reversible bronchospasm such as nocturnal bronchospasm. PMID:22348270

Impact Testing and Simulation of a Crashworthy Composite Fuselage Section with Energy-Absorbing Seats and Dummies

NASA Technical Reports Server (NTRS)

Fasanella, Edwin L.; Jackson, Karen E.

2002-01-01

A 25-ft/s vertical drop test of a composite fuselage section was conducted with two energy-absorbing seats occupied by anthropomorphic dummies to evaluate the crashworthy features of the fuselage section and to determine its interaction with the seats and dummies. The 5-ft. diameter fuselage section consists of a stiff structural floor and an energy-absorbing subfloor constructed of Rohacel foam blocks. The experimental data from this test were analyzed and correlated with predictions from a crash simulation developed using the nonlinear, explicit transient dynamic computer code, MSC.Dytran. The anthropomorphic dummies were simulated using the Articulated Total Body (ATB) code, which is integrated into MSC.Dytran.

Impact Testing and Simulation of a Crashworthy Composite Fuselage Section with Energy-Absorbing Seats and Dummies

NASA Technical Reports Server (NTRS)

Fasanella, Edwin L.; Jackson, Karen E.

2002-01-01

A 25-ft/s vertical drop test of a composite fuselage section was conducted with two energy-absorbing seats occupied by anthropomorphic dummies to evaluate the crashworthy features of the fuselage section and to determine its interaction with the seats and dummies. The 5-ft diameter fuselage section consists of a stiff structural floor and an energy-absorbing subfloor constructed of Rohacel foam blocks. The experimental data from this test were analyzed and correlated with predictions from a crash simulation developed using the nonlinear, explicit transient dynamic computer code, MSC.Dytran. The anthropomorphic dummies were simulated using the Articulated Total Body (ATB) code, which is integrated into MSC.Dytran.

Anthropometry for WorldSID, a World-Harmonized Midsize Male Side Impact Crash Dummy

DOE Office of Scientific and Technical Information (OSTI.GOV)

S. Moss; Z. Wang; M. Salloum

2000-06-19

The WorldSID project is a global effort to design a new generation side impact crash test dummy under the direction of the International Organization for Standardization (ISO). The first WorldSID crash dummy will represent a world-harmonized mid-size adult male. This paper discusses the research and rationale undertaken to define the anthropometry of a world standard midsize male in the typical automotive seated posture. Various anthropometry databases are compared region by region and in terms of the key dimensions needed for crash dummy design. The Anthropometry for Motor Vehicle Occupants (AMVO) dataset, as established by the University of Michigan Transportation Researchmore » Institute (UMTRI), is selected as the basis for the WorldSID mid-size male, updated to include revisions to the pelvis bone location. The proposed mass of the dummy is 77.3kg with full arms. The rationale for the selected mass is discussed. The joint location and surface landmark database is appended to this paper.« less

Object categorization by wild ranging birds-Winter feeder experiments.

PubMed

Nováková, Nela; Veselý, Petr; Fuchs, Roman

2017-10-01

The object categorization is only scarcely studied using untrained wild ranging animals and relevant stimuli. We tested the importance of the spatial position of features salient for categorization of a predator using wild ranging birds (titmice) visiting a winter feeder. As a relevant stimulus we used a dummy of a raptor, the European sparrowhawk (Accipiter nisus), placed at the feeding location. This dummy was designed to be dismantled into three parts and rearranged with the head in the correct position, in the middle or at the bottom of the dummy. When the birds had the option of visiting an alternative feeder with a dummy pigeon, they preferred this option to visiting the feeder with the dummy sparrowhawk with the head in any of the three positions. When the birds had the option of visiting an alternative feeder with an un-rearranged dummy sparrowhawk, they visited both feeders equally often, and very scarcely. This suggests that the titmice considered all of the sparrowhawk modifications as being dangerous, and equally dangerous as the un-rearranged sparrowhawk. The position of the head was not the most important cue for categorization. The presence of the key features was probably sufficient for categorization, and their mutual spatial position was of lower importance. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation of "dummy" l-phenylalanine molecularly imprinted microspheres by using ionic liquid as a template and functional monomer.

PubMed

Li, Ji; Hu, Xiaoling; Guan, Ping; Song, Dongmen; Qian, Liwei; Du, Chunbao; Song, Renyuan; Wang, Chaoli

2015-07-07

In this study, dummy imprinting technology was employed for the preparation of l-phenylalanine-imprinted microspheres. Ionic liquids were utilized as both a "dummy" template and functional monomer, and 4-vinylpyridine and ethylene glycol dimethacrylate were used as the assistant monomer and cross-linker, respectively, for preparing a surface-imprinted polymer on poly(divinylbenzene) microspheres. By the results obtained by theoretical investigation, the interaction between the template and monomer complex was improved as compared with that between the template and the traditional l-phenylalanine-imprinted polymer. The batch experiments indicated that the imprinting factor reached 2.5. Scatchard analysis demonstrated that the obtained "dummy" molecularly imprinted microspheres exhibited an affinity of 77.4 M·10 -4 , significantly higher that of a traditional polymer directly prepared by l-phenylalanine, which is in agreement with theoretical results. Competitive adsorption experiments also showed that the molecularly imprinted polymer with the dummy template effectively isolated l-phenylalanine from l-histidine and l-tryptophan with separation factors of 5.68 and 2.68, respectively. All these results demonstrated that the polymerizable ionic liquid as the dummy template could enhance the affinity and selectivity of molecularly imprinted polymer, thereby promoting the development of imprinting technology for biomolecules. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modeling and validation of a detailed FE viscoelastic lumbar spine model for vehicle occupant dummies.

PubMed

Amiri, Sorosh; Naserkhaki, Sadegh; Parnianpour, Mohamad

2018-06-19

The dummies currently used for predicting vehicle occupant response during frontal crashes or whole-body vibration provide insufficient information about spinal loads. Although they aptly approximate upper-body rotations in different loading scenarios, they overlook spinal loads, which are crucial to injury assessment. This paper aims to develop a modified dummy finite element (FE) model with a detailed viscoelastic lumbar spine. This model has been developed and validated against in-vitro and in-silico data under different loading conditions, and its predicted ranges of motion (RoM) and intradiscal pressure (IDP) maintain close correspondence with the in-vitro data. The dominant frequency of the model was f = 8.92 Hz, which was close to previous results. In the relaxation test, a force reduction of up to 21% was obtained, showing high agreement in force relaxation during the in-vitro test. The FE lumbar spine model was placed in the HYBRID III test dummy and aligned in a seated position based on available MRI data. Under two impulsive acceleration loadings in flexion and lateral directions with a peak acceleration of 60 m/s 2 , flexion responses of the modified and original dummies were close (RoMs of 29.1° and 29.6°, respectively), though not in lateral bending (RoMs of 34.1° and 15.6°, respectively), where the modified dummy was more flexible than the original. By reconstructing a real frontal crash, it was found that the modified dummy provided a 10% reduction in the Head Injury Criterion (HIC). Other than the more realistic behavior of this modified dummy, its capability of approximating lumbar loads and risk of lumbar spine injuries in vehicle crashes or whole-body vibration is of great importance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers

PubMed Central

Carter, Lawrence P.; Griffiths, Roland R.; Mintzer, Miriam Z.

2009-01-01

Rationale Illicit gamma-hydroxybutyrate (GHB) has received attention as a “date rape drug” that produces robust amnesia; however, there is little experimental evidence in support of GHB’s amnestic effects. Objectives This study compared the cognitive effects of GHB (sodium oxybate) with those of triazolam in healthy volunteers. Materials and methods Doses of sodium oxybate (1.125, 2.25, and 4.5 g/70 kg), triazolam (0.125, 0.25, and 0.5 mg/70 kg), and placebo were administered to 15 volunteers under repeated measures, counterbalanced, double-blind, double-dummy conditions. The time course and peak physiological, psychomotor, subjective, and cognitive effects were examined. Results Sodium oxybate and triazolam produced similar increases in participant ratings of drug effects. Performance on psychomotor, working memory, and episodic memory tasks was impaired to a greater extent after triazolam than sodium oxybate. Conclusions Together, these data suggest that sodium oxybate produces less psychomotor and cognitive impairment than triazolam at doses that produce equivalent participant-rated subjective effects in healthy volunteers. PMID:19543883

Correct titration of non-drugs and some other methodological issues.

PubMed

Beneke, M; Rasmus, W; Rød, I S; Fritze, J

1994-01-01

Doctors' prescription and dosing behaviour was investigated using data from 9 clinical trials in 550 patients treated with psychotropics. 7 trials were conducted under double- and 2 under single-blind conditions. In 3 of these trials, oral and i.m. preparations were used demanding a double-dummy design. All patients were evaluated on a weekly or 2-week basis using psychopathological rating scales (i.e. Hamilton Anxiety Scale, Hamilton Depression Scale, Clinical Global Impressions, Simpson and Angus EPS). It was found that (a) oral-medication titration was 3- to 4-fold more broad-ranging than i.m. medication titration, (b) oral placebo was titrated to the same extent as the oral investigational drugs, and (c) the titration schedule did not follow protocol requirements. Moreover, the average doses in all drug and placebo groups were the same. Concomitant medication like sleep inducers was found to be more closely related to doctors' habits than to actual medical need. Independent of trial and investigational drug, 10-33% of all patients received additional sleep inducers.

The repeatability and reproducibility of the BioRID IIg in a repeatable laboratory seat based on a production car seat.

PubMed

Hynd, David; Depinet, Paul; Lorenz, Bernd

2013-01-01

The United Nations Economic Commission for Europe Informal Group on GTR No. 7 Phase 2 are working to define a build level for the BioRID II rear impact (whiplash) crash test dummy that ensures repeatable and reproducible performance in a test procedure that has been proposed for future legislation. This includes the specification of dummy hardware, as well as the development of comprehensive certification procedures for the dummy. This study evaluated whether the dummy build level and certification procedures deliver the desired level of repeatability and reproducibility. A custom-designed laboratory seat was made using the seat base, back, and head restraint from a production car seat to ensure a representative interface with the dummy. The seat back was reinforced for use in multiple tests and the recliner mechanism was replaced by an external spring-damper mechanism. A total of 65 tests were performed with 6 BioRID IIg dummies using the draft GTR No.7 sled pulse and seating procedure. All dummies were subject to the build, maintenance, and certification procedures defined by the Informal Group. The test condition was highly repeatable, with a very repeatable pulse, a well-controlled seat back response, and minimal observed degradation of seat foams. The results showed qualitatively reasonable repeatability and reproducibility for the upper torso and head accelerations, as well as for T1 Fx and upper neck Fx . However, reproducibility was not acceptable for T1 and upper neck Fz or for T1 and upper neck My . The Informal Group has not selected injury or seat assessment criteria for use with BioRID II, so it is not known whether these channels would be used in the regulation. However, the ramping-up behavior of the dummy showed poor reproducibility, which would be expected to affect the reproducibility of dummy measurements in general. Pelvis and spine characteristics were found to significantly influence the dummy measurements for which poor reproducibility was observed. It was also observed that the primary neck response in these tests was flexion, not extension. This correlates well with recent findings from Japan and the United States showing a correlation between neck flexion and injury in accident replication simulations and postmortem human subjects (PMHS) studies, respectively. The present certification tests may not adequately control front cervical spine bumper characteristics, which are important for neck flexion response. The certification sled test also does not include the pelvis and so cannot be used to control pelvis response and does not substantially load the lumbar bumpers and so does not control these parts of the dummy. The stiffness of all spine bumpers and of the pelvis flesh should be much more tightly controlled. It is recommended that a method for certifying the front cervical bumpers should be developed. Recommendations are also made for tighter tolerance on the input parameters for the existing certification tests.

Parameter screening: the use of a dummy parameter to identify non-influential parameters in a global sensitivity analysis

NASA Astrophysics Data System (ADS)

Khorashadi Zadeh, Farkhondeh; Nossent, Jiri; van Griensven, Ann; Bauwens, Willy

2017-04-01

Parameter estimation is a major concern in hydrological modeling, which may limit the use of complex simulators with a large number of parameters. To support the selection of parameters to include in or exclude from the calibration process, Global Sensitivity Analysis (GSA) is widely applied in modeling practices. Based on the results of GSA, the influential and the non-influential parameters are identified (i.e. parameters screening). Nevertheless, the choice of the screening threshold below which parameters are considered non-influential is a critical issue, which has recently received more attention in GSA literature. In theory, the sensitivity index of a non-influential parameter has a value of zero. However, since numerical approximations, rather than analytical solutions, are utilized in GSA methods to calculate the sensitivity indices, small but non-zero indices may be obtained for the indices of non-influential parameters. In order to assess the threshold that identifies non-influential parameters in GSA methods, we propose to calculate the sensitivity index of a "dummy parameter". This dummy parameter has no influence on the model output, but will have a non-zero sensitivity index, representing the error due to the numerical approximation. Hence, the parameters whose indices are above the sensitivity index of the dummy parameter can be classified as influential, whereas the parameters whose indices are below this index are within the range of the numerical error and should be considered as non-influential. To demonstrated the effectiveness of the proposed "dummy parameter approach", 26 parameters of a Soil and Water Assessment Tool (SWAT) model are selected to be analyzed and screened, using the variance-based Sobol' and moment-independent PAWN methods. The sensitivity index of the dummy parameter is calculated from sampled data, without changing the model equations. Moreover, the calculation does not even require additional model evaluations for the Sobol' method. A formal statistical test validates these parameter screening results. Based on the dummy parameter screening, 11 model parameters are identified as influential. Therefore, it can be denoted that the "dummy parameter approach" can facilitate the parameter screening process and provide guidance for GSA users to define a screening-threshold, with only limited additional resources. Key words: Parameter screening, Global sensitivity analysis, Dummy parameter, Variance-based method, Moment-independent method

Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial.

PubMed

Molina, Jean-Michel; Cahn, Pedro; Grinsztejn, Beatriz; Lazzarin, Adriano; Mills, Anthony; Saag, Michael; Supparatpinyo, Khuanchai; Walmsley, Sharon; Crauwels, Herta; Rimsky, Laurence T; Vanveggel, Simon; Boven, Katia

2011-07-16

Efavirenz with tenofovir-disoproxil-fumarate and emtricitabine is a preferred antiretroviral regimen for treatment-naive patients infected with HIV-1. Rilpivirine, a new non-nucleoside reverse transcriptase inhibitor, has shown similar antiviral efficacy to efavirenz in a phase 2b trial with two nucleoside/nucleotide reverse transcriptase inhibitors. We aimed to assess the efficacy, safety, and tolerability of rilpivirine versus efavirenz, each combined with tenofovir-disoproxil-fumarate and emtricitabine. We did a phase 3, randomised, double-blind, double-dummy, active-controlled trial, in patients infected with HIV-1 who were treatment-naive. The patients were aged 18 years or older with a plasma viral load at screening of 5000 copies per mL or greater, and viral sensitivity to all study drugs. Our trial was done at 112 sites across 21 countries. Patients were randomly assigned by a computer-generated interactive web response system to receive either once-daily 25 mg rilpivirine or once-daily 600 mg efavirenz, each with tenofovir-disoproxil-fumarate and emtricitabine. Our primary objective was to show non-inferiority (12% margin) of rilpivirine to efavirenz in terms of the percentage of patients with confirmed response (viral load <50 copies per mL intention-to-treat time-to-loss-of-virological-response [ITT-TLOVR] algorithm) at week 48. Our primary analysis was by intention-to-treat. We also used logistic regression to adjust for baseline viral load. This trial is registered with ClinicalTrials.gov, number NCT00540449. 346 patients were randomly assigned to receive rilpivirine and 344 to receive efavirenz and received at least one dose of study drug, with 287 (83%) and 285 (83%) in the respective groups having a confirmed response at week 48. The point estimate from a logistic regression model for the percentage difference in response was -0.4 (95% CI -5.9 to 5.2), confirming non-inferiority with a 12% margin (primary endpoint). The incidence of virological failures was 13% (rilpivirine) versus 6% (efavirenz; 11%vs 4% by ITT-TLOVR). Grade 2-4 adverse events (55 [16%] on rilpivirine vs 108 [31%] on efavirenz, p<0.0001), discontinuations due to adverse events (eight [2%] on rilpivirine vs 27 [8%] on efavirenz), rash, dizziness, and abnormal dreams or nightmares were more common with efavirenz. Increases in plasma lipids were significantly lower with rilpivirine. Rilpivirine showed non-inferior efficacy compared with efavirenz, with a higher virological-failure rate, but a more favourable safety and tolerability profile. Tibotec. Copyright © 2011 Elsevier Ltd. All rights reserved.

New type of dummy layout pattern to control ILD etch rate

NASA Astrophysics Data System (ADS)

Pohland, Oliver; Spieker, Julie; Huang, Chih-Ta; Govindaswamy, Srikanth; Balasinski, Artur

2007-12-01

Adding dummy features (waffles) to drawn geometries of the circuit layout is a common practice to improve its manufacturability. As an example, local dummy pattern improves MOSFET line and space CD control by adjusting short range optical proximity and reducing the aggressiveness of its correction features (OPC) to widen the lithography process window. Another application of dummy pattern (waffles) is to globally equalize layout pattern density, to reduce long-range inter-layer dielectric (ILD) thickness variations after the CMP process and improve contact resistance uniformity over the die area. In this work, we discuss a novel type of dummy pattern with a mid-range interaction distance, to control the ILD composition driven by its deposition and etch process. This composition is reflected on sidewall spacers and depends on the topography of the underlying poly pattern. During contact etch, it impacts the etch rate of the ILD. As a result, the deposited W filling the damascene etched self-aligned trench contacts in the ILD may electrically short to the underlying gates in the areas of isolated poly. To mitigate the dependence of the ILD composition on poly pattern distribution, we proposed a special dummy feature generation with the interaction range defined by the ILD deposition and etch process. This helped equalize mid-range poly pattern density without disabling the routing capability with damascene trench contacts in the periphery which would have increased the layout footprint.

Development of a shear force measurement dummy for seat comfort.

PubMed

Kim, Seong Guk; Ko, Chang-Yong; Kim, Dong Hyun; Song, Ye Eun; Kang, Tae Uk; Ahn, Sungwoo; Lim, Dohyung; Kim, Han Sung

2017-01-01

Seat comfort is one of the main factors that consumers consider when purchasing a car. In this study, we develop a dummy with a shear-force sensor to evaluate seat comfort. The sensor has dimensions of 25 mm × 25 mm × 26 mm and is made of S45C. Electroless nickel plating is employed to coat its surface in order to prevent corrosion and oxidation. The proposed sensor is validated using a qualified load cell and shows high accuracy and precision (measurement range: -30-30 N; sensitivity: 0.1 N; linear relationship: R = 0.999; transverse sensitivity: <1%). The dummy is manufactured in compliance with the SAE standards (SAE J826) and incorporates shear sensors into its design. We measure the shear force under four driving conditions and at five different speeds using a sedan; results showed that the shear force increases with speed under all driving conditions. In the case of acceleration and deceleration, shear force significantly changes in the lower body of the dummy. During right and left turns, it significantly changes in the upper body of the dummy.

Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI).

PubMed

Wagenlehner, Florian M; Umeh, Obiamiwe; Steenbergen, Judith; Yuan, Guojun; Darouiche, Rabih O

2015-05-16

Treatment of complicated urinary-tract infections is challenging due to rising antimicrobial resistance. We assessed the efficacy and safety of ceftolozane-tazobactam, a novel antibacterial with Gram-negative activity, in the treatment of patients with complicated lower-urinary-tract infections or pyelonephritis. ASPECT-cUTI was a randomised, double-blind, double-dummy, non-inferiority trial done in 209 centres in 25 countries. Between July, 2011, and September, 2013, hospital inpatients aged 18 years or older who had pyuria and a diagnosis of a complicated lower-urinary-tract infection or pyelonephritis were randomly assigned in a 1:1 ratio to receive intravenous 1·5 g ceftolozane-tazobactam every 8 h or intravenous high-dose (750 mg) levofloxacin once daily for 7 days. The randomisation schedule was computer generated in blocks of four and stratified by study site. The next allocation was obtained by the study site pharmacist via an interactive voice-response system. The primary endpoint was a composite of microbiological eradication and clinical cure 5-9 days after treatment in the microbiological modified intention-to-treat (MITT) population, with a non-inferiority margin of 10%. This study is registered with ClinicalTrials.gov, numbers NCT01345929 and NCT01345955. Of 1083 patients enrolled, 800 (73·9%), of whom 656 (82·0%) had pyelonephritis, were included in the microbiological MITT population. Ceftolozane-tazobactam was non-inferior to levofloxacin for composite cure (306 [76·9%] of 398 vs 275 [68·4%] of 402, 95% CI 2·3-14·6) and, as the lower bound of the two-sided 95% CI around the treatment difference was positive and greater than zero, superiority was indicated. Adverse event profiles were similar in the two treatment groups and were mainly non-serious. Treatment with ceftolozane-tazobactam led to better responses than high-dose levofloxacin in patients with complicated lower-urinary-tract infections or pyelonephritis. Cubist Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Double blind, randomised study of continuous terbinafine compared with intermittent itraconazole in treatment of toenail onychomycosis

PubMed Central

Evans, E Glyn V; Sigurgeirsson, Bárdur

1999-01-01

Objective To compare the efficacy and safety of continuous terbinafine with intermittent itraconazole in the treatment of toenail onychomycosis. Design Prospective, randomised, double blind, double dummy, multicentre, parallel group study lasting 72 weeks. Setting 35 centres in six European countries. Subjects 496 patients aged 18 to 75 years with a clinical and mycological diagnosis of dermatophyte onychomycosis of the toenail. Interventions Study patients were randomly divided into four parallel groups to receive either terbinafine 250 mg a day for 12 or 16 weeks (groups T12 and T16) or itraconazole 400 mg a day for 1 week in every 4 weeks for 12 or 16 weeks (groups I3 and I4). Main outcome measures Assessment of primary efficacy at week 72 was mycological cure, defined as negative results on microscopy and culture of samples from the target toenail. Results At week 72 the mycological cure rates were 75.7% (81/107) in the T12 group and 80.8% (80/99) in the T16 group compared with 38.3% (41/107) in the I3 group and 49.1 % (53/108) in the I4 group. All comparisons (T12 v I3, T12 v I4, T16 v I3, T16 v I4) showed significantly higher cure rates in the terbinafine groups (all P<0.0001). Also, all secondary clinical outcome measures were significantly in favour of terbinafine at week 72. There were no differences in the number or type of adverse events recorded in the terbinafine or itraconazole groups. Conclusion Continuous terbinafine is significantly more effective than intermittent itraconazole in the treatment of patients with toenail onychomycosis. Key messagesGiven a correct diagnosis, fungal nail disease (onychomycosis) is curableTerbinafine is an allylamine antifungal with a primarily fungicidal mode of actionContinuous terbinafine treatment over 12 or 16 weeks achieves higher rates of clinical and mycological cure than intermittent itraconazole given over the same periodsTerbinafine is safe and well tolerated over 12 or 16 weeks of continuous treatmentContinuous terbinafine should be the current treatment of choice for onychomycosis PMID:10205099

Influence of standing or seated pelvis on dummy responses in rear impacts.

PubMed

Viano, David C; Parenteau, Chantal S; Burnett, Roger

2012-03-01

There is a question whether the standing or seated pelvis should be used in Hybrid III dummy evaluations of seats and belt restraint systems in severe rear impacts. This study compares the standing and seated Hybrid III pelvis in matched rear sled tests. Sixteen sled tests were found at 10, 16 and 24 km/h rear delta V in Ford's archives where matched tests were run with the standing and seated pelvis in a belted Hybrid III dummy. Two new tests were conducted at 40 km/h rear delta V to extend the severity range. The head, chest and pelvis were instrumented with triaxial accelerometers and the upper and lower neck, thoracic spine and lumbar spine had transducers measuring triaxial loads and moments. Belt Loads were measured. High-speed video recorded different views of the dummy motion. Dummy kinematics and biomechanical responses were compared for all of the data with the two different Hybrid III pelvic designs. In the 40 km/h sled tests, the dummy motion and excursion were essentially similar with the standing and seated pelvis. The similarities included the lap belt interaction with the pelvis and the leg movement upward flexing the hip joint. Overall, similar biomechanic and kinematic responses were found, including the pelvic acceleration, spinal forces and moments. For the lower speed tests at 10, 16 and 24 km/h, the motion sequence was also similar with the two different pelvises, including the upward movement of the legs as the seat was loaded and rebound kinematics. The biomechanical responses were similar. The seated pelvis involves only a small portion of the upper leg molded into the vinyl skin of the pelvis and does not limit leg rotation at the hip joint. Furthermore, lap belt loads were minimal during the rearward movement of the dummy. The matched testing showed no significant difference in occupant kinematics or biomechanical responses between the standing and seated pelvis in rear sled tests. The Hybrid III dummy with the seated pelvis is suitable for FMVSS 301 and other testing of seats and belt restraint systems in severe rear impacts. Copyright © 2011 Elsevier Ltd. All rights reserved.

49 CFR 572.41 - General description.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES Side Impact Dummy 50th... set forth in the Side Impact Dummy (SID) User's Manual, dated May 1994 except for pages 7, 20 and 23...

49 CFR 572.41 - General description.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES Side Impact Dummy 50th... set forth in the Side Impact Dummy (SID) User's Manual, dated May 1994 except for pages 7, 20 and 23...

49 CFR 572.41 - General description.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES Side Impact Dummy 50th... set forth in the Side Impact Dummy (SID) User's Manual, dated May 1994 except for pages 7, 20 and 23...

49 CFR 572.41 - General description.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES Side Impact Dummy 50th... set forth in the Side Impact Dummy (SID) User's Manual, dated May 1994 except for pages 7, 20 and 23...

49 CFR 572.41 - General description.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES Side Impact Dummy 50th... set forth in the Side Impact Dummy (SID) User's Manual, dated May 1994 except for pages 7, 20 and 23...

Average male and female virtual dummy model (BioRID and EvaRID) simulations with two seat concepts in the Euro NCAP low severity rear impact test configuration.

PubMed

Linder, Astrid; Holmqvist, Kristian; Svensson, Mats Y

2018-05-01

Soft tissue neck injuries, also referred to as whiplash injuries, which can lead to long term suffering accounts for more than 60% of the cost of all injuries leading to permanent medical impairment for the insurance companies, with respect to injuries sustained in vehicle crashes. These injuries are sustained in all impact directions, however they are most common in rear impacts. Injury statistics have since the mid-1960s consistently shown that females are subject to a higher risk of sustaining this type of injury than males, on average twice the risk of injury. Furthermore, some recently developed anti-whiplash systems have revealed they provide less protection for females than males. The protection of both males and females should be addresses equally when designing and evaluating vehicle safety systems to ensure maximum safety for everyone. This is currently not the case. The norm for crash test dummies representing humans in crash test laboratories is an average male. The female part of the population is not represented in tests performed by consumer information organisations such as NCAP or in regulatory tests due to the absence of a physical dummy representing an average female. Recently, the world first virtual model of an average female crash test dummy was developed. In this study, simulations were run with both this model and an average male dummy model, seated in a simplified model of a vehicle seat. The results of the simulations were compared to earlier published results from simulations run in the same test set-up with a vehicle concepts seat. The three crash pulse severities of the Euro NCAP low severity rear impact test were applied. The motion of the neck, head and upper torso were analysed in addition to the accelerations and the Neck Injury Criterion (NIC). Furthermore, the response of the virtual models was compared to the response of volunteers as well as the average male model, to that of the response of a physical dummy model. Simulations with the virtual male and female dummy models revealed differences in dynamic response related to the crash severity, as well as between the two dummies in the two different seat models. For the comparison of the response of the virtual models to the response of the volunteers and the physical dummy model, the peak angular motion of the first thoracic vertebra as found in the volunteer tests and mimicked by the physical dummy were not of the same magnitude in the virtual models. The results of the study highlight the need for an extended test matrix that includes an average female dummy model to evaluate the level of occupant protection different seats provide in vehicle crashes. This would provide developers with an additional tool to ensure that both male and female occupants receive satisfactory protection and promote seat concepts that provide the best possible protection for the whole adult population. This study shows that using the mathematical models available today can provide insights suitable for future testing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Injury risk curves for the WorldSID 50th male dummy.

PubMed

Petitjean, Audrey; Trosseille, Xavier; Praxl, Norbert; Hynd, David; Irwin, Annette

2012-10-01

The development of the WorldSID 50th percentile male dummy was initiated in 1997 by the International Organisation for Standardisation (ISO/TC22/SC12/WG5) with the objective of developing a more biofidelic side impact dummy and supporting the adoption of a harmonised dummy into regulations. The dummy is currently under evaluation at the Working Party on Passive Safety (GRSP) in order to be included in the pole side impact global technical regulation (GTR). Injury risk curves dedicated to this dummy and built on behalf of ISO/TC22/SC12/WG6 were proposed in order to assess the occupant safety performance (Petitjean et al. 2009). At that time, there was no recommendation yet on the injury criteria and no consensus on the most accurate statistical method to be used. Since 2009, ISO/TC22/SC12/WG6 reached a consensus on the definition of guidelines to build injury risk curves, including the use of the survival analysis, the distribution assessment and quality checks. These guidelines were applied to the WorldSID 50th results published in 2009 in order to be able to provide a final set of injury risk curves recommended by ISO/TC22/SC12/WG6. The paper presents the different steps of the guidelines as well as the recommended injury risk curves dedicated to the WorldSID 50th for lateral shoulder load, thoracic rib deflection, abdomen rib deflection and pubic force.

Upper and Lower Neck Loads in Belted Human Surrogates in Frontal Impacts

PubMed Central

Yoganandan, Narayan; Pintar, Frank A.; Moore, Jason; Rinaldi, James; Schlick, Michael; Maiman, Dennis J.

2012-01-01

The upper and lower neck loads in the restrained Hybrid III dummy and Test Device for Human Occupant Restraint (THOR) were computed in simulated frontal impact sled tests at low, medium, and high velocities; repeatability performance of the two dummies were evaluated at all energy inputs; peak forces and moments were compared with computed loads at the occipital condyles and cervical-thoracic junctions from tests using post mortem human surrogates (PMHS). A custom sled buck was used to position the surrogates. Repeated tests were conducted at each velocity for each dummy and sufficient time was allowed to elapse between the two experiments. The upper and lower neck forces and moments were determined from load cell measures and its locations with respect to the ends of the neck. Both dummies showed good repeatability for axial and shear forces and bending moments at all changes in velocity inputs. Morphological characteristics in the neck loading responses were similar in all surrogates, although the peak magnitudes of the variables differed. In general, the THOR better mimicked the PMHS response than the Hybrid III dummy, and factors such as neck design and chest compliance were attributed to the observed variations. While both dummies were not designed for use at the two extremes of the tested velocities, results from the present study indicate that, currently the THOR may be the preferred anthropomorphic testing device in crashworthiness research studies and full-scale vehicle tests at all velocities. PMID:23169123

49 CFR 572.194 - Shoulder.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., while the midsagittal plane of the dummy is in vertical orientation. (4) Push the dummy at the knees and... back until the back of the upper torso is in contact with the seat back. (5) While maintaining the...

Characterization of deformable materials in the THOR dummy

DOT National Transportation Integrated Search

2000-01-01

Methodologies used to characterize the mechanical behavior of various materials used in the construction of the crash test dummy called THOR (Test device for Human Occupant Restraint) are described. These materials include polyurethane, neoprene, and...

49 CFR 572.91 - General description.

Code of Federal Regulations, 2010 CFR

2010-10-01

... structural properties of the dummy are such that the dummy conforms to this part in every respect both before and after being used in dynamic tests specified in Standard No. 213 of this chapter (§ 571.213). ...

49 CFR 572.91 - General description.

Code of Federal Regulations, 2011 CFR

2011-10-01

... structural properties of the dummy are such that the dummy conforms to this part in every respect both before and after being used in dynamic tests specified in Standard No. 213 of this chapter (§ 571.213). ...

49 CFR 572.81 - General description.

Code of Federal Regulations, 2011 CFR

2011-10-01

... contacts that exist under static conditions. (c) The structural properties of the dummy are such that the dummy conforms to this part in every respect both before and after being used in dynamic tests such as...

The application of dummy noise adaptive Kalman filter in underwater navigation

NASA Astrophysics Data System (ADS)

Li, Song; Zhang, Chun-Hua; Luan, Jingde

2011-10-01

The track of underwater target is easy to be affected by the various by the various factors, which will cause poor performance in Kalman filter with the error in the state and measure model. In order to solve the situation, a method is provided with dummy noise compensative technology. Dummy noise is added to state and measure model artificially, and then the question can be solved by the adaptive Kalman filter with unknown time-changed statistical character. The simulation result of underwater navigation proves the algorithm is effective.

Deflections from two types of Human Surrogates in Oblique Side Impacts

PubMed Central

Yoganandan, Narayan; Pintar, Frank A.

2008-01-01

The objective of the study was to obtain time-dependent thoracic and abdominal deflections of an anthropomorphic test device, the WorldSID dummy, in oblique impact using sled tests, and compare with post mortem human subject (PMHS) data. To simulate the oblique loading vector, the load wall was configured such that the thorax and abdominal plates were offset by twenty or thirty degrees. Deflections were obtained from a chestband placed at the middle thoracic level and five internal deflection transducers. Data were compared from the chestband and the transducer located at the same level of the thorax. In addition, data were compared with deflections from similar PMHS tests obtained using chestbands placed at the level of the axilla, xyphoid process, and tenth rib, representing the upper thorax, middle thorax, and abdominal region of the biological specimen. Peak deflections ranged from 30 to 85 mm in the dummy tests. Peak deflections ranged from 60 to 115 mm in PMHS. Under both obliquities, dummy deflection-time histories at the location along the chestband in close proximity to the internal deflection transducer demonstrated similar profiles. However, the peak deflection magnitudes from the chestband were approximately 20 mm greater than those from the internal transducer. Acknowledging that the chestband measures external deflections in contrast to the transducer which records internal ribcage deformations, peak deflections match from the two sensors. Deflection time histories were also similar between the dummy and PMHS in terms of morphology, although thoracic deflection magnitudes from the dummy matched more closely with PMHS than abdominal deflection magnitudes. The dummy deformed in such a way that peak deflections occurred along the lateral vector. This was in contrast to PMHS tests wherein maximum deflections occurred along the antero-lateral direction, suggesting differing deformation responses in the two models. In addition, peak deflections occurred earlier in the dummy than in PMHS. These preliminary results are valuable in future crashworthiness studies. PMID:19026246

No effect of bipolar interferential electrotherapy and pulsed ultrasound for soft tissue shoulder disorders: a randomised controlled trial

PubMed Central

van der Heijden, G. J M G; Leffers, P.; Wolters, P.; Verheijden, J.; van Mameren, H.; Houben, J.; Bouter, L.; Knipschild, P.

1999-01-01

OBJECTIVE—To assess the efficacy of bipolar interferential electrotherapy (ET) and pulsed ultrasound (US) as adjuvants to exercise therapy for soft tissue shoulder disorders (SD).
METHODS—Randomised placebo controlled trial with a two by two factorial design plus an additional control group in 17 primary care physiotherapy practices in the south of the Netherlands. Patients with shoulder pain and/or restricted shoulder mobility, because of a soft tissue impairment without underlying specific or generalised condition, were enrolled if they had not recovered after six sessions of exercise therapy in two weeks. They were randomised to receive (1) active ET plus active US; (2) active ET plus dummy US; (3) dummy ET plus active US; (4) dummy ET plus dummy US; or (5) no adjuvants. Additionally, they received a maximum of 12 sessions of exercise therapy in six weeks. Measurements at baseline, 6 weeks and 3, 6, 9, and 12 months later were blinded for treatment. Outcome measures: recovery, functional status, chief complaint, pain, clinical status, and range of motion.
RESULTS—After written informed consent 180 patients were randomised: both the active treatments were given to 73 patients, both the dummy treatments to 72 patients, and 35 patients received no adjuvants. Prognosis of groups appeared similar at baseline. Blinding was successfully maintained. At six weeks seven patients (20%) without adjuvants reported very large improvement (including complete recovery), 17 (23%) and 16 (22%) with active and dummy ET, and 19 (26%) and 14 (19%) with active and dummy US. These proportions increased to about 40% at three months, but remained virtually stable thereafter. Up to 12 months follow up the 95% CI for differences between groups for all outcomes include zero.
CONCLUSION—Neither ET nor US prove to be effective as adjuvants to exercise therapy for soft tissue SD.

 PMID:10460185

49 CFR 572.131 - General description.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Female Test Dummy, Alpha Version § 572.131 General description. (a) The Hybrid III fifth percentile adult... Small Adult Female Crash Test Dummy (HIII-5F, Alpha Version) (June 2002) (refer to § 572.130(a)(1)(ix...

49 CFR 572.131 - General description.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Female Test Dummy, Alpha Version § 572.131 General description. (a) The Hybrid III fifth percentile adult... Small Adult Female Crash Test Dummy (HIII-5F, Alpha Version) (June 2002) (refer to § 572.130(a)(1)(ix...

49 CFR 572.131 - General description.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Female Test Dummy, Alpha Version § 572.131 General description. (a) The Hybrid III fifth percentile adult... Small Adult Female Crash Test Dummy (HIII-5F, Alpha Version) (June 2002) (refer to § 572.130(a)(1)(ix...

49 CFR 572.121 - General description.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Dummy, Beta Version § 572.121 General description. (a) The Hybrid III type 6-year-old dummy is defined... specifications package P/N 127-0000, the titles of which are listed in Table A; (2) Procedures for Assembly...

Quality assurance in MR image guided adaptive brachytherapy for cervical cancer: Final results of the EMBRACE study dummy run.

PubMed

Kirisits, Christian; Federico, Mario; Nkiwane, Karen; Fidarova, Elena; Jürgenliemk-Schulz, Ina; de Leeuw, Astrid; Lindegaard, Jacob; Pötter, Richard; Tanderup, Kari

2015-12-01

Upfront quality assurance (QA) is considered essential when starting a multicenter clinical trial in radiotherapy. Despite the long experience gained for external beam radiotherapy (EBRT) trials, there are only limited audit QA methods for brachytherapy (BT) and none include the specific aspects of image guided adaptive brachytherapy (IGABT). EMBRACE is a prospective multicenter trial aiming to assess the impact of (MRI)-based IGABT in locally advanced cervical cancer. An EMBRACE dummy run was designed to identify sources and magnitude of uncertainties and errors considered important for the evaluation of clinical, and dosimetric parameters and their relation to outcome. Contouring, treatment planning and dose reporting was evaluated and scored with a categorical scale of 1-10. Active feedback to centers was provided to improve protocol compliance and reporting. A second dummy run was required in case of major deviations (score <7) for any item. Overall 27/30 centers passed the dummy run. 16 centers had to repeat the dummy run in order to clarify major inconsistencies to the protocol. The most pronounced variations were related to contouring for both EBRT and BT. Centers with experience in IGABT (>30 cases) had better performance as compared to centers with limited experience. The comprehensive dummy run designed for the EMBRACE trial has been a feasible tool for QA in IGABT of cervix cancer. It should be considered for future IGABT trials and could serve as the basis for continuous quality checks for brachytherapy centers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Head Excursion of Restrained Human Volunteers and Hybrid III Dummies in Steady State Rollover Tests

PubMed Central

Moffatt, Edward; Hare, Barry; Hughes, Raymond; Lewis, Lance; Iiyama, Hiroshi; Curzon, Anne; Cooper, Eddie

2003-01-01

Seatbelts provide substantial benefits in rollover crashes, yet occupants still receive head and neck injuries from contacting the vehicle roof interior when the roof exterior strikes the ground. Prior research has evaluated rollover restraint performance utilizing anthropomorphic test devices (dummies), but little dynamic testing has been done with human volunteers to learn how they move during rollovers. In this study, the vertical excursion of the head of restrained dummies and human subjects was measured in a vehicle being rotated about its longitudinal roll axis at roll rates from 180-to-360 deg/sec and under static inversion conditions. The vehicle’s restraint design was the commonly used 3-point seatbelt with continuous loop webbing and a sliding latch plate. This paper presents an analysis of the observed occupant motion and provides a comparison of dummy and human motion under similar test conditions. Thirty-five tests (eighteen static and seventeen dynamic) were completed using two different sizes of dummies and human subjects in both near and far-side roll directions. The research indicates that far-side rollovers cause the restrained test subjects to have greater head excursion than near-side rollovers, and that static inversion testing underestimates head excursion for far-side occupants. Human vertical head excursion of up to 200 mm was found at a roll rate of 220 deg/sec. Humans exhibit greater variability in head excursion in comparison to dummies. Transfer of seatbelt webbing through the latch plate did not correlate directly with differences in head excursion. PMID:12941241

Techniques for Developing Child Dummy Protection Reference Values. Event Report

DOT National Transportation Integrated Search

1996-10-01

The purpose of this report is to present background information and techniques : for developing protection reference values (PRV) to use with child dummies in : out-of-position (OOP) child/air bag interaction testing. Biomechanics experts : agree tha...

Blood pressure control with amlodipine add-on therapy in patients with hypertension and diabetes: results of the Amlodipine Diabetic Hypertension Efficacy Response Evaluation Trial.

PubMed

Kloner, Robert A; Neutel, Joel; Roth, Eli M; Weiss, Robert; Weinberger, Myron H; Thakker, Kamlesh M; Schwartz, Brian; Shi, Harry; Gregg, Anne-Marie

2008-11-01

Attainment of blood pressure (BP) goals in patients with diabetes is critical both to reduce the risk of cardiovascular events and to delay the progression of renal disease. While therapeutic guidelines advise initial therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, monotherapy with these agents may not be sufficient to attain target BP. The ADHT (Amlodipine Diabetic Hypertension Efficacy Response Evaluation Trial) evaluated the efficacy and safety of adding amlodipine to the treatment regimen of patients with hypertension and diabetes who were already receiving either quinapril or losartan as monotherapy. ADHT was a double-blind, double-dummy, 22-week trial conducted in the US. After a washout period of 7-13 days, patients (aged 30-75 y) with hypertension and diabetes were randomized to receive quinapril 20 mg/day plus placebo or losartan 50 mg/day plus placebo for 4 weeks, titrated to 40 mg or 100 mg (if required), respectively, for an additional 4 weeks to achieve their BP goals (<130/80 mm Hg). At week 8, either amlodipine 5 mg/day or placebo was added for an additional 12 weeks, with titration to 10 mg at week 14 if the BP goal was not achieved. Efficacy of add-on therapy was evaluated in 411 patients (amlodipine 211, placebo 200). BP goal was reached by 27.5% of patients when amlodipine was added to quinapril or losartan monotherapy, compared with 12.5% when placebo was added (OR 2.73; 95% CI 1.61 to 4.64; p < 0.001). When added to quinapril or losartan monotherapy, amlodipine reduced BP by 8.1/5.4 mm Hg, compared with a 1.6/0.7 mm Hg decrease with add-on placebo (p < 0.001). Amlodipine, quinapril, and losartan were well tolerated. Amlodipine is safe and effective when added to quinapril or losartan monotherapy to help lower BP toward therapeutic targets in patients with hypertension and diabetes.

Neurological and psychiatric tolerability of rilpivirine (TMC278) vs. efavirenz in treatment-naïve, HIV-1-infected patients at 48 weeks.

PubMed

Mills, A M; Antinori, A; Clotet, B; Fourie, J; Herrera, G; Hicks, C; Madruga, J V; Vanveggel, S; Stevens, M; Boven, K

2013-08-01

The aim of the study was to compare the neuropsychiatric safety and tolerability of rilpivirine (TMC278) vs. efavirenz in a preplanned pooled analysis of data from the ECHO and THRIVE studies which compared the safety and efficacy of the two drugs in HIV-1 infected treatment naïve adults. ECHO and THRIVE were randomized, double-blind, double-dummy, 96-week, international, phase 3 trials comparing the efficacy, safety and tolerability of rilpivirine 25 mg vs. efavirenz 600 mg once daily in combination with two background nucleoside/tide reverse transcriptase inhibitors. Safety and tolerability analyses were conducted when all patients had received at least 48 weeks of treatment or discontinued earlier. Differences between treatments in the incidence of neurological and psychiatric adverse events (AEs) of interest were assessed in preplanned statistical analyses using Fisher's exact test. At the time of the week 48 analysis, the cumulative incidences in the rilpivirine vs. efavirenz groups of any grade 2-4 treatment-related AEs and of discontinuation because of AEs were 16% vs. 31% (P<0.0001) and 3% vs. 8% (P=0.0005), respectively. The incidence of treatment-related neuropsychiatric AEs was 27% vs. 48%, respectively (P<0.0001). The incidence of treatment-related neurological AEs of interest was 17% vs. 38% (P<0.0001), and that of treatment-related psychiatric AEs of interest was 15% vs. 23% (P=0.0002). Dizziness and abnormal dreams/nightmares occurred significantly less frequently with rilpivirine vs. efavirenz (P<0.01). In both groups, patients with prior neuropsychiatric history tended to report more neuropsychiatric AEs but rates remained lower for rilpivirine than for efavirenz. Rilpivirine was associated with fewer neurological and psychiatric AEs of interest than efavirenz over 48 weeks in treatment-naïve, HIV-1-infected adults. © 2013 British HIV Association.

Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis

PubMed Central

Specks, Ulrich; Merkel, Peter A.; Seo, Philip; Spiera, Robert; Langford, Carol A.; Hoffman, Gary S.; Kallenberg, Cees G.M.; St. Clair, E. William; Fessler, Barri J.; Ding, Linna; Viviano, Lisa; Tchao, Nadia K.; Phippard, Deborah J.; Asare, Adam L.; Lim, Noha; Ikle, David; Jepson, Brett; Brunetta, Paul; Allen, Nancy B.; Fervenza, Fernando C.; Geetha, Duvuru; Keogh, Karina; Kissin, Eugene Y.; Monach, Paul A.; Peikert, Tobias; Stegeman, Coen; Ytterberg, Steven R.; Mueller, Mark; Sejismundo, Lourdes P.; Mieras, Kathleen; Stone, John H.

2018-01-01

Background The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is unknown. Methods In a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months. Results A total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide–azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (P<0.001, with a noninferiority margin of 20%). There was no significant difference between the groups in any efficacy measure, including the duration of complete remission and the frequency or severity of relapses. Among the 101 patients who had relapsing disease at baseline, rituximab was superior to conventional immunosuppression at 6 months (P = 0.01) and at 12 months (P = 0.009) but not at 18 months (P = 0.06), at which time most patients in the rituximab group had reconstituted B cells. There was no significant between-group difference in adverse events. Conclusions In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, NCT00104299.) PMID:23902481

High-Dose Azithromycin versus High-Dose Amoxicillin-Clavulanate for Treatment of Children with Recurrent or Persistent Acute Otitis Media

PubMed Central

Arrieta, Antonio; Arguedas, Adriano; Fernandez, Pilar; Block, Stan L.; Emperanza, Paz; Vargas, Sergio L.; Erhardt, William A.; de Caprariis, Pascal J.; Rothermel, Constance D.

2003-01-01

Infants and young children, especially those in day care, are at risk for recurrent or persistent acute otitis media (AOM). There are no data on oral alternatives to high-dose amoxicillin-clavulanate for treating AOM in these high-risk patients. In this double-blind, double-dummy multicenter clinical trial, we compared a novel, high-dose azithromycin regimen with high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent AOM. Three hundred four children were randomized; 300 received either high-dose azithromycin (20 mg/kg of body weight once a day for 3 days) or high-dose amoxicillin-clavulanate (90 mg/kg divided twice a day for 10 days). Tympanocentesis was performed at baseline; clinical response was assessed at day 12 to 16 and day 28 to 32. Two-thirds of patients were aged ≤2 years. A history of recurrent, persistent, or recurrent plus persistent AOM was noted in 67, 18, and 14% of patients, respectively. Pathogens were isolated from 163 of 296 intent-to-treat patients (55%). At day 12 to 16, clinical success rates for azithromycin and amoxicillin-clavulanate were comparable for all patients (86 versus 84%, respectively) and for children aged ≤2 years (85 versus 79%, respectively). At day 28 to 32, clinical success rates for azithromycin were superior to those for amoxicillin-clavulanate for all patients (72 versus 61%, respectively; P = 0.047) and for those aged ≤2 years (68 versus 51%, respectively; P = 0.017). Per-pathogen clinical efficacy against Streptococcus pneumoniae and Haemophilus influenzae was comparable between the two regimens. The rates of treatment-related adverse events for azithromycin and amoxicillin-clavulanate were 32 and 42%, respectively (P = 0.095). Corresponding compliance rates were 99 and 93%, respectively (P = 0.018). These data demonstrate the efficacy and safety of high-dose azithromycin for treating recurrent or persistent AOM. PMID:14506028

Response to Individualized Homeopathic Treatment for Depression in Climacteric Women with History of Domestic Violence, Marital Dissatisfaction or Sexual Abuse: Results from the HOMDEP-MENOP Study.

PubMed

Macías-Cortés, Emma Del Carmen; Llanes-González, Lidia; Aguilar-Faisal, Leopoldo; Asbun-Bojalil, Juan

2018-06-05

 Although individualized homeopathic treatment is effective for depression in climacteric women, there is a lack of well-designed studies of its efficacy for depression in battered women or in post-traumatic stress disorder. The aim of this study was to assess the association between individualized homeopathic treatment or fluoxetine and response to depression treatment in climacteric women with high levels of domestic violence, sexual abuse or marital dissatisfaction.  One hundred and thirty-three Mexican climacteric women with moderate-to-severe depression enrolled in the HOMDEP-MENOP Study (a randomized, placebo-controlled, double-blind, double-dummy, three-arm trial, with a 6-week follow-up study) were evaluated. Domestic violence, marital dissatisfaction and sexual abuse were assessed at baseline. Response to depression treatment was defined by a decrease of 50% or more from baseline score of Hamilton scale. Association between domestic violence, sexual abuse, and marital dissatisfaction and response to depression treatment was analyzed with bivariate analysis in the three groups. Odds ratio (OR) and 95% confidence interval (CI) were calculated.  Homeopathy versus placebo had a statistically significant association with response to depression treatment after adjusting for sexual abuse (OR [95% CI]: 11.07 [3.22 to 37.96]), domestic violence (OR [95% CI]: 10.30 [3.24 to 32.76]) and marital dissatisfaction (OR [95% CI]: 8.61 [2.85 to 25.99]).  Individualized homeopathic treatment is associated with response to depression treatment in climacteric women with high levels of domestic violence, sexual abuse or marital dissatisfaction. Further studies should be conducted to evaluate its efficacy specifically for post-traumatic stress disorder in battered women. CLINICALTRIALS. NCT01635218,:  URL: http://clinicaltrials.gov/ct2/show/NCT01635218?term=depression+homeopathy&rank=1. The Faculty of Homeopathy.

Budesonide is more effective than mesalamine or placebo in short-term treatment of collagenous colitis.

PubMed

Miehlke, Stephan; Madisch, Ahmed; Kupcinskas, Limas; Petrauskas, Dalius; Böhm, Günter; Marks, Hans-Joachim; Neumeyer, Michael; Nathan, Torben; Fernández-Bañares, Fernando; Greinwald, Roland; Mohrbacher, Ralf; Vieth, Michael; Bonderup, Ole K

2014-05-01

Studies reporting that budesonide is effective for the treatment of collagenous colitis have been small and differed in efficacy measures. Mesalamine has been proposed as a treatment option for collagenous colitis, although its efficacy has never been investigated in placebo-controlled trials. We performed a phase 3, placebo-controlled, multicenter study to evaluate budesonide and mesalamine as short-term treatments for collagenous colitis. Patients with active collagenous colitis were randomly assigned to groups given pH-modified release oral budesonide capsules (9 mg budesonide once daily, Budenofalk, n = 30), mesalamine granules (3 g mesalamine once daily, Salofalk, n = 25), or placebo for 8 weeks (n = 37) in a double-blind, double-dummy fashion. The study was conducted in 31 centers (hospital clinics and private practices) in Germany, Denmark, Lithuania, Spain, and the United Kingdom. The primary end point was clinical remission at 8 weeks defined as ≤ 3 stools per day. Secondary end points included clinical remission at 8 weeks, according to the Hjortswang-Criteria of disease activity, taking stool consistency into account. A greater percentage of patients in the budesonide group were in clinical remission at week 8 than the placebo group (intention-to-treat analysis, 80.0% vs 59.5%; P = .072; per-protocol analysis, 84.8% vs 60.6%; P = .046). Based on the Hjortswang-Criteria, 80.0% of patients given budesonide achieved clinical remission compared with 37.8% of patients given placebo (P = .0006); 44.0% of patients given mesalamine achieved clinical remission, but budesonide was superior to mesalamine (P = .0035). Budesonide significantly improved stool consistency and mucosal histology, and alleviated abdominal pain. The rate of adverse events did not differ among groups. Oral budesonide (9 mg once daily) is effective and safe for short-term treatment of collagenous colitis. Short-term treatment with oral mesalamine (3 g once daily) appears to be ineffective. ClinicalTrials.gov number, NCT00450086. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Budesonide 9 mg is at least as effective as mesalamine 4.5 g in patients with mildly to moderately active Crohn's disease.

PubMed

Tromm, Andreas; Bunganič, Ivan; Tomsová, Eva; Tulassay, Zsolt; Lukáš, Milan; Kykal, Jan; Bátovský, Marian; Fixa, Bohumil; Gabalec, Libor; Safadi, Rifaat; Kramm, Heinz-Jochen; Altorjay, István; Löhr, Hanns; Koutroubakis, Ioannis; Bar-Meir, Simon; Stimac, Davor; Schäffeler, Elke; Glasmacher, Christoph; Dilger, Karin; Mohrbacher, Ralf; Greinwald, Roland

2011-02-01

Comparative data on budesonide vs mesalamine for the treatment of mild-to-moderately active Crohn's disease (CD) are sparse. We assessed the efficacy and safety of each therapy in patients with mildly to moderately active CD. We performed a randomized, double-blind, double-dummy, 8-week, multicenter study in which 309 patients with mildly to moderately active CD received pH-modified-release oral budesonide (9 mg/day once daily or 3 mg/day 3 times daily) or Eudragit-L-coated oral mesalamine (4.5 g/day). The primary efficacy variable, clinical remission (defined as Crohn's Disease Activity Index ≤150), at the final visit occurred in 69.5% (107 of 154) of patients given budesonide vs 62.1% (95 of 153) of patients given mesalamine (difference, 7.4%; 95% repeated confidence interval, -4.6% to 18.0%; P = .001 for noninferiority). Clinical remission rates did not differ significantly between the 2 budesonide groups. Treatment response, defined as Crohn's Disease Activity Index of 150 or less and/or a decrease of 70 or more (Δ70) or 100 or more (Δ100) points from baseline to final visit, did not differ significantly between patients given budesonide vs mesalamine (Δ70, P = .11; Δ100, P = .15), or between the 2 budesonide groups (Δ70, P = .38; Δ100, P = .78). No other efficacy end points differed significantly between groups. Discontinuation because of adverse events occurred in 3% and 5% of budesonide- and mesalamine-treated patients, respectively. There were no clinically relevant differences in adverse events between the 2 budesonide groups. Budesonide (9 mg/day) was numerically, but not statistically, more effective than Eudragit-L-coated mesalamine (4.5 g/day) in patients with mildly to moderately active CD. Budesonide (9 mg/day), administered once daily, was as effective as the standard (3 times daily) regimen. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers.

PubMed

Teng, Renli; Maya, Juan; Butler, Kathleen

2013-01-01

The results of two independent, randomized, two-period crossover, single-center studies, conducted to assess the pharmacokinetics of ticagrelor ± aspirin, inhibition of platelet aggregation (IPA) with ticagrelor/aspirin vs. clopidogrel/aspirin, and safety, tolerability, and bleeding times are reported here. In Study A (open-label), 16 volunteers received ticagrelor (50 mg bid Days 1-5; 200 mg bid Days 6-9; one 200 mg dose on Day 10) ± 300 mg qd aspirin (Days 1-10). In Study B (double-blind, double-dummy), 16 volunteers received aspirin (300 mg loading dose/75 mg qd Days 2-9) with either ticagrelor (200 mg bid Days 4-8, one 200 mg dose on Day 9) or clopidogrel (300 mg loading dose Day 4, 75 mg qd Days 5-9). At steady-state ticagrelor (50 mg bid, or 200 mg bid), concomitant aspirin (300 mg qd) had no effect on mean maximum plasma concentration (Cmax), median time to Cmax (tmax), or mean area under the plasma concentration-time curve for the dosing interval (AUC0-τ) for ticagrelor and its primary metabolite, AR-C124910XX. Following 200 mg bid ticagrelor, mean Cmax and AUC0-τ for both parent and metabolite were comparable with co-administration of aspirin at 75 mg and 300 mg qd. Aspirin (300 mg qd) had no effect on IPA (ADP-induced) by ticagrelor. However, aspirin and ticagrelor had an additive effect on IPA (collagen-induced). Ticagrelor/aspirin increased bleeding times vs. baseline. Ticagrelor/aspirin co-administration was well tolerated at all dose combinations evaluated. In summary, the findings of this study demonstrate that co-administration of aspirin (300 mg qd) with ticagrelor (50 mg bid, or 200 mg bid) had no effect on ticagrelor pharmacokinetics or IPA (ADP-induced) by ticagrelor.

In vivo comparison of the relative systemic bioavailability of fluticasone propionate from three anti-static spacers and a metered dose inhaler

PubMed Central

Nair, Arun; Menzies, Daniel; Hopkinson, Pippa; McFarlane, Lesley; Lipworth, Brian J

2009-01-01

AIMS The systemic bioavailability of inhaled fluticasone propionate (FP) depends primarily on lung absorption and can be quantified by measuring suppression of overnight and early morning urinary cortisol/creatinine (OUCC and EMUCC, respectively). The aim of the study was to determine the relative bioavailability of hydrofluoroalkane (HFA) FP to the lungs via anti-static plastic (Zerostat-V and Aerochamber Max), metal (Nebuchamber) anti-static spacers and metered dose inhaler [Flixotide Evohaler (EH) (pMDI)]. METHODS A randomized, double-blind, double-dummy, four-way crossover design was used. Eighteen mild to moderate asthmatics received single doses of placebo/HFA-FP 2 mg via the 280-ml Zerostat-V (ZS); 250-ml Nebuchamber (NC); 197-ml Aerochamber Max (AC); and pMDI (EH). Measurements of OUCC and EMUCC were made at baseline and 10 h after each dose. RESULTS Significant suppression of OUCC and EMUCC occurred from baseline with all three spacers, but not Evohaler (geometric mean fold suppression, 95% confidence interval): ZS, 2.74 (1.75, 4.30), P < 0.001; NC, 3.31 (1.81, 6.06), P < 0.001; AC, 4.98 (3.39, 7.31), P < 0.001; and for EH this was 1.42 (0.92, 2.21), P = 0.169 (equating to a 64, 70, 80 and 30% fall in OUCC via the ZS, NC, AC and EH devices, respectively). There were significant differences between all three spacers vs. EH. When compared with the Evohaler, the Zerostat V resulted in 48% greater suppression (P = 0.009); the Nebuchamber 57% greater suppression (P = 0.001); and the Aerochamber Max 71% greater suppression of OUCC (P < 0.001). CONCLUSION All three antistatic spacers significantly increased the relative systemic bioavailability of HFA-FP compared with the standard pMDI. PMID:19220273

Clinical efficacy of Spasmofen® suppository in the emergency treatment of renal colic: a randomized, double-blind, double-dummy comparative trial.

PubMed

Yakoot, Mostafa; Salem, Amel; Yousef, Sameh; Helmy, Sherine

2014-01-01

Renal colic is typically characterized by the sudden onset of severe pain radiating from the flank to the groin and its acute management in emergency departments essentially aims at rapid pain relief. Spasmofen(®) is a brand of Amriya Pharmaceutical Industries in the form of rectal suppositories containing ketoprofen 100 mg and hyoscine butylbromide 10 mg. This combination is intended for the rapid relief of severe colicky pain in the renal system, hepatobiliary system, or gastrointestinal tract. This trial aims to compare a single-dose of Spasmofen rectal suppository to a single intravenous (IV) ketorolac tromethamine 30 mg/2 mL dose in patients with acute renal colic. A total of 80 eligible consecutive patients presenting to the emergency departments of two medical centers with acute renal colic were included in the study. Eligible patients who signed the informed consent were randomly assigned into two treatment groups: an experimental group (Spasmofen group) who received one Spasmofen rectal suppository plus an IV injection of 2 mL of normal saline solution; and a control group (ketorolac group) who received one ketorolac 30 mg/2 mL ampoule IV plus one placebo suppository. Treatment success, defined as a change in the verbal rating score from severe or moderate pain to none or mild at 60 minutes after the dose, was compared between groups using the chi-square/Fisher's exact test. Percentage reductions in visual pain analog scale (VPAS) scores at 15 and 60 minutes after the dose were compared between groups using the Z-test for proportions. Successful treatment at 60 minutes occurred in 35 of 40 (87.5%) of Spasmofen-treated patients and in 33 of 40 (82.5%) of ketorolac-treated patients. The difference was not statistically significant by Fisher's exact test (P=0.755). The mean percentage reduction of VPAS after 15 minutes was 61.82% in the Spasmofen-treated group and 64.76% in the ketorolac-treated group. The difference was also not statistically significant by the Z-test for proportions (P=0.795). Sixty minutes after being treated, Spasmofen was associated with a statistically significant greater reduction in VPAS (mean% reduction =92.36%) than ketorolac (75.06%; P=0.0466). Single-dose Spasmofen rectal suppository might be a safe and effective first-aid treatment for the emergency department relief of acute renal colic.

LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD.

PubMed

Zhong, Nanshan; Wang, Changzheng; Zhou, Xiangdong; Zhang, Nuofu; Humphries, Michael; Wang, Linda; Thach, Chau; Patalano, Francesco; Banerji, Donald

2015-01-01

The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient's airflow limitation, their history of exacerbations, and symptoms. The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year. In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks. The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26. Overall, 676 patients completed the study. The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met. QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001). QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001). QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use. However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC. Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%). The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%). These findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year.

Efficacy of flurbiprofen 8.75 mg delivered as a spray or lozenge in patients with sore throat due to upper respiratory tract infection: a randomized, non-inferiority trial in the Russian Federation

PubMed Central

Radkova, Eugenia; Burova, Natalia; Bychkova, Valeria; DeVito, Robert

2017-01-01

Objective To assess the efficacy of flurbiprofen 8.75 mg delivered as a spray or lozenge in patients with sore throat due to upper respiratory tract infection (URTI). Materials and methods This multicenter, double-blind, double-dummy, non-inferiority study randomized 440 adults with recent-onset, moderate-to-severe sore throat due to URTI to a single dose of either flurbiprofen 8.75 mg spray (n=218) or flurbiprofen 8.75 mg lozenge (n=222). The presence or absence of beta-hemolytic streptococci (A or C) was confirmed by culture tests (throat swab). The primary efficacy end point was the difference from baseline to 2 hours post-dose in sore throat pain intensity scale (STPIS pain intensity difference [PID] 2h), a validated 100 mm visual analog scale (from 0=“no pain” to 100=“severe pain”), with a non-inferiority margin of −6 mm. Secondary end points included STPIS PID at 1 hour (STPIS PID 1h) and over 2 hours (STPIS sum of sore throat pain intensity differences [SPID]0–2h) and ratings of patient satisfaction and investigator assessment of drug efficacy at 2 hours. Safety (adverse events [AEs]) was also assessed. Results Reductions in sore throat pain intensity at 2 hours (STPIS PID 2h) were similar for spray (least square mean −40.51) and lozenge (−40.10) (difference: 0.41, 95% confidence interval [95% CI] −3.20, 4.01), with non-inferiority demonstrated. Subgroup analyses showed similar efficacy (STPIS PID 2h) for patients testing positive or negative for Strep A or C. There was no significant difference between spray and lozenge in STPIS PID 1h or STPIS SPID0–2h, and patient satisfaction and investigators’ assessment of efficacy at 2 hours were similar for both groups. There were no significant differences in AEs between the two groups, with 17 drug-related events across both groups, all being mild and none being serious. Conclusion Both formulations demonstrated comparable efficacy and safety profiles and provide patients with two different treatment formats to choose from for effective symptomatic relief of sore throat, depending on their preference. PMID:28740426

Efficacy of flurbiprofen 8.75 mg delivered as a spray or lozenge in patients with sore throat due to upper respiratory tract infection: a randomized, non-inferiority trial in the Russian Federation.

PubMed

Radkova, Eugenia; Burova, Natalia; Bychkova, Valeria; DeVito, Robert

2017-01-01

To assess the efficacy of flurbiprofen 8.75 mg delivered as a spray or lozenge in patients with sore throat due to upper respiratory tract infection (URTI). This multicenter, double-blind, double-dummy, non-inferiority study randomized 440 adults with recent-onset, moderate-to-severe sore throat due to URTI to a single dose of either flurbiprofen 8.75 mg spray (n=218) or flurbiprofen 8.75 mg lozenge (n=222). The presence or absence of beta-hemolytic streptococci (A or C) was confirmed by culture tests (throat swab). The primary efficacy end point was the difference from baseline to 2 hours post-dose in sore throat pain intensity scale (STPIS pain intensity difference [PID] 2h), a validated 100 mm visual analog scale (from 0="no pain" to 100="severe pain"), with a non-inferiority margin of -6 mm. Secondary end points included STPIS PID at 1 hour (STPIS PID 1h) and over 2 hours (STPIS sum of sore throat pain intensity differences [SPID] 0-2h ) and ratings of patient satisfaction and investigator assessment of drug efficacy at 2 hours. Safety (adverse events [AEs]) was also assessed. Reductions in sore throat pain intensity at 2 hours (STPIS PID 2h) were similar for spray (least square mean -40.51) and lozenge (-40.10) (difference: 0.41, 95% confidence interval [95% CI] -3.20, 4.01), with non-inferiority demonstrated. Subgroup analyses showed similar efficacy (STPIS PID 2h) for patients testing positive or negative for Strep A or C. There was no significant difference between spray and lozenge in STPIS PID 1h or STPIS SPID 0-2h , and patient satisfaction and investigators' assessment of efficacy at 2 hours were similar for both groups. There were no significant differences in AEs between the two groups, with 17 drug-related events across both groups, all being mild and none being serious. Both formulations demonstrated comparable efficacy and safety profiles and provide patients with two different treatment formats to choose from for effective symptomatic relief of sore throat, depending on their preference.

Techniques for developing child dummy protection reference values : event report

DOT National Transportation Integrated Search

1996-10-01

The purpose of this report is to present background information and techniques for developing protection reference values (PRV) to use with child dummies in out-of-position (OOP) child/air bag interaction testing. This report summarizes the literatur...

Potential technique for improving the survival of victims of tsunamis

PubMed Central

Suga, Hisami; Prochazka, Zdenek; Suzuki, Kojiro; Oguri, Kazumasa; Inoue, Tetsunori

2018-01-01

We investigated a method for surviving tsunamis that involved the use of personal flotation devices (PFDs). In our work, we succeeded in numerically demonstrating that the heads of all the dummies wearing PFDs remained on the surface and were not dragged underwater after the artificial tsunami wave hit them. In contrast, the heads of all the dummies not wearing PFDs were drawn underwater immediately; these dummies were subsequently entrapped in a vortex. The results of our series of experiments are important as a first step to preventing the tragedies caused by tsunamis. PMID:29791490

MULTIPLE SETS OF TWIN SLABS ON THE RUN OUT. THE ...

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

MULTIPLE SETS OF TWIN SLABS ON THE RUN OUT. THE RUN OUT INCLUDES THE TRAVELING TORCH WHICH CUTS SLABS TO DESIRED LENGTH, AN IDENTIFICATION SYSTEM TO INDICATE HEAT NUMBER AND TRACE IDENTITY OF EVERY SLAB, AND A DEBURRING DEVICE TO SMOOTH SLABS. AT LEFT OF ROLLS IS THE DUMMY BAR. DUMMY BAR IS INSERTED UP THROUGH CONTAINMENT SECTION INTO MOLD PRIOR TO START OF CAST. WHEN STEEL IS INTRODUCED INTO MOLD IT CONNECTS WITH BAR AS CAST BEGINS, AT RUN OUT DUMMY BAR DISCONNECTS AND IS STORED. - U.S. Steel, Fairfield Works, Continuous Caster, Fairfield, Jefferson County, AL

MULTIPLE SETS OF TWIN SLABS ON THE RUN OUT. THE ...

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

MULTIPLE SETS OF TWIN SLABS ON THE RUN OUT. THE RUN OUT INCLUDES THE TRAVELING TORCH WHICH CUTS SLABS TO DESIRED LENGTH, AN IDENTIFICATION SYSTEM TO INDICATE HEAT NUMBER AND TRACE IDENTITY OF EVERY SLAB, AND A DEBURRING DEVICE TO SMOOTH SLABS. AT LEFT OF ROLLS IS THE DUMMY BAR. DUMMY BAR IS INSERTED UP THROUGH CONTAINMENT SECTION INTO MOLD PRIOR TO START OF CAST. WHEN STEEL IS INTRODUCED INTO MOLD IT CONNECTS WITH BAR AS CAST BEGINS, AT RUN OUT DUMMY BAR DISCONNECTS AND IS STORED - U.S. Steel, Fairfield Works, Continuous Caster, Fairfield, Jefferson County, AL

Comparison of car seats in low speed rear-end impacts using the BioRID dummy and the new neck injury criterion (NIC).

PubMed

Boström, O; Fredriksson, R; Håland, Y; Jakobsson, L; Krafft, M; Lövsund, P; Muser, M H; Svensson, M Y

2000-03-01

Long-term whiplash associated disorders (WAD) 1-3 sustained in low velocity rear-end impacts is the most common disability injury in Sweden. Therefore, to determine neck injury mechanisms and develop methods to measure neck-injury related parameters are of importance for current crash-safety research. A new neck injury criterion (NIC) has previously been proposed and evaluated by means of dummy, human and mathematical rear-impact simulations. So far, the criterion appears to be sensitive to the major car and collision related risk factors for injuries with long-term consequences. To further evaluate the applicability of NIC, four seats were tested according to a recently proposed sled-test procedure. 'Good' as well as 'bad' seats were chosen on the basis of a recently presented disability risk ranking list. The dummy used in the current tests was the Biofidelic Rear Impact Dummy (BioRID). The results of this study showed that NICmax values were generally related to the real-world risk of long-term WAD 1-3. Furthermore, these results suggested that NICmax calculated from sled tests using the BioRID dummy can be used for evaluating the neck injury risk of different car seats.

Benefits of a Low Severity Frontal Crash Test

PubMed Central

Digges, Kennerly; Dalmotas, Dainius

2007-01-01

The US Federal Motor Vehicle Safety Standard for frontal protection requires vehicle crash tests into a rigid barrier with two belted dummies in the front seats. The standard was recently modified to require two separate 56 Kph frontal tests. In one test the dummies are 50% males. In the other test, the dummies are 5% females. Analysis of crash test data indicates that the 56 Kph test does not encourage technology to reduce chest injuries in lower severity crashes. Tests conducted by Transport Canada provide data from belted 5% female dummies in the front seats of vehicles that were subjected crashes into a rigid barrier at 40 Kph. An analysis of the results showed that for many vehicles, the risks of serious chest injuries were higher in the 40 Kph test than in a 56 Kph test. This paper examines the benefits that would result from a requirement for a low severity (40 Kph) frontal barrier crash test with two belted 5% female dummies and more stringent chest injury requirements. A preliminary benefits analysis for chest deflection allowable in the range of 28 mm. to 36 mm. was conducted. A standard that limits the chest deflection to 34 mm. would reduce serious chest injury by 16% to 24% for the belted population in frontal crashes. PMID:18184499

Benefits of a low severity frontal crash test.

PubMed

Digges, Kennerly; Dalmotas, Dainius

2007-01-01

The US Federal Motor Vehicle Safety Standard for frontal protection requires vehicle crash tests into a rigid barrier with two belted dummies in the front seats. The standard was recently modified to require two separate 56 Kph frontal tests. In one test the dummies are 50% males. In the other test, the dummies are 5% females. Analysis of crash test data indicates that the 56 Kph test does not encourage technology to reduce chest injuries in lower severity crashes. Tests conducted by Transport Canada provide data from belted 5% female dummies in the front seats of vehicles that were subjected crashes into a rigid barrier at 40 Kph. An analysis of the results showed that for many vehicles, the risks of serious chest injuries were higher in the 40 Kph test than in a 56 Kph test. This paper examines the benefits that would result from a requirement for a low severity (40 Kph) frontal barrier crash test with two belted 5% female dummies and more stringent chest injury requirements. A preliminary benefits analysis for chest deflection allowable in the range of 28 mm. to 36 mm. was conducted. A standard that limits the chest deflection to 34 mm. would reduce serious chest injury by 16% to 24% for the belted population in frontal crashes.

Coupling of a finite element human head model with a lumped parameter Hybrid III dummy model: preliminary results.

PubMed

Ruan, J S; Prasad, P

1995-08-01

A skull-brain finite element model of the human head has been coupled with a multilink rigid body model of the Hybrid III dummy. The experimental coupled model is intended to represent anatomically a 50th percentile human to the extent the dummy and the skull-brain model represent a human. It has been verified by simulating several human cadaver head impact tests as well as dummy head 'impacts" during barrier crashes in an automotive environment. Skull-isostress and brain-isostrain response curves were established based on model calibration of experimental human cadaver tolerance data. The skull-isostress response curve agrees with the JARI Human Head Impact Tolerance Curve for skull fracture. The brain-isostrain response curve predicts a higher G level for concussion than does the JARI concussion curve and the Wayne State Tolerance Curve at the longer time duration range. Barrier crash simulations consist of belted dummies impacting an airbag, a hard and soft steering wheel hub, and no head contact with vehicle interior components. Head impact force, intracranial pressures and strains, skull stress, and head center-of-gravity acceleration were investigated as injury parameters. Head injury criterion (HIC) was also calculated along with these parameters. Preliminary results of the model simulations in those impact conditions are discussed.

Lysine clonixinate vs. paracetamol/codeine in postepisiotomy pain.

PubMed

De los Santos, A R; Martí, M I; Espinosa, D; Di Girolamo, G; Vinacur, J C; Casadei, A

1998-01-01

This study was conducted to compare the analgesic action of Lysine Clonixinate (LC) vs Paracetamol/Codeine association (PC) in the treatment of postepisiotomy pain in primiparae women: 131 primiparous patients with moderate-to-severe postepisiotomy pain were enrolled in a double blind dummy design study and randomly allocated to either treatment with fixed doses of LC 125 mg or Paracetamol 500 mg+Codeine 30 mg 6 qh during 24 hours. Intensity of spontaneous pain and pain on walking was assessed according to a visual analog scale (VAS) and patient's assessment before receiving treatment and after 1, 2, 6 and 24 hours. Intensity of spontaneous pain was reduced in 24 hours from 4.28 +/- 2.11 to 1.73 +/- 1.46 (P < 0.0001) in the LC group and from 4.78 +/- 2.08 to 1.90 +/- 1.72 in the PC-treated group (p < 0.0001); with no significant differences between treatments. 54% of the patients treated with LC and 55% of those receiving PC showed onset of analgesic action 30 minutes following dose administration. Patient's final global assessment revealed that 95% of LC-treated patients and 96% of the PC group showed total or partial pain relief during the first treatment day. No sleep disturbances were seen during the night in 75% of patients. Only one patient receiving LC showed nausea not requiring treatment discontinuation. It is concluded that both treatments are equally effective to relieve moderate-to-severe postepisiotomy pain.

15. VIEW OF DUMMY FUEL ELEMENT ON FUEL ELEMENT HOLDER. ...

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

15. VIEW OF DUMMY FUEL ELEMENT ON FUEL ELEMENT HOLDER. SHOWS AIR FORCE MAN AT EDGE OF TANK. INEL PHOTO NUMBER 65-6176, TAKEN NOVEMBER 10, 1965. - Idaho National Engineering Laboratory, Advanced Reentry Vehicle Fusing System, Scoville, Butte County, ID

49 CFR 572.31 - General description.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., titled “Sign Convention for Vehicle Crash Testing”, dated 1994-12. (6) Exterior dimensions of the Hybrid... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES Hybrid III Test Dummy § 572.31 General description. (a) The Hybrid III 50th percentile size dummy consists of components and...

49 CFR 572.141 - General description.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES 3-year-Old Child Crash Test Dummy, Alpha Version § 572.141 General description. (a) The Hybrid III 3-year-old child dummy is described by the following materials: (1) Technical drawings and specifications package 210-0000 (refer to...

EFFECTS OF OVERPRESSURES IN GROUP SHELTERS ON ANIMALS AND DUMMIES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, J.E.; White, C.S.; Chiffelle, T.L.

1953-09-01

S>Relative biological hazards of blast were studied in two types of communal air-raid shelters during Shots 1 and 8. Dogs, restrained within the shelters during detonation, were studied pathologically and clinically for blast injuries. Two anthropometric dummies were test objects for displacement studies utilizing high-speed photography. Physical data included pressure vs time and air-drag determinations. During Shot 1, animals sustained marked blast damages (hemorrhages in lungs and abdominal organs), three dogs were ataxic. and the dummies were rather violently displaced. In Shot 8, however, no significant injuries were found in the animals, and the dummies were minimally displaced. Analysis ofmore » the physical data indicated that blast injuries and violent displacements may occur at much lower static overpressures than previously assumed from conventional explosion data. Furthermore, biological damage appeared to be related to the rate of rise of the overpressure and air drag, as well as the maximum overpressure values. (auth)« less

Magnetic dummy molecularly imprinted polymers based on multi-walled carbon nanotubes for rapid selective solid-phase extraction of 4-nonylphenol in aqueous samples.

PubMed

Rao, Wei; Cai, Rong; Yin, Yuli; Long, Fang; Zhang, Zhaohui

2014-10-01

In this paper, a highly selective sample clean-up procedure combining magnetic dummy molecular imprinting with solid-phase extraction was developed for rapid separation and determination of 4-nonylphenol (NP) in the environmental water samples. The magnetic dummy molecularly imprinted polymers (mag-DMIPs) based on multi-walled carbon nanotubes were successfully synthesized with a surface molecular imprinting technique using 4-tert-octylphenol as the dummy template and tetraethylorthosilicate as the cross-linker. The maximum adsorption capacity of the mag-DMIPs for NP was 52.4 mg g(-1) and it took about 20 min to achieve the adsorption equilibrium. The mag-DMIPs exhibited the specific selective adsorption toward NP. Coupled with high performance liquid chromatography analysis, the mag-DMIPs were used to extract solid-phase and detect NP in real water samples successfully with the recoveries of 88.6-98.1%. Copyright © 2014 Elsevier B.V. All rights reserved.

Transformer current sensor for superconducting magnetic coils

DOEpatents

Shen, S.S.; Wilson, C.T.

1985-04-16

The present invention is a current transformer for operating currents larger than 2kA (two kiloamps) that is capable of detecting a millivolt level resistive voltage in the presence of a large inductive voltage. Specifically, the present invention includes substantially cylindrical primary turns arranged to carry a primary current and substantially cylindrical secondary turns arranged coaxially with and only partially within the primary turns, the secondary turns including an active winding and a dummy winding, the active and dummy windings being coaxial, longitudinally separated and arranged to mutually cancel voltages excited by commonly experienced magnetic fields, the active winding but not the dummy winding being arranged within the primary turns.

Summary of new test dummies, injury criteria

DOT National Transportation Integrated Search

2000-06-17

Besides a plethora of new tests, the air bag standard issued recently calls for four new test dummies in addition to the average size adult male already used in testing: small adult female; 6 year old child; 3 year old child; and 1 year old infant. I...

Using Time-Series Regression to Predict Academic Library Circulations.

ERIC Educational Resources Information Center

Brooks, Terrence A.

1984-01-01

Four methods were used to forecast monthly circulation totals in 15 midwestern academic libraries: dummy time-series regression, lagged time-series regression, simple average (straight-line forecasting), monthly average (naive forecasting). In tests of forecasting accuracy, dummy regression method and monthly mean method exhibited smallest average…

Study of the two-phase dummy load shut-down strategy for proton exchange membrane fuel cells

NASA Astrophysics Data System (ADS)

Zhang, Q.; Lin, R.; Cui, X.; Xia, S. X.; Yang, Z.; Chang, Y. T.

2017-02-01

This paper presents a new system strategy designed to alleviate the performance decay caused by start-up/shut-down (SU/SD) conditions in proton exchange membrane fuel cells (PEMFCs). The innovative method was tested using a two-phase dummy load composed of a linearly declined main load and a fixed small auxiliary load. The initial value of the main load must be controlled within a proper range, and a closed-ended air exhaust is necessary. According to the analysis of in-situ current density distribution during SD processes, the two-phase dummy load can continuously fit the process of oxygen reduction in the cathode, whereas the conventional dummy load leads to local air starvation. Polarization curves and cyclic voltammetry (CV) were employed to evaluate the performance decay during SU/SD repetition. After tests of 900 cycles, the highest voltage degradation rate of the PEMFC was 3.33 μV cycle-1 (800 mA cm-2), and the electrochemical surface area (ECSA) loss was 0.0046 m2 g-1 cycle-1 with the two-phase dummy load strategy. After comparing results with similar work on a single PEMFC, the authors confirmed the preeminent effectiveness of this strategy. This strategy will also improve fuel cell stack performance due to controllable SD duration and comparatively low performance decay rates.

Leadership for Dummies: A Capstone Project for Leadership Students

ERIC Educational Resources Information Center

Moore, Lori L.; Odom, Summer F.; Wied, Lexi M.

2011-01-01

Capstone courses in leadership provide students opportunities to synthesize prior knowledge about various aspects of leadership. This article describes the "Leadership for Dummies" project, which could be used as a capstone experience for leadership majors. Based on his experiences as a psychological researcher, Gardner (2008) identified five…

Regression Analysis with Dummy Variables: Use and Interpretation.

ERIC Educational Resources Information Center

Hinkle, Dennis E.; Oliver, J. Dale

1986-01-01

Multiple regression analysis (MRA) may be used when both continuous and categorical variables are included as independent research variables. The use of MRA with categorical variables involves dummy coding, that is, assigning zeros and ones to levels of categorical variables. Caution is urged in results interpretation. (Author/CH)

49 CFR 572.181 - General description.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES 2re Side Impact Crash Test Dummy, 50th Percentile Adult Male § 572.181 General description. (a) The ES-2re Side Impact Crash Test... (PADI) of the ES-2re Side Impact Crash Test Dummy, February 2008, incorporated by reference, see § 572...

49 CFR 572.181 - General description.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES ES-2re Side Impact Crash Test Dummy, 50th Percentile Adult Male § 572.181 General description. (a) The ES-2re Side Impact Crash... (PADI) of the ES-2re Side Impact Crash Test Dummy, February 2008, incorporated by reference, see § 572...

49 CFR 572.191 - General description.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES SID-IIsD Side Impact Crash Test Dummy, Small Adult Female § 572.191 General description. (a) The SID-IIsD Side Impact Crash Test... test sensors for the SID-IIsD Side Impact Crash Test Dummy, 5th percentile adult female, is shown in...

49 CFR 572.181 - General description.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES ES-2re Side Impact Crash Test Dummy, 50th Percentile Adult Male § 572.181 General description. (a) The ES-2re Side Impact Crash... (PADI) of the ES-2re Side Impact Crash Test Dummy, February 2008, incorporated by reference, see § 572...

49 CFR 572.191 - General description.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES SID-IIsD Side Impact Crash Test Dummy, Small Adult Female § 572.191 General description. (a) The SID-IIsD Side Impact Crash Test... test sensors for the SID-IIsD Side Impact Crash Test Dummy, 5th percentile adult female, is shown in...

49 CFR 572.120 - Incorporation by reference.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Child Test Dummy, Beta Version § 572.120 Incorporation by reference. (a) The following materials are... List and Drawings, Hybrid III Six-year-old Child Test Dummy (H-III6C, Beta Version) (June 2002... (vii) The Hybrid III Six-year-old Child Parts/Drawing List. (2) A procedures manual entitled...

Segmented Polynomial Models in Quasi-Experimental Research.

ERIC Educational Resources Information Center

Wasik, John L.

1981-01-01

The use of segmented polynomial models is explained. Examples of design matrices of dummy variables are given for the least squares analyses of time series and discontinuity quasi-experimental research designs. Linear combinations of dummy variable vectors appear to provide tests of effects in the two quasi-experimental designs. (Author/BW)

The Japanese Copula: A Dummy?

ERIC Educational Resources Information Center

Wenck, G.

1973-01-01

Discussion of whether the Japanese copula can adequately be described as a dummy, i.e., as an element which although existing in the surface structure can be dispensed with in the deep structure of a sentence; based on a paper read at the 1970 meeting of the Societas Linguistica Europaea, Prague, Czechoslovakia. (RS)

Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) versus Extended-Release Morphine Administered Orally in Nondependent Recreational Opioid Users

PubMed Central

Webster, Lynn R.; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M.

2017-01-01

Objective. To compare the relative human abuse potential of intact and manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine sulfate ER tablets Methods. This randomized, double-blind, triple-dummy, active- and placebo-controlled, 4-way crossover, single-center study included adult volunteers who were experienced, nondependent, recreational opioid users. Participants were randomized 1:1:1:1 to placebo, morphine-ADER-IMT (60 mg, intact), morphine-ADER-IMT (60 mg, manipulated), and morphine ER (60 mg, manipulated) and received 1 dose of each oral agent in crossover fashion, separated by ≥5 days. Pharmacodynamic and pharmacokinetic endpoints were assessed, including the primary endpoint of peak effect of Drug Liking (Emax) via Drug Liking Visual Analog Scale (VAS) score and the secondary endpoints of time to Emax (TEmax) and mean abuse quotient (AQ; a pharmacokinetic parameter associated with drug liking). Results. Thirty-eight participants completed the study. Median Drug Liking VAS Emax was significantly lower after treatment with manipulated morphine-ADER-IMT (67) compared with manipulated morphine ER (74; P = 0.007). TEmax was significantly shorter after treatment with manipulated morphine ER compared with intact (P < 0.0001) or manipulated (P = 0.004) morphine-ADER-IMT. Mean AQ was lower after treatment with intact (5.7) or manipulated (16.4) morphine-ADER-IMT compared with manipulated morphine ER (45.9). Conclusions. Manipulated morphine-ADER-IMT demonstrated significantly lower Drug Liking Emax compared with manipulated morphine ER when administered orally. Morphine-ADER-IMT would be an important new AD, ER morphine product with lower potential for unintentional misuse by chewing or intentional manipulation for oral abuse than currently available non-AD morphine ER products. PMID:27633773

The acute effect of beta-guanidinopropionic acid versus creatine or placebo in healthy men (ABC Trial): study protocol for a randomized controlled trial.

PubMed

Karamat, Fares A; Horjus, Deborah L; Haan, Yentl C; van der Woude, Lisa; Oudman, Inge; van Montfrans, Gert A; Clark, Joseph F; Brewster, Lizzy M

2015-02-22

Despite adequate treatment, up to 30% of treated antihypertensive patients with primary, uncomplicated hypertension remain uncontrolled. We proposed that high intracellular activity of the ATP regenerating enzyme creatine kinase (CK) increases pressor responses and hypertension risk. In line with this, we found that plasma CK activity after rest, a surrogate measure of tissue activity, is the main predictor of blood pressure levels and failure of antihypertensive therapy in the general population. In addition, the creatine analog and competitive oral creatine kinase inhibitor beta-guanidinopropionic acid effectively and safely reduced blood pressure in the spontaneously hypertensive rat. However, to our knowledge there are no human data on the safety of oral supplementation with this substance. Therefore, we will assess the tolerability of beta-guanidinopropionic acid in men, compared to creatine and placebo. This is a randomized, active and placebo controlled, triple blind, double dummy, single center clinical intervention trial in 24 healthy male volunteers, 18 to 50 years old, recruited in the Netherlands. The intervention consists of one week of daily oral administration of beta-guanidinopropionic acid 100 mg, creatine 5 gram, or placebo. The primary outcome is the tolerability of beta-guanidinopropionic acid as a descriptive measure, in an intent-to-treat analysis. Other outcomes include the placebo-adjusted differences with baseline in biochemical and hemodynamic parameters, including plasma markers of muscle tissue damage, urine sodium excretion, resting sitting systolic and diastolic brachial blood pressure, supine systolic and diastolic central blood pressure, pulse wave velocity and augmentation index, heart rate, cardiac contractility, cardiac output, and total peripheral resistance. There is an unfulfilled need for new conservative options to treat resistant hypertension. This study will provide first-in-men data on creatine kinase inhibition as a potential new class of antihypertensive drugs. The Netherlands National Trial Register Trialregister.nl (identifier NTR 4444) , registered 9 March 2014.

16 CFR 1216.2 - Requirements for infant walkers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... coefficient of friction = 0.05 NCAMI = Normal force (for CAMI dummy scenario) = weight of CAMI dummy and... occupant seating area and arms placed on the walker tray. (ii) [Reserved] (8) Instead of complying with... horizontally (0 ± 0.5° with respect to the table surface). (ii) [Reserved] (9) Instead of complying with...

49 CFR 572.197 - Abdomen.

Code of Federal Regulations, 2010 CFR

2010-10-01

... vertical orientation. (4) Push the dummy at the knees and at mid-sternum of the upper torso with just sufficient horizontally oriented force towards the seat back until the back of the upper torso is in contact with the seat back. (5) While maintaining the dummy's position as specified in paragraph (b)(3) and (4...

49 CFR 572.196 - Thorax without arm.

Code of Federal Regulations, 2010 CFR

2010-10-01

... orientation. (4) Push the dummy at the knees and at mid-sternum of the upper torso with just sufficient horizontally oriented force towards the seat back until the back of the upper torso is in contact with the seat back. (5) While maintaining the dummy's position as specified in paragraphs (b)(3) and (4) of this...

49 CFR 572.186 - Abdomen assembly.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 7 2013-10-01 2013-10-01 false Abdomen assembly. 572.186 Section 572.186... Test Dummy, 50th Percentile Adult Male § 572.186 Abdomen assembly. (a) The abdomen assembly (175-5000) is part of the dummy assembly shown in drawing 175-0000 including load sensors specified in § 572.189...

49 CFR 572.186 - Abdomen assembly.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false Abdomen assembly. 572.186 Section 572.186... Dummy, 50th Percentile Adult Male § 572.186 Abdomen assembly. (a) The abdomen assembly (175-5000) is part of the dummy assembly shown in drawing 175-0000 including load sensors specified in § 572.189(e...

49 CFR 572.186 - Abdomen assembly.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Abdomen assembly. 572.186 Section 572.186... Dummy, 50th Percentile Adult Male § 572.186 Abdomen assembly. (a) The abdomen assembly (175-5000) is part of the dummy assembly shown in drawing 175-0000 including load sensors specified in § 572.189(e...

49 CFR 571.213 - Standard No. 213; Child restraint systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... the initial pre-test position of the respective knee pivot point, measured along a horizontal line... test dummy, specified in S7, when a child restraint system is tested in accordance with S6.1. Factory... body of a seated anthropomorphic test dummy, excluding the thighs, that lies between the top of the...

49 CFR 571.213 - Standard No. 213; Child restraint systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... the initial pre-test position of the respective knee pivot point, measured along a horizontal line... test dummy, specified in S7, when a child restraint system is tested in accordance with S6.1. Factory... body of a seated anthropomorphic test dummy, excluding the thighs, that lies between the top of the...

49 CFR 571.213 - Standard No. 213; Child restraint systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

... the initial pre-test position of the respective knee pivot point, measured along a horizontal line... the head or torso of the appropriate test dummy, specified in S7, when a child restraint system is... (§ 571.225). Torso means the portion of the body of a seated anthropomorphic test dummy, excluding the...

49 CFR 572.196 - Thorax without arm.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Thorax without arm. 572.196 Section 572.196... Dummy, Small Adult Female § 572.196 Thorax without arm. (a) The thorax is part of the upper torso... (drawing 180-0000) with the arm (180-6000) on the impacted side removed. The dummy's thorax is equipped...

49 CFR 572.196 - Thorax without arm.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 false Thorax without arm. 572.196 Section 572.196... Test Dummy, Small Adult Female § 572.196 Thorax without arm. (a) The thorax is part of the upper torso... (drawing 180-0000) with the arm (180-6000) on the impacted side removed. The dummy's thorax is equipped...

49 CFR 572.196 - Thorax without arm.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false Thorax without arm. 572.196 Section 572.196... Dummy, Small Adult Female § 572.196 Thorax without arm. (a) The thorax is part of the upper torso... (drawing 180-0000) with the arm (180-6000) on the impacted side removed. The dummy's thorax is equipped...

49 CFR 572.196 - Thorax without arm.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 7 2013-10-01 2013-10-01 false Thorax without arm. 572.196 Section 572.196... Test Dummy, Small Adult Female § 572.196 Thorax without arm. (a) The thorax is part of the upper torso... (drawing 180-0000) with the arm (180-6000) on the impacted side removed. The dummy's thorax is equipped...

49 CFR 572.150 - Incorporation by reference.

Code of Federal Regulations, 2014 CFR

2014-10-01

...-Month-Old Infant, Alpha Version § 572.150 Incorporation by reference. (a) The following materials are... Drawings, Subpart R, CRABI 12-Month-Old Infant Crash Test Dummy (CRABI-12, Alpha version) August 2001” and... Infant Crash Test Dummy (CRABI-12, Alpha version) August 2001” incorporated by reference in § 572.155; (3...

49 CFR 572.150 - Incorporation by reference.

Code of Federal Regulations, 2013 CFR

2013-10-01

...-Month-Old Infant, Alpha Version § 572.150 Incorporation by reference. (a) The following materials are... Drawings, Subpart R, CRABI 12-Month-Old Infant Crash Test Dummy (CRABI-12, Alpha version) August 2001” and... Infant Crash Test Dummy (CRABI-12, Alpha version) August 2001” incorporated by reference in § 572.155; (3...

49 CFR 572.150 - Incorporation by reference.

Code of Federal Regulations, 2012 CFR

2012-10-01

...-Month-Old Infant, Alpha Version § 572.150 Incorporation by reference. (a) The following materials are... Drawings, Subpart R, CRABI 12-Month-Old Infant Crash Test Dummy (CRABI-12, Alpha version) August 2001” and... Infant Crash Test Dummy (CRABI-12, Alpha version) August 2001” incorporated by reference in § 572.155; (3...

49 CFR 572.151 - General description.

Code of Federal Regulations, 2010 CFR

2010-10-01

... specifications package 921022-000 (refer to § 572.150(a)(1)), the titles of which are listed in Table A of this...)). (b) The dummy consists of the component assemblies set out in the following Table A: Table A... dummy are joined in a manner such that, except for contacts existing under static conditions, there is...

49 CFR 572.43 - Lumbar spine and pelvis.

Code of Federal Regulations, 2010 CFR

2010-10-01

... vertical plane which is tangent to the back of the dummy's buttocks. (3) Align the test probe so that at... vertical planes perpendicular to the midsagittal plane passing through the designated impact point. (4) Adjust the dummy so that its midsagittal plane is vertical and the rear surfaces of the thorax and...

Barbell-shaped stir bar sorptive extraction using dummy template molecularly imprinted polymer coatings for analysis of bisphenol A in water.

PubMed

Liu, Ruimei; Feng, Feng; Chen, Guolin; Liu, Zhimin; Xu, Zhigang

2016-07-01

This study reports the development of a novel dummy template molecularly imprinted polymer (MIP)-coated barbell-shaped stir bar. The MIP stir bar coatings were prepared by using 2,2-bis(4-hydroxyphenyl)butane (BPB), 4,4'-dihydroxydiphenylmethane (BPF), 4-tert-butylphenol (PTBP), and tetrabromobisphenol A (TBBA) as dummy templates using a capillary in situ polymerization method. Uniform coatings can be prepared controllably. The method is simple, easy, and reproducible. The barbell-shaped stir bar was developed by using medical silicone tubes as wheels. The wheels could be removed and reinstalled when necessary; therefore, the barbell-shaped stir bar was easy to disassemble and reassemble. The novel MIP-coated stir bar showed good selectivity for the target analyte, bisphenol A (BPA). The established method is selective and sensitive with a lower detection limit for BPA of 0.003 μg/L. The dummy template MIP-coated stir bar is suitable for trace BPA analysis in real environmental water samples without template leakage. The novel stir bar can be used at least 100 times.

The Influences of Arm Resist Motion on a CAR Crash Test Using Hybrid III Dummy with Human-Like Arm

NASA Astrophysics Data System (ADS)

Kim, Yongchul; Youm, Youngil; Bae, Hanil; Choi, Hyeonki

Safety of the occupant during the crash is very essential design element. Many researches have been investigated in reducing the fatal injury of occupant. They are focusing on the development of a dummy in order to obtain the real human-like motion. However, they have not considered the arm resist motion during the car accident. In this study, we would like to suggest the importance of the reactive force of the arm in a car crash. The influences of reactive force acting on the human upper extremity were investigated using the impedance experimental method with lumped mass model of hand system and a Hybrid III dummy with human-like arm. Impedance parameters (e.g. inertia, spring constant and damping coefficient) of the elbow joint in maximum activation level were measured by free oscillation test using single axis robot. The results showed that without seat belt, the reactive force of human arm reduced the head, chest, and femur injury, and the flexion moment of the neck is higher than that of the conventional dummy.

Measurement of Spindle Rigidity by using a Magnet Loader

NASA Astrophysics Data System (ADS)

Yamazaki, Taku; Matsubara, Atsushi; Fujita, Tomoya; Muraki, Toshiyuki; Asano, Kohei; Kawashima, Kazuyuki

The static rigidity of a rotating spindle in the radial direction is investigated in this research. A magnetic loading device (magnet loader) has been developed for the measurement. The magnet loader, which has coils and iron cores, generates the electromagnetic force and attracts a dummy tool attached to the spindle. However, the eddy current is generated in the dummy tool with the spindle rotation and reduces the attractive force at high spindle speed. In order to understand the magnetic flux and eddy current in the dummy tool, the electromagnetic field analysis by FEM was carried out. Grooves on the attraction surface of the dummy tool were designed to cut the eddy current flow. The dimension of the groove were decided based on the FEM analysis, and the designed tool were manufactured and tested. The test result shows that the designed tool successfully reduces the eddy current and recovers the attractive force. By using the magnet loader and the grooved tool, the spindle rigidity can be measured when the spindle rotates with a speed up to 10,000 min-1.

Biomechanical analysis of occupant kinematics in rollover motor vehicle accidents: dynamic spit test.

PubMed

Sances, Anthony; Kumaresan, Srirangam; Clarke, Richard; Herbst, Brian; Meyer, Steve

2005-01-01

A better understanding of occupant kinematics in rollover accidents helps to advance biomechanical knowledge and to enhance the safety features of motor vehicles. While many rollover accident simulation studies have adopted the static approach to delineate the occupant kinematics in rollover accidents, very few studies have attempted the dynamic approach. The present work was designed to study the biomechanics of restrained occupants during rollover accidents using the steady-state dynamic spit test and to address the importance of keeping the lap belt fastened. Experimental tests were conducted using an anthropometric 50% Hybrid III dummy in a vehicle. The vehicle was rotated at 180 degrees/second and the dummy was restrained using a standard three-point restraint system. The lap belt of the dummy was fastened either by using the cinching latch plate or by locking the retractor. Three configurations of shoulder belt harness were simulated: shoulder belt loose on chest with cinch plate, shoulder belt under the left arm and shoulder belt behind the chest. In all tests, the dummy stayed within the confinement of the vehicle indicating that the securely fastened lap belt holds the dummy with dynamic movement of 3 1/2" to 4". The results show that occupant movement in rollover accidents is least affected by various shoulder harness positions with a securely fastened lap belt. The present study forms a first step in delineating the biomechanics of occupants in rollover accidents.

Modal analysis of the human neck in vivo as a criterion for crash test dummy evaluation

NASA Astrophysics Data System (ADS)

Willinger, R.; Bourdet, N.; Fischer, R.; Le Gall, F.

2005-10-01

Low speed rear impact remains an acute automative safety problem because of a lack of knowledge of the mechanical behaviour of the human neck early after impact. Poorly validated mathematical models of the human neck or crash test dummy necks make it difficult to optimize automotive seats and head rests. In this study we have constructed an experimental and theoretical modal analysis of the human head-neck system in the sagittal plane. The method has allowed us to identify the mechanical properties of the neck and to validate a mathematical model in the frequency domain. The extracted modal characteristics consist of a first natural frequency at 1.3±0.1 Hz associated with head flexion-extension motion and a second mode at 8±0.7 Hz associated with antero-posterior translation of the head, also called retraction motion. Based on this new validation parameters we have been able to compare the human and crash test dummy frequency response functions and to evaluate their biofidelity. Three head-neck systems of current test dummies dedicated for use in rear-end car crash accident investigations have been evaluated in the frequency domain. We did not consider any to be acceptable, either because of excessive rigidity of their flexion-extension mode or because they poorly reproduce the head translation mode. In addition to dummy evaluation, this study provides new insight into injury mechanisms when a given natural frequency can be linked to a specific neck deformation.

Small female head and neck interaction with a deploying side airbag.

PubMed

Duma, Stefan M; Crandall, Jeff R; Rudd, Rodney W; Kent, Richard W

2003-09-01

This paper presents dummy and cadaver experiments designed to investigate the injury potential of an out-of-position small female head and neck from a deploying side airbag. Seat-mounted, thoracic-type, side airbags were selected for this study to represent those currently available on selected luxury automobiles. A computer simulation program was used to identify the worst case loading position for the small female head and neck. Once the initial position was identified, experiments were performed with the Hybrid III 5th percentile dummy and three small female cadavers, using three different inflators. Peak head center of gravity (CG) accelerations for the dummy ranged from 71x g to 154 x g, and were greater than cadaver values, which ranged from 68 x g to 103 x g. Peak neck tension as measured at the upper load cell of the dummy increased with inflator aggressivity from 992 to 1670N. A conservative modification of the US National Highway Traffic Safety Administration's (NHTSA's) N(ij) proposed neck injury criteria, which combines neck tension and bending, was used. All values were well below the 1.0 injury threshold for the dummy and suggested a very low possibility of neck injury. In agreement with this prediction, no injuries were observed. Even in a worst case position, small females are at low risk of head or neck injuries under loading from these thoracic-type airbags; however, injury risk increases with increasing inflator aggressivity.

Physical properties of the human head: mass, center of gravity and moment of inertia.

PubMed

Yoganandan, Narayan; Pintar, Frank A; Zhang, Jiangyue; Baisden, Jamie L

2009-06-19

This paper presents a synthesis of biomedical investigations of the human head with specific reference to certain aspects of physical properties and development of anthropometry data, leading to the advancement of dummies used in crashworthiness research. As a significant majority of the studies have been summarized as reports, an effort has been made to chronologically review the literature with the above objectives. The first part is devoted to early studies wherein the mass, center of gravity (CG), and moment of inertia (MOI) properties are obtained from human cadaver experiments. Unembalmed and preserved whole-body and isolated head and head-neck experiments are discussed. Acknowledging that the current version of the Hybrid III dummy is the most widely used anthropomorphic test device in motor vehicle crashworthiness research for frontal impact applications for over 30 years, bases for the mass and MOI-related data used in the dummy are discussed. Since the development and federalization of the dummy in the United States, description of methods used to arrive at these properties form a part of the manuscript. Studies subsequent to the development of this dummy including those from the US Military are also discussed. As the head and neck are coupled in any impact, and increasing improvements in technology such as advanced airbags, and pre-tensioners and load limiters in manual seatbelts affect the kinetics of the head-neck complex, the manuscript underscores the need to pursue studies to precisely determine all the physical properties of the head. Because the most critical parameters (locations of CG and occipital condyles (OC), mass, and MOI) have not been determined on a specimen-by-specimen basis in any single study, it is important to gather these data in future experiments. These critical data will be of value for improving occupant safety, designing advanced restraint systems, developing second generation dummies, and assessing the injury mitigating characteristics of modern vehicle components in all impact modalities.

Optimizing the passenger air bag of an adaptive restraint system for multiple size occupants.

PubMed

Bai, Zhonghao; Jiang, Binhui; Zhu, Feng; Cao, Libo

2014-01-01

The development of the adaptive occupant restraint system (AORS) has led to an innovative way to optimize such systems for multiple size occupants. An AORS consists of multiple units such as adaptive air bags, seat belts, etc. During a collision, as a supplemental protective device, air bags can provide constraint force and play a role in dissipating the crash energy of the occupants' head and thorax. This article presents an investigation into an adaptive passenger air bag (PAB). The purpose of this study is to develop a base shape of a PAB for different size occupants using an optimization method. Four typical base shapes of a PAB were designed based on geometric data on the passenger side. Then 4 PAB finite element (FE) models and a validated sled with different size dummy models were developed in MADYMO (TNO, Rijswijk, The Netherlands) to conduct the optimization to obtain the best baseline PAB that would be used in the AORS. The objective functions-that is, the minimum total probability of injuries (∑Pcomb) of the 5th percentile female and 50th and 95th percentile male dummies-were adopted to evaluate the optimal configurations. The injury probability (Pcomb) for each dummy was adopted from the U.S. New Car Assessment Program (US-NCAP). The parameters of the AORS were first optimized for different types of PAB base shapes in a frontal impact. Then, contact time duration and force between the PAB and dummy head/chest were optimized by adjusting the parameters of the PAB, such as the number and position of tethers, lower the Pcomb of the 95th percentile male dummy. According to the optimization results, 4 typical PABs could provide effective protection to 5th and 50th percentile dummies. However, due to the heavy and large torsos of the 95th percentile occupants, the current occupant restraint system does not demonstrate satisfactory protective function, particularly for the thorax.

The RID2 biofidelic rear impact dummy: a pilot study using human subjects in low speed rear impact full scale crash tests.

PubMed

Croft, Arthur C; Philippens, Mathieu M G M

2007-03-01

Human subjects and the recently developed RID2 rear impact crash test dummy were exposed to a series of full scale, vehicle-to-vehicle crash tests. To evaluate the biofidelity of the RID2 anthropometric test dummy on the basis of calculated neck injury criterion (NIC) values by comparing these values to those obtained from human subjects exposed in the very same crashes. The widely used and familiar hybrid III dummy has been said to lack biofidelity in the special application of low speed rear impact crashes. Several attempts have been made to modify this dummy with only marginal success. Two completely new dummies have been developed; the BioRID and the RID2. Neither have been tested under real world crash boundary conditions in side-by-side comparisons with live human subjects. Volunteer subjects, including a 50th percentile male, a 95th percentile male, and a 50th percentile female, were placed in the driver's seat of a vehicle and subjected to a series of three low speed rear impact crashes each. The RID2 dummy, which is modeled after a 50th percentile male, was placed in the passenger seat in each case. Both subjects and dummy were fully instrumented and acceleration-time histories were recorded. From this data, velocities of the heads and torsos were determined and both were used to calculate the NIC values for both crash test subjects and the RID2. The RID2 demonstrated generally higher head accelerations and NIC values than those of the human subjects. Most of the observed variations might be explained on the basis of differing head restraint geometry, posture, and body size. The RID2 NIC values compared most favorably with those of the 50th percentile male subject. For the whole group, the correlations between RID2 and human subjects did not reach statistical significance. The small number of test subjects and crash tests limited the statistical power of this pilot study, and the correlation between the RID2 and human subject NIC values were not statistically significant. The overall qualitative performance and biofidelity of the RID2 was reasonable when compared with the male human 50th percentile subject. Its overall higher ranges of head acceleration and calculated NIC values compared to all of the human subjects were generally consistent. This condition could likely be improved by increasing the stiffness of the RID2 neck. Biofidelic validation of the RID2 will require ongoing testing using a larger number of human subjects and varying boundary conditions. The results of this pilot study, while encouraging, should be considered preliminary.

Efficient Procedure for the Numerical Calculation of Harmonic Vibrational Frequencies Based on Internal Coordinates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miliordos, Evangelos; Xantheas, Sotiris S.

We propose a general procedure for the numerical calculation of the harmonic vibrational frequencies that is based on internal coordinates and Wilson’s GF methodology via double differentiation of the energy. The internal coordinates are defined as the geometrical parameters of a Z-matrix structure, thus avoiding issues related to their redundancy. Linear arrangements of atoms are described using a dummy atom of infinite mass. The procedure has been automated in FORTRAN90 and its main advantage lies in the nontrivial reduction of the number of single-point energy calculations needed for the construction of the Hessian matrix when compared to the corresponding numbermore » using double differentiation in Cartesian coordinates. For molecules of C 1 symmetry the computational savings in the energy calculations amount to 36N – 30, where N is the number of atoms, with additional savings when symmetry is present. Typical applications for small and medium size molecules in their minimum and transition state geometries as well as hydrogen bonded clusters (water dimer and trimer) are presented. Finally, in all cases the frequencies based on internal coordinates differ on average by <1 cm –1 from those obtained from Cartesian coordinates.« less

Loxoprofen: A Review in Pain and Inflammation.

PubMed

Greig, Sarah L; Garnock-Jones, Karly P

2016-09-01

Loxoprofen (Loxonin(®), Loxonin(®) Pap, Loxonin(®) Tape) is a prodrug-type NSAID that is available in several formulations, including 60 mg tablets, 100 mg hydrogel patches and 50 or 100 mg tape. In active comparator-controlled trials, oral loxoprofen therapy (ranging from 2 days to 6 weeks' duration depending on the pain type) provided analgesic efficacy that generally did not significantly differ from that of celecoxib for postoperative pain or frozen shoulder, ibuprofen for knee osteoarthritis or naproxen for lumbar pain. In double-blind, double-dummy, multicentre trials, loxoprofen hydrogel patches were noninferior to oral loxoprofen with regard to rates of final overall symptomatic improvement over 1-4 weeks in patients with knee osteoarthritis, myalgia or trauma-induced swelling and pain. Loxoprofen hydrogel patches were also noninferior to other commercially available patches (ketoprofen and indometacin) over 2 or 4 weeks in patients with knee osteoarthritis or myalgia in open-label studies. Oral and topical loxoprofen were generally well tolerated in clinical trials. Thus, loxoprofen is a useful analgesic option for patients with pain and inflammation, with topical loxoprofen potentially reducing the risk of gastrointestinal, cardiovascular and renal complications associated with oral NSAID use.

Equilibrium shift in solution: molecular shape recognition and precipitation of a synthetic double helix using helicene-grafted silica nanoparticles.

PubMed

Miyagawa, Masamichi; Ichinose, Wataru; Yamaguchi, Masahiko

2014-01-27

Chiral silica nanoparticles (70 nm) grafted with (P)-helicene recognized the molecular shape of double helix and random coil (P)-ethynylhelicene oligomers in solution. A mixture of the (P)-nanoparticles and double helix precipitated much faster than a mixture of the (P)-nanoparticles and random coil, and the precipitate contained only the double helix. The mixture of the (P)-nanoparticles and (P)-ethynylhelicene pentamer reversibly dispersed in trifluoromethylbenzene upon heating at 70 °C and precipitated upon cooling at 25 °C. When a 10:90 equilibrium mixture of the double helix and random coil in solution was treated with the (P)-nanoparticles, the double helix was precipitated in 53% yield and was accompanied by equilibrium shift. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Palonosetron versus ondansetron for prevention of chemotherapy-induced nausea and vomiting in paediatric patients with cancer receiving moderately or highly emetogenic chemotherapy: a randomised, phase 3, double-blind, double-dummy, non-inferiority study.

PubMed

Kovács, Gábor; Wachtel, Antonio E; Basharova, Elena V; Spinelli, Tulla; Nicolas, Pierre; Kabickova, Edita

2016-03-01

Palonosetron has shown efficacy in the prevention of chemotherapy-induced nausea and vomiting in adults undergoing moderately or highly emetogenic chemotherapy. We assessed the efficacy and safety of palonosetron versus ondansetron in the prevention of chemotherapy-induced nausea and vomiting in paediatric patients. In this multicentre, multinational, double-blind, double-dummy, phase 3 study, paediatric patients aged between 0 and younger than 17 years, who were naive or non-naive to chemotherapy, and scheduled to undergo moderately or highly emetogenic chemotherapy for the treatment of malignant disease were randomised centrally (1:1:1) to receive up to four cycles of 10 μg/kg or 20 μg/kg palonosetron on day 1, or three 150 μg/kg doses of ondansetron on day 1, scheduled 4 h apart, according to a static central permuted block randomisation scheme by an interactive web response system. Randomisation was stratified according to age and emetogenicity. Treatment allocation was masked to project team members involved in data collection and analysis, and members of the investigator's team. The primary endpoint was complete response (no vomiting, retching, or use of rescue drugs) during the acute phase (0-24 h post-chemotherapy) of the first on-study chemotherapy cycle, as assessed in the population of randomly assigned patients who received moderately or highly emetogenic chemotherapy and an active study drug. The primary efficacy objective was to show the non-inferiority of palonosetron versus ondansetron during the acute phase (0-24 h post-chemotherapy) of the first on-study chemotherapy cycle through comparison of the difference in the proportions of patients who achieved a complete response with palonosetron (πT) minus ondansetron (πR) versus a preset non-inferiority margin (δ -15%). To be considered as non-inferior to ondansetron, for at least one of the doses of palonosetron, the lower limit of the 97·5% CI for the weighted sum of the differences in complete response rates had to be superior to -15%. Safety was assessed, according to treatment received. This study is registered with ClinicalTrials.gov, number NCT01442376, and has been completed. Between Sept 12, 2011, and Oct 26, 2012, we randomly assigned 502 patients; 169 were assigned to receive 10 μg/kg palonosetron, 169 to receive 20 μg/kg palonosetron, and 164 to receive 3 × 150 μg/kg ondansetron, of whom 166, 165, and 162, respectively, were included in the efficacy analysis. In the acute phase, complete responses were recorded in 90 (54%) patients in the 10 μg/kg palonosetron group, 98 (59%) in the 20 μg/kg palonosetron group, and 95 (59%) in the ondansetron group. Non-inferiority versus ondansetron was shown for 20 μg/kg palonosetron in the acute phase (weighted sum of the differences in complete response rates 0·36% [97·5% CI -11·7 to 12·4]; p=0·0022). Non-inferiority versus ondansetron was not shown for 10 μg/kg palonosetron in the acute phase (weighted sum of the differences in complete response rates -4·41% [97·5% CI -16·4 to 7·6]). In the first on-study treatment cycle, treatment-emergent adverse events were reported in 134 (80%) of 167 patients who received 10 μg/kg palonosetron, 113 (69%) of 163 who received 20 μg/kg palonosetron, and 134 (82%) of 164 who received ondansetron. The most common drug-related treatment-emergent adverse events were nervous system disorders, mainly headache, which occurred in three (2%) patients who received 10 μg/kg palonosetron, one (<1%) patient who received 20 μg/kg palonosetron, and two (1%) patients who received ondansetron. The incidence of serious adverse events in the first on-study treatment cycle was lower in the 20 μg/kg palonosetron group (43 [26%]) than in the 10 μg/kg palonosetron group (52 [31%]) and the ondansetron group (55 [34%]). Non-inferiority was shown for 20 μg/kg palonosetron during the acute phase of the first on-study chemotherapy cycle. 20 μg/kg palonosetron is now indicated by the European Medicines Agency and the US Food and Drug Administration for the prevention of chemotherapy-induced nausea and vomiting in paediatric patients aged 1 month to younger than 17 years. Helsinn Healthcare. Copyright © 2016 Elsevier Ltd. All rights reserved.

49 CFR 572.186 - Abdomen assembly.

Code of Federal Regulations, 2010 CFR

2010-10-01

... part of the dummy assembly shown in drawing 175-0000 including load sensors specified in § 572.189(e... measuring sensor in the abdomen as shown in Figure U5; (5) The impactor impacts the dummy's abdomen at 4.0 m... of the forces of the three abdominal load sensors, specified in 572.189(e), shall be not less than...

Random effects coefficient of determination for mixed and meta-analysis models

PubMed Central

Demidenko, Eugene; Sargent, James; Onega, Tracy

2011-01-01

The key feature of a mixed model is the presence of random effects. We have developed a coefficient, called the random effects coefficient of determination, Rr2, that estimates the proportion of the conditional variance of the dependent variable explained by random effects. This coefficient takes values from 0 to 1 and indicates how strong the random effects are. The difference from the earlier suggested fixed effects coefficient of determination is emphasized. If Rr2 is close to 0, there is weak support for random effects in the model because the reduction of the variance of the dependent variable due to random effects is small; consequently, random effects may be ignored and the model simplifies to standard linear regression. The value of Rr2 apart from 0 indicates the evidence of the variance reduction in support of the mixed model. If random effects coefficient of determination is close to 1 the variance of random effects is very large and random effects turn into free fixed effects—the model can be estimated using the dummy variable approach. We derive explicit formulas for Rr2 in three special cases: the random intercept model, the growth curve model, and meta-analysis model. Theoretical results are illustrated with three mixed model examples: (1) travel time to the nearest cancer center for women with breast cancer in the U.S., (2) cumulative time watching alcohol related scenes in movies among young U.S. teens, as a risk factor for early drinking onset, and (3) the classic example of the meta-analysis model for combination of 13 studies on tuberculosis vaccine. PMID:23750070

The Effect of a New Sodium Bicarbonate Loading Regimen on Anaerobic Capacity and Wrestling Performance.

PubMed

Durkalec-Michalski, Krzysztof; Zawieja, Emilia Ewa; Podgórski, Tomasz; Zawieja, Bogna Ewa; Michałowska, Patrycja; Łoniewski, Igor; Jeszka, Jan

2018-05-30

Gastrointestinal side effects are the main problem with sodium bicarbonate (SB) use in sports. Therefore, our study assessed the effect of a new SB loading regimen on anaerobic capacity and wrestling performance. Fifty-eight wrestlers were randomized to either a progressive-dose regimen of up to 100 mg∙kg -1 of SB or a placebo for 10 days. Before and after treatment, athletes completed an exercise protocol that comprised, in sequence, the first Wingate, dummy throw, and second Wingate tests. Blood samples were taken pre- and post-exercise. No gastrointestinal side effects were reported during the study. After SB treatment, there were no significant improvements in the outcomes of the Wingate and dummy throw tests. The only index that significantly improved with SB, compared to the placebo ( p = 0.0142), was the time-to-peak power in the second Wingate test, which decreased from 3.44 ± 1.98 to 2.35 ± 1.17 s. There were also no differences in blood lactate or glucose concentrations. In conclusion, although the new loading regimen eliminated gastrointestinal symptoms, the doses could have been too small to elicit additional improvements in anaerobic power and wrestling performance. However, shortening the time-to-peak power during fatigue may be particularly valuable and is one of the variables contributing to the final success of a combat sports athlete.

Preparation of a hollow porous molecularly imprinted polymer using tetrabromobisphenol A as a dummy template and its application as SPE sorbent for determination of bisphenol A in tap water.

PubMed

Li, Jin; Zhang, Xuebin; Liu, Yuxin; Tong, Hongwu; Xu, Yeping; Liu, Shaomin

2013-12-15

In this paper, a highly selective sample cleanup procedure combing dummy molecular imprinting and solid-phase extraction (DMIP-SPE) was developed for the isolation and determination of bisphenol A (BPA) in tap water. The novel hollow porous dummy molecularly imprinted polymer (HPDMIP) was prepared adopting a sacrificial support approach, using tetrabromobisphenol A (TBBPA), whose structure was similar to that of BPA, as the dummy template and mesoporous MCM-48 nanospheres as the support. Owing to a very short distance between the binding sites and the surface, a large surface area and a good steric structure to match its imprint molecules, the maximum adsorption capacities (Qmax) of the dummy-imprinted and non-imprinted sorbents for BPA were as high as 445 and 340 μmol g(-1), respectively, and the adsorption reached about 73% of Qmax in 10 min. Meanwhile, a method was developed for the determination of BPA using HPDMIP as a solid-phase extraction enrichment sorbent coupled with HPLC. Under the optimum experimental conditions, HPDMIP exhibited satisfactory results in the enrichment and determination of BPA in tap water with a recovery rate of 95-105%, and relative standard deviations of below 6%, and it can achieve a limit of detection as low as 3 ng mL(-1). The developed extraction protocol eliminated the effect of template leakage on quantitative analysis and could be applied for the determination of BPA in complicated functional samples. © 2013 Elsevier B.V. All rights reserved.

Non-White, No More: Effect Coding as an Alternative to Dummy Coding with Implications for Higher Education Researchers

ERIC Educational Resources Information Center

Mayhew, Matthew J.; Simonoff, Jeffrey S.

2015-01-01

The purpose of this article is to describe effect coding as an alternative quantitative practice for analyzing and interpreting categorical, race-based independent variables in higher education research. Unlike indicator (dummy) codes that imply that one group will be a reference group, effect codes use average responses as a means for…

Crash tests of four low-wing twin-engine airplanes with truss-reinforced fuselage structure

NASA Technical Reports Server (NTRS)

Williams, M. S.; Fasanella, E. L.

1982-01-01

Four six-place, low-wing, twin-engine, general aviation airplane test specimens were crash tested under controlled free flight conditions. All airplanes were impacted on a concrete test surface at a nomial flight path velocity of 27 m/sec. Two tests were conducted at a -15 deg flight path angle (0 deg pitch angle and 15 deg pitch angle), and two were conducted at a -30 deg flight path angle (-30 deg pitch angle). The average acceleration time histories (crash pulses) in the cabin area for each principal direction were calculated for each crash test. In addition, the peak floor accelerations were calculated for each test as a function of aircraft fuselage longitudinal station number. Anthropomorphic dummy accelerations were analyzed using the dynamic response index and severity index (SI) models. Parameters affecting the dummy restraint system were studied; these parameters included the effect of no upper torso restraint, measurement of the amount of inertia-reel strap pullout before locking, measurement of dummy chest forward motion, and loads in the restraints. With the SI model, the dummies with no shoulder harness received head impacts above the concussive threshold.

Effects of vehicle front-end stiffness on rear seat dummies in NCAP and FMVSS208 tests.

PubMed

Sahraei, Elham; Digges, Kennerly; Marzougui, Dhafer

2013-01-01

This study is devoted to quantifying changes in mass and stiffness of vehicles tested by the National Highway Traffic Safety Administration (NHTSA) over the past 3 decades (model years 1982 to 2010) and understanding the effect of those changes on protection of rear seat occupants. A total of 1179 tests were used, and the changes in their mass and stiffness versus their model year was quantified. Additionally, data from 439 dummies tested in rear seats of NHTSA's full frontal crashes were analyzed. Dummies were divided into 3 groups based on their reference injury criteria. Multiple regressions were performed with speed, stiffness, and mass as predicting variables for head, neck, and chest injury criteria. A significant increase in mass and stiffness over model year of vehicles was observed, for passenger cars as well as large platform vehicles. The result showed a significant correlation (P-value < .05) between the increase in stiffness of the vehicles and increase in head and chest injury criteria for all dummy sizes. These results explain that stiffness is a significant contributor to previously reported decreases in protection of rear seat occupants over model years of vehicles.

The Influence of Neck Muscle Activation on Head and Neck Injuries of Occupants in Frontal Impacts.

PubMed

Li, Fan; Lu, Ronggui; Hu, Wei; Li, Honggeng; Hu, Shiping; Hu, Jiangzhong; Wang, Haibin; Xie, He

2018-01-01

The aim of the present paper was to study the influence of neck muscle activation on head and neck injuries of vehicle occupants in frontal impacts. A mixed dummy-human finite element model was developed to simulate a frontal impact. The head-neck part of a Hybrid III dummy model was replaced by a well-validated head-neck FE model with passive and active muscle characteristics. The mixed dummy-human FE model was validated by 15 G frontal volunteer tests conducted in the Naval Biodynamics Laboratory. The effects of neck muscle activation on the head dynamic responses and neck injuries of occupants in three frontal impact intensities, low speed (10 km/h), medium speed (30 km/h), and high speed (50 km/h), were studied. The results showed that the mixed dummy-human FE model has good biofidelity. The activation of neck muscles can not only lower the head resultant acceleration under different impact intensities and the head angular acceleration in medium- and high-speed impacts, thereby reducing the risks of head injury, but also protect the neck from injury in low-speed impacts.

Transformer current sensor for superconducting magnetic coils

DOEpatents

Shen, Stewart S.; Wilson, C. Thomas

1988-01-01

A transformer current sensor having primary turns carrying a primary current for a superconducting coil and secondary turns only partially arranged within the primary turns. The secondary turns include an active winding disposed within the primary turns and a dummy winding which is not disposed in the primary turns and so does not experience a magnetic field due to a flow of current in the primary turns. The active and dummy windings are wound in opposite directions or connected in series-bucking relationship, and are exposed to the same ambient magnetic field. Voltages which might otherwise develop in the active and dummy windings due to ambient magnetic fields thus cancel out. The resultant voltage is purely indicative of the rate of change of current flowing in the primary turns.

Xanthine-oxidase inhibitors and statins in chronic heart failure: effects on vascular and functional parameters.

PubMed

Greig, Douglas; Alcaino, Hernan; Castro, Pablo F; Garcia, Lorena; Verdejo, Hugo E; Navarro, Mario; López, Rafael; Mellado, Rosemarie; Tapia, Fabiola; Gabrielli, Luigi A; Nogerol, Camilo; Chiong, Mario; Godoy, Ivan; Lavandero, Sergio

2011-04-01

Increased oxidative stress in heart failure (HF) leads to inflammation and endothelial dysfunction (ED). Both statins and allopurinol have known anti-oxidant properties, but their utility in HF has not been fully assessed. This investigation was a prospective, double-blind, double-dummy study, performed between March 2007 and June 2009. Seventy-four HF patients, with New York Heart Association (NYHA) Class II or III status and left ventricular ejection fraction (LVEF) <40%, were included. Patients received placebo during 4 weeks and were then randomized to receive 4 weeks of either atorvastatin 20 mg/day plus placebo (ATV+PLA group) or atorvastatin 20 mg/day orally plus allopurinol 300 mg/day orally (ATV+ALLO group). Malondialdehyde (MDA), extracellular superoxide dismutase (ecSOD) activity and uric acid (UA) levels, among others, were determined at baseline and after 4 weeks of treatment. ED was assessed by flow-dependent endothelial-mediated vasodilation (FDD), and functional capacity by 6-minute walk test (6MWT). Thirty-two patients were randomized to ATV+PLA and 38 to ATV+ALLO. Mean age was 59 ± 2 years, 82% were male, and 22% had an ischemic etiology. Hypertension was present in 60% and diabetes in 15% of those studied. No significant differences were observed between baseline measurements and after placebo. After 4 weeks of treatment, both groups showed a significant decrease on MDA (0.9 ± 0.1 to 0.8 ± 0.1 and 1.0 ± 0.5 to 0.9 ± 0.1 μmol/liter, p = 0.88), UA (7.4 ± 0.4 to 6.8 ± 0.3 and 7.2 ± 0.4 to 5.0 ± 0.3 mg/dl, p < 0.01) and FDD (3.9 ± 0.2% to 5.6 ± 0.4% and 4.6 ± 0.3% to 7.1 ± 0.5%, p = 0.07) with increased ecSOD activity (109 ± 11 to 173 ± 13 and 98 ± 10 to 202 ± 16, U/ml/min, p = 0.41) and improved 6MWT (447 ± 18 to 487 ± 19 and 438 ± 17 to 481 ± 21 m, p = 0.83), with all values for ATV+PLA and ATV+ALLO, respectively; p-values are for comparison between groups after treatment. Short-term ATV treatment in heart failure (HF) patients reduces oxidative stress and improves FDD and functional capacity. These beneficial effects are not strengthened by the addition of allopurinol. Copyright © 2011 International Society of Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

The bioavailability and airway clearance of the steroid component of budesonide/formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial

PubMed Central

2009-01-01

Background Airway absorption and bioavailability of inhaled corticosteroids (ICSs) may be influenced by differences in pharmacokinetic properties such as lipophilicity and patient characteristics such as lung function. This study aimed to further investigate and clarify the distribution of budesonide and fluticasone in patients with severe chronic obstructive pulmonary disease (COPD) by measuring the systemic availability and sputum concentration of budesonide and fluticasone, administered via combination inhalers with the respective long-acting β2-agonists, formoterol and salmeterol. Methods This was a randomized, double-blind, double-dummy, two-way crossover, multicenter study. Following a run-in period, 28 patients with severe COPD (mean age 65 years, mean forced expiratory volume in 1 second [FEV1] 37.5% predicted normal) and 27 healthy subjects (mean age 31 years, FEV1 103.3% predicted normal) received two single-dose treatments of budesonide/formoterol (400/12 μg) and salmeterol/fluticasone (50/500 μg), separated by a 4–14-day washout period. ICS concentrations were measured over 10 hours post-inhalation in plasma in all subjects, and over 6 hours in spontaneously expectorated sputum in COPD patients. The primary end point was the area under the curve (AUC) of budesonide and fluticasone plasma concentrations in COPD patients relative to healthy subjects. Results Mean plasma AUC values were lower in COPD patients versus healthy subjects for budesonide (3.07 μM·hr versus 6.21 μM·hr) and fluticasone (0.84 μM·hr versus 1.50 μM·hr), and the dose-adjusted AUC (geometric mean) ratios in healthy subjects and patients with severe COPD for plasma budesonide and fluticasone were similar (2.02 versus 1.80; primary end point). In COPD patients, the Tmax and the mean residence time in the systemic circulation were shorter for budesonide versus fluticasone (15.5 min versus 50.8 min and 4.41 hrs versus 12.78 hrs, respectively) and Cmax was higher (1.08 μM versus 0.09 μM). The amount of expectorated fluticasone (percentage of estimated lung-deposited dose) in sputum over 6 hours was significantly higher versus budesonide (ratio 5.21; p = 0.006). Both treatments were well tolerated. Conclusion The relative systemic availabilities of budesonide and fluticasone between patients with severe COPD and healthy subjects were similar. In patients with COPD, a larger fraction of fluticasone was expectorated in the sputum as compared with budesonide. Trial registration Trial registration number NCT00379028 PMID:19878590

78 FR 69943 - Anthropomorphic Test Devices; Q3s 3-Year-Old Child Side Impact Test Dummy, Incorporation by...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-21

... design and by July 2007 Build Level C was released. b. Developments In 2007, the Occupant Safety Research... reference a parts list, a set of design drawings, and a ``Procedures for Assembly, Disassembly and Inspection (PADI)'' document, to ensure that all Q3s dummies are the same in their design and construction.\\2...

Aircraft Crash Survival Design Guide. Volume 2. Aircraft Crash Environment and Human Tolerance

DTIC Science & Technology

1980-01-01

anthropometry , and crash test dummies, all of which serves as background for the design information presented in the other volumes. .I / V. L...Aeromedical Institute furnished assistance in locat- ing recent information on human tolerance, anthropometry , and crash test dummies. .3 TABLE OF CONTENTS...83 6.1 INTRODUCTION . . . . . . .. ..... 83 6.2 ANTHROPOMETRY . . . . . . 83 6.2.1 Conventional Anthropometric Measurements

SU-C-BRB-06: Utilizing 3D Scanner and Printer for Dummy Eye-Shield: Artifact-Free CT Images of Tungsten Eye-Shield for Accurate Dose Calculation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J; Lee, J; Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul

Purpose: To evaluate the effect of a tungsten eye-shield on the dose distribution of a patient. Methods: A 3D scanner was used to extract the dimension and shape of a tungsten eye-shield in the STL format. Scanned data was transferred into a 3D printer. A dummy eye shield was then produced using bio-resin (3D systems, VisiJet M3 Proplast). For a patient with mucinous carcinoma, the planning CT was obtained with the dummy eye-shield placed on the patient’s right eye. Field shaping of 6 MeV was performed using a patient-specific cerrobend block on the 15 x 15 cm{sup 2} applicator. Themore » gantry angle was 330° to cover the planning target volume near by the lens. EGS4/BEAMnrc was commissioned from our measurement data from a Varian 21EX. For the CT-based dose calculation using EGS4/DOSXYZnrc, the CT images were converted to a phantom file through the ctcreate program. The phantom file had the same resolution as the planning CT images. By assigning the CT numbers of the dummy eye-shield region to 17000, the real dose distributions below the tungsten eye-shield were calculated in EGS4/DOSXYZnrc. In the TPS, the CT number of the dummy eye-shield region was assigned to the maximum allowable CT number (3000). Results: As compared to the maximum dose, the MC dose on the right lens or below the eye shield area was less than 2%, while the corresponding RTP calculated dose was an unrealistic value of approximately 50%. Conclusion: Utilizing a 3D scanner and a 3D printer, a dummy eye-shield for electron treatment can be easily produced. The artifact-free CT images were successfully incorporated into the CT-based Monte Carlo simulations. The developed method was useful in predicting the realistic dose distributions around the lens blocked with the tungsten shield.« less

Trial by Fire

NASA Technical Reports Server (NTRS)

Covault, Craig

2005-01-01

Boeing is preparing a range of Delta IV Heavy launcher options for NASA Crew Exploration Vehicle (CEV) and unmanned cargo transportation architectures to the Moon and Mars, now that the massive new rocket has been flight tested. The December 21 launch of the 232-ft. vehicle on 2 million lb. thrust marked the largest all-liquid expendable booster flown since the last Saturn V in 1973. A second Delta IV Heavy mission is scheduled for this summer carrying a U.S. Air Force missile warning satellite. The first launch carried a dummy payload. Boeing wants NASA to consider the Delta IV Heavy for manned CEV missions, but is also pushing the Heavy for unmanned exploration launch roles. One Delta IV Medium version could also be a CEV player. Boeing says even modest upgrades could double the Delta Heavy's Earth orbit capability to more than 50 metric tons, including being able to fire up to 20 metric tons on escape trajectories to Mars.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dougherty, B.L.

New limits on half-lives for several double beta decay modes of /sup 100/Mo were obtained with a novel experimental system which included thin source films interleaved with a coaxial array of windowless silicon detectors. Segmentation and timing information allowed backgrounds originating in the films to be studied in some detail. Dummy films containing /sup 96/Mo were used to assess remaining backgrounds. With 0.1 mole years of /sup 100/Mo data collected, the lower half-life limits at 90% confidence were 2.7 /times/ 10/sup 18/ years for decay via the two-neutrino mode, 5.2 /times/10/sup 19/ years for decay with the emission of amore » Majoron, and 1.6 /times/ 10/sup 20/ years and 2.2 /times/ 10/sup 21/ years for neutrinoless 0/sup +/ ..-->.. 2/sup +/ and 0/sup +/ ..-->.. 0/sup +/ transitions, respectively. 50 refs., 38 figs., 11 tabs.« less

Efficacy and safety of oral solithromycin versus oral moxifloxacin for treatment of community-acquired bacterial pneumonia: a global, double-blind, multicentre, randomised, active-controlled, non-inferiority trial (SOLITAIRE-ORAL).

PubMed

Barrera, Carlos M; Mykietiuk, Analia; Metev, Hristo; Nitu, Mimi Floarea; Karimjee, Najumuddin; Doreski, Pablo Alexis; Mitha, Ismail; Tanaseanu, Cristina Mihaela; Molina, Joseph McDermott; Antonovsky, Yuri; Van Rensburg, Dirkie Johanna; Rowe, Brian H; Flores-Figueroa, Jose; Rewerska, Barbara; Clark, Kay; Keedy, Kara; Sheets, Amanda; Scott, Drusilla; Horwith, Gary; Das, Anita F; Jamieson, Brian; Fernandes, Prabhavathi; Oldach, David

2016-04-01

Community-acquired bacterial pneumonia (CABP) is a leading cause of morbidity and mortality, and treatment recommendations, each with specific limitations, vary globally. We aimed to compare the efficacy and safety of solithromycin, a novel macrolide, with moxifloxacin for treatment of CABP. We did this global, double-blind, double-dummy, randomised, active-controlled, non-inferiority trial at 114 centres in North America, Latin America, Europe, and South Africa. Patients (aged ≥18 years) with clinically and radiographically confirmed pneumonia of Pneumonia Outcomes Research Team (PORT) risk class II, III, or IV were randomly assigned (1:1), via an internet-based central block randomisation procedure (block size of four), to receive either oral solithromycin (800 mg on day 1, 400 mg on days 2-5, placebo on days 6-7) or oral moxifloxacin (400 mg on days 1-7). Randomisation was stratified by geographical region, PORT risk class (II vs III or IV), and medical history of asthma or chronic obstructive pulmonary disease. The study sponsor, investigators, staff, and patients were masked to group allocation. The primary outcome was early clinical response, defined as an improvement in at least two of four symptoms (cough, chest pain, sputum production, dyspnoea) with no worsening in any symptom at 72 h after the first dose of study drug, with a 10% non-inferiority margin. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT-01756339. Between Jan 3, 2013, and Sept 24, 2014, we randomly assigned 860 patients to receive solithromycin (n=426) or moxifloxacin (n=434). Patients were followed up to days 28-35 after first dose. Solithromycin was non-inferior to moxifloxacin in achievement of early clinical response: 333 (78·2%) patients had an early clinical response in the solithromycin group versus 338 (77·9%) patients in the moxifloxacin group (difference 0·29, 95% CI -5·5 to 6·1). Both drugs had a similar safety profile. 43 (10%) of 155 treatment-emergent adverse events in the solithromycin group and 54 (13%) of 154 such events in the moxifloxacin group were deemed to be related to study drug. The most common adverse events, mostly of mild severity, were gastrointestinal disorders, including diarrhoea (18 [4%] patients in the solithromycin group vs 28 [6%] patients in the moxifloxacin group), nausea (15 [4%] vs 17 [4%] patients) and vomiting (ten [2%] patients in each group); and nervous system disorders, including headache (19 [4%] vs 11 [3%] patients) and dizziness (nine [2%] vs seven [2%] patients). Oral solithromycin was non-inferior to oral moxifloxacin for treatment of patients with CABP, showing the potential to restore macrolide monotherapy for this indication. Cempra. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dynamic Response of the Hybrid III 3 Year Old Dummy Head and Neck During Side Air Bag Loading

PubMed Central

Duma, Stefan M.; Crandall, Jeff R.; Pilkey, Walter D.; Seki, Kazuhiro; Aoki, Takashi

1998-01-01

This paper presents the results from fourteen (n = 14) tests designed to evaluate the response and injury potential of a Hybrid III 3 year old dummy subject to loading by a deploying seat mounted side air bag. An instrumented Hybrid III 3 year old dummy was used for tests in two different occupant positions chosen to maximize head and neck loading. Four seat mounted thoracic side air bags were used that varied only in the level of inflator output. NHTSA’s neck injury criteria for complex loading, referred to as Nij, was modified to include moment values for both anterioposterior and lateral directions. The results of this testing indicate that side air bag loading can result in forces and moments approaching injury threshold values. While there is considerable uncertainty as to the validity of published injury criteria due to the lack of child biomechanical data, this study demonstrates the sensitivity of child response to initial position which may provide insight into placement and geometry of side airbag systems. Furthermore, the data indicates a relationship between airbag inflator properties and child dummy response for a given airbag geometry. Recently, automobile manufacturers have begun implementing side air bags as a safety feature to mitigate injuries resulting from side impact collisions. Unlike the case for the passenger side air bag, the injury potential to an out-of-position child in side airbag loading has not been presented in the literature. The purpose of this research is to evaluate the response of a Hybrid III 3 year old dummy subject to loading by a deploying side air bag.

Development of stress boundary conditions in smoothed particle hydrodynamics (SPH) for the modeling of solids deformation

NASA Astrophysics Data System (ADS)

Douillet-Grellier, Thomas; Pramanik, Ranjan; Pan, Kai; Albaiz, Abdulaziz; Jones, Bruce D.; Williams, John R.

2017-10-01

This paper develops a method for imposing stress boundary conditions in smoothed particle hydrodynamics (SPH) with and without the need for dummy particles. SPH has been used for simulating phenomena in a number of fields, such as astrophysics and fluid mechanics. More recently, the method has gained traction as a technique for simulation of deformation and fracture in solids, where the meshless property of SPH can be leveraged to represent arbitrary crack paths. Despite this interest, application of boundary conditions within the SPH framework is typically limited to imposed velocity or displacement using fictitious dummy particles to compensate for the lack of particles beyond the boundary interface. While this is enough for a large variety of problems, especially in the case of fluid flow, for problems in solid mechanics there is a clear need to impose stresses upon boundaries. In addition to this, the use of dummy particles to impose a boundary condition is not always suitable or even feasibly, especially for those problems which include internal boundaries. In order to overcome these difficulties, this paper first presents an improved method for applying stress boundary conditions in SPH with dummy particles. This is then followed by a proposal of a formulation which does not require dummy particles. These techniques are then validated against analytical solutions to two common problems in rock mechanics, the Brazilian test and the penny-shaped crack problem both in 2D and 3D. This study highlights the fact that SPH offers a good level of accuracy to solve these problems and that results are reliable. This validation work serves as a foundation for addressing more complex problems involving plasticity and fracture propagation.

Abdominal Twin Pressure Sensors for the assessment of abdominal injuries in Q dummies: in-dummy evaluation and performance in accident reconstructions.

PubMed

Beillas, Philippe; Alonzo, François; Chevalier, Marie-Christine; Lesire, Philippe; Leopold, Franck; Trosseille, Xavier; Johannsen, Heiko

2012-10-01

The Abdominal Pressure Twin Sensors (APTS) for Q3 and Q6 dummies are composed of soft polyurethane bladders filled with fluid and equipped with pressure sensors. Implanted within the abdominal insert of child dummies, they can be used to detect abdominal loading due to the belt during frontal collisions. In the present study - which is part of the EC funded CASPER project - two versions of APTS (V1 and V2) were evaluated in abdominal belt compression tests, torso flexion test (V1 only) and two series of sled tests with degraded restraint conditions. The results suggest that the two versions have similar responses, and that the pressure sensitivity to torso flexion is limited. The APTS ability to detect abdominal loading in sled tests was also confirmed, with peak pressures typically below 1 bar when the belt loaded only the pelvis and the thorax (appropriate restraint) and values above that level when the abdomen was loaded directly (inappropriate restraint). Then, accident reconstructions performed as part of CASPER and previous EC funded projects were reanalyzed. Selected data from 19 dummies (12 Q6 and 7 Q3) were used to plot injury risk curves. Maximum pressure, maximum pressure rate and their product were all found to be injury predictors. Maximum pressure levels for a 50% risk of AIS3+ were consistent with the levels separating appropriate and inappropriate restraint in the sled tests (e.g. 50% risk of AIS3+ at 1.09 bar for pressure filtered CFC180). Further work is needed to refine the scaling techniques between ages and confirm the risk curves.

On the use of an Arduino-based controller to control the charging process of a wind turbine

NASA Astrophysics Data System (ADS)

Mahmuddin, Faisal; Yusran, Ahmad Muhtam; Klara, Syerly

2017-02-01

In order to avoid an excessive charging voltage which can damage power storage when converting wind energy using a turbine, it is necessary to control the charging voltage of the turbine generator. In the present study, a charging controller which uses an Arduino microcontroller, is designed. 3 (three) indicator lights are installed to indicate the battery charging process, power diversion to dummy load and battery power level. The performance of the designed controller is evaluated by simulating 3 cases. In this simulation, a battery with maximum voltage of 12.4 V is used. Case 1 is performed with input voltage equals the one set in Arduino which is 10 V. In this case, the battery is charged up to 10.8 V. In case 2, the input voltage is 13 V while the maximum voltage set in Arduino is also 13 V. In this case, the battery is charged up to maximum voltage of the battery. Moreover, the dummy load indicator is ON and charging indicator is OFF after the maximum charging voltage is reached because the electricity is flowed to the dummy load. In the final case, the input voltage is set to be 16 V while the maximum voltage set in Arduino is 13 V. In this case, the charging indicator is OFF and dummy load indicator is ON which means that the Arduino has successfully switched the power to be flowed to dummy load. From the 3 (three) cases, it can be concluded that the designed controller works perfectly to control the charging process of the wind turbine. Moreover, the charging time needed in each case can also be determined.

Rilpivirine versus efavirenz with emtricitabine/tenofovir disoproxil fumarate in treatment-naïve HIV-1-infected patients with HIV-1 RNA ≤100,000 copies/mL: week 96 pooled ECHO/THRIVE subanalysis.

PubMed

Behrens, Georg; Rijnders, Bart; Nelson, Mark; Orkin, Chloe; Cohen, Calvin; Mills, Anthony; Elion, Richard A; Vanveggel, Simon; Stevens, Marita; Rimsky, Laurence; Thorpe, David; Bosse, Matthew; White, Kirsten; Zhong, Lijie; DeMorin, Jennifer; Chuck, Susan K

2014-04-01

The once daily, single-tablet regimen (STR) combining rilpivirine (RPV), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) provides a simplified treatment option for antiretroviral therapy (ART)-naïve patients with baseline HIV-1 RNA (BLVL) of ≤100,000 copies/mL. The aim of this analysis is to compare long-term efficacy, safety, and tolerability of RPV+FTC/TDF vs. efavirenz (EFV)+FTC/TDF as individual components in subjects with BLVL ≤100,000 copies/mL. Week 96 efficacy and safety data from subjects with BLVL ≤100,000 copies/mL, who received daily RPV 25 mg or EFV 600 mg with FTC/TDF in the phase 3, randomized, double-blind, double-dummy, active-controlled, registrational trials ECHO and THRIVE, were analyzed. Virologic response was evaluated by intent-to-treat, time to loss of virological response (ITT-TLOVR), and Snapshot algorithms. Through Week 96, RPV+FTC/TDF demonstrated non-inferior efficacy to EFV+FTC/TDF (84% vs. 81%, respectively; ITT-TLOVR) in 543 subjects with BLVL ≤100,000 copies/mL, and overall rates of virologic failure (VF) were 5.9% vs. 2.4%, respectively. Resistance development was lower in Year 2 than Year 1. Subjects in both arms with suboptimal adherence (≤95%) had lower virologic responses (63% vs. 62%, respectively). Treatment with RPV+FTC/TDF was associated with significantly fewer treatment-related adverse events (AEs), grade 2-4 AEs, neurological and psychiatric AEs (including dizziness and abnormal dreams/nightmares), and rash. Additionally, grade 2-4 treatment-emergent laboratory abnormalities and grade 1-3 lipid abnormalities were significantly less common with RPV+FTC/TDF than EFV+FTC/TDF. RPV+FTC/TDF demonstrated non-inferior efficacy to EFV+FTC/TDF in ART-naïve subjects with BLVL ≤100,000 copies/mL and was associated with a higher rate of VF but a more favorable safety and tolerability profile through Week 96.

Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes.

PubMed

Lund, Søren S; Tarnow, Lise; Frandsen, Merete; Smidt, Ulla M; Pedersen, Oluf; Parving, Hans-Henrik; Vaag, Allan A

2008-01-01

Non-obese patients with type 2 diabetes (T2DM) are characterized by predominant defective insulin secretion. However, in non-obese T2DM patients, metformin, targeting insulin resistance, is non-inferior to the prandial insulin secretagogue, repaglinide, controlling overall glycaemia (HbA1c). Whether the same apply for postprandial glucose and lipid metabolism is unknown. Here, we compared the effect of metformin versus repaglinide on postprandial metabolism in non-obese T2DM patients. Single-centre, double-masked, double-dummy, crossover study during 2x4 months involving 96 non-obese (body mass index < or = 27 kg/m2) insulin-naïve T2DM patients. At enrolment, patients stopped prior oral hypoglycaemic agents therapies and after a 1-month run-in period on diet-only treatment, patients were randomized to repaglinide (2 mg) thrice daily followed by metformin (1 g) twice daily or vice versa each during 4 months with 1-month washout between interventions. Postprandial metabolism was evaluated by a standard test meal (3515 kJ; 54% fat, 13% protein and 33% carbohydrate) with blood sampling 0-6 h postprandially. Fasting levels and total area under the curve (AUC) for plasma glucose, triglycerides and free fatty acids (FFA) changed equally between treatments. In contrast, fasting levels and AUC of total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and serum insulin were lower during metformin than repaglinide (mean (95% confidence intervals), LDL cholesterol difference metformin versus repaglinide: AUC: -0.17 mmol/l (-0.26; -0.08)). AUC differences remained significant after adjusting for fasting levels. In non-obese T2DM patients, metformin reduced postprandial levels of glycaemia, triglycerides and FFA similarly compared to the prandial insulin secretagogue, repaglinide. Furthermore, metformin reduced fasting and postprandial cholesterolaemia and insulinaemia compared with repaglinide. These data support prescription of metformin as the preferred drug in non-obese patients with T2DM targeting fasting and postprandial glucose and lipid metabolism.

Improved glycemic control induced by both metformin and repaglinide is associated with a reduction in blood levels of 3-deoxyglucosone in nonobese patients with type 2 diabetes.

PubMed

Engelen, Lian; Lund, Søren S; Ferreira, Isabel; Tarnow, Lise; Parving, Hans-Henrik; Gram, Jørgen; Winther, Kaj; Pedersen, Oluf; Teerlink, Tom; Barto, Rob; Stehouwer, Coen D A; Vaag, Allan A; Schalkwijk, Casper G

2011-03-01

Metformin has been reported to reduce α-dicarbonyls, which are known to contribute to diabetic complications. It is unclear whether this is due to direct quenching of α-dicarbonyls or to an improvement in glycemic control. We therefore compared the effects of metformin versus repaglinide, an antihyperglycemic agent with an insulin-secreting mechanism, on the levels of the α-dicarbonyl 3-deoxyglucosone (3DG). We conducted a single-center, double-masked, double-dummy, crossover study involving 96 nonobese patients with type 2 diabetes. After a 1-month run-in on diet-only treatment, patients were randomized to either repaglinide (6 mg daily) followed by metformin (2 g daily) or vice versa each during 4 months with a 1-month washout between interventions. 3DG levels decreased after both metformin (-19.3% (95% confidence interval (CI): -23.5, -14.8)) and repaglinide (-20.8% (95% CI: -24.9, -16.3)) treatments, but no difference was found between treatments (1.8% (95% CI: -3.8, 7.8)). Regardless of the treatment, changes in glycemic variables were associated with changes in 3DG. Specifically, 3DG decreased by 22.7% (95% CI: 19.0, 26.5) per s.d. decrease in fasting plasma glucose (PG), by 20.0% (95% CI: 16.2, 23.9) per s.d. decrease in seven-point mean plasma glucose, by 22.5% (95% CI: 18.6, 26.6) per s.d. decrease in area under the curve for PG, by 17.2% (95% CI: 13.8, 20.6) per s.d. decrease in HbAlc, and by 10.9% (95% CI: 6.4, 15.5) per s.d. decrease in Amadori albumin. In addition, decreases in 3DG were associated with decreases in advanced glycation endproducts and endothelial markers. Improved glycemic control induced by both metformin and repaglinide is associated with a reduction in 3DG levels in nonobese individuals with type 2 diabetes. This may constitute a shared metabolic pathway through which both treatments have a beneficial impact on the cardiovascular risk.

Efficacy and safety of rivaroxaban compared with warfarin in patients with peripheral artery disease and non-valvular atrial fibrillation: insights from ROCKET AF.

PubMed

Jones, William Schuyler; Hellkamp, Anne S; Halperin, Jonathan; Piccini, Jonathan P; Breithardt, Gunter; Singer, Daniel E; Fox, Keith A A; Hankey, Graeme J; Mahaffey, Kenneth W; Califf, Robert M; Patel, Manesh R

2014-01-01

Vascular disease is included in a risk scoring system to predict stroke in patients with non-valvular atrial fibrillation (AF). This post hoc analysis of ROCKET AF aimed to determine the absolute rates of stroke and bleeding, and the relative effectiveness and safety of rivaroxaban vs. warfarin in patients with and without peripheral artery disease (PAD). Peripheral artery disease was defined on the case-report form as the presences of intermittent claudication, amputation for arterial insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention to the extremities, or previously documented abdominal aortic aneurysm. ROCKET AF was a double-blind, double-dummy, randomized-controlled trial comparing rivaroxaban and warfarin for the prevention of stroke or systemic embolism. A total of 839 (5.9%) patients in ROCKET AF had PAD. Patients with and without PAD had similar rates of stroke or systemic embolism [HR: 1.04, 95% CI (0.72, 1.50), P = 0.84] and major or non-major clinically relevant (NMCR) bleeding [HR: 1.11, 95% CI (0.96, 1.28), P = 0.17], respectively. The efficacy of rivaroxaban when compared with warfarin for the prevention of stroke or systemic embolism was similar in patients with PAD (HR: 1.19, 95% CI: 0.63-2.22) and without PAD (HR: 0.86, 95% CI: 0.73-1.02; interaction P = 0.34). There was a significant interaction for major or NMCR bleeding in patients with PAD treated with rivaroxaban compared with warfarin (HR: 1.40, 95% CI: 1.06-1.86) compared with those without PAD (HR: 1.03, 95% CI: 0.95-1.11; interaction P = 0.037). Patients with PAD in ROCKET AF did not have a statistically significant higher risk of stroke or systemic embolism than patients without PAD, and there were similar efficacy outcomes in patients treated with rivaroxaban and warfarin. In PAD patients, there was a higher risk of major bleeding or NMCR bleeding with rivaroxaban when compared with warfarin (interaction P = 0.037). Further investigation is warranted to validate this subgroup analysis and determine the optimal treatment in this high-risk cohort of AF patients with PAD.

Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF).

PubMed

Sherwood, Matthew W; Douketis, James D; Patel, Manesh R; Piccini, Jonathan P; Hellkamp, Anne S; Lokhnygina, Yuliya; Spyropoulos, Alex C; Hankey, Graeme J; Singer, Daniel E; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M; Becker, Richard C

2014-05-06

During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non-central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3-30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36-1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80-2.00]; P=0.32). TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation. http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Outcomes of Temporary Interruption of Rivaroxaban Compared With Warfarin in Patients With Nonvalvular Atrial Fibrillation

PubMed Central

Sherwood, Matthew W.; Douketis, James D.; Patel, Manesh R.; Piccini, Jonathan P.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Spyropoulos, Alex C.; Hankey, Graeme J.; Singer, Daniel E.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.; Becker, Richard C.

2014-01-01

Background During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. Methods and Results In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non–central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3–30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36–1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80–2.00]; P=0.32). Conclusions TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767. PMID:24552831

Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers

PubMed Central

Teng, Renli; Maya, Juan; Butler, Kathleen

2013-01-01

The results of two independent, randomized, two-period crossover, single-center studies, conducted to assess the pharmacokinetics of ticagrelor ± aspirin, inhibition of platelet aggregation (IPA) with ticagrelor/aspirin vs. clopidogrel/aspirin, and safety, tolerability, and bleeding times are reported here. In Study A (open-label), 16 volunteers received ticagrelor (50 mg bid Days 1–5; 200 mg bid Days 6–9; one 200 mg dose on Day 10) ± 300 mg qd aspirin (Days 1–10). In Study B (double-blind, double-dummy), 16 volunteers received aspirin (300 mg loading dose/75 mg qd Days 2–9) with either ticagrelor (200 mg bid Days 4–8, one 200 mg dose on Day 9) or clopidogrel (300 mg loading dose Day 4, 75 mg qd Days 5–9). At steady-state ticagrelor (50 mg bid, or 200 mg bid), concomitant aspirin (300 mg qd) had no effect on mean maximum plasma concentration (C max), median time to C max (t max), or mean area under the plasma concentration-time curve for the dosing interval (AUC0– τ) for ticagrelor and its primary metabolite, AR-C124910XX. Following 200 mg bid ticagrelor, mean C max and AUC0– τ for both parent and metabolite were comparable with co-administration of aspirin at 75 mg and 300 mg qd. Aspirin (300 mg qd) had no effect on IPA (ADP-induced) by ticagrelor. However, aspirin and ticagrelor had an additive effect on IPA (collagen-induced). Ticagrelor/aspirin increased bleeding times vs. baseline. Ticagrelor/aspirin co-administration was well tolerated at all dose combinations evaluated. In summary, the findings of this study demonstrate that co-administration of aspirin (300 mg qd) with ticagrelor (50 mg bid, or 200 mg bid) had no effect on ticagrelor pharmacokinetics or IPA (ADP-induced) by ticagrelor. PMID:23249161

Digital double random amplitude image encryption method based on the symmetry property of the parametric discrete Fourier transform

NASA Astrophysics Data System (ADS)

Bekkouche, Toufik; Bouguezel, Saad

2018-03-01

We propose a real-to-real image encryption method. It is a double random amplitude encryption method based on the parametric discrete Fourier transform coupled with chaotic maps to perform the scrambling. The main idea behind this method is the introduction of a complex-to-real conversion by exploiting the inherent symmetry property of the transform in the case of real-valued sequences. This conversion allows the encrypted image to be real-valued instead of being a complex-valued image as in all existing double random phase encryption methods. The advantage is to store or transmit only one image instead of two images (real and imaginary parts). Computer simulation results and comparisons with the existing double random amplitude encryption methods are provided for peak signal-to-noise ratio, correlation coefficient, histogram analysis, and key sensitivity.

Simultaneous transmission for an encrypted image and a double random-phase encryption key

NASA Astrophysics Data System (ADS)

Yuan, Sheng; Zhou, Xin; Li, Da-Hai; Zhou, Ding-Fu

2007-06-01

We propose a method to simultaneously transmit double random-phase encryption key and an encrypted image by making use of the fact that an acceptable decryption result can be obtained when only partial data of the encrypted image have been taken in the decryption process. First, the original image data are encoded as an encrypted image by a double random-phase encryption technique. Second, a double random-phase encryption key is encoded as an encoded key by the Rivest-Shamir-Adelman (RSA) public-key encryption algorithm. Then the amplitude of the encrypted image is modulated by the encoded key to form what we call an encoded image. Finally, the encoded image that carries both the encrypted image and the encoded key is delivered to the receiver. Based on such a method, the receiver can have an acceptable result and secure transmission can be guaranteed by the RSA cipher system.

Simultaneous transmission for an encrypted image and a double random-phase encryption key.

PubMed

Yuan, Sheng; Zhou, Xin; Li, Da-hai; Zhou, Ding-fu

2007-06-20

We propose a method to simultaneously transmit double random-phase encryption key and an encrypted image by making use of the fact that an acceptable decryption result can be obtained when only partial data of the encrypted image have been taken in the decryption process. First, the original image data are encoded as an encrypted image by a double random-phase encryption technique. Second, a double random-phase encryption key is encoded as an encoded key by the Rivest-Shamir-Adelman (RSA) public-key encryption algorithm. Then the amplitude of the encrypted image is modulated by the encoded key to form what we call an encoded image. Finally, the encoded image that carries both the encrypted image and the encoded key is delivered to the receiver. Based on such a method, the receiver can have an acceptable result and secure transmission can be guaranteed by the RSA cipher system.

Dummy run of quality assurance program in a phase 3 randomized trial investigating the role of internal mammary lymph node irradiation in breast cancer patients: Korean Radiation Oncology Group 08-06 study.

PubMed

Chung, Yoonsun; Kim, Jun Won; Shin, Kyung Hwan; Kim, Su Ssan; Ahn, Sung-Ja; Park, Won; Lee, Hyung-Sik; Kim, Dong Won; Lee, Kyu Chan; Suh, Hyun Suk; Kim, Jin Hee; Shin, Hyun Soo; Kim, Yong Bae; Suh, Chang-Ok

2015-02-01

The Korean Radiation Oncology Group (KROG) 08-06 study protocol allowed radiation therapy (RT) technique to include or exclude breast cancer patients from receiving radiation therapy to the internal mammary lymph node (IMN). The purpose of this study was to assess dosimetric differences between the 2 groups and potential influence on clinical outcome by a dummy run procedure. All participating institutions were asked to produce RT plans without irradiation (Arm 1) and with irradiation to the IMN (Arm 2) for 1 breast-conservation treatment case (breast-conserving surgery [BCS]) and 1 mastectomy case (modified radical mastectomy [MRM]) whose computed tomography images were provided. We assessed interinstitutional variations in IMN delineation and evaluated the dose-volume histograms of the IMN and normal organs. A reference IMN was delineated by an expert panel group based on the study guidelines. Also, we analyzed the potential influence of actual dose variation observed in this study on patient survival. Although physicians intended to exclude the IMN within the RT field, the data showed almost 59.0% of the prescribed dose was delivered to the IMN in Arm 1. However, the mean doses covering the IMN in Arm 1 and Arm 2 were significantly different for both cases (P<.001). Due to the probability of overdose in Arm 1, the estimated gain in 7-year disease-free survival rate would be reduced from 10% to 7.9% for BCS cases and 7.1% for MRM cases. The radiation doses to the ipsilateral lung, heart, and coronary artery were lower in Arm 1 than in Arm 2. Although this dummy run study indicated that a substantial dose was delivered to the IMN, even in the nonirradiation group, the dose differences between the 2 groups were statistically significant. However, this dosimetric profile should be studied further with actual patient samples and be taken into consideration when analyzing clinical outcomes according to IMN irradiation. Copyright © 2015 Elsevier Inc. All rights reserved.

Dummy Run of Quality Assurance Program in a Phase 3 Randomized Trial Investigating the Role of Internal Mammary Lymph Node Irradiation in Breast Cancer Patients: Korean Radiation Oncology Group 08-06 Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Yoonsun; Kim, Jun Won; Shin, Kyung Hwan

2015-02-01

Purpose: The Korean Radiation Oncology Group (KROG) 08-06 study protocol allowed radiation therapy (RT) technique to include or exclude breast cancer patients from receiving radiation therapy to the internal mammary lymph node (IMN). The purpose of this study was to assess dosimetric differences between the 2 groups and potential influence on clinical outcome by a dummy run procedure. Methods and Materials: All participating institutions were asked to produce RT plans without irradiation (Arm 1) and with irradiation to the IMN (Arm 2) for 1 breast-conservation treatment case (breast-conserving surgery [BCS]) and 1 mastectomy case (modified radical mastectomy [MRM]) whose computed tomographymore » images were provided. We assessed interinstitutional variations in IMN delineation and evaluated the dose-volume histograms of the IMN and normal organs. A reference IMN was delineated by an expert panel group based on the study guidelines. Also, we analyzed the potential influence of actual dose variation observed in this study on patient survival. Results: Although physicians intended to exclude the IMN within the RT field, the data showed almost 59.0% of the prescribed dose was delivered to the IMN in Arm 1. However, the mean doses covering the IMN in Arm 1 and Arm 2 were significantly different for both cases (P<.001). Due to the probability of overdose in Arm 1, the estimated gain in 7-year disease-free survival rate would be reduced from 10% to 7.9% for BCS cases and 7.1% for MRM cases. The radiation doses to the ipsilateral lung, heart, and coronary artery were lower in Arm 1 than in Arm 2. Conclusions: Although this dummy run study indicated that a substantial dose was delivered to the IMN, even in the nonirradiation group, the dose differences between the 2 groups were statistically significant. However, this dosimetric profile should be studied further with actual patient samples and be taken into consideration when analyzing clinical outcomes according to IMN irradiation.« less

Random effects coefficient of determination for mixed and meta-analysis models.

PubMed

Demidenko, Eugene; Sargent, James; Onega, Tracy

2012-01-01

The key feature of a mixed model is the presence of random effects. We have developed a coefficient, called the random effects coefficient of determination, [Formula: see text], that estimates the proportion of the conditional variance of the dependent variable explained by random effects. This coefficient takes values from 0 to 1 and indicates how strong the random effects are. The difference from the earlier suggested fixed effects coefficient of determination is emphasized. If [Formula: see text] is close to 0, there is weak support for random effects in the model because the reduction of the variance of the dependent variable due to random effects is small; consequently, random effects may be ignored and the model simplifies to standard linear regression. The value of [Formula: see text] apart from 0 indicates the evidence of the variance reduction in support of the mixed model. If random effects coefficient of determination is close to 1 the variance of random effects is very large and random effects turn into free fixed effects-the model can be estimated using the dummy variable approach. We derive explicit formulas for [Formula: see text] in three special cases: the random intercept model, the growth curve model, and meta-analysis model. Theoretical results are illustrated with three mixed model examples: (1) travel time to the nearest cancer center for women with breast cancer in the U.S., (2) cumulative time watching alcohol related scenes in movies among young U.S. teens, as a risk factor for early drinking onset, and (3) the classic example of the meta-analysis model for combination of 13 studies on tuberculosis vaccine.

Extraction of the gate capacitance coupling coefficient in floating gate non-volatile memories: Statistical study of the effect of mismatching between floating gate memory and reference transistor in dummy cell extraction methods

NASA Astrophysics Data System (ADS)

Rafhay, Quentin; Beug, M. Florian; Duane, Russell

2007-04-01

This paper presents an experimental comparison of dummy cell extraction methods of the gate capacitance coupling coefficient for floating gate non-volatile memory structures from different geometries and technologies. These results show the significant influence of mismatching floating gate devices and reference transistors on the extraction of the gate capacitance coupling coefficient. In addition, it demonstrates the accuracy of the new bulk bias dummy cell extraction method and the importance of the β function, introduced recently in [Duane R, Beug F, Mathewson A. Novel capacitance coupling coefficient measurement methodology for floating gate non-volatile memory devices. IEEE Electr Dev Lett 2005;26(7):507-9], to determine matching pairs of floating gate memory and reference transistor.

Effects of external radio transmitters on fish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ross, M.J.; McCormick, J.H.

1981-04-01

Yellow perch (Perca flavescens) and largemouth bass (Micropterus salmoides) were studied to determine the effects of externally attached radio transmitter tags. Perch that had been tagged with dummy radio tags were more susceptible to predation and more sensitive to environmental stress than were controls. Feeding and respiration rates were similar among dummy tagged and control groups of perch over a 6-week period. The feeding rate of dummy tagged largemouth bass was lower than that of untagged fish over a 3,5-week period. On the basis of these studies, we conclude that weights of external transmitters in water should be less thanmore » 1.5% of the fish weight. Design considerations should include streamlining components and an anterior attachment wire at the extreme leading edge of an external transmitter to prevent entanglement of the tag in surrounding vegetation.« less

The efficacy of infiltration anaesthesia for adult mandibular incisors: a randomised double-blind cross-over trial comparing articaine and lidocaine buccal and buccal plus lingual infiltrations.

PubMed

Jaber, A; Whitworth, J M; Corbett, I P; Al-Baqshi, B; Kanaa, M D; Meechan, J G

2010-11-01

To compare the efficacy of 2% lidocaine and 4% articaine both with 1:100,000 adrenaline in anaesthetising the pulps of mandibular incisors. Thirty-one healthy adult volunteers received the following local anaesthetic regimens adjacent to a mandibular central incisor: 1) buccal infiltration of 1.8 mL lidocaine plus dummy lingual injection (LB), 2) buccal plus lingual infiltrations of 0.9 mL lidocaine (LBL), 3) buccal infiltration of 1.8 mL articaine plus dummy lingual injection (AB), 4) buccal plus lingual infiltrations of 0.9 mL articaine (ABL). Pulp sensitivities of the central incisor and contralateral lateral incisor were assessed electronically. Anaesthetic efficacy was determined by two methods: 1) Recording the number of episodes with no responses to maximal electronic pulp tester stimulation during the course of the study period, 2) recording the number of volunteers with no response to maximal pulp tester stimulation within 15 min and maintained for 45 min (defined as sustained anaesthesia). Data were analysed by McNemar, chi-square, Mann-Whitney and paired t-tests. For both test teeth, the number of episodes of no sensation on maximal stimulation was significantly greater after articaine than lidocaine for both techniques. The split buccal plus lingual dose was more effective than the buccal injection alone for both solutions (p <0.001). 4% articaine was more effective than 2% lidocaine when comparing sustained anaesthesia in both teeth for each technique (p <0.001), however, there was no difference in sustained anaesthesia between techniques for either tooth or solution. 4% articaine was more effective than 2% lidocaine (both with 1:100,000 adrenaline) in anaesthetising the pulps of lower incisor teeth after buccal or buccal plus lingual infiltrations.

Process variation challenges and resolution in the negative-tone develop double patterning for 20nm and below technology node

NASA Astrophysics Data System (ADS)

Mehta, Sohan S.; Ganta, Lakshmi K.; Chauhan, Vikrant; Wu, Yixu; Singh, Sunil; Ann, Chia; Subramany, Lokesh; Higgins, Craig; Erenturk, Burcin; Srivastava, Ravi; Singh, Paramjit; Koh, Hui Peng; Cho, David

2015-03-01

Immersion based 20nm technology node and below becoming very challenging to chip designers, process and integration due to multiple patterning to integrate one design layer . Negative tone development (NTD) processes have been well accepted by industry experts for enabling technologies 20 nm and below. 193i double patterning is the technology solution for pitch down to 80 nm. This imposes tight control in critical dimension(CD) variation in double patterning where design patterns are decomposed in two different masks such as in litho-etch-litho etch (LELE). CD bimodality has been widely studied in LELE double patterning. A portion of CD tolerance budget is significantly consumed by variations in CD in double patterning. The objective of this work is to study the process variation challenges and resolution in the Negative Tone Develop Process for 20 nm and Below Technology Node. This paper describes the effect of dose slope on CD variation in negative tone develop LELE process. This effect becomes even more challenging with standalone NTD developer process due to q-time driven CD variation. We studied impact of different stacks with combination of binary and attenuated phase shift mask and estimated dose slope contribution individually from stack and mask type. Mask 3D simulation was carried out to understand theoretical aspect. In order to meet the minimum insulator requirement for the worst case on wafer the overlay and critical dimension uniformity (CDU) budget margins have slimmed. Besides the litho process and tool control using enhanced metrology feedback, the variation control has other dependencies too. Color balancing between the two masks in LELE is helpful in countering effects such as iso-dense bias, and pattern shifting. Dummy insertion and the improved decomposition techniques [2] using multiple lower priority constraints can help to a great extent. Innovative color aware routing techniques [3] can also help with achieving more uniform density and color balanced layouts.

In-die mask registration measurement on 28nm-node and beyond

NASA Astrophysics Data System (ADS)

Chen, Shen Hung; Cheng, Yung Feng; Chen, Ming Jui

2013-09-01

As semiconductor go to smaller node, the critical dimension (CD) of process become more and more small. For lithography, RET (Resolution Enhancement Technology) applications can be used for wafer printing of smaller CD/pitch on 28nm node and beyond. SMO (Source Mask Optimization), DPT (Double Patterning Technology) and SADP (Self-Align Double Patterning) can provide lower k1 value for lithography. In another way, image placement error and overlay control also become more and more important for smaller chip size (advanced node). Mask registration (image placement error) and mask overlay are important factors to affect wafer overlay control/performance especially for DPT or SADP. In traditional method, the designed registration marks (cross type, square type) with larger CD were put into scribe-line of mask frame for registration and overlay measurement. However, these patterns are far way from real patterns. It does not show the registration of real pattern directly and is not a convincing method. In this study, the in-die (in-chip) registration measurement is introduced. We extract the dummy patterns that are close to main pattern from post-OPC (Optical Proximity Correction) gds by our desired rule and choose the patterns that distribute over whole mask uniformly. The convergence test shows 100 points measurement has a reliable result.

Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group.

PubMed

Muir, J F; Bertin, L; Georges, D

1992-11-01

We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.

A comparison of sumanirole versus placebo or ropinirole for the treatment of patients with early Parkinson's disease.

PubMed

Singer, Carlos; Lamb, Janice; Ellis, Amanda; Layton, Gary

2007-03-15

To assess the safety and efficacy of sumanirole, a highly selective dopamine agonist, versus placebo and demonstrate its noninferiority to ropinirole, 614 patients with early Parkinson's disease (PD) were treated with sumanirole, 1 to 16 mg/day; ropinirole, 0.75 to 24 mg/day; or placebo. Primary end point in this flexible-dose, double-blind, double-dummy, parallel-group study of 40 weeks was the change in total sum of the United Parkinson's Disease Rating Scale (UPDRS) Parts II + III scores from baseline to end of maintenance. Approximately half the subjects in the sumanirole and placebo groups withdrew early from the study, most (51.8% and 68.5%, respectively) due to lack of efficacy. Of the ropinirole subjects who withdrew (50.5%), most discontinued because of adverse events. In sumanirole and ropinirole groups, mean changes from baseline of -2.48 and -5.20 in UPDRS II + III mean scores were significant versus 0.38 in the placebo group (P

MTR MAIN FLOOR. MEN DEMONSTRATE INSERTION OF DUMMY PLUG INTO ...

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

MTR MAIN FLOOR. MEN DEMONSTRATE INSERTION OF DUMMY PLUG INTO AN MTR BEAM HOLE. ONE MAN CHECKS RADIATION LEVEL AT THE END OF THE UNIVERSAL COFFIN, WHILE ANOTHER USES TOOL TO INSERT PLUG INTO HOLE THROUGH COFFIN. MEN WEAR "ANTI-C" (ANTI-CONTAMINATION) CLOTHING. INL NEGATIVE NO. 6198. R.G. Larsen, Photographer, 6/27/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

The Use of a Vehicle Acceleration Exposure Limit Model and a Finite Element Crash Test Dummy Model to Evaluate the Risk of Injuries During Orion Crew Module Landings

NASA Technical Reports Server (NTRS)

Lawrence, Charles; Fasanella, Edwin L.; Tabiei, Ala; Brinkley, James W.; Shemwell, David M.

2008-01-01

A review of astronaut whole body impact tolerance is discussed for land or water landings of the next generation manned space capsule named Orion. LS-DYNA simulations of Orion capsule landings are performed to produce a low, moderate, and high probability of injury. The paper evaluates finite element (FE) seat and occupant simulations for assessing injury risk for the Orion crew and compares these simulations to whole body injury models commonly referred to as the Brinkley criteria. The FE seat and crash dummy models allow for varying the occupant restraint systems, cushion materials, side constraints, flailing of limbs, and detailed seat/occupant interactions to minimize landing injuries to the crew. The FE crash test dummies used in conjunction with the Brinkley criteria provides a useful set of tools for predicting potential crew injuries during vehicle landings.

Modeling The Frontal Collison In Vehicles And Determining The Degree Of Injury On The Driver

NASA Astrophysics Data System (ADS)

Oţăt, Oana Victoria

2015-09-01

The present research study aims at analysing the kinematic and the dynamic behaviour of the vehicle's driver in a frontal collision. Hence, a subsequent objective of the research paper is to establish the degree of injury suffered by the driver. Therefore, in order to achieve the objectives set, first, we had to define the type of the dummy placed in the position of the driver, and then to design the three-element assembly, i.e. the chair-steering wheel-dashboard assembly. Based on this model, the following step focused on the positioning of the dummy, which has also integrated the defining of the contacts between the components of the dummy and the seat elements. Seeking to model such a behaviour that would highly accurately reflect the driver's movements in a frontal collision, passive safety systems have also been defined and simulated, namely the seatbelt and the frontal airbag.

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

PubMed

Wang, Xiaogang; Chen, Wen; Chen, Xudong

2015-03-09

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

Navy Electroplating Pollution Control Technology Assessment Manual.

DTIC Science & Technology

1984-02-01

quality. Dummying of chromium baths is used in the special case where high cathode-to-anode 5ea ratio has resulted in build up of trivalent chromium (Cr...Dummying with a high anode -to-cat hode area ratio can be 6used to reoxidize the trivalent to hexavalent chromium (Cr ).Proper scheduling of work can...unit processes: * Chromium reduction (if needed) of segregated chromium waste streams to reduce the chromium from its hexavalent form to the trivalent

Synthesis of lab-in-a-pipette-tip extraction using hydrophilic nano-sized dummy molecularly imprinted polymer for purification and analysis of prednisolone.

PubMed

Arabi, Maryam; Ghaedi, Mehrorang; Ostovan, Abbas; Wang, Shaobin

2016-10-15

A novel pipette-tip based on nano-sized dummy molecularly imprinted polymer (PT-DMIP) assisted by ultrasonication for the effective enrichment and analysis of prednisolone from urine samples was developed. The PT-DMIP cartridge was prepared by packing the dummy molecularly imprinted polymer at the tip of the micropipette. The polymerization used betamethasone (BM) as the dummy template, 3-aminopropyltrimethoxysilane (APTMS) as the functionalized monomer, tetraethyl orthosilicate (TEOS) as the cross-linker and aluminum ion (Al(3+)) as a dopant to produce Lewis acid sites in the silica matrix for metal coordinative interactions with the analyte. Compared to conventional solid phase extraction (SPE), the PT-DMIP is cost-effective, fast, and easy to handle, while the system is very approachable and reduces the consumption of toxic organic solvent. HPLC-UV analysis revealed successful applicability of the sorbent for highly efficient extraction of perdnisolone from urine matrices. The extraction recovery was investigated and optimum conditions were obtained using central composite design. Good linearity for prednisolone in the range of 0.22-220μgL(-1) with regression coefficients of 0.99 reveals high applicability of the method for trace analysis. Under the optimized conditions, the recoveries are 89.0-96.1 with relative standard deviations (RSD) of less than 9.0%. Copyright © 2016 Elsevier Inc. All rights reserved.

Process-based Assignment-Setting Change for Support of Overcoming Bottlenecks in Learning by Problem-Posing in Arithmetic Word Problems

NASA Astrophysics Data System (ADS)

Supianto, A. A.; Hayashi, Y.; Hirashima, T.

2017-02-01

Problem-posing is well known as an effective activity to learn problem-solving methods. Monsakun is an interactive problem-posing learning environment to facilitate arithmetic word problems learning for one operation of addition and subtraction. The characteristic of Monsakun is problem-posing as sentence-integration that lets learners make a problem of three sentences. Monsakun provides learners with five or six sentences including dummies, which are designed through careful considerations by an expert teacher as a meaningful distraction to the learners in order to learn the structure of arithmetic word problems. The results of the practical use of Monsakun in elementary schools show that many learners have difficulties in arranging the proper answer at the high level of assignments. The analysis of the problem-posing process of such learners found that their misconception of arithmetic word problems causes impasses in their thinking and mislead them to use dummies. This study proposes a method of changing assignments as a support for overcoming bottlenecks of thinking. In Monsakun, the bottlenecks are often detected as a frequently repeated use of a specific dummy. If such dummy can be detected, it is the key factor to support learners to overcome their difficulty. This paper discusses how to detect the bottlenecks and to realize such support in learning by problem-posing.

Factors that influence chest injuries in rollovers.

PubMed

Digges, Kennerly; Eigen, Ana; Tahan, Fadi; Grzebieta, Raphael

2014-01-01

The design of countermeasures to reduce serious chest injuries for belted occupants involved in rollover crashes requires an understanding of the cause of these injuries and of the test conditions to assure the effectiveness of the countermeasures. This study defines rollover environments and occupant-to-vehicle interactions that cause chest injuries for belted drivers. The NASS-CDS was examined to determine the frequency and crash severity for belted drivers with serious (Abbreviated Injury Scale [AIS] 3+) chest injuries in rollovers. Case studies of NASS crashes with serious chest injuries sustained by belted front occupants were undertaken and damage patterns were determined. Vehicle rollover tests with dummies were examined to determine occupant motion in crashes with damage similar to that observed in the NASS cases. Computer simulations were performed to further explore factors that could contribute to chest injury. Finite element model (FEM) vehicle models with both the FEM Hybrid III dummy and THUMS human model were used in the simulations. Simulation of rollovers with 6 quarter-turns or less indicated that increases in the vehicle pitch, either positive or negative, increased the severity of dummy chest loadings. This finding was consistent with vehicle damage observations from NASS cases. For the far-side occupant, the maximum chest loadings were caused by belt and side interactions during the third quarter-turn and by the center console loading during the fourth quarter-turn. The results showed that the THUMS dummy produced more realistic kinematics and improved insights into skeletal and chest organ loadings compared to the Hybrid III dummy. These results suggest that a dynamic rollover test to encourage chest injury reduction countermeasures should induce a roll of at least 4 quarter-turns and should also include initial vehicle pitch and/or yaw so that the vehicle's axis of rotation is not aligned with its inertial roll axis during the initial stage of the rollover.

Complex social waves of giant honeybees provoked by a dummy wasp support the special-agent hypothesis.

PubMed

Kastberger, Gerald; Weihmann, Frank; Hoetzl, Thomas

2010-03-01

The social waves in giant honeybees termed as shimmering are more complex than mexican waves. it has been demonstrated1 that shimmering is triggered by special agents at the nest surface. in this paper, we have used a nest that originated by amalgamation of two previously separated nests and stimulated waves by a dummy wasp moved on a miniature cable car. we illustrate the plausibility of the special-agent hypothesis1 also for complex shimmering processes.

Complex social waves of giant honeybees provoked by a dummy wasp support the special-agent hypothesis

PubMed Central

Weihmann, Frank; Hoetzl, Thomas

2010-01-01

The social waves in giant honeybees termed as shimmering are more complex than mexican waves. it has been demonstrated1 that shimmering is triggered by special agents at the nest surface. in this paper, we have used a nest that originated by amalgamation of two previously separated nests and stimulated waves by a dummy wasp moved on a miniature cable car. we illustrate the plausibility of the special-agent hypothesis1 also for complex shimmering processes. PMID:20585516

Evaluating the Effectiveness of Various Blast Loading Descriptors as Occupant Injury Predictors for Underbody Blast Events

DTIC Science & Technology

2014-01-09

of Hybrid III ATD LSDYNA model with FTSS v7.1.6 finite element dummy 6 Unclassified: Distribution Statement A. Approved for public release...descriptors as occupant injury predictors for underbody blast events Recording injury metrics Response from the dummy especially pelvic acceleration and...Ciip(H&ad CG,2) "’"’ "-......--------, I Max : 122.669 @59.81 7!; Time, ms Pelvic Z acceleration, g I I Clip: -4.75737 Ts:97.4138 Te: 104.414

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carpenter, John H.; Belcourt, Kenneth Noel

Completion of the CASL L3 milestone THM.CFD.P6.03 provides a tabular material properties capability to the Hydra code. A tabular interpolation package used in Sandia codes was modified to support the needs of multi-phase solvers in Hydra. Use of the interface is described. The package was released to Hydra under a government use license. A dummy physics was created in Hydra to prototype use of the interpolation routines. Finally, a test using the dummy physics verifies the correct behavior of the interpolation for a test water table. 3

Presentation of a dummy representing suit for simulation of huMAN heatloss (DRESSMAN).

PubMed

Mayer, E; Schwab, R

2004-09-01

DRESSMAN designates a novel dummy for climate measurements that allows predicting the human thermal comfort experienced inside rooms (buildings, vehicles, aircraft, railway compartments etc.) on the basis of indoor climate measurements. Measurements can be listed in tabular form and can also be represented by way of color gradations in a virtual 3D human model. Optionally, visualization may be rendered during or after measurement. Due to its very quick response, DRESSMAN is particularly suited for nonstationary processes.

Reducing questionnaire length did not improve physician response rate: a randomized trial.

PubMed

Bolt, Eva E; van der Heide, Agnes; Onwuteaka-Philipsen, Bregje D

2014-04-01

To examine the effect of reducing questionnaire length on the response rate in a physician survey. A postal four double-page questionnaire on end-of-life decision making was sent to a random sample of 1,100 general practitioners, 400 elderly care physicians, and 500 medical specialists. Another random sample of 500 medical specialists received a shorter questionnaire of two double pages. After 3 months and one reminder, all nonresponding physicians received an even shorter questionnaire of one double page. Total response was 64% (1,456 of 2,269 eligible respondents). Response rate of medical specialists for the four double-page questionnaire was equal to that of the two double-page questionnaire (190 and 191 questionnaires were returned, respectively). The total response rate increased from 53% to 64% after sending a short one double-page questionnaire (1,203-1,456 respondents). The results of our study suggest that reducing the length of a long questionnaire in a physician survey does not necessarily improve response rate. To improve response rate and gather more information, researchers could decide to send a drastically shortened version of the questionnaire to nonresponders. Copyright © 2014 Elsevier Inc. All rights reserved.

Human norovirus inactivation in oysters by high hydrostatic pressure processing: A randomized double-blinded study

USDA-ARS?s Scientific Manuscript database

This randomized, double-blinded, clinical trial assessed the effect of high hydrostatic pressure processing (HPP) on genogroup I.1 human norovirus (HuNoV) inactivation in virus-seeded oysters when ingested by subjects. The safety and efficacy of HPP treatments were assessed in three study phases wi...

Tic Reduction with Risperidone Versus Pimozide in a Randomized, Double-Blind, Crossover Trial

ERIC Educational Resources Information Center

Gilbert, Donald L.; Batterson, J. Robert; Sethuraman, Gopalan; Sallee, Floyd R.

2004-01-01

Objective: To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders. Method: This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic…

EEG Neurofeedback for ADHD: Double-Blind Sham-Controlled Randomized Pilot Feasibility Trial

ERIC Educational Resources Information Center

Arnold, L. Eugene; Lofthouse, Nicholas; Hersch, Sarah; Pan, Xueliang; Hurt, Elizabeth; Bates, Bethany; Kassouf, Kathleen; Moone, Stacey; Grantier, Cara

2013-01-01

Objective: Preparing for a definitive randomized clinical trial (RCT) of neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double-blind, sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week. Method: Unmedicated 6- to 12-year-olds with "Diagnostic and Statistical Manual of…

Digestive Enzyme Supplementation for Autism Spectrum Disorders: A Double-Blind Randomized Controlled Trial

ERIC Educational Resources Information Center

Munasinghe, Sujeeva A.; Oliff, Carolyn; Finn, Judith; Wray, John A.

2010-01-01

To examine the effects of a digestive enzyme supplement in improving expressive language, behaviour and other symptoms in children with Autism Spectrum Disorder. Randomized, double-blind placebo-controlled trial using crossover design over 6 months for 43 children, aged 3-8 years. Outcome measurement tools included monthly Global Behaviour Rating…

Three-dimensional image authentication scheme using sparse phase information in double random phase encoded integral imaging.

PubMed

Yi, Faliu; Jeoung, Yousun; Moon, Inkyu

2017-05-20

In recent years, many studies have focused on authentication of two-dimensional (2D) images using double random phase encryption techniques. However, there has been little research on three-dimensional (3D) imaging systems, such as integral imaging, for 3D image authentication. We propose a 3D image authentication scheme based on a double random phase integral imaging method. All of the 2D elemental images captured through integral imaging are encrypted with a double random phase encoding algorithm and only partial phase information is reserved. All the amplitude and other miscellaneous phase information in the encrypted elemental images is discarded. Nevertheless, we demonstrate that 3D images from integral imaging can be authenticated at different depths using a nonlinear correlation method. The proposed 3D image authentication algorithm can provide enhanced information security because the decrypted 2D elemental images from the sparse phase cannot be easily observed by the naked eye. Additionally, using sparse phase images without any amplitude information can greatly reduce data storage costs and aid in image compression and data transmission.

Randomized Trial of Long-Acting Sustained-Release Naltrexone Implant vs Oral Naltrexone or Placebo for Preventing Relapse to Opioid Dependence

PubMed Central

Krupitsky, Evgeny; Zvartau, Edwin; Blokhina, Elena; Verbitskaya, Elena; Wahlgren, Valentina; Tsoy-Podosenin, Marina; Bushara, Natalia; Burakov, Andrey; Masalov, Dmitry; Romanova, Tatyana; Tyurina, Arina; Palatkin, Vladimir; Slavina, Tatyana; Pecoraro, Anna; Woody, George E.

2013-01-01

Context Sustained-release naltrexone implants may improve outcomes of nonagonist treatment of opioid addiction. Objective To compare outcomes of naltrexone implants, oral naltrexone hydrochloride, and nonmedication treatment. Design Six-month double-blind, double-dummy, randomized trial. Setting Addiction treatment programs in St Petersburg, Russia. Participants Three hundred six opioid-addicted patients recently undergoing detoxification. Interventions Biweekly counseling and 1 of the following 3 treatments for 24 weeks: (1) 1000-mg naltrexone implant and oral placebo (NI+OP group; 102 patients); (2) placebo implant and 50-mg oral naltrexone hydrochloride (PI+ON group; 102 patients); or (3) placebo implant and oral placebo (PI+OP group; 102 patients). Main Outcome Measure Percentage of patients retained in treatment without relapse. Results By month 6, 54 of 102 patients in the NI+OP group (52.9%) remained in treatment without relapse compared with 16 of 102 patients in the PI+ON group (15.7%) (survival analysis, log-rank test, P<.001) and 11 of 102 patients in the PI+OP group (10.8%) (P<.001). The PI+ON vs PI+OP comparison showed a nonsignificant trend favoring the PI+ON group (P=.07). Counting missing test results as positive, the proportion of urine screening tests yielding negative results for opiates was 63.6% (95% CI, 60%-66%) for the NI+OP group; 42.7% (40%-45%) for the PI+ON group; and 34.1% (32%-37%) for the PI+OP group (P<.001, Fisher exact test, compared with the NI+OP group). Twelve wound infections occurred among 244 implantations (4.9%) in the NI+OP group, 2 among 181 (1.1%) in the PI+ON group, and 1 among 148 (0.7%) in the PI+OP group (P=.02). All events were in the first 2 weeks after implantation and resolved with antibiotic therapy. Four local-site reactions (redness and swelling) occurred in the second month after implantation in the NI+OP group (P=.12), and all resolved with antiallergy medication treatment. Other nonlocal-site adverse effects were reported in 8 of 886 visits (0.9%) in the NI+OP group, 4 of 522 visits (0.8%) in the PI+ON group, and 3 of 394 visits (0.8%) in the PI+ON group; all resolved and none were serious. No evidence of increased deaths from overdose after naltrexone treatment ended was found. Conclusions The implant is more effective than oral naltrexone or placebo. More patients in the NI+OP than in the other groups develop wound infections or local irritation, but none are serious and all resolve with treatment. PMID:22945623

Pharmacodynamic Comparison of Prasugrel Versus Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study.

PubMed

Franchi, Francesco; Rollini, Fabiana; Aggarwal, Niti; Hu, Jenny; Kureti, Megha; Durairaj, Ashwin; Duarte, Valeria E; Cho, Jung Rae; Been, Latonya; Zenni, Martin M; Bass, Theodore A; Angiolillo, Dominick J

2016-09-13

Patients with diabetes mellitus (DM) are at increased risk of atherothrombotic events, underscoring the importance of effective platelet inhibiting therapies. Prasugrel and ticagrelor reduce thrombotic complications to a greater extent than clopidogrel. Subgroup analyses of pivotal clinical trials testing prasugrel and ticagrelor versus clopidogrel showed DM patients to have benefits that were consistent with the overall trial populations, although the magnitude of the ischemic risk reduction appeared to be enhanced with prasugrel. Whether these findings may be attributed to differences in the pharmacodynamic profiles of these drugs in DM patients remains poorly explored and represented the aim of this study. In this prospective, randomized, double-blind, double-dummy, crossover pharmacodynamic study, aspirin-treated DM patients (n=50) with coronary artery disease were randomly assigned to receive prasugrel (60 mg loading dose [LD]/10 mg maintenance dose once daily) or ticagrelor (180 mg LD/90 mg maintenance dose twice daily) for 1 week. Pharmacodynamic assessments were conducted using 4 different assays, including VerifyNow P2Y12, vasodilator-stimulated phosphoprotein, light transmittance aggregometry, and Multiplate, which allowed us to explore ADP- and non-ADP-induced (arachidonic acid-, collagen-, thrombin receptor-activating, peptide-induced) platelet signaling pathways. The acute (baseline, 30 minutes, and 2 hours post-LD) and maintenance (1 week) effects of therapy were assessed. The primary end point of the study was the comparison of P2Y12 reaction units determined by VerifyNow P2Y12 at 1 week between prasugrel and ticagrelor. ADP- and non-ADP-induced measures of platelet reactivity reduced significantly with both prasugrel and ticagrelor LD and maintenance dose. P2Y12 reaction units defined by VerifyNow were similar between prasugrel and ticagrelor at 30 minutes and 2 hours post-LD. At 1 week, P2Y12 reaction units were significantly lower with ticagrelor than with prasugrel (52 [32-72] versus 83 [63-103]; least-square means difference: -31; 95% confidence interval, -57 to -4; P=0.022; primary end point). Pharmacodynamic assessments measured by vasodilator-stimulated phosphoprotein, light transmittance aggregometry, and Multiplate were similar between prasugrel and ticagrelor at each time point, including at 1 week. Rates of high on-treatment platelet reactivity were similar between groups with all assays at all time points. In DM patients with coronary artery disease, ticagrelor exerts similar or greater inhibition of ADP-induced platelet reactivity in comparison with prasugrel in the acute and chronic phases of treatment, whereas the inhibition of measures of non-ADP-induced platelet reactivity was not significantly different between the 2 agents. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01852214. © 2016 American Heart Association, Inc.

Pharmacokinetics and therapeutic effect of OROS methylphenidate under different breakfast conditions in children with attention-deficit/hyperactivity disorder.

PubMed

Wigal, Sharon B; Gupta, Suneel; Heverin, Erica; Starr, H Lynn

2011-06-01

To examine the pharmacokinetics (PKs) and pharmacodynamics (PDs) of OROS methylphenidate (OROS MPH) dosed once daily (QD) versus an early standard regimen (immediate-release [IR] MPH dosed three times daily [TID]) under various breakfast conditions. This single-center, double-blind, double-dummy, randomized, crossover study of OROS MPH (NCT00269815) in children aged 6 to 12 years with attention-deficit/hyperactivity disorder evaluated the PKs and PDs of MPH given with different breakfast conditions: OROS MPH administered after a high-fat breakfast, after a normal breakfast, or after fasting and IR MPH administered after a normal breakfast or after fasting in the morning and at two subsequent time points during the day. To maximize information, patients were divided into two groups, each receiving three of the five treatments for 1 day in a three-period, randomized, crossover design. Patients were assigned to 1 of 3 dosage levels (OROS MPH 18, 36, and 54 mg QD, and an assumed equivalent regimen of IR MPH 5, 10, and 15 mg given TID) based on their prestudy established clinical dose of IR MPH. PD measurements included Combined-Attention and Deportment scores on a rating scale of school behavior (the Swanson, Kotkin, Agler, M-Flynn, and Pelham), global assessments of efficacy, and activity monitor levels during academic seatwork. Serial blood samples for PK analysis were taken predose, and then every 60 to 90 minutes until 11.5 hours postdose. Vital signs were assessed predose, and then every 1.5 to 2.5 hours until 11.5 hours postdose. Of the 32 patients enrolled, 31 completed the study. The PK profiles for MPH after OROS MPH administration were similar under all conditions (with normal, high-fat breakfast, or fasting). No bioequivalence tests of OROS MPH and IR MPH under various breakfast conditions were done because there were so few patients in each dose level of treatment. The two IR MPH conditions (after normal breakfast and fasting) were not compared. The drug-to-metabolite ratios (area under the curve) for all OROS MPH and IR MPH treatments were similar. OROS MPH and IR MPH provided a similar therapeutic effect, irrespective of breakfast conditions, as demonstrated by the Swanson, Kotkin, Agler, M-Flynn, and Pelham Attention and Deportment measures and global assessments. No serious adverse events, no deaths, and no clinically significant changes in vital signs were reported, except for one patient who was discontinued early because of repeated systolic blood pressure elevations on study day 1. The results of this study demonstrate that in children with attention-deficit/hyperactivity disorder, administering OROS MPH with or without food produces similar PK and PD profiles.

Anthropometric specifications, development, and evaluation of EvaRID--a 50th percentile female rear impact finite element dummy model.

PubMed

Carlsson, Anna; Chang, Fred; Lemmen, Paul; Kullgren, Anders; Schmitt, Kai-Uwe; Linder, Astrid; Svensson, Mats Y

2014-01-01

Whiplash-associated disorders (WADs), or whiplash injuries, due to low-severity vehicle crashes are of great concern in motorized countries and it is well established that the risk of such injuries is higher for females than for males, even in similar crash conditions. Recent protective systems have been shown to be more beneficial for males than for females. Hence, there is a need for improved tools to address female WAD prevention when developing and evaluating the performance of whiplash protection systems. The objective of this study is to develop and evaluate a finite element model of a 50th percentile female rear impact crash test dummy. The anthropometry of the 50th percentile female was specified based on literature data. The model, called EvaRID (female rear impact dummy), was based on the same design concept as the existing 50th percentile male rear impact dummy, the BioRID II. A scaling approach was developed and the first version, EvaRID V1.0, was implemented. Its dynamic response was compared to female volunteer data from rear impact sled tests. The EvaRID V1.0 model and the volunteer tests compared well until ∼250 ms of the head and T1 forward accelerations and rearward linear displacements and of the head rearward angular displacement. Markedly less T1 rearward angular displacement was found for the EvaRID model compared to the female volunteers. Similar results were received for the BioRID II model when comparing simulated responses with experimental data under volunteer loading conditions. The results indicate that the biofidelity of the EvaRID V1.0 and BioRID II FE models have limitations, predominantly in the T1 rearward angular displacement, at low velocity changes (7 km/h). The BioRID II model was validated against dummy test results in a loading range close to consumer test conditions (EuroNCAP) and lower severity levels of volunteer testing were not considered. The EvaRID dummy model demonstrated the potential of becoming a valuable tool when evaluating and developing seats and whiplash protection systems. However, updates of the joint stiffness will be required to provide better correlation at lower load levels. Moreover, the seated posture, curvature of the spine, and head position of 50th percentile female occupants needs to be established and implemented in future models.

Selective isolation of gonyautoxins 1,4 from the dinoflagellate Alexandrium minutum based on molecularly imprinted solid-phase extraction.

PubMed

Lian, Ziru; Wang, Jiangtao

2017-09-15

Gonyautoxins 1,4 (GTX1,4) from Alexandrium minutum samples were isolated selectively and recognized specifically by an innovative and effective extraction procedure based on molecular imprinting technology. Novel molecularly imprinted polymer microspheres (MIPMs) were prepared by double-templated imprinting strategy using caffeine and pentoxifylline as dummy templates. The synthesized polymers displayed good affinity to GTX1,4 and were applied as sorbents. Further, an off-line molecularly imprinted solid-phase extraction (MISPE) protocol was optimized and an effective approach based on the MISPE coupled with HPLC-FLD was developed for selective isolation of GTX1,4 from the cultured A. minutum samples. The separation method showed good extraction efficiency (73.2-81.5%) for GTX1,4 and efficient removal of interferences matrices was also achieved after the MISPE process for the microalgal samples. The outcome demonstrated the superiority and great potential of the MISPE procedure for direct separation of GTX1,4 from marine microalgal extracts. Copyright © 2017. Published by Elsevier Ltd.

[Comparative effects of ginkgo biloba extracts on psychomotor performances and memory in healthy subjects].

PubMed

Warot, D; Lacomblez, L; Danjou, P; Weiller, E; Payan, C; Puech, A J

1991-01-01

The effect on psychomotor and mnesic performances of acute oral dose (600 mg) of 2 Ginkgo biloba extracts were evaluated in twelve healthy female in a dummy placebo-controlled double blind study. Tests were performed comprising: objective measures of vigilance [critical flicker frequency (CFF), choice reaction time (CRT)], memory tasks (pictures and Sternberg scanning tests) and self-rating evaluation (visual analogue scales). Tests session took place before and 1 hour post-dosing. No statistically significant changes from placebo were observed on CFF, CRT or subjective rating of drug effects. No differences between treatment were evidenced on Sternberg scanning test and pictures recognition. Comparing to baseline, free recall score, while decreasing under placebo and Ginkgo, remained the same under Tanakan. As the differences between treatment are localized on one test, it appears important to examine the reproductility in healthy subjects. In order to verify the clinical relevance of these results, they need to be replicated in older healthy volunteers with age-associated memory impairment.

Short-term outcomes of local infiltration anaesthetic in total knee arthroplasty: a randomized controlled double-blinded controlled trial.

PubMed

Mulford, Jonathan S; Watson, Anna; Broe, David; Solomon, Michael; Loefler, Andreas; Harris, Ian

2016-03-01

The primary objective of the study was to determine if local infiltration anaesthetic (LIA) reduced total length of hospital stay in total knee arthroplasty (TKA) patients. The study also examined whether LIA improves early pain management, patient satisfaction and range of motion in TKA patients. We conducted a randomized controlled double-blinded study. Fifty patients undergoing TKA were randomized to receive either placebo or LIA at the time of surgery and on the first day post-operatively. Pain scores, level of satisfaction and range of motion were recorded preoperatively and post-operatively. There was no statistical difference between the groups for length of stay, post-operative pain scores, satisfaction scores or range of motion 6 weeks post-operatively. This randomized double-blinded trial did not demonstrate a decrease in pain or reduction of length of stay due to local infiltration analgesia. © 2015 Royal Australasian College of Surgeons.

Effect of Atomoxetine on Executive Function Impairments in Adults with ADHD

ERIC Educational Resources Information Center

Brown, Thomas E.; Holdnack, James; Saylor, Keith; Adler, Lenard; Spencer, Thomas; Williams, David W.; Padival, Anoop K.; Schuh, Kory; Trzepacz, Paula T.; Kelsey, Douglas

2011-01-01

Objective: To assess the effect of atomoxetine on ADHD-related executive functions over a 6-month period using the Brown Attention-Deficit Disorder Scale (BADDS) for Adults, a normed, 40-item, self-report scale in a randomized, double-blind, placebo-controlled clinical trial. Method: In a randomized, double-blind clinical trial, adults with ADHD…

A Double-Blind, Randomized, Placebo-Controlled Trial of Escitalopram in the Treatment of Pediatric Depression

ERIC Educational Resources Information Center

Wagner, Karen Dineen; Jonas, Jeffrey; Findling, Robert L.; Ventura, Daniel; Saikali, Khalil

2006-01-01

Objective: Escitalopram is a selective serotonin reuptake inhibitor antidepressant indicated for use in adults. This trial examined the efficacy and safety of escitalopram in pediatric depression. Method: Patients (6-17 years old) with major depressive disorder were randomized to receive 8 weeks of double-blind flexibly dosed treatment with…

An Investigation of Technologies for Hazardous Sludge Reduction at AFLC (Air Force Logistics Command) Industrial Waste Treatment Plants. Volume 2. Literature Review of Available Technologies for Treating Heavy Metal Wastewaters.

DTIC Science & Technology

1983-12-01

plate quality. Dummying of chromium baths is used in the special case where high cathode-to-anode 15ea ratio has resulted in build up of trivalent ... chromium (Cr ).Dummying with a high anode -to-cat hode area ratio can be used to reoxidize the trivalent to hexavalent chromium (Cr +6 ). Proper...the trivalent state, which then can be precipitated as chromium hydroxide by alkali neutralization " Cyanide oxidation (if needed) of segregated

NASA general aviation crashworthiness seat development

NASA Technical Reports Server (NTRS)

Fasanella, E. L.; Alfaro-Bou, E.

1979-01-01

Three load limiting seat concepts for general aviation aircraft designed to lower the deceleration of the occupant in the event of a crash were sled tested and evaluated with reference to a standard seat. Dummy pelvis accelerations were reduced up to 50 percent with one of the concepts. Computer program MSOMLA (Modified Seat Occupant Model for Light Aircraft) was used to simulate the behavior of a dummy passenger in a NASA full-scale crash test of a twin engine light aircraft. A computer graphics package MANPLOT was developed to pictorially represent the occupant and seat motion.

Does EEG-Neurofeedback Improve Neurocognitive Functioning in Children with Attention-Deficit/Hyperactivity Disorder? A Systematic Review and a Double-Blind Placebo-Controlled Study

ERIC Educational Resources Information Center

Vollebregt, Madelon A.; van Dongen-Boomsma, Martine; Buitelaar, Jan K.; Slaats-Willemse, Dorine

2014-01-01

Background: The number of placebo-controlled randomized studies relating to EEG-neurofeedback and its effect on neurocognition in attention-deficient/hyperactivity disorder (ADHD) is limited. For this reason, a double blind, randomized, placebo-controlled study was designed to assess the effects of EEG-neurofeedback on neurocognitive functioning…

Intrathecal Baclofen in Children with Spastic Cerebral Palsy: A Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study

ERIC Educational Resources Information Center

Hoving, Marjanke A.; van Raak, Elisabeth P. M.; Spincemaille, Geert H. J. J.; Palmans, Liesbeth J.; Sleypen, Frans A. M.; Vles, Johan S. H.

2007-01-01

Intrathecal baclofen (ITB) therapy can be very effective in the treatment of intractable spasticity, but its effectiveness and safety have not yet been thoroughly studied in children with cerebral palsy (CP). The aims of this double-blind, randomized, placebo-controlled, dose-finding study were to select children eligible for continuous ITB…

A Double-Blind Randomized Pilot Study Comparing Quetiapine and Divalproex for Adolescent Mania

ERIC Educational Resources Information Center

Delbello, Melissa P.; Kowatch, Robert A.; Adler, Caleb M.; Stanford, Kevin E.; Welge, Jeffrey A.; Barzman, Drew H.; Nelson, Erik; Strakowski, Stephen M.

2006-01-01

Objective: To determine the comparative efficacy of quetiapine and divalproex for the treatment of adolescent mania. Method: Fifty adolescents (ages 12-18 years) with bipolar I disorder, manic or mixed episode, were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 [micro]g/mL) for 28 days for this double-blind study,…

Tolerability of extended-release quetiapine fumarate compared with immediate-release quetiapine fumarate in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation: a randomised, double-blind, parallel-group study.

PubMed

De Deyn, Peter Paul; Eriksson, Hans; Svensson, Hanna

2012-03-01

The objective of this study was to assess the safety and tolerability of extended-release quetiapine fumarate (quetiapine XR) compared with quetiapine immediate-release (quetiapine IR) in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation. This was a 6-week, double-blind, double-dummy, randomised study. Of the 109 patients screened, 100 were randomised to receive quetiapine XR (n = 68) or quetiapine IR (n = 32), at doses of 50 and 25 mg/day, respectively. Treatment was escalated to 100 mg/day by Day 4. At Day 8, a flexible-dose (50-300 mg/day) period began when dose adjustment was made at the investigator's discretion. The primary variable was incidence and type of adverse events (AEs). Secondary variables included efficacy and other safety assessments. Mean daily doses were 143.6 and 142.0 mg in the quetiapine XR and quetiapine IR groups, respectively. Ninety patients completed the study; only one withdrew (in the quetiapine XR group) because of an AE. Laboratory evaluations identified severe neutropaenia (one patient), mild neutropaenia (three patients) and eosinophilia (five patients); however, these were not reported, as AEs and confounding factors, such as patient age, concomitant illness and medication, made it difficult to determine any relationship to quetiapine treatment. Numerical improvements from baseline were seen across both treatment groups in Neuropsychiatric Inventory frequency × severity total, Neuropsychiatric Inventory-Nursing Home version, Cohen-Mansfield Agitation Inventory, Clinical Global Impression-Severity of Illness and Clinical Global Impression-Improvement scores. Quetiapine XR dosed up to 300 mg/day was generally well tolerated, with a similar profile to that of quetiapine IR. Copyright © 2011 John Wiley & Sons, Ltd.

Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain.

PubMed

Moore, R Andrew; Gay-Escoda, C; Figueiredo, R; Tóth-Bagi, Z; Dietrich, T; Milleri, S; Torres-Lagares, D; Hill, C M; García-García, A; Coulthard, P; Wojtowicz, A; Matenko, D; Peñarrocha-Diago, M; Cuadripani, S; Pizà-Vallespir, B; Guerrero-Bayón, C; Bertolotti, M; Contini, M P; Scartoni, S; Nizzardo, A; Capriati, A; Maggi, C A

2015-01-01

Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective. This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours. 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72%) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95% confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable. Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae. EudraCT (2010-022798-32); Clinicaltrials.gov (NCT01307020).

Rabeprazole is equivalent to omeprazole in the treatment of erosive gastro-oesophageal reflux disease. A randomised, double-blind, comparative study of rabeprazole and omeprazole 20 mg in acute treatment of reflux oesophagitis, followed by a maintenance open-label, low-dose therapy with rabeprazole.

PubMed

Pace, F; Annese, V; Prada, A; Zambelli, A; Casalini, S; Nardini, P; Bianchi Porro, G

2005-10-01

Previous studies have shown similar effects of rabeprazole and omeprazole, when used at the same dose in the treatment of reflux oesophagitis. However, such studies have been conducted as superiority studies but interpreted as equivalence ones. To properly assess the comparative efficacy of rabeprazole and omeprazole in inducing complete endoscopic healing and symptom relief in patients with reflux oesophagitis. Patients (n=560) with Savary-Miller grade I-III reflux oesophagitis were randomised in a double-blind, double-dummy fashion to rabeprazole or omeprazole 20 mg once daily for 4-8 weeks. Then, patients endoscopically healed and symptomatically relieved were openly maintained with rabeprazole 10 mg or 2x10 mg once daily (in the event of clinical and/or endoscopic relapse) for a maximum of 48 weeks. After 4-8 weeks of treatment, healing (primary end-point) was observed in 228/233 (97.9%) patients in the rabeprazole group and in 231/237 (97.5%) in the omeprazole one (equivalence effect demonstrated by p<0.0001 at Blackwelder test and an upper confidence limit at 97.5% of 0.023). However, rabeprazole was faster in inducing heartburn relief than omeprazole (2.8+/-0.2 versus 4.7+/-0.5 days of therapy to reach the first day with satisfactory heartburn relief, p=0.0045 at log-rank test). In the maintenance phase, 15.2% of patients had an endoscopic and/or clinical relapse. Rabeprazole is equivalent to omeprazole in healing reflux oesophagitis, but shows a faster activity on reflux symptoms in the early treatment phase.

Sublingual ketorolac versus sublingual tramadol for moderate to severe post-traumatic bone pain in children: a double-blind, randomised, controlled trial.

PubMed

Neri, Elena; Maestro, Alessandra; Minen, Federico; Montico, Marcella; Ronfani, Luca; Zanon, Davide; Favret, Anna; Messi, Gianni; Barbi, Egidio

2013-09-01

To assess the effectiveness of sublingual ketorolac versus sublingual tramadol in reducing the pain associated with fracture or dislocation of extremities in children. A double-blind, randomised, controlled, non-inferiority trial was conducted in the paediatric emergency department of a research institute. One hundred and thirty-one children aged 4-17 years with suspected bone fracture or dislocation were enrolled. Eligible children were randomised to ketorolac (0.5 mg/kg) and placebo, or to tramadol (2 mg/kg) and placebo by sublingual administration, using a double-dummy technique. Pain was assessed by the patients every 20 min, for a maximum period of 2 h, using the McGrath scale for patients up to 6 years of age, and the Visual Analogue Scale for those older than 6 years of age. The mean pain scores fell significantly from eight to four and five in the ketorolac and tramadol groups, respectively, by 100 min (Wilcoxon sign rank test, p<0.001). The mean pain scores for ketorolac were lower than those for tramadol, but these differences were not significant at any time point (Mann-Whitney U Test, p values: 0-20 min: 0.167; 20-40 min: 0.314; 40-60 min: 0.223; 60-80 min: 0.348; 80-100 min: 0.166; 100-120 min: 0.08). The rescue dose of paracetamol-codeine was administered in 2/60 children in the ketorolac group versus 8/65 in the tramadol group (Fisher exact test, p=0.098). There were no statistically significant differences between the two groups in the frequency of adverse effects. Both sublingual ketorolac and tramadol were equally effective for pain management in children with suspected fractures or dislocations.

Encoding plaintext by Fourier transform hologram in double random phase encoding using fingerprint keys

NASA Astrophysics Data System (ADS)

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

2012-09-01

It has been shown that biometric information can be used as a cipher key for binary data encryption by applying double random phase encoding. In such methods, binary data are encoded in a bit pattern image, and the decrypted image becomes a plain image when the key is genuine; otherwise, decrypted images become random images. In some cases, images decrypted by imposters may not be fully random, such that the blurred bit pattern can be partially observed. In this paper, we propose a novel bit coding method based on a Fourier transform hologram, which makes images decrypted by imposters more random. Computer experiments confirm that the method increases the randomness of images decrypted by imposters while keeping the false rejection rate as low as in the conventional method.

Application of a dummy eye shield for electron treatment planning

PubMed Central

Kang, Sei-Kwon; Park, Soah; Hwang, Taejin; Cheong, Kwang-Ho; Han, Taejin; Kim, Haeyoung; Lee, Me-Yeon; Kim, Kyoung Ju; Oh, Do Hoon; Bae, Hoonsik

2013-01-01

Metallic eye shields have been widely used for near-eye treatments to protect critical regions, but have never been incorporated into treatment plans because of the unwanted appearance of the metal artifacts on CT images. The purpose of this work was to test the use of an acrylic dummy eye shield as a substitute for a metallic eye shield during CT scans. An acrylic dummy shield of the same size as the tungsten eye shield was machined and CT scanned. The BEAMnrc and the DOSXYZnrc were used for the Monte Carlo (MC) simulation, with the appropriate material information and density for the aluminum cover, steel knob and tungsten body of the eye shield. The Pinnacle adopting the Hogstrom electron pencil-beam algorithm was used for the one-port 6-MeV beam plan after delineation and density override of the metallic parts. The results were confirmed with the metal oxide semiconductor field effect transistor (MOSFET) detectors and the Gafchromic EBT2 film measurements. For both the maximum eyelid dose over the shield and the maximum dose under the shield, the MC results agreed with the EBT2 measurements within 1.7%. For the Pinnacle plan, the maximum dose under the shield agreed with the MC within 0.3%; however, the eyelid dose differed by –19.3%. The adoption of the acrylic dummy eye shield was successful for the treatment plan. However, the Pinnacle pencil-beam algorithm was not sufficient to predict the eyelid dose on the tungsten shield, and more accurate algorithms like MC should be considered for a treatment plan. PMID:22915776

Layout finishing of a 28nm, 3 billions transistors, multi-core processor

NASA Astrophysics Data System (ADS)

Morey-Chaisemartin, Philippe; Beisser, Eric

2013-06-01

Designing a fully new 256 cores processor is a great challenge for a fabless startup. In addition to all architecture, functionalities and timing issues, the layout by itself is a bottleneck due to all the process constraints of a 28nm technology. As developers of advanced layout finishing solutions, we were involved in the design flow of this huge chip with its 3 billions transistors. We had to face the issue of dummy patterns instantiation with respect to design constraints. All the design rules to generate the "dummies" are clearly defined in the Design Rule Manual, and some automatic procedures are provided by the foundry itself, but these routines don't take care of the designer requests. Such a chip, embeds both digital parts and analog modules for clock and power management. These two different type of designs have each their own set of constraints. In both cases, the insertion of dummies should not introduce unexpected variations leading to malfunctions. For example, on digital parts were signal race conditions are critical on long wires or bus, introduction of uncontrolled parasitic along these nets are highly critical. For analog devices such as high frequency and high sensitivity comparators, the exact symmetry of the two parts of a current mirror generator should be guaranteed. Thanks to the easily customizable features of our dummies insertion tool, we were able to configure it in order to meet all the designer requirements as well as the process constraints. This paper will present all these advanced key features as well as the layout tricks used to fulfill all requirements.

Is metabolic dysregulation associated with antidepressant response in depressed women in climacteric treated with individualized homeopathic medicines or fluoxetine? The HOMDEP-MENOP Study.

PubMed

Macías-Cortés, Emma Del Carmen; Llanes-González, Lidia; Aguilar-Faisal, Leopoldo; Asbun-Bojalil, Juan

2017-02-01

Climacteric is associated with both depression and metabolic dysregulation. Scarce evidence suggests that metabolic dysregulation may predict poor response to conventional antidepressants. Response to depression treatment has not been studied in homeopathic medicine. The aim of this study was to investigate the prevalence of metabolic disorders in depressed climacteric women treated with homeopathic medicines, fluoxetine or placebo, and if these alterations have any association with response to depression treatment. One hundred and thirty-three Mexican women (40-65 years) with depression, enrolled in the HOMDEP-MENOP study, a randomized, placebo-controlled, double-blind, double-dummy, three-arm trial with a 6 week follow-up, underwent a complete medical history and clinical examination. Metabolic parameters were assessed at baseline. Association between baseline metabolic parameters and response to depression treatment was analyzed with bivariate analysis in the three groups. Odds ratios (OR) with their 95% confidence interval (95% CI) were calculated. Metabolic parameters were considered for inclusion in the logistic regression model if they had a statistically significant relationship with response rate on bivariate analysis at p<0.05 or if they were clinically relevant. Overall combined prevalence (obesity and overweight) was 86.5%; 52.3% had hypertriglyceridemia; 44.7% hypercholesterolemia; 46.7% insulin resistance; and 16% subclinical hypothyroidism. There was no statistically significant association between dyslipidemia, overweight, or insulin resistance and non-response in the homeopathy group [OR (95% CI) 1.57 (0.46-5.32), p=0.467; 0.37 (0.003-1.11), p=0.059; 0.67 (0.16-2.7), p=0.579, respectively]. Metabolic dysregulation was not significantly associated with response to depression treatment in depressed climacteric women treated with individualized homeopathic treatment (IHT), fluoxetine or placebo. Due to the high prevalence of metabolic disorders and its relationship with depression in the climacteric, further investigation should be focused on whether individualized prescriptions based on classical homeopathy for depressed climacteric women have an effect on metabolic parameters, and/or if treating the metabolic disorders at the same time could lead to higher response rates. ClinicalTrials.gov Identifier: NCT01635218 URL: http://clinicaltrials.gov/ct2/show/NCT01635218?term=depression+homeopathy&rank=1. Copyright © 2016 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Mepolizumab treatment in patients with severe eosinophilic asthma.

PubMed

Ortega, Hector G; Liu, Mark C; Pavord, Ian D; Brusselle, Guy G; FitzGerald, J Mark; Chetta, Alfredo; Humbert, Marc; Katz, Lynn E; Keene, Oliver N; Yancey, Steven W; Chanez, Pascal

2014-09-25

Some patients with severe asthma have frequent exacerbations associated with persistent eosinophilic inflammation despite continuous treatment with high-dose inhaled glucocorticoids with or without oral glucocorticoids. In this randomized, double-blind, double-dummy study, we assigned 576 patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled glucocorticoids to one of three study groups. Patients were assigned to receive mepolizumab, a humanized monoclonal antibody against interleukin-5, which was administered as either a 75-mg intravenous dose or a 100-mg subcutaneous dose, or placebo every 4 weeks for 32 weeks. The primary outcome was the rate of exacerbations. Other outcomes included the forced expiratory volume in 1 second (FEV1) and scores on the St. George's Respiratory Questionnaire (SGRQ) and the 5-item Asthma Control Questionnaire (ACQ-5). Safety was also assessed. The rate of exacerbations was reduced by 47% (95% confidence interval [CI], 29 to 61) among patients receiving intravenous mepolizumab and by 53% (95% CI, 37 to 65) among those receiving subcutaneous mepolizumab, as compared with those receiving placebo (P<0.001 for both comparisons). Exacerbations necessitating an emergency department visit or hospitalization were reduced by 32% in the group receiving intravenous mepolizumab and by 61% in the group receiving subcutaneous mepolizumab. At week 32, the mean increase from baseline in FEV1 was 100 ml greater in patients receiving intravenous mepolizumab than in those receiving placebo (P=0.02) and 98 ml greater in patients receiving subcutaneous mepolizumab than in those receiving placebo (P=0.03). The improvement from baseline in the SGRQ score was 6.4 points and 7.0 points greater in the intravenous and subcutaneous mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 4 points), and the improvement in the ACQ-5 score was 0.42 points and 0.44 points greater in the two mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 0.5 points) (P<0.001 for all comparisons). The safety profile of mepolizumab was similar to that of placebo. Mepolizumab administered either intravenously or subcutaneously significantly reduced asthma exacerbations and was associated with improvements in markers of asthma control. (Funded by GlaxoSmithKline; MENSA ClinicalTrials.gov number, NCT01691521.).

Efficacy and tolerance of lysine clonixinate versus paracetamol/codeine following inguinal hernioplasty.

PubMed

de los Santos, A R; Di Girolamo, G; Martí, M L

1998-01-01

In this study lysine clonixinate, a nonsteroidal antiinflammatory agent with selective inhibition of cyclooxygenase-2 and 5-lipooxygenase in in vitro and in vivo pharmacodynamic studies, was evaluated in a prospective, randomized, double-blind, double-dummy clinical study versus paracetamol/codeine, in 151 patients with pain following inguinal hernioplasty. Patients were treated with one 125 mg tablet of lysine clonixinate or paracetamol/codeine (500 mg + 30 mg) administered at fixed doses every 4 h during 2 days. Controls were carried out 1, 2 and 4 h after the first intake of day 1 and day 2. Each control included assessment of pain at rest, when coughing, sitting and upon moderate pressure. Both treatment groups (lysine clonixinate, 77 patients and paracetamol/codeine, 74 patients) were comparable in terms of demographic and baseline pain intensities. Spontaneous pain was reduced significantly in both treatment groups from the 1st-h control. The following values were recorded in the lysine clonixinate group during day 1: baseline: 6.86 +/- 1.24; 1st h: 4.49 +/- 1.77; 2nd h: 2.96 +/- 1.74; 4th h: 2.23 +/- 1.51. The following values for the same group during day 2 were: predose: 1.70 +/- 1.64; 1st h: 1.16 +/- 1.17; 2nd h: 0.78 +/- 1.06; 4th h: 0.63 +/- 1.05. The paracetamol/codeine group revealed the following values: day 1: baseline: 6.72 +/- 1.22; 1st h: 4.57 +/- 1.72; 2nd h: 2.97 +/- 1.68; 4th h: 2.47 +/- 1.68 and day 2: predose: 2.02 +/- 1.57; 1st h: 1.32 +/- 1.23; 2nd h: 0.82 +/- 0.99; 4th h: 0.66 +/- 0.89. Reduction of pain induced by coughing, sitting and pressure showed similar behavior patterns. No significant differences between both treatment groups were encountered in terms of analgesic efficacy. Incidence of adverse effects was significantly higher in the paracetamol/codeine group (X2: p < 0.05): 11 out of 74 patients; three patients had to discontinue treatment. In the lysine clonixinate group four out of 77 patients showed side effects but these did not require treatment discontinuation.

A Low-Cost Hand Trainer Device Based On Microcontroller Platform

NASA Astrophysics Data System (ADS)

Sabor, Muhammad Akmal Mohammad; Thamrin, Norashikin M.

2018-03-01

Conventionally, the rehabilitation equipment used in the hospital or recovery center to treat and train the muscle of the stroke patient is implementing the pneumatic or compressed air machine. The main problem caused by this equipment is that the arrangement of the machine is quite complex and the position of it has been locked and fixed, which can cause uncomfortable feeling to the patients throughout the recovery session. Furthermore, the harsh movement from the machine could harm the patient as it does not allow flexibility movement and the use of pneumatic actuator has increased the gripping force towards the patient which could hurt them. Therefore, the main aim of this paper is to propose the development of the Bionic Hand Trainer based on Arduino platform, for a low-cost solution for rehabilitation machine as well as allows flexibility and smooth hand movement for the patients during the healing process. The scope of this work is to replicate the structure of the hand only at the fingers structure that is the phalanges part, which inclusive the proximal, intermediate and distal of the fingers. In order to do this, a hand glove is designed by equipping with flex sensors at every finger and connected them to the Arduino platform. The movement of the hand will motorize the movement of the dummy hand that has been controlled by the servo motors, which have been equipped along the phalanges part. As a result, the bending flex sensors due to the movement of the fingers has doubled up the rotation of the servo motors to mimic this movement at the dummy hand. The voltage output from the bending sensors are ranging from 0 volt to 5 volts, which are suitable for low-cost hand trainer device implementation. Through this system, the patient will have the power to control their gripping operation slowly without having a painful force from the external actuators throughout the rehabilitation process.

Personal messages reduce vandalism and theft of unattended scientific equipment

PubMed Central

Clarin, B-Markus; Bitzilekis, Eleftherios; Siemers, Björn M; Goerlitz, Holger R

2014-01-01

Scientific equipment, such as animal traps and autonomous data collection systems, is regularly left in the field unattended, making it an easy target for vandalism or theft. We tested the effectiveness of three label types, which differed in their information content and tone of the message, that is, personal,neutral or threatening, for reducing incidents of vandalism and theft of unattended scientific field equipment. The three label types were attached to 20 scientific equipment dummies each, which were placed semi-hidden and evenly distributed in four public parks in Munich, Germany. While the label type had no effect on the severity of the interactions with our equipment dummies, the personal label reduced the overall number of interactions by c. 40–60%, compared with the dummies showing the neutral or threatening label type. We suggest that researchers, in addition to securing their field equipment, label it with personal and polite messages that inform about the ongoing research and directly appeal to the public not to disturb the equipment. Further studies should extend these results to areas with different socio-economic structure. PMID:25866614

The sight of an adult brood parasite near the nest is an insufficient cue for a honeyguide host to reject foreign eggs.

PubMed

Tong, Wenfei; Horrocks, Nicholas P C; Spottiswoode, Claire N

2015-07-01

Hosts of brood-parasitic birds typically evolve anti-parasitism defences, including mobbing of parasitic intruders at the nest and the ability to recognize and reject foreign eggs from their clutches. The Greater Honeyguide Indicator indicator is a virulent brood parasite that punctures host eggs and kills host young, and accordingly, a common host, the Little Bee-eater Merops pusillus frequently rejects entire clutches that have been parasitized. We predicted that given the high costs of accidentally rejecting an entire clutch, and that the experimental addition of a foreign egg is insufficient to induce this defence, Bee-eaters require the sight of an adult parasite near the nest as an additional cue for parasitism before they reject a clutch. We found that many Little Bee-eater parents mobbed Greater Honeyguide dummies while ignoring barbet control dummies, showing that they recognized them as a threat. Surprisingly, however, neither a dummy Honeyguide nor the presence of a foreign egg, either separately or in combination, was sufficient to stimulate egg rejection.

The sight of an adult brood parasite near the nest is an insufficient cue for a honeyguide host to reject foreign eggs

PubMed Central

Tong, Wenfei; Horrocks, Nicholas P C; Spottiswoode, Claire N

2015-01-01

Hosts of brood-parasitic birds typically evolve anti-parasitism defences, including mobbing of parasitic intruders at the nest and the ability to recognize and reject foreign eggs from their clutches. The Greater Honeyguide Indicator indicator is a virulent brood parasite that punctures host eggs and kills host young, and accordingly, a common host, the Little Bee-eater Merops pusillus frequently rejects entire clutches that have been parasitized. We predicted that given the high costs of accidentally rejecting an entire clutch, and that the experimental addition of a foreign egg is insufficient to induce this defence, Bee-eaters require the sight of an adult parasite near the nest as an additional cue for parasitism before they reject a clutch. We found that many Little Bee-eater parents mobbed Greater Honeyguide dummies while ignoring barbet control dummies, showing that they recognized them as a threat. Surprisingly, however, neither a dummy Honeyguide nor the presence of a foreign egg, either separately or in combination, was sufficient to stimulate egg rejection. PMID:26300559

Nestmate recognition in social wasps: manipulation of hydrocarbon profiles induces aggression in the European hornet

NASA Astrophysics Data System (ADS)

Ruther, Joachim; Sieben, Stefan; Schricker, Burkhard

2002-03-01

The influence of individual cuticular hydrocarbons on nestmate recognition in the European hornet, Vespa crabro L., was investigated. We observed the behavioural response of workers towards differently treated dead conspecifics in a bioassay. Dummies were extracted with dichloromethane and extracts were spiked with microgram amounts of synthetic hydrocarbons naturally occurring on the cuticle of V. crabro. These modified extracts were reapplied to extracted workers that were subsequently tested in the bioassay. Non-spiked nestmate dummies (negative control) and untreated non-nestmate dummies (positive control) were tested in control experiments. The addition of only heneicosane or a mixture of heneicosane, tricosane, and ( Z)-9-tricosene to the extracts led to a significant increase of agonistic behaviour in workers leaving the nest for foraging flights. Returning workers reacted much less aggressively than those leaving. This is one of the first behavioural proofs that manipulation of cuticular hydrocarbon profiles can be perceived by a social insect species. The results support the hypothesis that colony-specific cuticular hydrocarbon profiles are involved in the phenomenon of nestmate recognition among social insects.

Dispersive solid-phase extraction based on magnetic dummy molecularly imprinted microspheres for selective screening of phthalates in plastic bottled beverages.

PubMed

Qiao, Jindong; Wang, Mingyu; Yan, Hongyuan; Yang, Gengliang

2014-04-02

A new magnetic dummy molecularly imprinted dispersive solid-phase extraction (MAG-MIM-dSPE) coupled with gas chromatography-FID was developed for selective determination of phthalates in plastic bottled beverages. The new magnetic dummy molecularly imprinted microspheres (MAG-MIM) using diisononyl phthalate as a template mimic were synthesized by coprecipitation coupled with aqueous suspension polymerization and were successfully applied as the adsorbents for MAG-MIM-dSPE to extract and isolate five phthalates from plastic bottled beverages. Validation experiments showed that the MAG-MIM-dSPE method had good linearity at 0.0040-0.40 μg/mL (0.9991-0.9998), good precision (3.1-6.9%), and high recovery (89.5-101.3%), and limits of detection were obtained in a range of 0.53-1.2 μg/L. The presented MAG-MIM-dSPE method combines the quick separation of magnetic particles, special selectivity of MIM, and high extraction efficiency of dSPE, which could potentially be applied to selective screening of phthalates in beverage products.

Personal messages reduce vandalism and theft of unattended scientific equipment.

PubMed

Clarin, B-Markus; Bitzilekis, Eleftherios; Siemers, Björn M; Goerlitz, Holger R

2014-02-01

Scientific equipment, such as animal traps and autonomous data collection systems, is regularly left in the field unattended, making it an easy target for vandalism or theft. We tested the effectiveness of three label types, which differed in their information content and tone of the message, that is, personal , neutral or threatening , for reducing incidents of vandalism and theft of unattended scientific field equipment. The three label types were attached to 20 scientific equipment dummies each, which were placed semi-hidden and evenly distributed in four public parks in Munich, Germany. While the label type had no effect on the severity of the interactions with our equipment dummies, the personal label reduced the overall number of interactions by c . 40-60%, compared with the dummies showing the neutral or threatening label type. We suggest that researchers, in addition to securing their field equipment, label it with personal and polite messages that inform about the ongoing research and directly appeal to the public not to disturb the equipment. Further studies should extend these results to areas with different socio-economic structure.

Coarse Graining to Investigate Membrane Induced Peptide Folding of Anticancer Peptides

NASA Astrophysics Data System (ADS)

Ganesan, Sai; Xu, Hongcheng; Matysiak, Silvina

Information about membrane induced peptide folding mechanisms using all-atom molecular dynamics simulations is a challenge due to time and length scale issues.We recently developed a low resolution Water Explicit Polarizable PROtein coarse-grained Model by adding oppositely charged dummy particles inside protein backbone beads.These two dummy particles represent a fluctuating dipole,thus introducing structural polarization into the coarse-grained model.With this model,we were able to achieve significant α- β secondary structure content de novo,without any added bias.We extended the model to zwitterionic and anionic lipids,by adding oppositely charged dummy particles inside polar beads, to capture the ability of the head group region to form hydrogen bonds.We use zwitterionic POPC and anionic POPS as our model lipids, and a cationic anticancer peptide,SVS1,as our model peptide.We have characterized the driving forces for SVS1 folding on lipid bilayers with varying anionic and zwitterionic lipid compositions.Based on our results, dipolar interactions between peptide backbone and lipid head groups contribute to stabilize folded conformations.Cooperativity in folding is induced by both intra peptide and membrane-peptide interaction.

Novel strategy for synthesis of magnetic dummy molecularly imprinted nanoparticles based on functionalized silica as an efficient sorbent for the determination of acrylamide in potato chips: Optimization by experimental design methodology.

PubMed

Arabi, Maryam; Ostovan, Abbas; Ghaedi, Mehrorang; Purkait, Mihir K

2016-07-01

This study discusses a novel and simple method for the preparation of magnetic dummy molecularly imprinted nanoparticles (MDMINPs). Firstly, Fe3O4 magnetic nanoparticles (MNPs) were synthesized as a magnetic component. Subsequently, MDMINPs were constructed via the sol-gel strategy using APTMS as the functional monomer. Urethane was considered as dummy template to avoid residual template and TEOS as the cross linker. The prepared MDMINPs were used for the pre-concentration of acrylamide from potato chips. Quantification was carried out by high performance liquid chromatography with UV detection (HPLC-UV). The impact of influential variables such as pH, amount of sorbent, sonication time and eluent volume were well investigated and optimized using a central composite design. The particles had excellent magnetic property and high selectivity to the targeted molecule. In optimized conditions, the recovery ranged from 94.0% to 98.0% with the detection limit of 0.35µgkg(-1). Copyright © 2016 Elsevier B.V. All rights reserved.

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face

PubMed Central

Goldman, Mitchel P.

2017-01-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality. PMID:28670356

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face.

PubMed

Wu, Douglas C; Goldman, Mitchel P

2017-05-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality.

N-Acetylcysteine in the Treatment of Pediatric Trichotillomania: A Randomized, Double-Blind, Placebo-Controlled Add-On Trial

ERIC Educational Resources Information Center

Bloch, Michael H.; Panza, Kaitlyn E.; Grant, Jon E.; Pittenger, Christopher; Leckman, James F.

2013-01-01

Objective: To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. Method: A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary…

A Randomized, Double-Blind, Crossover Comparison of MK-0929 and Placebo in the Treatment of Adults with ADHD

ERIC Educational Resources Information Center

Rivkin, Anna; Alexander, Robert C.; Knighton, Jennifer; Hutson, Pete H.; Wang, Xiaojing J.; Snavely, Duane B.; Rosah, Thomas; Watt, Alan P.; Reimherr, Fred W.; Adler, Lenard A.

2012-01-01

Objective: Preclinical models, receptor localization, and genetic linkage data support the role of D4 receptors in the etiology of ADHD. This proof-of-concept study was designed to evaluate MK-0929, a selective D4 receptor antagonist as treatment for adult ADHD. Method: A randomized, double-blind, placebo-controlled, crossover study was conducted…

A Randomized, Double-Blind, Placebo-Controlled Study of Modafinil Film-Coated Tablets in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Greenhill, Laurence L.; Biederman, Joseph; Boellner, Samuel W.; Rugino, Thomas A.; Sangal, R. Bart; Earl, Craig Q.; Jiang, John G.; Swanson, James M.

2006-01-01

Objective: To evaluate the efficacy and tolerability of modafinil in children and adolescents, ages 7 to 17, with attention-deficit/hyperactivity disorder (ADHD). Method: In this 9-week, double-blind, flexible-dose study, patients were randomized to once-daily modafinil (170-425 mg) or placebo. Assessments included ADHD Rating Scale-IV…

Randomized, Double-Blind, Placebo-Controlled Trial of Asenapine Maintenance Therapy in Adults With an Acute Manic or Mixed Episode Associated With Bipolar I Disorder.

PubMed

Szegedi, Armin; Durgam, Suresh; Mackle, Mary; Yu, Sung Yun; Wu, Xiao; Mathews, Maju; Landbloom, Ronald P

2018-01-01

The authors determined the efficacy and safety of asenapine in preventing recurrence of any mood episode in adults with bipolar I disorder. Adults with an acute manic or mixed episode per DSM-IV-TR criteria were enrolled in this randomized, placebo-controlled trial consisting of an initial 12- to 16-week open-label period and a 26-week double-blind randomized withdrawal period. The target asenapine dosage was 10 mg b.i.d. in the open-label period but could be titrated down to 5 mg b.i.d. After completing the open-label period, subjects meeting stabilization/stable-responder criteria were randomized to asenapine or placebo treatment in the double-blind period. The primary efficacy endpoint was time to recurrence of any mood event during the double-blind period. Kaplan-Meier estimation was performed, and 95% confidence intervals were determined. Safety was assessed throughout. A total of 549 subjects entered the open-label period, of whom 253 enrolled in the double-blind randomized withdrawal period (127 in the placebo group; 126 in the asenapine group). Time to recurrence of any mood episode was statistically significantly longer for asenapine- than placebo-treated subjects. In post hoc analyses, significant differences in favor of asenapine over placebo were seen in time to recurrence of manic and depressive episodes. The most common treatment-emergent adverse events were somnolence (10.0%), akathisia (7.7%), and sedation (7.7%) in the open-label period and mania (11.9% of the placebo group compared with 4.0% of the asenapine group) and bipolar I disorder (6.3% compared with 1.6%) in the double-blind period. Long-term treatment with asenapine was more effective than placebo in preventing recurrence of mood events in adults with bipolar I disorder and was generally well-tolerated.

Status of the irradiation test vehicle for testing fusion materials in the Advanced Test Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, H.; Gomes, I.C.; Smith, D.L.

1998-09-01

The design of the irradiation test vehicle (ITV) for the Advanced Test Reactor (ATR) has been completed. The main application for the ITV is irradiation testing of candidate fusion structural materials, including vanadium-base alloys, silicon carbide composites, and low-activation steels. Construction of the vehicle is underway at the Lockheed Martin Idaho Technology Company (LMITCO). Dummy test trains are being built for system checkout and fine-tuning. Reactor insertion of the ITV with the dummy test trains is scheduled for fall 1998. Barring unexpected difficulties, the ITV will be available for experiments in early 1999.

[Final clinical indications and etiology in 1,023 enucleations. Descriptive databank evaluation with SPSS software in variable response mode with dummy variables].

PubMed

Becker, H; Bialasiewicz, A A; Schaudig, U; Schäfer, H; von Domarus, D

2002-05-01

A new data bank developed for ophthalmopathology using a computer-generated, multidigital data code is expected to be able to accomplish complex clinicopathologic correlations of diagnoses and signs, as provided by (multiple) clinical events and histopathologically proven etiologies, and to facilitate the documentation of new data. In the ophthalmopathology laboratory 2890 eyes were examined between January 20, 1975 and December 12, 1996. The main diagnoses and patient data from this 22-year period were recorded. To facilitate the presentation of data, a 10-year period with eyes of 976 patients enucleated from December, 1986 to December, 1996 was chosen. Principal and secondary diagnoses served for establishing the data bank. The frequencies of successive histologic and clinical diagnoses were evaluated by a descriptive computing program using an SPSS-multi-response mode with dummy variables and a categorical variable listing of the software (SPSS version 10.0) classified as (a) non-filtered random, (b) filtered by multiple etiologies, and (c) filtered by multiple events. The principal groups (e.g., histologic diagnoses concerning etiology) and subgroups (e.g., trauma, neoplasia, surgery, systemic diseases, and inflammations) were defined and correlated with 798 separate diagnoses. From 11 diagnoses/events ascribed to the clinical cases, 11,198 namings resulted. Thus, a comparative study of complex etiologies and events leading to enucleation in different hospitals of a specific area may be performed using this electronic ophthalmopathologic data bank system. The complexity of rare disease and integration into a superimposed structure can be managed with this custom-made data bank. A chronologically and demographically oriented consideration of reasons for enucleation is thus feasible.

Infant and child feeding practices: a preliminary investigation.

PubMed

Wyne, A H; Spencer, A J; Szuster, F S

1997-02-01

The objective of this preliminary investigation was to examine the feeding practices of infants and pre-school children in Adelaide, and thereby contribute to the development of appropriate preventive dental strategies. A stratified random sample of 160 two year old and three year old pre-school children in the Adelaide Statistical District was obtained. Information about feeding practices and use of comforters or 'dummies' was obtained through a self-administered questionnaire completed by parents of the selected children. Information was collected for the age periods of 0-3 months, 4-6 months, 7-12 months, 13-24 months and 25-36 months. Most of the children (81.8 per cent) were breast-fed at some stage. However the percentage of children being breast-fed decreased markedly across age periods, particularly to 13-24 months, when only 15.9 per cent of children were being breast-fed. Over half of the children, had been bottle-fed with infant formula at some stage. The highest percentage of children being bottle-fed with infant formula occurred in the 4-6 months (42.6 per cent) closely followed by the 7-12 months age period (37.4 per cent). Nearly two-thirds of children were bottle-fed with cow's milk at some stage. The highest percentage of children being bottle-fed with cow's milk occurred in the 13-24 months age period (49.6 per cent). A quarter (24.5 per cent) of the children were put to bed at some stage with a bottle containing cariogenic fluids. The majority of children used a 'dummy' at some stage during both day-time and night-time. Parents are in need of advice on appropriate feeding patterns for infants and young children.

Individual pore and interconnection size analysis of macroporous ceramic scaffolds using high-resolution X-ray tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jerban, Saeed, E-mail: saeed.jerban@usherbrooke.ca

2016-08-15

The pore interconnection size of β-tricalcium phosphate scaffolds plays an essential role in the bone repair process. Although, the μCT technique is widely used in the biomaterial community, it is rarely used to measure the interconnection size because of the lack of algorithms. In addition, discrete nature of the μCT introduces large systematic errors due to the convex geometry of interconnections. We proposed, verified and validated a novel pore-level algorithm to accurately characterize the individual pores and interconnections. Specifically, pores and interconnections were isolated, labeled, and individually analyzed with high accuracy. The technique was verified thoroughly by visually inspecting andmore » verifying over 3474 properties of randomly selected pores. This extensive verification process has passed a one-percent accuracy criterion. Scanning errors inherent in the discretization, which lead to both dummy and significantly overestimated interconnections, have been examined using computer-based simulations and additional high-resolution scanning. Then accurate correction charts were developed and used to reduce the scanning errors. Only after the corrections, both the μCT and SEM-based results converged, and the novel algorithm was validated. Material scientists with access to all geometrical properties of individual pores and interconnections, using the novel algorithm, will have a more-detailed and accurate description of the substitute architecture and a potentially deeper understanding of the link between the geometric and biological interaction. - Highlights: •An algorithm is developed to analyze individually all pores and interconnections. •After pore isolating, the discretization errors in interconnections were corrected. •Dummy interconnections and overestimated sizes were due to thin material walls. •The isolating algorithm was verified through visual inspection (99% accurate). •After correcting for the systematic errors, algorithm was validated successfully.« less

Thoracic and lumbar spine responses in high-speed rear sled tests.

PubMed

Viano, David C; Parenteau, Chantal S; Burnett, Roger

2018-07-04

This study analyzed thoracic and lumbar spine responses with in-position and out-of-position (OOP) seated dummies in 40.2 km/h (25 mph) rear sled tests with conventional and all-belts-to-seat (ABTS) seats. Occupant kinematics and spinal responses were determined with modern (≥2000 MY), older (<2000 MY), and ABTS seats. The seats were fixed in a sled buck subjected to a 40.2 km/h (25 mph) rear sled test. The pulse was a 15 g double-peak acceleration with 150 ms duration. The 50th percentile Hybrid III was lap-shoulder belted in the FMVSS 208 design position or OOP, including leaning forward and leaning inboard and forward. There were 26 in-position tests with 11 <2000 MY, 8 ≥2000 MY, and 7 ABTS and 14 OOP tests with 6 conventional and 8 ABTS seats. The dummy was fully instrumented. This study addressed the thoracic and lumbar spine responses. Injury assessment reference values are not approved for the thoracic and lumbar spine. Conservative thresholds exist. The peak responses were normalized by a threshold to compare responses. High-speed video documented occupant kinematics. The extension moments were higher in the thoracic than lumbar spine in the in-position tests. For <2000 MY seats, the thoracic extension moment was 76.8 ± 14.6% of threshold and the lumbar extension moment was 50.5 ± 17.9%. For the ≥2000 MY seats, the thoracic extension moment was 54.2 ± 26.6% of threshold and the lumbar extension moment was 49.8 ± 27.7%. ABTS seats provided similar thoracic and lumbar responses. Modern seat designs lowered thoracic and lumbar responses. For example, the 1996 Taurus had -1,696 N anterior lumbar shear force and -205.2 Nm extension moment. There was -1,184 N lumbar compression force and 1,512 N tension. In contrast, the 2015 F-150 had -500 N shear force and -49.7 Nm extension moment. There was -839 N lumbar compression force and 535 N tension. On average, the 2015 F-150 had 40% lower lumbar spine responses than the 1996 Taurus. The OOP tests had similar peak lumbar responses; however, they occurred later due to the forward lean of the dummy. The design and performance of seats have significantly changed over the past 20 years. Modern seats use a perimeter frame allowing the occupant to pocket into the seatback. Higher and more forward head restraints allow a stronger frame because the head, neck, and torso are more uniformly supported with the seat more upright in severe rear impacts. The overall effect has been a reduction in thoracic and lumbar loads and risks for injury.

Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil.

PubMed

Citrome, Leslie

2016-01-01

Aripiprazole monohydrate (AM) and aripiprazole lauroxil (AL) are two different long-acting injectable formulations of aripiprazole. AM 400 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial, as well as in a double-blind, placebo-controlled, randomized-withdrawal maintenance study, and in two non-inferiority maintenance studies. AL is a prodrug of aripiprazole and available in 441 mg, 662 mg or 882 mg strengths. AL 441 mg and 882 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial. The pharmacokinetic profile of AL also led to approval of dosing intervals of every 6 weeks for the 882 mg dose. The overall tolerability profiles of both products are consistent with what is known about oral aripiprazole.

Phase-retrieval attack free cryptosystem based on cylindrical asymmetric diffraction and double-random phase encoding

NASA Astrophysics Data System (ADS)

Wang, Jun; Li, Xiaowei; Hu, Yuhen; Wang, Qiong-Hua

2018-03-01

A phase-retrieval attack free cryptosystem based on the cylindrical asymmetric diffraction and double-random phase encoding (DRPE) is proposed. The plaintext is abstract as a cylinder, while the observed diffraction and holographic surfaces are concentric cylinders. Therefore, the plaintext can be encrypted through a two-step asymmetric diffraction process with double pseudo random phase masks located on the object surface and the first diffraction surface. After inverse diffraction from a holographic surface to an object surface, the plaintext can be reconstructed using a decryption process. Since the diffraction propagated from the inner cylinder to the outer cylinder is different from that of the reversed direction, the proposed cryptosystem is asymmetric and hence is free of phase-retrieval attack. Numerical simulation results demonstrate the flexibility and effectiveness of the proposed cryptosystem.

Omega 3/6 Fatty Acids for Reading in Children: A Randomized, Double-Blind, Placebo-Controlled Trial in 9-Year-Old Mainstream Schoolchildren in Sweden

ERIC Educational Resources Information Center

Johnson, Mats; Fransson, Gunnar; Östlund, Sven; Areskoug, Björn; Gillberg, Christopher

2017-01-01

Background: Previous research has shown positive effects of Omega 3/6 fatty acids in children with inattention and reading difficulties. We aimed to investigate if Omega 3/6 improved reading ability in mainstream schoolchildren. Methods: We performed a 3-month parallel, randomized, double-blind, placebo-controlled trial followed by 3-month active…

Supplementation with 1000 IU vitamin D/d leads to parathyroid hormone suppression, but not increased fractional calcium absorption, in 4-8-y-old children: A double-blind randomized controlled trial

USDA-ARS?s Scientific Manuscript database

The effects of vitamin D supplementation in healthy prepubertal children on physiologic outcomes have not been investigated. The objective was to evaluate the effects of supplementation with 1000 IU vitamin D(3)/d on calcium absorption. In a double-blind, placebo-controlled trial, we randomly assign...

A Randomized Double-Blind Study of Atomoxetine versus Placebo for Attention-Deficit/Hyperactivity Disorder Symptoms in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Harfterkamp, Myriam; van de Loo-Neus, Gigi; Minderaa, Ruud B.; van der Gaag, Rutger-Jan; Escobar, Rodrigo; Schacht, Alexander; Pamulapati, Sireesha; Buitelaar, Jan K.; Hoekstra, Pieter J.

2012-01-01

Objective: The efficacy of atomoxetine as treatment of symptoms of attention-deficit/hyperactivity disorder (ADHD) in patients with autism spectrum disorder (ASD) has not been established. Method: In this study, 97 patients aged 6 to 17 years with ADHD and ASD were randomly assigned to double-blind treatment with 1.2 mg/kg/day atomoxetine or…

Evaluation of the influence of velocity on dynamic passenger loads during a frontal minibus impact against an obstacle

NASA Astrophysics Data System (ADS)

Prochowski, L.; Dębowski, A.; Żuchowski, A.; Zielonka, K.

2016-09-01

The safety of people travelling by minibus is a very complex issue, in which the decisive role is played by load-bearing vehicle structure, passenger seats, and personal protection means. In order to maximize the number of people transported, the seats are spaced very closely to each other and this may pose a hazard to the passengers. Based on an analysis of experimental test results, a computer model representing a system composed of a minibus floor segment, seats, and dummies was built. For the analysis, seats integrated with seat belts were adopted. A seat of this type was based on a high-rigidity frame necessary to bear, inter alia, the strong force exerted (during a collision) by passenger's torso on the shoulder seat belt and transmitted to the upper seat belt anchorage point on the seat backrest. Within this work, the frontal minibus impact against an obstacle with velocities ranging from 20 km/h to 70 km/h was considered. The analysis covered the motion of, and dynamic loads on, a test dummy representing a 50th percentile adult male (Hybrid III dummy). Within the analysis, realizations of dynamic loads caused by inertial forces and reactions exerted by a three-point seat belt were taken into account. Special attention was paid to the extreme values of the loads that acted on dummy's head, neck, and torso when the head hit the backrest of the preceding seat in the culminating phase of the vehicle impact against an obstacle. The values of biomechanical indicators HIC, ThAC, Nij , and FAC and of the joint injury risk indicator were calculated.

ILP-based co-optimization of cut mask layout, dummy fill, and timing for sub-14nm BEOL technology

NASA Astrophysics Data System (ADS)

Han, Kwangsoo; Kahng, Andrew B.; Lee, Hyein; Wang, Lutong

2015-10-01

Self-aligned multiple patterning (SAMP), due to its low overlay error, has emerged as the leading option for 1D gridded back-end-of-line (BEOL) in sub-14nm nodes. To form actual routing patterns from a uniform "sea of wires", a cut mask is needed for line-end cutting or realization of space between routing segments. Constraints on cut shapes and minimum cut spacing result in end-of-line (EOL) extensions and non-functional (i.e. dummy fill) patterns; the resulting capacitance and timing changes must be consistent with signoff performance analyses and their impacts should be minimized. In this work, we address the co-optimization of cut mask layout, dummy fill, and design timing for sub-14nm BEOL design. Our central contribution is an optimizer based on integer linear programming (ILP) to minimize the timing impact due to EOL extensions, considering (i) minimum cut spacing arising in sub-14nm nodes; (ii) cut assignment to different cut masks (color assignment); and (iii) the eligibility to merge two unit-size cuts into a bigger cut. We also propose a heuristic approach to remove dummy fills after the ILP-based optimization by extending the usage of cut masks. Our heuristic can improve critical path performance under minimum metal density and mask density constraints. In our experiments, we study the impact of number of cut masks, minimum cut spacing and metal density under various constraints. Our studies of optimized cut mask solutions in these varying contexts give new insight into the tradeoff of performance and cost that is afforded by cut mask patterning technology options.

Double-layer versus single-layer bone-patellar tendon-bone anterior cruciate ligament reconstruction: a prospective randomized study with 3-year follow-up.

PubMed

Mei, Xiaoliang; Zhang, Zhenxiang; Yang, Jingwen

2016-12-01

To evaluate the clinical results of a randomized controlled trial of single-layer versus double-layer bone-patellar tendon-bone (BPTB) anterior cruciate ligament (ACL) reconstruction. Fifty-eight subjects who underwent primary ACL reconstruction with a BPTB allograft were prospectively randomized into two groups: single-layer reconstruction (n = 31) and double-layer reconstruction (n = 27). The following evaluation methods were used: clinical examination, KT-1000 arthrometer measurement, muscle strength, Tegner activity score, Lysholm score, subjective rating scale regarding patient satisfaction and sports performance level, graft retear, contralateral ACL tear, and additional meniscus surgery. Forty-eight subjects (24 in single-layer group and 24 in double-layer group) who were followed up for 3 years were evaluated. Preoperatively, there were no differences between the groups. At 3-year follow-up, the Lachman and pivot-shift test results were better in the double-layer group (P = 0.019 and P < 0.0001, respectively). KT measurements were better in the double-layer group (mean 2.9 versus 1.5 mm; P = 0.0025). The Tegner score was also better in the double-layer group (P = 0.024). There were no significant differences in range of motion, muscle strength, Lysholm score, subjective rating scale, graft retear, and secondary meniscal tear. In ACL reconstruction, double-layer BPTB reconstruction was significantly better than single-layer reconstruction regarding anterior and rotational stability at 3-year follow-up. The results of KT measurements and the Lachman and pivot-shift tests were significantly better in the double-layer group, whereas there was no difference in the anterior drawer test results. The Tegner score was also better in the double-layer group; however, there were no differences in the other subjective findings.

Key management of the double random-phase-encoding method using public-key encryption

NASA Astrophysics Data System (ADS)

Saini, Nirmala; Sinha, Aloka

2010-03-01

Public-key encryption has been used to encode the key of the encryption process. In the proposed technique, an input image has been encrypted by using the double random-phase-encoding method using extended fractional Fourier transform. The key of the encryption process have been encoded by using the Rivest-Shamir-Adelman (RSA) public-key encryption algorithm. The encoded key has then been transmitted to the receiver side along with the encrypted image. In the decryption process, first the encoded key has been decrypted using the secret key and then the encrypted image has been decrypted by using the retrieved key parameters. The proposed technique has advantage over double random-phase-encoding method because the problem associated with the transmission of the key has been eliminated by using public-key encryption. Computer simulation has been carried out to validate the proposed technique.

Discrete factor approximations in simultaneous equation models: estimating the impact of a dummy endogenous variable on a continuous outcome.

PubMed

Mroz, T A

1999-10-01

This paper contains a Monte Carlo evaluation of estimators used to control for endogeneity of dummy explanatory variables in continuous outcome regression models. When the true model has bivariate normal disturbances, estimators using discrete factor approximations compare favorably to efficient estimators in terms of precision and bias; these approximation estimators dominate all the other estimators examined when the disturbances are non-normal. The experiments also indicate that one should liberally add points of support to the discrete factor distribution. The paper concludes with an application of the discrete factor approximation to the estimation of the impact of marriage on wages.

Consistent differences in individual reactions to drugs and dummies

PubMed Central

Joyce, C. R. B.

1959-01-01

The tendency of some individuals to report changes of physical and mental state after taking pharmacologically inert substances has been investigated experimentally. In a class of healthy medical students, those individuals who reported symptoms and those who did not made significantly different scores on a number of behavioural tests. The likely reactions of the members of a second class (containing none of the previous participants) to dummies were then predicted from their scores on the same tests, some of which were found to be much more efficient predictors than would have been expected by chance. Some implications for further research and for clinical medicine are discussed. PMID:14408028

Oral continuous positive airway pressure (CPAP) following nasal injury in a preterm infant.

PubMed

Carlisle, H R; Kamlin, C O F; Owen, L S; Davis, P G; Morley, C J

2010-03-01

Non-invasive respiratory support is increasingly popular but is associated with complications including nasal trauma. The present report describes a novel method of oral continuous positive airway pressure (CPAP) delivery in an extremely premature infant with severe nasal septum erosion. The distal end of a cut down endotracheal tube was passed through a small hole made in the teat of a dummy (infant pacifier) and sutured in place. The dummy was secured in the infant's mouth and CPAP was delivered to the pharynx. The device was well tolerated and the infant was successfully managed using this technique for 48 days, avoiding endotracheal intubation and ventilation.

Boeing CST-100 Starliner Seat Test

NASA Image and Video Library

2017-02-21

Engineers working with Boeing's CST-100 Starliner test the spacecraft's seat design in Mesa, Arizona, focusing on how the spacecraft seats would protect an astronaut's head, neck and spine during the 240-mile descent from the International Space Station. The company incorporated test dummies for a detailed analysis of impacts on a crew returning to earth. The human-sized dummies were equipped with sensitive instrumentation and secured in the seats for 30 drop tests at varying heights, angles, velocities and seat orientations in order to mimic actual landing conditions. High-speed cameras captured the footage for further analysis. The Starliner spacecraft is being developed in partnership with NASA's Commercial Crew Program.

Mechanical qualification of the support structure for MQXF, the Nb 3Sn low-β quadrupole for the high luminosity LHC

DOE PAGES

Juchno, M.; Ambrosio, G.; Anerella, M.; ...

2016-01-26

Within the scope of the High Luminosity LHC project, the collaboration between CERN and U.S. LARP is developing new low-β quadrupoles using the Nb 3Sn superconducting technology for the upgrade of the LHC interaction regions. The magnet support structure of the first short model was designed and two units were fabricated and tested at CERN and at LBNL. The structure provides the preload to the collars-coils subassembly by an arrangement of outer aluminum shells pre-tensioned with water-pressurized bladders. For the mechanical qualification of the structure and the assembly procedure, superconducting coils were replaced with solid aluminum “dummy coils”, the structuremore » was preloaded at room temperature, and then cooled-down to 77 K. Mechanical behavior of the magnet structure was monitored with the use of strain gauges installed on the aluminum shells, the dummy coils and the axial preload system. As a result, this paper reports on the outcome of the assembly and the cool-down tests with dummy coils, which were performed at CERN and at LBNL, and presents the strain gauge measurements compared to the 3D finite element model predictions.« less

Energy Absorbing Seat System for an Agricultural Aircraft

NASA Technical Reports Server (NTRS)

Kellas, Sotiris; Jones, Lisa E. (Technical Monitor)

2002-01-01

A task was initiated to improve the energy absorption capability of an existing aircraft seat through cost-effective retrofitting, while keeping seat-weight increase to a minimum. This task was undertaken as an extension of NASA ongoing safety research and commitment to general aviation customer needs. Only vertical crash scenarios have been considered in this task which required the energy absorbing system to protect the seat occupant in a range of crash speeds up to 31 ft/sec. It was anticipated that, the forward and/or side crash accelerations could be attenuated with the aid of airbags, the technology of which is currently available in automobiles and military helicopters. Steps which were followed include, preliminary crush load determination, conceptual design of cost effective energy absorbers, fabrication and testing (static and dynamic) of energy absorbers, system analysis, design and fabrication of dummy seat/rail assembly, dynamic testing of dummy seat/rail assembly, and finally, testing of actual modified seat system with a dummy occupant. A total of ten full scale tests have been performed including three of the actual aircraft seat. Results from full-scale tests indicated that occupant loads were attenuated successfully to survivable levels.

Complex tibial fracture outcomes following treatment with low-intensity pulsed ultrasound.

PubMed

Leung, Kwok-Sui; Lee, Wing-Sze; Tsui, Hon-For; Liu, Paul Po-Lung; Cheung, Wing-Hoi

2004-03-01

A clinical study was conducted to investigate the effect of low-intensity pulsed ultrasound (US) stimulation (LIPUS) on the healing of complex tibial fractures. Thirty complex tibial fractures were randomly assigned to the treatment with LIPUS (n = 16) or by a dummy machine (sham-exposed: n = 14). The fractures were immobilized by either internal or external fixations according to the clinical indications. LIPUS was given 20 min/day for 90 days. Fracture healing was monitored by clinical, radiological, densitometric and biochemical assessments. The LIPUS-treated group showed statistically significantly better healing, as demonstrated by all assessments. Complications were minimal in the LIPUS group. There were two cases of delayed union, with one in each group. There were two cases of infection in the control group. The delayed-union cases were subsequently treated by LIPUS and the infection cases were treated with standard protocol. Fracture healing in these patients was again treated by LIPUS.

Double versus single cervical cerclage for patients with recurrent pregnancy loss: a randomized clinical trial.

PubMed

Zolghadri, Jaleh; Younesi, Masoumeh; Asadi, Nasrin; Khosravi, Dezire; Behdin, Shabnam; Tavana, Zohre; Ghaffarpasand, Fariborz

2014-02-01

To compare the effectiveness of the double cervical cerclage method versus the single method in women with recurrent second-trimester delivery. In this randomized clinical trial, we included 33 singleton pregnancies suffering from recurrent second-trimester pregnancy loss (≥2 consecutive fetal loss during second-trimester or with a history of unsuccessful procedures utilizing the McDonald method), due to cervical incompetence. Patients were randomly assigned to undergo either the classic McDonald method (n = 14) or the double cerclage method (n = 19). The successful pregnancy rate and gestational age at delivery was also compared between the two groups. The two study groups were comparable regarding their baseline characteristics. The successful pregnancy rate did not differ significantly between those who underwent the double cerclage method or the classic McDonald cerclage method (100% vs 85.7%; P = 0.172). In the same way, the preterm delivery rate (<34 weeks of gestation) was comparable between the two study groups (10.5% vs 35.7%; P = 0.106). Those undergoing the double cerclage method had longer gestational duration (37.2 ± 2.6 vs 34.3 ± 3.8 weeks; P = 0.016). The double cervical cerclage method seems to provide better cervical support, as compared with the classic McDonald cerclage method, in those suffering from recurrent pregnancy loss, due to cervical incompetence. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Prospective randomized assessment of single versus double-gloving for general surgical procedures.

PubMed

Na'aya, H U; Madziga, A G; Eni, U E

2009-01-01

There is increased tendency towards double-gloving by general surgeons in our practice, due probably to awareness of the risk of contamination with blood or other body fluids during surgery. The aim of the study was to compare the relative frequency of glove puncture in single-glove versus double glove sets in general surgical procedures, and to determine if duration of surgery affects perforation rate. Surgeons at random do single or double gloves at their discretion, for general surgical procedures. All the gloves used by the surgeons were assessed immediately after surgery for perforation. A total of 1120 gloves were tested, of which 880 were double-glove sets and 240 single-glove sets. There was no significant difference in the overall perforation rate between single and double glove sets (18.3% versus 20%). However, only 2.3% had perforations in both the outer and inner gloves in the double glove group. Therefore, there was significantly greater risk for blood-skin exposure in the single glove sets (p < 0.01). The perforation rate was also significantly greater during procedures lasting an hour or more compared to those lasting less than an hour (p < 0.01). Double-gloving reduces the risk of blood-skin contamination in all general surgical procedures, and especially so in procedures lasting an hour or more.

Vitamin D Supplementation in Elderly Black Women Does Not Prevent Bone Loss, a Randomized Controlled Trial.

PubMed

Aloia, John F; Fazzari, Melissa; Islam, Shahidul; Mikhail, Mageda; Katumuluwa, Subhashini; Dhaliwal, Ruban; Stolberg, Alexandra; Usera, Gianina; Ragolia, Louis

2018-06-15

Black Americans have lower levels of serum 25(OH)D but superior bone health compared to white Americans. There is controversy over whether they should be screened for vitamin D deficiency and have higher vitamin D requirements than recommended by the Institute of Medicine (IOM). The purpose of this trial was to determine whether Vitamin D supplementation in elderly black women prevents bone loss. 260 healthy black American women, 60 years of age and older were recruited to take part in a two arm, double-dummy 3 year RCT of vitamin D 3 vs. placebo. The study was conducted in an ambulatory clinical research center. Vitamin D 3 dose was adjusted to maintain serum 25(OH)D above 75 nmol/L. Bone mineral density (BMD) and serum were measured for [parathyroid hormone (PTH), C-terminal crosslink telopeptide (CTX) and bone specific alkaline phosphatase (BSAP) every 6 months. Baseline serum 25(OH)D 3 was 54.8 ± 16.8 nmol/L. There was no group xtime interaction effect for any BMD measurement. For all BMD measurements, except for total body and spine, there was a statistically significant negative effect of time (P < 0.001). An equivalency analysis showed that the treatment group was equivalent to the control group. Serum PTH and BSAP declined, with a greater decline of PTH in the treatment group. The rate of bone loss with serum 25(OH)D above 75 nmol/L is comparable to the rate of loss with serum 25(OH)D at the RDA of 50 nmol/L. Black Americans should have the same exposure to vitamin D as white Americans. The trial was registered at clinical trials.gov: NCT01153568. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.

PubMed

Rauck, Richard L; Hale, Martin E; Bass, Almasa; Bramson, Candace; Pixton, Glenn; Wilson, Jacquelyn G; Setnik, Beatrice; Meisner, Paul; Sommerville, Kenneth W; Malhotra, Bimal K; Wolfram, Gernot

2015-09-01

The objective of this multicenter, double-blind, placebo-controlled, randomized withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse-deterrent formulation containing pellets of extended-release oxycodone hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo in the treatment of moderate-to-severe chronic low back pain. An open-label titration period in which all patients received ALO-02 was followed by a double-blind treatment period where patients meeting treatment response criteria were randomized to either a fixed dose of ALO-02 or placebo. Daily average low back pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663 patients screened, 410 received ALO-02 during the open-label conversion and titration period and 281 patients were randomized to the double-blind treatment period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score from randomization baseline to the final 2 weeks of the treatment period was significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty-four percent of patients treated with placebo and 57.5% of patients treated with ALO-02 reported ≥30% improvement in weekly average NRS-Pain scores from screening to the final 2 weeks of the treatment period (P = 0.0248). In the double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of patients in the placebo group experienced a treatment-emergent adverse event (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment period were nausea, vomiting, and constipation, consistent with opioid therapy. ALO-02 has been demonstrated to provide significant reduction of pain in patients with chronic low back pain and has a safety profile similar to other opioids.

A randomized, double-blind, placebo controlled, parallel group, efficacy study of alpha BRAIN® administered orally.

PubMed

Solomon, Todd M; Leech, Jarrett; deBros, Guy B; Murphy, Cynthia A; Budson, Andrew E; Vassey, Elizabeth A; Solomon, Paul R

2016-03-01

Alpha BRAIN® is a nootropic supplement that purports to enhance cognitive functioning in healthy adults. The goal of this study was to investigate the efficacy of this self-described cognitive enhancing nootropic on cognitive functioning in a group of healthy adults by utilizing a randomized, double blind, placebo-controlled design. A total of 63-treatment naïve individuals between 18 and 35 years of age completed the randomized, double-blind, placebo controlled trial. All participants completed a 2-week placebo run in before receiving active product, Alpha BRAIN® or new placebo, for 6 weeks. Participants undertook a battery of neuropsychological tests at randomization and at study completion. Primary outcome measures included a battery of neuropsychological tests and measures of sleep. Compared with placebo, Alpha BRAIN® significantly improved on tasks of delayed verbal recall and executive functioning. Results also indicated significant time-by-group interaction in delayed verbal recall for the Alpha BRAIN® group. The use of Alpha BRAIN® for 6 weeks significantly improved recent verbal memory when compared with controls, in a group of healthy adults. While the outcome of the study is encouraging, this is the first randomized controlled trial of Alpha BRAIN®, and the results merit further study. Copyright © 2016 John Wiley & Sons, Ltd.

Simulation of diffuse-charge capacitance in electric double layer capacitors

NASA Astrophysics Data System (ADS)

Sun, Ning; Gersappe, Dilip

2017-01-01

We use a Lattice Boltzmann Model (LBM) in order to simulate diffuse-charge dynamics in Electric Double Layer Capacitors (EDLCs). Simulations are carried out for both the charge and the discharge processes on 2D systems of complex random electrode geometries (pure random, random spheres and random fibers). The steric effect of concentrated solutions is considered by using a Modified Poisson-Nernst-Planck (MPNP) equations and compared with regular Poisson-Nernst-Planck (PNP) systems. The effects of electrode microstructures (electrode density, electrode filler morphology, filler size, etc.) on the net charge distribution and charge/discharge time are studied in detail. The influence of applied potential during discharging process is also discussed. Our studies show how electrode morphology can be used to tailor the properties of supercapacitors.

Using resource use logs to reduce the amount of missing data in economic evaluations alongside trials.

PubMed

Marques, Elsa; Johnson, Emma C; Gooberman-Hill, Rachael; Blom, Ashley W; Noble, Sian

2013-01-01

Economic evaluations alongside randomized controlled trials that collect data using patient-completed questionnaires are prone to missing data. Our objective was to determine whether giving patients a resource use log (RUL) at baseline would improve the odds of completing questions in a follow-up resource use questionnaire (RUQ) and to identify patients' views on RUL's usefulness and acceptability. The RUL study was a randomized controlled trial and qualitative study nested within a larger randomized controlled trial (the Arthroplasty Pain Experience Study trial). Eighty-five patients were randomized at baseline to receive or not receive an RUL. At 3-month follow-up, all participants received a postal RUQ. We created dummy variables for 13 resource use categories indicating whether complete information had been given for each category. We compared the completion rates between arms by using descriptive statistics and logistic regression. We explored patients' experience of using the RUL by interviewing a different subsample of Arthroplasty Pain Experience Study patients (n = 24) at 2- to 4-week follow-up. At 3 months, 74 of the 85 (87% in each arm) patients returned the RUQ. Patients in the RUL arm were 3.5 times more likely to complete the National Health Service community-based services category (P = 0.08). The RUL was positively received by patients and was generally seen as a useful memory aid. The RUL is a useful and acceptable tool in reducing the amount of missing data for some types of resource use. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Vehicle performance evaluation in side impact (MDB) using ES-II dummy

NASA Astrophysics Data System (ADS)

Ganessh, T. S.; Bansode, Praveen; Revankar, Vidyakant; Kumar, Sunil

2018-02-01

Side impact collision is one of the leading causes of death. Protection of people during lateral collision is challenging because of relatively small space available to restraint occupant compared to front. Hence, it is imperative to protect the occupants in side collision. It is a function of vehicle type and restraints for side protection. This paper focuses on evaluation of injury parameters of the ES II dummy during the lateral collision of different vehicles with different spaces, sections and materials. Thus the comparison will enable us to understand the sensitivity of space, B-pillar section and material which affects the injury parameters. This study will help automotive engineers to design side impact crashworthy vehicles.

Cranial MRI in a young child with cochlear implants after bilateral magnet removal.

PubMed

Helbig, Silke; Stöver, Timo; Burck, Iris; Kramer, Sabine

2017-12-01

A young bilateral cochlear implant (CI) user required magnetic resonance imaging (MRI) to determine the cause of hydrocephalus. The images obtained with the CIs in place were not diagnostically useful due to large artefacts generated by the CI magnets. We obtained useful images by bilaterally explanting the CI-magnets and replacing them with non-magnetic placeholder dummies then conducted the imaging. The artefact in the new images was greatly reduced and the images were diagnostically useful. Lastly, we explanted the dummies and reimplanted the CI-magnets. This procedure should be useful to obtain useful images in CI users. Copyright © 2017 Elsevier B.V. All rights reserved.

Buffered Lidocaine With Sodium Bicarbonate did not Increase Inferior Alveolar Nerve Block Success Rate in Patients Having Symptomatic Irreversible Pulpitis.

PubMed

Parirokh, Masoud

2016-03-01

Effect of buffered 4% lidocaine on the success of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double-blind study. Schellenberg J, Drum M, Reader A, Nusstein J, Fowler S, Beck M. J Endod 2015;41(6):791-6. The study was supported by Meyers/Reader Graduate Endodontic Support Fund Double blinded randomized controlled trial. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhancing Security of Double Random Phase Encoding Based on Random S-Box

NASA Astrophysics Data System (ADS)

Girija, R.; Singh, Hukum

2018-06-01

In this paper, we propose a novel asymmetric cryptosystem for double random phase encoding (DRPE) using random S-Box. While utilising S-Box separately is not reliable and DRPE does not support non-linearity, so, our system unites the effectiveness of S-Box with an asymmetric system of DRPE (through Fourier transform). The uniqueness of proposed cryptosystem lies on employing high sensitivity dynamic S-Box for our DRPE system. The randomness and scalability achieved due to applied technique is an additional feature of the proposed solution. The firmness of random S-Box is investigated in terms of performance parameters such as non-linearity, strict avalanche criterion, bit independence criterion, linear and differential approximation probabilities etc. S-Boxes convey nonlinearity to cryptosystems which is a significant parameter and very essential for DRPE. The strength of proposed cryptosystem has been analysed using various parameters such as MSE, PSNR, correlation coefficient analysis, noise analysis, SVD analysis, etc. Experimental results are conferred in detail to exhibit proposed cryptosystem is highly secure.

Effects of specific alpha-1A/1D blocker on lower urinary tract symptoms due to double-J stent: a prospectively randomized study.

PubMed

Wang, Chung-Jing; Huang, Shi-Wei; Chang, Chien-Hsing

2009-06-01

The aim of our study was to evaluate the effect of tamsulosin in improving symptoms in patients with indwelling double-J ureteral stents. This prospective study lasted from April 2006 to March 2008. All the patients with symptomatic lower ureteral stones with <15 mm diameter were enrolled, and were prospectively randomized (random numbers table) into two groups. A total of 154 patients, with insertion of a double-J ureteral stent after ureteroscopic stone removal. In group 1, 75 patients were enrolled and received placebo for 2 weeks. Group 2 included 79 patients who received 0.4 mg of tamsulosin, once daily for 2 weeks. All patients completed the validated ureteral stent symptom questionnaire (USSQ) and quality of life of international prostate symptom scale (IPSS) for evaluating the symptoms of double-J stents and quality of life after double-J stent insertion and removal, respectively. The analysis of the questionnaire at W1 revealed a significant difference in the main score index of urinary symptoms, body pain and general health between groups 1 and 2. When comparing W1 evaluation with that of W4 after double-J removal, both groups showed significant worsening of urinary symptoms, body pain, general health and work performance, except sexual performance. The mean score of quality of life in IPSS was 4.21 in group 1 and 1.6 in group 2. Tamsulosin can improve a subset of stent-related urinary symptoms and quality of life effectively and may be applied in routine clinical practice.

Triple-Loaded Single-Row Versus Suture-Bridge Double-Row Rotator Cuff Tendon Repair With Platelet-Rich Plasma Fibrin Membrane: A Randomized Controlled Trial.

PubMed

Barber, F Alan

2016-05-01

To compare the structural healing and clinical outcomes of triple-loaded single-row with suture-bridging double-row repairs of full-thickness rotator cuff tendons when both repair constructs are augmented with platelet-rich plasma fibrin membrane. A prospective, randomized, consecutive series of patients diagnosed with full-thickness rotator cuff tears no greater than 3 cm in anteroposterior length were treated with a triple-loaded single-row (20) or suture-bridging double-row (20) repair augmented with platelet-rich plasma fibrin membrane. The primary outcome measure was cuff integrity by magnetic resonance imaging (MRI) at 12 months postoperatively. Secondary clinical outcome measures were American Shoulder and Elbow Surgeons, Rowe, Simple Shoulder Test, Constant, and Single Assessment Numeric Evaluation scores. The mean MRI interval was 12.6 months (range, 12-17 months). A total of 3 of 20 single-row repairs and 3 of 20 double-row repairs (15%) had tears at follow-up MRI. The single-row group had re-tears in 1 single tendon repair and 2 double tendon repairs. All 3 tears failed at the original attachment site (Cho type 1). In the double-row group, re-tears were found in 3 double tendon repairs. All 3 tears failed medial to the medial row near the musculotendinous junction (Cho type 2). All clinical outcome measures were significantly improved from the preoperative level (P < .0001), but there was no statistical difference between groups postoperatively. There is no MRI difference in rotator cuff tendon re-tear rate at 12 months postsurgery between a triple-loaded single-row repair or a suture-bridging double-row repair when both are augmented with platelet-rich plasma fibrin membrane. No difference could be demonstrated between these repairs on clinical outcome scores. I, Prospective randomized study. Copyright © 2016 Arthroscopy Association of North America. All rights reserved.

Highly selective stir bar coated with dummy molecularly imprinted polymers for trace analysis of bisphenol A in milk.

PubMed

Zhan, Wen; Wei, Fangdi; Xu, Guanhong; Cai, Zheng; Du, Shuhu; Zhou, Xuemin; Li, Fei; Hu, Qin

2012-04-01

A water compatible molecularly imprinted polymers (MIPs) coated stir bar for bisphenol A(BPA) was prepared with 3,3',5,5'-tetrabromobisphenol A as the dummy template molecule in this study. The dummy molecularly imprinted polymers coated stir bar (DMIPs-SB) showed better selectivity than the bars coated with polydimethylsiloxane or non-imprinted polymers when used to extract BPA and its three analogues. The saturated adsorption amount of the DMIPs coating was 3.0 times over that of the non-imprinted polymers coating. To achieve the optimum extraction performance, several parameters, including extraction and desorption time, pH value, adsorption temperature and stirring speed were investigated. The high-performance liquid chromatography combined with the DMIPs-SB was employed in the analysis of BPA in aqueous solution. The linear range of BPA concentration in aqueous medium was 0.0228-2.28 ng/mL with correlation coefficient of 0.9994 and the detection limit was about 6.84 × 10(-3) ng/mL based on three times ratio of signal to noise. This method was directly applied to the determination of trace BPA in milk with satisfactory results. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Political economy of transnational water pollution: what do the LMB data (1985-2000) say?

PubMed

Guo, Rongxing; Yang, Kaizhong

2003-10-01

On the basis of the cross-section and time-series data of the Lower Mekong Basin (LMB)--including large sections of Thailand, Lao PDR, Vietnam, and Cambodia, we find little evidence in support of the environmental Kuznets curve (EKC) hypothesis. Instead, our regressions support the general views that water pollution had been positively related to income level and that, as a result of the end of the Cold War era, it had been significantly reduced in the 1990s vis-à-vis the 1980s. In most circumstances, water resources were more seriously polluted in the transnational border areas than in the other areas. Specifically, the estimated coefficients on the political boundary dummies show that political influence on transnational water pollution was more significant in areas near "the international border along which the river runs" (denoted by BORDER2) than in places near "the international border across which the river runs" (denoted by BORDER1). The estimated coefficients on the ASEAN dummy present some information about the positive role of the Association for Southeast Asian Nations (ASEAN) membership in the reduction of transnational water pollution. Finally, the country-specific dummies are found to present conflicting information about the transnational differences of water pollution, although Thailand is found to have the least water pollution in the LMB.

[Pacifier use: risks and benefits].

PubMed

Martínez Sánchez, L; Díaz González, E; García-Tornel Florensa , S; Gaspà Martí , J

2000-12-01

The use of a dummy as a comforting object in childhood is widespread in civilized societies. The advisability of this practice, as well as the shape, material, or time of use of these objects, is controversial. Data on the possible beneficial effects of these objects are numerous, but there is also a long list of disorders which have been associated with their use. Their soothing effect is the most widely recognized beneficial effect and the possible relationship with a lower incidence of sudden infant death syndrome is the newest. The most important risks of this nonnutritive sucking habit are failure of breastfeeding, dental deformities, recurrent acute otitis media, and the risk of accidents. The development of latex allergy, tooth decay, oral ulcers and sleep disorders are other possible problems. The association with a lower intelligence quotient is disputed. Insufficient data are provided by a review of the pros and the cons of dummy use to encourage or discourage this habit. However, there are sufficient data on which to base firm recommendations such as not starting their use in the first days of life, restricting use after the age of 8 months and withdrawing these objects at the age of 1 year. Pediatricians should be aware of and recommend only dummies that meet safety requirements.

Cardiovascular Surgery Residency Program: Training Coronary Anastomosis Using the Arroyo Simulator and UNIFESP Models.

PubMed

Maluf, Miguel Angel; Gomes, Walter José; Bras, Ademir Massarico; Araújo, Thiago Cavalcante Vila Nova de; Mota, André Lupp; Cardoso, Caio Cesar; Coutinho, Rafael Viana dos S

2015-01-01

Engage the UNIFESP Cardiovascular Surgery residents in coronary anastomosis, assess their skills and certify results, using the Arroyo Anastomosis Simulator and UNIFESP surgical models. First to 6th year residents attended a weekly program of technical training in coronary anastomosis, using 4 simulation models: 1. Arroyo simulator; 2. Dummy with a plastic heart; 3. Dummy with a bovine heart; and 4. Dummy with a beating pig heart. The assessment test was comprised of 10 items, using a scale from 1 to 5 points in each of them, creating a global score of 50 points maximum. The technical performance of the candidate showed improvement in all items, especially manual skill and technical progress, critical sense of the work performed, confidence in the procedure and reduction of the time needed to perform the anastomosis after 12 weeks practice. In response to the multiplicity of factors that currently influence the cardiovascular surgeon training, there have been combined efforts to reform the practices of surgical medical training. 1 - The four models of simulators offer a considerable contribution to the field of cardiovascular surgery, improving the skill and dexterity of the surgeon in training. 2 - Residents have shown interest in training and cooperate in the development of innovative procedures for surgical medical training in the art.

Cardiovascular Surgery Residency Program: Training Coronary Anastomosis Using the Arroyo Simulator and UNIFESP Models

PubMed Central

Maluf, Miguel Angel; Gomes, Walter José; Bras, Ademir Massarico; de Araújo, Thiago Cavalcante Vila Nova; Mota, André Lupp; Cardoso, Caio Cesar; Coutinho, Rafael Viana dos S.

2015-01-01

OBJECTIVE Engage the UNIFESP Cardiovascular Surgery residents in coronary anastomosis, assess their skills and certify results, using the Arroyo Anastomosis Simulator and UNIFESP surgical models. METHODS First to 6th year residents attended a weekly program of technical training in coronary anastomosis, using 4 simulation models: 1. Arroyo simulator; 2. Dummy with a plastic heart; 3. Dummy with a bovine heart; and 4. Dummy with a beating pig heart. The assessment test was comprised of 10 items, using a scale from 1 to 5 points in each of them, creating a global score of 50 points maximum. RESULTS The technical performance of the candidate showed improvement in all items, especially manual skill and technical progress, critical sense of the work performed, confidence in the procedure and reduction of the time needed to perform the anastomosis after 12 weeks practice. In response to the multiplicity of factors that currently influence the cardiovascular surgeon training, there have been combined efforts to reform the practices of surgical medical training. CONCLUSION 1 - The four models of simulators offer a considerable contribution to the field of cardiovascular surgery, improving the skill and dexterity of the surgeon in training. 2 - Residents have shown interest in training and cooperate in the development of innovative procedures for surgical medical training in the art. PMID:26735604

Molecularly imprinted polymers with synthetic dummy template for simultaneously selective removal and enrichment of ginkgolic acids from Ginkgo biloba L. leaves extracts.

PubMed

Ji, Wenhua; Ma, Xiuli; Xie, Hongkai; Chen, Lingxiao; Wang, Xiao; Zhao, Hengqiang; Huang, Luqi

2014-11-14

Dummy molecularly imprinted polymers (DMIPs) for simultaneously selective removal and enrichment of ginkgolic acids (GAs) during the processing of Ginkgo biloba leaves have been prepared. Two dummy template molecule with similar structural skeleton to GAs, 6-methoxysalicylic acid (MOSA, DT-1) and 6-hexadecyloxysalicylic acid (HOSA, DT-2), have been designed and synthesized. The performance of the DMIPs and NIPs were evaluated including selective recognition capacity, adsorption isotherm, and adsorption kinetics. The selective recognition capacity of the three GAs with four analogues on the sorbents illustrated that the DMIPs sorbents have high specificity for GAs. An efficient method based on DMIP-HOSA coupled with solid-phase extraction (SPE) was developed for simultaneously selective removal and enrichment of ginkgolic acids (GAs) during the processing of Ginkgo biloba leaves. The method showed excellent recoveries (82.5-88.7%) and precision (RSD 0.5-2.6%, n=5) for licorice extracts, Gastrodia elata extracts and pepper extracts spiked at three concentration levels each (50, 100, 200 μg mL(-1)). The results indicated that GAs and standardized Ginkgo biloba leaves extracts could be obtained simultaneously through the DMIP-SPE. Copyright © 2014 Elsevier B.V. All rights reserved.

Outcomes of the modified Brostrom procedure using suture anchors for chronic lateral ankle instability--a prospective, randomized comparison between single and double suture anchors.

PubMed

Cho, Byung-Ki; Kim, Yong-Min; Kim, Dong-Soo; Choi, Eui-Sung; Shon, Hyun-Chul; Park, Kyoung-Jin

2013-01-01

The present prospective, randomized study was conducted to compare the clinical outcomes of the modified Brostrom procedure using single and double suture anchors for chronic lateral ankle instability. A total of 50 patients were followed up for more than 2 years after undergoing the modified Brostrom procedure. Of the 50 procedures, 25 each were performed using single and double suture anchors by 1 surgeon. The Karlsson scale had improved significantly to 89.8 points and 90.6 points in the single and double anchor groups, respectively. Using the Sefton grading system, 23 cases (92%) in the single anchor group and 22 (88%) in the double anchor group achieved satisfactory results. The talar tilt angle and anterior talar translation on stress radiographs using the Telos device had improved significantly to an average of 5.7° and 4.6 mm in the single anchor group and 4.5° and 4.3 mm in the double anchor group, respectively. The double anchor technique was superior with respect to the postoperative talar tilt. The single and double suture anchor techniques produced similar clinical and functional outcomes, with the exception of talar tilt as a reference of mechanical stability. The modified Brostrom procedure using both single and double suture anchors appears to be an effective treatment method for chronic lateral ankle instability. Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

A novel attack method about double-random-phase-encoding-based image hiding method

NASA Astrophysics Data System (ADS)

Xu, Hongsheng; Xiao, Zhijun; Zhu, Xianchen

2018-03-01

By using optical image processing techniques, a novel text encryption and hiding method applied by double-random phase-encoding technique is proposed in the paper. The first step is that the secret message is transformed into a 2-dimension array. The higher bits of the elements in the array are used to fill with the bit stream of the secret text, while the lower bits are stored specific values. Then, the transformed array is encoded by double random phase encoding technique. Last, the encoded array is embedded on a public host image to obtain the image embedded with hidden text. The performance of the proposed technique is tested via analytical modeling and test data stream. Experimental results show that the secret text can be recovered either accurately or almost accurately, while maintaining the quality of the host image embedded with hidden data by properly selecting the method of transforming the secret text into an array and the superimposition coefficient.

KC-135 aero-optical turbulent boundary layer/shear layer experiment revisited

NASA Technical Reports Server (NTRS)

Craig, J.; Allen, C.

1987-01-01

The aero-optical effects associated with propagating a laser beam through both an aircraft turbulent boundary layer and artificially generated shear layers are examined. The data present comparisons from observed optical performance with those inferred from aerodynamic measurements of unsteady density and correlation lengths within the same random flow fields. Using optical instrumentation with tens of microsecond temporal resolution through a finite aperture, optical performance degradation was determined and contrasted with the infinite aperture time averaged aerodynamic measurement. In addition, the optical data were artificially clipped to compare to theoretical scaling calculations. Optical instrumentation consisted of a custom Q switched Nd:Yag double pulsed laser, and a holographic camera which recorded the random flow field in a double pass, double pulse mode. Aerodynamic parameters were measured using hot film anemometer probes and a five hole pressure probe. Each technique is described with its associated theoretical basis for comparison. The effects of finite aperture and spatial and temporal frequencies of the random flow are considered.

Compressive response and helix formation of a semiflexible polymer confined in a nanochannel

NASA Astrophysics Data System (ADS)

Hayase, Yumino; Sakaue, Takahiro; Nakanishi, Hiizu

2017-05-01

Configurations of a single semiflexible polymer is studied when it is pushed into a nanochannel in the case where the polymer persistence length lp is much longer than the channel diameter D :lp/D ≫1 . Using numerical simulations, we show that the polymer undergoes a sequence of recurring structural transitions upon longitudinal compression: random deflection along the channel, a helix going around the channel wall, double-fold random deflection, double-fold helix, etc. We find that the helix transition can be understood as buckling of deflection segments, and the initial helix formation takes place at very small compression with no appreciable weak compression regime of the random deflection polymer.

Structural Design Strategies for Improved Small Overlap Crashworthiness Performance.

PubMed

Mueller, Becky C; Brethwaite, Andrew S; Zuby, David S; Nolan, Joseph M

2014-11-01

In 2012, the Insurance Institute for Highway Safety (IIHS) began a 64 km/h small overlap frontal crash test consumer information test program. Thirteen automakers already have redesigned models to improve test performance. One or more distinct strategies are evident in these redesigns: reinforcement of the occupant compartment, use of energy-absorbing fender structures, and the addition of engagement structures to induce vehicle lateral translation. Each strategy influences vehicle kinematics, posing additional challenges for the restraint systems. The objective of this two-part study was to examine how vehicles were modified to improve small overlap test performance and then to examine how these modifications affect dummy response and restraint system performance. Among eight models tested before and after design changes, occupant compartment intrusion reductions ranged from 6 cm to 45 cm, with the highest reductions observed in models with the largest number of modifications. All redesigns included additional occupant compartment reinforcement, one-third added structures to engage the barrier, and two modified a shotgun load path. Designs with engagement structures produced greater glance-off from the barrier and exhibited lower delta Vs but experienced more lateral outboard motion of the dummy. Designs with heavy reinforcement of the occupant compartment had higher vehicle accelerations and delta V. In three cases, these apparent trade-offs were not well addressed by concurrent changes in restraint systems and resulted in increased injury risk compared with the original tests. Among the 36 models tested after design changes, the extent of design changes correlated to structural performance. Half of the vehicles with the lowest intrusion levels incorporated aspects of all three design strategies. Vehicle kinematics and dummy and restraint system characteristics were similar to those observed in the before/after pairs. Different combinations of structural improvement strategies for improving small overlap test performance were found to be effective in reducing occupant compartment intrusion and improving dummy kinematics in the IIHS small overlap test with modest weight increase.

Objective biofidelity rating of a numerical human occupant model in frontal to lateral impact.

PubMed

de Lange, Ronald; van Rooij, Lex; Mooi, Herman; Wismans, Jac

2005-11-01

Both hardware crash dummies and mathematical human models have been developed largely using the same biomechanical data. For both, biofidelity is a main requirement. Since numerical modeling is not bound to hardware crash dummy design constraints, it allows more detailed modeling of the human and offering biofidelity for multiple directions. In this study the multi-directional biofidelity of the MADYMO human occupant model is assessed, to potentially protect occupants under various impact conditions. To evaluate the model's biofidelity, generally accepted requirements were used for frontal and lateral impact: tests proposed by EEVC and NHTSA and tests specified by ISO TR9790, respectively. A subset of the specified experiments was simulated with the human model. For lateral impact, the results were objectively rated according to the ISO protocol. Since no rating protocol was available for frontal impact, the ISO rating scheme for lateral was used for frontal, as far as possible. As a result, two scores show the overall model biofidelity for frontal and lateral impact, while individual ratings provide insight in the quality on body segment level. The results were compared with the results published for the THOR and WorldSID dummies, showing that the mathematical model exhibits a high level of multi-directional biofidelity. In addition, the performance of the human model in the NBDL 11G oblique test indicates a valid behavior of the model in intermediate directions as well. A new aspect of this study is the objective assessment of the multi-directional biofidelity of the mathematical human model according to accepted requirements. Although hardware dummies may always be used in regulations, it is expected that virtual testing with human models will serve in extrapolating outside the hardware test environment. This study was a first step towards simulating a wider range of impact conditions, such as angled impact and rollover.

Is ginger effective for the treatment of irritable bowel syndrome? A double blind randomized controlled pilot trial.

PubMed

van Tilburg, Miranda A L; Palsson, Olafur S; Ringel, Yehuda; Whitehead, William E

2014-02-01

Ginger is one of the most commonly used herbal medicines for irritable bowel syndrome (IBS) but no data exists about its effectiveness. Double blind randomized controlled trial. University of North Carolina, Chapel Hill, North Carolina, USA. Forty-five IBS patients were randomly assigned to three groups: placebo, 1g of ginger, and 2g of ginger daily for 28 days. The IBS severity scale (IBS-SS) was administered, as well as adequate relief of symptoms scale. A responder was defined as having at least 25% reduction in IBS-SS post-treatment. There were 57.1% responders to placebo, 46.7% to 1g and 33.3% to 2g of ginger. Adequate relief was reported by 53.3% on placebo and 53.3% in both ginger groups combined. Side effects were mild and reported by 35.7% in the placebo and 16.7% in the ginger groups. This double blind randomized controlled pilot study suggests ginger is well tolerated but did not perform better than placebo. Larger trials are needed before any definitive conclusions can be drawn. Copyright © 2014 Elsevier Ltd. All rights reserved.

Double versus single stenting for coronary bifurcation lesions: a meta-analysis.

PubMed

Katritsis, Demosthenes G; Siontis, George C M; Ioannidis, John P A

2009-10-01

Several trials have addressed whether bifurcation lesions require stenting of both the main vessel and side branch, but uncertainty remains on the benefits of such double versus single stenting of the main vessel only. We have conducted a meta-analysis of randomized trials including patients with coronary bifurcation lesions who were randomly selected to undergo percutaneous coronary intervention by either double or single stenting. Six studies (n=1642 patients) were eligible. There was increased risk of myocardial infarction with double stenting (risk ratio, 1.78; P=0.001 by fixed effects; risk ratio, 1.49 with Bayesian meta-analysis). The summary point estimate suggested also an increased risk of stent thrombosis with double stenting, but the difference was not nominally significant given the sparse data (risk ratio, 1.85; P=0.19). No obvious difference was seen for death (risk ratio, 0.81; P=0.66) and target lesion revascularization (risk ratio, 1.09; P=0.67). Stenting of both the main vessel and side branch in bifurcation lesions may increase myocardial infarction and stent thrombosis risk compared with stenting of the main vessel only.

Double-blind multicentre UK hospital studies of isoxicam vs naproxen

PubMed Central

Cardoe, N.; Hart, F. Dudley

1986-01-01

1 Two multicentre, parallel group, randomised, double-blind, double-dummy comparison studies were conducted between isoxicam in the usual dose of 200 mg once daily and naproxen 500 mg twice daily. 2 The drugs were administered for 4 weeks to 230 patients suffering from osteoarthritis of the hip and/or knee in the first trial and to 249 patients suffering from rheumatoid arthritis in the second. 3 The studies compared treatments for both safety and overall effectiveness in the relief of pain. 4 In the osteoarthritis trial, overall pain was reduced by both drugs after 2 weeks of therapy but only isoxicam produced further improvement after 4 weeks. 5 Isoxicam produced reductions comparable to those produced by naproxen in pain on standing from the sitting position, pain on walking, and pain on movement of the affected joint, after 2 and 4 weeks. 6 After 4 weeks, isoxicam given once daily in the morning was significantly more effective than naproxen given in the morning and the evening in relieving not only total pain as assessed by a visual analogue scale but, as importantly, night pain. 7 Compared to naproxen therapy, isoxicam therapy was associated with significantly more patients whose disease state was improved at 2 weeks, as assessed by physicians. 8 In the rheumatoid arthritis trial, isoxicam was equally as effective as naproxen in reducing joint tenderness, joint swelling, and pain; at 4 weeks there was a trend in favour of isoxicam in reduction of joint swelling and pain. 9 Isoxicam reduced morning stiffness significantly more than naproxen after 4 weeks; this trend was apparent at 2 weeks. 10 Patients thought that isoxicam was more effective than naproxen, to a significant difference. 11 In both trials, the two drugs were well tolerated and had similar side effects profiles, with the majority of adverse experiences being associated with the digestive system; no side effect was severe. PMID:3620277

Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study

PubMed Central

Schlesinger, Naomi; Mysler, Eduardo; Lin, Hsiao-Yi; De Meulemeester, Marc; Rovensky, Jozef; Arulmani, Udayasankar; Balfour, Alison; Krammer, Gerhard; Sallstig, Peter; So, Alexander

2011-01-01

Objective This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment. Methods In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4×4-weekly doses of canakinumab (50+50+25+25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks. Results A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses ≥50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28–0.38, p≤0.0083), and the percentage of patients experiencing ≥1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p<0.05). There was a 64% to 72% reduction in the risk of experiencing ≥1 flare for canakinumab doses ≥50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28–0.36, p≤0.05). The incidence of adverse events was similar across treatment groups. Conclusions Single canakinumab doses ≥50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg. PMID:21540198

Safety, tolerability, pharmacokinetics, and effects on human experimental pain of the selective ionotropic glutamate receptor 5 (iGluR5) antagonist LY545694 in healthy volunteers.

PubMed

Petersen, Karin L; Iyengar, Smriti; Chappell, Amy S; Lobo, Evelyn D; Reda, Haatem; Prucka, William R; Verfaille, Steven J

2014-05-01

The objective of this study was to establish in healthy volunteers the maximally tolerated multiple dose (MTMD) of the ionotropic glutamate receptor 5 antagonist LY545694 (part A), and to investigate whether that dose had analgesic or antihyperalgesic effects in the brief thermal stimulation (BTS) pain model (Part B). Part A was a double-blind, placebo-controlled study in 3 groups of 10 healthy men. To simulate an extended-release formulation, study drug was administered orally over 6hours (12 equally divided aliquots at 30-minute intervals). Part B was a double-blind, placebo-controlled, double-dummy, 3-way crossover study in 27 healthy men. At each of the 3 study periods, subjects received either LY545694 (MTMD; as determined during part A) as a simulated, twice daily extended-release formulation for 4 doses over 3days, gabapentin (600mg 8hours apart; 6 doses over 3days; positive control), or matching placebo. The BTS model was induced twice with a 1-hour interval on each of the 2 study days, before drug administration and at the time of expected peak analgesia of LY545694. Plasma exposure for LY545694 was approximately linear over the 25- to 75-mg dose range. The MTMD of LY545694 was 25mg twice daily. Areas of secondary hyperalgesia were significantly smaller after administration of LY545694 and gabapentin compared with placebo (P<.0001 and P=.0004, respectively), but there was no difference between areas after administration of gabapentin and LY545694 (P=.400). Neither gabapentin nor LY545694 reduced the painfulness of skin heating during BTS model induction. The most common treatment-emergent adverse event was dizziness. The results of this study suggest that LY545694 should be explored further as a potential treatment for chronic pain involving neuronal sensitization. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Acute Interaction of Baclofen in Combination with Alcohol in Heavy Social Drinkers

PubMed Central

Evans, Suzette M.; Bisaga, Adam

2008-01-01

Background There is growing evidence that GABA-B receptor agonists may be effective in the treatment of alcohol abuse or dependence. The primary goal of this study was to determine the safety of baclofen in combination with alcohol consumption in heavy drinkers. In addition, the effects of baclofen alone, and in combination with alcohol, on subjective effects, cognitive performance effects, as well as alcohol craving, were assessed. Methods Eighteen non-treatment seeking heavy social drinkers (mean of 28 drinks/week) who did not meet criteria for alcohol dependence participated. All individuals were tested using a double-blind double-dummy design with six 2-day inpatient phases. Baclofen (0, 40, and 80 mg) was administered 2.5 hours before alcohol (1.5 g/l body water or approximately 0.75 g/kg) or placebo beverages, given in 4 divided doses every 20 min. Results Baclofen, either alone, or in combination with alcohol, produced only modest increases in heart rate and blood pressure and no adverse effects were reported. Baclofen did not increase positive subjective effects (e.g., Stimulant effects, Drug Liking) but did increase sedation and impair performance. Even though both baclofen and alcohol impaired performance, for the most part performance was not impaired to a greater extent when baclofen was combined with alcohol. Among this population of non-dependent drinkers, baclofen did not alter alcohol craving or alcohol-induced positive subjective effects. Conclusions Baclofen alone has minimal abuse liability in heavy social drinkers and baclofen is relatively well tolerated and safe when given in combination with intoxicating doses of alcohol. PMID:18840257

Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential

PubMed Central

Reissig, Chad J.; Harrison, Joseph A.; Carter, Lawrence P.; Griffiths, Roland R.

2014-01-01

Rationale Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects. Objectives This study sought to determine if the rate of onset of subjective effects and abuse potential of alprazolam would be increased when administered via inhalation vs. the oral route. Methods Placebo, inhaled alprazolam (0.5, 1, 2 mg), and oral alprazolam (1, 2, 4 mg) were administered under double-blind, double-dummy conditions using a cross-over design in 14 healthy participants with histories of drug abuse. Participant and observer ratings, and behavioral and cognitive performance measures were assessed repeatedly during 9 hour sessions. Results Both routes of administration produced orderly dose and time-related effects, with higher doses producing greater and longer lasting effects. Onset of subjective effects following inhaled alprazolam was very rapid (e.g., 2 vs. 49 minutes after 2 mg inhaled vs. oral). On measures of abuse potential (e.g., liking and good effects), inhaled alprazolam was more potent, as evidenced by a leftward shift in the dose response curve. Despite the potency difference, at the highest doses, peak ratings of subjective effects related to abuse potential (e.g., “drug liking”) were similar across the two routes. On other measures (e.g., sedation and performance) the routes were equipotent. Conclusions The inhaled route of administration modestly increased the abuse potential of alprazolam despite significantly increasing its rate of onset. If marketed, the reduced availability and increased cost of inhaled alprazolam may render the societal risk of increased abuse to be low. PMID:25199955

Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential.

PubMed

Reissig, Chad J; Harrison, Joseph A; Carter, Lawrence P; Griffiths, Roland R

2015-03-01

Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects. This study sought to determine if the rate of onset of subjective effects and abuse potential of alprazolam would be increased when administered via inhalation vs. the oral route. Placebo, inhaled alprazolam (0.5, 1, and 2 mg), and oral alprazolam (1, 2, and 4 mg) were administered under double-blind, double-dummy conditions using a crossover design in 14 healthy participants with histories of drug abuse. Participant and observer ratings and behavioral and cognitive performance measures were assessed repeatedly during 9-h sessions. Both routes of administration produced orderly dose and time-related effects, with higher doses producing greater and longer-lasting effects. Onset of subjective effects following inhaled alprazolam was very rapid (e.g., 2 vs. 49 min after 2 mg inhaled vs. oral). On measures of abuse potential (e.g., liking and good effects), inhaled alprazolam was more potent, as evidenced by a leftward shift in the dose-response curve. Despite the potency difference, at the highest doses, peak ratings of subjective effects related to abuse potential (e.g., "drug liking") were similar across the two routes. On other measures (e.g., sedation and performance), the routes were equipotent. The inhaled route of administration modestly increased the abuse potential of alprazolam despite significantly increasing its rate of onset. If marketed, the reduced availability and increased cost of inhaled alprazolam may render the societal risk of increased abuse to be low.

Effect of low-level laser therapy in the treatment of cochlear tinnitus: a double-blind, placebo-controlled study.

PubMed

Dehkordi, Mahboobeh Adami; Einolghozati, Sasan; Ghasemi, Seyyed Mohsen; Abolbashari, Samaneh; Meshkat, Mojtaba; Behzad, Hadi

2015-01-01

Many treatments for chronic tinnitus have been attempted, but the condition remains difficult to cure, especially in the case of cochlear tinnitus. We conducted a prospective, double-blind, placebo-controlled study to assess the effect of low-dose laser therapy on chronic cochlear tinnitus. Our study population was made up of 66 patients-33 who received active laser treatment (case group) and 33 who received inactive dummy treatment (control group). Patients in the laser group received 5 mV with a wavelength of 650 nm for 20 minutes a day, 5 days a week, for 4 weeks. The controls followed the same schedule, but they were "treated" with an inactive device. The degree of tinnitus was evaluated before and after treatment in each group in three ways: (1) the Tinnitus Severity Index (TSI), (2) a subjective 10-point self-assessment scale for tinnitus loudness, and (3) the Tinnitus Evaluation Test (TET). At study's end, we found no statistically significant differences between the case and control groups in the number of patients who experienced a reduction in TSI values (p = 0.589) or a reduction in subjective self-assessment scores (p = 0.475). Nor did we find any significant reductions in the loudness (p = 0.665) and frequency (p = 0.396) of tinnitus as determined by the TET. We conclude that 5-mV laser therapy with a wavelength of 650 nm is no better than placebo for improving hearing thresholds overall or for treating tinnitus with regard to age, sex, environmental noise level, and the duration of tinnitus.

Frontal sled tests comparing rear and forward facing child restraints with 1-3 year old dummies.

PubMed

Sherwood, C P; Crandall, J R

2007-01-01

Although most countries recommend transitioning children from rear facing (RF) to forward facing (FF) child restraints at one year of age, Swedish data suggests that RF restraints are more effective. The objective of this study was to compare RF and FF orientations in frontal sled tests. Four dummies (CRABI 12 mo, Q1.5, Hybrid III 3 yr, and Q3) were used to represent children from 1 to 3 years of age. Restraint systems tested included both 1) LATCH and 2) rigid ISOFIX with support leg designs. Rear facing restraints with support legs provided the best results for all injury measures, while RF restraints in general provided the lowest chest displacements and neck loads.

Cryptographic salting for security enhancement of double random phase encryption schemes

NASA Astrophysics Data System (ADS)

Velez Zea, Alejandro; Fredy Barrera, John; Torroba, Roberto

2017-10-01

Security in optical encryption techniques is a subject of great importance, especially in light of recent reports of successful attacks. We propose a new procedure to reinforce the ciphertexts generated in double random phase encrypting experimental setups. This ciphertext is protected by multiplexing with a ‘salt’ ciphertext coded with the same setup. We present an experimental implementation of the ‘salting’ technique. Thereafter, we analyze the resistance of the ‘salted’ ciphertext under some of the commonly known attacks reported in the literature, demonstrating the validity of our proposal.

Symmetry breaking in tensor models

NASA Astrophysics Data System (ADS)

Benedetti, Dario; Gurau, Razvan

2015-11-01

In this paper we analyze a quartic tensor model with one interaction for a tensor of arbitrary rank. This model has a critical point where a continuous limit of infinitely refined random geometries is reached. We show that the critical point corresponds to a phase transition in the tensor model associated to a breaking of the unitary symmetry. We analyze the model in the two phases and prove that, in a double scaling limit, the symmetric phase corresponds to a theory of infinitely refined random surfaces, while the broken phase corresponds to a theory of infinitely refined random nodal surfaces. At leading order in the double scaling limit planar surfaces dominate in the symmetric phase, and planar nodal surfaces dominate in the broken phase.

Efficacy, safety and tolerability of ongoing statin plus ezetimibe versus doubling the ongoing statin dose in hypercholesterolemic Taiwanese patients: an open-label, randomized clinical trial

PubMed Central

2012-01-01

Background Reducing low-density lipoprotein cholesterol (LDL-C) is associated with reduced risk for major coronary events. Despite statin efficacy, a considerable proportion of statin-treated hypercholesterolemic patients fail to reach therapeutic LDL-C targets as defined by guidelines. This study compared the efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing statin in a population of Taiwanese patients with hypercholesterolemia. Methods This was a randomized, open-label, parallel-group comparison study of ezetimibe 10 mg added to ongoing statin compared with doubling the dose of ongoing statin. Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with previous statin treatment were randomized (N = 83) to ongoing statin + ezetimibe (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or 20/10 mg) or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin 20 mg or pravastatin 40 mg) for 8 weeks. Percent change in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides, and specified safety parameters were assessed at 4 and 8 weeks. Results At 8 weeks, patients treated with statin + ezetimibe experienced significantly greater reductions compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026) and total cholesterol (20.8% vs 12.2%, p = 0.0003). Percentage of patients achieving treatment goal was greater for statin + ezetimibe (58.6%) vs doubling statin (41.2%), but the difference was not statistically significant (p = 0.1675). The safety and tolerability profiles were similar between treatments. Conclusion Ezetimibe added to ongoing statin therapy resulted in significantly greater lipid-lowering compared with doubling the dose of statin in Taiwanese patients with hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT00652327 PMID:22621316

The effectiveness of nutrition education for overweight/obese mothers with stunted children (NEO-MOM) in reducing the double burden of malnutrition in Indonesia: study protocol for a randomized controlled trial.

PubMed

Mahmudiono, Trias; Nindya, Triska Susila; Andrias, Dini Ririn; Megatsari, Hario; Rosenkranz, Richard R

2016-06-08

Nutrition transition in developing countries were induced by rapid changes in food patterns and nutrient intake when populations adopt modern lifestyles during economic and social development, urbanization and acculturation. Consequently, these countries suffer from the double burden of malnutrition, consisting of unresolved undernutrition and the rise of overweight/obesity. The prevalence of the double burden of malnutrition tends to be highest for moderate levels (third quintile) of socioeconomic status. Evidence suggests that modifiable factors such as intra-household food distribution and dietary diversity are associated with the double burden of malnutrition, given household food security. This article describes the study protocol of a behaviorally based nutrition education intervention for overweight/obese mothers with stunted children (NEO-MOM) in reducing the double burden of malnutrition. NEO-MOM is a randomized controlled trial with a three-month behavioral intervention for households involving pairs of 72 stunted children aged 2-5 years old and overweight/obese mothers (SCOWT) in urban Indonesia. The SCOWT pairs were randomly assigned to either an intervention group or to a comparison group that received usual care plus printed educational materials. The intervention consisted of six classroom sessions on nutrition education and home visits performed by trained community health workers using a motivational interviewing approach. The primary outcomes of this study are the prevalence of double burden of malnutrition as measured in SCOWT, child's height-for-age z-score (HAZ) and maternal body mass index (BMI). Because previous studies are mainly observational in nature, this study advances understanding of the double burden of malnutrition through a fully powered randomized controlled trial. The intervention assists participants in self-administered goal setting to improve diet and child feeding behaviors by improving self-efficacy. Maternal self-efficacy may be enhanced through vicarious and active mastery of experiences gained during six sessions of nutrition education and verbal persuasion during home visits. The Universal Trial Number (UTN) for this study is U1111-1175-5834. This trial was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) and is allocated the registration number: ACTRN12615001243505 on 12 November 2015.

Development of a continuous motorcycle protection barrier system using computer simulation and full-scale crash testing.

PubMed

Atahan, Ali O; Hiekmann, J Marten; Himpe, Jeffrey; Marra, Joseph

2018-07-01

Road restraint systems are designed to minimize the undesirable effects of roadside accidents and improve safety of road users. These systems are utilized at either side or median section of roads to contain and redirect errant vehicles. Although restraint systems are mainly designed against car, truck and bus impacts there is an increasing pressure by the motorcycle industry to incorporate motorcycle protection systems into these systems. In this paper development details of a new and versatile motorcycle barrier, CMPS, coupled with an existing vehicle barrier is presented. CMPS is intended to safely contain and redirect motorcyclists during a collision event. First, crash performance of CMPS design is evaluated by means of a three dimensional computer simulation program LS-DYNA. Then full-scale crash tests are used to verify the acceptability of CMPS design. Crash tests were performed at CSI proving ground facility using a motorcycle dummy in accordance with prEN 1317-8 specification. Full-scale crash test results show that CMPS is able to successfully contain and redirect dummy with minimal injury risk on the dummy. Damage on the barrier is also minimal proving the robustness of the CMPS design. Based on the test findings and further review by the authorities the implementation of CMPS was recommended at highway system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preparation of dummy template imprinted polymers at surface of silica microparticles for the selective extraction of trace bisphenol A from water samples.

PubMed

Zhao, Wenhui; Sheng, Na; Zhu, Rong; Wei, Fangdi; Cai, Zheng; Zhai, Meijuan; Du, Shuhu; Hu, Qin

2010-07-15

Molecularly imprinted polymers for bisphenol A (BPA) were prepared by using surface molecular imprinting technique. Analogues of BPA, namely 4,4'-dihydroxybiphenyl and 3,3',5,5'-tetrabromobisphenol A, were used as the dummy templates instead of BPA, to avoid the leakage of a trace amount of the target analyte (BPA). The resulting dummy molecularly imprinted polymers (DMIPs) showed the large sorption capacity, high recognition ability and fast binding kinetics for BPA. The maximal sorption capacity was up to 958 micromol g(-1), and it only took 40 min for DMIPs to achieve the sorption equilibrium. The DMIPs were successfully applied to the solid-phase extraction coupled with HPLC/UV for the determination of BPA in water samples. The calibration graph of the analytical method was linear with a correlation coefficient more than 0.999 in the concentration range of 0.0760-0.912 ng mL(-1) of BPA. The limit of detection was 15.2 pg mL(-1) (S/N=3). Recoveries were in the range of 92.9-102% with relative standard deviation (RSD) less than 11%. The trace amounts of BPA in tap water, drinking water, rain and leachate of one-off tableware were determined by the method built, and the satisfactory results were obtained. 2010 Elsevier B.V. All rights reserved.

"Zero-Mass" Noninvasive Pressure Transducers

NASA Technical Reports Server (NTRS)

Hartley, Frank T.

2009-01-01

Extremely lightweight, compact, noninvasive, rugged, relatively inexpensive strain-gauge transducers have been developed for use in measuring pressures of fluids in tubes. These gauges were originally intended for measuring pressures of spacecraft-propulsion fluids, but they are also attractive for use in numerous terrestrial applications especially those involving fluids that are extremely chemically reactive, fluids that must be isolated for hygienic purposes, fluids that must be allowed to flow without obstruction, and fluid-containing tubes exposed to severe environments. A basic pressure transducer of this type comprises one or more pair(s) of thin-film strain gauges integral with a tube that contains the fluid of interest. Following established strain-gauge practice, the gauges in each pair are connected into opposite arms of a Wheatstone bridge (see figure). Typically, each pressure transducer includes one pair (the active pair) of strain gauges for measuring the hoop stress proportional to the pressure of the fluid in the tube and another pair (the dummy pair) of strain gauges that are nominally unstrained: The dummy gauges are mounted on a substrate that is made of the same material as that of the tube. The substrate is welded to the tube at only one spot so that stresses and strains are not coupled from the tube into the substrate. The dummy strain gauges measure neutral strains (basically, strains associated with thermal expansion), so that the neutral-strain contribution can be subtracted out of the final gauge reading.

Comparison of current ATDs with Chinese adults in anthropometry.

PubMed

Cao, Libo; Zhang, Kai; Lv, Xin; Yan, Lingbo

2016-05-18

Crash test dummies are full-scale anthropomorphic test devices (ATDs) that simulate the dimensions, weight proportions, and articulation of the human body and are used to measure human injury potential in vehicle crashes. The Hybrid III dummy family, which is widely used currently, takes selected percentiles of anthropometry dimensions of U.S. adults as design references. The objective of this study was to assess the difference in anthropometry between Chinese adults and the currently used dummy. Based on the Chinese National Physical Fitness Surveillance of the year 2000, 2005, 2010 and National Standard of China GB/T 10000-1988, a series of anthropometric parameters for Chinese adults were obtained, and data analysis was conducted between Chinese adults and ATDs that are currently used. The comparison revealed distinct anthropometric difference between ATDs and Chinese adults. Based on the latest data, median Chinese females were about 2.6% lower in stature and about 8.03% lower in body weight than the ATD design targets. Similarly, median Chinese males were about 3.48% shorter and weighed 11.89% less than the ATD design targets. Although the anthropometric differences between Chinese adults and the Hybrid III ATD specifications were modest and growing smaller, it is advisable to take the differences in anthropometry between ATDs and Chinese adults into consideration when developing new vehicles in China to provide effective protection specifically for Chinese occupants.

The Impact of Preoperative Enteral Nutrition Enriched with Eicosapentaenoic Acid on Postoperative Hypercytokinemia after Pancreatoduodenectomy: The Results of a Double-Blinded Randomized Controlled Trial.

PubMed

Ashida, Ryo; Okamura, Yukiyasu; Wakabayashi-Nakao, Kanako; Mizuno, Takashi; Aoki, Shuichi; Uesaka, Katsuhiko

2018-06-08

To investigate whether preoperative enteral diets -enriched in eicosapentaenoic acid (EPA) supplements could reduce the incidence of hypercytokinemia after pancreatoduodenectomy (PD) in a double-blinded randomized -controlled trial. Patients with resectable periampullary cancer were randomized into either the control group or the treatment group. Patients in the treatment group received oral supplementation (600 kcal/day) containing EPA for 7 days before surgery. Patients in the control group received isocaloric isonitrogenous standard nutrition (600 kcal/day) without EPA for 7 days before surgery. The primary endpoint was postoperative serum concentrations of interleukin-6 (IL-6). The secondary endpoints were the postoperative nutritional status and the incidence of postoperative infectious complications. Twenty-four patients were enrolled in the present study. After exclusion, 20 patients (control group, n = 9; treatment group, n = 11) were analyzed. There were no significant differences in the curves for the serum concentration of IL-6 (p = 0.68) or the incidence of infectious complications between the 2 groups (control group: 78%, treatment group: 55%, p = 0.37). The results of a double-blinded randomized controlled trial indicated that preoperative immunonutrition had no marked impact on the rates of postoperative hypercytokinemia or infectious complications after PD. © 2018 S. Karger AG, Basel.

Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial

PubMed Central

Amrutesh, Sunita; Malini, J; Tandur, Prakash S; Patki, Pralhad S

2010-01-01

Background The aim of this study was to evaluate the efficacy and safety of herbal dental cream in comparison to fluoride dental cream. Objectives Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial. Methods One hundred and two patients with established dental plaque were randomly assigned to either herbal dental group or fluoride dental group for six weeks in a double-blind design. Improvement in plaque index, oral hygiene status, bleeding index, and gingival index was evaluated in these patients along with microbiological study. Results Results indicated a significant reduction in plaque index, gingival index, oral hygiene index, and microbial growth in both groups. Difference between the groups was not significant. There was no significant change in bleeding index. No adverse events were reported and both the dental creams were well tolerated. Conclusion The finding of this preliminary study indicates that herbal dental cream is as safe and effective as fluoride dental cream, but not superior to it. PMID:27186096

Study Program to Determine the Acceleration Environment Capability of the GG159C Gas- Bearing Spinmotor Final Report

NASA Technical Reports Server (NTRS)

Erickson, G. J.

1964-01-01

The goal of this contract was to determine the g environment under which the GC159C Gas-Bearing Spinmotor (GBSM) could reliably operate. This was fulfilled by building and testing of four GBSM's, a test fixture, and a "dummy" gyro. The test program was divided into two phases when a gas bearing improvement was required to withstand JPL shock requirement of 200 g. Phase I determined existing g capabilities and performance of the GC159C GBSM and gimbal-case structure. Phase II increased GBSM capability to meet required JPL g environments. Life tests were run on two GBSM's which were shocked at a high level to obtain bearing contact while rotating at their operating speed of 23,000 rpm. A third (nonoperating) GBSM was exposed to JPL maximum shock levels, and a fourth (nonoperating) GBSM was exposed to random vibration. Both nonoperating GBSM's were then subjected to life testing.

Investigation on Prototype Superconducting Linear Synchronous Motor (LSM) for 600-km/h Wheel-Type Railway

NASA Astrophysics Data System (ADS)

Eom, Beomyong; Lee, Changhyeong; Kim, Seokho; Lee, Changyoung; Yun, Sangwon

The existing wheel-type high-speed railway with a rotatable motor has a limit of 600 km/h speed. The normal conducting electromagnet has several disadvantages to realize 600 km/h speed. Several disadvantages are the increased space and weight, and the decreased electric efficiency to generate the required high magnetic field. In order to reduce the volume and weight, superconducting electromagnets can be considered for LSM (Linear Synchronous Motor). Prior to the fabrication of the real system, a prototype demo-coil is designed and fabricated using 2G high temperature superconducting wire. The prototype HTS coil is cooled by the conduction using a GM cryocooler. To reduce the heat penetration, thermal design was performed for the current leads, supporting structure and radiation shield considering the thermal stress. The operating temperature and current are 30∼40 K and 100 A. The coil consists of two double pancake coils (N, S pole, respectively) and it is driven on a test rail, which is installed for the test car. This paper describes the design and test results of the prototype HTS LSM system. Thermal characteristics are investigated with additional dummy thermal mass on the coil after turning off the cryocooler.

Artificial fingerprint recognition by using optical coherence tomography with autocorrelation analysis.

PubMed

Cheng, Yezeng; Larin, Kirill V

2006-12-20

Fingerprint recognition is one of the most widely used methods of biometrics. This method relies on the surface topography of a finger and, thus, is potentially vulnerable for spoofing by artificial dummies with embedded fingerprints. In this study, we applied the optical coherence tomography (OCT) technique to distinguish artificial materials commonly used for spoofing fingerprint scanning systems from the real skin. Several artificial fingerprint dummies made from household cement and liquid silicone rubber were prepared and tested using a commercial fingerprint reader and an OCT system. While the artificial fingerprints easily spoofed the commercial fingerprint reader, OCT images revealed the presence of them at all times. We also demonstrated that an autocorrelation analysis of the OCT images could be potentially used in automatic recognition systems.

Genotype-environment interaction in passive avoidance learning of the paradise fish (Macropodus opercularis).

PubMed

Csányi, V; Gervai, J

1985-01-01

Passive dark avoidance conditioning and effects of the presence and absence of a fish-like dummy on the training process were studied in four inbred strains of paradise fish. Strain differences were found in the shuttle activity during habituation trials, and in the sensitivity to the mild electric shock punishment. The presence or absence of the dummy in the punished dark side of the shuttle box had a genotype-dependent effect on the measures taken during the conditioning process. The statistical analysis of the learning curves revealed differences in the way the strains varied in the different environments, i.e. genotype--environment interaction components of variances were identified. The results are discussed in the light of previous investigations and their implication in further genetic analysis.

Artificial fingerprint recognition by using optical coherence tomography with autocorrelation analysis

NASA Astrophysics Data System (ADS)

Cheng, Yezeng; Larin, Kirill V.

2006-12-01

Fingerprint recognition is one of the most widely used methods of biometrics. This method relies on the surface topography of a finger and, thus, is potentially vulnerable for spoofing by artificial dummies with embedded fingerprints. In this study, we applied the optical coherence tomography (OCT) technique to distinguish artificial materials commonly used for spoofing fingerprint scanning systems from the real skin. Several artificial fingerprint dummies made from household cement and liquid silicone rubber were prepared and tested using a commercial fingerprint reader and an OCT system. While the artificial fingerprints easily spoofed the commercial fingerprint reader, OCT images revealed the presence of them at all times. We also demonstrated that an autocorrelation analysis of the OCT images could be potentially used in automatic recognition systems.

The influence of a smoking ban on the profitability of Belgian restaurants.

PubMed

De Schoenmaker, Sofie; Van Cauwenberge, Philippe; Vander Bauwhede, Heidi

2013-05-01

To examine whether the nationwide smoking ban, imposed in 2007, had an impact on the profitability of Belgian restaurants. Objective financial reporting data on 1613 restaurants were analysed with return on assets as the outcome measure. The data were collected from the Belfirst database and cover the period 2004-2009. To assess the impact of the smoking ban, a differences-in-differences estimation method was used, with bars serving as the control group. The regression model was estimated, while controlling for firm-specific characteristics and unobserved firm-level heterogeneity. The variable of interest is the interaction between the smoking ban dummy and the dummy for the treatment group. The coefficient of this variable is insignificant. The adoption of the nationwide smoking ban did not affect the profitability of Belgian restaurants.

Aspect Ratio Model for Radiation-Tolerant Dummy Gate-Assisted n-MOSFET Layout.

PubMed

Lee, Min Su; Lee, Hee Chul

2014-01-01

In order to acquire radiation-tolerant characteristics in integrated circuits, a dummy gate-assisted n-type metal oxide semiconductor field effect transistor (DGA n-MOSFET) layout was adopted. The DGA n-MOSFET has a different channel shape compared with the standard n-MOSFET. The standard n-MOSFET has a rectangular channel shape, whereas the DGA n-MOSFET has an extended rectangular shape at the edge of the source and drain, which affects its aspect ratio. In order to increase its practical use, a new aspect ratio model is proposed for the DGA n-MOSFET and this model is evaluated through three-dimensional simulations and measurements of the fabricated devices. The proposed aspect ratio model for the DGA n-MOSFET exhibits good agreement with the simulation and measurement results.