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Sample records for model post-hoc analyses

  1. Post-Hoc Pattern-Oriented Testing and Tuning of an Existing Large Model

    DEFF Research Database (Denmark)

    Topping, Christopher John; Dalkvist, Trine; Grimm, Volker

    2012-01-01

    Pattern-oriented modeling (POM) is a general strategy for modeling complex systems. In POM, multiple patterns observed at different scales and hierarchical levels are used to optimize model structure, to test and select sub-models of key processes, and for calibration. So far, POM has been used...... environment closely. We therefore conclude that post-hoc POM is a useful and viable way to test a highly complex simulation model, but also warn against the dangers of over-fitting to real world patterns that lack details in their explanatory driving factors. To overcome some of these obstacles we suggest...... for developing new models and for models of low to moderate complexity. It remains unclear, though, whether the basic idea of POM to utilize multiple patterns, could also be used to test and possibly develop existing and established models of high complexity. Here, we use POM to test, calibrate, and further...

  2. Symptomatic efficacy of rasagiline monotherapy in early Parkinson's disease: post-hoc analyses from the ADAGIO trial.

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    Jankovic, Joseph; Berkovich, Elijahu; Eyal, Eli; Tolosa, Eduardo

    2014-06-01

    The ADAGIO study included a large cohort of patients with early PD (baseline total-UPDRS = 20) who were initially randomized to rasagiline and placebo, thereby allowing analyses of symptomatic efficacy. Post-hoc analyses comparing the efficacy of rasagiline 1 mg/day (n = 288) versus placebo (n = 588) on key symptoms at 36 weeks, and on total-UPDRS scores over 72 weeks (completer population: rasagiline 1 mg/day n = 221, placebo n = 392) were performed. Treatment with rasagiline resulted in significantly better tremor, bradykinesia, rigidity and postural-instability-gait-difficulty scores at week 36 versus placebo. Whereas the placebo group experienced progressive deterioration from baseline (2.6 UPDRS points at week 36), patients in the rasagiline group were maintained at baseline values at week 60 (UPDRS-change of 0.3 points). At week 72, patients who had received continuous monotherapy with rasagiline experienced a worsening of only 1.6 points. Treatment with rasagiline maintained motor function to baseline values for at least a year with significant benefits observed in all key PD motor symptoms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Rasagiline adjunct therapy in patients with Parkinson's disease: post hoc analyses of the PRESTO and LARGO trials.

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    Elmer, Lawrence W

    2013-11-01

    Rasagiline was safe and effective when used as adjunct therapy with levodopa in patients with moderate-to-advanced Parkinson's disease (PD) in the phase III PRESTO and LARGO studies. To assess clinical effects of rasagiline 1 mg/day on cardinal PD symptoms and motor fluctuations in defined patient subgroups using pooled data from PRESTO and LARGO. Both double-blind, randomized, and placebo-controlled studies included PD patients with motor fluctuations despite optimized therapy with levodopa, with or without concomitant dopamine agonists (DA) or catechol-O-methyltransferase inhibitor (COMT-I) treatment. These post hoc analyses measured effects of rasagiline 1 mg vs placebo on individual cardinal PD symptoms during ON time and mean change from baseline in daily OFF time in subgroups of patients who at baseline were receiving only levodopa, were considered "mild fluctuators" (daily OFF time ≤ 4 h), and who were or were not receiving concomitant DA or COMT-I therapy. Compared with placebo, rasagiline significantly improved all cardinal PD symptoms and significantly reduced adjusted mean daily OFF time when used as first adjunct therapy in levodopa-treated patients and in patients with mild motor fluctuations. Significant improvement in motor fluctuations was reported with rasagiline regardless of concomitant DA or COMT-I use. Overall incidence of dopaminergic adverse events did not increase with concomitant DA or COMT-I use. Rasagiline was an effective first adjunct therapy in levodopa-treated patients; benefited patients with signs of early "wearing off"; improved all cardinal PD symptoms; and further improved symptoms in patients already receiving other adjunctive dopaminergic treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Onset of efficacy and tolerability following the initiation dosing of long-acting paliperidone palmitate: post-hoc analyses of a randomized, double-blind clinical trial

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    Fu Dong-Jing

    2011-05-01

    Full Text Available Abstract Background Paliperidone palmitate is a long-acting injectable atypical antipsychotic for the acute and maintenance treatment of adults with schizophrenia. The recommended initiation dosing regimen is 234 mg on Day 1 and 156 mg on Day 8 via intramuscular (deltoid injection; followed by 39 to 234 mg once-monthly thereafter (deltoid or gluteal. These post-hoc analyses addressed two commonly encountered clinical issues regarding the initiation dosing: the time to onset of efficacy and the associated tolerability. Methods In a 13-week double-blind trial, 652 subjects with schizophrenia were randomized to paliperidone palmitate 39, 156, or 234 mg (corresponding to 25, 100, or 150 mg equivalents of paliperidone, respectively or placebo (NCT#00590577. Subjects randomized to paliperidone palmitate received 234 mg on Day 1, followed by their randomized fixed dose on Day 8, and monthly thereafter, with no oral antipsychotic supplementation. The onset of efficacy was defined as the first timepoint where the paliperidone palmitate group showed significant improvement in the Positive and Negative Syndrome Scale (PANSS score compared to placebo (Analysis of Covariance [ANCOVA] models and Last Observation Carried Forward [LOCF] methodology without adjusting for multiplicity using data from the Days 4, 8, 22, and 36 assessments. Adverse event (AE rates and relative risks (RR with 95% confidence intervals (CI versus placebo were determined. Results Paliperidone palmitate 234 mg on Day 1 was associated with greater improvement than placebo on Least Squares (LS mean PANSS total score at Day 8 (p = 0.037. After the Day 8 injection of 156 mg, there was continued PANSS improvement at Day 22 (p ≤ 0.007 vs. placebo and Day 36 (p Conclusions Significantly greater symptom improvement was observed by Day 8 with paliperidone palmitate (234 mg on Day 1 compared to placebo; this effect was maintained after the 156 mg Day 8 injection, with a trend towards a dose

  5. Post Hoc Analyses of Randomized Clinical Trial for the Effect of Clopidogrel Added to Aspirin on Kidney Function.

    Science.gov (United States)

    Ikeme, Jesse C; Pergola, Pablo E; Scherzer, Rebecca; Shlipak, Michael G; Benavente, Oscar R; Peralta, Carmen A

    2017-07-07

    Despite the high burden of CKD, few specific therapies are available that can halt disease progression. In animal models, clopidogrel has emerged as a potential therapy to preserve kidney function. The effect of clopidogrel on kidney function in humans has not been established. The Secondary Prevention of Small Subcortical Strokes Study randomized participants with prior lacunar stroke to treatment with aspirin or aspirin plus clopidogrel. We compared annual eGFR decline and incidence of rapid eGFR decline (≥30% from baseline) using generalized estimating equations and interval-censored proportional hazards regression, respectively. We also stratified our analyses by baseline eGFR, systolic BP target, and time after randomization. At randomization, median age was 62 (interquartile range, 55-71) years old; 36% had a history of diabetes, 90% had hypertension, and the median eGFR was 81 (interquartile range, 65-94) ml/min per 1 m 2 . Persons receiving aspirin plus clopidogrel had an average annual change in kidney function of -1.39 (95% confidence interval, -1.15 to -1.62) ml/min per 1.73 m 2 per year compared with -1.52 (95% confidence interval, -1.30 to -1.74) ml/min per 1.73 m 2 per year among persons receiving aspirin only ( P =0.42). Rapid kidney function decline occurred in 21% of participants receiving clopidogrel plus aspirin compared with 22% of participants receiving aspirin plus placebo (hazard ratio, 0.94; 95% confidence interval, 0.79 to 1.10; P =0.42). Findings did not vary by baseline eGFR, time after randomization, or systolic BP target (all P values for interaction were >0.3). We found no effect of clopidogrel added to aspirin compared with aspirin alone on kidney function decline among persons with prior lacunar stroke. Copyright © 2017 by the American Society of Nephrology.

  6. Relationship between disease activity and patient-reported outcomes in rheumatoid arthritis: Post hoc analyses of overall and Japanese results from two phase 3 clinical trials.

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    Ishiguro, Naoki; Dougados, Maxime; Cai, Zhihong; Zhu, Baojin; Ishida, Masato; Sato, Masayo; Gaich, Carol; Quebe, Amanda; Stoykov, Ivaylo; Tanaka, Yoshiya

    2018-02-02

    To examine patient-reported outcomes (PROs) in patients with different rheumatoid arthritis (RA) disease activity levels and identify residual symptoms. Post hoc analyses of overall and Japanese data from two randomized controlled trials including RA patients with previous inadequate responses to methotrexate (NCT01710358) or no/minimal previous disease-modifying antirheumatic drug treatment (NCT01711359) (sponsor: Eli Lilly and Company). Week 24 assessments were disease activity (Simplified Disease Activity Index, Disease Activity Score/Disease Activity Score 28 joints-erythrocyte sedimentation rate) and PROs (pain visual analog scale [VAS], morning joint stiffness [MJS], Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue, and Medical Outcomes Study Short Form 36 Health Survey Physical and Mental Component Scores). Patients achieving remission/low disease activity (LDA) at Week 24 had larger/significant improvements from baseline in pain, MJS, disability, fatigue, and physical and emotional quality of life versus patients with high/moderate disease activity. Some patients achieving remission and LDA, reported residual pain (pain VAS >10 mm): 20.8-39.3% and 48.7-70.0% (overall study populations), 16.0-34.5% and 47.1-62.0% (Japanese patients). Residual MJS and fatigue were also reported. Remission/LDA were associated with improvements in PROs in overall and Japanese patient populations; however, some patients achieving remission had residual symptoms, including pain.

  7. Nursing home placement in the Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO-AD) trial: secondary and post-hoc analyses.

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    Howard, Robert; McShane, Rupert; Lindesay, James; Ritchie, Craig; Baldwin, Ashley; Barber, Robert; Burns, Alistair; Dening, Tom; Findlay, David; Holmes, Clive; Jones, Robert; Jones, Roy; McKeith, Ian; Macharouthu, Ajay; O'Brien, John; Sheehan, Bart; Juszczak, Edmund; Katona, Cornelius; Hills, Robert; Knapp, Martin; Ballard, Clive; Brown, Richard G; Banerjee, Sube; Adams, Jessica; Johnson, Tony; Bentham, Peter; Phillips, Patrick P J

    2015-12-01

    Findings from observational studies have suggested a delay in nursing home placement with dementia drug treatment, but findings from a previous randomised trial of patients with mild-to-moderate Alzheimer's disease showed no effect. We investigated the effects of continuation or discontinuation of donepezil and starting of memantine on subsequent nursing home placement in patients with moderate-to-severe Alzheimer's disease. In the randomised, double-blind, placebo-controlled Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO-AD) trial, community-living patients with moderate-to-severe Alzheimer's disease (who had been prescribed donepezil continuously for at least 3 months at a dose of 10 mg for at least the previous 6 weeks and had a score of between 5 and 13 on the Standardised Mini-Mental State Examination) were recruited from 15 secondary care memory centres in England and Scotland and randomly allocated to continue donepezil 10 mg per day without memantine, discontinue donepezil without memantine, discontinue donepezil and start memantine 20 mg per day, or continue donepezil 10 mg per day and start memantine 20 mg per day, for 52 weeks. After 52 weeks, choice of treatment was left to participants and their physicians. Place of residence was recorded during the first 52 weeks of the trial and then every 26 weeks for a further 3 years. A secondary outcome of the trial, reported in this study, was nursing home placement: an irreversible move from independent accommodation to a residential caring facility. Analyses restricted to risk of placement in the first year of follow-up after the patients had completed the double-blind phase of the trial were post-hoc. The DOMINO-AD trial is registered with the ISRCTN Registry, number ISRCTN49545035. Between Feb 11, 2008, and March 5, 2010, 73 (25%) patients were randomly assigned to continue donepezil without memantine, 73 (25%) to discontinue donepezil without memantine, 76 (26%) to discontinue

  8. The efficacy of extended-release levomilnacipran in moderate to severe major depressive disorder: secondary and post-hoc analyses from a randomized, double-blind, placebo-controlled study.

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    Montgomery, Stuart A; Mansuy, Lucilla; Ruth, Adam C; Li, Dayong; Gommoll, Carl

    2014-01-01

    Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin and norepinephrine reuptake inhibitor that is Food and Drug Administration approved for once-daily treatment of major depressive disorder in adults. Secondary and post-hoc analyses were carried out on data from a positive 10-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter, proof-of-concept trial (EudraCT Number: 2006-002404-34) on 75 or 100 mg/day levomilnacipran extended release (ER). Included outpatients (18-70 years) met the criteria for a major depressive episode. There was a statistically significant difference in favor of levomilnacipran ER versus placebo in change from baseline to week 10 on every Montgomery Åsberg Depression Rating Scale (MADRS) single item (mixed-effects model for repeated measures; PDepression Rating Scale (HAMD17) single items. Significantly more levomilnacipran ER versus placebo patients (P depression subgroup (MADRS ≥ 30). These results demonstrate the benefit of levomilnacipran ER over placebo for patients with symptomatic and functional impairment associated with major depressive disorder.

  9. Effects of memantine on cognition in patients with moderate to severe Alzheimer's disease: post-hoc analyses of ADAS-cog and SIB total and single-item scores from six randomized, double-blind, placebo-controlled studies.

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    Mecocci, Patrizia; Bladström, Anna; Stender, Karina

    2009-05-01

    The post-hoc analyses reported here evaluate the specific effects of memantine treatment on ADAS-cog single-items or SIB subscales for patients with moderate to severe AD. Data from six multicentre, randomised, placebo-controlled, parallel-group, double-blind, 6-month studies were used as the basis for these post-hoc analyses. All patients with a Mini-Mental State Examination (MMSE) score of less than 20 were included. Analyses of patients with moderate AD (MMSE: 10-19), evaluated with the Alzheimer's disease Assessment Scale (ADAS-cog) and analyses of patients with moderate to severe AD (MMSE: 3-14), evaluated using the Severe Impairment Battery (SIB), were performed separately. The mean change from baseline showed a significant benefit of memantine treatment on both the ADAS-cog (p ADAS-cog single-item analyses showed significant benefits of memantine treatment, compared to placebo, for mean change from baseline for commands (p < 0.001), ideational praxis (p < 0.05), orientation (p < 0.01), comprehension (p < 0.05), and remembering test instructions (p < 0.05) for observed cases (OC). The SIB subscale analyses showed significant benefits of memantine, compared to placebo, for mean change from baseline for language (p < 0.05), memory (p < 0.05), orientation (p < 0.01), praxis (p < 0.001), and visuospatial ability (p < 0.01) for OC. Memantine shows significant benefits on overall cognitive abilities as well as on specific key cognitive domains for patients with moderate to severe AD. (c) 2009 John Wiley & Sons, Ltd.

  10. POST-HOC SEGMENTATION USING MARKETING RESEARCH

    Directory of Open Access Journals (Sweden)

    CRISTINEL CONSTANTIN

    2012-10-01

    Full Text Available This paper is about an instrumental research conducted in order to compare the information given by two multivariate data analysis used fordividing a population in clusters. These methods are K-means cluster and TwoStep cluster, which are available in SPSS system. Such methods could be used in post-hoc market segmentations, which allow companies to find segments with specific behaviours or attitudes. The research scope is to find which of the two methods is better for market segmentation practice. The outcomes reveal that every method has strong points and weaknesses. These ones are related to the relevance of segments description and the statistic significance of the difference between segments. In this respect, the researchers should compare the results of the named analyses and choose the method which better discriminate between the market segments.

  11. Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

    Science.gov (United States)

    Chin, Melanie P.; Bakris, George L.; Block, Geoffrey A.; Chertow, Glenn M.; Goldsberry, Angie; Inker, Lesley A.; Heerspink, Hiddo J.L.; O'Grady, Megan; Pergola, Pablo E.; Wanner, Christoph; Warnock, David G.; Meyer, Colin J.

    2018-01-01

    Background Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Methods Patients in ­BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; p < 0.0001). Conclusions Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. PMID:29402767

  12. Body weight affects ω-3 polyunsaturated fatty acid (PUFA) accumulation in youth following supplementation in post-hoc analyses of a randomized controlled trial.

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    Christian, Lisa M; Young, Andrea S; Mitchell, Amanda M; Belury, Martha A; Gracious, Barbara L; Arnold, L Eugene; Fristad, Mary A

    2017-01-01

    Guidelines for suggested intake of ω-3 polyunsaturated fatty acids (PUFAs) are limited in youth and rely primarily on age. However, body weight varies considerably within age classifications. The current analyses examined effects of body weight and body mass index (BMI) on fatty acid accumulation in 64 youth (7-14 years) with a diagnosed mood disorder in a double-blind randomized-controlled trial (2000mg ω-3 supplements or a control capsule) across 12 weeks. Weight and height were measured at the first study visit and EPA and DHA levels were determined using fasting blood samples obtained at both the first and end-of-study visits. In the ω-3 supplementation group, higher baseline body weight predicted less plasma accumulation of both EPA [B = -0.047, (95% CI = -0.077; -0.017), β = -0.54, p = 0.003] and DHA [B = -0.02, (95% CI = -0.034; -0.007), β = -0.52, p = 0.004]. Similarly, higher BMI percentile as well as BMI category (underweight, normal weight, overweight/obese) predicted less accumulation of EPA and DHA (ps≤0.01). Adherence to supplementation was negatively correlated with BMI percentile [B = -0.002 (95% CI = -0.004; 0.00), β = -0.44, p = 0.019], but did not meaningfully affect observed associations. As intended, the control supplement exerted no significant effect on plasma levels of relevant fatty acids regardless of youth body parameters. These data show strong linear relationships of both absolute body weight and BMI percentile with ω-3 PUFA accumulation in youth. A dose-response effect was observed across the BMI spectrum. Given increasing variability in weight within BMI percentile ranges as youth age, dosing based on absolute weight should be considered. Moreover, effects of weight should be incorporated into statistical models in studies examining clinical effects of ω-3 PUFAs in youth as well as adults, as weight-related differences in effects may contribute meaningfully to inconsistencies in the current literature. WHO International

  13. Post hoc subgroups in clinical trials: Anathema or analytics?

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    Weisberg, Herbert I; Pontes, Victor P

    2015-08-01

    There is currently much interest in generating more individualized estimates of treatment effects. However, traditional statistical methods are not well suited to this task. Post hoc subgroup analyses of clinical trials are fraught with methodological problems. We suggest that the alternative research paradigm of predictive analytics, widely used in many business contexts, can be adapted to help. We compare the statistical and analytics perspectives and suggest that predictive modeling should often replace subgroup analysis. We then introduce a new approach, cadit modeling, that can be useful to identify and test individualized causal effects. The cadit technique is particularly useful in the context of selecting from among a large number of potential predictors. We describe a new variable-selection algorithm that has been applied in conjunction with cadit. The cadit approach is illustrated through a reanalysis of data from the Randomized Aldactone Evaluation Study trial, which studied the efficacy of spironolactone in heart-failure patients. The trial was successful, but a serious adverse effect (hyperkalemia) was subsequently discovered. Our reanalysis suggests that it may be possible to predict the degree of hyperkalemia based on a logistic model and to identify a subgroup in which the effect is negligible. Cadit modeling is a promising alternative to subgroup analyses. Cadit regression is relatively straightforward to implement, generates results that are easy to present and explain, and can mesh straightforwardly with many variable-selection algorithms. © The Author(s) 2015.

  14. A double-blind, delayed-start trial of rasagiline in Parkinson's disease (the ADAGIO study): prespecified and post-hoc analyses of the need for additional therapies, changes in UPDRS scores, and non-motor outcomes.

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    Rascol, Olivier; Fitzer-Attas, Cheryl J; Hauser, Robert; Jankovic, Joseph; Lang, Anthony; Langston, J William; Melamed, Eldad; Poewe, Werner; Stocchi, Fabrizio; Tolosa, Eduardo; Eyal, Eli; Weiss, Yoni M; Olanow, C Warren

    2011-05-01

    The ADAGIO study investigated whether rasagiline has disease-modifying effects in Parkinson's disease. Rasagiline 1 mg per day, but not 2 mg per day, was shown to be efficacious in the primary analysis. Here, we report additional secondary and post-hoc analyses of the ADAGIO study. ADAGIO was a placebo-controlled, double-blind, multicentre, delayed-start study, in which 1176 patients with untreated early Parkinson's disease were randomly assigned to receive rasagiline 1 mg or 2 mg per day for 72 weeks (early-start groups) or placebo for 36 weeks followed by rasagiline 1 mg or 2 mg per day for 36 weeks (delayed-start groups). We assessed the need for additional antiparkinsonian therapy and changes in non-motor experiences of daily living and fatigue scales (prespecified outcomes) and changes in unified Parkinson's disease rating scale (UPDRS) scores and subscores in placebo and active groups (post-hoc outcomes). The ADAGIO study is registered with ClinicalTrials.gov, number NCT00256204. The need for additional antiparkinsonian therapy was reduced with rasagiline 1 mg (25 of 288 [9%] patients) and 2 mg (26 of 293 [9%]) versus placebo (108 of 593 [18%]; odds ratio for 1 mg rasagiline vs placebo 0·41, 95% CI 0·25-0·65, p=0·0002; 2 mg rasagiline vs placebo 0·41, 0·26-0·64, p=0·0001). At week 36, both doses significantly improved UPDRS motor subscores compared with placebo (1 mg rasagiline mean difference -1·88 [SE 0·35]; 2 mg rasagiline -2·18 [0·35]; both prasagiline -0·86 [0·18]; 2 mg rasagiline -0·88 [0·18]; both prasagiline significantly improved UPDRS mentation subscore (-0·22 [0·08]; p=0·004). At week 72, the only significant difference between early-start and delayed-start groups was for ADL subscore with the 1 mg dose (-0·62 [0·29]; p=0·035). When assessed for the effect on non-motor symptoms at week 36, both doses showed benefits on the Parkinson fatigue scale versus placebo (1 mg rasagiline mean difference -0·14 [SE 0·05], p=0·0032; 2

  15. Post hoc analyses of the impact of previous medication on the efficacy of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in a randomized, controlled trial

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    Coghill DR

    2014-10-01

    =317; LDX, -18.6 [-21.5, -15.7]; OROS- MPH, -13.0 [-15.9, -10.2] and treatment-naïve individuals (n=147; LDX, -15.1 [-19.4, -10.9]; OROS-MPH, -12.7 [-16.8, -8.5] or patients previously treated with any ADHD medication (n=170; LDX, -21.5 [-25.5, -17.6]; OROS-MPH, -14.2 [-18.1, -10.3]. In addition, similar proportions of patients receiving active treatment were categorized as improved based on CGI-I score (CGI-I of 1 or 2 in the overall study population and among treatment-naïve individuals or patients previously treated with any ADHD medication. Conclusion: In these post hoc analyses, the response to LDX treatment, and to the reference treatment OROS-MPH, was similar to that observed for the overall study population in subgroups of patients categorized according to whether or not they had previously received ADHD medication. Keywords: attention-deficit/hyperactivity disorder, lisdexamfetamine dimesylate, methylphenidate, central nervous system stimulants

  16. Impact of a switch to fingolimod versus staying on glatiramer acetate or beta interferons on patient- and physician-reported outcomes in relapsing multiple sclerosis: post hoc analyses of the EPOC trial.

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    Calkwood, Jonathan; Cree, Bruce; Crayton, Heidi; Kantor, Daniel; Steingo, Brian; Barbato, Luigi; Hashmonay, Ron; Agashivala, Neetu; McCague, Kevin; Tenenbaum, Nadia; Edwards, Keith

    2014-11-26

    The Evaluate Patient OutComes (EPOC) study assessed physician- and patient-reported outcomes in individuals with relapsing multiple sclerosis who switched directly from injectable disease-modifying therapy (iDMT; glatiramer acetate, intramuscular or subcutaneous interferon beta-1a, or interferon beta-1b) to once-daily, oral fingolimod. Post hoc analyses evaluated the impact of a switch to fingolimod versus staying on each of the four individual iDMTs. Overall, 1053 patients were randomized 3:1 to switch to fingolimod or remain on iDMT. The primary endpoint was the change in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction score. Secondary endpoints included changes in scores for TSQM Effectiveness, Side Effects and Convenience subscales, Beck Depression Inventory-II (BDI-II), Fatigue Severity Scale (FSS), Patient-Reported Outcome Indices for Multiple Sclerosis (PRIMUS) Activities, 36-item Short-Form Health Survey (SF-36) Mental Component Summary (MCS) and Physical Component Summary (PCS) and mean investigator-reported Clinical Global Impressions of Improvement (CGI-I). All outcomes were evaluated after 6 months of treatment. Changes in TSQM Global Satisfaction scores were superior after a switch to fingolimod when compared with scores in patients remaining on any of the iDMTs (all p <0.001). Likewise, all TSQM subscale scores improved following a switch to fingolimod (all p <0.001), except when compared with glatiramer acetate for the TSQM Side Effects subscale (p = 0.111). FSS scores were found to be superior for fingolimod versus remaining on subcutaneous interferon beta-1a and interferon beta-1b, BDI-II scores were significantly improved for fingolimod except for the comparison with intramuscular interferon beta-1a, and SF-36 scores were superior with fingolimod compared with remaining on interferon beta-1b (MCS and PCS; p = 0.030 and p = 0.022, respectively) and subcutaneous interferon beta-1a (PCS only; p = 0

  17. Modelling of increased homocysteine in ischaemic stroke: post-hoc cross-sectional matched case-control analysis in young patients Aumento de homocisteína em acidente vascular cerebral isquêmico: análise post-hoc com casos controles em pacientes jovens

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    Penka A. Atanassova

    2007-03-01

    Full Text Available BACKGROUND & PURPOSE: Hyperhomocysteinaemia has been postulated to participate in pathogenesis of ischaemic stroke (IS. However, especially in young adults, there is possibility of significantly increased IS risk due to increased ‘normal’ homocysteinaemia, i.e., ‘hidden’ (‘pathologically dormant’ prevalence within a healthy, normally-defined range. We performed a post-hoc modelling investigation on plasma total homocysteinaemia (THCY in gender- and age-matched young patients in the acute IS phase. We evaluated relationships between THCY and prevalence of other potential risk factors in 41 patients vs. 41 healthy controls. METHOD: We used clinical methods, instrumental and neuroimmaging procedures, risk factors examination, total plasma homocysteine measurements and other laboratory and statistical modelling techniques. RESULTS: IS patients and healthy controls were similar not only for matching variables, but also for smoking, main vitamin status, serum creatinine and lipid profile. Patients with IS, however, had lower vitamin B6 levels and higher THCY, fibrinogen and triglycerides (TGL. At multivariate stepwise logistic regression only increased THCY and TGL were significantly and independently associated with the risk for stroke (72% model accuracy, p model=0.001. An increase of THCY with 1.0 µmol/L was associated with 22% higher risk of ischaemic stroke [adjusted OR=1.22 (95%CI 1.03?1.44]. In this way, novel lower cut-off value for HCY of 11.58 µmol/L in younger patients has been revealed (ROC AUC= 0.67, 95CI% 0.55-0.78, p=0.009. CONCLUSION: The new THCY cut-off clearly discriminated between absence and presence of IS (sensitivity>63%, specificity>68% irrespectively of age and gender and may be applied to better evaluate and more precisely define, as earlier as possible, the young patients at increased IS risk.OBJETIVO: Hiperhomocisteinemia tem sido postulada como um dos fatores de risco na patogênese do acidente vascular

  18. Perioperative hyperoxia - Long-term impact on cardiovascular complications after abdominal surgery, a post hoc analysis of the PROXI trial

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    Fonnes, Siv; Gogenur, Ismail; Sondergaard, Edith Smed

    2016-01-01

    BACKGROUND: Increased long-term mortality was found in patients exposed to perioperative hyperoxia in the PROXI trial, where patients undergoing laparotomy were randomised to 80% versus 30% oxygen during and after surgery. This post hoc follow-up study assessed the impact of perioperative hyperoxia...... included myocardial infarction, other heart disease, and acute coronary syndrome or death. Data were analysed in the Cox proportional hazards model. RESULTS: The primary outcome, acute coronary syndrome, occurred in 2.5% versus 1.3% in the 80% versus 30% oxygen group; HR 2.15 (95% CI 0.96-4.84). Patients...

  19. The post hoc use of randomised controlled trials to explore drug associated cancer outcomes

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    Stefansdottir, Gudrun; Zoungas, Sophia; Chalmers, John

    2013-01-01

    INTRODUCTION: Drug-induced cancer risk is of increasing interest. Both observational studies and data from clinical trials have linked several widely used treatments to cancer. When a signal for a potential drug-cancer association is generated, substantiation is required to assess the impact...... on public health before proper regulatory action can be taken. This paper aims to discuss challenges of exploring drug-associated cancer outcomes by post-hoc analyses of Randomised controlled trials (RCTs) designed for other purposes. METHODOLOGICAL CHALLENGES TO CONSIDER: We set out to perform a post......-hoc nested case-control analysis in the ADVANCE trial in order to examine the association between insulin use and cancer. We encountered several methodological challenges that made the results difficult to interpret, including short duration of exposure of interest, lack of power, and correlation between...

  20. Preventive Ceftriaxone in Patients with Stroke Treated with Intravenous Thrombolysis: Post Hoc Analysis of the Preventive Antibiotics in Stroke Study

    NARCIS (Netherlands)

    Vermeij, Jan-Dirk; Westendorp, Willeke F.; Roos, Yvo B.; Brouwer, Matthijs C.; van de Beek, Diederik; Nederkoorn, Paul J.

    2016-01-01

    The Preventive Antibiotics in Stroke Study (PASS), a randomized open-label masked endpoint trial, showed that preventive ceftriaxone did not improve functional outcome at 3 months in patients with acute stroke (adjusted common OR 0.95; 95% CI 0.82-1.09). Post-hoc analyses showed that among patients

  1. Using in vitro prediction models instead of the rabbit eye irritation test to classify and label new chemicals: a post hoc data analysis of the international EC/HO validation study.

    Science.gov (United States)

    Moldenhauer, Ferdinand

    2003-01-01

    The international validation study on alternative methods to replace the Draize rabbit eye irritation test, funded by the European Commission (EC) and the British Home Office (HO), took place during 1992-1994, and the results were published in 1995. The results of this EC/HO study are analysed by employing discriminant analysis, taking into account the classification of the in vivo data into eye irritation classes A (risk of serious damage to eyes), B (irritating to eyes) and NI (non-irritant). A data set for 59 test items was analysed, together with three subsets: surfactants, water-soluble chemicals, and water-insoluble chemicals. The new statistical methods of feature selection and estimation of the discriminant functions classification error were used. Normal distributed random numbers were added to the mean values of each in vitro endpoint, depending on the observed standard deviations. Thereafter, the reclassification error of the random observations was estimated by applying the fixed function of the mean values. Moreover, the leaving-one-out cross-classification method was applied to this random data set. Subsequently, random data were generated r times (for example, r = 1000) for a feature combination. Eighteen features were investigated in nine in vitro test systems to predict the effects of a chemical in the rabbit eye. 72.5% of the chemicals in the undivided sample were correctly classified when applying the in vitro endpoints lgNRU of the neutral red uptake test and lgBCOPo5 of the bovine opacity and permeability test. The accuracy increased to 80.9% when six in vitro features were used, and the sample was subdivided. The subset of surfactants was correctly classified in more than 90% of cases, which is an excellent performance.

  2. simulate_CAT: A Computer Program for Post-Hoc Simulation for Computerized Adaptive Testing

    Directory of Open Access Journals (Sweden)

    İlker Kalender

    2015-06-01

    Full Text Available This paper presents a computer software developed by the author. The software conducts post-hoc simulations for computerized adaptive testing based on real responses of examinees to paper and pencil tests under different parameters that can be defined by user. In this paper, short information is given about post-hoc simulations. After that, the working principle of the software is provided and a sample simulation with required input files is shown. And last, output files are described

  3. Post hoc support vector machine learning for impedimetric biosensors based on weak protein-ligand interactions.

    Science.gov (United States)

    Rong, Y; Padron, A V; Hagerty, K J; Nelson, N; Chi, S; Keyhani, N O; Katz, J; Datta, S P A; Gomes, C; McLamore, E S

    2018-04-09

    Impedimetric biosensors for measuring small molecules based on weak/transient interactions between bioreceptors and target analytes are a challenge for detection electronics, particularly in field studies or in the analysis of complex matrices. Protein-ligand binding sensors have enormous potential for biosensing, but achieving accuracy in complex solutions is a major challenge. There is a need for simple post hoc analytical tools that are not computationally expensive, yet provide near real time feedback on data derived from impedance spectra. Here, we show the use of a simple, open source support vector machine learning algorithm for analyzing impedimetric data in lieu of using equivalent circuit analysis. We demonstrate two different protein-based biosensors to show that the tool can be used for various applications. We conclude with a mobile phone-based demonstration focused on the measurement of acetone, an important biomarker related to the onset of diabetic ketoacidosis. In all conditions tested, the open source classifier was capable of performing as well as, or better, than the equivalent circuit analysis for characterizing weak/transient interactions between a model ligand (acetone) and a small chemosensory protein derived from the tsetse fly. In addition, the tool has a low computational requirement, facilitating use for mobile acquisition systems such as mobile phones. The protocol is deployed through Jupyter notebook (an open source computing environment available for mobile phone, tablet or computer use) and the code was written in Python. For each of the applications, we provide step-by-step instructions in English, Spanish, Mandarin and Portuguese to facilitate widespread use. All codes were based on scikit-learn, an open source software machine learning library in the Python language, and were processed in Jupyter notebook, an open-source web application for Python. The tool can easily be integrated with the mobile biosensor equipment for rapid

  4. Lurasidone for major depressive disorder with mixed features and irritability: a post-hoc analysis.

    Science.gov (United States)

    Swann, Alan C; Fava, Maurizio; Tsai, Joyce; Mao, Yongcai; Pikalov, Andrei; Loebel, Antony

    2017-04-01

    The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating major depressive disorder (MDD) with mixed features including irritability. The data in this analysis were derived from a study of patients meeting DSM-IV-TR criteria for unipolar MDD, with a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, and who were randomized to 6 weeks of double-blind treatment with either lurasidone 20-60 mg/d (n=109) or placebo (n=100). We defined "irritability" as a score ≥2 on both the Young Mania Rating Scale (YMRS) irritability item (#5) and the disruptive-aggressive item (#9). Endpoint change in the MADRS and YMRS items 5 and 9 were analyzed using a mixed model for repeated measures for patients with and without irritability. Some 20.7% of patients met the criteria for irritability. Treatment with lurasidone was associated with a significant week 6 change vs. placebo in MADRS score in both patients with (-22.6 vs. -9.5, pdepressive symptoms in MDD patients with mixed features including irritability. In addition, irritability symptoms significantly improved in patients treated with lurasidone.

  5. A Priori Versus Post-Hoc: Comparing Statistical Power among ANOVA, Block Designs, and ANCOVA.

    Science.gov (United States)

    Wu, Yi-Cheng; McLean, James E.

    By employing a concomitant variable, block designs and analysis of covariance (ANCOVA) can be used to improve the power of traditional analysis of variance (ANOVA) by reducing error. If subjects are randomly assigned to treatments without considering the concomitant variable, an experiment uses a post-hoc approach. Otherwise, an a priori approach…

  6. Impulse control disorder related behaviours during long-term rotigotine treatment: a post hoc analysis.

    Science.gov (United States)

    Antonini, A; Chaudhuri, K R; Boroojerdi, B; Asgharnejad, M; Bauer, L; Grieger, F; Weintraub, D

    2016-10-01

    Dopamine agonists in Parkinson's disease (PD) are associated with impulse control disorders (ICDs) and other compulsive behaviours (together called ICD behaviours). The frequency of ICD behaviours reported as adverse events (AEs) in long-term studies of rotigotine transdermal patch in PD was evaluated. This was a post hoc analysis of six open-label extension studies up to 6 years in duration. Analyses included patients treated with rotigotine for at least 6 months and administered the modified Minnesota Impulse Disorders Interview. ICD behaviours reported as AEs were identified and categorized. For 786 patients, the mean (±SD) exposure to rotigotine was 49.4 ± 17.6 months. 71 (9.0%) patients reported 106 ICD AEs cumulatively. Occurrence was similar across categories: 2.5% patients reported 'compulsive sexual behaviour', 2.3% 'buying disorder', 2.0% 'compulsive gambling', 1.7% 'compulsive eating' and 1.7% 'punding behaviour'. Examining at 6-month intervals, the incidence was relatively low during the first 30 months; it was higher over the next 30 months, peaking in the 54-60-month period. No ICD AEs were serious, and 97% were mild or moderate in intensity. Study discontinuation occurred in seven (9.9%) patients with ICD AEs; these then resolved in five patients. Dose reduction occurred for 23 AEs, with the majority (73.9%) resolving. In this analysis of >750 patients with PD treated with rotigotine, the frequency of ICD behaviour AEs was 9.0%, with a specific incidence timeline observed. Active surveillance as duration of treatment increases may help early identification and management; once ICD behaviours are present rotigotine dose reduction may be considered. © 2016 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

  7. Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial.

    Science.gov (United States)

    Heyland, Daren K; Elke, Gunnar; Cook, Deborah; Berger, Mette M; Wischmeyer, Paul E; Albert, Martin; Muscedere, John; Jones, Gwynne; Day, Andrew G

    2015-05-01

    The recent large randomized controlled trial of glutamine and antioxidant supplementation suggested that high-dose glutamine is associated with increased mortality in critically ill patients with multiorgan failure. The objectives of the present analyses were to reevaluate the effect of supplementation after controlling for baseline covariates and to identify potentially important subgroup effects. This study was a post hoc analysis of a prospective factorial 2 × 2 randomized trial conducted in 40 intensive care units in North America and Europe. In total, 1223 mechanically ventilated adult patients with multiorgan failure were randomized to receive glutamine, antioxidants, both glutamine and antioxidants, or placebo administered separate from artificial nutrition. We compared each of the 3 active treatment arms (glutamine alone, antioxidants alone, and glutamine + antioxidants) with placebo on 28-day mortality. Post hoc, treatment effects were examined within subgroups defined by baseline patient characteristics. Logistic regression was used to estimate treatment effects within subgroups after adjustment for baseline covariates and to identify treatment-by-subgroup interactions (effect modification). The 28-day mortality rates in the placebo, glutamine, antioxidant, and combination arms were 25%, 32%, 29%, and 33%, respectively. After adjusting for prespecified baseline covariates, the adjusted odds ratio of 28-day mortality vs placebo was 1.5 (95% confidence interval, 1.0-2.1, P = .05), 1.2 (0.8-1.8, P = .40), and 1.4 (0.9-2.0, P = .09) for glutamine, antioxidant, and glutamine plus antioxidant arms, respectively. In the post hoc subgroup analysis, both glutamine and antioxidants appeared most harmful in patients with baseline renal dysfunction. No subgroups suggested reduced mortality with supplements. After adjustment for baseline covariates, early provision of high-dose glutamine administered separately from artificial nutrition was not beneficial and may be

  8. Preventive Ceftriaxone in Patients with Stroke Treated with Intravenous Thrombolysis: Post Hoc Analysis of the Preventive Antibiotics in Stroke Study.

    Science.gov (United States)

    Vermeij, Jan-Dirk; Westendorp, Willeke F; Roos, Yvo B; Brouwer, Matthijs C; van de Beek, Diederik; Nederkoorn, Paul J

    2016-01-01

    The Preventive Antibiotics in Stroke Study (PASS), a randomized open-label masked endpoint trial, showed that preventive ceftriaxone did not improve functional outcome at 3 months in patients with acute stroke (adjusted common OR 0.95; 95% CI 0.82-1.09). Post-hoc analyses showed that among patients who received intravenous thrombolysis (IVT), patients who received ceftriaxone had a significantly better outcome as compared with the control group. This study aimed to gain more insight into the characteristics of these patients. In PASS, 2,550 patients were randomly assigned to preventive antibiotic treatment with ceftriaxone or standard care. In current post-hoc analysis, 836 patients who received IVT were included. Primary outcome included functional status on the modified Rankin Scale, analyzed with adjusted ordinal regression. Secondary outcomes included infection rate and symptomatic intracerebral hemorrhage (sICH) rate. For all patients in PASS, the p value for the interaction between IVT and preventive ceftriaxone regarding functional outcome was 0.03. Of the 836 IVT-treated patients, 437 were administered ceftriaxone and 399 were allocated to the control group. Baseline characteristics were similar. In the IVT subgroup, preventive ceftriaxone was associated with a significant reduction in unfavorable outcome (adjusted common OR 0.77; 95% CI 0.61-0.99; p = 0.04). Mortality at 3 months was similar (OR 0.75; 95% CI 0.48-1.18). Preventive ceftriaxone was associated with a reduction in infections (OR 0.43; 95% CI 0.28-0.66), and a trend towards an increased risk for sICH (OR 3.09; 95% CI 0.85-11.31). Timing of ceftriaxone administration did not influence the outcome (aOR 1.00; 95% CI 0.98-1.03; p = 0.85). According to the post-hoc analysis of PASS, preventive ceftriaxone may improve the functional outcome in IVT-treated patients with acute stroke, despite a trend towards an increased rate of post-IVT-sICH. © 2016 S. Karger AG, Basel.

  9. Outcome when adrenaline (epinephrine) was actually given vs. not given - post hoc analysis of a randomized clinical trial.

    Science.gov (United States)

    Olasveengen, Theresa M; Wik, Lars; Sunde, Kjetil; Steen, Petter A

    2012-03-01

    IV line insertion and drugs did not affect long-term survival in an out-of-hospital cardiac arrest (OHCA) randomized clinical trial (RCT). In a previous large registry study adrenaline was negatively associated with survival from OHCA. The present post hoc analysis on the RCT data compares outcomes for patients actually receiving adrenaline to those not receiving adrenaline. Patients from a RCT performed May 2003 to April 2008 were included. Three patients from the original intention-to-treat analysis were excluded due to insufficient documentation of adrenaline administration. Quality of cardiopulmonary resuscitation (CPR) and clinical outcomes were compared. Clinical characteristics were similar and CPR quality comparable and within guideline recommendations for 367 patients receiving adrenaline and 481 patients not receiving adrenaline. Odds ratio (OR) for being admitted to hospital, being discharged from hospital and surviving with favourable neurological outcome for the adrenaline vs. no-adrenaline group was 2.5 (CI 1.9, 3.4), 0.5 (CI 0.3, 0.8) and 0.4 (CI 0.2, 0.7), respectively. Ventricular fibrillation, response interval, witnessed arrest, gender, age and endotracheal intubation were confounders in multivariate logistic regression analysis. OR for survival for adrenaline vs. no-adrenaline adjusted for confounders was 0.52 (95% CI: 0.29, 0.92). Receiving adrenaline was associated with improved short-term survival, but decreased survival to hospital discharge and survival with favourable neurological outcome after OHCA. This post hoc survival analysis is in contrast to the previous intention-to-treat analysis of the same data, but agrees with previous non-randomized registry data. This shows limitations of non-randomized or non-intention-to-treat analyses. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Quantitative Research Methods in Chaos and Complexity: From Probability to Post Hoc Regression Analyses

    Science.gov (United States)

    Gilstrap, Donald L.

    2013-01-01

    In addition to qualitative methods presented in chaos and complexity theories in educational research, this article addresses quantitative methods that may show potential for future research studies. Although much in the social and behavioral sciences literature has focused on computer simulations, this article explores current chaos and…

  11. A post hoc evaluation of a sample size re-estimation in the Secondary Prevention of Small Subcortical Strokes study.

    Science.gov (United States)

    McClure, Leslie A; Szychowski, Jeff M; Benavente, Oscar; Hart, Robert G; Coffey, Christopher S

    2016-10-01

    achieve, statistical significance with the larger sample (n = 3020 HR (95% confidence interval): 0.81 (0.63, 1.0), p = 0.089; n = 2500 HR (95% confidence interval): 0.89 (0.68, 1.17), p = 0.40). The results from the safety analyses were similar to 3020 and 2500 patients for both study interventions. Other trial-related factors, such as contracts, finances, and study management, were impacted as well. Adaptive designs can have benefits in randomized clinical trials, but do not always result in significant findings. The impact of adaptive designs should be measured in terms of both trial results, as well as practical issues related to trial management. More post hoc analyses of study adaptations will lead to better understanding of the balance between the benefits and the costs. © The Author(s) 2016.

  12. Evolution of Blood Lactate and 90-Day Mortality in Septic Shock. A Post Hoc Analysis of the FINNAKI Study.

    Science.gov (United States)

    Varis, Elina; Pettilä, Ville; Poukkanen, Meri; Jakob, Stephan M; Karlsson, Sari; Perner, Anders; Takala, Jukka; Wilkman, Erika

    2017-05-01

    Hyperlactatemia predicts mortality in patients with sepsis and septic shock, and its normalization is a potential treatment goal. We investigated the association of blood lactate and its changes over time with 90-day mortality in septic shock. We performed a post hoc analysis of 513 septic shock patients with admission blood lactate measurements in the prospective, observational, multicenter FINNAKI study. Repetitive lactate measurements were available in 496 patients for analyses of change in lactate values during intensive care unit stay.The 90-day mortality for all patients was 33.3%. Patients with admission lactate >2 mmol/L had higher 90-day mortality than those with admission lactate ≤2 mmol/L (43.4% vs. 22.6%, P 2 mmol/L) at ≥72 h had higher 90-day mortality compared with those with a lactate value of ≤2.0 mmol/L (52.0% vs. 24.3%, P septic shock patients.

  13. A post hoc analysis of d-threo-methylphenidate hydrochloride (focalin) versus d,l-threo-methylphenidate hydrochloride (ritalin).

    Science.gov (United States)

    Weiss, Margaret; Wasdell, Michael; Patin, John

    2004-11-01

    To evaluate clinical measures of the benefit/risk ratio in a post hoc analysis of a clinical trial of d-threo-methylphenidate hydrochloride (d-MPH) and d,l-threo-methylphenidate hydrochloride (d,l-MPH). Data from a phase III clinical trial was used to compare equimolar doses of d-MPH and d,l-MPH treatment for attention-deficit/hyperactivity disorder (ADHD) on clinician ratings of improvement/deterioration, teacher ratings of remission, and duration of action. d-MPH was clinically and statistically significantly superior to d,l-MPH on clinician's dimensional ratings of global improvement, teacher ratings of remission of ADHD symptoms and parent 6:00 p.m. ADHD symptom ratings. No treatment differences were observed for symptom ratings at 3:00 p.m. and for 6:00 p.m. math test performance. The results suggest that the two drugs may have distinct profiles on the measures analyzed. Because d-MPH may have be more than twice the potency of d,l-MPH, the differences reported here are only applicable to the doses of the study drugs involved in the clinical trial. The results are limited by the exploratory nature of our analysis, small samples, and multiple analyses. The findings are suggestive that further study is warranted to look at these differences prospectively but cannot be used to draw clinical conclusions at this time.

  14. Long-term healthcare costs and functional outcomes associated with lack of remission in schizophrenia: a post-hoc analysis of a prospective observational study

    Directory of Open Access Journals (Sweden)

    Haynes Virginia S

    2012-12-01

    Full Text Available Abstract Background Little is known about the long-term outcomes for patients with schizophrenia who fail to achieve symptomatic remission. This post-hoc analysis of a 3-year study compared the costs of mental health services and functional outcomes between individuals with schizophrenia who met or did not meet cross-sectional symptom remission at study enrollment. Methods This post-hoc analysis used data from a large, 3-year prospective, non-interventional observational study of individuals treated for schizophrenia in the United States conducted between July 1997 and September 2003. At study enrollment, individuals were classified as non-remitted or remitted using the Schizophrenia Working Group Definition of symptom remission (8 core symptoms rated as mild or less. Mental health service use was measured using medical records. Costs were based on the sites’ medical information systems. Functional outcomes were measured with multiple patient-reported measures and the clinician-rated Quality of Life Scale (QLS. Symptoms were measured using the Positive and Negative Syndrome Scale (PANSS. Outcomes for non-remitted and remitted patients were compared over time using mixed effects models for repeated measures or generalized estimating equations after adjusting for multiple baseline characteristics. Results At enrollment, most of the 2,284 study participants (76.1% did not meet remission criteria. Non-remitted patients had significantly higher PANSS total scores at baseline, a lower likelihood of being Caucasian, a higher likelihood of hospitalization in the previous year, and a greater likelihood of a substance use diagnosis (all p Conclusions In this post-hoc analysis of a 3-year prospective observational study, the failure to achieve symptomatic remission at enrollment was associated with higher subsequent healthcare costs and worse functional outcomes. Further examination of outcomes for schizophrenia patients who fail to achieve remission at

  15. Post hoc pattern matching: assigning significance to statistically defined expression patterns in single channel microarray data

    Directory of Open Access Journals (Sweden)

    Blalock Eric M

    2007-07-01

    Full Text Available Abstract Background Researchers using RNA expression microarrays in experimental designs with more than two treatment groups often identify statistically significant genes with ANOVA approaches. However, the ANOVA test does not discriminate which of the multiple treatment groups differ from one another. Thus, post hoc tests, such as linear contrasts, template correlations, and pairwise comparisons are used. Linear contrasts and template correlations work extremely well, especially when the researcher has a priori information pointing to a particular pattern/template among the different treatment groups. Further, all pairwise comparisons can be used to identify particular, treatment group-dependent patterns of gene expression. However, these approaches are biased by the researcher's assumptions, and some treatment-based patterns may fail to be detected using these approaches. Finally, different patterns may have different probabilities of occurring by chance, importantly influencing researchers' conclusions about a pattern and its constituent genes. Results We developed a four step, post hoc pattern matching (PPM algorithm to automate single channel gene expression pattern identification/significance. First, 1-Way Analysis of Variance (ANOVA, coupled with post hoc 'all pairwise' comparisons are calculated for all genes. Second, for each ANOVA-significant gene, all pairwise contrast results are encoded to create unique pattern ID numbers. The # genes found in each pattern in the data is identified as that pattern's 'actual' frequency. Third, using Monte Carlo simulations, those patterns' frequencies are estimated in random data ('random' gene pattern frequency. Fourth, a Z-score for overrepresentation of the pattern is calculated ('actual' against 'random' gene pattern frequencies. We wrote a Visual Basic program (StatiGen that automates PPM procedure, constructs an Excel workbook with standardized graphs of overrepresented patterns, and lists of

  16. Evolution of Blood Lactate and 90-Day Mortality in Septic Shock. A Post Hoc Analysis of the FINNAKI Study

    DEFF Research Database (Denmark)

    Varis, Elina; Pettilä, Ville; Poukkanen, Meri

    2017-01-01

    Hyperlactatemia predicts mortality in patients with sepsis and septic shock, and its normalization is a potential treatment goal. We investigated the association of blood lactate and its changes over time with 90-day mortality in septic shock. We performed a post hoc analysis of 513 septic shock...... surrogate endpoints for mortality in septic shock patients....

  17. Atomoxetine treatment outcomes in adolescents and young adults with attention-deficit/hyperactivity disorder: results from a post hoc, pooled analysis.

    Science.gov (United States)

    Adler, Lenard A; Wilens, Timothy; Zhang, Shuyu; Dittmann, Ralf W; D'Souza, Deborah N; Schuh, Leslie; Durell, Todd M

    2012-02-01

    Many children with attention-deficit/hyperactivity disorder (ADHD) continue to experience this disorder as adults, which may, in part, be due to the discontinuity of health care that often occurs during the transition period between late adolescence and young adulthood. Although atomoxetine is reported to be efficacious in both adolescents and young adults, no longitudinal studies have been designed to assess directly the effects of atomoxetine treatment during this transition period. As a first step, we present the results of a post hoc, pooled analysis that compared the efficacy and safety profile of atomoxetine in these 2 patient populations. The aim of the present study was to assess the efficacy and safety profile of atomoxetine treatment in adolescents and young adults with ADHD. A post hoc, pooled analysis was conducted by combining data from 6 double-blind trials (6-9 weeks in duration) that studied adolescents (12-17 years of age; atomoxetine, n = 154; placebo, n = 88; mean final dose = 1.38 mg/kg) and 3 trials (10 weeks in duration) that studied young adults (18-30 years of age; atomoxetine, n = 117; placebo, n = 125; mean final dose = 1.21 mg/kg). Efficacy measures used in these analyses were ADHD Rating Scale (ADHDRS) for adolescents, Conners' Adult ADHD Rating Scale (CAARS) for young adults, and Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) for both age groups. Treatment response was defined as ≥30% reduction from baseline in total ADHD symptom score. In adolescents (mean age, 13.4 years), atomoxetine improved ADHD significantly compared with placebo (ADHDRS total score change, -12.9 vs -7.5; P young adults (mean age, 24.7 years), atomoxetine improved ADHD significantly (CAARS total score change, -13.6 vs -7.7; P young adults (13.7% vs 4.8%, respectively; P = 0.024); in adolescents no statistically significant differences were observed in frequency of nausea between atomoxetine and placebo treatment (4.5% vs 10.2%, respectively; P = 0

  18. A post hoc study on gene panel analysis for the diagnosis of dystonia.

    Science.gov (United States)

    van Egmond, Martje E; Lugtenberg, Coen H A; Brouwer, Oebele F; Contarino, Maria Fiorella; Fung, Victor S C; Heiner-Fokkema, M Rebecca; van Hilten, Jacobus J; van der Hout, Annemarie H; Peall, Kathryn J; Sinke, Richard J; Roze, Emmanuel; Verschuuren-Bemelmans, Corien C; Willemsen, Michel A; Wolf, Nicole I; Tijssen, Marina A; de Koning, Tom J

    2017-04-01

    Genetic disorders causing dystonia show great heterogeneity. Recent studies have suggested that next-generation sequencing techniques such as gene panel analysis can be effective in diagnosing heterogeneous conditions. The objective of this study was to investigate whether dystonia patients with a suspected genetic cause could benefit from the use of gene panel analysis. In this post hoc study, we describe gene panel analysis results of 61 dystonia patients (mean age, 31 years; 72% young onset) in our tertiary referral center. The panel covered 94 dystonia-associated genes. As comparison with a historic cohort was not possible because of the rapidly growing list of dystonia genes, we compared the diagnostic workup with and without gene panel analysis in the same patients. The workup without gene panel analysis (control group) included theoretical diagnostic strategies formulated by independent experts in the field, based on detailed case descriptions. The primary outcome measure was diagnostic yield; secondary measures were cost and duration of diagnostic workup. Workup with gene panel analysis led to a confirmed molecular diagnosis in 14.8%, versus 7.4% in the control group (P = 0.096). In the control group, on average 3 genes/case were requested. The mean costs were lower in the gene panel analysis group (€1822/case) than in the controls (€2660/case). The duration of the workup was considerably shorter with gene panel analysis (28 vs 102 days). Gene panel analysis facilitates molecular diagnosis in complex cases of dystonia, with a good diagnostic yield (14.8%), a quicker diagnostic workup, and lower costs, representing a major improvement for patients and their families. © 2016 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  19. Effects of asenapine on depressive symptoms in patients with bipolar I disorder experiencing acute manic or mixed episodes: a post hoc analysis of two 3-week clinical trials

    Directory of Open Access Journals (Sweden)

    Nations Kari R

    2011-06-01

    Full Text Available Abstract Background Asenapine demonstrated superiority over placebo for mania in bipolar I disorder patients experiencing acute current manic or mixed episodes in 2 randomized, placebo-and olanzapine-controlled trials. We report the results of exploratory pooled post hoc analyses from these trials evaluating asenapine's effects on depressive symptoms in patients from these trials with significant baseline depressive symptoms. Methods In the original trials (A7501004 [NCT00159744], A7501005 [NCT00159796], 977 patients were randomized to flexible-dose sublingual asenapine (10 mg twice daily on day 1; 5 or 10 mg twice daily thereafter, placebo, or oral olanzapine 5-20 mg once daily for 3 weeks. Three populations were defined using baseline depressive symptoms: (1 Montgomery-Asberg Depression Rating Scale (MADRS total score ≥20 (n = 132; (2 Clinical Global Impression for Bipolar Disorder-Depression (CGI-BP-D scale severity score ≥4 (n = 170; (3 diagnosis of mixed episodes (n = 302 by investigative site screening. For each population, asenapine and olanzapine were independently compared with placebo using least squares mean change from baseline on depressive symptom measures. Results Decreases in MADRS total score were statistically greater with asenapine versus placebo at days 7 and 21 in all populations; differences between olanzapine and placebo were not significant. Decreases in CGI-BP-D score were significantly greater with asenapine versus placebo at day 7 in all categories and day 21 in population 1; CGI-BP-D score reductions were significantly greater with olanzapine versus placebo at day 21 in population 1 and day 7 in populations 2 and 3. Conclusions These post hoc analyses show that asenapine reduced depressive symptoms in bipolar I disorder patients experiencing acute manic or mixed episodes with clinically relevant depressive symptoms at baseline; olanzapine results appeared to be less consistent. Controlled studies of asenapine in

  20. Mediterranean Diet, Retinopathy, Nephropathy, and Microvascular Diabetes Complications: A Post Hoc Analysis of a Randomized Trial.

    Science.gov (United States)

    Díaz-López, Andrés; Babio, Nancy; Martínez-González, Miguel A; Corella, Dolores; Amor, Antonio J; Fitó, Montse; Estruch, Ramon; Arós, Fernando; Gómez-Gracia, Enrique; Fiol, Miquel; Lapetra, José; Serra-Majem, Lluís; Basora, Josep; Basterra-Gortari, F Javier; Zanon-Moreno, Vicente; Muñoz, Miguel Ángel; Salas-Salvadó, Jordi

    2015-11-01

    To date no clinical trials have evaluated the role of dietary patterns on the incidence of microvascular diabetes complications. We hypothesized that a nutritional intervention based on the Mediterranean diet (MedDiet) would have greater protective effect on diabetic retinopathy and nephropathy than a low-fat control diet. This was a post hoc analysis of a cohort of patients with type 2 diabetes participating in the PREvención con DIeta MEDiterránea (PREDIMED) study, a multicenter randomized nutritional intervention trial conducted in a population at high cardiovascular risk. Individuals with type 2 diabetes who were free of microvascular complications at enrollment (n = 3,614, aged 55-80 years) were randomly assigned to one of three dietary interventions: MedDiet supplemented with extravirgin olive oil (MedDiet+EVOO), MedDiet supplemented with mixed nuts (MedDiet+Nuts), or a low-fat control diet. Two independent outcomes were considered: new onset of diabetic retinopathy and nephropathy. Hazard ratios (HRs) were calculated using multivariable-adjusted Cox regression. During a median follow-up of 6.0 years, we identified 74 new cases of retinopathy and 168 of nephropathy. Compared with the control diet, multivariable-adjusted HRs for diabetic retinopathy were 0.56 (95% CI 0.32-0.97) for the MedDiet+EVOO and 0.63 (0.35-1.11) for the MedDiet+Nuts. No between-group differences were found for nephropathy. When the yearly updated information on adherence to the MedDiet was considered, the HR for retinopathy in the highest versus the lowest quintile was 0.34 (0.13-0.89; P = 0.001 for trend). No significant associations were found for nephropathy. A MedDiet enriched with EVOO may protect against diabetic retinopathy but not diabetic nephropathy. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  1. Response to duloxetine in chronic low back pain: exploratory post hoc analysis of a Japanese Phase III randomized study

    Directory of Open Access Journals (Sweden)

    Tsuji T

    2017-09-01

    Full Text Available Toshinaga Tsuji,1 Naohiro Itoh,1 Mitsuhiro Ishida,2 Toshimitsu Ochiai,3 Shinichi Konno4 1Medical Affairs Department, 2Clinical Research Development, 3Biostatistics Department, Shionogi & Co. Ltd, Osaka, 4Department of Orthopedic Surgery, Fukushima Medical University, Fukushima, Japan Purpose: Duloxetine is efficacious for chronic low back pain (CLBP. This post hoc analysis of a Japanese randomized, placebo-controlled trial (ClinicalTrials.gov, NCT01855919 assessed whether patients with CLBP with early pain reduction or treatment-related adverse events of special interest (TR-AESIs; nausea, somnolence, constipation have enhanced responses to duloxetine. Patients and methods: Patients (N = 456 with CLBP for ≥6 months and Brief Pain Inventory (BPI average pain severity score of ≥4 were randomized (1:1 to duloxetine 60 mg/day or placebo for 14 weeks. Primary outcome was change from baseline in BPI average pain severity score (pain reduction. Subgroup analyses included early pain reduction (≥30%, 10%–30%, or <10% at Week 4 and early TR-AESIs (with or without TR-AESIs by Week 2. Measures included changes from baseline in BPI average pain severity score and BPI Interference scores (quality of life; QOL, and response rate (≥30% or ≥50% pain reduction at Week 14. Results: Patients with ≥30% early pain reduction (n = 108 or early TR-AESIs (n = 50 had significantly greater improvements in pain and QOL than placebo-treated patients (n = 226, whereas patients with 10%–30% (n = 63 or <10% (n = 48 pain reduction did not; patients without early TR-AESIs (n = 180 had significant improvements in pain at Week 14. Response rates (≥30%/≥50% pain reduction were 94.4%/82.4%, 66.7%/49.2%, and 25.0%/18.8% for patients with ≥30%, 10%–30%, and <10% early pain reduction, respectively, 74.0%/64.0% for patients with early TR-AESIs, 67.2%/54.4% for patients without early TR-AESIs, and 52.2%/39.4% for placebo.Conclusion: Early pain reduction or TR

  2. Prevalence of Chronic Kidney Disease in Turkish Adults With Obesity and Metabolic Syndrome: A Post Hoc Analysis from Chronic Renal Disease in Turkey Study.

    Science.gov (United States)

    Arinsoy, Turgay; Deger, Serpil Muge; Ates, Kenan; Altun, Bulent; Ecder, Tevfik; Camsari, Taner; Serdengecti, Kamil; Suleymanlar, Gultekin

    2016-11-01

    Obesity confers an increased risk of chronic kidney disease (CKD), which is increased further by accompanying metabolic abnormalities. To investigate the relationship of the risk of CKD with obesity and metabolic syndrome (MS) in adults by means of post hoc analysis of data from the Chronic Renal Disease in Turkey (CREDIT) study. The anthropometric measurements of a total of 9,100 adult participants in the CREDIT study were included in the analyses. Subjects were classified according to the presence or absence of obesity (body mass index [BMI] > 30) and MS. Logistic regression analyses were used to estimate odds ratio for CKD. Effect modification analyses were also performed. The prevalence of obesity was 20.6% and that of MS was 31.3%. The prevalence of CKD was higher among obese subjects compared to those with a normal BMI (20.5% vs. 14%; P obesity, 1.983 (95% CI, 1.489-2.641) for those with class II obesity and 2.799 (95% CI, 1.719-4.557) for subjects with extreme obesity (P obese subjects with MS (adjusted OR, 1.321; 95% CI, 1.109-1.573; P = .002). The stratification of obese individuals based on their metabolic phenotype is important for prevention and treatment of CKD. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  3. Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Bone Kerry M

    2009-06-01

    Full Text Available Abstract Background Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms. Methods A post hoc analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects. Results Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, low anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm. Conclusion This study was a post hoc analysis

  4. Subsequent Chemotherapy and Treatment Patterns After Abiraterone Acetate in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

    Science.gov (United States)

    de Bono, Johann S; Smith, Matthew R; Saad, Fred; Rathkopf, Dana E; Mulders, Peter F A; Small, Eric J; Shore, Neal D; Fizazi, Karim; De Porre, Peter; Kheoh, Thian; Li, Jinhui; Todd, Mary B; Ryan, Charles J; Flaig, Thomas W

    2017-04-01

    Treatment patterns for metastatic castration-resistant prostate cancer (mCRPC) have changed substantially in the last few years. In trial COU-AA-302 (chemotherapy-naïve men with mCRPC), abiraterone acetate plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival (OS) when compared to placebo plus prednisone (P). This post hoc analysis investigated clinical responses to docetaxel as first subsequent therapy (FST) among patients who progressed following protocol-specified treatment with AA, and characterized subsequent treatment patterns among older (≥75 yr) and younger (AA arm received subsequent treatment with one or more agents approved for mCRPC. Efficacy analysis was performed for patients for whom baseline and at least one post-baseline prostate-specific antigen (PSA) values were available. Baseline and at least one post-baseline PSA values were available for 100 AA patients who received docetaxel as FST. While acknowledging the limitations of post hoc analyses, 40% (40/100) of these patients had an unconfirmed ≥50% PSA decline with first subsequent docetaxel therapy, and 27% (27/100) had a confirmed ≥50% PSA decline. The median docetaxel treatment duration among these 100 patients was 4.2 mo. Docetaxel was the most common FST among older and younger patients from each treatment arm. However, 43% (79/185) of older patients who progressed on AA received no subsequent therapy for mCRPC, compared with 17% (60/361) of younger patients. Patients with mCRPC who progress with AA treatment may still derive benefit from subsequent docetaxel therapy. These data support further assessment of treatment patterns following AA treatment for mCRPC, particularly among older patients. ClinicalTrials.gov NCT00887198. Treatment patterns for advanced prostate cancer have changed substantially in the last few years. This additional analysis provides evidence of clinical benefit for subsequent chemotherapy in men with advanced

  5. Once-monthly injection of paliperidone palmitate in patients with recently diagnosed and chronic schizophrenia: a post-hoc comparison of efficacy and safety.

    Science.gov (United States)

    Si, Tianmei; Zhuo, Jianmin; Turkoz, Ibrahim; Mathews, Maju; Tan, Wilson; Feng, Yu

    2017-12-01

    The use of long-acting injectable antipsychotics in recently diagnosed schizophrenia remains less explored. We evaluated the efficacy and safety of paliperidone palmitate once-monthly (PP1M) treatment in adult patients with recently diagnosed vs. chronic schizophrenia. These post-hoc analyses included two multicenter studies. Study 1 (NCT01527305) enrolled recently diagnosed (≤5 years) and chronic (>5 years) patients; Study 2 (NCT01051531) enrolled recently diagnosed patients only. Recently diagnosed patients were further sub-grouped into ≤2 years or 2-5 years. The primary efficacy endpoint was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score. In Study 1, 41.5% patients had recent diagnosis (≤2 years: 56.8%; 2-5 years: 43.2%); 58.5% had chronic schizophrenia. In Study 2, 52.8% and 47.2% patients were grouped into ≤2 years and 2-5 years, respectively. PANSS total score showed significantly greater improvement in patients with recently diagnosed vs. chronic schizophrenia. Similar results were obtained for PANSS responder rate, improvements in PANSS, and CGI-S scores. PP1M was efficacious in both recently diagnosed and chronic schizophrenia, with the benefits being more pronounced in patients with recently diagnosed schizophrenia. This adds to growing evidence recommending long-acting antipsychotic interventions at early stages of schizophrenia.

  6. Duloxetine Compared with Pregabalin for Diabetic Peripheral Neuropathic Pain Management in Patients with Suboptimal Pain Response to Gabapentin and Treated with or without Antidepressants: A Post Hoc Analysis.

    Science.gov (United States)

    Tanenberg, Robert J; Clemow, David B; Giaconia, Joseph M; Risser, Richard C

    2014-09-01

    To examine the efficacy of duloxetine vs. pregabalin in the treatment for diabetic peripheral neuropathic pain (DPNP), comparing patient subgroups with and without concomitant antidepressant use. This post hoc analysis assessed data from a randomized 12-week study that confirmed the noninferiority of duloxetine to pregabalin. In the previously published study, patients with DPNP with inadequate response to gabapentin were switched to duloxetine monotherapy, combination therapy of duloxetine plus gabapentin, or pregabalin monotherapy. Current, stable antidepressant use was allowed; 79 patients were concomitantly treated with antidepressants and 328 without antidepressants. In this post hoc analysis, improvement in the weekly mean of diary-based average daily pain ratings (numerical rating scale: 0-10) in antidepressant users and nonusers was analyzed using a longitudinal mixed-models repeated-measures (MMRM) analysis, including a test of the 3-way interaction (antidepressant subgroup by treatment by week) to assess whether the differences among treatment groups over 12 weeks differ between the antidepressant-use subgroups. The 3-way interaction was significant (P = 0.035), demonstrating that treatment-group differences in pain reduction over time differ between the subgroups. Among patients without antidepressant use, patients treated with duloxetine had significantly greater pain reduction than pregabalin at Week 4 and at each successive week up to the 12-week endpoint (-2.8 for duloxetine and -2.1 for pregabalin; P = 0.031); patients treated with duloxetine plus gabapentin had greater pain reduction than pregabalin at Weeks 2, 3, 5, and 7 to 9 (P ≤ 0.05) but not at endpoint (-2.4; P = 0.222). Among concomitant antidepressant users, no treatment-group differences were found. In patients with DPNP inadequately treated with gabapentin without the concomitant use of antidepressants, switching to duloxetine instead of pregabalin may provide better pain

  7. A review and additional post-hoc analyses of the incidence and impact of constipation observed in darifenacin clinical trials

    Directory of Open Access Journals (Sweden)

    Tack J

    2012-09-01

    Full Text Available Jan Tack,1 Jean-Jacques Wyndaele,2 Greg Ligozio,3 Mathias Egermark41University of Leuven, Gastroenterology Section, Leuven, 2University of Antwerp, Department of Urology, Antwerp, Belgium; 3Novartis Pharmaceuticals Corporation, NJ, USA; 4Roche Diagnostics Scandinavia AB, Bromma, Sweden and formerly of Novartis Pharma AG, Basel, SwitzerlandBackground: Constipation is a common side effect of antimuscarinic treatment for overactive bladder (OAB. This review evaluates the incidence and impact of constipation on the lives of patients with OAB being treated with darifenacin.Methods: Constipation data from published Phase III and Phase IIIb/IV darifenacin studies were reviewed and analyzed. Over 4000 patients with OAB (aged 18–89 years; ≥80% female enrolled in nine studies (three Phase III [data from these fixed-dose studies were pooled and provide the primary focus for this review], three Phase IIIb, and three Phase IV. The impact of constipation was assessed by discontinuations, use of concomitant laxatives, patient-reported perception of treatment, and a bowel habit questionnaire.Results: In the pooled Phase III trials, 14.8% (50/337 of patients on darifenacin 7.5 mg/day and 21.3% (71/334 on 15 mg/day experienced constipation compared with 12.6% (28/223 and 6.2% (24/388 with tolterodine and placebo, respectively. In addition, a few patients discontinued treatment due to constipation (0.6% [2/337], 1.2% [4/334], 1.8% [4/223], and 0.3% [1/388] in the darifenacin 7.5 mg/day or 15 mg/day, tolterodine, and placebo groups, respectively, or required concomitant laxatives (3.3% [11/337], 6.6% [22/334], 7.2% [16/223], and 1.5% [6/388] in the darifenacin 7.5 mg/day or 15 mg/day, tolterodine, and placebo groups, respectively. Patient-reported perception of treatment quality was observed to be similar between patients who experienced constipation and those who did not. During the long-term extension study, a bowel habit questionnaire showed only small numerical changes over time in frequency of bowel movements, straining to empty bowels, or number of days with hard stools.Conclusion: While constipation associated with darifenacin was reported in ≤21% of the patient population, it only led to concomitant laxative use in approximately one-third of these patients and a low incidence of treatment discontinuation. These data suggest that constipation did not impact patient perception of treatment quality.Keywords: antimuscarinics, tolerability, overactive bladder

  8. Illustrating, Quantifying, and Correcting for Bias in Post-hoc Analysis of Gene-Based Rare Variant Tests of Association

    Directory of Open Access Journals (Sweden)

    Kelsey E. Grinde

    2017-09-01

    Full Text Available To date, gene-based rare variant testing approaches have focused on aggregating information across sets of variants to maximize statistical power in identifying genes showing significant association with diseases. Beyond identifying genes that are associated with diseases, the identification of causal variant(s in those genes and estimation of their effect is crucial for planning replication studies and characterizing the genetic architecture of the locus. However, we illustrate that straightforward single-marker association statistics can suffer from substantial bias introduced by conditioning on gene-based test significance, due to the phenomenon often referred to as “winner's curse.” We illustrate the ramifications of this bias on variant effect size estimation and variant prioritization/ranking approaches, outline parameters of genetic architecture that affect this bias, and propose a bootstrap resampling method to correct for this bias. We find that our correction method significantly reduces the bias due to winner's curse (average two-fold decrease in bias, p < 2.2 × 10−6 and, consequently, substantially improves mean squared error and variant prioritization/ranking. The method is particularly helpful in adjustment for winner's curse effects when the initial gene-based test has low power and for relatively more common, non-causal variants. Adjustment for winner's curse is recommended for all post-hoc estimation and ranking of variants after a gene-based test. Further work is necessary to continue seeking ways to reduce bias and improve inference in post-hoc analysis of gene-based tests under a wide variety of genetic architectures.

  9. Effect of smoking reduction and cessation on the plasma levels of the oxidative stress biomarker glutathione--Post-hoc analysis of data from a smoking cessation trial.

    Science.gov (United States)

    Mons, Ute; Muscat, Joshua E; Modesto, Jennifer; Richie, John P; Brenner, Hermann

    2016-02-01

    Cigarette smoke contains high concentrations of free radical components that induce oxidative stress. Smoking-induced oxidative stress is thought to contribute to chronic obstructive pulmonary disease, cardiovascular disease and lung cancer through degenerative processes in the lung and other tissues. It is uncertain however whether smoking cessation lowers the burden of oxidative stress. We used data from a randomized controlled cessation trial of 434 current smokers for a post-hoc examination of the effects of smoking cessation on blood plasma levels of total glutathione (tGSH), the most abundant endogenous antioxidant in cells, and total cysteine (tCys), an amino acid and constituent of glutathione. Smoking status was validated based on serum cotinine levels. Multivariate linear mixed models were fitted to examine the association of smoking cessation and change in cigarette consumption with tGSH and tCys. After 12 months follow-up, quitters (n=55) had significantly increased levels of tGSH compared to subjects who continued to smoke (Psmoke but reduced their intensity of smoking. No significant effect of smoking cessation or reduction was observed on levels of tCys. These results suggest that smoking cessation but not smoking reduction reduces levels of oxidative stress. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial.

    Science.gov (United States)

    Jaspers Focks, Jeroen; Brouwer, Marc A; Wojdyla, Daniel M; Thomas, Laine; Lopes, Renato D; Washam, Jeffrey B; Lanas, Fernando; Xavier, Denis; Husted, Steen; Wallentin, Lars; Alexander, John H; Granger, Christopher B; Verheugt, Freek W A

    2016-06-15

     To determine whether the treatment effect of apixaban versus warfarin differs with increasing numbers of concomitant drugs used by patients with atrial fibrillation.  Post hoc analysis performed in 2015 of results from ARISTOTLE (apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation)-a multicentre, double blind, double dummy trial that started in 2006 and ended in 2011.  18 201 ARISTOTLE trial participants.  In the ARISTOTLE trial, patients were randomised to either 5 mg apixaban twice daily (n=9120) or warfarin (target international normalised ratio range 2.0-3.0; n=9081). In the post hoc analysis, patients were divided into groups according to the number of concomitant drug treatments used at baseline (0-5, 6-8, ≥9 drugs) with a median follow-up of 1.8 years.  Clinical outcomes and treatment effects of apixaban versus warfarin (adjusted for age, sex, and country).  Each patient used a median of six drugs (interquartile range 5-9); polypharmacy (≥5 drugs) was seen in 13 932 (76.5%) patients. Greater numbers of concomitant drugs were used in older patients, women, and patients in the United States. The number of comorbidities increased across groups of increasing numbers of drugs (0-5, 6-8, ≥9 drugs), as did the proportions of patients treated with drugs that interact with warfarin or apixaban. Mortality also rose significantly with the number of drug treatments (PARISTOTLE trial, three quarters of patients had polypharmacy; this subgroup had an increased comorbidity, more interacting drugs, increased mortality, and higher rates of thromboembolic and bleeding complications. In terms of a potential differential response to anticoagulation therapy in patients with atrial fibrillation and polypharmacy, apixaban was more effective than warfarin, and is at least just as safe.Trial registration ARISTOTLE trial, ClinicalTrials.gov NCT00412984. Published by the BMJ Publishing Group Limited. For permission to use (where

  11. Influencing Anesthesia Provider Behavior Using Anesthesia Information Management System Data for Near Real-Time Alerts and Post Hoc Reports.

    Science.gov (United States)

    Epstein, Richard H; Dexter, Franklin; Patel, Neil

    2015-09-01

    In this review article, we address issues related to using data from anesthesia information management systems (AIMS) to deliver near real-time alerts via AIMS workstation popups and/or alphanumeric pagers and post hoc reports via e-mail. We focus on reports and alerts for influencing the behavior of anesthesia providers (i.e., anesthesiologists, anesthesia residents, and nurse anesthetists). Multiple studies have shown that anesthesia clinical decision support (CDS) improves adherence to protocols and increases financial performance through facilitation of billing, regulatory, and compliance documentation; however, improved clinical outcomes have not been demonstrated. We inform developers and users of feedback systems about the multitude of concerns to consider during development and implementation of CDS to increase its effectiveness and to mitigate its potentially disruptive aspects. We discuss the timing and modalities used to deliver messages, implications of outlier-only versus individualized feedback, the need to consider possible unintended consequences of such feedback, regulations, sustainability, and portability among systems. We discuss statistical issues related to the appropriate evaluation of CDS efficacy. We provide a systematic review of the published literature (indexed in PubMed) of anesthesia CDS and offer 2 case studies of CDS interventions using AIMS data from our own institution illustrating the salient points. Because of the considerable expense and complexity of maintaining near real-time CDS systems, as compared with providing individual reports via e-mail after the fact, we suggest that if the same goal can be accomplished via delayed reporting versus immediate feedback, the former approach is preferable. Nevertheless, some processes require near real-time alerts to produce the desired improvement. Post hoc e-mail reporting from enterprise-wide electronic health record systems is straightforward and can be accomplished using system

  12. Lenient vs. strict rate control in patients with atrial fibrillation and heart failure: a post-hoc analysis of the RACE II study

    NARCIS (Netherlands)

    Mulder, Bart A.; van Veldhuisen, Dirk J.; Crijns, Harry J. G. M.; Tijssen, Jan G. P.; Hillege, Hans L.; Alings, Marco; Rienstra, Michiel; Groenveld, Hessel F.; van den Berg, Maarten P.; van Gelder, Isabelle C.

    2013-01-01

    It is unknown whether lenient rate control is an acceptable strategy in patients with AF and heart failure. We evaluated differences in outcome in patients with AF and heart failure treated with lenient or strict rate control. This post-hoc analysis of the RACE II trial included patients with an

  13. The dose-response effects of aerobic exercise on musculoskeletal injury: a post hoc analysis of a randomized trial.

    Science.gov (United States)

    Brown, Justin C; Schmitz, Kathryn H

    2017-01-01

    In a post hoc analysis, we quantified the risk of musculoskeletal injury (MSI) associated with different volumes of aerobic exercise in a randomized trial. Premenopausal women (n = 119) were randomized to one of three groups: low-dose aerobic exercise (150 min·per week), high-dose aerobic exercise (300 min·per week) or control (usual activity) for 5 months. Compared to the control group, the risk of reporting an acute MSI increased with higher volumes of aerobic exercise, with a similar pattern observed for recurrent MSI. The risk of reporting an MSI severe enough to impair activities of daily living did not increase with higher volumes of aerobic exercise. Approximately half of MSI were causally attributed to aerobic exercise. The risk of experiencing an acute or recurrent MSI increases with higher volumes of aerobic exercise; however, the risk of experiencing an MSI severe enough to impair activities of daily living does not increase with higher volumes of aerobic exercise.

  14. Hematologic responses in patients with aplastic anemia treated with deferasirox: a post hoc analysis from the EPIC study

    Science.gov (United States)

    Lee, Jong Wook; Yoon, Sung-Soo; Shen, Zhi Xiang; Ganser, Arnold; Hsu, Hui-Chi; El-Ali, Ali; Habr, Dany; Martin, Nicolas; Porter, John B.

    2013-01-01

    Reports are emerging of hematologic responses associated with iron chelation therapy; however, studies are limited in aplastic anemia patients. Deferasirox reduced iron overload in aplastic anemia patients enrolled in the EPIC (Evaluation of Patients’ Iron Chelation with Exjade®) study (n=116). A post hoc analysis of hematologic responses was conducted on 72 patients with evaluable hematologic parameters (according to UK guideline criteria), 24 of whom received deferasirox without concomitant immunosuppressive treatment. Partial hematologic responses were observed in 11 of 24 (45.8%) patients; all became transfusion-independent. One patient had an additional platelet response and one patient had an additional platelet and hemoglobin response. Mean serum ferritin levels at end of study were significantly reduced in partial hematologic responders (n=11; −3948±4998 ng/mL; baseline 6693±7014 ng/mL; percentage change from baseline −45.7%; P=0.0029). In non-responders, the reduction in serum ferritin was less pronounced (n=13; −2021±3242 ng/mL; baseline 4365±3063 ng/mL; % change from baseline −27.6%; P=0.0171). Alongside reduction in iron overload, deferasirox may, therefore, improve hematologic parameters in a subset of aplastic anemia patients. Further investigation is required to elucidate the mechanisms involved. (Clinicaltrials.gov identifier: NCT00171821) PMID:23585526

  15. An extensible analysable system model

    DEFF Research Database (Denmark)

    Probst, Christian W.; Hansen, Rene Rydhof

    2008-01-01

    Analysing real-world systems for vulnerabilities with respect to security and safety threats is a difficult undertaking, not least due to a lack of availability of formalisations for those systems. While both formalisations and analyses can be found for artificial systems such as software......, this does not hold for real physical systems. Approaches such as threat modelling try to target the formalisation of the real-world domain, but still are far from the rigid techniques available in security research. Many currently available approaches to assurance of critical infrastructure security...... are based on (quite successful) ad-hoc techniques. We believe they can be significantly improved beyond the state-of-the-art by pairing them with static analyses techniques. In this paper we present an approach to both formalising those real-world systems, as well as providing an underlying semantics, which...

  16. Dose-related beneficial and harmful effects of gabapentin in postoperative pain management - post hoc analyses from a systematic review with meta-analyses and trial sequential analyses

    DEFF Research Database (Denmark)

    Fabritius, Maria Louise; Wetterslev, Jørn; Mathiesen, Ole

    2017-01-01

    of Systematic Reviews published protocol: PROSPERO (ID: CRD42013006538). The methods followed Cochrane guidelines. The Cochrane Library’s CENTRAL, PubMed, EMBASE, Science Citation Index Expanded, Google Scholar, and FDA database were searched for relevant trials. Randomized clinical trials comparing gabapentin...... numerically the most prominent reduction in morphine consumption. Twenty-seven trials reported 72 SAEs, of which 83% were reported in the >1050 mg subgroup. No systematic increase in SAEs was observed with increasing doses of gabapentin. Conclusion: Data were sparse, and the small number of trials with low...

  17. Relationship between response to aripiprazole once-monthly and paliperidone palmitate on work readiness and functioning in schizophrenia: A post-hoc analysis of the QUALIFY study.

    Directory of Open Access Journals (Sweden)

    Steven G Potkin

    Full Text Available Schizophrenia is a chronic disease with negative impact on patients' employment status and quality of life. This post-hoc analysis uses data from the QUALIFY study to elucidate the relationship between work readiness and health-related quality of life and functioning. QUALIFY was a 28-week, randomized study (NCT01795547 comparing the treatment effectiveness of aripiprazole once-monthly 400 mg and paliperidone palmitate once-monthly using the Heinrichs-Carpenter Quality-of-Life Scale as the primary endpoint. Also, patients' capacity to work and work readiness (Yes/No was assessed with the Work Readiness Questionnaire. We categorized patients, irrespective of treatment, by work readiness at baseline and week 28: No to Yes (n = 41, Yes to Yes (n = 49, or No at week 28 (n = 118. Quality-of-Life Scale total, domains, and item scores were assessed with a mixed model of repeated measures. Patients who shifted from No to Yes in work readiness showed robust improvements on Quality-of-Life Scale total scores, significantly greater than patients not ready to work at week 28 (least squares mean difference: 11.6±2.6, p<0.0001. Scores on Quality-of-Life Scale instrumental role domain and items therein-occupational role, work functioning, work levels, work satisfaction-significantly improved in patients shifting from No to Yes in work readiness (vs patients No at Week 28. Quality-of-Life Scale total scores also significantly predicted work readiness at week 28. Overall, these results highlight a strong association between improvements in health-related quality of life and work readiness, and suggest that increasing patients' capacity to work is an achievable and meaningful goal in the treatment of impaired functioning in schizophrenia.

  18. Post hoc interlaboratory comparison of single particle ICP-MS size measurements of NIST gold nanoparticle reference materials.

    Science.gov (United States)

    Montoro Bustos, Antonio R; Petersen, Elijah J; Possolo, Antonio; Winchester, Michael R

    2015-09-01

    Single particle inductively coupled plasma-mass spectrometry (spICP-MS) is an emerging technique that enables simultaneous measurement of nanoparticle size and number quantification of metal-containing nanoparticles at realistic environmental exposure concentrations. Such measurements are needed to understand the potential environmental and human health risks of nanoparticles. Before spICP-MS can be considered a mature methodology, additional work is needed to standardize this technique including an assessment of the reliability and variability of size distribution measurements and the transferability of the technique among laboratories. This paper presents the first post hoc interlaboratory comparison study of the spICP-MS technique. Measurement results provided by six expert laboratories for two National Institute of Standards and Technology (NIST) gold nanoparticle reference materials (RM 8012 and RM 8013) were employed. The general agreement in particle size between spICP-MS measurements and measurements by six reference techniques demonstrates the reliability of spICP-MS and validates its sizing capability. However, the precision of the spICP-MS measurement was better for the larger 60 nm gold nanoparticles and evaluation of spICP-MS precision indicates substantial variability among laboratories, with lower variability between operators within laboratories. Global particle number concentration and Au mass concentration recovery were quantitative for RM 8013 but significantly lower and with a greater variability for RM 8012. Statistical analysis did not suggest an optimal dwell time, because this parameter did not significantly affect either the measured mean particle size or the ability to count nanoparticles. Finally, the spICP-MS data were often best fit with several single non-Gaussian distributions or mixtures of Gaussian distributions, rather than the more frequently used normal or log-normal distributions.

  19. Perampanel with concomitant levetiracetam and topiramate: Post hoc analysis of adverse events related to hostility and aggression.

    Science.gov (United States)

    Chung, Steve; Williams, Betsy; Dobrinsky, Cindy; Patten, Anna; Yang, Haichen; Laurenza, Antonio

    2017-10-01

    In 4 Phase III registration trials (3 in patients with partial seizures, N=1480; 1 in patients with PGTCS, N=163), perampanel administered to patients already receiving 1-3 concomitant antiepileptic drugs (AEDs) demonstrated statistically superior efficacy compared to placebo in reducing seizure frequency. However, use of perampanel in these studies was associated with a risk of psychiatric and behavioral adverse reactions, including aggression, hostility, irritability, anger, and homicidal ideation and threats. The present study is a post hoc analysis of pooled data from these 4 trials to determine if concomitant treatment with levetiracetam and/or topiramate increased the risk of hostility- and aggression-related AEs. Treatment-emergent AEs (TEAEs) were determined using a "Narrow & Broad" search based on the Medical Dictionary for Regulatory Activities (MedDRA) standard MedDRA query (SMQ) for hostility- and aggression-related events. The rate of hostility- and aggression-related TEAEs was observed to be similar among perampanel-treated patients: a) receiving levetiracetam (N=340) compared to those not receiving levetiracetam (N=779); b) receiving topiramate (N=223) compared to those not receiving topiramate (N=896); and c) receiving both levetiracetam and topiramate (N=47) compared to those not receiving levetiracetam and topiramate (N=1072). Severe and serious TEAEs related to hostility and aggression were rare and occurred at a similar rate regardless of concomitant levetiracetam and/or topiramate therapy. Taken together, these results suggest that concomitant treatment with levetiracetam and/or topiramate has no appreciable effect on the occurrence of hostility- or aggression-related TEAEs in patients receiving perampanel. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Is a reduction in albuminuria associated with renal and cardiovascular protection? A post hoc analysis of the ALTITUDE trial.

    Science.gov (United States)

    Heerspink, H J L; Ninomiya, T; Persson, F; Brenner, B M; Brunel, P; Chaturvedi, N; Desai, A S; Haffner, S M; Mcmurray, J J V; Solomon, S D; Pfeffer, M A; Parving, H-H; de Zeeuw, D

    2016-02-01

    To investigate whether the degree of albuminuria reduction observed in the ALTITUDE trial is associated with renal and cardiovascular protection, and secondly, whether the reduction in albuminuria was too small to afford clinical benefit. In a post hoc analysis of the ALTITUDE trial in 8561 patients with type 2 diabetes and chronic kidney disease or cardiovascular disease we examined the effect of albuminuria changes at 6 months on renal and cardiovascular outcomes using Cox proportional hazard regression. The median change in albuminuria in the first 6 months in the aliskiren arm of the trial was -12% (25th to 75th percentile: -48.7_to_ +41.9%) and 0.0% (25th to 75th percentile: -40.2_to_55%) in the placebo arm. Changes in albuminuria in the first 6 months were linearly associated with renal and cardiovascular endpoints: a >30% reduction in albuminuria in the first 6 months was associated with a 62% reduction in renal risk and a 25% reduction in cardiovascular risk compared with an increase in albuminuria. The association between changes at 6 months in albuminuria and renal or cardiovascular endpoints was similar in the two treatment groups (p for interaction >0.1 for both endpoints). The addition of aliskiren to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy resulted in albuminuria changes that were associated with renal and cardiovascular risk changes. This did not translate into renal or cardiovascular protection because the overall reduction in albuminuria in the aliskiren arm was too small and nearly similar to that in the placebo arm. © 2015 John Wiley & Sons Ltd.

  1. Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.

    Science.gov (United States)

    Bryce, A H; Alumkal, J J; Armstrong, A; Higano, C S; Iversen, P; Sternberg, C N; Rathkopf, D; Loriot, Y; de Bono, J; Tombal, B; Abhyankar, S; Lin, P; Krivoshik, A; Phung, D; Beer, T M

    2017-06-01

    Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.

  2. Post-hoc principal component analysis on a largely illiterate elderly population from North-west India to identify important elements of mini-mental state examination

    OpenAIRE

    Raina, Sunil Kumar; Chander, Vishav; Raina, Sujeet; Grover, Ashoo

    2016-01-01

    Background: Mini-mental state examination (MMSE) scale measures cognition using specific elements that can be isolated, defined, and subsequently measured. This study was conducted with the aim to analyze the factorial structure of MMSE in a largely, illiterate, elderly population in India and to reduce the number of variables to a few meaningful and interpretable combinations. Methodology: Principal component analysis (PCA) was performed post-hoc on the data generated by a research project c...

  3. Impact of bone-targeted therapies in chemotherapy-naïve metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: post hoc analysis of study COU-AA-302.

    Science.gov (United States)

    Saad, Fred; Shore, Neal; Van Poppel, Hendrik; Rathkopf, Dana E; Smith, Matthew R; de Bono, Johann S; Logothetis, Christopher J; de Souza, Paul; Fizazi, Karim; Mulders, Peter F A; Mainwaring, Paul; Hainsworth, John D; Beer, Tomasz M; North, Scott; Fradet, Yves; Griffin, Thomas A; De Porre, Peter; Londhe, Anil; Kheoh, Thian; Small, Eric J; Scher, Howard I; Molina, Arturo; Ryan, Charles J

    2015-10-01

    Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy. Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients. This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial. Patients were grouped by concomitant BTT use or no BTT use. Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models. While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p=0.01) and increased the time to ECOG deterioration (HR 0.75; pAA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in AA with concomitant BTT was safe and well tolerated in men with chemotherapy-naïve mCRPC. The benefits of AA on clinical outcomes were increased with concomitant BTT. Treatment of advanced prostate cancer often includes bone-targeted therapy. This post hoc analysis showed that in patients with advanced prostate cancer who were treated with abiraterone acetate and

  4. Categorical improvements in disease severity in patients with major depressive disorder treated with vilazodone: post hoc analysis of four randomized, placebo-controlled trials

    Directory of Open Access Journals (Sweden)

    Durgam S

    2016-12-01

    Full Text Available Suresh Durgam,1 Changzheng Chen,1 Carl P Gommoll,1 John Edwards,1 Leslie Citrome2 1Allergan, Jersey City, NJ, USA; 2Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA Background: In three 8-week studies of vilazodone 40 mg/d (NCT00285376, NCT00683592, and NCT01473394 and a 10-week study of vilazodone 20 or 40 mg/d (NCT01473381, adults with major depressive disorder (MDD showed significantly greater improvement with vilazodone versus placebo in global disease severity as measured by mean change from baseline in Clinical Global Impression of Severity (CGI-S score. To assess the proportion of patients achieving clinically meaningful improvement, a post hoc pooled analysis was conducted using categorical shifts in disease severity based on CGI-S scores at baseline and end of treatment (EOT. Methods: Analyses were conducted in the pooled intent-to-treat population (N=2,218. Definitions of categorical shifts included CGI-S ≥4 (moderately ill or worse at baseline to CGI-S ≤2 (normal or borderline ill at EOT; CGI-S ≥5 (markedly ill or worse at baseline to CGI-S ≤2 at EOT; and CGI-S ≥6 (severely ill or worse at baseline to CGI-S ≤3 (mildly ill or better at EOT. Results: At baseline, 2,217 patients were moderately ill or worse. The percentage who improved to normal or borderline ill was significantly higher with vilazodone than with placebo (40.0% versus 27.8%; odds ratio [OR] =1.7, P<0.001; number needed to treat [NNT] =9. In the 979 patients who were markedly ill or worse at baseline, the percentage who improved to normal or borderline ill was significantly higher with vilazodone than with placebo (36.8% versus 25.5%; OR =1.7, P<0.001; NNT =9. The small number of severely ill patients at baseline (n =43 provided inadequate power to detect statistically significant between-group differences, but an NNT =5 was found for improvement to mildly ill or better. Conclusion: Categorical shift analyses

  5. Relationship between intraoperative regional cerebral oxygen saturation trends and cognitive decline after total knee replacement: a post-hoc analysis.

    Science.gov (United States)

    Salazar, Fátima; Doñate, Marta; Boget, Teresa; Bogdanovich, Ana; Basora, Misericordia; Torres, Ferran; Gracia, Isabel; Fàbregas, Neus

    2014-01-01

    Bilateral regional brain oxygen saturation (rSO2) trends, reflecting intraoperative brain oxygen imbalance, could warn of brain dysfunction. Various types of cognitive impairment, such as memory decline, alterations in executive function or subjective complaints, have been described three months after surgery. Our aim was to explore the potential utility of rSO2 values as a warning sign for the development of different types of decline in postoperative psychological function. Observational post-hoc analysis of data for the patient sample (n = 125) of a previously conducted clinical trial in patients over the age of 65 years undergoing total knee replacement under spinal anesthesia. Demographic, hemodynamic and bilateral rSO2 intraoperative values were recorded. An absolute rSO2 value of 20% or >25% below baseline were chosen as relevant cutoffs. Composite function test scores were created from baseline to three months for each patient and adjusted for the mean (SD) score changes for a control group (n = 55). Tests were used to assess visual-motor coordination and executive function (VM-EF) (Wechsler Digit Symbol-Coding and Visual Reproduction, Trail Making Test) and memory (Auditory Verbal Learning, Wechsler Memory Scale); scales were used to assess psychological symptoms. We observed no differences in baseline rSO2 values; rSO2 decreased significantly in all patients during surgery (P memory decline, 3 (2.4%) had VM-EF decline, and 33 (26.4%) had psychological symptoms. Left and right rSO2 values were asymmetric in patients who had memory decline (mean [SD] left-right ratio of 95.03 [8.51] vs 101.29 [6.7] for patients with no changes, P = 0.0012). The mean right-left difference in rSO2 was also significant in these patients (-2.87% [4.73%], lower on the right, P = 0.0034). Detection of a trend to asymmetry in rSO2 values can warn of possible postoperative onset of memory decline. Psychological symptoms and memory decline were common three months after

  6. Relationship between exercise endurance and static hyperinflation in a post hoc analysis of two clinical trials in patients with COPD

    Science.gov (United States)

    Singh, Sally; Maltais, François; Tombs, Lee; Fahy, William A; Vahdati-Bolouri, Mitra; Locantore, Nicholas; Riley, John H

    2018-01-01

    Background Lung hyperinflation and exercise intolerance are hallmarks of chronic obstructive pulmonary disease (COPD). However, their relationship remains uncertain. A combined analysis of two placebo-controlled, randomized studies examined the effects of the long-acting muscarinic antagonist umeclidinium (UMEC) and long-acting β2-agonist vilanterol (VI) separately and in combination on static hyperinflation, exercise endurance time (EET), and their relationship in patients with COPD. Methods Patients with moderate-to-severe stable COPD and resting functional residual capacity >120% predicted were randomized to UMEC/VI 62.5/25 μg, UMEC 62.5 μg, VI 25 μg, or placebo for 12 weeks. Inspiratory capacity (IC), residual volume (RV), total lung capacity (TLC), and EET in an endurance shuttle-walk test were measured. In this post hoc analysis, IC/TLC, RV/TLC, and IC were used as hyperinflation markers. Results After 12 weeks, UMEC/VI and UMEC and VI showed significant improvements in hyperinflation versus placebo when measured by absolute change from baseline in IC/TLC (trough and 3 hours postdose [P≤0.011]). UMEC/VI showed significant improvements versus UMEC and VI in absolute changes in IC/TLC (trough and 3 hours postdose [P≤0.001]). Statistical significance for comparisons with placebo and between treatments for absolute changes in IC and percentage changes in RV/TLC followed similar patterns to those for absolute changes in IC/TLC. UMEC/VI showed significant improvements in EET versus placebo at day 2 and week 12, measured as change from baseline in seconds (P≤0.002) and as a percentage from baseline (P≤0.005). There was a lack of evidence to suggest a correlation between improvements in static hyperinflation and EET at any time point. Conclusion Although the dual bronchodilator UMEC/VI demonstrated greater improvements in static hyperinflation markers than UMEC or VI and significant improvements in exercise endurance, no direct relationship was observed

  7. Efficacy and tolerability of adjunct perampanel based on number of antiepileptic drugs at baseline and baseline predictors of efficacy: A phase III post-hoc analysis.

    Science.gov (United States)

    Glauser, Tracy; Laurenza, Antonio; Yang, Haichen; Williams, Betsy; Ma, Tony; Fain, Randi

    2016-01-01

    Perampanel is a selective, noncompetitive AMPA receptor antagonist with demonstrated efficacy and tolerability in partial seizures in patients aged ≥ 12 years in Phase III studies. Post-hoc analysis of these studies was conducted to determine the efficacy and tolerability of perampanel based on the number of concomitant antiepileptic drugs (AEDs) at baseline, as well as to examine which baseline characteristics, if any, were predictors of efficacy. Efficacy parameters were based on the number of baseline AEDs, and logistic regression analyses were used to evaluate the association of demographic and baseline clinical factors with probability of ≥ 50% reduction in seizure frequency. Patients on 1 AED at baseline were significantly more likely to have reduced seizure frequency (P<0.02) and improved 50% responder rate (P<0.02) than patients on 3 AEDs at baseline. Secondarily generalized seizures at baseline, unknown etiology, and use of concomitant non-inducer AEDs were also established as positive predictors of efficacy (50% responder rate; P<0.01). Patients with more AEDs at baseline were associated with greater use of inducers (P<0.01), which may result in decreased exposure of perampanel in these patients and lower efficacy. Patients with 1 AED at baseline had a significantly shorter time since diagnosis compared with patients in the 3 (P<0.01) AEDs group, as well as a lower median seizure frequency at baseline compared to patients on 3 AEDs (P<0.05), suggesting that the reduced efficacy of perampanel with 3 AEDs may also be associated with the greater severity of seizures in the patient groups. The incidence of adverse events in perampanel-treated patients was similar regardless of the number of AEDs at baseline. Greater efficacy is predicted for patients receiving fewer concomitant AEDs when starting perampanel, as well as for those receiving concomitant treatment with AEDs that are not CYP3A4 enzyme-inducers, compared to patients treated with multiple

  8. Post hoc analysis of plasma amino acid profiles: towards a specific pattern in autism spectrum disorder and intellectual disability.

    Science.gov (United States)

    Delaye, Jean-Baptiste; Patin, Franck; Lagrue, Emmanuelle; Le Tilly, Olivier; Bruno, Clement; Vuillaume, Marie-Laure; Raynaud, Martine; Benz-De Bretagne, Isabelle; Laumonnier, Frederic; Vourc'h, Patrick; Andres, Christian; Blasco, Helene

    2018-01-01

    Objectives Autism spectrum disorders and intellectual disability present a challenge for therapeutic and dietary management. We performed a re-analysis of plasma amino acid chromatography of children with autism spectrum disorders ( n = 22) or intellectual disability ( n = 29) to search for a metabolic signature that can distinguish individuals with these disorders from controls ( n = 30). Methods We performed univariate and multivariate analyses using different machine learning strategies, from the raw data of the amino acid chromatography. Finally, we analysed the metabolic pathways associated with discriminant biomarkers. Results Multivariate analysis revealed models to discriminate patients with autism spectrum disorders or intellectual disability and controls from plasma amino acid profiles ( P intellectual disability patients shared similar differences relative to controls, including lower glutamate ( P intellectual disability revealed the involvement of urea, 3-methyl-histidine and histidine metabolism. Biosigner analysis and univariate analysis confirmed the role of 3-methylhistidine ( P = 0.004), histidine ( P = 0.003), urea ( P = 0.0006) and lysine ( P = 0.002). Conclusions We revealed discriminant metabolic patterns between autism spectrum disorders, intellectual disability and controls. Amino acids known to play a role in neurotransmission were discriminant in the models comparing autism spectrum disorders or intellectual disability to controls, and histidine and b-alanine metabolism was specifically highlighted in the model.

  9. Graphical models for genetic analyses

    DEFF Research Database (Denmark)

    Lauritzen, Steffen Lilholt; Sheehan, Nuala A.

    2003-01-01

    This paper introduces graphical models as a natural environment in which to formulate and solve problems in genetics and related areas. Particular emphasis is given to the relationships among various local computation algorithms which have been developed within the hitherto mostly separate areas...... of graphical models and genetics. The potential of graphical models is explored and illustrated through a number of example applications where the genetic element is substantial or dominating....

  10. Comparison of Efficacy and Safety of Liraglutide 3.0 mg in Individuals with BMI above and below 35 kg/m²: A Post-hoc Analysis

    Directory of Open Access Journals (Sweden)

    Carel le Roux

    2017-11-01

    Full Text Available Objective: To investigate whether the efficacy and safety of liraglutide 3.0 mg differed between two subgroups, BMI 27 to Methods: A post-hoc analysis of two 56-week, randomized, double-blind, placebo-controlled trials (SCALE Obesity and Prediabetes; SCALE Diabetes. Subgroup differences in treatment effects of liraglutide 3.0 mg were evaluated by testing the interaction between treatment group and baseline BMI subgroup. Results: Significantly greater weight loss (0-56 weeks was observed with liraglutide 3.0 mg versus placebo in all patient groups while on treatment. There was no evidence that the weight-lowering effect of liraglutide 3.0 mg differed between BMI subgroups (interaction p > 0.05. Similarly, for most secondary endpoints significantly greater improvements were observed with liraglutide 3.0 mg versus placebo, with no indication treatment effects differing between subgroups. The safety profile of liraglutide 3.0 mg was broadly similar across BMI subgroups. Conclusion: This post-hoc analysis did not indicate any differences in the treatment effects, or safety profile, of liraglutide 3.0 mg for individuals with BMI 27 to <35 or ≥35 kg/m². Liraglutide 3.0 mg can therefore be considered for individuals with a BMI of ≥35 as well as for those with a BMI of 27 to <35 kg/m².

  11. Short-term blood pressure variability in acute stroke: post hoc analysis of the controlling hypertension and hypotension immediately post stroke and continue or stop post-stroke antihypertensives collaborative study trials.

    Science.gov (United States)

    Manning, Lisa S; Mistri, Amit K; Potter, John; Rothwell, Peter M; Robinson, Thompson G

    2015-06-01

    Short-term blood pressure variability (BPV) may predict outcome in acute stroke. We undertook a post hoc analysis of data from 2 randomized controlled trials to determine the effect of short-term BPV on 2-week outcome. Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS) was a trial of BP-lowering, enrolling 179 acute stroke patients (onset3) at 2 weeks. Seven hundred six (92.5%) and 171 (95.5%) participants were included in the analysis for the COSSACS and CHHIPS data sets, respectively. Adjusted logistic regression analyses revealed no statistically significant associations between any of the included BPV parameters with 2-week death or disability in either study data set: COSSACS, odds ratio SD systolic BP 0.98 (0.78-1.23); CHHIPS, odds ratio SD systolic BP 0.97 (0.90-1.11). When derived from casual cuff BP measures, short-term BPV is not a useful predictor of early (2 weeks) outcome after acute stroke. Differing methodology may account for the discordance with previous studies indicating long-term (casual BPV) and short-term (beat-to-beat BPV) prognostic value. COSSACS was registered on the International Standard Randomised Controlled Trial Register; URL: http://www.isrctn.com. Unique identifier: ISRCTN89712435. CHHIPS was registered on the National Research Register; URL: http://public.ukcrn.org.uk. Unique identifier: N0484128008. © 2015 American Heart Association, Inc.

  12. Post-hoc principal component analysis on a largely illiterate elderly population from North-west India to identify important elements of mini-mental state examination

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Raina

    2016-01-01

    Full Text Available Background: Mini-mental state examination (MMSE scale measures cognition using specific elements that can be isolated, defined, and subsequently measured. This study was conducted with the aim to analyze the factorial structure of MMSE in a largely, illiterate, elderly population in India and to reduce the number of variables to a few meaningful and interpretable combinations. Methodology: Principal component analysis (PCA was performed post-hoc on the data generated by a research project conducted to estimate the prevalence of dementia in four geographically defined habitations in Himachal Pradesh state of India. Results: Questions on orientation and registration account for high percentage of cumulative variance in comparison to other questions. Discussion: The PCA conducted on the data derived from a largely, illiterate population reveals that the most important components to consider for the estimation of cognitive impairment in illiterate Indian population are temporal orientation, spatial orientation, and immediate memory.

  13. Post-hoc principal component analysis on a largely illiterate elderly population from North-west India to identify important elements of mini-mental state examination.

    Science.gov (United States)

    Raina, Sunil Kumar; Chander, Vishav; Raina, Sujeet; Grover, Ashoo

    2016-01-01

    Mini-mental state examination (MMSE) scale measures cognition using specific elements that can be isolated, defined, and subsequently measured. This study was conducted with the aim to analyze the factorial structure of MMSE in a largely, illiterate, elderly population in India and to reduce the number of variables to a few meaningful and interpretable combinations. Principal component analysis (PCA) was performed post-hoc on the data generated by a research project conducted to estimate the prevalence of dementia in four geographically defined habitations in Himachal Pradesh state of India. Questions on orientation and registration account for high percentage of cumulative variance in comparison to other questions. The PCA conducted on the data derived from a largely, illiterate population reveals that the most important components to consider for the estimation of cognitive impairment in illiterate Indian population are temporal orientation, spatial orientation, and immediate memory.

  14. Quality of life in Japanese women with postmenopausal osteoporosis treated with raloxifene and vitamin D: post hoc analysis of a postmarketing study.

    Science.gov (United States)

    Ohta, Hiroaki; Hamaya, Etsuro; Taketsuna, Masanori; Sowa, Hideaki

    2015-01-01

    To assess the effect of active vitamin D3 on quality of life (QOL) and pain in raloxifene-treated Japanese women with postmenopausal osteoporosis. This is a post hoc analysis of a previous prospective postmarketing observational study conducted without a comparator group. This study was conducted in 60 Japanese hospitals from September 2007 to February 2009. We compared changes from baseline in QOL and pain in patients receiving raloxifene plus active vitamin D3 with those in patients receiving raloxifene monotherapy at 8 and 24 weeks after treatment. Japan Pharmaceutical Information Center (JapicCTI-070465). QOL and pain were assessed using Short Form-8 (SF-8), European Quality of Life Instrument 5 Dimensions (EQ-5D), Japanese Osteoporosis Quality of Life Questionnaire (JOQOL), visual analogue pain scales (VAS pain), and pain frequency scores. A total of 506 patients were included in the post hoc analysis. Both raloxifene monotherapy (RLX, n = 354) and active vitamin D3 cotreatment (COMBI, n = 152) significantly improved QOL and reduced pain from the baseline at Week 8 and Week 24. The COMBI group had significantly greater improvements in JOQOL total score and activity of daily living (total) domain at Week 24 and last observation carried forward (LOCF) than the RLX group. The COMBI group also had significantly greater improvements in SF-8 domains of general health (at Week 8, Week 24, and LOCF), role physical (at Week 24 and LOCF), and mental health (at LOCF) than the RLX group. The COMBI group also had significantly greater reduction in VAS pain at LOCF than the RLX group (mean [SD]: RLX = -0.99 [2.72], COMBI = -1.54 [2.21], P = 0.042). Active vitamin D3 supplementation to raloxifene treatment for 24 weeks may have additional benefits in improving QOL and relieving pain in Japanese women with postmenopausal osteoporosis.

  15. Insight and Treatment Outcomes in Schizophrenia:Post-hocAnalysis of a Long-term, Double-blind Study Comparing Lurasidone and Quetiapine XR.

    Science.gov (United States)

    Harvey, Philip D; Siu, Cynthia O; Loebel, Antony D

    2017-12-01

    Objective: The objective of this post-hoc analysis was to evaluate the effect of lurasidone and quetiapine extended-release (XR) on insight and judgment and assess the longitudinal relationships between improvement in insight and cognitive performance, functional capacity, quality of well-being, and depressive symptoms in patients with schizophrenia. Design: Clinically unstable patients with schizophrenia (N=488) were randomized to once-daily, fixed-dose treatment with lurasidone 80mg, lurasidone 160mg, quetiapine XR 600mg, or placebo, followed by a long-term, double-blind, flexible-dose continuation study involving these agents. Results: Significantly greater improvement in insight and judgment (assessed by the Positive and Negative Syndrome Scale G12 item) for the lurasidone and quetiapine XR groups, compared to the placebo group, was observed at Week 6. Over a subsequent six-month continuation period, the flexible dose lurasidone group showed significantly greater improvement in insight from acute phase baseline compared to the flexible-dose quetiapine XR group (QXR-QXR) (p=0.032). Improvement in insight was significantly correlated with improvement in cognition ( p =0.014), functional capacity (p=0.006, UPSA-B), quality of well-being ( p =0.033, QWB), and depressive symptoms ( p =0.05, Montgomery-Åsberg Depression Rating Scale [MADRS] score) across treatment groups and study periods. Conclusion: In this post-hoc analysis, flexibly dosed lurasidone 40 to 160mg/d was found to be associated with significantly greater improvement in insight compared to flexibly dosed quetiapine XR 200 to 800mg/d over long-term treatment in patients with schizophrenia. Across treatment groups, improvement in insight and judgment was significantly associated with improvement in cognition, functional capacity, quality of well-being, and depressive symptoms over time.

  16. Safety and effectiveness of daily teriparatide for osteoporosis in patients with severe stages of chronic kidney disease: post hoc analysis of a postmarketing observational study.

    Science.gov (United States)

    Nishikawa, Atsushi; Yoshiki, Fumito; Taketsuna, Masanori; Kajimoto, Kenta; Enomoto, Hiroyuki

    2016-01-01

    Teriparatide (recombinant 1-34 N-terminal sequence of human parathyroid hormone) for the treatment of osteoporosis should be prescribed with caution in patients with severe stages of chronic kidney disease (CKD). However, in clinical settings, physicians and surgeons who treat such patients have few available options. We sought to further explore the safety and effectiveness of teriparatide for the treatment of osteoporosis in Japanese patients with severe stages of CKD. This was a post hoc analysis of a postmarketing surveillance study that included patients with osteoporosis at high risk of fracture and stage 4 or 5 CKD. Patients received subcutaneous teriparatide 20 μg daily for up to 24 months. Safety profiles were assessed by physician-reported adverse drug reactions (ADRs). Effectiveness was assessed by measuring bone formation (via procollagen type 1 N-terminal propeptide [P1NP]), bone mineral density (BMD), and the incidence of clinical vertebral or nonvertebral fragility fractures. A total of 33 patients with severe stages of CKD (stage 4, n=30; stage 5, n=3) were included. All patients were female, and 81.8% had a history of previous fracture. No serious ADRs were recorded; a total of 4 ADRs were recorded for 4 of 33 patients. Increases in BMD and P1NP levels were observed both overall and in most individual patients. New fractures occurred in 1 patient with stage 5 CKD, but not in patients with stage 4 CKD. In this post hoc analysis conducted in Japan, teriparatide appeared to be effective for the treatment of osteoporosis in elderly female patients with severe stages of CKD, and no new safety concerns were observed.

  17. Nausea and Vomiting following Balanced Xenon Anesthesia Compared to Sevoflurane: A Post-Hoc Explorative Analysis of a Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Astrid V Fahlenkamp

    Full Text Available Like other inhalational anesthetics xenon seems to be associated with post-operative nausea and vomiting (PONV. We assessed nausea incidence following balanced xenon anesthesia compared to sevoflurane, and dexamethasone for its prophylaxis in a randomized controlled trial with post-hoc explorative analysis.220 subjects with elevated PONV risk (Apfel score ≥2 undergoing elective abdominal surgery were randomized to receive xenon or sevoflurane anesthesia and dexamethasone or placebo after written informed consent. 93 subjects in the xenon group and 94 subjects in the sevoflurane group completed the trial. General anesthesia was maintained with 60% xenon or 2.0% sevoflurane. Dexamethasone 4mg or placebo was administered in the first hour. Subjects were analyzed for nausea and vomiting in predefined intervals during a 24h post-anesthesia follow-up.Logistic regression, controlled for dexamethasone and anesthesia/dexamethasone interaction, showed a significant risk to develop nausea following xenon anesthesia (OR 2.30, 95% CI 1.02-5.19, p = 0.044. Early-onset nausea incidence was 46% after xenon and 35% after sevoflurane anesthesia (p = 0.138. After xenon, nausea occurred significantly earlier (p = 0.014, was more frequent and rated worse in the beginning. Dexamethasone did not markedly reduce nausea occurrence in both groups. Late-onset nausea showed no considerable difference between the groups.In our study setting, xenon anesthesia was associated with an elevated risk to develop nausea in sensitive subjects. Dexamethasone 4mg was not effective preventing nausea in our study. Group size or dosage might have been too small, and change of statistical analysis parameters in the post-hoc evaluation might have further contributed to a limitation of our results. Further trials will be needed to address prophylaxis of xenon-induced nausea.EU Clinical Trials EudraCT-2008-004132-20 ClinicalTrials.gov NCT00793663.

  18. Predictive value of {sup 18}F-FDG PET/CT in adults with T-cell lymphoblastic lymphoma. Post hoc analysis of results from the GRAALL-LYSA LLO3 trial

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Stephanie; Vera, Pierre [Centre Henri-Becquerel, Department of Nuclear Medicine, Rouen (France); University of Rouen, QuantIF-LITIS (EA [Equipe d' Accueil] 4108), Faculty of Medicine, Rouen (France); Vermeulin, Thomas [Rouen University Hospital, Department of Biostatistics, Rouen (France); Cottereau, Anne-Segolene [Hopital Tenon, AP-HP, Department of Nuclear Medicine, Paris (France); Boissel, Nicolas [Universite Paris Diderot, Department of Hematology, Hopital Saint-Louis, AP-HP, Paris (France); Lepretre, Stephane [Centre Henri Becquerel and Normandie Univ UNIROUEN, Inserm U1245 and Department of Hematology, Rouen (France)

    2017-11-15

    We examined whether FDG PET can be used to predict outcome in patients with lymphoblastic lymphoma (LL). This was a retrospective post hoc analysis of data from the GRAAL-LYSA LL03 trial, in which the treatment of LL using an adapted paediatric-like acute lymphoblastic leukaemia protocol was evaluated. PET data acquired at baseline and after induction were analysed. Maximum standardized uptake values (SUV{sub max}), total metabolic tumour volume and total lesion glycolysis were measured at baseline. The relative changes in SUV{sub max} from baseline (ΔSUV{sub max}) and the Deauville score were determined after induction. The population analysed comprised 36 patients with T-type LL. SUV{sub max} using a cut-off value of ≤8.76 vs. >8.76 was predictive of 3-year event-free survival (31.6% vs. 80.4%; p = 0.013) and overall survival (35.0% vs. 83.7%; p = 0.028). ΔSUV{sub max} using a cut-off value of ≤80% vs. >80% tended also to be predictive of 3-year event-free survival (40.0% vs. 76.0%; p = 0.054) and overall survival (49.2% vs. 85.6%; p = 0.085). Total metabolic tumour volume, baseline total lesion glycolysis and response according to the Deauville score were not predictive of outcome. A low initial SUV{sub max} was predictive of worse outcomes in our series of patients with T-type LL. Although relatively few patients were included, the study also suggested that ΔSUV{sub max} may be useful for predicting therapeutic efficacy. (orig.)

  19. Predictive value of 18F-FDG PET/CT in adults with T-cell lymphoblastic lymphoma. Post hoc analysis of results from the GRAALL-LYSA LLO3 trial

    International Nuclear Information System (INIS)

    Becker, Stephanie; Vera, Pierre; Vermeulin, Thomas; Cottereau, Anne-Segolene; Boissel, Nicolas; Lepretre, Stephane

    2017-01-01

    We examined whether FDG PET can be used to predict outcome in patients with lymphoblastic lymphoma (LL). This was a retrospective post hoc analysis of data from the GRAAL-LYSA LL03 trial, in which the treatment of LL using an adapted paediatric-like acute lymphoblastic leukaemia protocol was evaluated. PET data acquired at baseline and after induction were analysed. Maximum standardized uptake values (SUV max ), total metabolic tumour volume and total lesion glycolysis were measured at baseline. The relative changes in SUV max from baseline (ΔSUV max ) and the Deauville score were determined after induction. The population analysed comprised 36 patients with T-type LL. SUV max using a cut-off value of ≤8.76 vs. >8.76 was predictive of 3-year event-free survival (31.6% vs. 80.4%; p = 0.013) and overall survival (35.0% vs. 83.7%; p = 0.028). ΔSUV max using a cut-off value of ≤80% vs. >80% tended also to be predictive of 3-year event-free survival (40.0% vs. 76.0%; p = 0.054) and overall survival (49.2% vs. 85.6%; p = 0.085). Total metabolic tumour volume, baseline total lesion glycolysis and response according to the Deauville score were not predictive of outcome. A low initial SUV max was predictive of worse outcomes in our series of patients with T-type LL. Although relatively few patients were included, the study also suggested that ΔSUV max may be useful for predicting therapeutic efficacy. (orig.)

  20. Effect of moderate alcohol consumption on fetuin-A levels in men and women: Post-hoc analyses of three open-label randomized crossover trials

    NARCIS (Netherlands)

    Joosten, M.M.; Schrieks, I.C.; Hendriks, H.F.J.

    2014-01-01

    Background: Fetuin-A, a liver-derived glycoprotein that impairs insulin-signalling, has emerged as a biomarker for diabetes risk. Although moderate alcohol consumption has been inversely associated with fetuin-A, data from clinical trials are lacking. Thus, we evaluated whether moderate alcohol

  1. Effect of moderate alcohol consumption on fetuin-A levels in men and women: post-hoc analyses of three open-label randomized crossover trials

    NARCIS (Netherlands)

    Joosten, M.M.; Schrieks, I.C.; Hendriks, H.F.J.

    2014-01-01

    Background Fetuin-A, a liver-derived glycoprotein that impairs insulin-signalling, has emerged as a biomarker for diabetes risk. Although moderate alcohol consumption has been inversely associated with fetuin-A, data from clinical trials are lacking. Thus, we evaluated whether moderate alcohol

  2. Effect of moderate alcohol consumption on fetuin-A levels in men and women : post-hoc analyses of three open-label randomized crossover trials

    NARCIS (Netherlands)

    Joosten, Michel M.; Schrieks, Ilse C.; Hendriks, Henk F. J.

    2014-01-01

    Background: Fetuin-A, a liver-derived glycoprotein that impairs insulin-signalling, has emerged as a biomarker for diabetes risk. Although moderate alcohol consumption has been inversely associated with fetuin-A, data from clinical trials are lacking. Thus, we evaluated whether moderate alcohol

  3. Effect of General Anesthesia versus Conscious Sedation for Stroke Thrombectomy on Angiographic Workflow in a Randomized Trial: A Post Hoc Analysis of the SIESTA Trial.

    Science.gov (United States)

    Pfaff, Johannes A R; Schönenberger, Silvia; Nagel, Simon; Ringleb, Peter A; Hacke, Werner; Bendszus, Martin; Bösel, Julian; Möhlenbruch, Markus Alfred

    2018-03-01

    Purpose To investigate whether the sedation mode (ie, conscious sedation [CS] vs general anesthesia [GA]) affects the angiographic workflow applied for treatment of endovascular stroke in a post hoc analysis of a recent randomized controlled trial, Sedation versus Intubation for Endovascular Stroke Treatment (SIESTA). Materials and Methods SIESTA was an institutional review board-approved, single-center, prospective, randomized, parallel-group, open-label treatment trial with a blinded end-point evaluation to compare GA with CS for treatment of endovascular stroke in 73 and 77 patients, respectively. By using descriptive data from SIESTA, the influence of the mode of sedation on angiographic workflow during treatment for endovascular stroke (eg, procedure times) and other radiologic outcome parameters (eg, radiation exposure) were analyzed. The time between angiographic key steps for patients who underwent GA and CS was evaluated with t tests. P values were corrected for false discovery rate. Results The median time from groin puncture to first intracranial flow restoration with CS was 47 minutes (interquartile range [IQR], 29-70 minutes), and for GA, it was 41 minutes (IQR, 28-60 minutes) (P = .546). The median time to the end of angiography with CS was 104 minutes (IQR, 75-150 minutes), and with GA, it was 73 minutes (IQR, 53-125 minutes) (P = .052). Fluoroscopy time with CS was 49 minutes (IQR, 25-85 minutes), and with GA, it was 35 minutes (IQR, 20-74 minutes) (P = .098). The times were comparable in both groups for these measures. The time from groin puncture to the final angiographic result with GA, at 72 minutes (IQR, 45-109 minutes) was shorter than that with CS, at 98 minutes (IQR, 64-135 minutes) (P = .048). Conclusion This post hoc analysis of the single-center SIESTA trial revealed that time from groin puncture to final angiographic result was shorter with patients under GA than that with patients under CS. © RSNA, 2017 Online supplemental material is

  4. Efficacy, safety, and tolerability of brivaracetam with concomitant lamotrigine or concomitant topiramate in pooled Phase III randomized, double-blind trials: A post-hoc analysis.

    Science.gov (United States)

    Benbadis, Selim; Klein, Pavel; Schiemann, Jimmy; Diaz, Anyzeila; Elmoufti, Sami; Whitesides, John

    2018-03-01

    The objective was to assess the efficacy and safety of adjunctive brivaracetam (BRV) with concomitant use of lamotrigine (LTG) or topiramate (TPM) in patients with uncontrolled focal seizures. Data were pooled from three randomized, placebo-controlled Phase III studies (NCT00490035/N01252, NCT00464269/N01253, NCT01261325/N01358) of adults with focal (partial-onset) seizures. Patients taking concomitant levetiracetam were excluded from the efficacy populations, but included in the safety populations. This post-hoc analysis reports data from patients taking BRV in the approved therapeutic range (50-200mg/day) concomitantly with LTG or TPM. The number of patients in each of the three BRV dosage groups was small, particularly for the TPM subgroup. Mean percent reduction over placebo in baseline-adjusted focal seizure frequency/28days for BRV 50, 100, and 200mg/day was 8.7, 5.3, and 8.9 in the LTG subgroup (n=220), and 8.4, 21.3, and -4.2 in the TPM subgroup (n=122). The ≥50% responder rate with concomitant LTG or TPM with BRV 50, 100, and 200mg/day or placebo was LTG: 28.1%, 36.1%, 34.1%, and 29.1%; and TPM: 14.3%, 44.4%, 25.0%, and 17.5%. There were numerically ≥50%, ≥75%, ≥90%, and 100% responder rates for patients taking BRV ≥50mg/day compared with placebo in both subgroups. In the LTG and TPM safety populations (n=245 versus n=125), treatment-emergent adverse events (TEAEs) were reported with LTG 68.7% versus 68.4%, and TPM 65.6% versus 57.8% (BRV ≥50mg/day versus placebo). Discontinuations due to TEAEs versus placebo were LTG 7.3% versus 6.3% and TPM 8.2% versus 4.7%. The three most frequently reported TEAEs for both subgroups were somnolence, dizziness, and fatigue. Of these, the incidence of fatigue in the LTG population appeared to increase with dose. In this post-hoc pooled analysis, BRV administered with concomitant LTG or TPM reduced seizure frequency and was generally well tolerated for BRV doses of 50-200mg/day. Copyright © 2018 UCB, Brussels

  5. Safety and effectiveness of daily teriparatide for osteoporosis in patients with severe stages of chronic kidney disease: post hoc analysis of a postmarketing observational study

    Directory of Open Access Journals (Sweden)

    Nishikawa A

    2016-11-01

    Full Text Available Atsushi Nishikawa,1 Fumito Yoshiki,2 Masanori Taketsuna,2 Kenta Kajimoto,2 Hiroyuki Enomoto2 1Global Patient Safety Japan, Quality and Patient Safety, Eli Lilly Japan K.K., 2Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan Abstract: Teriparatide (recombinant 1–34 N-terminal sequence of human parathyroid hormone for the treatment of osteoporosis should be prescribed with caution in patients with severe stages of chronic kidney disease (CKD. However, in clinical settings, physicians and surgeons who treat such patients have few available options. We sought to further explore the safety and effectiveness of teriparatide for the treatment of osteoporosis in Japanese patients with severe stages of CKD. This was a post hoc analysis of a postmarketing surveillance study that included patients with osteoporosis at high risk of fracture and stage 4 or 5 CKD. Patients received subcutaneous teriparatide 20 µg daily for up to 24 months. Safety profiles were assessed by physician-reported adverse drug reactions (ADRs. Effectiveness was assessed by measuring bone formation (via procollagen type 1 N-terminal propeptide [P1NP], bone mineral density (BMD, and the incidence of clinical vertebral or nonvertebral fragility fractures. A total of 33 patients with severe stages of CKD (stage 4, n=30; stage 5, n=3 were included. All patients were female, and 81.8% had a history of previous fracture. No serious ADRs were recorded; a total of 4 ADRs were recorded for 4 of 33 patients. Increases in BMD and P1NP levels were observed both overall and in most individual patients. New fractures occurred in 1 patient with stage 5 CKD, but not in patients with stage 4 CKD. In this post hoc analysis conducted in Japan, teriparatide appeared to be effective for the treatment of osteoporosis in elderly female patients with severe stages of CKD, and no new safety concerns were observed. Keywords: bone mineral density, chronic kidney disease, fragility

  6. A post hoc analysis of the effect of nightly administration of eszopiclone and a selective serotonin reuptake inhibitor in patients with insomnia and anxious depression.

    Science.gov (United States)

    Fava, Maurizio; Schaefer, Kendyl; Huang, Holly; Wilson, Amy; Iosifescu, Dan V; Mischoulon, David; Wessel, Thomas C

    2011-04-01

    Patients with major depressive disorder (MDD) and significant anxiety are less responsive to antidepressants than those without anxiety. In this post hoc analysis of patients with insomnia and comorbid anxious depression, eszopiclone cotherapy with a selective serotonin reuptake inhibitor (SSRI) was compared with placebo cotherapy. Data were pooled from 2 randomized, double-blind, 8-week trials. One trial (conducted from January 2004 to October 2004) included patients with DSM-IV insomnia and comorbid MDD treated with fluoxetine concurrently with eszopiclone 3 mg/d or placebo. The other trial (conducted from July 2005 to April 2006) included patients with DSM-IV-TR insomnia and comorbid generalized anxiety disorder treated with escitalopram concurrently with eszopiclone 3 mg/d or placebo. Anxious depression was defined as a baseline 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 14 (excluding insomnia items) and an anxiety/somatization factor score ≥ 7. Treatment group differences were determined for mean changes in HDRS-17 scores (with and without insomnia items), HDRS anxiety/somatization scores, and response and remission rates. Severity of insomnia was assessed by the Insomnia Severity Index (ISI). In the combined dataset, 347 of 1,136 patients (30.5%) had insomnia and comorbid anxious depression. Significant improvements in insomnia were observed for eszopiclone cotherapy relative to placebo cotherapy (mean change from baseline on the ISI: -11.0 vs -7.8, respectively; P insomnia items were included (mean change: -14.1 vs -11.2, respectively; P anxiety/somatization (-4.3 vs -4.1; P = .23). Response rates were greater for eszopiclone cotherapy than for placebo cotherapy (55.6% vs 42.0%, respectively; P = .01; 50.0% vs 44.4% when insomnia items were removed; P = .3). Remission rates were not significantly different (32.6% vs 27.2%, respectively; P = .28). In this post hoc analysis of patients with insomnia and comorbid anxious depression derived

  7. Neuromathematical Trichotomous Mixed Methods Analysis: Using the Neuroscientific Tri-Squared Test Statistical Metric as a Post Hoc Analytic to Determine North Carolina School of Science and Mathematics Leadership Efficacy

    Science.gov (United States)

    Osler, James Edward, II; Mason, Letita R.

    2016-01-01

    This study examines the leadership efficacy amongst graduates of The North Carolina School of Science and Mathematics (NCSSM) for the classes of 2000 through 2007 from a neuroscientific and neuromathematic perspective. NCSSM alumni (as the primary unit of analysis) were examined using a novel neuromathematic post hoc method of analysis. This study…

  8. History of early abuse as a predictor of treatment response in patients with fibromyalgia : A post-hoc analysis of a 12-week, randomized, double-blind, placebo-controlled trial of paroxetine controlled release

    NARCIS (Netherlands)

    Pae, Chi-Un; Masand, Prakash S.; Marks, David M.; Krulewicz, Stan; Han, Changsu; Peindl, Kathleen; Mannelli, Paolo; Patkar, Ashwin A.

    2009-01-01

    Objectives. We conducted a post-hoc analysis to determine whether a history of physical or sexual abuse was associated with response to treatment in a double-blind, randomized, placebo-controlled trial of paroxetine controlled release (CR) in fibromyalgia. Methods. A randomized, double-blind,

  9. Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial

    NARCIS (Netherlands)

    van de Ven, J.; Fransen, A F; Schuit, E.; van Runnard Heimel, P.J.; Mol, Ben W.; Oei, Swan G.

    2017-01-01

    Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial. J van de Ven, AF Fransen, E Schuit, PJ van Runnard Heimel, BW Mol, SG Oei Objective To investigate whether the effect of a

  10. Effects of vilazodone on suicidal ideation and behavior in adults with major depressive disorder or generalized anxiety disorder: post-hoc analysis of randomized, double-blind, placebo-controlled trials.

    Science.gov (United States)

    Thase, Michael E; Edwards, John; Durgam, Suresh; Chen, Changzheng; Chang, Cheng-Tao; Mathews, Maju; Gommoll, Carl P

    2017-09-01

    Treatment-emergent suicidal ideation and behavior are ongoing concerns with antidepressants. Vilazodone, currently approved for the treatment of major depressive disorder (MDD) in adults, has also been evaluated in generalized anxiety disorder (GAD). Post-hoc analyses of vilazodone trials were carried out to examine its effects on suicidal ideation and behavior in adults with MDD or GAD. Data were pooled from vilazodone trials in MDD (four studies) and GAD (three studies). The incidence of suicide-related events was analyzed on the basis of treatment-emergent adverse event reporting and Columbia-Suicide Severity Rating Scale (C-SSRS) monitoring. Treatment-emergent suicidal ideation was analyzed on the basis of a C-SSRS category shift from no suicidal ideation/behavior (C-SSRS=0) at baseline to suicide ideation (C-SSRS=1-5) during treatment. In pooled safety populations (MDD, n=2233; GAD, n=1475), suicide-related treatment-emergent adverse events occurred in less than 1% of vilazodone-treated and placebo-treated patients. Incidences of C-SSRS suicidal ideation were as follows: MDD (vilazodone=19.9%, placebo=24.7%); GAD (vilazodone=7.7%, placebo=9.4%). Shifts from no suicidal ideation/behavior at baseline to suicidal ideation during treatment were as follows: MDD (vilazodone=9.4%, placebo=10.3%); GAD (vilazodone=4.4%, placebo=6.1%). Data from placebo-controlled studies indicate little or no risk of treatment-emergent suicidal ideation or behavior with vilazodone in adults with MDD or GAD. Nevertheless, all patients should be monitored for suicidal thoughts and behaviors during antidepressant treatment.

  11. Inherent Risk Factors for Nosocomial Infection in the Long Stay Critically Ill Child Without Known Baseline Immunocompromise: A Post Hoc Analysis of the CRISIS Trial.

    Science.gov (United States)

    Carcillo, Joseph A; Dean, J Michael; Holubkov, Richard; Berger, John; Meert, Kathleen L; Anand, Kanwaljeet J S; Zimmerman, Jerry; Newth, Christopher J; Harrison, Rick; Burr, Jeri; Willson, Douglas F; Nicholson, Carol; Bell, Michael J; Berg, Robert A; Shanley, Thomas P; Heidemann, Sabrina M; Dalton, Heidi; Jenkins, Tammara L; Doctor, Allan; Webster, Angie

    2016-11-01

    Nosocomial infection remains an important health problem in long stay (>3 days) pediatric intensive care unit (PICU) patients. Admission risk factors related to the development of nosocomial infection in long stay immune competent patients in particular are not known. Post-hoc analysis of the previously published Critical Illness Stress induced Immune Suppression (CRISIS) prevention trial database, to identify baseline risk factors for nosocomial infection. Because there was no difference between treatment arms of that study in nosocomial infection in the population without known baseline immunocompromise, both arms were combined and the cohort that developed nosocomial infection was compared with the cohort that did not. There were 254 long stay PICU patients without known baseline immunocompromise. Ninety (35%) developed nosocomial infection, and 164 (65%) did not. Admission characteristics associated with increased nosocomial infection risk were increased age, higher Pediatric Risk of Mortality version III score, the diagnoses of trauma or cardiac arrest and lymphopenia (P risk of developing nosocomial infection (P risk factors (P < 0.05); whereas trauma tended to be related to nosocomial infection development (P = 0.07). These data suggest that increasing age, cardiac arrest and lymphopenia predispose long stay PICU patients without known baseline immunocompromise to nosocomial infection. These findings may inform pre-hoc stratification randomization strategies for prospective studies designed to prevent nosocomial infection in this population.

  12. Efficacy of adjunctive brexpiprazole on the core symptoms of major depressive disorder: A post hoc analysis of two pooled clinical studies.

    Science.gov (United States)

    Nelson, J Craig; Weiller, Emmanuelle; Zhang, Peter; Weiss, Catherine; Hobart, Mary

    2018-02-01

    Patients with major depressive disorder (MDD) who do not adequately respond to antidepressant treatment (ADT) may benefit from adjunctive atypical antipsychotics; however, certain agents target specific symptoms of depression and not the full syndrome. The aim of this analysis was to examine the effects of brexpiprazole, adjunct to ADT, on the core symptoms of MDD, defined using Montgomery-Åsberg Depression Rating Scale (MADRS) items. This was a post hoc analysis of data from two 6-week, randomized, double-blind studies of adjunctive brexpiprazole in patients with MDD and inadequate response to ADTs (n = 1056). Efficacy was assessed using the MADRS core symptom subscale (MADRS 6 ) and individual items (apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts). At Week 6, adjunctive brexpiprazole showed a greater effect than adjunctive placebo on the MADRS 6 (within-group Cohen's d effect sizes: brexpiprazole, 1.05; placebo, 0.71; p core symptoms (effect sizes: brexpiprazole, 0.64-0.94; placebo, 0.39-0.64; all p core symptoms (all p core symptoms of MDD. Brexpiprazole is thought to exert its effects in MDD by treating the core symptoms of the disease. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. The role of perceived social support after psychiatric hospitalisation: Post hoc analysis of a randomised controlled trial testing the effectiveness of a transitional intervention.

    Science.gov (United States)

    Hengartner, Michael P; Passalacqua, Silvia; Andreae, Andreas; Rössler, Wulf; von Wyl, Agnes

    2017-06-01

    The association between social support, readmissions and psychopathology following discharge from psychiatric hospitals is not clear. To examine the prospective effects of perceived social support on rehospitalisation rates and psychopathology and to focus on the moderators of a transitional intervention. This post hoc analysis of a multisite randomised controlled trial included 151 patients with no more than three hospitalisations within the last 3 years, a Global Assessment of Functioning (GAF) score ≤60 and aged 18-64 years, assessed at two psychiatric hospitals from Zurich, Switzerland, between September 2011 and February 2014. Participants received either a transitional intervention aimed at improving social support during the transition from inpatient to outpatient care provided by a social worker or treatment as usual. Lack of perceived social support at discharge significantly predicted subsequent rehospitalisation rates and increased psychopathological impairment across 12-month follow-up. Significant interaction effects between patient characteristics and the intervention on perceived social support comprised living at parent's home, having no children and being of younger age. Perceived social support at discharge from inpatient care may reduce rehospitalisation rates and psychopathological impairment in the long term. A transitional intervention aimed at improving social support may negatively impact on the perceived social support in some patient groups.

  14. Effect of dutasteride on clinical progression of benign prostatic hyperplasia in asymptomatic men with enlarged prostate: a post hoc analysis of the REDUCE study.

    Science.gov (United States)

    Toren, Paul; Margel, David; Kulkarni, Girish; Finelli, Antonio; Zlotta, Alexandre; Fleshner, Neil

    2013-04-15

    To assess the role of dutasteride in preventing clinical progression of benign prostatic hyperplasia in asymptomatic men with larger prostates. Post hoc analysis of four year, double blind Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study 1617 men randomised to dutasteride or placebo with a prostate size >40 mL and baseline International Prostate Symptom Score (IPSS) benign prostatic hyperplasia were excluded at study entry. Placebo or dutasteride 0.5 mg daily. Comparison of risk of clinical progression of benign prostatic hyperplasia at four years (defined as a ≥ 4 point worsening on IPSS, acute urinary retention, urinary tract infection, or surgery related to benign prostatic hyperplasia). 825 participants took placebo, 792 took dutasteride. A total of 464 (29%) experienced clinical progression benign prostatic hyperplasia, 297(36%) taking placebo, 167 (21%) taking dutasteride (Pbenign prostatic hyperplasia, the absolute risk reduction for dutasteride was 6.0% and 3.8%, respectively. On multivariable regression analysis adjusting for covariates, dutasteride significantly reduced clinical progression of benign prostatic hyperplasia with an odds ratio of 0.47 (95% CI 0.37 to 0.59, Pprostate. Dutasteride significantly decreased the incidence of benign prostatic hyperplasia clinical progression.

  15. Derived neutrophil lymphocyte ratio is predictive of survival from intermittent therapy in advanced colorectal cancer: a post hoc analysis of the MRC COIN study.

    Science.gov (United States)

    Grenader, Tal; Nash, Stephen; Adams, Richard; Kaplan, Richard; Fisher, David; Maughan, Tim; Bridgewater, John

    2016-03-15

    The phase III COntinuous or INtermittent (COIN) trial failed to show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in overall survival (OS). The present analysis evaluated whether the derived neutrophil to lymphocyte ratio (dNLR) could predict the effect of intermittent vs continuous chemotherapy on OS in patients with advanced colorectal cancer. A post hoc exploratory analysis of COIN arms A and C was performed. Landmark analysis was conducted on all patients with available WBC and neutrophils data. The dNLR was calculated using a formula which has previously demonstrated predictive power in cancer patients: dNLR = ANC/(WBC-ANC). A high dNLR was defined using a cut-off value of ⩾ 2.22. Derived neutrophil to lymphocyte ratio was then correlated with clinical outcomes. Survival curves were generated based on dNLR using the Kaplan-Meier method. Comparison between groups was performed using Cox regression. A total of 1630 patients were assigned to the continuous (N = 815) or intermittent (N = 815) arms. There was a strong association between dNLR level and OS. The median survival times in the ITT population were 18.6 months and 12.5 months for patients with low and high dNLR, respectively (HR = 1.70; 95% CI = 1.52-1.90; P COIN intermittent vs continuous treatment arms. Derived neutrophil to lymphocyte ratio does not predict for detrimental survival in patients treated with intermittent therapy.

  16. Modelling and analysing oriented fibrous structures

    International Nuclear Information System (INIS)

    Rantala, M; Lassas, M; Siltanen, S; Sampo, J; Takalo, J; Timonen, J

    2014-01-01

    A mathematical model for fibrous structures using a direction dependent scaling law is presented. The orientation of fibrous nets (e.g. paper) is analysed with a method based on the curvelet transform. The curvelet-based orientation analysis has been tested successfully on real data from paper samples: the major directions of fibrefibre orientation can apparently be recovered. Similar results are achieved in tests on data simulated by the new model, allowing a comparison with ground truth

  17. Does education level affect the efficacy of a community based salt reduction program? - A post-hoc analysis of the China Rural Health Initiative Sodium Reduction Study (CRHI-SRS).

    Science.gov (United States)

    Wang, Xin; Li, Xian; Vaartjes, Ilonca; Neal, Bruce; Bots, Michiel L; Hoes, Arno W; Wu, Yangfeng

    2016-08-11

    Whether educational level influences the effects of health education is not clearly defined. This study examined whether the impact of a community-based dietary salt reduction program was affected by the level of education of participants. The China Rural Health Initiative Sodium Reduction Study (CRHI-SRS) was a cluster-randomized controlled trial conducted in 120 villages from five Northern Chinese provinces. The intervention comprised a village-wide health education program and availability of salt substitute at village shops. 24-h urine samples were collected among 1903 participants for primary evaluation of the intervention effect. A post-hoc analysis was done to explore for heterogeneity of intervention effects by education level using generalized estimating equations. All models were adjusted for age, sex, body mass index and province. Daily salt intake was lower in intervention than in control at all educational levels with no evidence of a difference in the effect of the intervention across different levels of education. P value for the interaction term between education level and the intervention was 0.35. There was likewise no evidence of an interaction for effects of the intervention on potassium intake (p = 0.71), the sodium to potassium ratio (p = 0.07), or knowledge and behaviors related to salt (all p > 0.05). The study suggests that the effects of the intervention were achieved regardless of the level of education and that the intervention should therefore be broadly effective in rural Chinese populations. The trial was registered with clinicaltrial.gov ( NCT01259700 ).

  18. Does education level affect the efficacy of a community based salt reduction program? - A post-hoc analysis of the China Rural Health Initiative Sodium Reduction Study (CRHI-SRS

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2016-08-01

    Full Text Available Abstract Background Whether educational level influences the effects of health education is not clearly defined. This study examined whether the impact of a community-based dietary salt reduction program was affected by the level of education of participants. Methods The China Rural Health Initiative Sodium Reduction Study (CRHI-SRS was a cluster-randomized controlled trial conducted in 120 villages from five Northern Chinese provinces. The intervention comprised a village-wide health education program and availability of salt substitute at village shops. 24-h urine samples were collected among 1903 participants for primary evaluation of the intervention effect. A post-hoc analysis was done to explore for heterogeneity of intervention effects by education level using generalized estimating equations. All models were adjusted for age, sex, body mass index and province. Results Daily salt intake was lower in intervention than in control at all educational levels with no evidence of a difference in the effect of the intervention across different levels of education. P value for the interaction term between education level and the intervention was 0.35. There was likewise no evidence of an interaction for effects of the intervention on potassium intake (p = 0.71, the sodium to potassium ratio (p = 0.07, or knowledge and behaviors related to salt (all p > 0.05. Conclusions The study suggests that the effects of the intervention were achieved regardless of the level of education and that the intervention should therefore be broadly effective in rural Chinese populations. Trial registration The trial was registered with clinicaltrial.gov ( NCT01259700 .

  19. Pregabalin versus SSRIs and SNRIs in benzodiazepine-refractory outpatients with generalized anxiety disorder: a post hoc cost-effectiveness analysis in usual medical practice in Spain

    Directory of Open Access Journals (Sweden)

    De Salas-Cansado M

    2012-06-01

    Full Text Available Marina De Salas-Cansado,1 José M Olivares,2 Enrique Álvarez,3 Jose L Carrasco,4 Andoni Barrueta,5 Javier Rejas,51Trial Form Support Spain, Madrid; 2Department of Psychiatry, Hospital Meixoeiro, Complejo Hospitalario Universitario, Vigo; 3Department of Psychiatry, Hospital de la Santa Creu i San Pau, Barcelona; 4Department of Psychiatry, Hospital Clínico San Carlos, Madrid; 5Health Outcomes Research Department, Medical Unit, Pfizer Spain, Alcobendas, Madrid, SpainBackground: Generalized anxiety disorder (GAD is a prevalent health condition which seriously affects both patient quality of life and the National Health System. The aim of this research was to carry out a post hoc cost-effectiveness analysis of the effect of pregabalin versus selective serotonin reuptake inhibitors (SSRIs/serotonin norepinephrine reuptake inhibitors (SNRIs in treated benzodiazepine-refractory outpatients with GAD.Methods: This post hoc cost-effectiveness analysis used secondary data extracted from the 6-month cohort, prospective, noninterventional ADAN study, which was conducted to ascertain the cost of illness in GAD subjects diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Benzodiazepine-refractory subjects were those who claimed persistent symptoms of anxiety and showed a suboptimal response (Hamilton Anxiety Rating Scale ≥16 to benzodiazepines, alone or in combination, over 6 months. Patients could switch to pregabalin (as monotherapy or addon or to an SSRI or SNRI, alone or in combination. Effectiveness was expressed as quality-adjusted life years gained, and the perspective was that of the National Health System in the year 2008. A sensitivity analysis was performed using bootstrapping techniques (10,000 resamples were obtained in order to obtain a cost-effectiveness plane and a corresponding acceptability curve.Results: A total of 282 subjects (mean Hamilton Anxiety Rating Scale score 25.8 were

  20. Long-term effect on symptoms and quality of life of maintenance therapy with esomeprazole 20 mg daily: a post hoc analysis of the LOTUS trial.

    Science.gov (United States)

    Lundell, Lars; Hatlebakk, Jan; Galmiche, Jean-Paul; Attwood, Stephen E; Ell, Christian; Fiocca, Roberto; Persson, Tore; Nagy, Péter; Eklund, Stefan; Lind, Tore

    2015-01-01

    To assess the long-term effect on symptoms and quality of life of esomeprazole 20 mg once daily, a recommended dose for maintenance therapy of gastroesophageal reflux disease (GERD). This is a post hoc analysis of 5 year data from patients in the LOTUS trial (ClinicalTrials.gov identifier: NCT00251927) who were randomized to esomeprazole 20 mg once daily. All participants had chronic, symptomatic GERD responsive to treatment. Gastrointestinal symptoms were assessed by physicians and by using patient-reported outcome instruments. Investigations included gastrointestinal endoscopy (with biopsy sampling), 24 hour esophageal pH monitoring and laboratory measurements. In total, 157 of 256 patients randomized to esomeprazole 20 mg once daily remained on this dose until the end of follow-up or study discontinuation, whereas 99 patients had their dose increased because of inadequate symptom control (of these, 29 subsequently returned to the allocated dose). On logistic regression, a long objectively defined GERD history, smoking, female sex, absence of Helicobacter pylori infection and high supine baseline acid reflux into the esophagus were associated with an increased likelihood of requiring dose escalation to esomeprazole 40 mg daily (all p esomeprazole 20 mg once daily, with no more than mild symptom severity, and mean (standard deviation) percentage time with intraesophageal pH Esomeprazole at a maintenance dose of 20 mg once daily offers effective long-term treatment for chronic GERD in patients initially responsive to the medication, with durable symptom control and sustained reductions in intraesophageal acid exposure.

  1. Post hoc analysis of pregabalin vs. non-pregabalin treatment in patients with cancer-related neuropathic pain: better pain relief, sleep and physical health.

    Science.gov (United States)

    Mańas, Ana; Ciria, Juan Pablo; Fernández, María Carmen; Gonzálvez, María Luisa; Morillo, Virginia; Pérez, María; Masramon, Xavier; López-Gómez, Vanessa

    2011-09-01

    A previous study of cancer-related neuropathic pain (NP) found that a 10-fold increase in pregabalin (PGB) use increased patients' satisfaction with treatment. Further research of PGB vs. non-pregabalin (non-PGB) treatment was carried out to assess if the use of more specific NP-targeting drugs, such as PGB, in combined therapy, in patients with cancer-related NP, provides better health outcomes. Post hoc analysis of PGB- vs. non- PGB-treated patients in a 2-month epidemiological, prospective, multicentre study to assess NP prevalence and management in cancer pain patients visiting radiotherapy oncologic units. Patients undertook the Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), the Medical Outcomes Sleep Scale (MOS-Sleep) and the short form (SF-12) Health Survey. A total of 273 patients with no previous PGB treatment: 162 were treated with PGB polytherapy and 111 with other treatments. At 8 weeks, satisfaction with treatment was 92.6% (PGB) vs. 78.9% (non-PGB), p=0.0024, and benzodiazepine use 37.8% (non-PGB) vs. 19.8% (PGB), p=0.0009. The decreases in BPI total pain intensity and total interference with activities and in MOS overall sleep problems index were significantly larger in the PGB group. The addition of more specific NP-targeting drugs to usual treatment, such as PGB, in NP cancer patients provides more satisfaction with treatment and better outcomes in terms of pain intensity, interference with activities and sleep than treatments without specific NP-targeting drugs. Anxiolytic profile of PGB could allow for less use of benzodiazepines.

  2. Blood transfusion strategy and risk of postoperative delirium in nursing homes residents with hip fracture. A post hoc analysis based on the TRIFE randomized controlled trial.

    Science.gov (United States)

    Blandfort, Sif; Gregersen, Merete; Borris, Lars Carl; Damsgaard, Else Marie

    2017-06-01

    To investigate whether a liberal blood transfusion strategy [Hb levels ≥11.3 g/dL (7 mmol/L)] reduces the risk of postoperative delirium (POD) on day 10, among nursing home residents with hip fracture, compared to a restrictive transfusion strategy [Hb levels ≥9.7 g/dL (6 mmol/L)]. Furthermore, to investigate whether POD influences mortality within 90 days after hip surgery. This is a post hoc analysis based on The TRIFE - a randomized controlled trial. Frail anemic patients from the Orthopedic Surgical Ward at Aarhus University Hospital were enrolled consecutively between January 18, 2010 and June 6, 2013. These patients (aged ≥65 years) had been admitted from nursing homes for unilateral hip fracture surgery. After surgery, 179 patients were included in this study. On the first day of hospitalization, all enrolled patients were examined for cognitive impairment (assessed by MMSE) and delirium (assessed by CAM). Delirium was also assessed on the tenth postoperative day. The prevalence of delirium was 10 % in patients allocated to a liberal blood transfusion strategy (LB) and 21 % in the group with a restrictive blood transfusion strategy (RB). LB prevents development of delirium on day 10, compared to RB, odds ratio 0.41 (95 % CI 0.17-0.96), p = 0.04. Development of POD on day 10 increased the risk of 90-day death, hazard ratio 3.14 (95 % CI 1.72-5.78), p < 0.001. In nursing home residents undergoing surgery for hip fracture, maintaining hemoglobin level above 11.3 g/dL reduces the rate of POD on day 10 compared to a RB. Development of POD is associated with increased mortality.

  3. Brexpiprazole as adjunctive treatment of major depressive disorder with anxious distress: Results from a post-hoc analysis of two randomised controlled trials.

    Science.gov (United States)

    McIntyre, Roger S; Weiller, Emmanuelle; Zhang, Peter; Weiss, Catherine

    2016-09-01

    Anxiety symptoms are prevalent in major depressive disorder (MDD) and are associated with greater illness severity, suicidality, impaired functioning and poor response to antidepressant treatment (ADT). The efficacy and safety of brexpiprazole - a serotonin-dopamine activity modulator - as adjunctive treatment in patients with MDD was recently evaluated in two phase 3 studies. We here present a post-hoc analysis of the efficacy of adjunctive brexpiprazole in patients with MDD and symptoms of anxious distress, defined using proxies for DSM-5 criteria. Eligible patients were randomized to 2mg brexpiprazole+ADT or placebo+ADT (NCT01360645); or 1mg brexpiprazole+ADT, 3mg brexpiprazole+ADT, or placebo+ADT (NCT01360632), respectively. Patients were defined as having anxious distress if they had ≥2 of the symptoms tension (MADRS item 3 score ≥3), restlessness (IDS item 24 score ≥2), concentration (MADRS item 6 score ≥3), or apprehension (HAM-D item 10 score ≥3). Primary efficacy endpoint was change in MADRS total score from baseline to Week 6. 55% of the patients had anxious distress at baseline. Adjunctive brexpiprazole showed greater improvement than adjunctive placebo on the primary efficacy endpoint in both patients with (least square mean difference to placebo+ADT: 2mg+ADT: -2.95, p=0.0023; 3mg+ADT: -2.81, p=0.0027); and without anxious distress (1mg+ADT: -2.37, p=0.0093; 3mg+ADT: -2.23, p=0.0131). Brexpiprazole in patients with anxious distress was not associated with an increased incidence of activating adverse events (e.g., akathisia). Adjunctive brexpiprazole 2-3mg may be efficacious in reducing depressive symptoms and is well tolerated, in patients with MDD and anxious distress. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Importance of Contrast Aortography With Lotus Transcatheter Aortic Valve Replacement: A Post Hoc Analysis From the RESPOND Post-Market Study.

    Science.gov (United States)

    van Gils, Lennart; Wöhrle, Jochen; Hildick-Smith, David; Bleiziffer, Sabine; Blackman, Daniel J; Abdel-Wahab, Mohamed; Gerckens, Ulrich; Brecker, Stephen; Bapat, Vinayak; Modine, Thomas; Soliman, Osama I; Nersesov, Andrey; Allocco, Dominic; Falk, Volkmar; Van Mieghem, Nicolas M

    2018-01-22

    The aim of this post hoc analysis from the RESPOND (Repositionable Lotus Valve System-Post-Market Evaluation of Real World Clinical Outcomes) post-market study was to assess the final implantation depth on the contrast aortogram after Lotus valve (Boston Scientific, Marlborough, Massachusetts) transcatheter aortic valve replacement (TAVR) and to correlate with permanent pacemaker implantation (PPI) and paravalvular leak (PVL). Contrast aortography allows for the assessment of implantation depth and PVL during and after TAVR. Previous reports suggested an association between final device position and rates of PPI and PVL. The RESPOND study was a prospective, open-label, single-arm study in 41 centers evaluating outcomes after Lotus TAVR in routine clinical practice. Aortograms were collected at the Erasmus Medical Center and analyzed by researchers who were blinded to clinical outcomes. The primary analysis correlated implantation depth with PPI and PVL and required aortograms in a coaxial projection. The relation between implantation depth and need for PPI was assessed by multivariate logistic regression, adjusting for pre-defined confounders. A secondary analysis compared PVL analysis by contrast aortography with transthoracic echocardiography (TTE) performed by the independent core laboratory. A total of 724 angiographic studies were included in this analysis. Mean Lotus implantation depth was 6.67 ± 2.19 mm. The overall PPI rate was 35%. PPI rate was lower with shallow implants (analysis of the RESPOND study PPI was highly correlated with implantation depth, whereas PVL was not. Higher Lotus implantation may reduce need for PPI. Copyright © 2018. Published by Elsevier Inc.

  5. Costs and health resources utilization following switching to pregabalin in individuals with gabapentin-refractory neuropathic pain: a post hoc analysis.

    Science.gov (United States)

    Navarro, Ana; Saldaña, María T; Pérez, Concepción; Masramón, Xavier; Rejas, Javier

    2012-06-01

    To analyze the changes in pain severity and associated costs resulting from resource utilization and reduced productivity in patients with gabapentin-refractory peripheral neuropathic pain who switched to pregabalin therapy in primary care settings in Spain. This is a post hoc analysis of a 12-week, multicentre, noninterventional cost-of-illness study. Patients were included in the study if they were over 18 years of age and had a diagnosis of chronic, treatment-refractory peripheral neuropathic pain. The analysis included all pregabalin-naïve patients who had previously shown an inadequate response to gabapentin and switched to pregabalin. Severity of pain before and after treatment with pregabalin, alone or as an add-on therapy, was assessed using the Short-Form McGill Pain Questionnaire (SF-MPQ) and its related visual analogue scale (VA). Healthcare resource utilization, productivity (including lost-workday equivalents [LWDE]), and related costs were assessed at baseline and after pregabalin treatment. A total of 174 patients switched to pregabalin had significant and clinically relevant reductions in pain severity (mean [SD] change on SF-MPQ VA scale, -31.9 [22.1]; P use [in pregabalin add-on group], ancillary tests, and unscheduled medical visits) were observed at the end of trial. Additionally, there were substantial improvements in productivity, including a reduction in the number of LWDE following pregabalin treatment (-18.9 [26.0]; P < 0.0001). These changes correlated with substantial reductions in both direct (-652.9 ± 1622.4 €; P < 0.0001) and indirect healthcare costs (-851.6 [1259.6] €; P < 0.0001). The cost of care in patients with gabapentin-refractory peripheral neuropathic pain appeared to be significantly reduced after switching to pregabalin treatment, alone or in combination with other analgesic drugs, in a real-life setting. © 2011 The Authors. Pain Practice © 2011 World Institute of Pain.

  6. Factors associated with dose escalation of fesoterodine for treatment of overactive bladder in people >65 years of age: A post hoc analysis of data from the SOFIA study.

    Science.gov (United States)

    Wagg, Adrian; Darekar, Amanda; Arumi, Daniel; Khullar, Vik; Oelke, Matthias

    2015-06-01

    To investigate factors which may influence dose escalation of antimuscarinics for overactive bladder (OAB) in older patients and how dose escalation affects treatment efficacy. A post hoc analysis of data from the 12-week randomized, placebo controlled phase of the SOFIA study investigating treatment with fesoterodine in older people with OAB. Predictors and outcomes in patients aged ≥65 years with OAB who did or did not choose to escalate from fesoterodine 4 to 8 mg before the first dose-escalation choice point (week 4) and at the end of the study (week 12) were assessed. Variables which significantly increased likelihood of dose escalation were, at baseline, body mass index (OR: 1.06, 95% CI 1.01, 1.12; P = 0.0222), and male gender (OR: 2.06, 95% CI 1.28, 3.32; P = 0.0028) and at week 4, change from baseline in urgency episodes (OR: 1.12, 95% CI 1.05, 1.20; P = 0.0008), patient perception of bladder control (PPBC) (OR: 1.44, 95% CI 1.12, 1.84; P = 0.004). At week 12, dose escalation was associated with slightly reduced treatment outcomes compared to week 4 non-escalators. No baseline disease related factor associated with dose escalation was identified. Magnitude of change in urgency episodes and reduction in PPBC at 4 weeks were associated with dose escalation. These data may be of use to healthcare providers as they allow judgement to be made in individual patients, allowing treatment decisions to be made. At end of treatment, improvements in efficacy and quality of life were achieved in both escalators and non-escalators. © 2014 Wiley Periodicals, Inc.

  7. Demographic Characteristics and Clinical Outcomes in Patients from Latin America Versus the Rest of the World: A TIOSPIR® Post-Hoc Analysis.

    Science.gov (United States)

    Anzueto, Antonio; Calverley, Peter M A; Mueller, Achim; Metzdorf, Norbert; Haensel, Michaela; Jardim, José R; Pizzichini, Emilio; Giraldo, Horacio; Ramirez-Venegas, Alejandra; Giugno, Eduardo R

    2018-03-01

    Geographical variations may impact outcomes in chronic obstructive pulmonary disease (COPD). We evaluated differences in baseline characteristics and outcomes between patients enrolled in Latin America compared with the rest of the world (RoW) in the TIOtropium Safety and Performance In Respimat ® (TIOSPIR ® ) trial. TIOSPIR ® , a 2-3-year, randomized, double-blind trial (n=17116; treated set), compared safety and efficacy of once-daily tiotropium Respimat ® 5 and 2.5μg with tiotropium HandiHaler ® 18μg. This post-hoc analysis pooled data from all treatment arms to assess mortality, exacerbations, cardiac events, and serious adverse events (SAEs) between both regions. At baseline, patients enrolled in Latin America (n=1000) versus RoW (n=16116) were older, with higher pack-years of smoking history and more exacerbations, but less cardiac history. In this analysis, patients in Latin America versus RoW had an increased risk of death (hazard ratio [HR] [95% confidence interval (CI)]: 1.52 [1.24-1.86]; PLatin America were lower versus RoW (incidence rate ratio [IRR] [95% CI]: 0.82 [0.72-0.92]), including cardiac disorders (IRR [95% CI]: 0.68 [0.48-0.97]). Risk of major adverse cardiovascular events were similar (HR [95% CI]: 0.99 [0.71-1.40]; P=.9677). TIOSPIR ® patients in Latin America had a higher risk of death or moderate-to-severe exacerbation, but a lower risk of severe exacerbation than those in RoW. Geographical differences may impact outcomes in COPD trials. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Dose-Dependent Effect of Sitagliptin on Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus Receiving Insulin Treatment: A Post Hoc Analysis.

    Science.gov (United States)

    Mita, Tomoya; Katakami, Naoto; Shiraiwa, Toshihiko; Yoshii, Hidenori; Gosho, Masahiko; Shimomura, Iichiro; Watada, Hirotaka

    2017-10-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce blood glucose in a dose-dependent manner, but the dose-dependent effect relationship between DPP-4 inhibitors and atherosclerosis has not been investigated. Patients with type 2 diabetes mellitus (T2DM) treated with insulin were randomized to the sitagliptin (n = 137) or conventional treatment group (n = 137). In the sitagliptin group, each investigator was allowed to adjust the sitagliptin dose to avoid hypoglycemia. In this post hoc analysis, subjects in the sitagliptin group were divided into two groups based on the average dose of sitagliptin during the study period: greater than or equal to median (higher sitagliptin dose group) or less than median (lower sitagliptin dose group). In this study, subjects were divided into three groups: the conventional treatment group (n = 137), lower sitagliptin dose group (n = 42), and higher sitagliptin dose group (n = 95). The higher sitagliptin dose group had a significantly larger reduction in HbA1c (-0.62 ± 1.05%) than the conventional treatment group (-0.20 ± 0.91%, P = 0.007). Over 104 weeks, the higher sitagliptin dose significantly reduced the mean intima media thickness-common carotid artery (IMT-CCA) and left max-IMT-CCA relative to baseline. In addition, the higher sitagliptin dose significantly inhibited the progression in mean-IMT-CCA compared with conventional treatment. Multiple linear regression analysis showed that changes in mean-IMT-CCA and left max-IMT-CCA decreased with higher sitagliptin dose. Addition of sitagliptin to insulin therapy might attenuate the progression of atherosclerosis in patients with T2DM in a dose-dependent manner. Mitsubishi Tanabe Pharma Co., Ono Pharmaceutical Co., and Novo Nordisk. UMIN000007396.

  9. The Impact of Conscious Sedation versus General Anesthesia for Stroke Thrombectomy on the Predictive Value of Collateral Status: A Post Hoc Analysis of the SIESTA Trial.

    Science.gov (United States)

    Schönenberger, S; Pfaff, J; Uhlmann, L; Klose, C; Nagel, S; Ringleb, P A; Hacke, W; Kieser, M; Bendszus, M; Möhlenbruch, M A; Bösel, J

    2017-08-01

    Radiologic selection criteria to identify patients likely to benefit from endovascular stroke treatment are still controversial. In this post hoc analysis of the recent randomized Sedation versus Intubation for Endovascular Stroke TreAtment (SIESTA) trial, we aimed to investigate the impact of sedation mode (conscious sedation versus general anesthesia) on the predictive value of collateral status. Using imaging data from SIESTA, we assessed collateral status with the collateral score of Tan et al and graded it from absent to good collaterals (0-3). We examined the association of collateral status with 24-hour improvement of the NIHSS score, infarct volume, and mRS at 3 months according to the sedation regimen. In a cohort of 104 patients, the NIHSS score improved significantly in patients with moderate or good collaterals (2-3) compared with patients with no or poor collaterals (0-1) ( P = .011; mean, -5.8 ± 7.6 versus -1.1 ± 10.7). Tan 2-3 was also associated with significantly higher ASPECTS before endovascular stroke treatment (median, 9 versus 7; P collateral status (0.1 versus 2.3), the sedation modes conscious sedation and general anesthesia were not associated with significant differences in the predictive value of collateral status regarding infarction size or functional outcome. The sedation mode, conscious sedation or general anesthesia, did not influence the predictive value of collaterals in patients with large-vessel occlusion anterior circulation stroke undergoing thrombectomy in the SIESTA trial. © 2017 by American Journal of Neuroradiology.

  10. Oral supplementation with probiotic L. reuteri NCIMB 30242 increases mean circulating 25-hydroxyvitamin D: a post hoc analysis of a randomized controlled trial.

    Science.gov (United States)

    Jones, Mitchell L; Martoni, Christopher J; Prakash, Satya

    2013-07-01

    Low serum 25-hydroxyvitamin D is a risk factor for osteoporosis, cardiovascular disease, diabetes, and cancer. Disruption of noncholesterol sterol absorption due to cholesterol-lowering therapies may result in reduced fat-soluble vitamin absorption. We have previously reported on the cholesterol-lowering efficacy and reduced sterol absorption of probiotic bile salt hydrolase active Lactobacillus reuteri NCIMB 30242; however, the effects on fat-soluble vitamins was previously unknown and the objective of the present study. DESIGN, SETTINGS, PATIENTS, AND INTERVENTION: The study was double-blind, placebo-controlled, randomized, parallel-arm, multicenter lasting 13 weeks. A total of 127 otherwise healthy hypercholesterolemic adults with low-density lipoprotein-cholesterol >3.4 mmol/L, triglycerides L, and body mass index of 22 to 32 kg/m² were included. Subjects were recruited from 6 private practices in Prague, Czech Republic, and randomized to consume L. reuteri NCIMB 30242 or placebo capsules over a 9-week intervention period. The primary outcome measure was the change in serum low-density lipoprotein-cholesterol over the 9-week intervention. Analysis of fat-soluble vitamins at weeks 0 and 9 were performed post hoc. There were no significant differences between L. reuteri NCIMB 30242 and placebo capsule groups in serum vitamin A, vitamin E, or β-carotene or dietary intake over the intervention period (P > .05). L. reuteri NCIMB 30242 increased serum 25-hydroxyvitamin D by 14.9 nmol/L, or 25.5%, over the intervention period, which was a significant mean change relative to placebo of 17.1 nmol/L, or 22.4%, respectively (P = .003). To our knowledge, this is the first report of increased circulating 25-hydroxyvitamin D in response to oral probiotic supplementation.

  11. Pharmacogenetic influence of eNOS gene variant on endothelial and glucose metabolism responses to L-arginine supplementation: Post hoc analysis of the L-arginine trial.

    Science.gov (United States)

    Monti, Lucilla D; Galluccio, Elena; Fontana, Barbara; Spadoni, Serena; Comola, Mauro; Marrocco Trischitta, Massimiliano M; Chiesa, Roberto; Comi, Giancarlo; Bosi, Emanuele; Piatti, Piermarco

    2015-11-01

    To evaluate whether variants of the eNOS gene are associated with endothelial and metabolic responses to L-arginine (L-arg) supplementation. We examined a single nucleotide polymorphism of the eNOS gene (rs753482-A>C) to investigate the effects of this variant on endothelial function (EF), colony-forming unit-endothelial cell (CFU-EC) number, asymmetric-dimethylarginine (ADMA) level, insulin sensitivity index (ISI), and insulin secretion (IS) in a post hoc analysis of the L-arg trial. The L-arg trial (6.4 g/day for 18 months) was a single-center, randomized, double-blind, parallel-group, placebo-controlled, phase III trial in individuals with impaired glucose tolerance and metabolic syndrome. followed by a 12-month extended follow-up period after termination of the study drug (NCT 00917449). At baseline, EF, CFU-EC numbers, ADMA levels, and ISI were impaired in subjects carrying minor allele C (both heterozygotes, AC and homozygotes, CC) as compared to subjects carrying major allele A (homozygotes, AA) (p<0.01). Compared to placebo, L-arg increased EF, CFU-EC numbers, and ISI, and improved ADMA levels and IS (p<0.01). The greatest improvements were found in AA subjects treated with L-arg, while the worst results were found in AC+CC subjects treated with placebo. In the placebo-treated subjects, EF, CFU-EC, ISI, and IS were significantly lower and ADMA was significantly higher in AC+CC subjects than in AA subjects. Treatment with L-arg induced similar improvements in EF, CFU-EC numbers, ADMA levels, ISI, and IS in both AA subjects and AC+CC subjects. The presence of minor allele resulted in the worst prognosis in terms of EF, CFU-EC numbers, ADMA levels, ISI, and IS during the 30-month observation period. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Clinical Outcomes and Testosterone Levels Following Continuous Androgen Deprivation in Patients with Relapsing or Locally Advanced Prostate Cancer: A Post Hoc Analysis of the ICELAND Study.

    Science.gov (United States)

    Tombal, Bertrand; Cornel, Erik B; Persad, Raj; Stari, Anny; Gómez Veiga, Francisco; Schulman, Claude

    2017-11-01

    Lower serum testosterone levels correlate with improved cause specific survival and longer time to progression in year 1 of continuous androgen deprivation in men with prostate cancer. ICELAND was a large European study demonstrating the efficacy of leuprorelin (Eligard®) during continuous androgen deprivation. In this post hoc analysis we investigated serum testosterone levels within year 1 of continuous androgen deprivation to determine survival and time to progression. In ICELAND (ClinicalTrials.gov NCT00378690) patients with locally advanced or relapsing nonmetastatic prostate cancer and with prostate specific antigen 1 ng/ml or less following 6-month induction with leuprorelin 3-month depot 22.5 mg (plus bicalutamide 50 mg per day for 1 month) were randomized 1:1 to continuous androgen deprivation (361) or intermittent androgen deprivation (340) with leuprorelin for 36 months. Patients receiving continuous androgen deprivation were stratified by minimum, median and maximum testosterone levels during year 1 of therapy into 20 or less, greater than 20 to 50 and greater than 50 ng/dl subgroups. Cause specific survival and time to prostate specific antigen (castrate resistant prostate cancer) progression were analyzed. A total of 90.1%, 83.5% and 74.5% of patients receiving continuous androgen deprivation achieved minimum, median and maximum serum testosterone levels of 20 ng/dl or less, respectively. Cause specific survival rates and time to prostate specific antigen progression did not differ among the testosterone subgroups. In patients receiving continuous androgen deprivation cause specific survival and time to prostate specific antigen progression did not differ according to testosterone levels in year 1 of therapy. This finding may in part be due to the induction period and the effectiveness of leuprorelin in lowering testosterone. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  13. An initial reduction in serum uric acid during angiotensin receptor blocker treatment is associated with cardiovascular protection: a post-hoc analysis of the RENAAL and IDNT trials.

    Science.gov (United States)

    Smink, Paul A; Bakker, Stephan J L; Laverman, Gozewijn D; Berl, Tomas; Cooper, Mark E; de Zeeuw, Dick; Lambers Heerspink, Hiddo J

    2012-05-01

    Increased levels of serum uric acid (SUA) are thought to be an independent risk marker for cardiovascular complications. Treatment with the angiotensin receptor blocker (ARB) losartan lowers SUA in contrast to other ARBs. Whether reductions in SUA during ARB therapy are associated with cardiovascular protection is unclear. We aimed to investigate this. In a post-hoc analysis of the Reduction of Endpoints in Non insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) and Irbesartan Diabetic Nephropathy (IDNT) trials we determined whether the short-term effect of losartan and of irbesartan on SUA is related with long-term cardiovascular outcome by means of Cox regression. Compared to placebo, losartan significantly changed SUA [-0.16  mg/dl; 95% confidence interval (CI) -0.01 to -0.30; P = 0.031], whereas irbesartan did not (-0.09  mg/dl; (95% CI 0.09 to -0.28; P = 0.30). Each 0.5  mg/dl decrement in SUA during losartan treatment in the first 6 months resulted in a reduction in the risk of cardiovascular outcomes by 5.3% (95% CI 0.9 to 9.9; P = 0.017). Losartan reduced the risk of cardiovascular outcomes by 9.2% (95% CI -7.9 to 23.6). Adjustment for the 6-month change in SUA attenuated the treatment effect to 4.6% (95% CI -16.2 to 22.0), suggesting that part of the cardiovascular protective effect of losartan is attributable to its short-term effect on SUA. Losartan but not irbesartan significantly lowers SUA compared to placebo in patients with type 2 diabetes and nephropathy. The degree of reduction in SUA explains part of the cardiovascular effect of losartan. This supports the hypothesis that SUA is a modifiable risk factor for cardiovascular disease, at least in type 2 diabetics with nephropathy.

  14. Influence of Renal Impairment on Outcome for Thrombolysis-Treated Acute Ischemic Stroke: ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) Post Hoc Analysis.

    Science.gov (United States)

    Carr, Susan J; Wang, Xia; Olavarria, Veronica V; Lavados, Pablo M; Rodriguez, Jorge A; Kim, Jong S; Lee, Tsong-Hai; Lindley, Richard I; Pontes-Neto, Octavio M; Ricci, Stefano; Sato, Shoichiro; Sharma, Vijay K; Woodward, Mark; Chalmers, John; Anderson, Craig S; Robinson, Thompson G

    2017-09-01

    Renal dysfunction (RD) is associated with poor prognosis after stroke. We assessed the effects of RD on outcomes and interaction with low- versus standard-dose alteplase in a post hoc subgroup analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). A total of 3220 thrombolysis-eligible patients with acute ischemic stroke (mean age, 66.5 years; 37.8% women) were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset. Six hundred and fifty-nine (19.8%) patients had moderate-to-severe RD (estimated glomerular filtration rate, 90 mL/min per 1.73 m 2 ), those with severe RD (stroke. There was no significant association with modified Rankin Scale scores 2 to 6 (adjusted odds ratio, 1.03; 95% confidence interval, 0.62-1.70; P =0.81 for trend), modified Rankin Scale 3 to 6 (adjusted odds ratio, 1.20; 95% confidence interval, 0.72-2.01; P =0.44 for trend), or symptomatic intracerebral hemorrhage, or any heterogeneity in comparative treatment effects between low-dose and standard-dose alteplase by RD grades. RD is associated with increased mortality but not disability or symptomatic intracerebral hemorrhage in thrombolysis-eligible and treated acute ischemic stroke patients. Uncertainty persists as to whether low-dose alteplase confers benefits over standard-dose alteplase in acute ischemic stroke patients with RD. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616. © 2017 American Heart Association, Inc.

  15. Modelling and Analysing Socio-Technical Systems

    DEFF Research Database (Denmark)

    Aslanyan, Zaruhi; Ivanova, Marieta Georgieva; Nielson, Flemming

    2015-01-01

    Modern organisations are complex, socio-technical systems consisting of a mixture of physical infrastructure, human actors, policies and processes. An in-creasing number of attacks on these organisations exploits vulnerabilities on all different levels, for example combining a malware attack...... with social engineering. Due to this combination of attack steps on technical and social levels, risk assessment in socio-technical systems is complex. Therefore, established risk assessment methods often abstract away the internal structure of an organisation and ignore human factors when modelling...... and assessing attacks. In our work we model all relevant levels of socio-technical systems, and propose evaluation techniques for analysing the security properties of the model. Our approach simplifies the identification of possible attacks and provides qualified assessment and ranking of attacks based...

  16. Effect of fenofibrate on uric acid and gout in type 2 diabetes: a post-hoc analysis of the randomised, controlled FIELD study.

    Science.gov (United States)

    Waldman, Boris; Ansquer, Jean-Claude; Sullivan, David R; Jenkins, Alicia J; McGill, Neil; Buizen, Luke; Davis, Timothy M E; Best, James D; Li, Liping; Feher, Michael D; Foucher, Christelle; Kesaniemi, Y Antero; Flack, Jeffrey; d'Emden, Michael C; Scott, Russell S; Hedley, John; Gebski, Val; Keech, Anthony C

    2018-04-01

    Gout is a painful disorder and is common in type 2 diabetes. Fenofibrate lowers uric acid and reduces gout attacks in small, short-term studies. Whether fenofibrate produces sustained reductions in uric acid and gout attacks is unknown. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, participants aged 50-75 years with type 2 diabetes were randomly assigned to receive either co-micronised fenofibrate 200 mg once per day or matching placebo for a median of 5 years follow-up. We did a post-hoc analysis of recorded on-study gout attacks and plasma uric acid concentrations according to treatment allocation. The outcomes of this analysis were change in uric acid concentrations and risk of on-study gout attacks. The FIELD study is registered with ISRCTN, number ISRCTN64783481. Between Feb 23, 1998, and Nov 3, 2000, 9795 patients were randomly assigned to fenofibrate (n=4895) or placebo (n=4900) in the FIELD study. Uric acid concentrations fell by 20·2% (95% CI 19·9-20·5) during the 6-week active fenofibrate run-in period immediately pre-randomisation (a reduction of 0·06 mmol/L or 1 mg/dL) and remained -20·1% (18·5-21·7, puric acid concentration higher than 0·36 mmol/L and 13·9% in those with baseline uric acid concentration higher than 0·42 mmol/L, compared with 3·4% and 5·7%, respectively, in the fenofibrate group. Risk reductions were similar among men and women and those with dyslipidaemia, on diuretics, and with elevated uric acid concentrations. For participants with elevated baseline uric acid concentrations despite taking allopurinol at study entry, there was no heterogeneity of the treatment effect of fenofibrate on gout risk. Taking account of all gout events, fenofibrate treatment halved the risk (HR 0·48, 95% CI 0·37-0·60; puric acid concentrations by 20%, and almost halved first on-study gout events over 5 years of treatment. Fenofibrate could be a useful adjunct for preventing gout in diabetes. None. Copyright

  17. Indomethacin reduces glomerular and tubular damage markers but not renal inflammation in chronic kidney disease patients: a post-hoc analysis.

    Directory of Open Access Journals (Sweden)

    Martin H de Borst

    Full Text Available Under specific conditions non-steroidal anti-inflammatory drugs (NSAIDs may be used to lower therapy-resistant proteinuria. The potentially beneficial anti-proteinuric, tubulo-protective, and anti-inflammatory effects of NSAIDs may be offset by an increased risk of (renal side effects. We investigated the effect of indomethacin on urinary markers of glomerular and tubular damage and renal inflammation. We performed a post-hoc analysis of a prospective open-label crossover study in chronic kidney disease patients (n = 12 with mild renal function impairment and stable residual proteinuria of 4.7±4.1 g/d. After a wash-out period of six wks without any RAAS blocking agents or other therapy to lower proteinuria (untreated proteinuria (UP, patients subsequently received indomethacin 75 mg BID for 4 wks (NSAID. Healthy subjects (n = 10 screened for kidney donation served as controls. Urine and plasma levels of total IgG, IgG4, KIM-1, beta-2-microglobulin, H-FABP, MCP-1 and NGAL were determined using ELISA. Following NSAID treatment, 24 h -urinary excretion of glomerular and proximal tubular damage markers was reduced in comparison with the period without anti-proteinuric treatment (total IgG: UP 131[38-513] vs NSAID 38[17-218] mg/24 h, p<0.01; IgG4: 50[16-68] vs 10[1-38] mg/24 h, p<0.001; beta-2-microglobulin: 200[55-404] vs 50[28-110] ug/24 h, p = 0.03; KIM-1: 9[5]-[14] vs 5[2]-[9] ug/24 h, p = 0.01. Fractional excretions of these damage markers were also reduced by NSAID. The distal tubular marker H-FABP showed a trend to reduction following NSAID treatment. Surprisingly, NSAID treatment did not reduce urinary excretion of the inflammation markers MCP-1 and NGAL, but did reduce plasma MCP-1 levels, resulting in an increased fractional MCP-1 excretion. In conclusion, the anti-proteinuric effect of indomethacin is associated with reduced urinary excretion of glomerular and tubular damage markers, but not with reduced excretion of renal

  18. Relations of GlycA and lipoprotein particle subspecies with cardiovascular events and mortality: A post hoc analysis of the AIM-HIGH trial.

    Science.gov (United States)

    Otvos, James D; Guyton, John R; Connelly, Margery A; Akapame, Sydney; Bittner, Vera; Kopecky, Steven L; Lacy, Megan; Marcovina, Santica M; Muhlestein, Joseph B; Boden, William E

    The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial showed no incremental benefit of extended-release niacin (ERN) therapy added to simvastatin in subjects with cardiovascular disease (CVD). To examine the effects of ERN treatment on lipoprotein particles and GlycA, a new marker of systemic inflammation, and their relations with incident CVD events including mortality. GlycA and very low-density lipoprotein, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particle subclasses were quantified by nuclear magnetic resonance spectroscopy using available stored baseline (n = 2754) and 1-year in-trial (n = 2581) samples. Associations with CVD events and all-cause mortality were assessed using multivariable Cox proportional hazards regression adjusted for age, sex, diabetes, treatment assignment, and lipoproteins. Compared to placebo, ERN treatment lowered very low-density lipoprotein and LDL and increased HDL particle concentrations, increased LDL and HDL particle sizes (all P < .0001), but did not affect GlycA. Baseline and in-trial GlycA levels were associated with increased risk of CVD events: hazard ratio (HR) per SD increment, 1.17 (95% confidence interval [CI], 1.06-1.28) and 1.13 (1.02-1.26), respectively. However, none of the lipoprotein particle classes or subclasses was associated with incident CVD. By contrast, all-cause mortality was significantly associated with both GlycA (baseline HR: 1.46 [1.22-1.75]; in-trial HR: 1.41 [1.24-1.60]) and low levels of small HDL particles (baseline HR: 0.69 [0.56-0.86]; in-trial HR: 0.69 [0.56-0.86]). This Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial post hoc substudy indicates that inflammation, as indexed by GlycA, is unaffected by ERN treatment but is significantly associated with the residual risk of CVD and death in patients treated to low

  19. Treatment with macrolides and glucocorticosteroids in severe community-acquired pneumonia: A post-hoc exploratory analysis of a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Adrian Ceccato

    Full Text Available Systemic corticosteroids have anti-inflammatory effects, whereas macrolides also have immunomodulatory activity in addition to their primary antimicrobial actions. We aimed to evaluate the potential interaction effect between corticosteroids and macrolides on the systemic inflammatory response in patients with severe community-acquired pneumonia to determine if combining these two immunomodulating agents was harmful, or possibly beneficial.We performed a post-hoc exploratory analysis of a randomized clinical trial conducted in three tertiary hospitals in Spain. This trial included patients with severe community-acquired pneumonia with high inflammatory response (C-reactive protein [CRP] >15 mg/dL who were randomized to receive methylprednisolone 0.5 mg/kg/tpd or placebo. The choice of antibiotic treatment was at the physician's discretion. One hundred and six patients were classified into four groups according to antimicrobial therapy combination (β-lactam plus macrolide or β-lactam plus fluoroquinolone and corticosteroid arm (placebo or corticosteroids. The primary outcome was treatment failure (composite outcome of early treatment failure, or of late treatment failure, or of both early and late treatment failure.The methylprednisolone with β-lactam plus macrolide group had more elderly patients, with comorbidities, and higher pneumonia severity index (PSI risk class V, but a lower proportion of intensive care unit admission, compared to the other groups. We found non differences in treatment failure between groups (overall p = 0.374; however, a significant difference in late treatment failure was observed (4 patients in the placebo with β-lactam plus macrolide group (31% vs. 9 patients in the placebo with β-lactam plus fluoroquinolone group (24% vs. 0 patients in the methylprednisolone with β-lactam plus macrolide group (0% vs. 2 patients [5%] in the methylprednisolone with β-lactam plus fluoroquinolone group overall p = 0.009. We found

  20. Derived neutrophil to lymphocyte ratio as a prognostic factor in patients with advanced colorectal cancer according to RAS and BRAF status: a post-hoc analysis of the MRC COIN study.

    Science.gov (United States)

    Wood, Georgina; Grenader, Tal; Nash, Stephen; Adams, Richard; Kaplan, Richard; Fisher, David; Maughan, Tim; Bridgewater, John

    2017-06-01

    The phase III Continuous or Intermittent (COIN) trial failed to show a benefit in overall survival (OS) of cetuximab in combination with chemotherapy for patients with metastatic colorectal cancer. High derived neutrophil to lymphocyte ratio (dNLR) has been shown to be prognostic in patients with metastatic colorectal cancer. The aim of this analysis is to evaluate dNLR as a predictive biomarker of the survival according to RAS and BRAF mutations status within the COIN trial. A post-hoc exploratory analysis of the COIN trial arms A and B was carried out. All patients with available white blood cell and neutrophil data were analysed. The dNLR was calculated using a formula that has previously shown predictive power in cancer patients: dNLR=ANC/(WBC-ANC). A high dNLR was defined as a value of 2.2 or more. dNLR was correlated with clinical outcomes using Kaplan-Meier and Cox regression analysis. A total of 1603 patients were assigned to the oxaliplatin-based chemotherapy (arm A, N=815) or oxaliplatin-based chemotherapy plus cetuximab (arm B, N=815) arms. There was a strong association between dNLR level and overall survival (OS) using Kaplan-Meier analysis. In all mutation groups, dNLR less than 2.2 was associated with better OS compared to dNLR of 2.2 or more. The median OS in patients with wild-type disease (dNLR<2.2 vs. dNLR≥2.2) was 22.8 versus 13.1 months [hazard ratio (HR)=1.33]; 16.9 versus 11.8 months (HR=1.36) in patients with RAS mutant tumours; and 12.6 versus 6.8 months (HR=1.67) in patients with BRAF mutant tumours. In patients with dNLR less than 2.2, the median OS was 19.2 months in arm A compared to 18.0 months in arm B (HR=1.11). Among patients with dNLR greater than or equal to 2.2, the median OS was 13.0 months in arm A compared with 13.1 months in arm B (HR=0.96). dNLR is strongly prognostic for survival in all mutation groups. dNLR does not predict for benefit from the addition of cetuximab.

  1. Cost-effectiveness of zofenopril in patients with left ventricular systolic dysfunction after acute myocardial infarction: a post hoc analysis of SMILE-4

    Directory of Open Access Journals (Sweden)

    Borghi C

    2013-07-01

    Full Text Available Claudio Borghi,1 Ettore Ambrosioni,1 Stefano Omboni,2 Arrigo FG Cicero,1 Stefano Bacchelli,1 Daniela Degli Esposti,1 Salvatore Novo,3 Dragos Vinereanu,4 Giuseppe Ambrosio,5 Giorgio Reggiardo,6 Dario Zava7 1Unit of Internal Medicine, Policlinico S Orsola, University of Bologna, Bologna, Italy; 2Italian Institute of Telemedicine, Varese, Italy; 3Division of Cardiology, University of Palermo, Palermo, Italy; 4University and Emergency Hospital, Bucharest, Romania; 5Division of Cardiology, University of Perugia, Perugia, Italy; 6Mediservice, Milano, Italy; 7Istituto Lusofarmaco d'Italia SpA, Peschiera Borromeo, Italy Background: In SMILE-4 (the Survival of Myocardial Infarction Long-term Evaluation 4 study, zofenopril + acetylsalicylic acid (ASA was superior to ramipril + ASA in reducing the occurrence of major cardiovascular events in patients with left ventricular dysfunction following acute myocardial infarction. The present post hoc analysis was performed to compare the cost-effectiveness of zofenopril and ramipril. Methods: In total, 771 patients with left ventricular dysfunction and acute myocardial infarction were randomized in a double-blind manner to receive zofenopril 60 mg/day (n = 389 or ramipril 10 mg/day (n = 382 + ASA 100 mg/day and were followed up for one year. The primary study endpoint was the one-year combined occurrence of death or hospitalization for cardiovascular causes. The economic analysis was based on evaluation of cost of medications and hospitalizations and was applied to the intention-to-treat population (n = 716. Cost data were drawn from the National Health Service databases of the European countries participating in the study. The incremental cost-effectiveness ratio was used to quantify the cost per event prevented with zofenopril versus ramipril. Results: Zofenopril significantly (P = 0.028 reduced the risk of the primary study endpoint by 30% as compared with ramipril (95% confidence interval, 4%–49%. The number

  2. Duloxetine for the management of diabetic peripheral neuropathic pain: evidence-based findings from post hoc analysis of three multicenter, randomized, double-blind, placebo-controlled, parallel-group studies

    DEFF Research Database (Denmark)

    Kajdasz, Daniel K; Iyengar, Smriti; Desaiah, Durisala

    2007-01-01

    % and >or=50% reductions from baseline in the weekly mean of the 24-hour average pain severity scores); NNH was calculated based on rates of discontinuation due to adverse events (AEs). RESULTS: Patients receiving duloxetine 60 mg QD and 60 mg BID had NNTs (95% CI) of 5.2 (3.8-8.3) and 4.9 (3.......3-14.7) in the 60-mg BID group. CONCLUSION: These post hoc results suggest that duloxetine was effective and well tolerated for the management of DPNP and further support the importance of duloxetine as a treatment option for clinicians and patients to assist with the management of DPNP. Udgivelsesdato: 2007-null...

  3. Externalizing Behaviour for Analysing System Models

    DEFF Research Database (Denmark)

    Ivanova, Marieta Georgieva; Probst, Christian W.; Hansen, René Rydhof

    2013-01-01

    System models have recently been introduced to model organisations and evaluate their vulnerability to threats and especially insider threats. Especially for the latter these models are very suitable, since insiders can be assumed to have more knowledge about the attacked organisation than outside......, if not impossible task to change behaviours. Especially when considering social engineering or the human factor in general, the ability to use different kinds of behaviours is essential. In this work we present an approach to make the behaviour a separate component in system models, and explore how to integrate...

  4. Photovoltaic System Modeling. Uncertainty and Sensitivity Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Clifford W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Martin, Curtis E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-08-01

    We report an uncertainty and sensitivity analysis for modeling AC energy from ph otovoltaic systems . Output from a PV system is predicted by a sequence of models. We quantify u ncertainty i n the output of each model using empirical distribution s of each model's residuals. We propagate uncertainty through the sequence of models by sampli ng these distributions to obtain a n empirical distribution of a PV system's output. We consider models that: (1) translate measured global horizontal, direct and global diffuse irradiance to plane - of - array irradiance; (2) estimate effective irradiance; (3) predict cell temperature; (4) estimate DC voltage, current and power ; (5) reduce DC power for losses due to inefficient maximum power point tracking or mismatch among modules; and (6) convert DC to AC power . O ur analysis consider s a notional PV system com prising an array of FirstSolar FS - 387 modules and a 250 kW AC inverter ; we use measured irradiance and weather at Albuquerque, NM. We found the uncertainty in PV syste m output to be relatively small, on the order of 1% for daily energy. We found that unce rtainty in the models for POA irradiance and effective irradiance to be the dominant contributors to uncertainty in predicted daily energy. Our analysis indicates that efforts to reduce the uncertainty in PV system output predictions may yield the greatest improvements by focusing on the POA and effective irradiance models.

  5. Impact of echinocandin on prognosis of proven invasive candidiasis in ICU: A post-hoc causal inference model using the AmarCAND2 study.

    Science.gov (United States)

    Bailly, Sébastien; Leroy, Olivier; Azoulay, Elie; Montravers, Philippe; Constantin, Jean-Michel; Dupont, Hervé; Guillemot, Didier; Lortholary, Olivier; Mira, Jean-Paul; Perrigault, Pierre-François; Gangneux, Jean-Pierre; Timsit, Jean-François

    2017-04-01

    guidelines recommend first-line systemic antifungal therapy (SAT) with echinocandins in invasive candidiasis (IC), especially in critically ill patients. This study aimed at assessing the impact of echinocandins compared to azoles as initial SAT on the 28-day prognosis in adult ICU patients. From the prospective multicenter AmarCAND2 cohort (835 patients), we selected those with documented IC and treated with echinocandins (ECH) or azoles (AZO). The average causal effect of echinocandins on 28-day mortality was assessed using an inverse probability of treatment weight (IPTW) estimator. 397 patients were selected, treated with echinocandins (242 patients, 61%) or azoles (155 patients, 39%); septic shock: 179 patients (45%). The median SAPSII was higher in the ECH group (48 [35; 62] vs. 43 [31; 58], p = 0.01). Crude mortality was 34% (ECH group) vs. 25% (AZO group). After adjustment on baseline confounders, no significant association emerged between initial SAT with echinocandins and 28-day mortality (HR: 0.95; 95% CI: [0.60; 1.49]; p = 0.82). However, echinocandin tended to benefit patients with septic shock (HR: 0.46 [0.19; 1.07]; p = 0.07). Patients who received echinocandins were more severely ill. Echinocandin use was associated with a non-significant 7% decrease of 28-day mortality and a trend to a beneficial effect for patient with septic shock. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  6. Modelling and Analyses of Embedded Systems Design

    DEFF Research Database (Denmark)

    Brekling, Aske Wiid

    We present the MoVES languages: a language with which embedded systems can be specified at a stage in the development process where an application is identified and should be mapped to an execution platform (potentially multi- core). We give a formal model for MoVES that captures and gives......-based verification is a promising approach for assisting developers of embedded systems. We provide examples of system verifications that, in size and complexity, point in the direction of industrially-interesting systems....... semantics to the elements of specifications in the MoVES language. We show that even for seem- ingly simple systems, the complexity of verifying real-time constraints can be overwhelming - but we give an upper limit to the size of the search-space that needs examining. Furthermore, the formal model exposes...

  7. Radiobiological analyse based on cell cluster models

    International Nuclear Information System (INIS)

    Lin Hui; Jing Jia; Meng Damin; Xu Yuanying; Xu Liangfeng

    2010-01-01

    The influence of cell cluster dimension on EUD and TCP for targeted radionuclide therapy was studied using the radiobiological method. The radiobiological features of tumor with activity-lack in core were evaluated and analyzed by associating EUD, TCP and SF.The results show that EUD will increase with the increase of tumor dimension under the activity homogeneous distribution. If the extra-cellular activity was taken into consideration, the EUD will increase 47%. Under the activity-lack in tumor center and the requirement of TCP=0.90, the α cross-fire influence of 211 At could make up the maximum(48 μm)3 activity-lack for Nucleus source, but(72 μm)3 for Cytoplasm, Cell Surface, Cell and Voxel sources. In clinic,the physician could prefer the suggested dose of Cell Surface source in case of the future of local tumor control for under-dose. Generally TCP could well exhibit the effect difference between under-dose and due-dose, but not between due-dose and over-dose, which makes TCP more suitable for the therapy plan choice. EUD could well exhibit the difference between different models and activity distributions,which makes it more suitable for the research work. When the user uses EUD to study the influence of activity inhomogeneous distribution, one should keep the consistency of the configuration and volume of the former and the latter models. (authors)

  8. Exploring the variation in implementation of a COPD disease management programme and its impact on health outcomes: a post hoc analysis of the RECODE cluster randomised trial

    Science.gov (United States)

    Boland, Melinde R S; Kruis, Annemarije L; Huygens, Simone A; Tsiachristas, Apostolos; Assendelft, Willem J J; Gussekloo, Jacobijn; Blom, Coert M G; Chavannes, Niels H; Rutten-van Mölken, Maureen P M H

    2015-01-01

    This study aims to (1) examine the variation in implementation of a 2-year chronic obstructive pulmonary disease (COPD) management programme called RECODE, (2) analyse the facilitators and barriers to implementation and (3) investigate the influence of this variation on health outcomes. Implementation variation among the 20 primary-care teams was measured directly using a self-developed scale and indirectly through the level of care integration as measured with the Patient Assessment of Chronic Illness Care (PACIC) and the Assessment of Chronic Illness Care (ACIC). Interviews were held to obtain detailed information regarding the facilitators and barriers to implementation. Multilevel models were used to investigate the association between variation in implementation and change in outcomes. The teams implemented, on average, eight of the 19 interventions, and the specific package of interventions varied widely. Important barriers and facilitators of implementation were (in)sufficient motivation of healthcare provider and patient, the high starting level of COPD care, the small size of the COPD population per team, the mild COPD population, practicalities of the information and communication technology (ICT) system, and hurdles in reimbursement. Level of implementation as measured with our own scale and the ACIC was not associated with health outcomes. A higher level of implementation measured with the PACIC was positively associated with improved self-management capabilities, but this association was not found for other outcomes. There was a wide variety in the implementation of RECODE, associated with barriers at individual, social, organisational and societal level. There was little association between extent of implementation and health outcomes. PMID:26677770

  9. Remission and recovery associated with lurasidone in the treatment of major depressive disorder with subthreshold hypomanic symptoms (mixed features): post-hoc analysis of a randomized, placebo-controlled study with longer-term extension.

    Science.gov (United States)

    Goldberg, Joseph F; Ng-Mak, Daisy; Siu, Cynthia; Chuang, Chien-Chia; Rajagopalan, Krithika; Loebel, Antony

    2017-04-01

    This post-hoc analysis assessed rates of symptomatic and functional remission, as well as recovery (combination of symptomatic and functional remission), in patients treated with lurasidone for major depressive disorder (MDD) associated with subthreshold hypomanic symptoms (mixed features). Patients with MDD plus two or three manic symptoms (defined as per the DSM-5 mixed-features specifier) were randomly assigned to flexible-dose lurasidone 20-60 mg/day (n=109) or placebo (n=100) for 6 weeks, followed by a 3-month open-label, flexible-dose extension study for U.S. sites only (n=48). Cross-sectional recovery was defined as the presence of both symptomatic remission (Montgomery-Åsberg Depression Rating Scale score ≤ 12) and functional remission (all Sheehan Disability Scale [SDS] domain scores ≤3) at week 6, and at both months 1 and 3 of the extension study ("sustained recovery"). A significantly higher proportion of lurasidone-treated patients (31.3%) achieved recovery (assessed cross-sectionally) compared to placebo (12.2%, p=0.002) at week 6. The number of manic symptoms at baseline moderated the effect size for attaining cross-sectional recovery for lurasidone treatment (vs. placebo) (p=0.028). Sustained recovery rates were higher in patients initially treated with lurasidone (20.8%) versus placebo (12.5%). In this post-hoc analysis of a placebo-controlled study with open-label extension that involved patients with MDD and mixed features, lurasidone was found to significantly improve the rate of recovery at 6 weeks (vs. placebo) that was sustained at month 3 of the extension study. The presence of two (as opposed to three) manic symptoms moderated recovery at the acute study endpoint.

  10. Relationships Between Functional Outcomes and Symptomatic Improvement in Atomoxetine-Treated Adult Patients with Attention-Deficit/Hyperactivity Disorder: Post Hoc Analysis of an Integrated Database.

    Science.gov (United States)

    De Bruyckere, Katrien; Bushe, Chris; Bartel, Christoph; Berggren, Lovisa; Kan, Cornelis C; Dittmann, Ralf W

    2016-06-01

    Atomoxetine treatment is associated with improvements in functional outcomes in patients with attention-deficit/hyperactivity disorder (ADHD), although relationships between improvements in these outcomes and reductions in ADHD symptoms have not been comprehensively investigated in adults. The aim of this study was to assess relationships between functional outcomes and ADHD symptoms (primary objective), and to assess time courses of changes in functional outcomes from baseline to weeks 10 and 24 (secondary objective). We analyzed data pooled from seven Eli Lilly-sponsored placebo-controlled trials of atomoxetine in adults with ADHD that had Conners' Adult ADHD Rating Scales-Investigator Rated: Screening Version (CAARS-Inv:SV) total scores and functional outcome data at baseline and at week 10. Two trials also had these data at week 24. Patients were included in these pooled analyses if they had a CAARS-Inv:SV total score at baseline and at one or more post-baseline visits at weeks 10 or 24, or had post-baseline scores that would allow missing scores at weeks 10 or 24 to be imputed. To address the primary objective, changes in functional outcomes during treatment with atomoxetine versus placebo were assessed using last observation carried forward (LOCF) analysis of covariance (ANCOVA) and mixed-effects model repeated measures (MMRM) analysis, and correlations between score changes in CAARS-Inv:SV total and functional outcomes were assessed using Spearman's rank correlation coefficient (r) at weeks 10 and 24. The secondary objective was addressed using MMRM. At baseline, patients generally had moderately severe or worse ADHD symptoms (based on CAARS-Inv:SV total scores) and impaired functional outcomes (based on Adult ADHD Quality-of-Life [AAQoL], Behavior Rating Inventory of Executive Function-Adult Version [BRIEF-A], Sheehan Disability Scale [SDS], and 36-item Short-Form Health Survey [SF-36] scores). These baseline characteristics were comparable in the

  11. Efficacy and safety of teriparatide in bisphosphonate-pretreated and treatment-naive patients with osteoporosis at high risk of fracture: Post hoc analysis of a prospective observational study.

    Science.gov (United States)

    Yoshiki, Fumito; Nishikawa, Atsushi; Taketsuna, Masanori; Kajimoto, Kenta; Enomoto, Hiroyuki

    2017-03-01

    Teriparatide is the first anabolic agent shown to reduce the risk of fractures in patients with osteoporosis. In Japan, teriparatide is prescribed to treat patients at high risk of fracture. Given that bisphosphonates are commonly used prior to teriparatide as treatment for osteoporosis, information on the effectiveness and safety of teriparatide with or without previous bisphosphonate treatment is helpful for physicians in clinical practice. This study aims to report the effectiveness and safety of teriparatide in treatment-naive and bisphosphonate-pretreated patients in Japan as real-world evidence. A post hoc analysis of a postmarketing surveillance study was conducted in Japanese patients with osteoporosis at high risk of fracture who received 24-month treatment of daily teriparatide. Changes in bone turnover biomarkers and bone mineral density and incidence of new fractures were analyzed in treatment-naive as well as bisphosphonate-pretreated patients. The analysis included 1433 patients (treatment-naive, n = 659; bisphosphonate-pretreated, n = 774). Bone mineral density increased significantly from baseline at 24 months in both treatment-naive (lumbar spine, 13.45%; femoral neck, 5.16%; total hip, 4.46%) and bisphosphonate-pretreated (lumbar spine, 11.20%; femoral neck, 2.22%; total hip, 0.67%) patients. The incidence rates of new vertebral and nonvertebral fractures at 24 months were 1.69% and 3.37%, respectively, in treatment-naive patients and 3.60% and 5.56%, respectively, in bisphosphonate-pretreated patients. The incidence of adverse drug reactions was 6% in treatment-naive patients and 10% in bisphosphonate-pretreated patients. The most common adverse drug reaction in treatment-naive and bisphosphonate-pretreated patients was nausea (0.91%) and hyperuricaemia (1.81%), respectively. In this post hoc analysis, no new safety concerns and similar effectiveness of teriparatide were observed in Japanese patients with osteoporosis at high risk of fracture

  12. Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial.

    Science.gov (United States)

    van de Ven, J; Fransen, A F; Schuit, E; van Runnard Heimel, P J; Mol, B W; Oei, S G

    2017-09-01

    Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial. J van de Ven, AF Fransen, E Schuit, PJ van Runnard Heimel, BW Mol, SG Oei OBJECTIVE: To investigate whether the effect of a one-day simulation-based obstetric team training on patient outcome changes over time. Post-hoc analysis of a multicentre, open, randomised controlled trial that evaluated team training in obstetrics (TOSTI study).We studied women with a singleton pregnancy beyond 24 weeks of gestation in 24 obstetric units. Included obstetric units were randomised to either a one-day, multi-professional simulation-based team training focusing on crew resource management in a medical simulation centre (12 units) or to no team training (12 units). We assessed whether outcomes differed between both groups in each of the first four quarters following the team training and compared the effect of team training over quarters. Primary outcome was a composite outcome of low Apgar score, severe postpartum haemorrhage, trauma due to shoulder dystocia, eclampsia and hypoxic-ischemic encephalopathy. During a one year period after the team training the rate of obstetric complications, both on the composite level and the individual component level, did not differ between any of the quarters. For trauma due to shoulder dystocia team training led to a significant decrease in the first quarter (0.06% versus 0.26%, OR 0.19, 95% CI 0.03 to 0.98) but in the subsequent quarters no significant reductions were observed. Similar results were found for invasive treatment for severe postpartum haemorrhage where a significant increase was only seen in the first quarter (0.4% versus 0.03%, OR 19, 95% CI 2.5-147), and not thereafter. The beneficial effect of a one-day, simulation-based, multiprofessional, obstetric team training seems to decline after three months. If team training is further evaluated or

  13. Effects of Dalfampridine Extended-release Tablets on 6-minute Walk Distance in Patients With Multiple Sclerosis: A Post Hoc Analysis of a Double-blind, Placebo-controlled Trial.

    Science.gov (United States)

    Applebee, Angela; Goodman, Andrew D; Mayadev, Angeli S; Bethoux, Francois; Goldman, Myla D; Klingler, Michael; Blight, Andrew R; Carrazana, Enrique J

    2015-12-01

    Dalfampridine extended-release (ER) tablets 10 mg BID have been approved for use in improving walking in people with multiple sclerosis (MS). This subgroup analysis evaluated the effects of dalfampridine ER 5 and 10 mg BID on distance walked, as assessed using the 6-minute walk (6MW) test. This analysis of data from a randomized, placebo-controlled, double-blind study (N = 430) included only the 153 patients with 6MW data available. Participants (aged 18-70 years) were randomly assigned in a 1:1:1 ratio to receive dalfampridine ER 5 or 10 mg or placebo, BID for 4 weeks. The 6MW was used for assessing walking distance at baseline and 2 weeks after the start of treatment at the 26 study sites that were able to perform this test. Participants were administered the 12-item MS Walking Scale (MSWS-12), a patient-reported measure of the impact of MS on walking. Post hoc outcomes included the percentages of patients who achieved an increase from baseline in 6MW distance of ≥20% and who achieved a minimal clinically important difference (MCID) from baseline in 6MW distance, defined as ≥+55 m. Changes from baseline in walking speed (MSWS-12) were compared, stratified by subgroup that achieved ≥20% versus walking speed over time and subgroup (by change in distance walked) was evaluated. The tolerability of dalfampridine was assessed based on the prevalence of treatment-emergent adverse events (TEAEs). In the post hoc analysis, the percentage of patients with an improvement in 6MW distance that met or exceeded the MCID was significantly greater with dalfampridine ER 10 mg BID relative to placebo (37.3% vs 12.2%; nominal P = 0.004). Similarly, the percentage with an improvement in 6MW distance of ≥20% was significantly greater with dalfampridine 10 mg BID relative to placebo (45.1% vs 14.3%; nominal P walking relative to placebo. The correlation between improvement on MSWS-12 and the 20% increase in 6MW distance suggests that an improvement on MSWS-12 is clinically

  14. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels : a post hoc analysis of a double-blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144)

    NARCIS (Netherlands)

    Nolen, Willem A.; Weisler, Richard H.

    Nolen WA, Weisler RH. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double-blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144). Bipolar Disord 2012:

  15. VIPRE modeling of VVER-1000 reactor core for DNB analyses

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Y.; Nguyen, Q. [Westinghouse Electric Corporation, Pittsburgh, PA (United States); Cizek, J. [Nuclear Research Institute, Prague, (Czech Republic)

    1995-09-01

    Based on the one-pass modeling approach, the hot channels and the VVER-1000 reactor core can be modeled in 30 channels for DNB analyses using the VIPRE-01/MOD02 (VIPRE) code (VIPRE is owned by Electric Power Research Institute, Palo Alto, California). The VIPRE one-pass model does not compromise any accuracy in the hot channel local fluid conditions. Extensive qualifications include sensitivity studies of radial noding and crossflow parameters and comparisons with the results from THINC and CALOPEA subchannel codes. The qualifications confirm that the VIPRE code with the Westinghouse modeling method provides good computational performance and accuracy for VVER-1000 DNB analyses.

  16. Seismic Soil-Structure Interaction Analyses of a Deeply Embedded Model Reactor – SASSI Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Nie J.; Braverman J.; Costantino, M.

    2013-10-31

    This report summarizes the SASSI analyses of a deeply embedded reactor model performed by BNL and CJC and Associates, as part of the seismic soil-structure interaction (SSI) simulation capability project for the NEAMS (Nuclear Energy Advanced Modeling and Simulation) Program of the Department of Energy. The SASSI analyses included three cases: 0.2 g, 0.5 g, and 0.9g, all of which refer to nominal peak accelerations at the top of the bedrock. The analyses utilized the modified subtraction method (MSM) for performing the seismic SSI evaluations. Each case consisted of two analyses: input motion in one horizontal direction (X) and input motion in the vertical direction (Z), both of which utilized the same in-column input motion. Besides providing SASSI results for use in comparison with the time domain SSI results obtained using the DIABLO computer code, this study also leads to the recognition that the frequency-domain method should be modernized so that it can better serve its mission-critical role for analysis and design of nuclear power plants.

  17. Physicians Experience with and Expectations of the Safety and Tolerability of WHO-Step III Opioids for Chronic (Low Back Pain: Post Hoc Analysis of Data from a German Cross-Sectional Physician Survey

    Directory of Open Access Journals (Sweden)

    Michael A. Ueberall

    2015-01-01

    Full Text Available Objective. To describe physicians’ daily life experience with WHO-step III opioids in the treatment of chronic (low back pain (CLBP. Methods. Post hoc analysis of data from a cross-sectional online survey with 4.283 Germany physicians. Results. With a reported median use in 17% of affected patients, WHO-step III opioids play a minor role in treatment of CLBP in daily practice associated with a broad spectrum of positive and negative effects. If prescribed, potent opioids were reported to show clinically relevant effects (such as ≥50% pain relief in approximately 3 of 4 patients (median 72%. Analgesic effects reported are frequently related with adverse events (AEs. Only 20% of patients were reported to remain free of any AE. Most frequently reported AE was constipation (50%, also graded highest for AE-related daily life restrictions (median 46%. Specific AE countermeasures were reported to be necessary in approximately half of patients (median 45%; nevertheless AE-related premature discontinuation rates reported were high (median 22%. Fentanyl/morphine were the most/least prevalently prescribed potent opioids mentioned (median 20 versus 8%. Conclusion. Overall, use of WHO-step III opioids for CLBP is low. AEs, especially constipation, are commonly reported and interfere significantly with analgesic effects in daily practice. Nevertheless, beneficial effects outweigh related AEs in most patients with CLBP.

  18. Omega-3 fatty acid supplementation in adolescents with borderline personality disorder and ultra-high risk criteria for psychosis: a post hoc subgroup analysis of a double-blind, randomized controlled trial.

    Science.gov (United States)

    Amminger, G Paul; Chanen, Andrew M; Ohmann, Susanne; Klier, Claudia M; Mossaheb, Nilufar; Bechdolf, Andreas; Nelson, Barnaby; Thompson, Andrew; McGorry, Patrick D; Yung, Alison R; Schäfer, Miriam R

    2013-07-01

    To investigate whether long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs) improve functioning and psychiatric symptoms in young people with borderline personality disorder (BPD) who also meet ultra-high risk criteria for psychosis. We conducted a post hoc subgroup analysis of a double-blind, randomized controlled trial. Fifteen adolescents with BPD (mean age 16.2 years, [SD 2.1]) were randomized to either 1.2 g/day n-3 PUFAs or placebo. The intervention period was 12 weeks. Study measures included the Positive and Negative Syndrome Scale, the Montgomery-Åsberg Depression Rating Scale, and the Global Assessment of Functioning. Side effects were documented with the Udvalg for Kliniske Undersøgelser. Fatty acids in erythrocytes were analyzed using capillary gas chromatography. At baseline, erythrocyte n-3 PUFA levels correlated positively with psychosocial functioning and negatively with psychopathology. By the end of the intervention, n-3 PUFAs significantly improved functioning and reduced psychiatric symptoms, compared with placebo. Side effects did not differ between the treatment groups. Long-chain n-3 PUFAs should be further explored as a viable treatment strategy with minimal associated risk in young people with BPD. ( NCT00396643).

  19. Analysing the temporal dynamics of model performance for hydrological models

    NARCIS (Netherlands)

    Reusser, D.E.; Blume, T.; Schaefli, B.; Zehe, E.

    2009-01-01

    The temporal dynamics of hydrological model performance gives insights into errors that cannot be obtained from global performance measures assigning a single number to the fit of a simulated time series to an observed reference series. These errors can include errors in data, model parameters, or

  20. Modeling Citable Textual Analyses for the Homer Multitext

    Directory of Open Access Journals (Sweden)

    Christopher William Blackwell

    2016-12-01

    Full Text Available The 'Homer Multitext' project (hmt is documenting the language and structure of Greek epic poetry, and the ancient tradition of commentary on it. The project’s primary data consist of editions of Greek texts; automated and manually created readings analyze the texts across historical and thematic axes. This paper describes an abstract model we follow in documenting an open-ended body of diverse analyses. The analyses apply to passages of texts at different levels of granularity; they may refer to overlapping or mutually exclusive passages of text; and they may apply to non-contiguous passages of text. All are recorded in with explicit, concise, machine-actionable canonical citation of both text passage and analysis in a scheme aligning all analyses to a common notional text. We cite our texts with urns that capture a passage’s position in an 'Ordered Hierarchy of Citation Objects' (ohco2. Analyses are modeled as data-objects with five properties. We create collections of ‘analytical objects’, each uniquely identified by its own urn and each aligned to a particular edition of a text by a urn citation. We can view these analytical objects as an extension of the edition’s citation hierarchy; since they are explicitly ordered by their alignment with the edition they analyze, each collection of analyses meets satisfies the (ohco2 model of a citable text. We call these texts that are derived from and aligned to an edition ‘analytical exemplars’.

  1. Use of flow models to analyse loss of coolant accidents

    International Nuclear Information System (INIS)

    Pinet, Bernard

    1978-01-01

    This article summarises current work on developing the use of flow models to analyse loss-of-coolant accident in pressurized-water plants. This work is being done jointly, in the context of the LOCA Technical Committee, by the CEA, EDF and FRAMATOME. The construction of the flow model is very closely based on some theoretical studies of the two-fluid model. The laws of transfer at the interface and at the wall are tested experimentally. The representativity of the model then has to be checked in experiments involving several elementary physical phenomena [fr

  2. Insights into the efficacy of golimumab plus methotrexate in patients with active rheumatoid arthritis who discontinued prior anti-tumour necrosis factor therapy: post-hoc analyses from the GO-AFTER study

    NARCIS (Netherlands)

    Smolen, Josef S.; Kay, Jonathan; Matteson, Eric L.; Landewé, Robert; Hsia, Elizabeth C.; Xu, Stephen; Zhou, Yiying; Doyle, Mittie K.

    2014-01-01

    Evaluate golimumab in patients with active rheumatoid arthritis (RA) and previous tumour necrosis factor-α (TNF) inhibitor use. Patients (n=461) previously receiving ≥1 TNF inhibitor were randomised to subcutaneous injections of placebo, golimumab 50 mg or golimumab 100 mg q4 weeks. Primary endpoint

  3. Post Hoc Analysis of Data from Two Clinical Trials Evaluating the Minimal Clinically Important Change in International Restless Legs Syndrome Sum Score in Patients with Restless Legs Syndrome (Willis-Ekbom Disease).

    Science.gov (United States)

    Ondo, William G; Grieger, Frank; Moran, Kimberly; Kohnen, Ralf; Roth, Thomas

    2016-01-01

    Determine the minimal clinically important change (MCIC), a measure determining the minimum change in scale score perceived as clinically beneficial, for the international restless legs syndrome (IRLS) and restless legs syndrome 6-item questionnaire (RLS-6) in patients with moderate to severe restless legs syndrome (RLS/Willis-Ekbom disease) treated with the rotigotine transdermal system. This post hoc analysis analyzed data from two 6-mo randomized, double-blind, placebo-controlled studies (SP790 [NCT00136045]; SP792 [NCT00135993]) individually and as a pooled analysis in rotigotine-treated patients, with baseline and end of maintenance IRLS and Clinical Global Impressions of change (CGI Item 2) scores available for analysis. An anchor-based approach and receiver operating characteristic (ROC) curves were used to determine the MCIC for the IRLS and RLS-6. We specifically compared "much improved vs minimally improved," "much improved/very much improved vs minimally improved or worse," and "minimally improved or better vs no change or worse" on the CGI-2 using the full analysis set (data as observed). The MCIC IRLS cut-off scores for SP790 and SP792 were similar. Using the pooled SP790+SP792 analysis, the MCIC total IRLS cut-off score (sensitivity, specificity) for "much improved vs minimally improved" was -9 (0.69, 0.66), for "much improved/very much improved vs minimally improved or worse" was -11 (0.81, 0.84), and for "minimally improved or better vs no change or worse" was -9 (0.79, 0.88). MCIC ROC cut-offs were also calculated for each RLS-6 item. In patients with RLS, the MCIC values derived in the current analysis provide a basis for defining meaningful clinical improvement based on changes in the IRLS and RLS-6 following treatment with rotigotine. © 2016 American Academy of Sleep Medicine.

  4. The association of targeted temperature management at 33 and 36 °C with outcome in patients with moderate shock on admission after out-of-hospital cardiac arrest: a post hoc analysis of the Target Temperature Management trial.

    Science.gov (United States)

    Annborn, Martin; Bro-Jeppesen, John; Nielsen, Niklas; Ullén, Susann; Kjaergaard, Jesper; Hassager, Christian; Wanscher, Michael; Hovdenes, Jan; Pellis, Tommaso; Pelosi, Paolo; Wise, Matt P; Cronberg, Tobias; Erlinge, David; Friberg, Hans

    2014-09-01

    We hypothesized that a targeted temperature of 33 °C as compared to that of 36 °C would increase survival and reduce the severity of circulatory shock in patients with shock on admission after out-of-hospital cardiac arrest (OHCA). The recently published Target Temperature Management trial (TTM-trial) randomized 939 OHCA patients with no difference in outcome between groups and no difference in mortality at the end of the trial in a predefined subgroup of patients with shock at admission. Shock was defined as a systolic blood pressure of 30 min or the need of supportive measures to maintain a blood pressure ≥90 mmHg and/or clinical signs of end-organ hypoperfusion. In this post hoc analysis reported here, we further analyzed the 139 patients with shock at admission; all had been randomized to receive intervention at 33 °C (TTM33; n = 71) or 36 °C (TTM36; n = 68). Primary outcome was 180-day mortality. Secondary outcomes were intensive care unit (ICU) and 30-day mortality, severity of circulatory shock assessed by mean arterial pressure, serum lactate, fluid balance and the extended Sequential Organ Failure assessment (SOFA) score. There was no significance difference between targeted temperature management at 33 °C or 36 °C on 180-day mortality [log-rank test, p = 0.17, hazard ratio 1.33, 95 % confidence interval (CI) 0.88-1.98] or ICU mortality (61 vs. 44 %, p = 0.06; relative risk 1.37, 95 % CI 0.99-1.91). Serum lactate and the extended cardiovascular SOFA score were higher in the TTM33 group (p shock with targeted temperature management at 33 °C as compared to 36 °C in patients with shock on admission after OHCA.

  5. Safety of daily teriparatide treatment: a post hoc analysis of a Phase III study to investigate the possible association of teriparatide treatment with calcium homeostasis in patients with serum procollagen type I N-terminal propeptide elevation.

    Science.gov (United States)

    Yamamoto, Takanori; Tsujimoto, Mika; Sowa, Hideaki

    2015-01-01

    Serum procollagen type I N-terminal propeptide (PINP), a representative marker of bone anabolic action, is strongly related to bone mineral density during teriparatide therapy. This post hoc study analyzed data from a Phase III study (ClinicalTrials.gov identifier NCT00433160) to determine if there was an association between serum PINP elevation and serum calcium concentration or calcium metabolism-related disorders. Japanese subjects with osteoporosis at high risk of fracture were randomized 2:1 to teriparatide 20 μg/day (n=137) or placebo (n=70) for a 12-month double-blind treatment period, followed by 12 months of open-label teriparatide treatment of all subjects. Serum PINP levels were measured at baseline, and after 1, 3, 6, 12, 18, and 24 months of treatment. Serum calcium levels were measured at baseline, and after 1, 3, 6, 9, 12, 15, 18, 21, and 24 months of treatment. Serum PINP increased from baseline to 1 month of treatment and then remained high through 24 months. Twenty-eight of 195 subjects experienced PINP elevations >200 μg/L during teriparatide treatment. Serum calcium concentration in both the teriparatide and placebo groups remained within the normal range. There was no clinically relevant difference in serum calcium concentration between subjects with PINP >200 μg/L and subjects with PINP ≤200 μg/L. Two subjects experienced hypercalcemia and recovered without altering teriparatide treatment. Adverse events possibly related to calcium metabolism disorders included periarthritis calcarea (one subject) and chondrocalcinosis pyrophosphate (two subjects), but neither was accompanied with a significant increase in PINP or serum calcium concentration. Although the moderate size of this study prevented statistical analysis of any potential association between calcium metabolism-related disorders and elevated PINP, this analysis suggests that there was no association between serum PINP elevation during daily teriparatide treatment and serum calcium

  6. Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial

    Directory of Open Access Journals (Sweden)

    Ma Yi-Wen

    2011-04-01

    Full Text Available Abstract Background This post hoc analysis (trial registration: ClinicalTrials.gov NCT00590577 assessed onset of efficacy and tolerability of acute treatment with once-monthly paliperidone palmitate (PP, a long-acting atypical antipsychotic initiated by day 1 and day 8 injections, in a markedly to severely ill schizophrenia population. Methods Subjects entering the 13-week, double-blind trial were randomized to PP (39, 156, or 234 mg [25, 100, and 150 mg eq of paliperidone, respectively] or placebo. This subgroup analysis included those with a baseline Clinical Global Impressions-Severity (CGI-S score indicating marked to severe illness. PP subjects received a 234-mg day 1 injection (deltoid, followed by their assigned dose on day 8 and monthly thereafter (deltoid or gluteal. Thus, data for PP groups were pooled for days 4 and 8. Measures included Positive and Negative Syndrome Scale (PANSS, CGI-S, Personal and Social Performance (PSP, and adverse events (AEs. Analysis of covariance (ANCOVA and last-observation-carried-forward (LOCF methodologies, without multiplicity adjustments, were used to assess changes in continuous measures. Onset of efficacy was defined as the first time point a treatment group showed significant PANSS improvement (assessed days 4, 8, 22, 36, 64, and 92 versus placebo, which was maintained through end point. Results A total of 312 subjects met inclusion criterion for this subgroup analysis. After the day 1 injection, mean PANSS total scores improved significantly with PP (all received 234 mg versus placebo at day 4 (P = 0.012 and day 8 (P = 0.007. After the day 8 injection, a significant PANSS improvement persisted at all subsequent time points in the 234-mg group versus placebo (P P P P Conclusions In this markedly to severely ill population, acute treatment with 234 mg PP improved psychotic symptoms compared with placebo by day 4. After subsequent injections, observed improvements are suggestive of a dose

  7. Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction: post-hoc analysis of the Kremezin Study against renal disease progression in Korea

    Directory of Open Access Journals (Sweden)

    Ran-hui Cha

    2017-03-01

    Full Text Available Background: We investigated the long-term effect of AST-120, which has been proposed as a therapeutic option against renal disease progression, in patients with advanced chronic kidney disease (CKD. Methods: We performed post-hoc analysis with a per-protocol group of the K-STAR study (Kremezin study against renal disease progression in Korea that randomized participants into an AST-120 and a control arm. Patients in the AST-120 arm were given 6 g of AST-120 in three divided doses, and those in both arms received standard conventional treatment. Results: The two arms did not differ significantly in the occurrence of composite primary outcomes (log-rank P = 0.41. For AST-120 patients with higher compliance, there were fewer composite primary outcomes: intermediate tertile hazard ratio (HR 0.62, 95% confidence interval (CI 0.38 to 1.01, P = 0.05; highest tertile HR 0.436, 95% CI 0.25 to 0.76, P = 0.003. The estimated glomerular filtration rate level was more stable in the AST-120 arm, especially in diabetic patients. At one year, the AST-120-induced decrease in the serum indoxyl sulfate concentration inversely correlated with the occurrence of composite primary outcomes: second tertile HR 1.59, 95% CI 0.82 to 3.07, P = 0.17; third tertile HR 2.11, 95% CI 1.07 to 4.17, P = 0.031. Furthermore, AST-120 showed a protective effect against the major cardiovascular adverse events (HR 0.51, 95% CI 0.26 to 0.99, P = 0.046. Conclusion: Long-term use of AST-120 has potential for renal protection, especially in diabetic patients, as well as cardiovascular benefits. Reduction of the serum indoxyl sulfate level may be used to identify patients who would benefit from AST-120 administration.

  8. The Effect of Sitagliptin on the Regression of Carotid Intima-Media Thickening in Patients with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation

    Directory of Open Access Journals (Sweden)

    Tomoya Mita

    2017-01-01

    Full Text Available Background. The effect of dipeptidyl peptidase-4 (DPP-4 inhibitors on the regression of carotid IMT remains largely unknown. The present study aimed to clarify whether sitagliptin, DPP-4 inhibitor, could regress carotid intima-media thickness (IMT in insulin-treated patients with type 2 diabetes mellitus (T2DM. Methods. This is an exploratory analysis of a randomized trial in which we investigated the effect of sitagliptin on the progression of carotid IMT in insulin-treated patients with T2DM. Here, we compared the efficacy of sitagliptin treatment on the number of patients who showed regression of carotid IMT of ≥0.10 mm in a post hoc analysis. Results. The percentages of the number of the patients who showed regression of mean-IMT-CCA (28.9% in the sitagliptin group versus 16.4% in the conventional group, P = 0.022 and left max-IMT-CCA (43.0% in the sitagliptin group versus 26.2% in the conventional group, P = 0.007, but not right max-IMT-CCA, were higher in the sitagliptin treatment group compared with those in the non-DPP-4 inhibitor treatment group. In multiple logistic regression analysis, sitagliptin treatment significantly achieved higher target attainment of mean-IMT-CCA ≥0.10 mm and right and left max-IMT-CCA ≥0.10 mm compared to conventional treatment. Conclusions. Our data suggested that DPP-4 inhibitors were associated with the regression of carotid atherosclerosis in insulin-treated T2DM patients. This study has been registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000007396.

  9. Social Network Analyses and Nutritional Behavior: An Integrated Modeling Approach

    Directory of Open Access Journals (Sweden)

    Alistair McNair Senior

    2016-01-01

    Full Text Available Animals have evolved complex foraging strategies to obtain a nutritionally balanced diet and associated fitness benefits. Recent advances in nutrition research, combining state-space models of nutritional geometry with agent-based models of systems biology, show how nutrient targeted foraging behavior can also influence animal social interactions, ultimately affecting collective dynamics and group structures. Here we demonstrate how social network analyses can be integrated into such a modeling framework and provide a tangible and practical analytical tool to compare experimental results with theory. We illustrate our approach by examining the case of nutritionally mediated dominance hierarchies. First we show how nutritionally explicit agent-based models that simulate the emergence of dominance hierarchies can be used to generate social networks. Importantly the structural properties of our simulated networks bear similarities to dominance networks of real animals (where conflicts are not always directly related to nutrition. Finally, we demonstrate how metrics from social network analyses can be used to predict the fitness of agents in these simulated competitive environments. Our results highlight the potential importance of nutritional mechanisms in shaping dominance interactions in a wide range of social and ecological contexts. Nutrition likely influences social interaction in many species, and yet a theoretical framework for exploring these effects is currently lacking. Combining social network analyses with computational models from nutritional ecology may bridge this divide, representing a pragmatic approach for generating theoretical predictions for nutritional experiments.

  10. SVM models for analysing the headstreams of mine water inrush

    Energy Technology Data Exchange (ETDEWEB)

    Yan Zhi-gang; Du Pei-jun; Guo Da-zhi [China University of Science and Technology, Xuzhou (China). School of Environmental Science and Spatial Informatics

    2007-08-15

    The support vector machine (SVM) model was introduced to analyse the headstrean of water inrush in a coal mine. The SVM model, based on a hydrogeochemical method, was constructed for recognising two kinds of headstreams and the H-SVMs model was constructed for recognising multi- headstreams. The SVM method was applied to analyse the conditions of two mixed headstreams and the value of the SVM decision function was investigated as a means of denoting the hydrogeochemical abnormality. The experimental results show that the SVM is based on a strict mathematical theory, has a simple structure and a good overall performance. Moreover the parameter W in the decision function can describe the weights of discrimination indices of the headstream of water inrush. The value of the decision function can denote hydrogeochemistry abnormality, which is significant in the prevention of water inrush in a coal mine. 9 refs., 1 fig., 7 tabs.

  11. Performance of neutron kinetics models for ADS transient analyses

    International Nuclear Information System (INIS)

    Rineiski, A.; Maschek, W.; Rimpault, G.

    2002-01-01

    Within the framework of the SIMMER code development, neutron kinetics models for simulating transients and hypothetical accidents in advanced reactor systems, in particular in Accelerator Driven Systems (ADSs), have been developed at FZK/IKET in cooperation with CE Cadarache. SIMMER is a fluid-dynamics/thermal-hydraulics code, coupled with a structure model and a space-, time- and energy-dependent neutronics module for analyzing transients and accidents. The advanced kinetics models have also been implemented into KIN3D, a module of the VARIANT/TGV code (stand-alone neutron kinetics) for broadening application and for testing and benchmarking. In the paper, a short review of the SIMMER and KIN3D neutron kinetics models is given. Some typical transients related to ADS perturbations are analyzed. The general models of SIMMER and KIN3D are compared with more simple techniques developed in the context of this work to get a better understanding of the specifics of transients in subcritical systems and to estimate the performance of different kinetics options. These comparisons may also help in elaborating new kinetics models and extending existing computation tools for ADS transient analyses. The traditional point-kinetics model may give rather inaccurate transient reaction rate distributions in an ADS even if the material configuration does not change significantly. This inaccuracy is not related to the problem of choosing a 'right' weighting function: the point-kinetics model with any weighting function cannot take into account pronounced flux shape variations related to possible significant changes in the criticality level or to fast beam trips. To improve the accuracy of the point-kinetics option for slow transients, we have introduced a correction factor technique. The related analyses give a better understanding of 'long-timescale' kinetics phenomena in the subcritical domain and help to evaluate the performance of the quasi-static scheme in a particular case. One

  12. Mathematical and Numerical Analyses of Peridynamics for Multiscale Materials Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Du, Qiang [Pennsylvania State Univ., State College, PA (United States)

    2014-11-12

    The rational design of materials, the development of accurate and efficient material simulation algorithms, and the determination of the response of materials to environments and loads occurring in practice all require an understanding of mechanics at disparate spatial and temporal scales. The project addresses mathematical and numerical analyses for material problems for which relevant scales range from those usually treated by molecular dynamics all the way up to those most often treated by classical elasticity. The prevalent approach towards developing a multiscale material model couples two or more well known models, e.g., molecular dynamics and classical elasticity, each of which is useful at a different scale, creating a multiscale multi-model. However, the challenges behind such a coupling are formidable and largely arise because the atomistic and continuum models employ nonlocal and local models of force, respectively. The project focuses on a multiscale analysis of the peridynamics materials model. Peridynamics can be used as a transition between molecular dynamics and classical elasticity so that the difficulties encountered when directly coupling those two models are mitigated. In addition, in some situations, peridynamics can be used all by itself as a material model that accurately and efficiently captures the behavior of materials over a wide range of spatial and temporal scales. Peridynamics is well suited to these purposes because it employs a nonlocal model of force, analogous to that of molecular dynamics; furthermore, at sufficiently large length scales and assuming smooth deformation, peridynamics can be approximated by classical elasticity. The project will extend the emerging mathematical and numerical analysis of peridynamics. One goal is to develop a peridynamics-enabled multiscale multi-model that potentially provides a new and more extensive mathematical basis for coupling classical elasticity and molecular dynamics, thus enabling next

  13. Safety of daily teriparatide treatment: a post hoc analysis of a Phase III study to investigate the possible association of teriparatide treatment with calcium homeostasis in patients with serum procollagen type I N-terminal propeptide elevation

    Directory of Open Access Journals (Sweden)

    Yamamoto T

    2015-07-01

    Full Text Available Takanori Yamamoto,1 Mika Tsujimoto,2 Hideaki Sowa11Medical Science, Lilly Research Laboratories, Medicines Development Unit Japan, 2Asia Pacific Statistical Science-Japan, Science and Regulatory Affairs, LRL MDU-Japan, Eli Lilly Japan K.K, Kobe, Hyogo, JapanObjective: Serum procollagen type I N-terminal propeptide (PINP, a representative marker of bone anabolic action, is strongly related to bone mineral density during teriparatide therapy. This post hoc study analyzed data from a Phase III study (ClinicalTrials.gov identifier NCT00433160 to determine if there was an association between serum PINP elevation and serum calcium concentration or calcium metabolism-related disorders.Research design and methods: Japanese subjects with osteoporosis at high risk of fracture were randomized 2:1 to teriparatide 20 µg/day (n=137 or placebo (n=70 for a 12-month double-blind treatment period, followed by 12 months of open-label teriparatide treatment of all subjects.Main outcome measures: Serum PINP levels were measured at baseline, and after 1, 3, 6, 12, 18, and 24 months of treatment. Serum calcium levels were measured at baseline, and after 1, 3, 6, 9, 12, 15, 18, 21, and 24 months of treatment.Results: Serum PINP increased from baseline to 1 month of treatment and then remained high through 24 months. Twenty-eight of 195 subjects experienced PINP elevations >200 µg/L during teriparatide treatment. Serum calcium concentration in both the teriparatide and placebo groups remained within the normal range. There was no clinically relevant difference in serum calcium concentration between subjects with PINP >200 µg/L and subjects with PINP ≤200 µg/L. Two subjects experienced hypercalcemia and recovered without altering teriparatide treatment. Adverse events possibly related to calcium metabolism disorders included periarthritis calcarea (one subject and chondrocalcinosis pyrophosphate (two subjects, but neither was accompanied with a significant increase

  14. Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial

    Science.gov (United States)

    2011-01-01

    Background This post hoc analysis (trial registration: ClinicalTrials.gov NCT00590577) assessed onset of efficacy and tolerability of acute treatment with once-monthly paliperidone palmitate (PP), a long-acting atypical antipsychotic initiated by day 1 and day 8 injections, in a markedly to severely ill schizophrenia population. Methods Subjects entering the 13-week, double-blind trial were randomized to PP (39, 156, or 234 mg [25, 100, and 150 mg eq of paliperidone, respectively]) or placebo. This subgroup analysis included those with a baseline Clinical Global Impressions-Severity (CGI-S) score indicating marked to severe illness. PP subjects received a 234-mg day 1 injection (deltoid), followed by their assigned dose on day 8 and monthly thereafter (deltoid or gluteal). Thus, data for PP groups were pooled for days 4 and 8. Measures included Positive and Negative Syndrome Scale (PANSS), CGI-S, Personal and Social Performance (PSP), and adverse events (AEs). Analysis of covariance (ANCOVA) and last-observation-carried-forward (LOCF) methodologies, without multiplicity adjustments, were used to assess changes in continuous measures. Onset of efficacy was defined as the first time point a treatment group showed significant PANSS improvement (assessed days 4, 8, 22, 36, 64, and 92) versus placebo, which was maintained through end point. Results A total of 312 subjects met inclusion criterion for this subgroup analysis. After the day 1 injection, mean PANSS total scores improved significantly with PP (all received 234 mg) versus placebo at day 4 (P = 0.012) and day 8 (P = 0.007). After the day 8 injection, a significant PANSS improvement persisted at all subsequent time points in the 234-mg group versus placebo (P < 0.05). PANSS improvements were greater from day 36 through end point in the 156-mg group (P < 0.05) and only at end point in the 39-mg group (P < 0.05). CGI-S and PSP scores improved significantly in the 234-mg and 156-mg PP groups versus placebo at end

  15. Progression of Adjacent-level Degeneration After Lumbar Total Disc Replacement: Results of a Post-hoc Analysis of Patients with Available Radiographs from a Prospective Study with 5-year Follow-up.

    Science.gov (United States)

    Zigler, Jack E; Blumenthal, Scott L; Guyer, Richard D; Ohnmeiss, Donna D; Patel, Leena

    2018-03-21

    Post-hoc analysis of 5-year follow-up data from a randomized, multicenter trial. To investigate the incidence of progression in radiographic adjacent-level degeneration (ΔALD) from preoperative assessment to 5 years after total disc replacement (TDR) and the relationship of these changes with range of motion and clinical adjacent-level disease. A secondary objective was to compare ALD outcomes between TDR and fusion. Fusion is associated with high rates of ALD in symptomatic lumbar disc degeneration. Total disc replacement may reduce this risk. In total, 175 patients with single-level, symptomatic, lumbar disc degeneration who had received activL or ProDisc-L and had a preoperative and 5-year postoperative radiograph available were included. Over 5-year follow-up, ΔALD was defined as an increase in ALD of ≥1 grade and clinical ALD was defined as surgical treatment at the level adjacent to an index TDR. Matching adjusted indirect comparisons were conducted to compare ALD outcomes after TDR (current trial) with those after fusion (published trial). At 5-year follow-up, 9.7% (17/175) of TDR patients had ΔALD at the superior level. In patients with preoperative ALD at the superior level, most (88% [23/26]) showed no radiographic progression over 5 years. The rate of clinical ALD was 2.3% (4/175) and none of these patients had ALD at baseline. For each degree of range of motion (ROM) gained at the TDR level, there was a consistent decrease in the percentage of patients with ΔALD. After matching and adjustment of baseline characteristics, TDR had a significantly lower likelihood of ΔALD than fusion (OR 0.32; 95% CI 0.13, 0.76). The rates of ΔALD and clinical ALD in this TDR population were similar to those previously reported in the literature for TDR at 5-year follow-up. TDR had a significantly lower rate of ΔALD than fusion. 3.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4

  16. History of early abuse as a predictor of treatment response in patients with fibromyalgia: a post-hoc analysis of a 12-week, randomized, double-blind, placebo-controlled trial of paroxetine controlled release.

    Science.gov (United States)

    Pae, Chi-Un; Masand, Prakash S; Marks, David M; Krulewicz, Stan; Han, Changsu; Peindl, Kathleen; Mannelli, Paolo; Patkar, Ashwin A

    2009-01-01

    We conducted a post-hoc analysis to determine whether a history of physical or sexual abuse was associated with response to treatment in a double-blind, randomized, placebo-controlled trial of paroxetine controlled release (CR) in fibromyalgia. A randomized, double-blind, placebo-controlled trial of paroxetine controlled release (CR) (dose 12.5-62.5 mg/day) was conducted in patients with fibromyalgia for 12 weeks. A total of 112 subjects provided complete information on childhood history of abuse that was recorded using the Sexual and Physical Abuse Questionnaire and randomized to treatments. Outcome evaluations in the abuse subgroup were identical to those in the entire sample. Health Status was determined using the 36-Item Short Form Health Survey (SF-36), the Sheehan Disability Scale (SDS), and the Perceived Stress Scale (PSS). Fibromylagia symptom severity was determined using the Fibromyalgia Impact Questionnaire (FIQ) and the Visual Analogue Scale for Pain (VAS). The primary outcome was treatment response defined as > or = 25% reduction in the FIQ-total score. Secondary outcomes include changes in scores on the Clinical Global Impression-Severity and Improvement (CGI-S and CGI-I respectively) and SF-36. The rate of childhood physical and/or sexual abuse was 52.7% (n=59). The baseline characteristics (health status, perceived stress, symptom severity) were not associated with abuse history. In logistic regression, the history of abuse did not predict treatment response as measured by > or = 25% reduction in FIQ-total score (OR = 1.16, 95% CI = 1.18-1.60, P = 0.35), while the drug status (paroxetine CR) was significantly associated with treatment response (OR = 2.51, 95% CI = 1.12-5.64, P = 0.02). Abuse history did not predict CGI-I (P = 0.32) or CGI-S (P = 0.74) improvements during treatment. After 12 weeks of treatment, subjects with sexual abuse history showed significantly lower mean change in health status (SF-36) than those without sexual abuse history (P

  17. Integration efficiency for model reduction in micro-mechanical analyses

    Science.gov (United States)

    van Tuijl, Rody A.; Remmers, Joris J. C.; Geers, Marc G. D.

    2017-11-01

    Micro-structural analyses are an important tool to understand material behavior on a macroscopic scale. The analysis of a microstructure is usually computationally very demanding and there are several reduced order modeling techniques available in literature to limit the computational costs of repetitive analyses of a single representative volume element. These techniques to speed up the integration at the micro-scale can be roughly divided into two classes; methods interpolating the integrand and cubature methods. The empirical interpolation method (high-performance reduced order modeling) and the empirical cubature method are assessed in terms of their accuracy in approximating the full-order result. A micro-structural volume element is therefore considered, subjected to four load-cases, including cyclic and path-dependent loading. The differences in approximating the micro- and macroscopic quantities of interest are highlighted, e.g. micro-fluctuations and stresses. Algorithmic speed-ups for both methods with respect to the full-order micro-structural model are quantified. The pros and cons of both classes are thereby clearly identified.

  18. A 1024 channel analyser of model FH 465

    International Nuclear Information System (INIS)

    Tang Cunxun

    1988-01-01

    The FH 465 is renewed type of the 1024 Channel Analyser of model FH451. Besides simple operation and fine display, featured by the primary one, the core memory is replaced by semiconductor memory; the integration has been improved; employment of 74LS low power consumpted devices widely used in the world has not only greatly decreased the cost, but also can be easily interchanged with Apple-II, Great Wall-0520-CH or IBM-PC/XT Microcomputers. The operating principle, main specifications and test results are described

  19. Multi-state models: metapopulation and life history analyses

    Directory of Open Access Journals (Sweden)

    Arnason, A. N.

    2004-06-01

    Full Text Available Multi–state models are designed to describe populations that move among a fixed set of categorical states. The obvious application is to population interchange among geographic locations such as breeding sites or feeding areas (e.g., Hestbeck et al., 1991; Blums et al., 2003; Cam et al., 2004 but they are increasingly used to address important questions of evolutionary biology and life history strategies (Nichols & Kendall, 1995. In these applications, the states include life history stages such as breeding states. The multi–state models, by permitting estimation of stage–specific survival and transition rates, can help assess trade–offs between life history mechanisms (e.g. Yoccoz et al., 2000. These trade–offs are also important in meta–population analyses where, for example, the pre–and post–breeding rates of transfer among sub–populations can be analysed in terms of target colony distance, density, and other covariates (e.g., Lebreton et al. 2003; Breton et al., in review. Further examples of the use of multi–state models in analysing dispersal and life–history trade–offs can be found in the session on Migration and Dispersal. In this session, we concentrate on applications that did not involve dispersal. These applications fall in two main categories: those that address life history questions using stage categories, and a more technical use of multi–state models to address problems arising from the violation of mark–recapture assumptions leading to the potential for seriously biased predictions or misleading insights from the models. Our plenary paper, by William Kendall (Kendall, 2004, gives an overview of the use of Multi–state Mark–Recapture (MSMR models to address two such violations. The first is the occurrence of unobservable states that can arise, for example, from temporary emigration or by incomplete sampling coverage of a target population. Such states can also occur for life history reasons, such

  20. Comparison between tests and analyses for ground-foundation models

    International Nuclear Information System (INIS)

    Moriyama, Ken-ichi; Hibino, Hirosi; Izumi, Masanori; Kiya, Yukiharu.

    1991-01-01

    The laboratory tests were carried out on two ground models made of silicone rubber (hard and soft ground models) and a foundation model made of aluminum in order to confirm the embedment effects on soil-structure interaction system experimentally. The detail of the procedure and the results of the test are described in the companion paper. Up till now, the analytical studies on the embedment effect on seismic response of buildings have been performed in recent years and the analysis tools have been used in the seismic design procedure of the nuclear power plant facilities. The embedment effects on soil-structure interaction system are confirmed by the simulation analysis and the verification of analysis tools are investigated through the simulation analysis in this paper. The following conclusions can be drawn from comparison between laboratory test results and analysis results. (1) The effects of embedment, such as increase in the impedance functions and the rotational component of foundation input motions, were clarified by the simulation analyses and laboratory tests. (2) The analysis results of axisymmetric FEM showed good agreement with processed test results by means of the transient response to eliminate the reflected waves and the analysis tools were confirmed experimentally. (3) The excavated portion of the soil affected the foundation input motion rather than the impedance function since there was little difference between the impedance functions obtained by wave propagation theory and those obtained by the axisymmetric FEM and the rotational component of the foundation input motions increased significantly. (J.P.N.)

  1. Antiplatelet therapy and the effects of B vitamins in patients with previous stroke or transient ischaemic attack: a post-hoc subanalysis of VITATOPS, a randomised, placebo-controlled trial.

    Science.gov (United States)

    Hankey, Graeme J; Eikelboom, John W; Yi, Qilong; Lees, Kennedy R; Chen, Christopher; Xavier, Denis; Navarro, Jose C; Ranawaka, Udaya K; Uddin, Wasim; Ricci, Stefano; Gommans, John; Schmidt, Reinhold

    2012-06-01

    Previous studies have suggested that any benefits of folic acid-based therapy to lower serum homocysteine in prevention of cardiovascular events might be offset by concomitant use of antiplatelet therapy. We aimed to establish whether there is an interaction between antiplatelet therapy and the effects of folic acid-based homocysteine-lowering therapy on major vascular events in patients with stroke or transient ischaemic attack enrolled in the vitamins to prevent stroke (VITATOPS) trial. In the VITATOPS trial, 8164 patients with recent stroke or transient ischaemic attack were randomly allocated to double-blind treatment with one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B(6), and 500 μg vitamin B(12)) and followed up for a median 3·4 years (IQR 2·0-5·5) for the primary composite outcome of stroke, myocardial infarction, or death from vascular causes. In our post-hoc analysis of the interaction between antiplatelet therapy and the effects of treatment with B vitamins on the primary outcome, we used Cox proportional hazards regression before and after adjusting for imbalances in baseline prognostic factors in participants who were and were not taking antiplatelet drugs at baseline and in participants assigned to receive B vitamins or placebo. We also assessed the interaction in different subgroups of patients and different secondary outcomes. The VITATOPS trial is registered with ClinicalTrials.gov, number NCT00097669, and Current Controlled Trials, number ISRCTN74743444. At baseline, 6609 patients were taking antiplatelet therapy and 1463 were not. Patients not receiving antiplatelet therapy were more likely to be younger, east Asian, and disabled, to have a haemorrhagic stroke or cardioembolic ischaemic stroke, and to have a history of hypertension or atrial fibrillation. They were less likely to be smokers and to have a history of peripheral artery disease, hypercholesterolaemia, diabetes, ischaemic heart disease, and a

  2. A theoretical model for analysing gender bias in medicine

    Directory of Open Access Journals (Sweden)

    Johansson Eva E

    2009-08-01

    Full Text Available Abstract During the last decades research has reported unmotivated differences in the treatment of women and men in various areas of clinical and academic medicine. There is an ongoing discussion on how to avoid such gender bias. We developed a three-step-theoretical model to understand how gender bias in medicine can occur and be understood. In this paper we present the model and discuss its usefulness in the efforts to avoid gender bias. In the model gender bias is analysed in relation to assumptions concerning difference/sameness and equity/inequity between women and men. Our model illustrates that gender bias in medicine can arise from assuming sameness and/or equity between women and men when there are genuine differences to consider in biology and disease, as well as in life conditions and experiences. However, gender bias can also arise from assuming differences when there are none, when and if dichotomous stereotypes about women and men are understood as valid. This conceptual thinking can be useful for discussing and avoiding gender bias in clinical work, medical education, career opportunities and documents such as research programs and health care policies. Too meet the various forms of gender bias, different facts and measures are needed. Knowledge about biological differences between women and men will not reduce bias caused by gendered stereotypes or by unawareness of health problems and discrimination associated with gender inequity. Such bias reflects unawareness of gendered attitudes and will not change by facts only. We suggest consciousness-rising activities and continuous reflections on gender attitudes among students, teachers, researchers and decision-makers.

  3. A theoretical model for analysing gender bias in medicine.

    Science.gov (United States)

    Risberg, Gunilla; Johansson, Eva E; Hamberg, Katarina

    2009-08-03

    During the last decades research has reported unmotivated differences in the treatment of women and men in various areas of clinical and academic medicine. There is an ongoing discussion on how to avoid such gender bias. We developed a three-step-theoretical model to understand how gender bias in medicine can occur and be understood. In this paper we present the model and discuss its usefulness in the efforts to avoid gender bias. In the model gender bias is analysed in relation to assumptions concerning difference/sameness and equity/inequity between women and men. Our model illustrates that gender bias in medicine can arise from assuming sameness and/or equity between women and men when there are genuine differences to consider in biology and disease, as well as in life conditions and experiences. However, gender bias can also arise from assuming differences when there are none, when and if dichotomous stereotypes about women and men are understood as valid. This conceptual thinking can be useful for discussing and avoiding gender bias in clinical work, medical education, career opportunities and documents such as research programs and health care policies. Too meet the various forms of gender bias, different facts and measures are needed. Knowledge about biological differences between women and men will not reduce bias caused by gendered stereotypes or by unawareness of health problems and discrimination associated with gender inequity. Such bias reflects unawareness of gendered attitudes and will not change by facts only. We suggest consciousness-rising activities and continuous reflections on gender attitudes among students, teachers, researchers and decision-makers.

  4. Comparison of two potato simulation models under climate change. I. Model calibration and sensitivity analyses

    NARCIS (Netherlands)

    Wolf, J.

    2002-01-01

    To analyse the effects of climate change on potato growth and production, both a simple growth model, POTATOS, and a comprehensive model, NPOTATO, were applied. Both models were calibrated and tested against results from experiments and variety trials in The Netherlands. The sensitivity of model

  5. Impact of sophisticated fog spray models on accident analyses

    International Nuclear Information System (INIS)

    Roblyer, S.P.; Owzarski, P.C.

    1978-01-01

    The N-Reactor confinement system release dose to the public in a postulated accident is reduced by washing the confinement atmosphere with fog sprays. This allows a low pressure release of confinement atmosphere containing fission products through filters and out an elevated stack. The current accident analysis required revision of the CORRAL code and other codes such as CONTEMPT to properly model the N Reactor confinement into a system of multiple fog-sprayed compartments. In revising these codes, more sophisticated models for the fog sprays and iodine plateout were incorporated to remove some of the conservatism of steam condensing rate, fission product washout and iodine plateout than used in previous studies. The CORRAL code, which was used to describe the transport and deposition of airborne fission products in LWR containment systems for the Rasmussen Study, was revised to describe fog spray removal of molecular iodine (I 2 ) and particulates in multiple compartments for sprays having individual characteristics of on-off times, flow rates, fall heights, and drop sizes in changing containment atmospheres. During postulated accidents, the code determined the fission product removal rates internally rather than from input decontamination factors. A discussion is given of how the calculated plateout and washout rates vary with time throughout the analysis. The results of the accident analyses indicated that more credit could be given to fission product washout and plateout. An important finding was that the release of fission products to the atmosphere and adsorption of fission products on the filters were significantly lower than previous studies had indicated

  6. Mathematical and Numerical Analyses of Peridynamics for Multiscale Materials Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Gunzburger, Max [Florida State Univ., Tallahassee, FL (United States)

    2015-02-17

    We have treated the modeling, analysis, numerical analysis, and algorithmic development for nonlocal models of diffusion and mechanics. Variational formulations were developed and finite element methods were developed based on those formulations for both steady state and time dependent problems. Obstacle problems and optimization problems for the nonlocal models were also treated and connections made with fractional derivative models.

  7. Improved analyses using function datasets and statistical modeling

    Science.gov (United States)

    John S. Hogland; Nathaniel M. Anderson

    2014-01-01

    Raster modeling is an integral component of spatial analysis. However, conventional raster modeling techniques can require a substantial amount of processing time and storage space and have limited statistical functionality and machine learning algorithms. To address this issue, we developed a new modeling framework using C# and ArcObjects and integrated that framework...

  8. An electrodynamic model to analyse field emission thrusters

    Energy Technology Data Exchange (ETDEWEB)

    Cardelli, E.; Del Zoppo, R.; Venturini, G.

    1987-12-01

    After a short description of the working principle of field emission thrusters, a surface emission electrodynamic model, capable of describing the required propulsive effects, is shown. The model, developed according to cylindrical geometry, provides one-dimensional differential relations and, therefore, easy resolution. The characteristic curves obtained are graphed. Comparison with experimental data confirms the validity of the proposed model.

  9. A didactic Input-Output model for territorial ecology analyses

    OpenAIRE

    Garry Mcdonald

    2010-01-01

    This report describes a didactic input-output modelling framework created jointly be the team at REEDS, Universite de Versailles and Dr Garry McDonald, Director, Market Economics Ltd. There are three key outputs associated with this framework: (i) a suite of didactic input-output models developed in Microsoft Excel, (ii) a technical report (this report) which describes the framework and the suite of models1, and (iii) a two week intensive workshop dedicated to the training of REEDS researcher...

  10. Modelling, singular perturbation and bifurcation analyses of bitrophic food chains.

    Science.gov (United States)

    Kooi, B W; Poggiale, J C

    2018-04-20

    Two predator-prey model formulations are studied: for the classical Rosenzweig-MacArthur (RM) model and the Mass Balance (MB) chemostat model. When the growth and loss rate of the predator is much smaller than that of the prey these models are slow-fast systems leading mathematically to singular perturbation problem. In contradiction to the RM-model, the resource for the prey are modelled explicitly in the MB-model but this comes with additional parameters. These parameter values are chosen such that the two models become easy to compare. In both models a transcritical bifurcation, a threshold above which invasion of predator into prey-only system occurs, and the Hopf bifurcation where the interior equilibrium becomes unstable leading to a stable limit cycle. The fast-slow limit cycles are called relaxation oscillations which for increasing differences in time scales leads to the well known degenerated trajectories being concatenations of slow parts of the trajectory and fast parts of the trajectory. In the fast-slow version of the RM-model a canard explosion of the stable limit cycles occurs in the oscillatory region of the parameter space. To our knowledge this type of dynamics has not been observed for the RM-model and not even for more complex ecosystem models. When a bifurcation parameter crosses the Hopf bifurcation point the amplitude of the emerging stable limit cycles increases. However, depending of the perturbation parameter the shape of this limit cycle changes abruptly from one consisting of two concatenated slow and fast episodes with small amplitude of the limit cycle, to a shape with large amplitude of which the shape is similar to the relaxation oscillation, the well known degenerated phase trajectories consisting of four episodes (concatenation of two slow and two fast). The canard explosion point is accurately predicted by using an extended asymptotic expansion technique in the perturbation and bifurcation parameter simultaneously where the small

  11. Analysing the Linux kernel feature model changes using FMDiff

    NARCIS (Netherlands)

    Dintzner, N.J.R.; van Deursen, A.; Pinzger, M.

    Evolving a large scale, highly variable system is a challenging task. For such a system, evolution operations often require to update consistently both their implementation and its feature model. In this context, the evolution of the feature model closely follows the evolution of the system. The

  12. Analysing the Linux kernel feature model changes using FMDiff

    NARCIS (Netherlands)

    Dintzner, N.J.R.; Van Deursen, A.; Pinzger, M.

    2015-01-01

    Evolving a large scale, highly variable system is a challenging task. For such a system, evolution operations often require to update consistently both their implementation and its feature model. In this context, the evolution of the feature model closely follows the evolution of the system. The

  13. Analysing Models as a Knowledge Technology in Transport Planning

    DEFF Research Database (Denmark)

    Gudmundsson, Henrik

    2011-01-01

    critical analytic literature on knowledge utilization and policy influence. A simple scheme based in this literature is drawn up to provide a framework for discussing the interface between urban transport planning and model use. A successful example of model use in Stockholm, Sweden is used as a heuristic......Models belong to a wider family of knowledge technologies, applied in the transport area. Models sometimes share with other such technologies the fate of not being used as intended, or not at all. The result may be ill-conceived plans as well as wasted resources. Frequently, the blame...... device to illuminate how such an analytic scheme may allow patterns of insight about the use, influence and role of models in planning to emerge. The main contribution of the paper is to demonstrate that concepts and terminologies from knowledge use literature can provide interpretations of significance...

  14. Phase I/II trials of {sup 186}Re-HEDP in metastatic castration-resistant prostate cancer: post-hoc analysis of the impact of administered activity and dosimetry on survival

    Energy Technology Data Exchange (ETDEWEB)

    Denis-Bacelar, Ana M.; Chittenden, Sarah J.; Divoli, Antigoni; Flux, Glenn D. [The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, Joint Department of Physics, London (United Kingdom); Dearnaley, David P.; Johnson, Bernadette [The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, Division of Radiotherapy and Imaging, London (United Kingdom); O' Sullivan, Joe M. [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast (United Kingdom); McCready, V.R. [Brighton and Sussex University Hospitals NHS Trust, Department of Nuclear Medicine, Brighton (United Kingdom); Du, Yong [The Royal Marsden Hospital NHS Foundation Trust, Department of Nuclear Medicine and PET/CT, London (United Kingdom)

    2017-04-15

    To investigate the role of patient-specific dosimetry as a predictive marker of survival and as a potential tool for individualised molecular radiotherapy treatment planning of bone metastases from castration-resistant prostate cancer, and to assess whether higher administered levels of activity are associated with a survival benefit. Clinical data from 57 patients who received 2.5-5.1 GBq of {sup 186}Re-HEDP as part of NIH-funded phase I/II clinical trials were analysed. Whole-body and SPECT-based absorbed doses to the whole body and bone lesions were calculated for 22 patients receiving 5 GBq. The patient mean absorbed dose was defined as the mean of all bone lesion-absorbed doses in any given patient. Kaplan-Meier curves, log-rank tests, Cox's proportional hazards model and Pearson's correlation coefficients were used for overall survival (OS) and correlation analyses. A statistically significantly longer OS was associated with administered activities above 3.5 GBq in the 57 patients (20.1 vs 7.1 months, hazard ratio: 0.39, 95 % CI: 0.10-0.58, P = 0.002). A total of 379 bone lesions were identified in 22 patients. The mean of the patient mean absorbed dose was 19 (±6) Gy and the mean of the whole-body absorbed dose was 0.33 (±0.11) Gy for the 22 patients. The patient mean absorbed dose (r = 0.65, P = 0.001) and the whole-body absorbed dose (r = 0.63, P = 0.002) showed a positive correlation with disease volume. Significant differences in OS were observed for the univariate group analyses according to disease volume as measured from SPECT imaging of {sup 186}Re-HEDP (P = 0.03) and patient mean absorbed dose (P = 0.01), whilst only the disease volume remained significant in a multivariable analysis (P = 0.004). This study demonstrated that higher administered activities led to prolonged survival and that for a fixed administered activity, the whole-body and patient mean absorbed doses correlated with the extent of disease, which, in turn, correlated

  15. GOTHIC MODEL OF BWR SECONDARY CONTAINMENT DRAWDOWN ANALYSES

    International Nuclear Information System (INIS)

    Hansen, P.N.

    2004-01-01

    This article introduces a GOTHIC version 7.1 model of the Secondary Containment Reactor Building Post LOCA drawdown analysis for a BWR. GOTHIC is an EPRI sponsored thermal hydraulic code. This analysis is required by the Utility to demonstrate an ability to restore and maintain the Secondary Containment Reactor Building negative pressure condition. The technical and regulatory issues associated with this modeling are presented. The analysis includes the affect of wind, elevation and thermal impacts on pressure conditions. The model includes a multiple volume representation which includes the spent fuel pool. In addition, heat sources and sinks are modeled as one dimensional heat conductors. The leakage into the building is modeled to include both laminar as well as turbulent behavior as established by actual plant test data. The GOTHIC code provides components to model heat exchangers used to provide fuel pool cooling as well as area cooling via air coolers. The results of the evaluation are used to demonstrate the time that the Reactor Building is at a pressure that exceeds external conditions. This time period is established with the GOTHIC model based on the worst case pressure conditions on the building. For this time period the Utility must assume the primary containment leakage goes directly to the environment. Once the building pressure is restored below outside conditions the release to the environment can be credited as a filtered release

  16. Plasma-safety assessment model and safety analyses of ITER

    International Nuclear Information System (INIS)

    Honda, T.; Okazaki, T.; Bartels, H.-H.; Uckan, N.A.; Sugihara, M.; Seki, Y.

    2001-01-01

    A plasma-safety assessment model has been provided on the basis of the plasma physics database of the International Thermonuclear Experimental Reactor (ITER) to analyze events including plasma behavior. The model was implemented in a safety analysis code (SAFALY), which consists of a 0-D dynamic plasma model and a 1-D thermal behavior model of the in-vessel components. Unusual plasma events of ITER, e.g., overfueling, were calculated using the code and plasma burning is found to be self-bounded by operation limits or passively shut down due to impurity ingress from overheated divertor targets. Sudden transition of divertor plasma might lead to failure of the divertor target because of a sharp increase of the heat flux. However, the effects of the aggravating failure can be safely handled by the confinement boundaries. (author)

  17. Modeling theoretical uncertainties in phenomenological analyses for particle physics

    Energy Technology Data Exchange (ETDEWEB)

    Charles, Jerome [CNRS, Aix-Marseille Univ, Universite de Toulon, CPT UMR 7332, Marseille Cedex 9 (France); Descotes-Genon, Sebastien [CNRS, Univ. Paris-Sud, Universite Paris-Saclay, Laboratoire de Physique Theorique (UMR 8627), Orsay Cedex (France); Niess, Valentin [CNRS/IN2P3, UMR 6533, Laboratoire de Physique Corpusculaire, Aubiere Cedex (France); Silva, Luiz Vale [CNRS, Univ. Paris-Sud, Universite Paris-Saclay, Laboratoire de Physique Theorique (UMR 8627), Orsay Cedex (France); Univ. Paris-Sud, CNRS/IN2P3, Universite Paris-Saclay, Groupe de Physique Theorique, Institut de Physique Nucleaire, Orsay Cedex (France); J. Stefan Institute, Jamova 39, P. O. Box 3000, Ljubljana (Slovenia)

    2017-04-15

    The determination of the fundamental parameters of the Standard Model (and its extensions) is often limited by the presence of statistical and theoretical uncertainties. We present several models for the latter uncertainties (random, nuisance, external) in the frequentist framework, and we derive the corresponding p values. In the case of the nuisance approach where theoretical uncertainties are modeled as biases, we highlight the important, but arbitrary, issue of the range of variation chosen for the bias parameters. We introduce the concept of adaptive p value, which is obtained by adjusting the range of variation for the bias according to the significance considered, and which allows us to tackle metrology and exclusion tests with a single and well-defined unified tool, which exhibits interesting frequentist properties. We discuss how the determination of fundamental parameters is impacted by the model chosen for theoretical uncertainties, illustrating several issues with examples from quark flavor physics. (orig.)

  18. Analysing earthquake slip models with the spatial prediction comparison test

    KAUST Repository

    Zhang, L.

    2014-11-10

    Earthquake rupture models inferred from inversions of geophysical and/or geodetic data exhibit remarkable variability due to uncertainties in modelling assumptions, the use of different inversion algorithms, or variations in data selection and data processing. A robust statistical comparison of different rupture models obtained for a single earthquake is needed to quantify the intra-event variability, both for benchmark exercises and for real earthquakes. The same approach may be useful to characterize (dis-)similarities in events that are typically grouped into a common class of events (e.g. moderate-size crustal strike-slip earthquakes or tsunamigenic large subduction earthquakes). For this purpose, we examine the performance of the spatial prediction comparison test (SPCT), a statistical test developed to compare spatial (random) fields by means of a chosen loss function that describes an error relation between a 2-D field (‘model’) and a reference model. We implement and calibrate the SPCT approach for a suite of synthetic 2-D slip distributions, generated as spatial random fields with various characteristics, and then apply the method to results of a benchmark inversion exercise with known solution. We find the SPCT to be sensitive to different spatial correlations lengths, and different heterogeneity levels of the slip distributions. The SPCT approach proves to be a simple and effective tool for ranking the slip models with respect to a reference model.

  19. Compound dislocation models (CDMs) for volcano deformation analyses

    Science.gov (United States)

    Nikkhoo, Mehdi; Walter, Thomas R.; Lundgren, Paul R.; Prats-Iraola, Pau

    2017-02-01

    Volcanic crises are often preceded and accompanied by volcano deformation caused by magmatic and hydrothermal processes. Fast and efficient model identification and parameter estimation techniques for various sources of deformation are crucial for process understanding, volcano hazard assessment and early warning purposes. As a simple model that can be a basis for rapid inversion techniques, we present a compound dislocation model (CDM) that is composed of three mutually orthogonal rectangular dislocations (RDs). We present new RD solutions, which are free of artefact singularities and that also possess full rotational degrees of freedom. The CDM can represent both planar intrusions in the near field and volumetric sources of inflation and deflation in the far field. Therefore, this source model can be applied to shallow dikes and sills, as well as to deep planar and equidimensional sources of any geometry, including oblate, prolate and other triaxial ellipsoidal shapes. In either case the sources may possess any arbitrary orientation in space. After systematically evaluating the CDM, we apply it to the co-eruptive displacements of the 2015 Calbuco eruption observed by the Sentinel-1A satellite in both ascending and descending orbits. The results show that the deformation source is a deflating vertical lens-shaped source at an approximate depth of 8 km centred beneath Calbuco volcano. The parameters of the optimal source model clearly show that it is significantly different from an isotropic point source or a single dislocation model. The Calbuco example reflects the convenience of using the CDM for a rapid interpretation of deformation data.

  20. Model analyses for sustainable energy supply under CO2 restrictions

    International Nuclear Information System (INIS)

    Matsuhashi, Ryuji; Ishitani, Hisashi.

    1995-01-01

    This paper aims at clarifying key points for realizing sustainable energy supply under restrictions on CO 2 emissions. For this purpose, possibility of solar breeding system is investigated as a key technology for the sustainable energy supply. The authors describe their mathematical model simulating global energy supply and demand in ultra-long term. Depletion of non-renewable resources and constraints on CO 2 emissions are taken into consideration in the model. Computed results have shown that present energy system based on non-renewable resources shifts to a system based on renewable resources in the ultra-long term with appropriate incentives

  1. Vegetable parenting practices scale: Item response modeling analyses

    Science.gov (United States)

    Our objective was to evaluate the psychometric properties of a vegetable parenting practices scale using multidimensional polytomous item response modeling which enables assessing item fit to latent variables and the distributional characteristics of the items in comparison to the respondents. We al...

  2. A Hamiltonian approach to model and analyse networks of ...

    Indian Academy of Sciences (India)

    2015-09-24

    Sep 24, 2015 ... Over the past twelve years, ideas and methods from nonlinear dynamics system theory, in particular, group theoretical methods in bifurcation theory, have been ... In this manuscript, a review of the most recent work on modelling and analysis of two seemingly different systems, an array of gyroscopes and an ...

  3. Gene Discovery and Functional Analyses in the Model Plant Arabidopsis

    DEFF Research Database (Denmark)

    Feng, Cai-ping; Mundy, J.

    2006-01-01

    The present mini-review describes newer methods and strategies, including transposon and T-DNA insertions, TILLING, Deleteagene, and RNA interference, to functionally analyze genes of interest in the model plant Arabidopsis. The relative advantages and disadvantages of the systems are also...

  4. Capacity allocation in wireless communication networks - models and analyses

    NARCIS (Netherlands)

    Litjens, Remco

    2003-01-01

    This monograph has concentrated on capacity allocation in cellular and Wireless Local Area Networks, primarily with a network operator’s perspective. In the introduc- tory chapter, a reference model has been proposed for the extensive suite of capacity allocation mechanisms that can be applied at

  5. Theoretical modeling and experimental analyses of laminated wood composite poles

    Science.gov (United States)

    Cheng Piao; Todd F. Shupe; Vijaya Gopu; Chung Y. Hse

    2005-01-01

    Wood laminated composite poles consist of trapezoid-shaped wood strips bonded with synthetic resin. The thick-walled hollow poles had adequate strength and stiffness properties and were a promising substitute for solid wood poles. It was necessary to develop theoretical models to facilitate the manufacture and future installation and maintenance of this novel...

  6. Complex accident scenarios modelled and analysed by Stochastic Petri Nets

    International Nuclear Information System (INIS)

    Nývlt, Ondřej; Haugen, Stein; Ferkl, Lukáš

    2015-01-01

    This paper is focused on the usage of Petri nets for an effective modelling and simulation of complicated accident scenarios, where an order of events can vary and some events may occur anywhere in an event chain. These cases are hardly manageable by traditional methods as event trees – e.g. one pivotal event must be often inserted several times into one branch of the tree. Our approach is based on Stochastic Petri Nets with Predicates and Assertions and on an idea, which comes from the area of Programmable Logic Controllers: an accidental scenario is described as a net of interconnected blocks, which represent parts of the scenario. So the scenario is firstly divided into parts, which are then modelled by Petri nets. Every block can be easily interconnected with other blocks by input/output variables to create complex ones. In the presented approach, every event or a part of a scenario is modelled only once, independently on a number of its occurrences in the scenario. The final model is much more transparent then the corresponding event tree. The method is shown in two case studies, where the advanced one contains a dynamic behavior. - Highlights: • Event & Fault trees have problems with scenarios where an order of events can vary. • Paper presents a method for modelling and analysis of dynamic accident scenarios. • The presented method is based on Petri nets. • The proposed method solves mentioned problems of traditional approaches. • The method is shown in two case studies: simple and advanced (with dynamic behavior)

  7. A Formal Model to Analyse the Firewall Configuration Errors

    Directory of Open Access Journals (Sweden)

    T. T. Myo

    2015-01-01

    Full Text Available The firewall is widely known as a brandmauer (security-edge gateway. To provide the demanded security, the firewall has to be appropriately adjusted, i.e. be configured. Unfortunately, when configuring, even the skilled administrators may make mistakes, which result in decreasing level of a network security and network infiltration undesirable packages.The network can be exposed to various threats and attacks. One of the mechanisms used to ensure network security is the firewall.The firewall is a network component, which, using a security policy, controls packages passing through the borders of a secured network. The security policy represents the set of rules.Package filters work in the mode without inspection of a state: they investigate packages as the independent objects. Rules take the following form: (condition, action. The firewall analyses the entering traffic, based on the IP address of the sender and recipient, the port number of the sender and recipient, and the used protocol. When the package meets rule conditions, the action specified in the rule is carried out. It can be: allow, deny.The aim of this article is to develop tools to analyse a firewall configuration with inspection of states. The input data are the file with the set of rules. It is required to submit the analysis of a security policy in an informative graphic form as well as to reveal discrepancy available in rules. The article presents a security policy visualization algorithm and a program, which shows how the firewall rules act on all possible packages. To represent a result in an intelligible form a concept of the equivalence region is introduced.Our task is the program to display results of rules action on the packages in a convenient graphic form as well as to reveal contradictions between the rules. One of problems is the large number of measurements. As it was noted above, the following parameters are specified in the rule: Source IP address, appointment IP

  8. Analyses of homologous rotavirus infection in the mouse model.

    Science.gov (United States)

    Burns, J W; Krishnaney, A A; Vo, P T; Rouse, R V; Anderson, L J; Greenberg, H B

    1995-02-20

    The group A rotaviruses are significant human and veterinary pathogens in terms of morbidity, mortality, and economic loss. Despite its importance, an effective vaccine remains elusive due at least in part to our incomplete understanding of rotavirus immunity and protection. Both large and small animal model systems have been established to address these issues. One significant drawback of these models is the lack of well-characterized wild-type homologous viruses and their cell culture-adapted variants. We have characterized four strains of murine rotaviruses, EC, EHP, EL, and EW, in the infant and adult mouse model using wild-type isolates and cell culture-adapted variants of each strain. Wild-type murine rotaviruses appear to be equally infectious in infant and adult mice in terms of the intensity and duration of virus shedding following primary infection. Spread of infection to naive cagemates is seen in both age groups. Clearance of shedding following primary infection appears to correlate with the development of virus-specific intestinal IgA. Protective immunity is developed in both infant and adult mice following oral infection as demonstrated by a lack of shedding after subsequent wild-type virus challenge. Cell culture-adapted murine rotaviruses appear to be highly attenuated when administered to naive animals and do not spread efficiently to nonimmune cagemates. The availability of these wild-type and cell culture-adapted virus preparations should allow a more systematic evaluation of rotavirus infection and immunity. Furthermore, future vaccine strategies can be evaluated in the mouse model using several fully virulent homologous viruses for challenge.

  9. Analysing the Competency of Mathematical Modelling in Physics

    OpenAIRE

    Redish, Edward F.

    2016-01-01

    A primary goal of physics is to create mathematical models that allow both predictions and explanations of physical phenomena. We weave maths extensively into our physics instruction beginning in high school, and the level and complexity of the maths we draw on grows as our students progress through a physics curriculum. Despite much research on the learning of both physics and math, the problem of how to successfully teach most of our students to use maths in physics effectively remains unso...

  10. A workflow model to analyse pediatric emergency overcrowding.

    Science.gov (United States)

    Zgaya, Hayfa; Ajmi, Ines; Gammoudi, Lotfi; Hammadi, Slim; Martinot, Alain; Beuscart, Régis; Renard, Jean-Marie

    2014-01-01

    The greatest source of delay in patient flow is the waiting time from the health care request, and especially the bed request to exit from the Pediatric Emergency Department (PED) for hospital admission. It represents 70% of the time that these patients occupied in the PED waiting rooms. Our objective in this study is to identify tension indicators and bottlenecks that contribute to overcrowding. Patient flow mapping through the PED was carried out in a continuous 2 years period from January 2011 to December 2012. Our method is to use the collected real data, basing on accurate visits made in the PED of the Regional University Hospital Center (CHRU) of Lille (France), in order to construct an accurate and complete representation of the PED processes. The result of this representation is a Workflow model of the patient journey in the PED representing most faithfully possible the reality of the PED of CHRU of Lille. This model allowed us to identify sources of delay in patient flow and aspects of the PED activity that could be improved. It must be enough retailed to produce an analysis allowing to identify the dysfunctions of the PED and also to propose and to estimate prevention indicators of tensions. Our survey is integrated into the French National Research Agency project, titled: "Hospital: optimization, simulation and avoidance of strain" (ANR HOST).

  11. Intensive multifactorial treatment modifies the effect of family history of diabetes on glycaemic control in people with Type 2 diabetes: a post hoc analysis of the ADDITION-Denmark randomized controlled trial.

    Science.gov (United States)

    Eliraqi, G M; Vistisen, D; Lauritzen, T; Sandbaek, A; Jørgensen, M E; Faerch, K

    2015-08-01

    To investigate whether intensive multifactorial treatment can reverse the predisposed adverse phenotype of people with Type 2 diabetes who have a family history of diabetes. Data from the randomized controlled trial ADDITION-Denmark were used. A total of 1441 newly diagnosed patients with diabetes (598 with family history of diabetes) were randomized to intensive treatment or routine care. Family history of diabetes was defined as having one parent and/or sibling with diabetes. Linear mixed-effects models were used to assess the changes in risk factors (BMI, waist circumference, blood pressure, lipids and HbA1c ) after 5 years of follow-up in participants with and without a family history of diabetes. An interaction term between family history of diabetes and treatment group was included in the models to test for a modifying effect of the intervention. All analyses were adjusted for age, sex, baseline value of the risk factor and general practice (random effect). At baseline, participants with a family history of diabetes were younger and had a 1.1 mmol/mol (0.1%) higher HbA1c concentration at the time of diagnosis than those without a family history of diabetes. Family history of diabetes modified the effect of the intervention on changes in HbA1c levels. In the group receiving routine care, participants with a family history of diabetes experienced an improvement in HbA1c concentration that was 3.3 mmol/mol (0.3%) lower than the improvement found in those without a family history of diabetes after 5 years of follow-up. In the intensive treatment group, however, there was no difference in HbA1c concentrations between participants with and without a family history of diabetes after 5 years of treatment. Intensive treatment of diabetes may partly remove the adverse effects of family history of diabetes on glycaemic control. The effect of this improvement on long-term diabetic complications warrants further investigation. © 2015 The Authors. Diabetic Medicine

  12. Genomic, Biochemical, and Modeling Analyses of Asparagine Synthetases from Wheat

    Directory of Open Access Journals (Sweden)

    Hongwei Xu

    2018-01-01

    Full Text Available Asparagine synthetase activity in cereals has become an important issue with the discovery that free asparagine concentration determines the potential for formation of acrylamide, a probably carcinogenic processing contaminant, in baked cereal products. Asparagine synthetase catalyses the ATP-dependent transfer of the amino group of glutamine to a molecule of aspartate to generate glutamate and asparagine. Here, asparagine synthetase-encoding polymerase chain reaction (PCR products were amplified from wheat (Triticum aestivum cv. Spark cDNA. The encoded proteins were assigned the names TaASN1, TaASN2, and TaASN3 on the basis of comparisons with other wheat and cereal asparagine synthetases. Although very similar to each other they differed slightly in size, with molecular masses of 65.49, 65.06, and 66.24 kDa, respectively. Chromosomal positions and scaffold references were established for TaASN1, TaASN2, and TaASN3, and a fourth, more recently identified gene, TaASN4. TaASN1, TaASN2, and TaASN4 were all found to be single copy genes, located on chromosomes 5, 3, and 4, respectively, of each genome (A, B, and D, although variety Chinese Spring lacked a TaASN2 gene in the B genome. Two copies of TaASN3 were found on chromosome 1 of each genome, and these were given the names TaASN3.1 and TaASN3.2. The TaASN1, TaASN2, and TaASN3 PCR products were heterologously expressed in Escherichia coli (TaASN4 was not investigated in this part of the study. Western blot analysis identified two monoclonal antibodies that recognized the three proteins, but did not distinguish between them, despite being raised to epitopes SKKPRMIEVAAP and GGSNKPGVMNTV in the variable C-terminal regions of the proteins. The heterologously expressed TaASN1 and TaASN2 proteins were found to be active asparagine synthetases, producing asparagine and glutamate from glutamine and aspartate. The asparagine synthetase reaction was modeled using SNOOPY® software and information from

  13. Longitudinal Data Analyses Using Linear Mixed Models in SPSS: Concepts, Procedures and Illustrations

    OpenAIRE

    Shek, Daniel T. L.; Ma, Cecilia M. S.

    2011-01-01

    Although different methods are available for the analyses of longitudinal data, analyses based on generalized linear models (GLM) are criticized as violating the assumption of independence of observations. Alternatively, linear mixed models (LMM) are commonly used to understand changes in human behavior over time. In this paper, the basic concepts surrounding LMM (or hierarchical linear models) are outlined. Although SPSS is a statistical analyses package commonly used by researchers, documen...

  14. Using System Dynamic Model and Neural Network Model to Analyse Water Scarcity in Sudan

    Science.gov (United States)

    Li, Y.; Tang, C.; Xu, L.; Ye, S.

    2017-07-01

    Many parts of the world are facing the problem of Water Scarcity. Analysing Water Scarcity quantitatively is an important step to solve the problem. Water scarcity in a region is gauged by WSI (water scarcity index), which incorporate water supply and water demand. To get the WSI, Neural Network Model and SDM (System Dynamic Model) that depict how environmental and social factors affect water supply and demand are developed to depict how environmental and social factors affect water supply and demand. The uneven distribution of water resource and water demand across a region leads to an uneven distribution of WSI within this region. To predict WSI for the future, logistic model, Grey Prediction, and statistics are applied in predicting variables. Sudan suffers from severe water scarcity problem with WSI of 1 in 2014, water resource unevenly distributed. According to the result of modified model, after the intervention, Sudan’s water situation will become better.

  15. Numerical analyses of interaction of steel-fibre reinforced concrete slab model with subsoil

    Directory of Open Access Journals (Sweden)

    Jana Labudkova

    2017-01-01

    Full Text Available Numerical analyses of contact task were made with FEM. The test sample for the task was a steel-fibre reinforced concrete foundation slab model loaded during experimental loading test. Application of inhomogeneous half-space was used in FEM analyses. Results of FEM analyses were also confronted with the values measured during the experiment.

  16. Facet personality and surface-level diversity as team mental model antecedents: implications for implicit coordination.

    Science.gov (United States)

    Fisher, David M; Bell, Suzanne T; Dierdorff, Erich C; Belohlav, James A

    2012-07-01

    Team mental models (TMMs) have received much attention as important drivers of effective team processes and performance. Less is known about the factors that give rise to these shared cognitive structures. We examined potential antecedents of TMMs, with a specific focus on team composition variables, including various facets of personality and surface-level diversity. Further, we examined implicit coordination as an important outcome of TMMs. Results suggest that team composition in terms of the cooperation facet of agreeableness and racial diversity were significantly related to team-focused TMM similarity. TMM similarity was also positively predictive of implicit coordination, which mediated the relationship between TMM similarity and team performance. Post hoc analyses revealed a significant interaction between the trust facet of agreeableness and racial diversity in predicting TMM similarity. Results are discussed in terms of facilitating the emergence of TMMs and corresponding implications for team-related human resource practices. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  17. Analyses of tumor-suppressor genes in germline mouse models of cancer.

    Science.gov (United States)

    Wang, Jingqiang; Abate-Shen, Cory

    2014-08-01

    Tumor-suppressor genes are critical regulators of growth and functioning of cells, whose loss of function contributes to tumorigenesis. Accordingly, analyses of the consequences of their loss of function in genetically engineered mouse models have provided important insights into mechanisms of human cancer, as well as resources for preclinical analyses and biomarker discovery. Nowadays, most investigations of genetically engineered mouse models of tumor-suppressor function use conditional or inducible alleles, which enable analyses in specific cancer (tissue) types and overcome the consequences of embryonic lethality of germline loss of function of essential tumor-suppressor genes. However, historically, analyses of genetically engineered mouse models based on germline loss of function of tumor-suppressor genes were very important as these early studies established the principle that loss of function could be studied in mouse cancer models and also enabled analyses of these essential genes in an organismal context. Although the cancer phenotypes of these early germline models did not always recapitulate the expected phenotypes in human cancer, these models provided the essential foundation for the more sophisticated conditional and inducible models that are currently in use. Here, we describe these "first-generation" germline models of loss of function models, focusing on the important lessons learned from their analyses, which helped in the design and analyses of "next-generation" genetically engineered mouse models. © 2014 Cold Spring Harbor Laboratory Press.

  18. Provisional safety analyses for SGT stage 2 -- Models, codes and general modelling approach

    International Nuclear Information System (INIS)

    2014-12-01

    In the framework of the provisional safety analyses for Stage 2 of the Sectoral Plan for Deep Geological Repositories (SGT), deterministic modelling of radionuclide release from the barrier system along the groundwater pathway during the post-closure period of a deep geological repository is carried out. The calculated radionuclide release rates are interpreted as annual effective dose for an individual and assessed against the regulatory protection criterion 1 of 0.1 mSv per year. These steps are referred to as dose calculations. Furthermore, from the results of the dose calculations so-called characteristic dose intervals are determined, which provide input to the safety-related comparison of the geological siting regions in SGT Stage 2. Finally, the results of the dose calculations are also used to illustrate and to evaluate the post-closure performance of the barrier systems under consideration. The principal objective of this report is to describe comprehensively the technical aspects of the dose calculations. These aspects comprise: · the generic conceptual models of radionuclide release from the solid waste forms, of radionuclide transport through the system of engineered and geological barriers, of radionuclide transfer in the biosphere, as well as of the potential radiation exposure of the population, · the mathematical models for the explicitly considered release and transport processes, as well as for the radiation exposure pathways that are included, · the implementation of the mathematical models in numerical codes, including an overview of these codes and the most relevant verification steps, · the general modelling approach when using the codes, in particular the generic assumptions needed to model the near field and the geosphere, along with some numerical details, · a description of the work flow related to the execution of the calculations and of the software tools that are used to facilitate the modelling process, and · an overview of the

  19. Longitudinal data analyses using linear mixed models in SPSS: concepts, procedures and illustrations.

    Science.gov (United States)

    Shek, Daniel T L; Ma, Cecilia M S

    2011-01-05

    Although different methods are available for the analyses of longitudinal data, analyses based on generalized linear models (GLM) are criticized as violating the assumption of independence of observations. Alternatively, linear mixed models (LMM) are commonly used to understand changes in human behavior over time. In this paper, the basic concepts surrounding LMM (or hierarchical linear models) are outlined. Although SPSS is a statistical analyses package commonly used by researchers, documentation on LMM procedures in SPSS is not thorough or user friendly. With reference to this limitation, the related procedures for performing analyses based on LMM in SPSS are described. To demonstrate the application of LMM analyses in SPSS, findings based on six waves of data collected in the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in Hong Kong are presented.

  20. Lower vegetable protein intake and higher dietary acid load associated with lower carbohydrate intake are risk factors for metabolic syndrome in patients with type 2 diabetes: Post-hoc analysis of a cross-sectional study.

    Science.gov (United States)

    Iwase, Hiroya; Tanaka, Muhei; Kobayashi, Yukiko; Wada, Sayori; Kuwahata, Masashi; Kido, Yasuhiro; Hamaguchi, Masahide; Asano, Mai; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto; Fukui, Michiaki

    2015-07-01

    A low-carbohydrate diet based on animal sources is associated with higher all-cause mortality, whereas a vegetable-based low-carbohydrate diet is associated with lower cardiovascular disease mortality. It has been suggested that acid/base imbalance might play an important role in some cardiometabolic abnormalities. The aims of the present study were to evaluate whether carbohydrate intake is associated with quality of dietary protein and acid load, and whether these are related to metabolic syndrome in patients with type 2 diabetes. The present cross-sectional study involved 149 patients with type 2 diabetes. Dietary intake was assessed using a validated self-administered diet history questionnaire. Dietary acid load was assessed by potential renal acid load and net endogenous acid production. Mean daily total energy intake, carbohydrate intake, animal protein intake and vegetable protein intake were 1821.5 kcal, 248.8 g, 36.1 g and 31.1 g, respectively. Carbohydrate energy/total energy was negatively correlated with animal protein energy/total energy, potential renal acid load or net endogenous acid production score, and was positively correlated with vegetable protein energy/total energy. Logistic regression analyses showed that the subgroup of patients with a lower vegetable protein energy/total energy or higher potential renal acid load or net endogenous acid production score was significantly associated with the prevalence of metabolic syndrome. The present study showed that carbohydrate intake was associated with the quality of dietary protein and dietary acid load. Furthermore, decreased vegetable protein intake and increased dietary acid load were associated with the prevalence of metabolic syndrome.

  1. French adults' cognitive performance after daily supplementation with antioxidant vitamins and minerals at nutritional doses: a post hoc analysis of the Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) trial.

    Science.gov (United States)

    Kesse-Guyot, Emmanuelle; Fezeu, Léopold; Jeandel, Claude; Ferry, Monique; Andreeva, Valentina; Amieva, Hélène; Hercberg, Serge; Galan, Pilar

    2011-09-01

    Antioxidant properties of some vitamins and trace elements may help to prevent cognitive decline. The aim of the current study was to estimate the long-term effects of antioxidant nutrient supplementation on the cognitive performance of participants in the Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) study 6 y after the end of the trial. This study included 4447 French participants aged 45-60 y who were enrolled in the SU.VI.MAX study (1994-2002), which was a double-blind, placebo-controlled, randomized trial. From 1994 to 2002, participants received daily vitamin C (120 mg), β-carotene (6 mg), vitamin E (30 mg), selenium (100 μg), and zinc (20 mg) in combination or as a placebo. In 2007-2009, the cognitive performance of participants was assessed with 4 neuropsychological tests (6 tasks). Principal components analysis (PCA) was performed to identify cognitive-function summary scores. Associations between antioxidant supplementation and cognitive functions, in the full sample and by subgroups, were estimated through ANOVA and expressed as mean differences and 95% CIs. Subgroup analyses were performed according to baseline characteristics. Subjects receiving active antioxidant supplementation had better episodic memory scores (mean difference: 0.61; 95% CI: 0.02, 1.20). PCA indicated 2 factors that were interpreted as showing verbal memory and executive functioning. Verbal memory was improved by antioxidant supplementation only in subjects who were nonsmokers or who had low serum vitamin C concentrations at baseline. This study supports the role of an adequate antioxidant nutrient status in the preservation of verbal memory under certain conditions. This trial was registered at clinicaltrials.gov as NCT00272428.

  2. Quality measure attainment with dapagliflozin plus metformin extended-release as initial combination therapy in patients with type 2 diabetes: a post hoc pooled analysis of two clinical studies

    Directory of Open Access Journals (Sweden)

    Bell KF

    2016-10-01

    Full Text Available Kelly F Bell, Arie Katz, John J Sheehan AstraZeneca, Wilmington, DE, USA Background: The use of quality measures attempts to improve safety and health outcomes and to reduce costs. In two Phase III trials in treatment-naive patients with type 2 diabetes, dapagliflozin 5 or 10 mg/d as initial combination therapy with metformin extended-release (XR significantly reduced glycated hemoglobin (A1C from baseline to 24 weeks and allowed higher proportions of patients to achieve A1C <7% vs dapagliflozin or metformin monotherapy. Objective: A pooled analysis of data from these two studies assessed the effect of dapagliflozin 5 or 10 mg/d plus metformin XR (combination therapy compared with placebo plus metformin XR (metformin monotherapy on diabetes quality measures. Quality measures include laboratory measures of A1C and low-density lipoprotein cholesterol (LDL-C as well as vital status measures of blood pressure (BP and body mass index (BMI. The proportion of patients achieving A1C, BP, and LDL-C individual and composite measures was assessed, as was the proportion with baseline BMI ≥25 kg/m2 who lost ≥4.5 kg. Subgroup analyses by baseline BMI were also performed. Results: A total of 194 and 211 patients were treated with dapagliflozin 5- or 10-mg/d combination therapy, respectively, and 409 with metformin monotherapy. Significantly higher proportions of patients achieved A1C ≤6.5%, <7%, or <8% with combination therapy vs metformin monotherapy (P<0.02. Significantly higher proportions of patients achieved BP <140/90 mmHg (P<0.02 for each dapagliflozin dose and BP <130/80 mmHg (P<0.02 with dapagliflozin 5 mg/d only with combination therapy vs metformin monotherapy. Similar proportions (29%–33% of patients had LDL-C <100 mg/dL across treatment groups. A higher proportion of patients with baseline BMI ≥25 kg/m2 lost ≥4.5 kg with combination therapy. Combination therapy had a more robust effect on patients with higher baseline BMI. Conclusion

  3. Effect of glatiramer acetate three-times weekly on the evolution of new, active multiple sclerosis lesions into T1-hypointense "black holes": a post hoc magnetic resonance imaging analysis.

    Science.gov (United States)

    Zivadinov, Robert; Dwyer, Michael; Barkay, Hadas; Steinerman, Joshua R; Knappertz, Volker; Khan, Omar

    2015-03-01

    Conversion of active lesions to black holes has been associated with disability progression in subjects with relapsing-remitting multiple sclerosis (RRMS) and represents a complementary approach to evaluating clinical efficacy. The objective of this study was to assess the conversion of new active magnetic resonance imaging (MRI) lesions, identified 6 months after initiating treatment with glatiramer acetate 40 mg/mL three-times weekly (GA40) or placebo, to T1-hypointense black holes in subjects with RRMS. Subjects received GA40 (n = 943) or placebo (n = 461) for 12 months. MRI was obtained at baseline and Months 6 and 12. New lesions were defined as either gadolinium-enhancing T1 or new T2 lesions at Month 6 that were not present at baseline. The adjusted mean numbers of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a negative binomial model; adjusted proportions of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a logistic regression model. Of 1,292 subjects with complete MRI data, 433 (50.3 %) GA-treated and 247 (57.2 %) placebo-treated subjects developed new lesions at Month 6. Compared with placebo, GA40 significantly reduced the mean number (0.31 versus 0.45; P = .0258) and proportion (15.8 versus 19.6 %; P = .006) of new lesions converting to black holes. GA significantly reduced conversion of new active lesions to black holes, highlighting the ability of GA40 to prevent tissue damage in RRMS.

  4. Relationship of the adherence to the Mediterranean diet with health-related quality of life and treatment satisfaction in patients with type 2 diabetes mellitus: a post-hoc analysis of a cross-sectional study.

    Science.gov (United States)

    Alcubierre, Nuria; Martinez-Alonso, Montserrat; Valls, Joan; Rubinat, Esther; Traveset, Alicia; Hernández, Marta; Martínez-González, Maria Dolores; Granado-Casas, Minerva; Jurjo, Carmen; Vioque, Jesus; Navarrete-Muñoz, Eva Maria; Mauricio, Didac

    2016-05-04

    The main aim of this study was to assess the association between adherence to the traditional Mediterranean diet (MedDiet) and health-related quality of life (HRQoL) and treatment satisfaction in patients with type 2 diabetes mellitus (T2DM). This cross-sectional study included 294 patients with T2DM (146 with diabetic retinopathy and 148 without retinopathy). HRQoL and treatment satisfaction were assessed with the Audit Diabetes-Dependent Quality of Life and Diabetes Treatment Satisfaction Questionnaires, respectively. Adherence to the MedDiet was evaluated with the relative Mediterranean Diet Score (rMED). The rMED was added to multivariate linear regression models to assess its relative contribution as a quantitative as well as a qualitative variable after recoding to maximize each of the model's coefficients of determination to explain quality of life as well as treatment satisfaction dimensions. The adherence to the Mediterranean diet showed no significant association with the overall quality of life score. However, rMED was associated with some HRQoL dimensions: travels, self-confidence and freedom to eat and drink (p = 0.020, p = 0.015, p = 0.037 and p = 0.015, respectively). Concerning treatment satisfaction, rMED was positively associated with its overall score (p = 0.046), and especially with the understanding of diabetes (p = 0.0004) and treatment recommendation (p = 0.036), as well as with the perceived frequency of hyperglycaemias (p = 0.039). Adherence to the Mediterranean diet was associated with greater treatment satisfaction in patients with T2DM. Although we found no association with overall HRQoL, adherence to this dietary pattern was associated with some quality of life dimensions.

  5. Relationship between patient-reported outcomes and clinical outcomes in metastatic castration-resistant prostate cancer: post hoc analysis of COU-AA-301 and COU-AA-302.

    Science.gov (United States)

    Cella, D; Traina, S; Li, T; Johnson, K; Ho, K F; Molina, A; Shore, N D

    2018-02-01

    Patient-reported outcomes (PROs) are used to assess benefit-risk in drug development. The relationship between PROs and clinical outcomes is not well understood. We aim to elucidate the relationships between changes in PRO measures and clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC). We investigated relationships between changes in self-reported fatigue, pain, functional well-being (FWB), physical well-being (PWB) and prostate cancer-specific symptoms with overall survival (OS) and radiographic progression-free survival (rPFS) after 6 and 12 months of treatment in COU-AA-301 (N = 1195) or COU-AA-302 (N = 1088). Eligible COU-AA-301 patients had progressed after docetaxel and had Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2. Eligible COU-AA-302 patients had no prior chemotherapy and ECOG PS 0 or 1. Patients were treated with abiraterone acetate (1000 mg/day) plus prednisone (10 mg/day) or prednisone alone daily. Association between self-reported fatigue, pain and functional status, and OS and/or rPFS, using pooled data regardless of treatment, was assessed. Cox proportional hazard regression modeled time to death or radiographic progression. In COU-AA-301 patients, PRO improvements were associated with longer OS and longer time to radiographic progression versus worsening or stable PROs (P AA-302 patients, worsening PROs were associated with higher likelihood of radiographic progression (P ≤ 0.025) compared with improved or stable PROs. In multivariate models, worsening PWB remained associated with worse rPFS. The 12-month analysis confirmed the 6-month results. PROs are significantly associated with clinically relevant time-to-event efficacy outcomes in clinical trials and may complement and help predict traditional clinical practice methods for monitoring patients for disease progression. © The Author 2017. Published by Oxford University Press on behalf of the European Society for

  6. An improved lake model for climate simulations: Model structure, evaluation, and sensitivity analyses in CESM1

    Directory of Open Access Journals (Sweden)

    Zachary Subin

    2012-02-01

    Full Text Available Lakes can influence regional climate, yet most general circulation models have, at best, simple and largely untested representations of lakes. We developed the Lake, Ice, Snow, and Sediment Simulator(LISSS for inclusion in the land-surface component (CLM4 of an earth system model (CESM1. The existing CLM4 lake modelperformed poorly at all sites tested; for temperate lakes, summer surface water temperature predictions were 10–25uC lower than observations. CLM4-LISSS modifies the existing model by including (1 a treatment of snow; (2 freezing, melting, and ice physics; (3 a sediment thermal submodel; (4 spatially variable prescribed lakedepth; (5 improved parameterizations of lake surface properties; (6 increased mixing under ice and in deep lakes; and (7 correction of previous errors. We evaluated the lake model predictions of water temperature and surface fluxes at three small temperate and boreal lakes where extensive observational data was available. We alsoevaluated the predicted water temperature and/or ice and snow thicknesses for ten other lakes where less comprehensive forcing observations were available. CLM4-LISSS performed very well compared to observations for shallow to medium-depth small lakes. For large, deep lakes, the under-prediction of mixing was improved by increasing the lake eddy diffusivity by a factor of 10, consistent with previouspublished analyses. Surface temperature and surface flux predictions were improved when the aerodynamic roughness lengths were calculated as a function of friction velocity, rather than using a constant value of 1 mm or greater. We evaluated the sensitivity of surface energy fluxes to modeled lake processes and parameters. Largechanges in monthly-averaged surface fluxes (up to 30 W m22 were found when excluding snow insulation or phase change physics and when varying the opacity, depth, albedo of melting lake ice, and mixing strength across ranges commonly found in real lakes. Typical

  7. Economic evaluation among Chinese patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus and treated with linezolid or vancomycin: a secondary, post-hoc analysis based on a Phase 4 clinical trial study.

    Science.gov (United States)

    Wan, Yin; Li, Qiang; Chen, Yixi; Haider, Seema; Liu, Sizhu; Gao, Xin

    2016-01-01

    To assess cost-effectiveness of linezolid vs vancomycin in treating nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA-NP) in China and the impact of renal failure on healthcare resource utilization (HCRU) and costs. Cost-effectiveness analysis was conducted based on data from the ZEPHyR trial, with efficacy measured by treatment success and costs calculated from HCRU. Confidence intervals (CI) for cost, efficacy and incremental cost-effectiveness ratios (ICER) were calculated by non-parametric bootstrap. Chi-square test was used for renal failure rate and t-test for HCRU/cost comparisons. Impact of renal failure was assessed using regression model. Data from 448 patients (1:1 linezolid:vancomycin) were analyzed. More patients treated with linezolid achieved success (55% [95% CI = 48-62%]) than with vancomycin (45% [38-52%]). Treatment cost were ¥79,551 (95% CI = ¥72,421-¥86,680) for linezolid vs ¥77,587 (¥70,656-¥84,519) for vancomycin in Beijing, ¥90,995 (¥82,598-¥99,393) vs ¥89,448 (¥81,295-¥97,601) in Guangzhou, ¥82,383 (¥74,956-¥89,810) vs ¥80,799 (¥73,545-¥88,054) in Nanjing and ¥59,413 (¥54,366-¥64,460) vs ¥57,804 (¥52,613-¥62,996) in Xi'an. Per successful treatment, the ICER of linezolid over vancomycin were ¥19,719 (-¥143,553 to ¥320,980) (Beijing), ¥15,532 (-¥185,411 to ¥349,693) (Guangzhou), ¥15,904 (-¥161,935 to ¥314,987) (Nanjing) and ¥16,145 (-¥100,738 to ¥234,412) (Xi'an). From simulations, the majority of linezolid cases had greater efficacy and higher costs and more than one third had greater efficacy and lower costs. More vancomycin patients developed renal failure (15% vs 4%, p vancomycin in treating MRSA-NP from a Chinese payer's perspective, and associated with less renal failure, HCRU and cost.

  8. Global analyses of historical masonry buildings: Equivalent frame vs. 3D solid models

    Science.gov (United States)

    Clementi, Francesco; Mezzapelle, Pardo Antonio; Cocchi, Gianmichele; Lenci, Stefano

    2017-07-01

    The paper analyses the seismic vulnerability of two different masonry buildings. It provides both an advanced 3D modelling with solid elements and an equivalent frame modelling. The global structural behaviour and the dynamic properties of the compound have been evaluated using the Finite Element Modelling (FEM) technique, where the nonlinear behaviour of masonry has been taken into account by proper constitutive assumptions. A sensitivity analysis is done to evaluate the effect of the choice of the structural models.

  9. Random regression analyses using B-splines to model growth of Australian Angus cattle

    Directory of Open Access Journals (Sweden)

    Meyer Karin

    2005-09-01

    Full Text Available Abstract Regression on the basis function of B-splines has been advocated as an alternative to orthogonal polynomials in random regression analyses. Basic theory of splines in mixed model analyses is reviewed, and estimates from analyses of weights of Australian Angus cattle from birth to 820 days of age are presented. Data comprised 84 533 records on 20 731 animals in 43 herds, with a high proportion of animals with 4 or more weights recorded. Changes in weights with age were modelled through B-splines of age at recording. A total of thirteen analyses, considering different combinations of linear, quadratic and cubic B-splines and up to six knots, were carried out. Results showed good agreement for all ages with many records, but fluctuated where data were sparse. On the whole, analyses using B-splines appeared more robust against "end-of-range" problems and yielded more consistent and accurate estimates of the first eigenfunctions than previous, polynomial analyses. A model fitting quadratic B-splines, with knots at 0, 200, 400, 600 and 821 days and a total of 91 covariance components, appeared to be a good compromise between detailedness of the model, number of parameters to be estimated, plausibility of results, and fit, measured as residual mean square error.

  10. USE OF THE SIMPLE LINEAR REGRESSION MODEL IN MACRO-ECONOMICAL ANALYSES

    Directory of Open Access Journals (Sweden)

    Constantin ANGHELACHE

    2011-10-01

    Full Text Available The article presents the fundamental aspects of the linear regression, as a toolbox which can be used in macroeconomic analyses. The article describes the estimation of the parameters, the statistical tests used, the homoscesasticity and heteroskedasticity. The use of econometrics instrument in macroeconomics is an important factor that guarantees the quality of the models, analyses, results and possible interpretation that can be drawn at this level.

  11. Taxing CO2 and subsidising biomass: Analysed in a macroeconomic and sectoral model

    DEFF Research Database (Denmark)

    Klinge Jacobsen, Henrik

    2000-01-01

    This paper analyses the combination of taxes and subsidies as an instrument to enable a reduction in CO2 emission. The objective of the study is to compare recycling of a CO2 tax revenue as a subsidy for biomass use as opposed to traditional recycling such as reduced income or corporate taxation....... A model of Denmark's energy supply sector is used to analyse the e€ect of a CO2 tax combined with using the tax revenue for biomass subsidies. The energy supply model is linked to a macroeconomic model such that the macroeconomic consequences of tax policies can be analysed along with the consequences...... for speci®c sectors such as agriculture. Electricity and heat are produced at heat and power plants utilising fuels which minimise total fuel cost, while the authorities regulate capacity expansion technologies. The e€ect of fuel taxes and subsidies on fuels is very sensitive to the fuel substitution...

  12. Experimental and Computational Modal Analyses for Launch Vehicle Models considering Liquid Propellant and Flange Joints

    Directory of Open Access Journals (Sweden)

    Chang-Hoon Sim

    2018-01-01

    Full Text Available In this research, modal tests and analyses are performed for a simplified and scaled first-stage model of a space launch vehicle using liquid propellant. This study aims to establish finite element modeling techniques for computational modal analyses by considering the liquid propellant and flange joints of launch vehicles. The modal tests measure the natural frequencies and mode shapes in the first and second lateral bending modes. As the liquid filling ratio increases, the measured frequencies decrease. In addition, as the number of flange joints increases, the measured natural frequencies increase. Computational modal analyses using the finite element method are conducted. The liquid is modeled by the virtual mass method, and the flange joints are modeled using one-dimensional spring elements along with the node-to-node connection. Comparison of the modal test results and predicted natural frequencies shows good or moderate agreement. The correlation between the modal tests and analyses establishes finite element modeling techniques for modeling the liquid propellant and flange joints of space launch vehicles.

  13. Present status of theories and data analyses of mathematical models for carcinogenesis

    International Nuclear Information System (INIS)

    Kai, Michiaki; Kawaguchi, Isao

    2007-01-01

    Reviewed are the basic mathematical models (hazard functions), present trend of the model studies and that for radiation carcinogenesis. Hazard functions of carcinogenesis are described for multi-stage model and 2-event model related with cell dynamics. At present, the age distribution of cancer mortality is analyzed, relationship between mutation and carcinogenesis is discussed, and models for colorectal carcinogenesis are presented. As for radiation carcinogenesis, models of Armitage-Doll and of generalized MVK (Moolgavkar, Venson, Knudson, 1971-1990) by 2-stage clonal expansion have been applied to analysis of carcinogenesis in A-bomb survivors, workers in uranium mine (Rn exposure) and smoking doctors in UK and other cases, of which characteristics are discussed. In analyses of A-bomb survivors, models above are applied to solid tumors and leukemia to see the effect, if any, of stage, age of exposure, time progression etc. In miners and smokers, stages of the initiation, promotion and progression in carcinogenesis are discussed on the analyses. Others contain the analyses of workers in Canadian atomic power plant, and of patients who underwent the radiation therapy. Model analysis can help to understand the carcinogenic process in a quantitative aspect rather than to describe the process. (R.T.)

  14. Comparison of linear measurements and analyses taken from plaster models and three-dimensional images.

    Science.gov (United States)

    Porto, Betina Grehs; Porto, Thiago Soares; Silva, Monica Barros; Grehs, Renésio Armindo; Pinto, Ary dos Santos; Bhandi, Shilpa H; Tonetto, Mateus Rodrigues; Bandéca, Matheus Coelho; dos Santos-Pinto, Lourdes Aparecida Martins

    2014-11-01

    Digital models are an alternative for carrying out analyses and devising treatment plans in orthodontics. The objective of this study was to evaluate the accuracy and the reproducibility of measurements of tooth sizes, interdental distances and analyses of occlusion using plaster models and their digital images. Thirty pairs of plaster models were chosen at random, and the digital images of each plaster model were obtained using a laser scanner (3Shape R-700, 3Shape A/S). With the plaster models, the measurements were taken using a caliper (Mitutoyo Digimatic(®), Mitutoyo (UK) Ltd) and the MicroScribe (MS) 3DX (Immersion, San Jose, Calif). For the digital images, the measurement tools used were those from the O3d software (Widialabs, Brazil). The data obtained were compared statistically using the Dahlberg formula, analysis of variance and the Tukey test (p < 0.05). The majority of the measurements, obtained using the caliper and O3d were identical, and both were significantly different from those obtained using the MS. Intra-examiner agreement was lowest when using the MS. The results demonstrated that the accuracy and reproducibility of the tooth measurements and analyses from the plaster models using the caliper and from the digital models using O3d software were identical.

  15. Comparison of plasma input and reference tissue models for analysing [(11)C]flumazenil studies

    NARCIS (Netherlands)

    Klumpers, Ursula M. H.; Veltman, Dick J.; Boellaard, Ronald; Comans, Emile F.; Zuketto, Cassandra; Yaqub, Maqsood; Mourik, Jurgen E. M.; Lubberink, Mark; Hoogendijk, Witte J. G.; Lammertsma, Adriaan A.

    2008-01-01

    A single-tissue compartment model with plasma input is the established method for analysing [(11)C]flumazenil ([(11)C]FMZ) studies. However, arterial cannulation and measurement of metabolites are time-consuming. Therefore, a reference tissue approach is appealing, but this approach has not been

  16. Kinetic analyses and mathematical modeling of primary photochemical and photoelectrochemical processes in plant photosystems

    NARCIS (Netherlands)

    Vredenberg, W.J.

    2011-01-01

    In this paper the model and simulation of primary photochemical and photo-electrochemical reactions in dark-adapted intact plant leaves is presented. A descriptive algorithm has been derived from analyses of variable chlorophyll a fluorescence and P700 oxidation kinetics upon excitation with

  17. Analysing and controlling the tax evasion dynamics via majority-vote model

    International Nuclear Information System (INIS)

    Lima, F W S

    2010-01-01

    Within the context of agent-based Monte-Carlo simulations, we study the well-known majority-vote model (MVM) with noise applied to tax evasion on simple square lattices, Voronoi-Delaunay random lattices, Barabasi-Albert networks, and Erdoes-Renyi random graphs. In the order to analyse and to control the fluctuations for tax evasion in the economics model proposed by Zaklan, MVM is applied in the neighborhood of the noise critical q c to evolve the Zaklan model. The Zaklan model had been studied recently using the equilibrium Ising model. Here we show that the Zaklan model is robust because this can be studied using equilibrium dynamics of Ising model also through the nonequilibrium MVM and on various topologies cited above giving the same behavior regardless of dynamic or topology used here.

  18. Analysing and controlling the tax evasion dynamics via majority-vote model

    Energy Technology Data Exchange (ETDEWEB)

    Lima, F W S, E-mail: fwslima@gmail.co, E-mail: wel@ufpi.edu.b [Departamento de Fisica, Universidade Federal do PiauI, 64049-550, Teresina - PI (Brazil)

    2010-09-01

    Within the context of agent-based Monte-Carlo simulations, we study the well-known majority-vote model (MVM) with noise applied to tax evasion on simple square lattices, Voronoi-Delaunay random lattices, Barabasi-Albert networks, and Erdoes-Renyi random graphs. In the order to analyse and to control the fluctuations for tax evasion in the economics model proposed by Zaklan, MVM is applied in the neighborhood of the noise critical q{sub c} to evolve the Zaklan model. The Zaklan model had been studied recently using the equilibrium Ising model. Here we show that the Zaklan model is robust because this can be studied using equilibrium dynamics of Ising model also through the nonequilibrium MVM and on various topologies cited above giving the same behavior regardless of dynamic or topology used here.

  19. Nurses' intention to leave: critically analyse the theory of reasoned action and organizational commitment model.

    Science.gov (United States)

    Liou, Shwu-Ru

    2009-01-01

    To systematically analyse the Organizational Commitment model and Theory of Reasoned Action and determine concepts that can better explain nurses' intention to leave their job. The Organizational Commitment model and Theory of Reasoned Action have been proposed and applied to understand intention to leave and turnover behaviour, which are major contributors to nursing shortage. However, the appropriateness of applying these two models in nursing was not analysed. Three main criteria of a useful model were used for the analysis: consistency in the use of concepts, testability and predictability. Both theories use concepts consistently. Concepts in the Theory of Reasoned Action are defined broadly whereas they are operationally defined in the Organizational Commitment model. Predictability of the Theory of Reasoned Action is questionable whereas the Organizational Commitment model can be applied to predict intention to leave. A model was proposed based on this analysis. Organizational commitment, intention to leave, work experiences, job characteristics and personal characteristics can be concepts for predicting nurses' intention to leave. Nursing managers may consider nurses' personal characteristics and experiences to increase their organizational commitment and enhance their intention to stay. Empirical studies are needed to test and cross-validate the re-synthesized model for nurses' intention to leave their job.

  20. A model finite-element to analyse the mechanical behavior of a PWR fuel rod

    International Nuclear Information System (INIS)

    Galeao, A.C.N.R.; Tanajura, C.A.S.

    1988-01-01

    A model to analyse the mechanical behavior of a PWR fuel rod is presented. We drew our attention to the phenomenon of pellet-pellet and pellet-cladding contact by taking advantage of an elastic model which include the effects of thermal gradients, cladding internal and external pressures, swelling and initial relocation. The problem of contact gives rise ro a variational formulation which employs Lagrangian multipliers. An iterative scheme is constructed and the finite element method is applied to obtain the numerical solution. Some results and comments are presented to examine the performance of the model. (author) [pt

  1. Analysing, Interpreting, and Testing the Invariance of the Actor-Partner Interdependence Model

    Directory of Open Access Journals (Sweden)

    Gareau, Alexandre

    2016-09-01

    Full Text Available Although in recent years researchers have begun to utilize dyadic data analyses such as the actor-partner interdependence model (APIM, certain limitations to the applicability of these models still exist. Given the complexity of APIMs, most researchers will often use observed scores to estimate the model's parameters, which can significantly limit and underestimate statistical results. The aim of this article is to highlight the importance of conducting a confirmatory factor analysis (CFA of equivalent constructs between dyad members (i.e. measurement equivalence/invariance; ME/I. Different steps for merging CFA and APIM procedures will be detailed in order to shed light on new and integrative methods.

  2. Joint analyses model for total cholesterol and triglyceride in human serum with near-infrared spectroscopy

    Science.gov (United States)

    Yao, Lijun; Lyu, Ning; Chen, Jiemei; Pan, Tao; Yu, Jing

    2016-04-01

    The development of a small, dedicated near-infrared (NIR) spectrometer has promising potential applications, such as for joint analyses of total cholesterol (TC) and triglyceride (TG) in human serum for preventing and treating hyperlipidemia of a large population. The appropriate wavelength selection is a key technology for developing such a spectrometer. For this reason, a novel wavelength selection method, named the equidistant combination partial least squares (EC-PLS), was applied to the wavelength selection for the NIR analyses of TC and TG in human serum. A rigorous process based on the various divisions of calibration and prediction sets was performed to achieve modeling optimization with stability. By applying EC-PLS, a model set was developed, which consists of various models that were equivalent to the optimal model. The joint analyses model of the two indicators was further selected with only 50 wavelengths. The random validation samples excluded from the modeling process were used to validate the selected model. The root-mean-square errors, correlation coefficients and ratio of performance to deviation for the prediction were 0.197 mmol L- 1, 0.985 and 5.6 for TC, and 0.101 mmol L- 1, 0.992 and 8.0 for TG, respectively. The sensitivity and specificity for hyperlipidemia were 96.2% and 98.0%. These findings indicate high prediction accuracy and low model complexity. The proposed wavelength selection provided valuable references for the designing of a small, dedicated spectrometer for hyperlipidemia. The methodological framework and optimization algorithm are universal, such that they can be applied to other fields.

  3. Distinguishing Mediational Models and Analyses in Clinical Psychology: Atemporal Associations Do Not Imply Causation.

    Science.gov (United States)

    Winer, E Samuel; Cervone, Daniel; Bryant, Jessica; McKinney, Cliff; Liu, Richard T; Nadorff, Michael R

    2016-09-01

    A popular way to attempt to discern causality in clinical psychology is through mediation analysis. However, mediation analysis is sometimes applied to research questions in clinical psychology when inferring causality is impossible. This practice may soon increase with new, readily available, and easy-to-use statistical advances. Thus, we here provide a heuristic to remind clinical psychological scientists of the assumptions of mediation analyses. We describe recent statistical advances and unpack assumptions of causality in mediation, underscoring the importance of time in understanding mediational hypotheses and analyses in clinical psychology. Example analyses demonstrate that statistical mediation can occur despite theoretical mediation being improbable. We propose a delineation of mediational effects derived from cross-sectional designs into the terms temporal and atemporal associations to emphasize time in conceptualizing process models in clinical psychology. The general implications for mediational hypotheses and the temporal frameworks from within which they may be drawn are discussed. © 2016 Wiley Periodicals, Inc.

  4. Groundwater flow analyses in preliminary site investigations. Modelling strategy and computer codes

    International Nuclear Information System (INIS)

    Taivassalo, V.; Koskinen, L.; Meling, K.

    1994-02-01

    The analyses of groundwater flow comprised a part of the preliminary site investigations which were carried out by Teollisuuden Voima Oy (TVO) for five areas in Finland during 1987 -1992. The main objective of the flow analyses was to characterize groundwater flow at the sites. The flow simulations were also used to identify and study uncertainties and inadequacies which are inherent in the results of earlier modelling phases. The flow analyses were performed for flow conditions similar to the present conditions. The modelling approach was based on the concept of an equivalent continuum. Each fracture zone and the rock matrix among the zones was, however, considered separately as a hydrogeologic unit. The numerical calculations were carried out with a computer code package, FEFLOW. The code is based upon the finite element method. With the code two- and one-dimensional elements can also be used by way of embedding them in a three-dimensional element mesh. A set of new algorithms was developed and employed to create element meshes for FEFLOW. The most useful program in the preliminary site investigations was PAAWI, which adds two-dimensional elements for fracture zones to an existing three-dimensional element mesh. The new algorithms reduced significantly the time required to create spatial discretization for complex geometries. Three element meshes were created for each site. The boundaries of the regional models coincide with those of the flow models. (55 refs., 40 figs., 1 tab.)

  5. To transform or not to transform: using generalized linear mixed models to analyse reaction time data

    Science.gov (United States)

    Lo, Steson; Andrews, Sally

    2015-01-01

    Linear mixed-effect models (LMMs) are being increasingly widely used in psychology to analyse multi-level research designs. This feature allows LMMs to address some of the problems identified by Speelman and McGann (2013) about the use of mean data, because they do not average across individual responses. However, recent guidelines for using LMM to analyse skewed reaction time (RT) data collected in many cognitive psychological studies recommend the application of non-linear transformations to satisfy assumptions of normality. Uncritical adoption of this recommendation has important theoretical implications which can yield misleading conclusions. For example, Balota et al. (2013) showed that analyses of raw RT produced additive effects of word frequency and stimulus quality on word identification, which conflicted with the interactive effects observed in analyses of transformed RT. Generalized linear mixed-effect models (GLMM) provide a solution to this problem by satisfying normality assumptions without the need for transformation. This allows differences between individuals to be properly assessed, using the metric most appropriate to the researcher's theoretical context. We outline the major theoretical decisions involved in specifying a GLMM, and illustrate them by reanalysing Balota et al.'s datasets. We then consider the broader benefits of using GLMM to investigate individual differences. PMID:26300841

  6. Evaluation of Uncertainties in hydrogeological modeling and groundwater flow analyses. Model calibration

    International Nuclear Information System (INIS)

    Ijiri, Yuji; Ono, Makoto; Sugihara, Yutaka; Shimo, Michito; Yamamoto, Hajime; Fumimura, Kenichi

    2003-03-01

    This study involves evaluation of uncertainty in hydrogeological modeling and groundwater flow analysis. Three-dimensional groundwater flow in Shobasama site in Tono was analyzed using two continuum models and one discontinuous model. The domain of this study covered area of four kilometers in east-west direction and six kilometers in north-south direction. Moreover, for the purpose of evaluating how uncertainties included in modeling of hydrogeological structure and results of groundwater simulation decreased with progress of investigation research, updating and calibration of the models about several modeling techniques of hydrogeological structure and groundwater flow analysis techniques were carried out, based on the information and knowledge which were newly acquired. The acquired knowledge is as follows. As a result of setting parameters and structures in renewal of the models following to the circumstances by last year, there is no big difference to handling between modeling methods. The model calibration is performed by the method of matching numerical simulation with observation, about the pressure response caused by opening and closing of a packer in MIU-2 borehole. Each analysis technique attains reducing of residual sum of squares of observations and results of numerical simulation by adjusting hydrogeological parameters. However, each model adjusts different parameters as water conductivity, effective porosity, specific storage, and anisotropy. When calibrating models, sometimes it is impossible to explain the phenomena only by adjusting parameters. In such case, another investigation may be required to clarify details of hydrogeological structure more. As a result of comparing research from beginning to this year, the following conclusions are obtained about investigation. (1) The transient hydraulic data are effective means in reducing the uncertainty of hydrogeological structure. (2) Effective porosity for calculating pore water velocity of

  7. Performance Assessment Modeling and Sensitivity Analyses of Generic Disposal System Concepts.

    Energy Technology Data Exchange (ETDEWEB)

    Sevougian, S. David; Freeze, Geoffrey A.; Gardner, William Payton; Hammond, Glenn Edward; Mariner, Paul

    2014-09-01

    directly, rather than through simplified abstractions. It also a llows for complex representations of the source term, e.g., the explicit representation of many individual waste packages (i.e., meter - scale detail of an entire waste emplacement drift). This report fulfills the Generic Disposal System Analysis Work Packa ge Level 3 Milestone - Performance Assessment Modeling and Sensitivity Analyses of Generic Disposal System Concepts (M 3 FT - 1 4 SN08080 3 2 ).

  8. Generic uncertainty model for DETRA for environmental consequence analyses. Application and sample outputs

    Energy Technology Data Exchange (ETDEWEB)

    Suolanen, V.; Ilvonen, M. [VTT Energy, Espoo (Finland). Nuclear Energy

    1998-10-01

    Computer model DETRA applies a dynamic compartment modelling approach. The compartment structure of each considered application can be tailored individually. This flexible modelling method makes it possible that the transfer of radionuclides can be considered in various cases: aquatic environment and related food chains, terrestrial environment, food chains in general and food stuffs, body burden analyses of humans, etc. In the former study on this subject, modernization of the user interface of DETRA code was carried out. This new interface works in Windows environment and the usability of the code has been improved. The objective of this study has been to further develop and diversify the user interface so that also probabilistic uncertainty analyses can be performed by DETRA. The most common probability distributions are available: uniform, truncated Gaussian and triangular. The corresponding logarithmic distributions are also available. All input data related to a considered case can be varied, although this option is seldomly needed. The calculated output values can be selected as monitored values at certain simulation time points defined by the user. The results of a sensitivity run are immediately available after simulation as graphical presentations. These outcomes are distributions generated for varied parameters, density functions of monitored parameters and complementary cumulative density functions (CCDF). An application considered in connection with this work was the estimation of contamination of milk caused by radioactive deposition of Cs (10 kBq(Cs-137)/m{sup 2}). The multi-sequence calculation model applied consisted of a pasture modelling part and a dormant season modelling part. These two sequences were linked periodically simulating the realistic practice of care taking of domestic animals in Finland. The most important parameters were varied in this exercise. The performed diversifying of the user interface of DETRA code seems to provide an

  9. BWR Mark III containment analyses using a GOTHIC 8.0 3D model

    International Nuclear Information System (INIS)

    Jimenez, Gonzalo; Serrano, César; Lopez-Alonso, Emma; Molina, M del Carmen; Calvo, Daniel; García, Javier; Queral, César; Zuriaga, J. Vicente; González, Montserrat

    2015-01-01

    Highlights: • The development of a 3D GOTHIC code model of BWR Mark-III containment is described. • Suppression pool modelling based on the POOLEX STB-20 and STB-16 experimental tests. • LOCA and SBO transient simulated to verify the behaviour of the 3D GOTHIC model. • Comparison between the 3D GOTHIC model and MAAP4.07 model is conducted. • Accurate reproduction of pre severe accident conditions with the 3D GOTHIC model. - Abstract: The purpose of this study is to establish a detailed three-dimensional model of Cofrentes NPP BWR/6 Mark III containment building using the containment code GOTHIC 8.0. This paper presents the model construction, the phenomenology tests conducted and the selected transient for the model evaluation. In order to study the proper settings for the model in the suppression pool, two experiments conducted with the experimental installation POOLEX have been simulated, allowing to obtain a proper behaviour of the model under different suppression pool phenomenology. In the transient analyses, a Loss of Coolant Accident (LOCA) and a Station Blackout (SBO) transient have been performed. The main results of the simulations of those transients were qualitative compared with the results obtained from simulations with MAAP 4.07 Cofrentes NPP model, used by the plant for simulating severe accidents. From this comparison, a verification of the model in terms of pressurization, asymmetric discharges and high pressure release were obtained. The completeness of this model has proved to adequately simulate the thermal hydraulic phenomena which occur in the containment during accidental sequences

  10. Computational model for supporting SHM systems design: Damage identification via numerical analyses

    Science.gov (United States)

    Sartorato, Murilo; de Medeiros, Ricardo; Vandepitte, Dirk; Tita, Volnei

    2017-02-01

    This work presents a computational model to simulate thin structures monitored by piezoelectric sensors in order to support the design of SHM systems, which use vibration based methods. Thus, a new shell finite element model was proposed and implemented via a User ELement subroutine (UEL) into the commercial package ABAQUS™. This model was based on a modified First Order Shear Theory (FOST) for piezoelectric composite laminates. After that, damaged cantilever beams with two piezoelectric sensors in different positions were investigated by using experimental analyses and the proposed computational model. A maximum difference in the magnitude of the FRFs between numerical and experimental analyses of 7.45% was found near the resonance regions. For damage identification, different levels of damage severity were evaluated by seven damage metrics, including one proposed by the present authors. Numerical and experimental damage metrics values were compared, showing a good correlation in terms of tendency. Finally, based on comparisons of numerical and experimental results, it is shown a discussion about the potentials and limitations of the proposed computational model to be used for supporting SHM systems design.

  11. Using Weather Data and Climate Model Output in Economic Analyses of Climate Change

    Energy Technology Data Exchange (ETDEWEB)

    Auffhammer, M.; Hsiang, S. M.; Schlenker, W.; Sobel, A.

    2013-06-28

    Economists are increasingly using weather data and climate model output in analyses of the economic impacts of climate change. This article introduces a set of weather data sets and climate models that are frequently used, discusses the most common mistakes economists make in using these products, and identifies ways to avoid these pitfalls. We first provide an introduction to weather data, including a summary of the types of datasets available, and then discuss five common pitfalls that empirical researchers should be aware of when using historical weather data as explanatory variables in econometric applications. We then provide a brief overview of climate models and discuss two common and significant errors often made by economists when climate model output is used to simulate the future impacts of climate change on an economic outcome of interest.

  12. An open-population hierarchical distance sampling model

    Science.gov (United States)

    Sollmann, Rachel; Beth Gardner,; Richard B Chandler,; Royle, J. Andrew; T Scott Sillett,

    2015-01-01

    Modeling population dynamics while accounting for imperfect detection is essential to monitoring programs. Distance sampling allows estimating population size while accounting for imperfect detection, but existing methods do not allow for direct estimation of demographic parameters. We develop a model that uses temporal correlation in abundance arising from underlying population dynamics to estimate demographic parameters from repeated distance sampling surveys. Using a simulation study motivated by designing a monitoring program for island scrub-jays (Aphelocoma insularis), we investigated the power of this model to detect population trends. We generated temporally autocorrelated abundance and distance sampling data over six surveys, using population rates of change of 0.95 and 0.90. We fit the data generating Markovian model and a mis-specified model with a log-linear time effect on abundance, and derived post hoc trend estimates from a model estimating abundance for each survey separately. We performed these analyses for varying number of survey points. Power to detect population changes was consistently greater under the Markov model than under the alternatives, particularly for reduced numbers of survey points. The model can readily be extended to more complex demographic processes than considered in our simulations. This novel framework can be widely adopted for wildlife population monitoring.

  13. NUMERICAL MODELLING AS NON-DESTRUCTIVE METHOD FOR THE ANALYSES AND DIAGNOSIS OF STONE STRUCTURES: MODELS AND POSSIBILITIES

    Directory of Open Access Journals (Sweden)

    Nataša Štambuk-Cvitanović

    1999-12-01

    Full Text Available Assuming the necessity of analysis, diagnosis and preservation of existing valuable stone masonry structures and ancient monuments in today European urban cores, numerical modelling become an efficient tool for the structural behaviour investigation. It should be supported by experimentally found input data and taken as a part of general combined approach, particularly non-destructive techniques on the structure/model within it. For the structures or their detail which may require more complex analyses three numerical models based upon finite elements technique are suggested: (1 standard linear model; (2 linear model with contact (interface elements; and (3 non-linear elasto-plastic and orthotropic model. The applicability of these models depend upon the accuracy of the approach or type of the problem, and will be presented on some characteristic samples.

  14. Risk Factor Analyses for the Return of Spontaneous Circulation in the Asphyxiation Cardiac Arrest Porcine Model

    Directory of Open Access Journals (Sweden)

    Cai-Jun Wu

    2015-01-01

    Full Text Available Background: Animal models of asphyxiation cardiac arrest (ACA are frequently used in basic research to mirror the clinical course of cardiac arrest (CA. The rates of the return of spontaneous circulation (ROSC in ACA animal models are lower than those from studies that have utilized ventricular fibrillation (VF animal models. The purpose of this study was to characterize the factors associated with the ROSC in the ACA porcine model. Methods: Forty-eight healthy miniature pigs underwent endotracheal tube clamping to induce CA. Once induced, CA was maintained untreated for a period of 8 min. Two minutes following the initiation of cardiopulmonary resuscitation (CPR, defibrillation was attempted until ROSC was achieved or the animal died. To assess the factors associated with ROSC in this CA model, logistic regression analyses were performed to analyze gender, the time of preparation, the amplitude spectrum area (AMSA from the beginning of CPR and the pH at the beginning of CPR. A receiver-operating characteristic (ROC curve was used to evaluate the predictive value of AMSA for ROSC. Results: ROSC was only 52.1% successful in this ACA porcine model. The multivariate logistic regression analyses revealed that ROSC significantly depended on the time of preparation, AMSA at the beginning of CPR and pH at the beginning of CPR. The area under the ROC curve in for AMSA at the beginning of CPR was 0.878 successful in predicting ROSC (95% confidence intervals: 0.773∼0.983, and the optimum cut-off value was 15.62 (specificity 95.7% and sensitivity 80.0%. Conclusions: The time of preparation, AMSA and the pH at the beginning of CPR were associated with ROSC in this ACA porcine model. AMSA also predicted the likelihood of ROSC in this ACA animal model.

  15. Integrated Process Model Development and Systems Analyses for the LIFE Power Plant

    Energy Technology Data Exchange (ETDEWEB)

    Meier, W R; Anklam, T; Abbott, R; Erlandson, A; Halsey, W; Miles, R; Simon, A J

    2009-07-15

    We have developed an integrated process model (IPM) for a Laser Inertial Fusion-Fission Energy (LIFE) power plant. The model includes cost and performance algorithms for the major subsystems of the plant, including the laser, fusion target fabrication and injection, fusion-fission chamber (including the tritium and fission fuel blankets), heat transfer and power conversion systems, and other balance of plant systems. The model has been developed in Visual Basic with an Excel spreadsheet user interface in order to allow experts in various aspects of the design to easily integrate their individual modules and provide a convenient, widely accessible platform for conducting the system studies. Subsystem modules vary in level of complexity; some are based on top-down scaling from fission power plant costs (for example, electric plant equipment), while others are bottom-up models based on conceptual designs being developed by LLNL (for example, the fusion-fission chamber and laser systems). The IPM is being used to evaluate design trade-offs, do design optimization, and conduct sensitivity analyses to identify high-leverage areas for R&D. We describe key aspects of the IPM and report on the results of our systems analyses. Designs are compared and evaluated as a function of key design variables such as fusion target yield and pulse repetition rate.

  16. Considerations when loading spinal finite element models with predicted muscle forces from inverse static analyses.

    Science.gov (United States)

    Zhu, Rui; Zander, Thomas; Dreischarf, Marcel; Duda, Georg N; Rohlmann, Antonius; Schmidt, Hendrik

    2013-04-26

    Mostly simplified loads were used in biomechanical finite element (FE) studies of the spine because of a lack of data on muscular physiological loading. Inverse static (IS) models allow the prediction of muscle forces for predefined postures. A combination of both mechanical approaches - FE and IS - appears to allow a more realistic modeling. However, it is unknown what deviations are to be expected when muscle forces calculated for models with rigid vertebrae and fixed centers of rotation, as generally found in IS models, are applied to a FE model with elastic vertebrae and discs. The aim of this study was to determine the effects of these disagreements. Muscle forces were estimated for 20° flexion and 10° extension in an IS model and transferred to a FE model. The effects of the elasticity of bony structures (rigid vs. elastic) and the definition of the center of rotation (fixed vs. non-fixed) were quantified using the deviation of actual intervertebral rotation (IVR) of the FE model and the targeted IVR from the IS model. For extension, the elasticity of the vertebrae had only a minor effect on IVRs, whereas a non-fixed center of rotation increased the IVR deviation on average by 0.5° per segment. For flexion, a combination of the two parameters increased IVR deviation on average by 1° per segment. When loading FE models with predicted muscle forces from IS analyses, the main limitations in the IS model - rigidity of the segments and the fixed centers of rotation - must be considered. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Multi-model finite element scheme for static and free vibration analyses of composite laminated beams

    Directory of Open Access Journals (Sweden)

    U.N. Band

    Full Text Available Abstract A transition element is developed for the local global analysis of laminated composite beams. It bridges one part of the domain modelled with a higher order theory and other with a 2D mixed layerwise theory (LWT used at critical zone of the domain. The use of developed transition element makes the analysis for interlaminar stresses possible with significant accuracy. The mixed 2D model incorporates the transverse normal and shear stresses as nodal degrees of freedom (DOF which inherently ensures continuity of these stresses. Non critical zones are modelled with higher order equivalent single layer (ESL theory leading to the global mesh with multiple models applied simultaneously. Use of higher order ESL in non critical zones reduces the total number of elements required to map the domain. A substantial reduction in DOF as compared to a complete 2D mixed model is obvious. This computationally economical multiple modelling scheme using the transition element is applied to static and free vibration analyses of laminated composite beams. Results obtained are in good agreement with benchmarks available in literature.

  18. A chip-level modeling approach for rail span collapse and survivability analyses

    International Nuclear Information System (INIS)

    Marvis, D.G.; Alexander, D.R.; Dinger, G.L.

    1989-01-01

    A general semiautomated analysis technique has been developed for analyzing rail span collapse and survivability of VLSI microcircuits in high ionizing dose rate radiation environments. Hierarchical macrocell modeling permits analyses at the chip level and interactive graphical postprocessing provides a rapid visualization of voltage, current and power distributions over an entire VLSIC. The technique is demonstrated for a 16k C MOS/SOI SRAM and a CMOS/SOS 8-bit multiplier. The authors also present an efficient method to treat memory arrays as well as a three-dimensional integration technique to compute sapphire photoconduction from the design layout

  19. Analyses and testing of model prestressed concrete reactor vessels with built-in planes of weakness

    International Nuclear Information System (INIS)

    Dawson, P.; Paton, A.A.; Fleischer, C.C.

    1990-01-01

    This paper describes the design, construction, analyses and testing of two small scale, single cavity prestressed concrete reactor vessel models, one without planes of weakness and one with planes of weakness immediately behind the cavity liner. This work was carried out to extend a previous study which had suggested the likely feasibility of constructing regions of prestressed concrete reactor vessels and biological shields, which become activated, using easily removable blocks, separated by a suitable membrane. The paper describes the results obtained and concludes that the planes of weakness concept could offer a means of facilitating the dismantling of activated regions of prestressed concrete reactor vessels, biological shields and similar types of structure. (author)

  20. Incorporating uncertainty of management costs in sensitivity analyses of matrix population models.

    Science.gov (United States)

    Salomon, Yacov; McCarthy, Michael A; Taylor, Peter; Wintle, Brendan A

    2013-02-01

    The importance of accounting for economic costs when making environmental-management decisions subject to resource constraints has been increasingly recognized in recent years. In contrast, uncertainty associated with such costs has often been ignored. We developed a method, on the basis of economic theory, that accounts for the uncertainty in population-management decisions. We considered the case where, rather than taking fixed values, model parameters are random variables that represent the situation when parameters are not precisely known. Hence, the outcome is not precisely known either. Instead of maximizing the expected outcome, we maximized the probability of obtaining an outcome above a threshold of acceptability. We derived explicit analytical expressions for the optimal allocation and its associated probability, as a function of the threshold of acceptability, where the model parameters were distributed according to normal and uniform distributions. To illustrate our approach we revisited a previous study that incorporated cost-efficiency analyses in management decisions that were based on perturbation analyses of matrix population models. Incorporating derivations from this study into our framework, we extended the model to address potential uncertainties. We then applied these results to 2 case studies: management of a Koala (Phascolarctos cinereus) population and conservation of an olive ridley sea turtle (Lepidochelys olivacea) population. For low aspirations, that is, when the threshold of acceptability is relatively low, the optimal strategy was obtained by diversifying the allocation of funds. Conversely, for high aspirations, the budget was directed toward management actions with the highest potential effect on the population. The exact optimal allocation was sensitive to the choice of uncertainty model. Our results highlight the importance of accounting for uncertainty when making decisions and suggest that more effort should be placed on

  1. Sensitivity analyses of a global flood model in different geoclimatic regions

    Science.gov (United States)

    Moylan, C.; Neal, J. C.; Freer, J. E.; Pianosi, F.; Wagener, T.; Sampson, C. C.; Smith, A.

    2017-12-01

    Flood models producing global hazard maps now exist, although with significant variation in the modelled hazard extent. Besides explicit structural differences, reasons for this variation is unknown. Understanding the behaviour of these global flood models is necessary to determine how they can be further developed. Preliminary sensitivity analysis was performed using Morris method on the Bristol global flood model, which has 37 parameters, required to translate the remotely sensed data into input for the underlying hydrodynamic model. This number of parameters implies an excess of complexity for flood modelling and should ideally be mitigated. The analysis showed an order of magnitude difference in parameter sensitivities, when comparing total flooded extent. It also showed the most important parameters' influence to be highly interactive rather than just direct; there were surprises in expectation of which parameters are the most important. Despite these findings, conclusions about the model are limited due to the fixed geoclimatic features of the location analysed. Hence more locations with varied geoclimatic characteristics must be chosen, so the consistencies and deviations of parameter sensitivities across these features become quantifiable. Locations are selected using a novel sampling technique, which aggregates the input data of a domain into representative metrics of the geoclimatic features, hypothesised to correlate with one or more parameters. Combinations of these metrics are sampled across a range of geoclimatic areas, and the sensitivities found are correlated with the sampled metrics. From this work, we find the main influences on flood risk prediction at the global scale for the used model structure, which as a methodology is transferable to the other global flood models.

  2. Analysing the Effects of Flood-Resilience Technologies in Urban Areas Using a Synthetic Model Approach

    Directory of Open Access Journals (Sweden)

    Reinhard Schinke

    2016-11-01

    Full Text Available Flood protection systems with their spatial effects play an important role in managing and reducing flood risks. The planning and decision process as well as the technical implementation are well organized and often exercised. However, building-related flood-resilience technologies (FReT are often neglected due to the absence of suitable approaches to analyse and to integrate such measures in large-scale flood damage mitigation concepts. Against this backdrop, a synthetic model-approach was extended by few complementary methodical steps in order to calculate flood damage to buildings considering the effects of building-related FReT and to analyse the area-related reduction of flood risks by geo-information systems (GIS with high spatial resolution. It includes a civil engineering based investigation of characteristic properties with its building construction including a selection and combination of appropriate FReT as a basis for derivation of synthetic depth-damage functions. Depending on the real exposition and the implementation level of FReT, the functions can be used and allocated in spatial damage and risk analyses. The application of the extended approach is shown at a case study in Valencia (Spain. In this way, the overall research findings improve the integration of FReT in flood risk management. They provide also some useful information for advising of individuals at risk supporting the selection and implementation of FReT.

  3. A STRONGLY COUPLED REACTOR CORE ISOLATION COOLING SYSTEM MODEL FOR EXTENDED STATION BLACK-OUT ANALYSES

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Haihua [Idaho National Laboratory; Zhang, Hongbin [Idaho National Laboratory; Zou, Ling [Idaho National Laboratory; Martineau, Richard Charles [Idaho National Laboratory

    2015-03-01

    The reactor core isolation cooling (RCIC) system in a boiling water reactor (BWR) provides makeup cooling water to the reactor pressure vessel (RPV) when the main steam lines are isolated and the normal supply of water to the reactor vessel is lost. The RCIC system operates independently of AC power, service air, or external cooling water systems. The only required external energy source is from the battery to maintain the logic circuits to control the opening and/or closure of valves in the RCIC systems in order to control the RPV water level by shutting down the RCIC pump to avoid overfilling the RPV and flooding the steam line to the RCIC turbine. It is generally considered in almost all the existing station black-out accidents (SBO) analyses that loss of the DC power would result in overfilling the steam line and allowing liquid water to flow into the RCIC turbine, where it is assumed that the turbine would then be disabled. This behavior, however, was not observed in the Fukushima Daiichi accidents, where the Unit 2 RCIC functioned without DC power for nearly three days. Therefore, more detailed mechanistic models for RCIC system components are needed to understand the extended SBO for BWRs. As part of the effort to develop the next generation reactor system safety analysis code RELAP-7, we have developed a strongly coupled RCIC system model, which consists of a turbine model, a pump model, a check valve model, a wet well model, and their coupling models. Unlike the traditional SBO simulations where mass flow rates are typically given in the input file through time dependent functions, the real mass flow rates through the turbine and the pump loops in our model are dynamically calculated according to conservation laws and turbine/pump operation curves. A simplified SBO demonstration RELAP-7 model with this RCIC model has been successfully developed. The demonstration model includes the major components for the primary system of a BWR, as well as the safety

  4. Establishing a Numerical Modeling Framework for Hydrologic Engineering Analyses of Extreme Storm Events

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiaodong; Hossain, Faisal; Leung, L. Ruby

    2017-08-01

    In this study a numerical modeling framework for simulating extreme storm events was established using the Weather Research and Forecasting (WRF) model. Such a framework is necessary for the derivation of engineering parameters such as probable maximum precipitation that are the cornerstone of large water management infrastructure design. Here this framework was built based on a heavy storm that occurred in Nashville (USA) in 2010, and verified using two other extreme storms. To achieve the optimal setup, several combinations of model resolutions, initial/boundary conditions (IC/BC), cloud microphysics and cumulus parameterization schemes were evaluated using multiple metrics of precipitation characteristics. The evaluation suggests that WRF is most sensitive to IC/BC option. Simulation generally benefits from finer resolutions up to 5 km. At the 15km level, NCEP2 IC/BC produces better results, while NAM IC/BC performs best at the 5km level. Recommended model configuration from this study is: NAM or NCEP2 IC/BC (depending on data availability), 15km or 15km-5km nested grids, Morrison microphysics and Kain-Fritsch cumulus schemes. Validation of the optimal framework suggests that these options are good starting choices for modeling extreme events similar to the test cases. This optimal framework is proposed in response to emerging engineering demands of extreme storm events forecasting and analyses for design, operations and risk assessment of large water infrastructures.

  5. A conceptual model for analysing informal learning in online social networks for health professionals.

    Science.gov (United States)

    Li, Xin; Gray, Kathleen; Chang, Shanton; Elliott, Kristine; Barnett, Stephen

    2014-01-01

    Online social networking (OSN) provides a new way for health professionals to communicate, collaborate and share ideas with each other for informal learning on a massive scale. It has important implications for ongoing efforts to support Continuing Professional Development (CPD) in the health professions. However, the challenge of analysing the data generated in OSNs makes it difficult to understand whether and how they are useful for CPD. This paper presents a conceptual model for using mixed methods to study data from OSNs to examine the efficacy of OSN in supporting informal learning of health professionals. It is expected that using this model with the dataset generated in OSNs for informal learning will produce new and important insights into how well this innovation in CPD is serving professionals and the healthcare system.

  6. Transformation of Baumgarten's aesthetics into a tool for analysing works and for modelling

    DEFF Research Database (Denmark)

    Thomsen, Bente Dahl

    2006-01-01

      Abstract: Is this the best form, or does it need further work? The aesthetic object does not possess the perfect qualities; but how do I proceed with the form? These are questions that all modellers ask themselves at some point, and with which they can grapple for days - even weeks - before...... the inspiration to deliver the form finally presents itself. This was the outlet for our plan to devise a tool for analysing works and the practical development of forms. The tool is a set of cards with suggestions for investigations that may assist the modeller in identifying the weaknesses of the form......, or convince him-/herself about its strengths. The cards also contain aesthetical reflections that may be of inspiration in the development of the form....

  7. Reading Ability Development from Kindergarten to Junior Secondary: Latent Transition Analyses with Growth Mixture Modeling

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2016-10-01

    Full Text Available The present study examined the reading ability development of children in the large scale Early Childhood Longitudinal Study (Kindergarten Class of 1998-99 data; Tourangeau, Nord, Lê, Pollack, & Atkins-Burnett, 2006 under the dynamic systems. To depict children's growth pattern, we extended the measurement part of latent transition analysis to the growth mixture model and found that the new model fitted the data well. Results also revealed that most of the children stayed in the same ability group with few cross-level changes in their classes. After adding the environmental factors as predictors, analyses showed that children receiving higher teachers' ratings, with higher socioeconomic status, and of above average poverty status, would have higher probability to transit into the higher ability group.

  8. Estimating required information size by quantifying diversity in random-effects model meta-analyses

    DEFF Research Database (Denmark)

    Wetterslev, Jørn; Thorlund, Kristian; Brok, Jesper

    2009-01-01

    BACKGROUND: There is increasing awareness that meta-analyses require a sufficiently large information size to detect or reject an anticipated intervention effect. The required information size in a meta-analysis may be calculated from an anticipated a priori intervention effect or from...... an intervention effect suggested by trials with low-risk of bias. METHODS: Information size calculations need to consider the total model variance in a meta-analysis to control type I and type II errors. Here, we derive an adjusting factor for the required information size under any random-effects model meta......-trial variability and a sampling error estimate considering the required information size. D2 is different from the intuitively obvious adjusting factor based on the common quantification of heterogeneity, the inconsistency (I2), which may underestimate the required information size. Thus, D2 and I2 are compared...

  9. Biosphere Modeling and Analyses in Support of Total System Performance Assessment

    International Nuclear Information System (INIS)

    Tappen, J. J.; Wasiolek, M. A.; Wu, D. W.; Schmitt, J. F.; Smith, A. J.

    2002-01-01

    The Nuclear Waste Policy Act of 1982 established the obligations of and the relationship between the U.S. Environmental Protection Agency (EPA), the U.S. Nuclear Regulatory Commission (NRC), and the U.S. Department of Energy (DOE) for the management and disposal of high-level radioactive wastes. In 1985, the EPA promulgated regulations that included a definition of performance assessment that did not consider potential dose to a member of the general public. This definition would influence the scope of activities conducted by DOE in support of the total system performance assessment program until 1995. The release of a National Academy of Sciences (NAS) report on the technical basis for a Yucca Mountain-specific standard provided the impetus for the DOE to initiate activities that would consider the attributes of the biosphere, i.e. that portion of the earth where living things, including man, exist and interact with the environment around them. The evolution of NRC and EPA Yucca Mountain-specific regulations, originally proposed in 1999, was critical to the development and integration of biosphere modeling and analyses into the total system performance assessment program. These proposed regulations initially differed in the conceptual representation of the receptor of interest to be considered in assessing performance. The publication in 2001 of final regulations in which the NRC adopted standard will permit the continued improvement and refinement of biosphere modeling and analyses activities in support of assessment activities

  10. Biosphere Modeling and Analyses in Support of Total System Performance Assessment

    International Nuclear Information System (INIS)

    Jeff Tappen; M.A. Wasiolek; D.W. Wu; J.F. Schmitt

    2001-01-01

    The Nuclear Waste Policy Act of 1982 established the obligations of and the relationship between the U.S. Environmental Protection Agency (EPA), the U.S. Nuclear Regulatory Commission (NRC), and the U.S. Department of Energy (DOE) for the management and disposal of high-level radioactive wastes. In 1985, the EPA promulgated regulations that included a definition of performance assessment that did not consider potential dose to a member of the general public. This definition would influence the scope of activities conducted by DOE in support of the total system performance assessment program until 1995. The release of a National Academy of Sciences (NAS) report on the technical basis for a Yucca Mountain-specific standard provided the impetus for the DOE to initiate activities that would consider the attributes of the biosphere, i.e. that portion of the earth where living things, including man, exist and interact with the environment around them. The evolution of NRC and EPA Yucca Mountain-specific regulations, originally proposed in 1999, was critical to the development and integration of biosphere modeling and analyses into the total system performance assessment program. These proposed regulations initially differed in the conceptual representation of the receptor of interest to be considered in assessing performance. The publication in 2001 of final regulations in which the NRC adopted standard will permit the continued improvement and refinement of biosphere modeling and analyses activities in support of assessment activities

  11. Quantifying the Representation Error of Land Biosphere Models using High Resolution Footprint Analyses and UAS Observations

    Science.gov (United States)

    Hanson, C. V.; Schmidt, A.; Law, B. E.; Moore, W.

    2015-12-01

    The validity of land biosphere model outputs rely on accurate representations of ecosystem processes within the model. Typically, a vegetation or land cover type for a given area (several Km squared or larger resolution), is assumed to have uniform properties. The limited spacial and temporal resolution of models prevents resolving finer scale heterogeneous flux patterns that arise from variations in vegetation. This representation error must be quantified carefully if models are informed through data assimilation in order to assign appropriate weighting of model outputs and measurement data. The representation error is usually only estimated or ignored entirely due to the difficulty in determining reasonable values. UAS based gas sensors allow measurements of atmospheric CO2 concentrations with unprecedented spacial resolution, providing a means of determining the representation error for CO2 fluxes empirically. In this study we use three dimensional CO2 concentration data in combination with high resolution footprint analyses in order to quantify the representation error for modelled CO2 fluxes for typical resolutions of regional land biosphere models. CO2 concentration data were collected using an Atlatl X6A hexa-copter, carrying a highly calibrated closed path infra-red gas analyzer based sampling system with an uncertainty of ≤ ±0.2 ppm CO2. Gas concentration data was mapped in three dimensions using the UAS on-board position data and compared to footprints generated using WRF 3.61. Chad Hanson, Oregon State University, Corvallis, OR Andres Schmidt, Oregon State University, Corvallis, OR Bev Law, Oregon State University, Corvallis, OR

  12. Challenges of Analysing Gene-Environment Interactions in Mouse Models of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Peter L. Oliver

    2011-01-01

    Full Text Available The modelling of neuropsychiatric disease using the mouse has provided a wealth of information regarding the relationship between specific genetic lesions and behavioural endophenotypes. However, it is becoming increasingly apparent that synergy between genetic and nongenetic factors is a key feature of these disorders that must also be taken into account. With the inherent limitations of retrospective human studies, experiments in mice have begun to tackle this complex association, combining well-established behavioural paradigms and quantitative neuropathology with a range of environmental insults. The conclusions from this work have been varied, due in part to a lack of standardised methodology, although most have illustrated that phenotypes related to disorders such as schizophrenia are consistently modified. Far fewer studies, however, have attempted to generate a “two-hit” model, whereby the consequences of a pathogenic mutation are analysed in combination with environmental manipulation such as prenatal stress. This significant, yet relatively new, approach is beginning to produce valuable new models of neuropsychiatric disease. Focussing on prenatal and perinatal stress models of schizophrenia, this review discusses the current progress in this field, and highlights important issues regarding the interpretation and comparative analysis of such complex behavioural data.

  13. D Recording for 2d Delivering - the Employment of 3d Models for Studies and Analyses -

    Science.gov (United States)

    Rizzi, A.; Baratti, G.; Jiménez, B.; Girardi, S.; Remondino, F.

    2011-09-01

    In the last years, thanks to the advances of surveying sensors and techniques, many heritage sites could be accurately replicated in digital form with very detailed and impressive results. The actual limits are mainly related to hardware capabilities, computation time and low performance of personal computer. Often, the produced models are not visible on a normal computer and the only solution to easily visualized them is offline using rendered videos. This kind of 3D representations is useful for digital conservation, divulgation purposes or virtual tourism where people can visit places otherwise closed for preservation or security reasons. But many more potentialities and possible applications are available using a 3D model. The problem is the ability to handle 3D data as without adequate knowledge this information is reduced to standard 2D data. This article presents some surveying and 3D modeling experiences within the APSAT project ("Ambiente e Paesaggi dei Siti d'Altura Trentini", i.e. Environment and Landscapes of Upland Sites in Trentino). APSAT is a multidisciplinary project funded by the Autonomous Province of Trento (Italy) with the aim documenting, surveying, studying, analysing and preserving mountainous and hill-top heritage sites located in the region. The project focuses on theoretical, methodological and technological aspects of the archaeological investigation of mountain landscape, considered as the product of sequences of settlements, parcelling-outs, communication networks, resources, and symbolic places. The mountain environment preserves better than others the traces of hunting and gathering, breeding, agricultural, metallurgical, symbolic activities characterised by different lengths and environmental impacts, from Prehistory to the Modern Period. Therefore the correct surveying and documentation of this heritage sites and material is very important. Within the project, the 3DOM unit of FBK is delivering all the surveying and 3D material to

  14. APF530 versus ondansetron, each in a guideline-recommended three-drug regimen, for the prevention of chemotherapy-induced nausea and vomiting due to anthracycline plus cyclophosphamide–based highly emetogenic chemotherapy regimens: a post hoc subgroup analysis of the Phase III randomized MAGIC trial

    Directory of Open Access Journals (Sweden)

    Schnadig ID

    2017-05-01

    Full Text Available Ian D Schnadig1, Richy Agajanian2, Christopher Dakhil3, Nashat Gabrail4, Jeffrey Vacirca5, Charles Taylor6, Sharon Wilks7, Eduardo Braun8, Michael C Mosier9, Robert B Geller10, Lee Schwartzberg11, Nicholas Vogelzang12 1Compass Oncology, US Oncology Research, Tualatin, OR, 2The Oncology Institute of Hope and Innovation, Whittier, CA, 3Cancer Center of Kansas, Wichita, KS, 4Gabrail Cancer Center, Canton, OH, 5North Shore Hematology Oncology, East Setauket, NY, 6Tulsa Cancer Institute, Tulsa, OK, 7Cancer Care Centers of South Texas, San Antonio, TX, 8Michiana Hematology Oncology, Westville, IN, 9Biostatistics, EMB Statistical Solutions, LLC, Overland Park, KS, 10Medical Affairs, Heron Therapeutics, Inc., San Diego, CA, 11West Cancer Center, Germantown, TN, 12Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA Background: APF530, a novel extended-release granisetron injection, was superior to ondansetron in a guideline-recommended three-drug regimen in preventing delayed-phase chemotherapy-induced nausea and vomiting (CINV among patients receiving highly emetogenic chemotherapy (HEC in the double-blind Phase III Modified Absorption of Granisetron In the prevention of CINV (MAGIC trial.Patients and methods: This MAGIC post hoc analysis evaluated CINV prevention efficacy and safety of APF530 versus ondansetron, each with fosaprepitant and dexamethasone, in patient subgroup receiving an anthracycline plus cyclophosphamide (AC regimen. Patients were randomized 1:1 to APF530 500 mg subcutaneously (granisetron 10 mg or ondansetron 0.15 mg/kg intravenously (IV (≤16 mg; stratification was by planned cisplatin ≥50 mg/m2 (yes/no. Patients were to receive fosaprepitant 150 mg IV and dexamethasone 12 mg IV on day 1, then dexamethasone 8 mg orally once daily on day 2 and twice daily on days 3 and 4. Patients were mostly younger females (APF530 arm, mean age 54.1 years, female, 99.3%; ondansetron arm, 53.8 years, female 98.3%. The primary

  15. Role of stent type and of duration of dual antiplatelet therapy in patients with chronic kidney disease undergoing percutaneous coronary interventions. Is bare metal stent implantation still a justifiable choice? A post-hoc analysis of the all comer PRODIGY trial.

    Science.gov (United States)

    Crimi, Gabriele; Leonardi, Sergio; Costa, Francesco; Adamo, Marianna; Ariotti, Sara; Valgimigli, Marco

    2016-06-01

    Chronic kidney disease (CKD) is a powerful predictor of major cardiovascular events and stent thrombosis (ST) in patients undergoing percutaneous coronary interventions (PCI). No randomized data are available to compare, and guide the selection of type of stent between bare metal (BMS) or drug eluting stent (DES) in this population. We performed a post-hoc analysis of the PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY (PRODIGY) trial, in which stable or unstable patients with coronary artery disease undergoing PCI were randomized 1:1:1:1 to receive BMS, paclitaxel- (PES), zotarolimus- (ZES-S), or everolimus- (EES) eluting stent. A total of 2003 patients were randomized, and 22 patients were excluded for missing serum creatinine leading to a final population of 1981 patients. Primary outcome was definite or probable ST. We also assessed MACE (myocardial infarction, stroke, or death), and all-cause death, as secondary outcome. CKD, defined with estimated glomerular filtration rate <60ml/min/1.73m(2), was found in 373 patients (18.8%). The incidence of ST at 2years was 5.1% in CKD and 2.1% in non-CKD patients (HR 2.57, 95% confidence interval (CI) 1.46 to 4.52, p<0.001). At multivariable regression we found that patients randomized to EES or ZES-S, but not PES, had lower risk of ST at two years as compared with BMS: adjusted HR=0.288, 95% CI [0.107-0.778, p=0.014] and HR=0.394, 95% CI [0.164-0.947, p=0.037] respectively. The number of patients needed to be treated to prevent 1 ST with an EES vs BMS was 20 in CKD and 50 in patients without CKD. EES patients had the lowest incident MACE events 26.4% as compared to BMS 35.1%, ZES-S 33.0%, or PES 35.7% patients, p=0.551. All-cause death was lowest in ZES-S group 10.6% as compared to BMS 18.1%, PES 25.5% and EES 14.9%, p=0.040. We found no significant interaction between DAPT duration (6 vs 24months) and stent type on primary outcome, PINT=0.47 for BMS, PINT=0.57 for PES, PINT

  16. Theoretical and experimental stress analyses of ORNL thin-shell cylinder-to-cylinder model 3

    International Nuclear Information System (INIS)

    Gwaltney, R.C.; Bolt, S.E.; Corum, J.M.; Bryson, J.W.

    1975-06-01

    The third in a series of four thin-shell cylinder-to-cylinder models was tested, and the experimentally determined elastic stress distributions were compared with theoretical predictions obtained from a thin-shell finite-element analysis. The models are idealized thin-shell structures consisting of two circular cylindrical shells that intersect at right angles. There are no transitions, reinforcements, or fillets in the junction region. This series of model tests serves two basic purposes: the experimental data provide design information directly applicable to nozzles in cylindrical vessels; and the idealized models provide test results for use in developing and evaluating theoretical analyses applicable to nozzles in cylindrical vessels and to thin piping tees. The cylinder of model 3 had a 10 in. OD and the nozzle had a 1.29 in. OD, giving a d 0 /D 0 ratio of 0.129. The OD/thickness ratios for the cylinder and the nozzle were 50 and 7.68 respectively. Thirteen separate loading cases were analyzed. In each, one end of the cylinder was rigidly held. In addition to an internal pressure loading, three mutually perpendicular force components and three mutually perpendicular moment components were individually applied at the free end of the cylinder and at the end of the nozzle. The experimental stress distributions for all the loadings were obtained using 158 three-gage strain rosettes located on the inner and outer surfaces. The loading cases were also analyzed theoretically using a finite-element shell analysis developed at the University of California, Berkeley. The analysis used flat-plate elements and considered five degrees of freedom per node in the final assembled equations. The comparisons between theory and experiment show reasonably good agreement for this model. (U.S.)

  17. Theoretical and experimental stress analyses of ORNL thin-shell cylinder-to-cylinder model 4

    International Nuclear Information System (INIS)

    Gwaltney, R.C.; Bolt, S.E.; Bryson, J.W.

    1975-06-01

    The last in a series of four thin-shell cylinder-to-cylinder models was tested, and the experimentally determined elastic stress distributions were compared with theoretical predictions obtained from a thin-shell finite-element analysis. The models in the series are idealized thin-shell structures consisting of two circular cylindrical shells that intersect at right angles. There are no transitions, reinforcements, or fillets in the junction region. This series of model tests serves two basic purposes: (1) the experimental data provide design information directly applicable to nozzles in cylindrical vessels, and (2) the idealized models provide test results for use in developing and evaluating theoretical analyses applicable to nozzles in cylindrical vessels and to thin piping tees. The cylinder of model 4 had an outside diameter of 10 in., and the nozzle had an outside diameter of 1.29 in., giving a d 0 /D 0 ratio of 0.129. The OD/thickness ratios were 50 and 20.2 for the cylinder and nozzle respectively. Thirteen separate loading cases were analyzed. For each loading condition one end of the cylinder was rigidly held. In addition to an internal pressure loading, three mutually perpendicular force components and three mutually perpendicular moment components were individually applied at the free end of the cylinder and at the end of the nozzle. The experimental stress distributions for each of the 13 loadings were obtained using 157 three-gage strain rosettes located on the inner and outer surfaces. Each of the 13 loading cases was also analyzed theoretically using a finite-element shell analysis developed at the University of California, Berkeley. The analysis used flat-plate elements and considered five degrees of freedom per node in the final assembled equations. The comparisons between theory and experiment show reasonably good agreement for this model. (U.S.)

  18. Genetic analyses of partial egg production in Japanese quail using multi-trait random regression models.

    Science.gov (United States)

    Karami, K; Zerehdaran, S; Barzanooni, B; Lotfi, E

    2017-12-01

    1. The aim of the present study was to estimate genetic parameters for average egg weight (EW) and egg number (EN) at different ages in Japanese quail using multi-trait random regression (MTRR) models. 2. A total of 8534 records from 900 quail, hatched between 2014 and 2015, were used in the study. Average weekly egg weights and egg numbers were measured from second until sixth week of egg production. 3. Nine random regression models were compared to identify the best order of the Legendre polynomials (LP). The most optimal model was identified by the Bayesian Information Criterion. A model with second order of LP for fixed effects, second order of LP for additive genetic effects and third order of LP for permanent environmental effects (MTRR23) was found to be the best. 4. According to the MTRR23 model, direct heritability for EW increased from 0.26 in the second week to 0.53 in the sixth week of egg production, whereas the ratio of permanent environment to phenotypic variance decreased from 0.48 to 0.1. Direct heritability for EN was low, whereas the ratio of permanent environment to phenotypic variance decreased from 0.57 to 0.15 during the production period. 5. For each trait, estimated genetic correlations among weeks of egg production were high (from 0.85 to 0.98). Genetic correlations between EW and EN were low and negative for the first two weeks, but they were low and positive for the rest of the egg production period. 6. In conclusion, random regression models can be used effectively for analysing egg production traits in Japanese quail. Response to selection for increased egg weight would be higher at older ages because of its higher heritability and such a breeding program would have no negative genetic impact on egg production.

  19. DESCRIPTION OF MODELING ANALYSES IN SUPPORT OF THE 200-ZP-1 REMEDIAL DESIGN/REMEDIAL ACTION

    Energy Technology Data Exchange (ETDEWEB)

    VONGARGEN BH

    2009-11-03

    The Feasibility Study/or the 200-ZP-1 Groundwater Operable Unit (DOE/RL-2007-28) and the Proposed Plan/or Remediation of the 200-ZP-1 Groundwater Operable Unit (DOE/RL-2007-33) describe the use of groundwater pump-and-treat technology for the 200-ZP-1 Groundwater Operable Unit (OU) as part of an expanded groundwater remedy. During fiscal year 2008 (FY08), a groundwater flow and contaminant transport (flow and transport) model was developed to support remedy design decisions at the 200-ZP-1 OU. This model was developed because the size and influence of the proposed 200-ZP-1 groundwater pump-and-treat remedy will have a larger areal extent than the current interim remedy, and modeling is required to provide estimates of influent concentrations and contaminant mass removal rates to support the design of the aboveground treatment train. The 200 West Area Pre-Conceptual Design/or Final Extraction/Injection Well Network: Modeling Analyses (DOE/RL-2008-56) documents the development of the first version of the MODFLOW/MT3DMS model of the Hanford Site's Central Plateau, as well as the initial application of that model to simulate a potential well field for the 200-ZP-1 remedy (considering only the contaminants carbon tetrachloride and technetium-99). This document focuses on the use of the flow and transport model to identify suitable extraction and injection well locations as part of the 200 West Area 200-ZP-1 Pump-and-Treat Remedial Design/Remedial Action Work Plan (DOEIRL-2008-78). Currently, the model has been developed to the extent necessary to provide approximate results and to lay a foundation for the design basis concentrations that are required in support of the remedial design/remediation action (RD/RA) work plan. The discussion in this document includes the following: (1) Assignment of flow and transport parameters for the model; (2) Definition of initial conditions for the transport model for each simulated contaminant of concern (COC) (i.e., carbon

  20. Noise exposure during pregnancy, birth outcomes and fetal development: meta-analyses using quality effects model.

    Science.gov (United States)

    Dzhambov, Angel M; Dimitrova, Donka D; Dimitrakova, Elena D

    2014-01-01

    Many women are exposed daily to high levels of occupational and residential noise, so the effect of noise exposure on pregnancy should be considered because noise affects both the fetus and the mother herself. However, there is a controversy in the literature regarding the adverse effects of occupational and residential noise on pregnant women and their fetuses. The aim of this study was to conduct systematic review of previously analyzed studies, to add additional information omitted in previous reviews and to perform meta-analyses on the effects of noise exposure on pregnancy, birth outcomes and fetal development. Previous reviews and meta-analyses on the topic were consulted. Additionally, a systematic search in MEDLINE, EMBASE and Internet was carried out. Twenty nine studies were included in the meta-analyses. Quality effects meta-analytical model was applied. Women exposed to high noise levels (in most of the studies ≥ 80 dB) during pregnancy are at a significantly higher risk for having small-for-gestational-age newborn (RR = 1.19, 95% CI: 1.03, 1.38), gestational hypertension (RR = 1.27, 95% CI: 1.03, 1.58) and infant with congenital malformations (RR = 1.47, 95% CI: 1.21, 1.79). The effect was not significant for preeclampsia, perinatal death, spontaneous abortion and preterm birth. The results are consistent with previous findings regarding a higher risk for small-for-gestational-age. They also highlight the significance of residential and occupational noise exposure for developing gestational hypertension and especially congenital malformations.

  1. Normalisation genes for expression analyses in the brown alga model Ectocarpus siliculosus

    Directory of Open Access Journals (Sweden)

    Rousvoal Sylvie

    2008-08-01

    Full Text Available Abstract Background Brown algae are plant multi-cellular organisms occupying most of the world coasts and are essential actors in the constitution of ecological niches at the shoreline. Ectocarpus siliculosus is an emerging model for brown algal research. Its genome has been sequenced, and several tools are being developed to perform analyses at different levels of cell organization, including transcriptomic expression analyses. Several topics, including physiological responses to osmotic stress and to exposure to contaminants and solvents are being studied in order to better understand the adaptive capacity of brown algae to pollution and environmental changes. A series of genes that can be used to normalise expression analyses is required for these studies. Results We monitored the expression of 13 genes under 21 different culture conditions. These included genes encoding proteins and factors involved in protein translation (ribosomal protein 26S, EF1alpha, IF2A, IF4E and protein degradation (ubiquitin, ubiquitin conjugating enzyme or folding (cyclophilin, and proteins involved in both the structure of the cytoskeleton (tubulin alpha, actin, actin-related proteins and its trafficking function (dynein, as well as a protein implicated in carbon metabolism (glucose 6-phosphate dehydrogenase. The stability of their expression level was assessed using the Ct range, and by applying both the geNorm and the Normfinder principles of calculation. Conclusion Comparisons of the data obtained with the three methods of calculation indicated that EF1alpha (EF1a was the best reference gene for normalisation. The normalisation factor should be calculated with at least two genes, alpha tubulin, ubiquitin-conjugating enzyme or actin-related proteins being good partners of EF1a. Our results exclude actin as a good normalisation gene, and, in this, are in agreement with previous studies in other organisms.

  2. Models for regionalizing economic data and their applications within the scope of forensic disaster analyses

    Science.gov (United States)

    Schmidt, Hanns-Maximilian; Wiens, rer. pol. Marcus, , Dr.; Schultmann, rer. pol. Frank, Prof. _., Dr.

    2015-04-01

    The impact of natural hazards on the economic system can be observed in many different regions all over the world. Once the local economic structure is hit by an event direct costs instantly occur. However, the disturbance on a local level (e.g. parts of city or industries along a river bank) might also cause monetary damages in other, indirectly affected sectors. If the impact of an event is strong, these damages are likely to cascade and spread even on an international scale (e.g. the eruption of Eyjafjallajökull and its impact on the automotive sector in Europe). In order to determine these special impacts, one has to gain insights into the directly hit economic structure before being able to calculate these side effects. Especially, regarding the development of a model used for near real-time forensic disaster analyses any simulation needs to be based on data that is rapidly available or easily to be computed. Therefore, we investigated commonly used or recently discussed methodologies for regionalizing economic data. Surprisingly, even for German federal states there is no official input-output data available that can be used, although it might provide detailed figures concerning economic interrelations between different industry sectors. In the case of highly developed countries, such as Germany, we focus on models for regionalizing nationwide input-output table which is usually available at the national statistical offices. However, when it comes to developing countries (e.g. South-East Asia) the data quality and availability is usually much poorer. In this case, other sources need to be found for the proper assessment of regional economic performance. We developed an indicator-based model that can fill this gap because of its flexibility regarding the level of aggregation and the composability of different input parameters. Our poster presentation brings up a literature review and a summary on potential models that seem to be useful for this specific task

  3. Evaluation of Temperature and Humidity Profiles of Unified Model and ECMWF Analyses Using GRUAN Radiosonde Observations

    Directory of Open Access Journals (Sweden)

    Young-Chan Noh

    2016-07-01

    Full Text Available Temperature and water vapor profiles from the Korea Meteorological Administration (KMA and the United Kingdom Met Office (UKMO Unified Model (UM data assimilation systems and from reanalysis fields from the European Centre for Medium-Range Weather Forecasts (ECMWF were assessed using collocated radiosonde observations from the Global Climate Observing System (GCOS Reference Upper-Air Network (GRUAN for January–December 2012. The motivation was to examine the overall performance of data assimilation outputs. The difference statistics of the collocated model outputs versus the radiosonde observations indicated a good agreement for the temperature, amongst datasets, while less agreement was found for the relative humidity. A comparison of the UM outputs from the UKMO and KMA revealed that they are similar to each other. The introduction of the new version of UM into the KMA in May 2012 resulted in an improved analysis performance, particularly for the moisture field. On the other hand, ECMWF reanalysis data showed slightly reduced performance for relative humidity compared with the UM, with a significant humid bias in the upper troposphere. ECMWF reanalysis temperature fields showed nearly the same performance as the two UM analyses. The root mean square differences (RMSDs of the relative humidity for the three models were larger for more humid conditions, suggesting that humidity forecasts are less reliable under these conditions.

  4. Integrated optimization analyses of aerodynamic/stealth characteristics of helicopter rotor based on surrogate model

    Directory of Open Access Journals (Sweden)

    Jiang Xiangwen

    2015-06-01

    Full Text Available Based on computational fluid dynamics (CFD method, electromagnetic high-frequency method and surrogate model optimization techniques, an integration design method about aerodynamic/stealth has been established for helicopter rotor. The developed integration design method is composed of three modules: integrated grids generation (the moving-embedded grids for CFD solver and the blade grids for radar cross section (RCS solver are generated by solving Poisson equations and folding approach, aerodynamic/stealth solver (the aerodynamic characteristics are simulated by CFD method based upon Navier–Stokes equations and Spalart–Allmaras (S–A turbulence model, and the stealth characteristics are calculated by using a panel edge method combining the method of physical optics (PO, equivalent currents (MEC and quasi-stationary (MQS, and integrated optimization analysis (based upon the surrogate model optimization technique with full factorial design (FFD and radial basis function (RBF, an integrated optimization analyses on aerodynamic/stealth characteristics of rotor are conducted. Firstly, the scattering characteristics of the rotor with different blade-tip swept and twist angles have been carried out, then time–frequency domain grayscale with strong scattering regions of rotor have been given. Meanwhile, the effects of swept-tip and twist angles on the aerodynamic characteristic of rotor have been performed. Furthermore, by choosing suitable object function and constraint condition, the compromised design about swept and twist combinations of rotor with high aerodynamic performances and low scattering characteristics has been given at last.

  5. Analyses of Research Topics in the Field of Informetrics Based on the Method of Topic Modeling

    Directory of Open Access Journals (Sweden)

    Sung-Chien Lin

    2014-07-01

    Full Text Available In this study, we used the approach of topic modeling to uncover the possible structure of research topics in the field of Informetrics, to explore the distribution of the topics over years, and to compare the core journals. In order to infer the structure of the topics in the field, the data of the papers published in the Journal of Informetricsand Scientometrics during 2007 to 2013 are retrieved from the database of the Web of Science as input of the approach of topic modeling. The results of this study show that when the number of topics was set to 10, the topic model has the smallest perplexity. Although data scopes and analysis methodsare different to previous studies, the generating topics of this study are consistent with those results produced by analyses of experts. Empirical case studies and measurements of bibliometric indicators were concerned important in every year during the whole analytic period, and the field was increasing stability. Both the two core journals broadly paid more attention to all of the topics in the field of Informetrics. The Journal of Informetricsput particular emphasis on construction and applications ofbibliometric indicators and Scientometrics focused on the evaluation and the factors of productivity of countries, institutions, domains, and journals.

  6. Application of a weighted spatial probability model in GIS to analyse landslides in Penang Island, Malaysia

    Directory of Open Access Journals (Sweden)

    Samy Ismail Elmahdy

    2016-01-01

    Full Text Available In the current study, Penang Island, which is one of the several mountainous areas in Malaysia that is often subjected to landslide hazard, was chosen for further investigation. A multi-criteria Evaluation and the spatial probability weighted approach and model builder was applied to map and analyse landslides in Penang Island. A set of automated algorithms was used to construct new essential geological and morphometric thematic maps from remote sensing data. The maps were ranked using the weighted probability spatial model based on their contribution to the landslide hazard. Results obtained showed that sites at an elevation of 100–300 m, with steep slopes of 10°–37° and slope direction (aspect in the E and SE directions were areas of very high and high probability for the landslide occurrence; the total areas were 21.393 km2 (11.84% and 58.690 km2 (32.48%, respectively. The obtained map was verified by comparing variogram models of the mapped and the occurred landslide locations and showed a strong correlation with the locations of occurred landslides, indicating that the proposed method can successfully predict the unpredictable landslide hazard. The method is time and cost effective and can be used as a reference for geological and geotechnical engineers.

  7. Comparative modeling analyses of Cs-137 fate in the rivers impacted by Chernobyl and Fukushima accidents

    Energy Technology Data Exchange (ETDEWEB)

    Zheleznyak, M.; Kivva, S. [Institute of Environmental Radioactivity, Fukushima University (Japan)

    2014-07-01

    The consequences of two largest nuclear accidents of the last decades - at Chernobyl Nuclear Power Plant (ChNPP) (1986) and at Fukushima Daiichi NPP (FDNPP) (2011) clearly demonstrated that radioactive contamination of water bodies in vicinity of NPP and on the waterways from it, e.g., river- reservoir water after Chernobyl accident and rivers and coastal marine waters after Fukushima accident, in the both cases have been one of the main sources of the public concerns on the accident consequences. The higher weight of water contamination in public perception of the accidents consequences in comparison with the real fraction of doses via aquatic pathways in comparison with other dose components is a specificity of public perception of environmental contamination. This psychological phenomenon that was confirmed after these accidents provides supplementary arguments that the reliable simulation and prediction of the radionuclide dynamics in water and sediments is important part of the post-accidental radioecological research. The purpose of the research is to use the experience of the modeling activities f conducted for the past more than 25 years within the Chernobyl affected Pripyat River and Dnieper River watershed as also data of the new monitoring studies in Japan of Abukuma River (largest in the region - the watershed area is 5400 km{sup 2}), Kuchibuto River, Uta River, Niita River, Natsui River, Same River, as also of the studies on the specific of the 'water-sediment' {sup 137}Cs exchanges in this area to refine the 1-D model RIVTOX and 2-D model COASTOX for the increasing of the predictive power of the modeling technologies. The results of the modeling studies are applied for more accurate prediction of water/sediment radionuclide contamination of rivers and reservoirs in the Fukushima Prefecture and for the comparative analyses of the efficiency of the of the post -accidental measures to diminish the contamination of the water bodies. Document

  8. Continuous spatial modelling to analyse planning and economic consequences of offshore wind energy

    International Nuclear Information System (INIS)

    Moeller, Bernd

    2011-01-01

    Offshore wind resources appear abundant, but technological, economic and planning issues significantly reduce the theoretical potential. While massive investments are anticipated and planners and developers are scouting for viable locations and consider risk and impact, few studies simultaneously address potentials and costs together with the consequences of proposed planning in an analytical and continuous manner and for larger areas at once. Consequences may be investments short of efficiency and equity, and failed planning routines. A spatial resource economic model for the Danish offshore waters is presented, used to analyse area constraints, technological risks, priorities for development and opportunity costs of maintaining competing area uses. The SCREAM-offshore wind model (Spatially Continuous Resource Economic Analysis Model) uses raster-based geographical information systems (GIS) and considers numerous geographical factors, technology and cost data as well as planning information. Novel elements are weighted visibility analysis and geographically recorded shipping movements as variable constraints. A number of scenarios have been described, which include restrictions of using offshore areas, as well as alternative uses such as conservation and tourism. The results comprise maps, tables and cost-supply curves for further resource economic assessment and policy analysis. A discussion of parameter variations exposes uncertainties of technology development, environmental protection as well as competing area uses and illustrates how such models might assist in ameliorating public planning, while procuring decision bases for the political process. The method can be adapted to different research questions, and is largely applicable in other parts of the world. - Research Highlights: → A model for the spatially continuous evaluation of offshore wind resources. → Assessment of spatial constraints, costs and resources for each location. → Planning tool for

  9. Development and application of model RAIA uranium on-line analyser

    International Nuclear Information System (INIS)

    Dong Yanwu; Song Yufen; Zhu Yaokun; Cong Peiyuan; Cui Songru

    1999-01-01

    The working principle, structure, adjustment and application of model RAIA on-line analyser are reported. The performance of this instrument is reliable. For identical sample, the signal fluctuation in continuous monitoring for four months is less than +-1%. According to required measurement range, appropriate length of sample cell is chosen. The precision of measurement process is better than 1% at 100 g/L U. The detection limit is 50 mg/L. The uranium concentration in process stream can be displayed automatically and printed at any time. It presents 4∼20 mA current signal being proportional to the uranium concentration. This makes a long step towards process continuous control and computer management

  10. A model for analysing factors which may influence quality management procedures in higher education

    Directory of Open Access Journals (Sweden)

    Cătălin MAICAN

    2015-12-01

    Full Text Available In all universities, the Office for Quality Assurance defines the procedure for assessing the performance of the teaching staff, with a view to establishing students’ perception as regards the teachers’ activity from the point of view of the quality of the teaching process, of the relationship with the students and of the assistance provided for learning. The present paper aims at creating a combined model for evaluation, based on Data Mining statistical methods: starting from the findings revealed by the evaluations teachers performed to students, using the cluster analysis and the discriminant analysis, we identified the subjects which produced significant differences between students’ grades, subjects which were subsequently subjected to an evaluation by students. The results of these analyses allowed the formulation of certain measures for enhancing the quality of the evaluation process.

  11. Developing a system dynamics model to analyse environmental problem in construction site

    Science.gov (United States)

    Haron, Fatin Fasehah; Hawari, Nurul Nazihah

    2017-11-01

    This study aims to develop a system dynamics model at a construction site to analyse the impact of environmental problem. Construction sites may cause damages to the environment, and interference in the daily lives of residents. A proper environmental management system must be used to reduce pollution, enhance bio-diversity, conserve water, respect people and their local environment, measure performance and set targets for the environment and sustainability. This study investigates the damaging impact normally occur during the construction stage. Environmental problem will cause costly mistake in project implementation, either because of the environmental damages that are likely to arise during project implementation, or because of modification that may be required subsequently in order to make the action environmentally acceptable. Thus, findings from this study has helped in significantly reducing the damaging impact towards environment, and improve the environmental management system performance at construction site.

  12. Applying the Land Use Portfolio Model with Hazus to analyse risk from natural hazard events

    Science.gov (United States)

    Dinitz, Laura B.; Taketa, Richard A.

    2013-01-01

    This paper describes and demonstrates the integration of two geospatial decision-support systems for natural-hazard risk assessment and management. Hazus is a risk-assessment tool developed by the Federal Emergency Management Agency to identify risks and estimate the severity of risk from natural hazards. The Land Use Portfolio Model (LUPM) is a risk-management tool developed by the U.S. Geological Survey to evaluate plans or actions intended to reduce risk from natural hazards. We analysed three mitigation policies for one earthquake scenario in the San Francisco Bay area to demonstrate the added value of using Hazus and the LUPM together. The demonstration showed that Hazus loss estimates can be input to the LUPM to obtain estimates of losses avoided through mitigation, rates of return on mitigation investment, and measures of uncertainty. Together, they offer a more comprehensive approach to help with decisions for reducing risk from natural hazards.

  13. Testing a dual-systems model of adolescent brain development using resting-state connectivity analyses.

    Science.gov (United States)

    van Duijvenvoorde, A C K; Achterberg, M; Braams, B R; Peters, S; Crone, E A

    2016-01-01

    The current study aimed to test a dual-systems model of adolescent brain development by studying changes in intrinsic functional connectivity within and across networks typically associated with cognitive-control and affective-motivational processes. To this end, resting-state and task-related fMRI data were collected of 269 participants (ages 8-25). Resting-state analyses focused on seeds derived from task-related neural activation in the same participants: the dorsal lateral prefrontal cortex (dlPFC) from a cognitive rule-learning paradigm and the nucleus accumbens (NAcc) from a reward-paradigm. Whole-brain seed-based resting-state analyses showed an age-related increase in dlPFC connectivity with the caudate and thalamus, and an age-related decrease in connectivity with the (pre)motor cortex. nAcc connectivity showed a strengthening of connectivity with the dorsal anterior cingulate cortex (ACC) and subcortical structures such as the hippocampus, and a specific age-related decrease in connectivity with the ventral medial PFC (vmPFC). Behavioral measures from both functional paradigms correlated with resting-state connectivity strength with their respective seed. That is, age-related change in learning performance was mediated by connectivity between the dlPFC and thalamus, and age-related change in winning pleasure was mediated by connectivity between the nAcc and vmPFC. These patterns indicate (i) strengthening of connectivity between regions that support control and learning, (ii) more independent functioning of regions that support motor and control networks, and (iii) more independent functioning of regions that support motivation and valuation networks with age. These results are interpreted vis-à-vis a dual-systems model of adolescent brain development. Copyright © 2015. Published by Elsevier Inc.

  14. Individual-level space-time analyses of emergency department data using generalized additive modeling

    Directory of Open Access Journals (Sweden)

    Vieira Verónica M

    2012-08-01

    Full Text Available Abstract Background Although daily emergency department (ED data is a source of information that often includes residence, its potential for space-time analyses at the individual level has not been fully explored. We propose that ED data collected for surveillance purposes can also be used to inform spatial and temporal patterns of disease using generalized additive models (GAMs. This paper describes the methods for adapting GAMs so they can be applied to ED data. Methods GAMs are an effective approach for modeling spatial and temporal distributions of point-wise data, producing smoothed surfaces of continuous risk while adjusting for confounders. In addition to disease mapping, the method allows for global and pointwise hypothesis testing and selection of statistically optimum degree of smoothing using standard statistical software. We applied a two-dimensional GAM for location to ED data of overlapping calendar time using a locally-weighted regression smoother. To illustrate our methods, we investigated the association between participants’ address and the risk of gastrointestinal illness in Cape Cod, Massachusetts over time. Results The GAM space-time analyses simultaneously smooth in units of distance and time by using the optimum degree of smoothing to create data frames of overlapping time periods and then spatially analyzing each data frame. When resulting maps are viewed in series, each data frame contributes a movie frame, allowing us to visualize changes in magnitude, geographic size, and location of elevated risk smoothed over space and time. In our example data, we observed an underlying geographic pattern of gastrointestinal illness with risks consistently higher in the eastern part of our study area over time and intermittent variations of increased risk during brief periods. Conclusions Spatial-temporal analysis of emergency department data with GAMs can be used to map underlying disease risk at the individual-level and view

  15. Parameterization and sensitivity analyses of a radiative transfer model for remote sensing plant canopies

    Science.gov (United States)

    Hall, Carlton Raden

    A major objective of remote sensing is determination of biochemical and biophysical characteristics of plant canopies utilizing high spectral resolution sensors. Canopy reflectance signatures are dependent on absorption and scattering processes of the leaf, canopy properties, and the ground beneath the canopy. This research investigates, through field and laboratory data collection, and computer model parameterization and simulations, the relationships between leaf optical properties, canopy biophysical features, and the nadir viewed above-canopy reflectance signature. Emphasis is placed on parameterization and application of an existing irradiance radiative transfer model developed for aquatic systems. Data and model analyses provide knowledge on the relative importance of leaves and canopy biophysical features in estimating the diffuse absorption a(lambda,m-1), diffuse backscatter b(lambda,m-1), beam attenuation alpha(lambda,m-1), and beam to diffuse conversion c(lambda,m-1 ) coefficients of the two-flow irradiance model. Data sets include field and laboratory measurements from three plant species, live oak (Quercus virginiana), Brazilian pepper (Schinus terebinthifolius) and grapefruit (Citrus paradisi) sampled on Cape Canaveral Air Force Station and Kennedy Space Center Florida in March and April of 1997. Features measured were depth h (m), projected foliage coverage PFC, leaf area index LAI, and zenith leaf angle. Optical measurements, collected with a Spectron SE 590 high sensitivity narrow bandwidth spectrograph, included above canopy reflectance, internal canopy transmittance and reflectance and bottom reflectance. Leaf samples were returned to laboratory where optical and physical and chemical measurements of leaf thickness, leaf area, leaf moisture and pigment content were made. A new term, the leaf volume correction index LVCI was developed and demonstrated in support of model coefficient parameterization. The LVCI is based on angle adjusted leaf

  16. Sensitivity analyses of a colloid-facilitated contaminant transport model for unsaturated heterogeneous soil conditions.

    Science.gov (United States)

    Périard, Yann; José Gumiere, Silvio; Rousseau, Alain N.; Caron, Jean

    2013-04-01

    Certain contaminants may travel faster through soils when they are sorbed to subsurface colloidal particles. Indeed, subsurface colloids may act as carriers of some contaminants accelerating their translocation through the soil into the water table. This phenomenon is known as colloid-facilitated contaminant transport. It plays a significant role in contaminant transport in soils and has been recognized as a source of groundwater contamination. From a mechanistic point of view, the attachment/detachment of the colloidal particles from the soil matrix or from the air-water interface and the straining process may modify the hydraulic properties of the porous media. Šimůnek et al. (2006) developed a model that can simulate the colloid-facilitated contaminant transport in variably saturated porous media. The model is based on the solution of a modified advection-dispersion equation that accounts for several processes, namely: straining, exclusion and attachement/detachement kinetics of colloids through the soil matrix. The solutions of these governing, partial differential equations are obtained using a standard Galerkin-type, linear finite element scheme, implemented in the HYDRUS-2D/3D software (Šimůnek et al., 2012). Modeling colloid transport through the soil and the interaction of colloids with the soil matrix and other contaminants is complex and requires the characterization of many model parameters. In practice, it is very difficult to assess actual transport parameter values, so they are often calibrated. However, before calibration, one needs to know which parameters have the greatest impact on output variables. This kind of information can be obtained through a sensitivity analysis of the model. The main objective of this work is to perform local and global sensitivity analyses of the colloid-facilitated contaminant transport module of HYDRUS. Sensitivity analysis was performed in two steps: (i) we applied a screening method based on Morris' elementary

  17. Modeling and analysing storage systems in agricultural biomass supply chain for cellulosic ethanol production

    International Nuclear Information System (INIS)

    Ebadian, Mahmood; Sowlati, Taraneh; Sokhansanj, Shahab; Townley-Smith, Lawrence; Stumborg, Mark

    2013-01-01

    Highlights: ► Studied the agricultural biomass supply chain for cellulosic ethanol production. ► Evaluated the impact of storage systems on different supply chain actors. ► Developed a combined simulation/optimization model to evaluate storage systems. ► Compared two satellite storage systems with roadside storage in terms of costs and emitted CO 2 . ► SS would lead to a more cost-efficient supply chain compared to roadside storage. -- Abstract: In this paper, a combined simulation/optimization model is developed to better understand and evaluate the impact of the storage systems on the costs incurred by each actor in the agricultural biomass supply chain including farmers, hauling contractors and the cellulosic ethanol plant. The optimization model prescribes the optimum number and location of farms and storages. It also determines the supply radius, the number of farms required to secure the annual supply of biomass and also the assignment of farms to storage locations. Given the specific design of the supply chain determined by the optimization model, the simulation model determines the number of required machines for each operation, their daily working schedule and utilization rates, along with the capacities of storages. To evaluate the impact of the storage systems on the delivered costs, three storage systems are molded and compared: roadside storage (RS) system and two satellite storage (SS) systems including SS with fixed hauling distance (SF) and SS with variable hauling distance (SV). In all storage systems, it is assumed the loading equipment is dedicated to storage locations. The obtained results from a real case study provide detailed cost figures for each storage system since the developed model analyses the supply chain on an hourly basis and considers time-dependence and stochasticity of the supply chain. Comparison of the storage systems shows SV would outperform SF and RS by reducing the total delivered cost by 8% and 6%, respectively

  18. CERES model application for increasing preparedness to climate variability in agricultural planning—risk analyses

    Science.gov (United States)

    Popova, Zornitsa; Kercheva, Milena

    The role of soil, crop, climate and crop management for year-to-year variation of yield and groundwater pollution was quantified by simulation analyses with CERES-maize and CERES-wheat models over a 30-year period for four “soil-crop” combinations. It was established that “Chromic Luvisol-maize-dry land” combination was associated with the greatest coefficient of variability of yields ( Cv = 43%) and drought frequency (in 22 years with yield losses more than 20%) over the analysed period. Average yield losses in dry vegetation seasons were 60% of maize productivity potential under sufficient soil moisture. Traditional and drainage controlling precise irrigation scheduling mitigated drought consequences by reducing year-to-year variability of yield to Cv = 5.6-11.6% on risky Chromic Luvisol. Long-term wheat yields were much more stable ( Cv = 23-26%) than those of maize on Chromic Luvisol. In this case droughts covered 12 of the studied 30 years in which yield losses were 25-30% on the average. Soils of high water holding capacity (as Vertisol) stored 50-150 mm additional precipitation for crop evapotranspiration and thus reduced frequency of drought under both crops to 6-7 cases in 30 years. Agriculture should be more sustainable on this soil since variability of yield dropped to Cv = 13% for wheat and respectively Cv = 21% for maize. As a result Vertisol mitigated yield losses during dry vegetation periods by 10-15% for wheat and 22% for maize if compared with productivity under sufficient soil water. Thirty-year frequency analyses of seasonal nitrogen (N)-leaching, proved that ten of wheat and only one of maize vegetation seasons were susceptible to significant (10-45 kg N/ha/year) ground water pollution on Chromic Luvisol. Simulated precise irrigation scenario did not influence drainage in vegetation period. Another risky situations occurred under maize in the wettest fallow state after extremely dry vegetation (in one more of the studied years) when up

  19. Neural Spike-Train Analyses of the Speech-Based Envelope Power Spectrum Model

    Directory of Open Access Journals (Sweden)

    Varsha H. Rallapalli

    2016-10-01

    Full Text Available Diagnosing and treating hearing impairment is challenging because people with similar degrees of sensorineural hearing loss (SNHL often have different speech-recognition abilities. The speech-based envelope power spectrum model (sEPSM has demonstrated that the signal-to-noise ratio (SNRENV from a modulation filter bank provides a robust speech-intelligibility measure across a wider range of degraded conditions than many long-standing models. In the sEPSM, noise (N is assumed to: (a reduce S + N envelope power by filling in dips within clean speech (S and (b introduce an envelope noise floor from intrinsic fluctuations in the noise itself. While the promise of SNRENV has been demonstrated for normal-hearing listeners, it has not been thoroughly extended to hearing-impaired listeners because of limited physiological knowledge of how SNHL affects speech-in-noise envelope coding relative to noise alone. Here, envelope coding to speech-in-noise stimuli was quantified from auditory-nerve model spike trains using shuffled correlograms, which were analyzed in the modulation-frequency domain to compute modulation-band estimates of neural SNRENV. Preliminary spike-train analyses show strong similarities to the sEPSM, demonstrating feasibility of neural SNRENV computations. Results suggest that individual differences can occur based on differential degrees of outer- and inner-hair-cell dysfunction in listeners currently diagnosed into the single audiological SNHL category. The predicted acoustic-SNR dependence in individual differences suggests that the SNR-dependent rate of susceptibility could be an important metric in diagnosing individual differences. Future measurements of the neural SNRENV in animal studies with various forms of SNHL will provide valuable insight for understanding individual differences in speech-in-noise intelligibility.

  20. Using an operating cost model to analyse the selection of aircraft type on short-haul routes

    CSIR Research Space (South Africa)

    Ssamula, B

    2006-08-01

    Full Text Available operating cost model to analyse suitable aircraft choices, for short haul routes, in terms of cost-related parameters, for aircraft commonly used within Africa. In this paper all the parameters that are crucial in analysing a transport service are addressed...

  1. Analysing model fit of psychometric process models: An overview, a new test and an application to the diffusion model.

    Science.gov (United States)

    Ranger, Jochen; Kuhn, Jörg-Tobias; Szardenings, Carsten

    2017-05-01

    Cognitive psychometric models embed cognitive process models into a latent trait framework in order to allow for individual differences. Due to their close relationship to the response process the models allow for profound conclusions about the test takers. However, before such a model can be used its fit has to be checked carefully. In this manuscript we give an overview over existing tests of model fit and show their relation to the generalized moment test of Newey (Econometrica, 53, 1985, 1047) and Tauchen (J. Econometrics, 30, 1985, 415). We also present a new test, the Hausman test of misspecification (Hausman, Econometrica, 46, 1978, 1251). The Hausman test consists of a comparison of two estimates of the same item parameters which should be similar if the model holds. The performance of the Hausman test is evaluated in a simulation study. In this study we illustrate its application to two popular models in cognitive psychometrics, the Q-diffusion model and the D-diffusion model (van der Maas, Molenaar, Maris, Kievit, & Boorsboom, Psychol Rev., 118, 2011, 339; Molenaar, Tuerlinckx, & van der Maas, J. Stat. Softw., 66, 2015, 1). We also compare the performance of the test to four alternative tests of model fit, namely the M 2 test (Molenaar et al., J. Stat. Softw., 66, 2015, 1), the moment test (Ranger et al., Br. J. Math. Stat. Psychol., 2016) and the test for binned time (Ranger & Kuhn, Psychol. Test. Asess. , 56, 2014b, 370). The simulation study indicates that the Hausman test is superior to the latter tests. The test closely adheres to the nominal Type I error rate and has higher power in most simulation conditions. © 2017 The British Psychological Society.

  2. Molecular approaches for viable bacterial population and transcriptional analyses in a rodent model of dental caries

    Science.gov (United States)

    Klein, Marlise I.; Scott-Anne, Kathleen M.; Gregoire, Stacy; Rosalen, Pedro L.; Koo, Hyun

    2012-01-01

    SUMMARY Culturing methods are the primary approach for microbiological analysis of plaque-biofilms in rodent models of dental caries. In this study, we developed strategies for isolation of DNA and RNA from in vivo formed plaque-biofilms to analyze the viable bacterial population and gene expression. Plaque-biofilm samples from rats were treated with propidium monoazide to isolate DNA from viable cells, and the purified DNA was used to quantify total bacteria and S. mutans population via qPCR and specific primers; the same samples were also analyzed by colony forming unit (CFU) counting. In parallel, RNA was isolated from plaque-biofilm samples (from same animals) and used for transcriptional analyses via RT-qPCR. The viable population of both S. mutans and total bacteria assessed by qPCR were positively correlated with the CFU data (P0.8). However, the qPCR data showed higher bacterial cell counts, particularly for total bacteria (vs. CFU). Moreover, S. mutans proportion in the plaque-biofilm determined by qPCR analysis showed strong correlation with incidence of smooth-surface caries (P=0.0022, r=0.71). The purified RNAs presented high RNA integrity numbers (>7), which allowed measurement of the expression of genes that are critical for S. mutans virulence (e.g. gtfB and gtfC). Our data show that the viable microbial population and the gene expression can be analyzed simultaneously, providing a global assessment of the infectious aspect of the disease dental caries. Our approach could enhance the value of the current rodent model in further understanding the pathophysiology of this disease and facilitating the exploration of novel anti-caries therapies. PMID:22958384

  3. Evaluating and Refining the Conceptual Model Used in the Study of Health and Activity in Preschool Environments (SHAPES) Intervention.

    Science.gov (United States)

    Saunders, Ruth P; Pfeiffer, Karin; Brown, William H; Howie, Erin K; Dowda, Marsha; O'Neill, Jennifer R; McIver, Kerry; Pate, Russell R

    2017-12-01

    This study investigated the utility of the Study of Health and Activity in Preschool Environments (SHAPES) conceptual model, which targeted physical activity (PA) behavior in preschool children, by examining the relationship between implementation monitoring data and child PA during the school day. We monitored implementation completeness and fidelity based on multiple elements identified in the conceptual model. Comparing high-implementing, low-implementing, and control groups revealed no association between implementation and outcomes. We performed post hoc analyses, using process data, to refine our conceptual model's depiction of an effective preschool PA-promoting environment. Results suggest that a single component of the original four-component conceptual model, providing opportunities for moderate-to-vigorous physical activity through recess for 4-year-old children in preschool settings, may be a good starting place for increasing moderate-to-vigorous physical activity. Interventions that are implemented with optimal levels of completeness and fidelity are more likely to achieve behavior change if they are based on accurate conceptual models. Examining the mechanisms through which an intervention produces its effects, as articulated in the conceptual model that guides it, is particularly important for environmentally focused interventions because they are guided by emerging frameworks. The results of this study underscore the utility of using implementation monitoring data to examine the conceptual model on which the intervention is based.

  4. Targeting the robo-advice customer: the development of a psychographic segmentation model for financial advice robots

    OpenAIRE

    van Thiel, D.; van Raaij, W.F.

    2017-01-01

    The purpose of this study is to develop the world’s first psychographic market segmentation model that supports personalization, customer education, customer activation, and customer engagement strategies with financial advice robots. As traditional segmentation models in consumer finance primarily focus on externally observed demographics or economic criteria such as profession, age, income, or wealth, post-hoc psychographic segmentation further supports personalization in the digital adviso...

  5. VOC composition of current motor vehicle fuels and vapors, and collinearity analyses for receptor modeling.

    Science.gov (United States)

    Chin, Jo-Yu; Batterman, Stuart A

    2012-03-01

    The formulation of motor vehicle fuels can alter the magnitude and composition of evaporative and exhaust emissions occurring throughout the fuel cycle. Information regarding the volatile organic compound (VOC) composition of motor fuels other than gasoline is scarce, especially for bioethanol and biodiesel blends. This study examines the liquid and vapor (headspace) composition of four contemporary and commercially available fuels: gasoline (gasoline), ultra-low sulfur diesel (ULSD), and B20 (20% soy-biodiesel and 80% ULSD). The composition of gasoline and E85 in both neat fuel and headspace vapor was dominated by aromatics and n-heptane. Despite its low gasoline content, E85 vapor contained higher concentrations of several VOCs than those in gasoline vapor, likely due to adjustments in its formulation. Temperature changes produced greater changes in the partial pressures of 17 VOCs in E85 than in gasoline, and large shifts in the VOC composition. B20 and ULSD were dominated by C(9) to C(16)n-alkanes and low levels of the aromatics, and the two fuels had similar headspace vapor composition and concentrations. While the headspace composition predicted using vapor-liquid equilibrium theory was closely correlated to measurements, E85 vapor concentrations were underpredicted. Based on variance decomposition analyses, gasoline and diesel fuels and their vapors VOC were distinct, but B20 and ULSD fuels and vapors were highly collinear. These results can be used to estimate fuel related emissions and exposures, particularly in receptor models that apportion emission sources, and the collinearity analysis suggests that gasoline- and diesel-related emissions can be distinguished. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Modeling ecological drivers in marine viral communities using comparative metagenomics and network analyses.

    Science.gov (United States)

    Hurwitz, Bonnie L; Westveld, Anton H; Brum, Jennifer R; Sullivan, Matthew B

    2014-07-22

    Long-standing questions in marine viral ecology are centered on understanding how viral assemblages change along gradients in space and time. However, investigating these fundamental ecological questions has been challenging due to incomplete representation of naturally occurring viral diversity in single gene- or morphology-based studies and an inability to identify up to 90% of reads in viral metagenomes (viromes). Although protein clustering techniques provide a significant advance by helping organize this unknown metagenomic sequence space, they typically use only ∼75% of the data and rely on assembly methods not yet tuned for naturally occurring sequence variation. Here, we introduce an annotation- and assembly-free strategy for comparative metagenomics that combines shared k-mer and social network analyses (regression modeling). This robust statistical framework enables visualization of complex sample networks and determination of ecological factors driving community structure. Application to 32 viromes from the Pacific Ocean Virome dataset identified clusters of samples broadly delineated by photic zone and revealed that geographic region, depth, and proximity to shore were significant predictors of community structure. Within subsets of this dataset, depth, season, and oxygen concentration were significant drivers of viral community structure at a single open ocean station, whereas variability along onshore-offshore transects was driven by oxygen concentration in an area with an oxygen minimum zone and not depth or proximity to shore, as might be expected. Together these results demonstrate that this highly scalable approach using complete metagenomic network-based comparisons can both test and generate hypotheses for ecological investigation of viral and microbial communities in nature.

  7. Inverse analyses of effective diffusion parameters relevant for a two-phase moisture model of cementitious materials

    DEFF Research Database (Denmark)

    Addassi, Mouadh; Johannesson, Björn; Wadsö, Lars

    2018-01-01

    Here we present an inverse analyses approach to determining the two-phase moisture transport properties relevant to concrete durability modeling. The purposed moisture transport model was based on a continuum approach with two truly separate equations for the liquid and gas phase being connected...

  8. Usefulness of non-linear input-output models for economic impact analyses in tourism and recreation

    NARCIS (Netherlands)

    Klijs, J.; Peerlings, J.H.M.; Heijman, W.J.M.

    2015-01-01

    In tourism and recreation management it is still common practice to apply traditional input–output (IO) economic impact models, despite their well-known limitations. In this study the authors analyse the usefulness of applying a non-linear input–output (NLIO) model, in which price-induced input

  9. Experimental and modeling analyses for interactions between graphene oxide and quartz sand.

    Science.gov (United States)

    Kang, Jin-Kyu; Park, Jeong-Ann; Yi, In-Geol; Kim, Song-Bae

    2017-03-21

    The aim of this study was to quantify the interactions between graphene oxide (GO) and quartz sand by conducting experimental and modeling analyses. The results show that both GO and quartz sand were negatively charged in the presence of 0-50 mM NaCl and 5 mM CaCl 2 (GO = -43.10 to -17.60 mV, quartz sand = -40.97 to -8.44 mV). In the Derjaguin-Landau-Verwey-Overbeek (DLVO) energy profiles, the adhesion of GO to quartz sand becomes more favorable with increasing NaCl concentration from 0 to 10 mM because the interaction energy profile was compressed and the primary maximum energy barrier was lowered. At 50 mM NaCl and 5 mM CaCl 2 , the primary maximum energy barrier even disappeared, resulting in highly favorable conditions for GO retention to quartz sand. In the Maxwell model analysis, the probability of GO adhesion to quartz sand (α m ) increased from 2.46 × 10 -4 to 9.98 × 10 -1 at ionic strengths of 0-10 mM NaCl. In the column experiments (column length = 10 cm, inner diameter = 2.5 cm, flow rate = 0.5 mL min -1 ), the mass removal (Mr) of GO in quartz sand increased from 5.4% to 97.8% as the NaCl concentration was increased from 0 to 50 mM, indicating that the mobility of GO was high in low ionic strength solutions and decreased with increasing ionic strength. The Mr value of GO at 5 mM CaCl 2 was 100%, demonstrating that Ca 2+ had a much stronger effect than Na + on the mobility of GO. In addition, the mobility of GO was lower than that of chloride (Mr = 1.4%) but far higher than that of multi-walled carbon nanotubes (Mr = 87.0%) in deionized water. In aluminum oxide-coated sand, the Mr value of GO was 98.1% at 0 mM NaCl, revealing that the mobility of GO was reduced in the presence of metal oxides. The transport model analysis indicates that the value of the dimensionless attachment rate coefficient (D a ) increased from 0.11 to 4.47 as the NaCl concentration was increased from 0 to 50 mM. In the colloid filtration model analysis, the

  10. A simple beam model to analyse the durability of adhesively bonded tile floorings in presence of shrinkage

    Directory of Open Access Journals (Sweden)

    S. de Miranda

    2014-07-01

    Full Text Available A simple beam model for the evaluation of tile debonding due to substrate shrinkage is presented. The tile-adhesive-substrate package is modeled as an Euler-Bernoulli beam laying on a two-layer elastic foundation. An effective discrete model for inter-tile grouting is introduced with the aim of modelling workmanship defects due to partial filled groutings. The model is validated using the results of a 2D FE model. Different defect configurations and adhesive typologies are analysed, focusing the attention on the prediction of normal stresses in the adhesive layer under the assumption of Mode I failure of the adhesive.

  11. Environmental regulation impacts on international trade: aggregate and sectoral analyses with a bilateral trade flow model

    NARCIS (Netherlands)

    van Beers, C.; van den Bergh, J.C.J.M.

    2003-01-01

    An important barrier to the implementation of strict environmental regulations is that they are perceived to negatively affect a country's competitiveness, visible through changes in international trade. Whereas theoretical analyses of trade and the environment indicate that relatively strict

  12. Dynamic causal modelling of brain-behaviour relationships.

    Science.gov (United States)

    Rigoux, L; Daunizeau, J

    2015-08-15

    In this work, we expose a mathematical treatment of brain-behaviour relationships, which we coin behavioural Dynamic Causal Modelling or bDCM. This approach aims at decomposing the brain's transformation of stimuli into behavioural outcomes, in terms of the relative contribution of brain regions and their connections. In brief, bDCM places the brain at the interplay between stimulus and behaviour: behavioural outcomes arise from coordinated activity in (hidden) neural networks, whose dynamics are driven by experimental inputs. Estimating neural parameters that control network connectivity and plasticity effectively performs a neurobiologically-constrained approximation to the brain's input-outcome transform. In other words, neuroimaging data essentially serves to enforce the realism of bDCM's decomposition of input-output relationships. In addition, post-hoc artificial lesions analyses allow us to predict induced behavioural deficits and quantify the importance of network features for funnelling input-output relationships. This is important, because this enables one to bridge the gap with neuropsychological studies of brain-damaged patients. We demonstrate the face validity of the approach using Monte-Carlo simulations, and its predictive validity using empirical fMRI/behavioural data from an inhibitory control task. Lastly, we discuss promising applications of this work, including the assessment of functional degeneracy (in the healthy brain) and the prediction of functional recovery after lesions (in neurological patients). Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Comparison of prosthetic models produced by traditional and additive manufacturing methods.

    Science.gov (United States)

    Park, Jin-Young; Kim, Hae-Young; Kim, Ji-Hwan; Kim, Jae-Hong; Kim, Woong-Chul

    2015-08-01

    The purpose of this study was to verify the clinical-feasibility of additive manufacturing by comparing the accuracy of four different manufacturing methods for metal coping: the conventional lost wax technique (CLWT); subtractive methods with wax blank milling (WBM); and two additive methods, multi jet modeling (MJM), and micro-stereolithography (Micro-SLA). Thirty study models were created using an acrylic model with the maxillary upper right canine, first premolar, and first molar teeth. Based on the scan files from a non-contact blue light scanner (Identica; Medit Co. Ltd., Seoul, Korea), thirty cores were produced using the WBM, MJM, and Micro-SLA methods, respectively, and another thirty frameworks were produced using the CLWT method. To measure the marginal and internal gap, the silicone replica method was adopted, and the silicone images obtained were evaluated using a digital microscope (KH-7700; Hirox, Tokyo, Japan) at 140X magnification. Analyses were performed using two-way analysis of variance (ANOVA) and Tukey post hoc test (α=.05). The mean marginal gaps and internal gaps showed significant differences according to tooth type (Pmanufacturing method (Pmanufacturing methods were within a clinically allowable range, and, thus, the clinical use of additive manufacturing methods is acceptable as an alternative to the traditional lost wax-technique and subtractive manufacturing.

  14. A Conceptual Model for Analysing Management Development in the UK Hospitality Industry

    Science.gov (United States)

    Watson, Sandra

    2007-01-01

    This paper presents a conceptual, contingent model of management development. It explains the nature of the UK hospitality industry and its potential influence on MD practices, prior to exploring dimensions and relationships in the model. The embryonic model is presented as a model that can enhance our understanding of the complexities of the…

  15. From intermediate to final behavioral endpoints; Modeling cognitions in (cost-)effectiveness analyses in health promotion

    NARCIS (Netherlands)

    Prenger, Hendrikje Cornelia

    2012-01-01

    Cost-effectiveness analyses (CEAs) are considered an increasingly important tool in health promotion and psychology. In health promotion adequate effectiveness data of innovative interventions are often lacking. In case of many promising interventions the available data are inadequate for CEAs due

  16. Developing computational model-based diagnostics to analyse clinical chemistry data

    NARCIS (Netherlands)

    Schalkwijk, D.B. van; Bochove, K. van; Ommen, B. van; Freidig, A.P.; Someren, E.P. van; Greef, J. van der; Graaf, A.A. de

    2010-01-01

    This article provides methodological and technical considerations to researchers starting to develop computational model-based diagnostics using clinical chemistry data.These models are of increasing importance, since novel metabolomics and proteomics measuring technologies are able to produce large

  17. Bio-economic farm modelling to analyse agricultural land productivity in Rwanda

    NARCIS (Netherlands)

    Bidogeza, J.C.

    2011-01-01

    Keywords: Rwanda; farm household typology; sustainable technology adoption; multivariate analysis;
    land degradation; food security; bioeconomic model; crop simulation models; organic fertiliser; inorganic fertiliser; policy incentives

    In Rwanda, land degradation contributes to the

  18. Bio-economic farm modelling to analyse agricultural land productivity in Rwanda

    NARCIS (Netherlands)

    Bidogeza, J.C.

    2011-01-01

    Keywords: Rwanda; farm household typology; sustainable technology adoption; multivariate analysis;
    land degradation; food security; bioeconomic model; crop simulation models; organic fertiliser; inorganic fertiliser; policy incentives In Rwanda, land degradation contributes to the low and

  19. Reference model for measuring and analysing costs – particularly in business informatics

    OpenAIRE

    Milos Maryska

    2010-01-01

    This paper is devoted to problems of management of cost efficiency of business informatics with Business Intelligence (BI) assistance. It defines basic critical points that must be taken into account during creating models for management of cost efficiency of business informatics. It proposes new model for management of cost efficiency, this model include also definitions of dimensions and indicators for measuring of this cost efficiency. The model takes into account requirements that pose cl...

  20. Quantifying and Analysing Neighbourhood Characteristics Supporting Urban Land-Use Modelling

    DEFF Research Database (Denmark)

    Hansen, Henning Sten

    2009-01-01

    Land-use modelling and spatial scenarios have gained increased attention as a means to meet the challenge of reducing uncertainty in the spatial planning and decision-making. Several organisations have developed software for land-use modelling. Many of the recent modelling efforts incorporate cel...

  1. Phenology in Germany in the 20th century : methods, analyses and models

    Science.gov (United States)

    Schaber, Jörg

    2002-07-01

    locally combined time series increasing the available data for model development. Apart from analyzed protocolling errors, microclimatic site influences, genetic variation and the observers were identified as sources of uncertainty of phenological observational data. It was concluded that 99% of all phenological observations at a certain site will vary within approximately 24 days around the parametric mean. This supports to the proposed 30-day rule to detect outliers. New phenology models that predict local BB from daily temperature time series were developed. These models were based on simple interactions between inhibitory and promotory agents that are assumed to control the developmental status of a plant. Apart from the fact that, in general, the new models fitted and predicted the observations better than classical models, the main modeling results were: - The bias of the classical models, i.e. overestimation of early observations and underestimation of late observations, could be reduced but not completely removed. - The different favored model structures for each species indicated that for the late spring phases photoperiod played a more dominant role than for early spring phases. - Chilling only plays a subordinate role for spring BB compared to temperatures directly preceding BB. Die Länge der Vegetationsperiode (VP) spielt eine zentrale Rolle für die interannuelle Variation der Kohlenstoffspeicherung terrestrischer Ökosysteme. Die Analyse von Beobachtungsdaten hat gezeigt, dass sich die VP in den letzten Jahrzehnten in den nördlichen Breiten verlängert hat. Dieses Phänomen wurde oft im Zusammenhang mit der globalen Erwärmung diskutiert, da die Phänologie von der Temperatur beeinflusst wird. Die Analyse der Pflanzenphänologie in Süddeutschland im 20. Jahrhundert zeigte: - Die starke Verfrühung der Frühjahrsphasen in dem Jahrzehnt vor 1999 war kein singuläres Ereignis im 20. Jahrhundert. Schon in früheren Dekaden gab es ähnliche Trends. Es konnten

  2. Pathway models for analysing and managing the introduction of alien plant pests—an overview and categorization

    Science.gov (United States)

    J.C. Douma; M. Pautasso; R.C. Venette; C. Robinet; L. Hemerik; M.C.M. Mourits; J. Schans; W. van der Werf

    2016-01-01

    Alien plant pests are introduced into new areas at unprecedented rates through global trade, transport, tourism and travel, threatening biodiversity and agriculture. Increasingly, the movement and introduction of pests is analysed with pathway models to provide risk managers with quantitative estimates of introduction risks and effectiveness of management options....

  3. Economical analyses of build-operate-transfer model in establishing alternative power plants

    International Nuclear Information System (INIS)

    Yumurtaci, Zehra; Erdem, Hasan Hueseyin

    2007-01-01

    The most widely employed method to meet the increasing electricity demand is building new power plants. The most important issue in building new power plants is to find financial funds. Various models are employed, especially in developing countries, in order to overcome this problem and to find a financial source. One of these models is the build-operate-transfer (BOT) model. In this model, the investor raises all the funds for mandatory expenses and provides financing, builds the plant and, after a certain plant operation period, transfers the plant to the national power organization. In this model, the object is to decrease the burden of power plants on the state budget. The most important issue in the BOT model is the dependence of the unit electricity cost on the transfer period. In this study, the model giving the unit electricity cost depending on the transfer of the plants established according to the BOT model, has been discussed. Unit electricity investment cost and unit electricity cost in relation to transfer period for plant types have been determined. Furthermore, unit electricity cost change depending on load factor, which is one of the parameters affecting annual electricity production, has been determined, and the results have been analyzed. This method can be employed for comparing the production costs of different plants that are planned to be established according to the BOT model, or it can be employed to determine the appropriateness of the BOT model

  4. A Shell/3D Modeling Technique for the Analyses of Delaminated Composite Laminates

    Science.gov (United States)

    Krueger, Ronald; OBrien, T. Kevin

    2001-01-01

    A shell/3D modeling technique was developed for which a local three-dimensional solid finite element model is used only in the immediate vicinity of the delamination front. The goal was to combine the accuracy of the full three-dimensional solution with the computational efficiency of a plate or shell finite element model. Multi-point constraints provided a kinematically compatible interface between the local three-dimensional model and the global structural model which has been meshed with plate or shell finite elements. Double Cantilever Beam (DCB), End Notched Flexure (ENF), and Single Leg Bending (SLB) specimens were modeled using the shell/3D technique to study the feasibility for pure mode I (DCB), mode II (ENF) and mixed mode I/II (SLB) cases. Mixed mode strain energy release rate distributions were computed across the width of the specimens using the virtual crack closure technique. Specimens with a unidirectional layup and with a multidirectional layup where the delamination is located between two non-zero degree plies were simulated. For a local three-dimensional model, extending to a minimum of about three specimen thicknesses on either side of the delamination front, the results were in good agreement with mixed mode strain energy release rates obtained from computations where the entire specimen had been modeled with solid elements. For large built-up composite structures modeled with plate elements, the shell/3D modeling technique offers a great potential for reducing the model size, since only a relatively small section in the vicinity of the delamination front needs to be modeled with solid elements.

  5. Comparative study analysing women's childbirth satisfaction and obstetric outcomes across two different models of maternity care

    Science.gov (United States)

    Conesa Ferrer, Ma Belén; Canteras Jordana, Manuel; Ballesteros Meseguer, Carmen; Carrillo García, César; Martínez Roche, M Emilia

    2016-01-01

    Objectives To describe the differences in obstetrical results and women's childbirth satisfaction across 2 different models of maternity care (biomedical model and humanised birth). Setting 2 university hospitals in south-eastern Spain from April to October 2013. Design A correlational descriptive study. Participants A convenience sample of 406 women participated in the study, 204 of the biomedical model and 202 of the humanised model. Results The differences in obstetrical results were (biomedical model/humanised model): onset of labour (spontaneous 66/137, augmentation 70/1, p=0.0005), pain relief (epidural 172/132, no pain relief 9/40, p=0.0005), mode of delivery (normal vaginal 140/165, instrumental 48/23, p=0.004), length of labour (0–4 hours 69/93, >4 hours 133/108, p=0.011), condition of perineum (intact perineum or tear 94/178, episiotomy 100/24, p=0.0005). The total questionnaire score (100) gave a mean (M) of 78.33 and SD of 8.46 in the biomedical model of care and an M of 82.01 and SD of 7.97 in the humanised model of care (p=0.0005). In the analysis of the results per items, statistical differences were found in 8 of the 9 subscales. The highest scores were reached in the humanised model of maternity care. Conclusions The humanised model of maternity care offers better obstetrical outcomes and women's satisfaction scores during the labour, birth and immediate postnatal period than does the biomedical model. PMID:27566632

  6. Integrated freight network model : a GIS-based platform for transportation analyses.

    Science.gov (United States)

    2015-01-01

    The models currently used to examine the behavior transportation systems are usually mode-specific. That is, they focus on a single mode (i.e. railways, highways, or waterways). The lack of : integration limits the usefulness of models to analyze the...

  7. Evidence to Support the Componential Model of Creativity: Secondary Analyses of Three Studies.

    Science.gov (United States)

    Conti, Regina; And Others

    1996-01-01

    Three studies with overlapping participant populations evaluated Amabile's componential model of creativity, which postulates three major creativity components: (1) skills specific to the task domain, (2) general (cross-domain) creativity-relevant skills, and (3) task motivation. Findings of the three studies support Amabile's model. (DB)

  8. Analysing empowerment-oriented email consultation for parents : development of the Guiding the Empowerment Process model

    NARCIS (Netherlands)

    dr. Christa C.C. Nieuwboer

    2014-01-01

    Online consultation is increasingly offered by parenting practitioners, but it is not clear if it is feasible to provide empowerment-oriented support in a single session email consultation. Based on the empowerment theory, we developed the Guiding the Empowerment Process model (GEP model) to

  9. A laboratory-calibrated model of coho salmon growth with utility for ecological analyses

    Science.gov (United States)

    Manhard, Christopher V.; Som, Nicholas A.; Perry, Russell W.; Plumb, John M.

    2018-01-01

    We conducted a meta-analysis of laboratory- and hatchery-based growth data to estimate broadly applicable parameters of mass- and temperature-dependent growth of juvenile coho salmon (Oncorhynchus kisutch). Following studies of other salmonid species, we incorporated the Ratkowsky growth model into an allometric model and fit this model to growth observations from eight studies spanning ten different populations. To account for changes in growth patterns with food availability, we reparameterized the Ratkowsky model to scale several of its parameters relative to ration. The resulting model was robust across a wide range of ration allocations and experimental conditions, accounting for 99% of the variation in final body mass. We fit this model to growth data from coho salmon inhabiting tributaries and constructed ponds in the Klamath Basin by estimating habitat-specific indices of food availability. The model produced evidence that constructed ponds provided higher food availability than natural tributaries. Because of their simplicity (only mass and temperature are required as inputs) and robustness, ration-varying Ratkowsky models have utility as an ecological tool for capturing growth in freshwater fish populations.

  10. Solving scheduling problems by untimed model checking. The clinical chemical analyser case study

    NARCIS (Netherlands)

    Margaria, T.; Wijs, Anton J.; Massink, M.; van de Pol, Jan Cornelis; Bortnik, Elena M.

    2009-01-01

    In this article, we show how scheduling problems can be modelled in untimed process algebra, by using special tick actions. A minimal-cost trace leading to a particular action, is one that minimises the number of tick steps. As a result, we can use any (timed or untimed) model checking tool to find

  11. Stochastic Spatio-Temporal Models for Analysing NDVI Distribution of GIMMS NDVI3g Images

    Directory of Open Access Journals (Sweden)

    Ana F. Militino

    2017-01-01

    Full Text Available The normalized difference vegetation index (NDVI is an important indicator for evaluating vegetation change, monitoring land surface fluxes or predicting crop models. Due to the great availability of images provided by different satellites in recent years, much attention has been devoted to testing trend changes with a time series of NDVI individual pixels. However, the spatial dependence inherent in these data is usually lost unless global scales are analyzed. In this paper, we propose incorporating both the spatial and the temporal dependence among pixels using a stochastic spatio-temporal model for estimating the NDVI distribution thoroughly. The stochastic model is a state-space model that uses meteorological data of the Climatic Research Unit (CRU TS3.10 as auxiliary information. The model will be estimated with the Expectation-Maximization (EM algorithm. The result is a set of smoothed images providing an overall analysis of the NDVI distribution across space and time, where fluctuations generated by atmospheric disturbances, fire events, land-use/cover changes or engineering problems from image capture are treated as random fluctuations. The illustration is carried out with the third generation of NDVI images, termed NDVI3g, of the Global Inventory Modeling and Mapping Studies (GIMMS in continental Spain. This data are taken in bymonthly periods from January 2011 to December 2013, but the model can be applied to many other variables, countries or regions with different resolutions.

  12. Factor analyses of the Hospital Anxiety and Depression Scale: a Bayesian structural equation modeling approach.

    Science.gov (United States)

    Fong, Ted Chun Tat; Ho, Rainbow Tin Hung

    2013-12-01

    The latent structure of the Hospital Anxiety and Depression Scale (HADS) has caused inconsistent results in the literature. The HADS is frequently analyzed via maximum likelihood confirmatory factor analysis (ML-CFA). However, the overly restrictive assumption of exact zero cross-loadings and residual correlations in ML-CFA can lead to poor model fits and distorted factor structures. This study applied Bayesian structural equation modeling (BSEM) to evaluate the latent structure of the HADS. Three a priori models, the two-factor, three-factor, and bifactor models, were investigated in a Chinese community sample (N = 312) and clinical sample (N = 198) using ML-CFA and BSEM. BSEM specified approximate zero cross-loadings and residual correlations through the use of zero-mean, small-variance informative priors. The model comparison was based on the Bayesian information criterion (BIC). Using ML-CFA, none of the three models provided an adequate fit for either sample. The BSEM two-factor model with approximate zero cross-loadings and residual correlations fitted both samples well with the lowest BIC of the three models and displayed a simple and parsimonious factor-loading pattern. The study demonstrated that the two-factor structure fitted the HADS well, suggesting its usefulness in assessing the symptoms of anxiety and depression in clinical practice. BSEM is a sophisticated and flexible statistical technique that better reflects substantive theories and locates the source of model misfit. Future use of BSEM is recommended to evaluate the latent structure of other psychological instruments.

  13. Analyses of precooling parameters for a bottom flooding ECCS rewetting velocity model

    International Nuclear Information System (INIS)

    Chun, M.H.

    1981-01-01

    An extension work of the previous paper on the rewetting velocity model is presented. Application of the rewetting velocity model presented elsewhere requires a priori values of phi. In the absence of phi values, film boiling heat transfer coefficient (hsub(df)) and fog-film length (1) data are needed. To provide these informations, a modified Bromley's correlation is first derived and used to obtain hsub(df) values at higher pressure conditions. In addition, the analysis of the precooling parameters, such as phi and 1 is further extended using much more expensive PWR FLECHT data. Thus, the applicable range of the rewetting velocity model is further expanded in this work. (author)

  14. Model-Based Fault Diagnosis: Performing Root Cause and Impact Analyses in Real Time

    Science.gov (United States)

    Figueroa, Jorge F.; Walker, Mark G.; Kapadia, Ravi; Morris, Jonathan

    2012-01-01

    Generic, object-oriented fault models, built according to causal-directed graph theory, have been integrated into an overall software architecture dedicated to monitoring and predicting the health of mission- critical systems. Processing over the generic fault models is triggered by event detection logic that is defined according to the specific functional requirements of the system and its components. Once triggered, the fault models provide an automated way for performing both upstream root cause analysis (RCA), and for predicting downstream effects or impact analysis. The methodology has been applied to integrated system health management (ISHM) implementations at NASA SSC's Rocket Engine Test Stands (RETS).

  15. Statistical Modelling of Synaptic Vesicles Distribution and Analysing their Physical Characteristics

    DEFF Research Database (Denmark)

    Khanmohammadi, Mahdieh

    This Ph.D. thesis deals with mathematical and statistical modeling of synaptic vesicle distribution, shape, orientation and interactions. The first major part of this thesis treats the problem of determining the effect of stress on synaptic vesicle distribution and interactions. Serial section...... transmission electron microscopy is used to acquire images from two experimental groups of rats: 1) rats subjected to a behavioral model of stress and 2) rats subjected to sham stress as the control group. The synaptic vesicle distribution and interactions are modeled by employing a point process approach...... on differences of statistical measures in section and the same measures in between sections. Three-dimensional (3D) datasets are reconstructed by using image registration techniques and estimated thicknesses. We distinguish the effect of stress by estimating the synaptic vesicle densities and modeling...

  16. Wave modelling for the North Indian Ocean using MSMR analysed winds

    Digital Repository Service at National Institute of Oceanography (India)

    Vethamony, P.; Sudheesh, K.; Rupali, S.P.; Babu, M.T.; Jayakumar, S.; Saran, A.K.; Basu, S.K.; Kumar, R.; Sarkar, A.

    NCMRWF (National Centre for Medium Range Weather Forecast) winds assimilated with MSMR (Multi-channel Scanning Microwave Radiometer) winds are used as input to MIKE21 Offshore Spectral Wave model (OSW) which takes into account wind induced wave...

  17. Reference model for measuring and analysing costs – particularly in business informatics

    Directory of Open Access Journals (Sweden)

    Milos Maryska

    2010-04-01

    Full Text Available This paper is devoted to problems of management of cost efficiency of business informatics with Business Intelligence (BI assistance. It defines basic critical points that must be taken into account during creating models for management of cost efficiency of business informatics. It proposes new model for management of cost efficiency, this model include also definitions of dimensions and indicators for measuring of this cost efficiency. The model takes into account requirements that pose claim on management of cost efficiency necessitated by accounting and requirements from consultancy with managers of companies. It also takes into account requirement of methodologies for management business informatics and methods and processes for evaluating and measuring business informatics. This methodologies, methods and processes are transformed into procedures that are appropriate for measuring and evaluating business informatics. This model is intended for monitoring of actual situation, evolution cost efficiency of business informatics and it can be used for making decisions about convenience of outsourcing of business informatics. There are presented some examples from presentation level of mentioned model for measuring of cost efficiency of business informatics. This presentation level is in the form of tables and also in the form of dashboards.

  18. Analysing stratified medicine business models and value systems: innovation-regulation interactions.

    Science.gov (United States)

    Mittra, James; Tait, Joyce

    2012-09-15

    Stratified medicine offers both opportunities and challenges to the conventional business models that drive pharmaceutical R&D. Given the increasingly unsustainable blockbuster model of drug development, due in part to maturing product pipelines, alongside increasing demands from regulators, healthcare providers and patients for higher standards of safety, efficacy and cost-effectiveness of new therapies, stratified medicine promises a range of benefits to pharmaceutical and diagnostic firms as well as healthcare providers and patients. However, the transition from 'blockbusters' to what might now be termed 'niche-busters' will require the adoption of new, innovative business models, the identification of different and perhaps novel types of value along the R&D pathway, and a smarter approach to regulation to facilitate innovation in this area. In this paper we apply the Innogen Centre's interdisciplinary ALSIS methodology, which we have developed for the analysis of life science innovation systems in contexts where the value creation process is lengthy, expensive and highly uncertain, to this emerging field of stratified medicine. In doing so, we consider the complex collaboration, timing, coordination and regulatory interactions that shape business models, value chains and value systems relevant to stratified medicine. More specifically, we explore in some depth two convergence models for co-development of a therapy and diagnostic before market authorisation, highlighting the regulatory requirements and policy initiatives within the broader value system environment that have a key role in determining the probable success and sustainability of these models. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Analysing the Costs of Integrated Care: A Case on Model Selection for Chronic Care Purposes

    Directory of Open Access Journals (Sweden)

    Marc Carreras

    2016-08-01

    Full Text Available Background: The objective of this study is to investigate whether the algorithm proposed by Manning and Mullahy, a consolidated health economics procedure, can also be used to estimate individual costs for different groups of healthcare services in the context of integrated care. Methods: A cross-sectional study focused on the population of the Baix Empordà (Catalonia-Spain for the year 2012 (N = 92,498 individuals. A set of individual cost models as a function of sex, age and morbidity burden were adjusted and individual healthcare costs were calculated using a retrospective full-costing system. The individual morbidity burden was inferred using the Clinical Risk Groups (CRG patient classification system. Results: Depending on the characteristics of the data, and according to the algorithm criteria, the choice of model was a linear model on the log of costs or a generalized linear model with a log link. We checked for goodness of fit, accuracy, linear structure and heteroscedasticity for the models obtained. Conclusion: The proposed algorithm identified a set of suitable cost models for the distinct groups of services integrated care entails. The individual morbidity burden was found to be indispensable when allocating appropriate resources to targeted individuals.

  20. Thermo-mechanical analyses and model validation in the HAW test field. Final report

    International Nuclear Information System (INIS)

    Heijdra, J.J.; Broerse, J.; Prij, J.

    1995-01-01

    An overview is given of the thermo-mechanical analysis work done for the design of the High Active Waste experiment and for the purpose of validation of the used models through comparison with experiments. A brief treatise is given on the problems of validation of models used for the prediction of physical behaviour which cannot be determined with experiments. The analysis work encompasses investigations into the initial state of stress in the field, the constitutive relations, the temperature rise, and the pressure on the liner tubes inserted in the field to guarantee the retrievability of the radioactive sources used for the experiment. The measurements of temperatures, deformations, and stresses are described and an evaluation is given of the comparison of measured and calculated data. An attempt has been made to qualify or even quantify the discrepancies, if any, between measurements and calculations. It was found that the model for the temperature calculations performed adequately. For the stresses the general tendency was good, however, large discrepancies exist mainly due to inaccuracies in the measurements. For the deformations again the general tendency of the model predictions was in accordance with the measurements. However, from the evaluation it appears that in spite of the efforts to estimate the correct initial rock pressure at the location of the experiment, this pressure has been underestimated. The evaluation has contributed to a considerable increase in confidence in the models and gives no reason to question the constitutive model for rock salt. However, due to the quality of the measurements of the stress and the relatively short period of the experiments no quantitatively firm support for the constitutive model is acquired. Collections of graphs giving the measured and calculated data are attached as appendices. (orig.)

  1. Comprehensive analyses of ventricular myocyte models identify targets exhibiting favorable rate dependence.

    Directory of Open Access Journals (Sweden)

    Megan A Cummins

    2014-03-01

    Full Text Available Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP. The prolongation caused by reverse rate dependent agents is greater at slow heart rates, resulting in both reduced arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates. The opposite property, forward rate dependence, would theoretically overcome these parallel problems, yet forward rate dependent (FRD antiarrhythmics remain elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic property of perturbations to the AP. We have addressed the possibility of forward rate dependence by performing a comprehensive analysis of 13 ventricular myocyte models. By simulating populations of myocytes with varying properties and analyzing population results statistically, we simultaneously predicted the rate-dependent effects of changes in multiple model parameters. An average of 40 parameters were tested in each model, and effects on AP duration were assessed at slow (0.2 Hz and fast (2 Hz rates. The analysis identified a variety of FRD ionic current perturbations and generated specific predictions regarding their mechanisms. For instance, an increase in L-type calcium current is FRD when this is accompanied by indirect, rate-dependent changes in slow delayed rectifier potassium current. A comparison of predictions across models identified inward rectifier potassium current and the sodium-potassium pump as the two targets most likely to produce FRD AP prolongation. Finally, a statistical analysis of results from the 13 models demonstrated that models displaying minimal rate-dependent changes in AP shape have little capacity for FRD perturbations, whereas models with large shape changes have considerable FRD potential. This can explain differences between species and between ventricular cell types. Overall, this study provides new insights, both specific and general, into the determinants of

  2. Scenario sensitivity analyses performed on the PRESTO-EPA LLW risk assessment models

    International Nuclear Information System (INIS)

    Bandrowski, M.S.

    1988-01-01

    The US Environmental Protection Agency (EPA) is currently developing standards for the land disposal of low-level radioactive waste. As part of the standard development, EPA has performed risk assessments using the PRESTO-EPA codes. A program of sensitivity analysis was conducted on the PRESTO-EPA codes, consisting of single parameter sensitivity analysis and scenario sensitivity analysis. The results of the single parameter sensitivity analysis were discussed at the 1987 DOE LLW Management Conference. Specific scenario sensitivity analyses have been completed and evaluated. Scenario assumptions that were analyzed include: site location, disposal method, form of waste, waste volume, analysis time horizon, critical radionuclides, use of buffer zones, and global health effects

  3. Human Atrial Cell Models to Analyse Haemodialysis-Related Effects on Cardiac Electrophysiology: Work in Progress

    Directory of Open Access Journals (Sweden)

    Elisa Passini

    2014-01-01

    Full Text Available During haemodialysis (HD sessions, patients undergo alterations in the extracellular environment, mostly concerning plasma electrolyte concentrations, pH, and volume, together with a modification of sympathovagal balance. All these changes affect cardiac electrophysiology, possibly leading to an increased arrhythmic risk. Computational modeling may help to investigate the impact of HD-related changes on atrial electrophysiology. However, many different human atrial action potential (AP models are currently available, all validated only with the standard electrolyte concentrations used in experiments. Therefore, they may respond in different ways to the same environmental changes. After an overview on how the computational approach has been used in the past to investigate the effect of HD therapy on cardiac electrophysiology, the aim of this work has been to assess the current state of the art in human atrial AP models, with respect to the HD context. All the published human atrial AP models have been considered and tested for electrolytes, volume changes, and different acetylcholine concentrations. Most of them proved to be reliable for single modifications, but all of them showed some drawbacks. Therefore, there is room for a new human atrial AP model, hopefully able to physiologically reproduce all the HD-related effects. At the moment, work is still in progress in this specific field.

  4. Modelling and simulation of complex sociotechnical systems: envisioning and analysing work environments

    Science.gov (United States)

    Hettinger, Lawrence J.; Kirlik, Alex; Goh, Yang Miang; Buckle, Peter

    2015-01-01

    Accurate comprehension and analysis of complex sociotechnical systems is a daunting task. Empirically examining, or simply envisioning the structure and behaviour of such systems challenges traditional analytic and experimental approaches as well as our everyday cognitive capabilities. Computer-based models and simulations afford potentially useful means of accomplishing sociotechnical system design and analysis objectives. From a design perspective, they can provide a basis for a common mental model among stakeholders, thereby facilitating accurate comprehension of factors impacting system performance and potential effects of system modifications. From a research perspective, models and simulations afford the means to study aspects of sociotechnical system design and operation, including the potential impact of modifications to structural and dynamic system properties, in ways not feasible with traditional experimental approaches. This paper describes issues involved in the design and use of such models and simulations and describes a proposed path forward to their development and implementation. Practitioner Summary: The size and complexity of real-world sociotechnical systems can present significant barriers to their design, comprehension and empirical analysis. This article describes the potential advantages of computer-based models and simulations for understanding factors that impact sociotechnical system design and operation, particularly with respect to process and occupational safety. PMID:25761227

  5. The Computational Fluid Dynamics Analyses on Hemodynamic Characteristics in Stenosed Arterial Models

    Directory of Open Access Journals (Sweden)

    Yue Zhou

    2018-01-01

    Full Text Available Arterial stenosis plays an important role in the progressions of thrombosis and stroke. In the present study, a standard axisymmetric tube model of the stenotic artery is introduced and the degree of stenosis η is evaluated by the area ratio of the blockage to the normal vessel. A normal case (η=0 and four stenotic cases of η=0.25, 0.5, 0.625, and 0.75 with a constant Reynolds number of 300 are simulated by computational fluid dynamics (CFD, respectively, with the Newtonian and Carreau models for comparison. Results show that for both models, the poststenotic separation vortex length increases exponentially with the growth of stenosis degree. However, the vortex length of the Carreau model is shorter than that of the Newtonian model. The artery narrowing accelerates blood flow, which causes high blood pressure and wall shear stress (WSS. The pressure drop of the η=0.75 case is nearly 8 times that of the normal value, while the WSS peak at the stenosis region of η=0.75 case even reaches up to 15 times that of the normal value. The present conclusions are of generality and contribute to the understanding of the dynamic mechanisms of artery stenosis diseases.

  6. Monte Carlo modeling of Standard Model multi-boson production processes for $\\sqrt{s} = 13$ TeV ATLAS analyses

    CERN Document Server

    Li, Shu; The ATLAS collaboration

    2017-01-01

    Proceeding for the poster presentation at LHCP2017, Shanghai, China on the topic of "Monte Carlo modeling of Standard Model multi-boson production processes for $\\sqrt{s} = 13$ TeV ATLAS analyses" (ATL-PHYS-SLIDE-2017-265 https://cds.cern.ch/record/2265389) Deadline: 01/09/2017

  7. Latent Variable Modelling and Item Response Theory Analyses in Marketing Research

    Directory of Open Access Journals (Sweden)

    Brzezińska Justyna

    2016-12-01

    Full Text Available Item Response Theory (IRT is a modern statistical method using latent variables designed to model the interaction between a subject’s ability and the item level stimuli (difficulty, guessing. Item responses are treated as the outcome (dependent variables, and the examinee’s ability and the items’ characteristics are the latent predictor (independent variables. IRT models the relationship between a respondent’s trait (ability, attitude and the pattern of item responses. Thus, the estimation of individual latent traits can differ even for two individuals with the same total scores. IRT scores can yield additional benefits and this will be discussed in detail. In this paper theory and application with R software with the use of packages designed for modelling IRT will be presented.

  8. Analysing improvements to on-street public transport systems: a mesoscopic model approach

    DEFF Research Database (Denmark)

    Ingvardson, Jesper Bláfoss; Kornerup Jensen, Jonas; Nielsen, Otto Anker

    2017-01-01

    Light rail transit and bus rapid transit have shown to be efficient and cost-effective in improving public transport systems in cities around the world. As these systems comprise various elements, which can be tailored to any given setting, e.g. pre-board fare-collection, holding strategies...... a mesoscopic model which makes it possible to evaluate public transport operations in details, including dwell times, intelligent traffic signal timings and holding strategies while modelling impacts from other traffic using statistical distributional data thereby ensuring simplicity in use and fast...... and other advanced public transport systems (APTS), the attractiveness of such systems depends heavily on their implementation. In the early planning stage it is advantageous to deploy simple and transparent models to evaluate possible ways of implementation. For this purpose, the present study develops...

  9. Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses.

    Science.gov (United States)

    Welton, Nicky J; Soares, Marta O; Palmer, Stephen; Ades, Anthony E; Harrison, David; Shankar-Hari, Manu; Rowan, Kathy M

    2015-07-01

    Cost-effectiveness analysis (CEA) models are routinely used to inform health care policy. Key model inputs include relative effectiveness of competing treatments, typically informed by meta-analysis. Heterogeneity is ubiquitous in meta-analysis, and random effects models are usually used when there is variability in effects across studies. In the absence of observed treatment effect modifiers, various summaries from the random effects distribution (random effects mean, predictive distribution, random effects distribution, or study-specific estimate [shrunken or independent of other studies]) can be used depending on the relationship between the setting for the decision (population characteristics, treatment definitions, and other contextual factors) and the included studies. If covariates have been measured that could potentially explain the heterogeneity, then these can be included in a meta-regression model. We describe how covariates can be included in a network meta-analysis model and how the output from such an analysis can be used in a CEA model. We outline a model selection procedure to help choose between competing models and stress the importance of clinical input. We illustrate the approach with a health technology assessment of intravenous immunoglobulin for the management of adult patients with severe sepsis in an intensive care setting, which exemplifies how risk of bias information can be incorporated into CEA models. We show that the results of the CEA and value-of-information analyses are sensitive to the model and highlight the importance of sensitivity analyses when conducting CEA in the presence of heterogeneity. The methods presented extend naturally to heterogeneity in other model inputs, such as baseline risk. © The Author(s) 2015.

  10. Features and analyses of W7-X cryostat system FE model

    Energy Technology Data Exchange (ETDEWEB)

    Eeten, Paul van, E-mail: paul.van.eeten@ipp.mpg.de; Bräuer, Torsten; Bykov, Victor; Carls, Andre; Fellinger, Joris; Kallmeyer, J.P.

    2015-10-15

    The Wendelstein 7-X stellarator is presently under construction at the Max-Planck-Institute for Plasma Physics in Greifswald with the goal to verify that a stellarator magnetic confinement concept is a viable option for a fusion power plant. The main components of the W7-X cryostat system are the plasma vessel (PV), outer vessel (OV), ports, thermal insulation, vessel supports and the machine base (MB). The main task of the cryostat system is to provide an insulating vacuum for the cryogenic magnet system while allowing external access to the PV through ports for diagnostic, supply and heating systems. The cryostat is subjected to different types of loads during assembly, maintenance and operation. This ranges from basic weight loads from all installed components to mechanical, vacuum and thermal loads. To predict the behavior of the cryostat in terms of deformations, stresses and support load distribution a finite element (FE) global model has been created called the Global Model of the Cryostat System (GMCS). A complete refurbishment of the GM CS has been done in the last 2 years to prepare the model for future applications. This involved a complete mesh update of the model, an improvement of many model features, an update of the applied operational loads and boundary conditions as well as the creation of automatic post processing procedures. Currently the GMCS is used to support several significant assembly and commissioning steps of W7-X that involve the cryostat system, e.g. the removal of temporary supports beneath the MB, transfer of the PV from temporary to the final supports and evacuation of the cryostat. In the upcoming months the model will be used for further support of the commissioning of W7-X which includes the first evacuation of the PV.

  11. Features and analyses of W7-X cryostat system FE model

    International Nuclear Information System (INIS)

    Eeten, Paul van; Bräuer, Torsten; Bykov, Victor; Carls, Andre; Fellinger, Joris; Kallmeyer, J.P.

    2015-01-01

    The Wendelstein 7-X stellarator is presently under construction at the Max-Planck-Institute for Plasma Physics in Greifswald with the goal to verify that a stellarator magnetic confinement concept is a viable option for a fusion power plant. The main components of the W7-X cryostat system are the plasma vessel (PV), outer vessel (OV), ports, thermal insulation, vessel supports and the machine base (MB). The main task of the cryostat system is to provide an insulating vacuum for the cryogenic magnet system while allowing external access to the PV through ports for diagnostic, supply and heating systems. The cryostat is subjected to different types of loads during assembly, maintenance and operation. This ranges from basic weight loads from all installed components to mechanical, vacuum and thermal loads. To predict the behavior of the cryostat in terms of deformations, stresses and support load distribution a finite element (FE) global model has been created called the Global Model of the Cryostat System (GMCS). A complete refurbishment of the GM CS has been done in the last 2 years to prepare the model for future applications. This involved a complete mesh update of the model, an improvement of many model features, an update of the applied operational loads and boundary conditions as well as the creation of automatic post processing procedures. Currently the GMCS is used to support several significant assembly and commissioning steps of W7-X that involve the cryostat system, e.g. the removal of temporary supports beneath the MB, transfer of the PV from temporary to the final supports and evacuation of the cryostat. In the upcoming months the model will be used for further support of the commissioning of W7-X which includes the first evacuation of the PV.

  12. Modeling human papillomavirus and cervical cancer in the United States for analyses of screening and vaccination

    Directory of Open Access Journals (Sweden)

    Ortendahl Jesse

    2007-10-01

    Full Text Available Abstract Background To provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV and cervical cancer, explicitly incorporating uncertainty about the natural history of disease. Methods We developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN, HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies. Results Approximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69–82% and 69% (60–77%, respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter

  13. GSEVM v.2: MCMC software to analyse genetically structured environmental variance models

    DEFF Research Database (Denmark)

    Ibáñez-Escriche, N; Garcia, M; Sorensen, D

    2010-01-01

    This note provides a description of software that allows to fit Bayesian genetically structured variance models using Markov chain Monte Carlo (MCMC). The gsevm v.2 program was written in Fortran 90. The DOS and Unix executable programs, the user's guide, and some example files are freely available...... for research purposes at http://www.bdporc.irta.es/estudis.jsp. The main feature of the program is to compute Monte Carlo estimates of marginal posterior distributions of parameters of interest. The program is quite flexible, allowing the user to fit a variety of linear models at the level of the mean...

  14. Studies of the Earth Energy Budget and Water Cycle Using Satellite Observations and Model Analyses

    Science.gov (United States)

    Campbell, G. G.; VonderHarr, T. H.; Randel, D. L.; Kidder, S. Q.

    1997-01-01

    During this research period we have utilized the ERBE data set in comparisons to surface properties and water vapor observations in the atmosphere. A relationship between cloudiness and surface temperature anomalies was found. This same relationship was found in a general circulation model, verifying the model. The attempt to construct a homogeneous time series from Nimbus 6, Nimbus 7 and ERBE data is not complete because we are still waiting for the ERBE reanalysis to be completed. It will be difficult to merge the Nimbus 6 data in because its observations occurred when the average weather was different than the other periods, so regression adjustments are not effective.

  15. Empirical analyses of a choice model that captures ordering among attribute values

    DEFF Research Database (Denmark)

    Mabit, Stefan Lindhard

    2017-01-01

    an alternative additionally because it has the highest price. In this paper, we specify a discrete choice model that takes into account the ordering of attribute values across alternatives. This model is used to investigate the effect of attribute value ordering in three case studies related to alternative-fuel...... vehicles, mode choice, and route choice. In our application to choices among alternative-fuel vehicles, we see that especially the price coefficient is sensitive to changes in ordering. The ordering effect is also found in the applications to mode and route choice data where both travel time and cost...

  16. Survival data analyses in ecotoxicology: critical effect concentrations, methods and models. What should we use?

    Science.gov (United States)

    Forfait-Dubuc, Carole; Charles, Sandrine; Billoir, Elise; Delignette-Muller, Marie Laure

    2012-05-01

    In ecotoxicology, critical effect concentrations are the most common indicators to quantitatively assess risks for species exposed to contaminants. Three types of critical effect concentrations are classically used: lowest/ no observed effect concentration (LOEC/NOEC), LC( x) (x% lethal concentration) and NEC (no effect concentration). In this article, for each of these three types of critical effect concentration, we compared methods or models used for their estimation and proposed one as the most appropriate. We then compared these critical effect concentrations to each other. For that, we used nine survival data sets corresponding to D. magna exposition to nine different contaminants, for which the time-course of the response was monitored. Our results showed that: (i) LOEC/NOEC values at day 21 were method-dependent, and that the Cochran-Armitage test with a step-down procedure appeared to be the most protective for the environment; (ii) all tested concentration-response models we compared gave close values of LC50 at day 21, nevertheless the Weibull model had the lowest global mean deviance; (iii) a simple threshold NEC-model both concentration and time dependent more completely described whole data (i.e. all timepoints) and enabled a precise estimation of the NEC. We then compared the three critical effect concentrations and argued that the use of the NEC might be a good option for environmental risk assessment.

  17. Cyclodextrin--piroxicam inclusion complexes: analyses by mass spectrometry and molecular modelling

    Science.gov (United States)

    Gallagher, Richard T.; Ball, Christopher P.; Gatehouse, Deborah R.; Gates, Paul J.; Lobell, Mario; Derrick, Peter J.

    1997-11-01

    Mass spectrometry has been used to investigate the natures of non-covalent complexes formed between the anti-inflammatory drug piroxicam and [alpha]-, [beta]- and [gamma]-cyclodextrins. Energies of these complexes have been calculated by means of molecular modelling. There is a correlation between peak intensities in the mass spectra and the calculated energies.

  18. Quantitative analyses and modelling to support achievement of the 2020 goals for nine neglected tropical diseases

    NARCIS (Netherlands)

    T.D. Hollingsworth (T. Déirdre); E.R. Adams (Emily R.); R.M. Anderson (Roy); K. Atkins (Katherine); S. Bartsch (Sarah); M-G. Basáñez (María-Gloria); M. Behrend (Matthew); D.J. Blok (David); L.A.C. Chapman (Lloyd A. C.); L.E. Coffeng (Luc); O. Courtenay (Orin); R.E. Crump (Ron E.); S.J. de Vlas (Sake); A.P. Dobson (Andrew); L. Dyson (Louise); H. Farkas (Hajnal); A.P. Galvani (Alison P.); M. Gambhir (Manoj); D. Gurarie (David); M.A. Irvine (Michael A.); S. Jervis (Sarah); M.J. Keeling (Matt J.); L. Kelly-Hope (Louise); C. King (Charles); B.Y. Lee (Bruce Y.); E.A. le Rutte (Epke); T.M. Lietman (Thomas M.); M. Ndeffo-Mbah (Martial); G.F. Medley (Graham F.); E. Michael (Edwin); A. Pandey (Abhishek); J.K. Peterson (Jennifer K.); A. Pinsent (Amy); T.C. Porco (Travis C.); J.H. Richardus (Jan Hendrik); L. Reimer (Lisa); K.S. Rock (Kat S.); B.K. Singh (Brajendra K.); W.A. Stolk (Wilma); S. Swaminathan (Subramanian); S.J. Torr (Steve J.); J. Townsend (Jeffrey); J. Truscott (James); M. Walker (Martin); A. Zoueva (Alexandra)

    2015-01-01

    textabstractQuantitative analysis and mathematical models are useful tools in informing strategies to control or eliminate disease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals for neglected tropical diseases (NTDs). In this paper we give an

  19. Analyses of gust fronts by means of limited area NWP model outputs

    Czech Academy of Sciences Publication Activity Database

    Kašpar, Marek

    67-68, - (2003), s. 559-572 ISSN 0169-8095 R&D Projects: GA ČR GA205/00/1451 Institutional research plan: CEZ:AV0Z3042911 Keywords : gust front * limited area NWP model * output Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 1.012, year: 2003

  20. Using Latent Trait Measurement Models to Analyse Attitudinal Data: A Synthesis of Viewpoints.

    Science.gov (United States)

    Andrich, David

    A Rasch model for ordered response categories is derived and it is shown that it retains the key features of both the Thurstone and Likert approaches to studying attitude. Key features of the latter approaches are reviewed. Characteristics in common with the Thurstone approach are: statements are scaled with respect to their affective values;…

  1. Lightning NOx Statistics Derived by NASA Lightning Nitrogen Oxides Model (LNOM) Data Analyses

    Science.gov (United States)

    Koshak, William; Peterson, Harold

    2013-01-01

    What is the LNOM? The NASA Marshall Space Flight Center (MSFC) Lightning Nitrogen Oxides Model (LNOM) [Koshak et al., 2009, 2010, 2011; Koshak and Peterson 2011, 2013] analyzes VHF Lightning Mapping Array (LMA) and National Lightning Detection Network(TradeMark) (NLDN) data to estimate the lightning nitrogen oxides (LNOx) produced by individual flashes. Figure 1 provides an overview of LNOM functionality. Benefits of LNOM: (1) Does away with unrealistic "vertical stick" lightning channel models for estimating LNOx; (2) Uses ground-based VHF data that maps out the true channel in space and time to < 100 m accuracy; (3) Therefore, true channel segment height (ambient air density) is used to compute LNOx; (4) True channel length is used! (typically tens of kilometers since channel has many branches and "wiggles"); (5) Distinction between ground and cloud flashes are made; (6) For ground flashes, actual peak current from NLDN used to compute NOx from lightning return stroke; (7) NOx computed for several other lightning discharge processes (based on Cooray et al., 2009 theory): (a) Hot core of stepped leaders and dart leaders, (b) Corona sheath of stepped leader, (c) K-change, (d) Continuing Currents, and (e) M-components; and (8) LNOM statistics (see later) can be used to parameterize LNOx production for regional air quality models (like CMAQ), and for global chemical transport models (like GEOS-Chem).

  2. Testing Mediation Using Multiple Regression and Structural Equation Modeling Analyses in Secondary Data

    Science.gov (United States)

    Li, Spencer D.

    2011-01-01

    Mediation analysis in child and adolescent development research is possible using large secondary data sets. This article provides an overview of two statistical methods commonly used to test mediated effects in secondary analysis: multiple regression and structural equation modeling (SEM). Two empirical studies are presented to illustrate the…

  3. Quantitative structure-activity relationship models of chemical transformations from matched pairs analyses.

    Science.gov (United States)

    Beck, Jeremy M; Springer, Clayton

    2014-04-28

    The concepts of activity cliffs and matched molecular pairs (MMP) are recent paradigms for analysis of data sets to identify structural changes that may be used to modify the potency of lead molecules in drug discovery projects. Analysis of MMPs was recently demonstrated as a feasible technique for quantitative structure-activity relationship (QSAR) modeling of prospective compounds. Although within a small data set, the lack of matched pairs, and the lack of knowledge about specific chemical transformations limit prospective applications. Here we present an alternative technique that determines pairwise descriptors for each matched pair and then uses a QSAR model to estimate the activity change associated with a chemical transformation. The descriptors effectively group similar transformations and incorporate information about the transformation and its local environment. Use of a transformation QSAR model allows one to estimate the activity change for novel transformations and therefore returns predictions for a larger fraction of test set compounds. Application of the proposed methodology to four public data sets results in increased model performance over a benchmark random forest and direct application of chemical transformations using QSAR-by-matched molecular pairs analysis (QSAR-by-MMPA).

  4. Neural Network-Based Model for Landslide Susceptibility and Soil Longitudinal Profile Analyses

    DEFF Research Database (Denmark)

    Farrokhzad, F.; Barari, Amin; Choobbasti, A. J.

    2011-01-01

    trained with geotechnical data obtained from an investigation of the study area. The quality of the modeling was improved further by the application of some controlling techniques involved in ANN. The observed >90% overall accuracy produced by the ANN technique in both cases is promising for future...

  5. Analysing outsourcing policies in an asset management context : A six-stage model

    NARCIS (Netherlands)

    Schoenmaker, R.; Verlaan, J.G.

    2013-01-01

    Asset managers of civil infrastructure are increasingly outsourcing their maintenance. Whereas maintenance is a cyclic process, decisions to outsource decisions are often project-based, and confusing the discussion on the degree of outsourcing. This paper presents a six-stage model that facilitates

  6. Supporting custom quality models to analyse and compare open-source software

    NARCIS (Netherlands)

    D. Di Ruscio (Davide); D.S. Kolovos (Dimitrios); I. Korkontzelos (Ioannis); N. Matragkas (Nicholas); J.J. Vinju (Jurgen)

    2017-01-01

    textabstractThe analysis and comparison of open source software can be improved by means of quality models supporting the evaluation of the software systems being compared and the final decision about which of them has to be adopted. Since software quality can mean different things in different

  7. Ultrasonic vocalizations in Shank mouse models for autism spectrum disorders: detailed spectrographic analyses and developmental profiles.

    Science.gov (United States)

    Wöhr, Markus

    2014-06-01

    Autism spectrum disorders (ASD) are a class of neurodevelopmental disorders characterized by persistent deficits in social behavior and communication across multiple contexts, together with repetitive patterns of behavior, interests, or activities. The high concordance rate between monozygotic twins supports a strong genetic component. Among the most promising candidate genes for ASD is the SHANK gene family, including SHANK1, SHANK2 (ProSAP1), and SHANK3 (ProSAP2). SHANK genes are therefore important candidates for modeling ASD in mice and various genetic models were generated within the last few years. As the diagnostic criteria for ASD are purely behaviorally defined, the validity of mouse models for ASD strongly depends on their behavioral phenotype. Behavioral phenotyping is therefore a key component of the current translational approach and requires sensitive behavioral test paradigms with high relevance to each diagnostic symptom category. While behavioral phenotyping assays for social deficits and repetitive patterns of behavior, interests, or activities are well-established, the development of sensitive behavioral test paradigms to assess communication deficits in mice is a daunting challenge. Measuring ultrasonic vocalizations (USV) appears to be a promising strategy. In the first part of the review, an overview on the different types of mouse USV and their communicative functions will be provided. The second part is devoted to studies on the emission of USV in Shank mouse models for ASD. Evidence for communication deficits was obtained in Shank1, Shank2, and Shank3 genetic mouse models for ASD, often paralleled by behavioral phenotypes relevant to social deficits seen in ASD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Animal models of bone cancer pain: systematic review and meta-analyses.

    Science.gov (United States)

    Currie, Gillian L; Delaney, Ada; Bennett, Michael I; Dickenson, Anthony H; Egan, Kieren J; Vesterinen, Hanna M; Sena, Emily S; Macleod, Malcolm R; Colvin, Lesley A; Fallon, Marie T

    2013-06-01

    Pain can significantly decrease the quality of life of patients with advanced cancer. Current treatment strategies often provide inadequate analgesia and unacceptable side effects. Animal models of bone cancer pain are used in the development of novel pharmacological approaches. Here we conducted a systematic review and meta-analysis of publications describing in vivo modelling of bone cancer pain in which behavioural, general health, macroscopic, histological, biochemical, or electrophysiological outcomes were reported and compared to appropriate controls. In all, 150 publications met our inclusion criteria, describing 38 different models of bone cancer pain. Reported methodological quality was low; only 31% of publications reported blinded assessment of outcome, and 11% reported random allocation to group. No publication reported a sample size calculation. Studies that reported measures to reduce bias reported smaller differences in behavioural outcomes between tumour-bearing and control animals, and studies that presented a statement regarding a conflict of interest reported larger differences in behavioural outcomes. Larger differences in behavioural outcomes were reported in female animals, when cancer cells were injected into either the tibia or femur, and when MatLyLu prostate or Lewis Lung cancer cells were used. Mechanical-evoked pain behaviours were most commonly reported; however, the largest difference was observed in spontaneous pain behaviours. In the spinal cord astrocyte activation and increased levels of Substance P receptor internalisation, c-Fos, dynorphin, tumor necrosis factor-α and interleukin-1β have been reported in bone cancer pain models, suggesting several potential therapeutic targets. However, the translational impact of animal models on clinical pain research could be enhanced by improving methodological quality. Copyright © 2013. Published by Elsevier B.V.

  9. Analyses of Spring Barley Evapotranspiration Rates Based on Gradient Measurements and Dual Crop Coefficient Model

    Directory of Open Access Journals (Sweden)

    Gabriela Pozníková

    2014-01-01

    Full Text Available The yield of agricultural crops depends on water availability to a great extent. According some projections, the likelihood of stress caused by drought is increasing in future climates expected for the Central Europe. Therefore, in order to manage agro-ecosystems properly, it is necessary to know water demand of particular crops as precisely as possible. Evapotranspiration (ET is the main part of water balance which takes the water from agro-ecosystems away. The ET consists of evaporation from the soil (E and transpiration (T through the stomata of plants. In this study, we investigated ET of spring barley 1-ha field (Domanínek, Czech Republic measured by Bowen ratio/energy balance method during growing period 2013 (May 8 to July 31. Special focus was dedicated to comparison of barley ET with the reference grass ETo calculated according FAO-56 model, i.e. the determination of barley crop coefficient (Kc. This crop coefficient was subsequently separated into soil evaporation (Ke and transpiration fraction (Kcb by adjusting soil and phenological parameters of dual crop coefficient model to minimize the root mean square error between measured and modelled ET. The resulting Kcb of barley was 0.98 during mid-growing period and 0.05 during initial and end periods. According to FAO-56, typical values are 1.10 and 0.15 for Kcb mid and Kcb end, respectively. Modelled and measured ET show satisfactory agreement with root mean square error equal 0.41 mm. Based on the sums of ET and E for the whole growing season of the spring barley, ET partitioning by FAO-56 dual crop coefficient model resulted in E/ET ratio being 0.24.

  10. A CAD Approach to Developing Mass Distribution and Composition Models for Spaceflight Radiation Risk Analyses

    Science.gov (United States)

    Zapp, E.; Shelfer, T.; Semones, E.; Johnson, A.; Weyland, M.; Golightly, M.; Smith, G.; Dardano, C.

    For roughly the past three decades, combinatorial geometries have been the predominant mode for the development of mass distribution models associated with the estimation of radiological risk for manned space flight. Examples of these are the MEVDP (Modified Elemental Volume Dose Program) vehicle representation of Liley and Hamilton, and the quadratic functional representation of the CAM/CAF (Computerized Anatomical Male/Female) human body models as modified by Billings and Yucker. These geometries, have the advantageous characteristics of being simple for a familiarized user to maintain, and because of the relative lack of any operating system or run-time library dependence, they are also easy to transfer from one computing platform to another. Unfortunately they are also limited in the amount of modeling detail possible, owing to the abstract geometric representation. In addition, combinatorial representations are also known to be error-prone in practice, since there is no convenient method for error identification (i.e. overlap, etc.), and extensive calculation and/or manual comparison may is often necessary to demonstrate that the geometry is adequately represented. We present an alternate approach linking materials -specific, CAD-based mass models directly to geometric analysis tools requiring no approximation with respect to materials , nor any meshing (i.e. tessellation) of the representative geometry. A new approach to ray tracing is presented which makes use of the fundamentals of the CAD representation to perform geometric analysis directly on the NURBS (Non-Uniform Rational BSpline) surfaces themselves. In this way we achieve a framework for- the rapid, precise development and analysis of materials-specific mass distribution models.

  11. Using species abundance distribution models and diversity indices for biogeographical analyses

    Science.gov (United States)

    Fattorini, Simone; Rigal, François; Cardoso, Pedro; Borges, Paulo A. V.

    2016-01-01

    We examine whether Species Abundance Distribution models (SADs) and diversity indices can describe how species colonization status influences species community assembly on oceanic islands. Our hypothesis is that, because of the lack of source-sink dynamics at the archipelago scale, Single Island Endemics (SIEs), i.e. endemic species restricted to only one island, should be represented by few rare species and consequently have abundance patterns that differ from those of more widespread species. To test our hypothesis, we used arthropod data from the Azorean archipelago (North Atlantic). We divided the species into three colonization categories: SIEs, archipelagic endemics (AZEs, present in at least two islands) and native non-endemics (NATs). For each category, we modelled rank-abundance plots using both the geometric series and the Gambin model, a measure of distributional amplitude. We also calculated Shannon entropy and Buzas and Gibson's evenness. We show that the slopes of the regression lines modelling SADs were significantly higher for SIEs, which indicates a relative predominance of a few highly abundant species and a lack of rare species, which also depresses diversity indices. This may be a consequence of two factors: (i) some forest specialist SIEs may be at advantage over other, less adapted species; (ii) the entire populations of SIEs are by definition concentrated on a single island, without possibility for inter-island source-sink dynamics; hence all populations must have a minimum number of individuals to survive natural, often unpredictable, fluctuations. These findings are supported by higher values of the α parameter of the Gambin mode for SIEs. In contrast, AZEs and NATs had lower regression slopes, lower α but higher diversity indices, resulting from their widespread distribution over several islands. We conclude that these differences in the SAD models and diversity indices demonstrate that the study of these metrics is useful for

  12. Evaluation of a dentoalveolar model for testing mouthguards: stress and strain analyses.

    Science.gov (United States)

    Verissimo, Crisnicaw; Costa, Paulo Victor Moura; Santos-Filho, Paulo César Freitas; Fernandes-Neto, Alfredo Júlio; Tantbirojn, Daranee; Versluis, Antheunis; Soares, Carlos José

    2016-02-01

    Custom-fitted mouthguards are devices used to decrease the likelihood of dental trauma. The aim of this study was to develop an experimental bovine dentoalveolar model with periodontal ligament to evaluate mouthguard shock absorption, and impact strain and stress behavior. A pendulum impact device was developed to perform the impact tests with two different impact materials (steel ball and baseball). Five bovine jaws were selected with standard age and dimensions. Six-mm mouthguards were made for the impact tests. The jaws were fixed in a pendulum device and impacts were performed from 90, 60, and 45° angles, with and without mouthguard. Strain gauges were attached at the palatal surface of the impacted tooth. The strain and shock absorption of the mouthguards was calculated and data were analyzed with 3-way anova and Tukey's test (α = 0.05). Two-dimensional finite element models were created based on the cross-section of the bovine dentoalveolar model used in the experiment. A nonlinear dynamic impact analysis was performed to evaluate the strain and stress distributions. Without mouthguards, the increase in impact angulation significantly increased strains and stresses. Mouthguards reduced strain and stress values. Impact velocity, impact object (steel ball or baseball), and mouthguard presence affected the impact stresses and strains in a bovine dentoalveolar model. Experimental strain measurements and finite element models predicted similar behavior; therefore, both methodologies are suitable for evaluating the biomechanical performance of mouthguards. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Evaluation et analyse de sensibilite du modele CERES-Maize en conditions alsaciennes

    OpenAIRE

    Plantureux, Sylvain; Girardin, Philippe; Fouquet, D.; Chapot, Jean Yves

    1991-01-01

    CERES-Maize est un modèle de simulation de la croissance et du développement du maïs élaboré et validé aux Etats-Unis. Afin d’estimer les possibilités de transposition du modèle dans des conditions européennes, des simulations ont été réalisées pour 2 variétés de maïs (LG11 et DEA) cultivées en Alsace 2 années consécutives. Pour chaque variété, le modèle a été calibré sur 1 année et validé sur la suivante. L’analyse de sensibilité des paramètres liés à la variété et au sol montre que la r...

  14. Analysing the strength of friction stir welded dissimilar aluminium alloys using Sugeno Fuzzy model

    Science.gov (United States)

    Barath, V. R.; Vaira Vignesh, R.; Padmanaban, R.

    2018-02-01

    Friction stir welding (FSW) is a promising solid state joining technique for aluminium alloys. In this study, FSW trials were conducted on two dissimilar plates of aluminium alloy AA2024 and AA7075 by varying the tool rotation speed (TRS) and welding speed (WS). Tensile strength (TS) of the joints were measured and a Sugeno - Fuzzy model was developed to interconnect the FSW process parameters with the tensile strength. From the developed model, it was observed that the optimum heat generation at WS of 15 mm.min-1 and TRS of 1050 rpm resulted in dynamic recovery and dynamic recrystallization of the material. This refined the grains in the FSW zone and resulted in peak tensile strength among the tested specimens. Crest parabolic trend was observed in tensile strength with variation of TRS from 900 rpm to 1200 rpm and TTS from 10 mm.min-1 to 20 mm.min-1.

  15. Evaluation and Improvement of Cloud and Convective Parameterizations from Analyses of ARM Observations and Models

    Energy Technology Data Exchange (ETDEWEB)

    Del Genio, Anthony D. [NASA Goddard Inst. for Space Studies (GISS), New York, NY (United States)

    2016-03-11

    Over this period the PI and his performed a broad range of data analysis, model evaluation, and model improvement studies using ARM data. These included cloud regimes in the TWP and their evolution over the MJO; M-PACE IOP SCM-CRM intercomparisons; simulations of convective updraft strength and depth during TWP-ICE; evaluation of convective entrainment parameterizations using TWP-ICE simulations; evaluation of GISS GCM cloud behavior vs. long-term SGP cloud statistics; classification of aerosol semi-direct effects on cloud cover; depolarization lidar constraints on cloud phase; preferred states of the winter Arctic atmosphere, surface, and sub-surface; sensitivity of convection to tropospheric humidity; constraints on the parameterization of mesoscale organization from TWP-ICE WRF simulations; updraft and downdraft properties in TWP-ICE simulated convection; insights from long-term ARM records at Manus and Nauru.

  16. Modelling and Analysing Access Control Policies in XACML 3.0

    DEFF Research Database (Denmark)

    Ramli, Carroline Dewi Puspa Kencana

    and verification of properties of XACML policies. Overall, we focus into two different area. The first part focuses on the access control language. More specifically our focus is on the understanding XACML 3.0. The second part focuses on how we use Logic Programming (LP) to model access control policies. We show...... semantics is described normatively using natural language. The use of English text in standardisation leads to the risk of misinterpretation and ambiguity. In order to avoid this drawback, we define an abstract syntax of XACML 3.0 and a formal XACML semantics. Second, we propose a logic-based XACML analysis...... framework using Answer Set Programming (ASP). With ASP we model an XACML PDP that loads XACML policies and evaluates XACML requests against these policies. The expressivity of ASP and the existence of efficient implementations of the answer set semantics provide the means for declarative specification...

  17. MONTE CARLO ANALYSES OF THE YALINA THERMAL FACILITY WITH SERPENT STEREOLITHOGRAPHY GEOMETRY MODEL

    Energy Technology Data Exchange (ETDEWEB)

    Talamo, A.; Gohar, Y.

    2015-01-01

    This paper analyzes the YALINA Thermal subcritical assembly of Belarus using two different Monte Carlo transport programs, SERPENT and MCNP. The MCNP model is based on combinatorial geometry and universes hierarchy, while the SERPENT model is based on Stereolithography geometry. The latter consists of unstructured triangulated surfaces defined by the normal and vertices. This geometry format is used by 3D printers and it has been created by: the CUBIT software, MATLAB scripts, and C coding. All the Monte Carlo simulations have been performed using the ENDF/B-VII.0 nuclear data library. Both MCNP and SERPENT share the same geometry specifications, which describe the facility details without using any material homogenization. Three different configurations have been studied with different number of fuel rods. The three fuel configurations use 216, 245, or 280 fuel rods, respectively. The numerical simulations show that the agreement between SERPENT and MCNP results is within few tens of pcms.

  18. Modeling Freight Ocean Rail and Truck Transportation Flows to Support Policy Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Gearhart, Jared Lee [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wang, Hao [Cornell Univ., Ithaca, NY (United States); Nozick, Linda Karen [Cornell Univ., Ithaca, NY (United States); Xu, Ningxiong [Cornell Univ., Ithaca, NY (United States)

    2017-11-01

    Freight transportation represents about 9.5% of GDP, is responsible for about 8% of greenhouse gas emissions and supports the import and export of about 3.6 trillion in international trade; hence it is important that our national freight transportation system is designed and operated efficiently and embodies user fees and other policies that balance costs and environmental consequences. Hence, this paper develops a mathematical model to estimate international and domestic freight flows across ocean, rail and truck modes which can be used to study the impacts of changes in our infrastructure as well as the imposition of new user fees and changes in operating policies. This model is applied to two case studies: (1) a disruption of the maritime ports at Los Angeles/Long Beach similar to the impacts that would be felt in an earthquake; and (2) implementation of new user fees at the California ports.

  19. Integrate urban‐scale seismic hazard analyses with the U.S. National Seismic Hazard Model

    Science.gov (United States)

    Moschetti, Morgan P.; Luco, Nicolas; Frankel, Arthur; Petersen, Mark D.; Aagaard, Brad T.; Baltay, Annemarie S.; Blanpied, Michael; Boyd, Oliver; Briggs, Richard; Gold, Ryan D.; Graves, Robert; Hartzell, Stephen; Rezaeian, Sanaz; Stephenson, William J.; Wald, David J.; Williams, Robert A.; Withers, Kyle

    2018-01-01

    For more than 20 yrs, damage patterns and instrumental recordings have highlighted the influence of the local 3D geologic structure on earthquake ground motions (e.g., M">M 6.7 Northridge, California, Gao et al., 1996; M">M 6.9 Kobe, Japan, Kawase, 1996; M">M 6.8 Nisqually, Washington, Frankel, Carver, and Williams, 2002). Although this and other local‐scale features are critical to improving seismic hazard forecasts, historically they have not been explicitly incorporated into the U.S. National Seismic Hazard Model (NSHM, national model and maps), primarily because the necessary basin maps and methodologies were not available at the national scale. Instead,...

  20. Analyses of the energy-dependent single separable potential models for the NN scattering

    International Nuclear Information System (INIS)

    Ahmad, S.S.; Beghi, L.

    1981-08-01

    Starting from a systematic study of the salient features regarding the quantum-mechanical two-particle scattering off an energy-dependent (ED) single separable potential and its connection with the rank-2 energy-independent (EI) separable potential in the T-(K-) amplitude formulation, the present status of the ED single separable potential models due to Tabakin (M1), Garcilazo (M2) and Ahmad (M3) has been discussed. It turned out that the incorporation of a self-consistent optimization procedure improves considerably the results of the 1 S 0 and 3 S 1 scattering phase shifts for the models (M2) and (M3) up to the CM wave number q=2.5 fm -1 , although the extrapolation of the results up to q=10 fm -1 reveals that the two models follow the typical behaviour of the well-known super-soft core potentials. It has been found that a variant of (M3) - i.e. (M4) involving one more parameter - gives the phase shifts results which are generally in excellent agreement with the data up to q=2.5 fm -1 and the extrapolation of the results for the 1 S 0 case in the higher wave number range not only follows the corresponding data qualitatively but also reflects a behaviour similar to the Reid soft core and Hamada-Johnston potentials together with a good agreement with the recent [4/3] Pade fits. A brief discussion regarding the features resulting from the variations in the ED parts of all the four models under consideration and their correlations with the inverse scattering theory methodology concludes the paper. (author)

  1. Analyses of Spring Barley Evapotranspiration Rates Based on Gradient Measurements and Dual Crop Coefficient Model

    Czech Academy of Sciences Publication Activity Database

    Pozníková, Gabriela; Fischer, Milan; Pohanková, Eva; Trnka, Miroslav

    2014-01-01

    Roč. 62, č. 5 (2014), s. 1079-1086 ISSN 1211-8516 R&D Projects: GA MŠk LH12037; GA MŠk(CZ) EE2.3.20.0248 Institutional support: RVO:67179843 Keywords : evapotranspiration * dual crop coefficient model * Bowen ratio/energy balance method * transpiration * soil evaporation * spring barley Subject RIV: EH - Ecology, Behaviour OBOR OECD: Environmental sciences (social aspects to be 5.7)

  2. Modeling and analyses of postulated UF6 release accidents in gaseous diffusion plant

    International Nuclear Information System (INIS)

    Kim, S.H.; Taleyarkhan, R.P.; Keith, K.D.; Schmidt, R.W.; Carter, J.C.; Dyer, R.H.

    1995-10-01

    Computer models have been developed to simulate the transient behavior of aerosols and vapors as a result of a postulated accident involving the release of uranium hexafluoride (UF 6 ) into the process building of a gaseous diffusion plant. UF 6 undergoes an exothermic chemical reaction with moisture (H 2 O) in the air to form hydrogen fluoride (HF) and radioactive uranyl fluoride (UO 2 F 2 ). As part of a facility-wide safety evaluation, this study evaluated source terms consisting of UO 2 F 2 as well as HF during a postulated UF 6 release accident in a process building. In the postulated accident scenario, ∼7900 kg (17,500 lb) of hot UF 6 vapor is released over a 5 min period from the process piping into the atmosphere of a large process building. UO 2 F 2 mainly remains as airborne-solid particles (aerosols), and HF is in a vapor form. Some UO 2 F 2 aerosols are removed from the air flow due to gravitational settling. The HF and the remaining UO 2 F 2 are mixed with air and exhausted through the building ventilation system. The MELCOR computer code was selected for simulating aerosols and vapor transport in the process building. MELCOR model was first used to develop a single volume representation of a process building and its results were compared with those from past lumped parameter models specifically developed for studying UF 6 release accidents. Preliminary results indicate that MELCOR predicted results (using a lumped formulation) are comparable with those from previously developed models

  3. Theoretical and experimental stress analyses of ORNL thin-shell cylinder-to-cylinder model 2

    International Nuclear Information System (INIS)

    Gwaltney, R.C.; Bolt, S.E.; Bryson, J.W.

    1975-10-01

    Model 2 in a series of four thin-shell cylinder-to-cylinder models was tested, and the experimentally determined elastic stress distributions were compared with theoretical predictions obtained from a thin-shell finite-element analysis. Both the cylinder and the nozzle of model 2 had outside diameters of 10 in., giving a d 0 /D 0 ratio of 1.0, and both had outside diameter/thickness ratios of 100. Sixteen separate loading cases in which one end of the cylinder was rigidly held were analyzed. An internal pressure loading, three mutually perpendicular force components, and three mutually perpendicular moment components were individually applied at the free end of the cylinder and at the end of the nozzle. In addition to these 13 loadings, 3 additional loads were applied to the nozzle (in-plane bending moment, out-of-plane bending moment, and axial force) with the free end of the cylinder restrained. The experimental stress distributions for each of the 16 loadings were obtained using 152 three-gage strain rosettes located on the inner and outer surfaces. All the 16 loading cases were also analyzed theoretically using a finite-element shell analysis. The analysis used flat-plate elements and considered five degrees of freedom per node in the final assembled equations. The comparisons between theory and experiment show reasonably good general agreement, and it is felt that the analysis would be satisfactory for most engineering purposes. (auth)

  4. Consequence modeling for nuclear weapons probabilistic cost/benefit analyses of safety retrofits

    Energy Technology Data Exchange (ETDEWEB)

    Harvey, T.F.; Peters, L.; Serduke, F.J.D.; Hall, C.; Stephens, D.R.

    1998-01-01

    The consequence models used in former studies of costs and benefits of enhanced safety retrofits are considered for (1) fuel fires; (2) non-nuclear detonations; and, (3) unintended nuclear detonations. Estimates of consequences were made using a representative accident location, i.e., an assumed mixed suburban-rural site. We have explicitly quantified land- use impacts and human-health effects (e.g. , prompt fatalities, prompt injuries, latent cancer fatalities, low- levels of radiation exposure, and clean-up areas). Uncertainty in the wind direction is quantified and used in a Monte Carlo calculation to estimate a range of results for a fuel fire with uncertain respirable amounts of released Pu. We define a nuclear source term and discuss damage levels of concern. Ranges of damages are estimated by quantifying health impacts and property damages. We discuss our dispersal and prompt effects models in some detail. The models used to loft the Pu and fission products and their particle sizes are emphasized.

  5. Analysing the origin of long-range interactions in proteins using lattice models

    Directory of Open Access Journals (Sweden)

    Unger Ron

    2009-01-01

    Full Text Available Abstract Background Long-range communication is very common in proteins but the physical basis of this phenomenon remains unclear. In order to gain insight into this problem, we decided to explore whether long-range interactions exist in lattice models of proteins. Lattice models of proteins have proven to capture some of the basic properties of real proteins and, thus, can be used for elucidating general principles of protein stability and folding. Results Using a computational version of double-mutant cycle analysis, we show that long-range interactions emerge in lattice models even though they are not an input feature of them. The coupling energy of both short- and long-range pairwise interactions is found to become more positive (destabilizing in a linear fashion with increasing 'contact-frequency', an entropic term that corresponds to the fraction of states in the conformational ensemble of the sequence in which the pair of residues is in contact. A mathematical derivation of the linear dependence of the coupling energy on 'contact-frequency' is provided. Conclusion Our work shows how 'contact-frequency' should be taken into account in attempts to stabilize proteins by introducing (or stabilizing contacts in the native state and/or through 'negative design' of non-native contacts.

  6. Drying of mint leaves in a solar dryer and under open sun: Modelling, performance analyses

    International Nuclear Information System (INIS)

    Akpinar, E. Kavak

    2010-01-01

    In this study was investigated the thin-layer drying characteristics in solar dryer with forced convection and under open sun with natural convection of mint leaves, and, performed energy analysis and exergy analysis of solar drying process of mint leaves. An indirect forced convection solar dryer consisting of a solar air collector and drying cabinet was used in the experiments. The drying data were fitted to ten the different mathematical models. Among the models, Wang and Singh model for the forced solar drying and the natural sun drying were found to best explain thin-layer drying behaviour of mint leaves. Using the first law of thermodynamics, the energy analysis throughout solar drying process was estimated. However, exergy analysis during solar drying process was determined by applying the second law of thermodynamics. Energy utilization ratio (EUR) values of drying cabinet varied in the ranges between 7.826% and 46.285%. The values of exergetic efficiency were found to be in the range of 34.760-87.717%. The values of improvement potential varied between 0 and 0.017 kJ s -1 . Energy utilization ratio and improvement potential decreased with increasing drying time and ambient temperature while exergetic efficiency increased.

  7. Bag-model analyses of proton-antiproton scattering and atomic bound states

    International Nuclear Information System (INIS)

    Alberg, M.A.; Freedman, R.A.; Henley, E.M.; Hwang, W.P.; Seckel, D.; Wilets, L.

    1983-01-01

    We study proton-antiproton (pp-bar ) scattering using the static real potential of Bryan and Phillips outside a cutoff radius rsub0 and two different shapes for the imaginary potential inside a radius R*. These forms, motivated by bag models, are a one-gluon-annihilation potential and a simple geometric-overlap form. In both cases there are three adjustable parameters: the effective bag radius R*, the effective strong coupling constant αsubssup*, and rsub0. There is also a choice for the form of the real potential inside the cutoff radius rsub0. Analysis of the pp-bar scattering data in the laboratory-momentum region 0.4--0.7 GeV/c yields an effective nucleon bag radius R* in the range 0.6--1.1 fm, with the best fit obtained for R* = 0.86 fm. Arguments are presented that the deduced value of R* is likely to be an upper bound on the isolated nucleon bag radius. The present results are consistent with the range of bag radii in current bag models. We have also used the resultant optical potential to calculate the shifts and widths of the sup3Ssub1 and sup1Ssub0 atomic bound states of the pp-bar system. For both states we find upward (repulsive) shifts and widths of about 1 keV. We find no evidence for narrow, strongly bound pp-bar states in our potential model

  8. Promoting Social Inclusion through Sport for Refugee-Background Youth in Australia: Analysing Different Participation Models

    Directory of Open Access Journals (Sweden)

    Karen Block

    2017-06-01

    Full Text Available Sports participation can confer a range of physical and psychosocial benefits and, for refugee and migrant youth, may even act as a critical mediator for achieving positive settlement and engaging meaningfully in Australian society. This group has low participation rates however, with identified barriers including costs; discrimination and a lack of cultural sensitivity in sporting environments; lack of knowledge of mainstream sports services on the part of refugee-background settlers; inadequate access to transport; culturally determined gender norms; and family attitudes. Organisations in various sectors have devised programs and strategies for addressing these participation barriers. In many cases however, these responses appear to be ad hoc and under-theorised. This article reports findings from a qualitative exploratory study conducted in a range of settings to examine the benefits, challenges and shortcomings associated with different participation models. Interview participants were drawn from non-government organisations, local governments, schools, and sports clubs. Three distinct models of participation were identified, including short term programs for refugee-background children; ongoing programs for refugee-background children and youth; and integration into mainstream clubs. These models are discussed in terms of their relative challenges and benefits and their capacity to promote sustainable engagement and social inclusion for this population group.

  9. Reproduction of the Yucca Mountain Project TSPA-LA Uncertainty and Sensitivity Analyses and Preliminary Upgrade of Models

    Energy Technology Data Exchange (ETDEWEB)

    Hadgu, Teklu [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Nuclear Waste Disposal Research and Analysis; Appel, Gordon John [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Nuclear Waste Disposal Research and Analysis

    2016-09-01

    Sandia National Laboratories (SNL) continued evaluation of total system performance assessment (TSPA) computing systems for the previously considered Yucca Mountain Project (YMP). This was done to maintain the operational readiness of the computing infrastructure (computer hardware and software) and knowledge capability for total system performance assessment (TSPA) type analysis, as directed by the National Nuclear Security Administration (NNSA), DOE 2010. This work is a continuation of the ongoing readiness evaluation reported in Lee and Hadgu (2014) and Hadgu et al. (2015). The TSPA computing hardware (CL2014) and storage system described in Hadgu et al. (2015) were used for the current analysis. One floating license of GoldSim with Versions 9.60.300, 10.5 and 11.1.6 was installed on the cluster head node, and its distributed processing capability was mapped on the cluster processors. Other supporting software were tested and installed to support the TSPA-type analysis on the server cluster. The current tasks included verification of the TSPA-LA uncertainty and sensitivity analyses, and preliminary upgrade of the TSPA-LA from Version 9.60.300 to the latest version 11.1. All the TSPA-LA uncertainty and sensitivity analyses modeling cases were successfully tested and verified for the model reproducibility on the upgraded 2014 server cluster (CL2014). The uncertainty and sensitivity analyses used TSPA-LA modeling cases output generated in FY15 based on GoldSim Version 9.60.300 documented in Hadgu et al. (2015). The model upgrade task successfully converted the Nominal Modeling case to GoldSim Version 11.1. Upgrade of the remaining of the modeling cases and distributed processing tasks will continue. The 2014 server cluster and supporting software systems are fully operational to support TSPA-LA type analysis.

  10. Towards an Industrial Application of Statistical Uncertainty Analysis Methods to Multi-physical Modelling and Safety Analyses

    International Nuclear Information System (INIS)

    Zhang, Jinzhao; Segurado, Jacobo; Schneidesch, Christophe

    2013-01-01

    Since 1980's, Tractebel Engineering (TE) has being developed and applied a multi-physical modelling and safety analyses capability, based on a code package consisting of the best estimate 3D neutronic (PANTHER), system thermal hydraulic (RELAP5), core sub-channel thermal hydraulic (COBRA-3C), and fuel thermal mechanic (FRAPCON/FRAPTRAN) codes. A series of methodologies have been developed to perform and to license the reactor safety analysis and core reload design, based on the deterministic bounding approach. Following the recent trends in research and development as well as in industrial applications, TE has been working since 2010 towards the application of the statistical sensitivity and uncertainty analysis methods to the multi-physical modelling and licensing safety analyses. In this paper, the TE multi-physical modelling and safety analyses capability is first described, followed by the proposed TE best estimate plus statistical uncertainty analysis method (BESUAM). The chosen statistical sensitivity and uncertainty analysis methods (non-parametric order statistic method or bootstrap) and tool (DAKOTA) are then presented, followed by some preliminary results of their applications to FRAPCON/FRAPTRAN simulation of OECD RIA fuel rod codes benchmark and RELAP5/MOD3.3 simulation of THTF tests. (authors)

  11. Efficacy of extended release quetiapine fumarate monotherapy in elderly patients with major depressive disorder: secondary analyses in subgroups of patients according to baseline anxiety, sleep disturbance, and pain levels.

    Science.gov (United States)

    Montgomery, Stuart A; Altamura, A Carlo; Katila, Heikki; Datto, Catherine; Szamosi, Johan; Eriksson, Hans

    2014-03-01

    This study evaluated extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder (MDD) according to baseline levels of anxiety, sleep disturbance, and pain. Post-hoc analyses of data from an 11-week (9-week randomized-treatment, 2-week post-treatment phase), double-blind, placebo-controlled study of quetiapine XR (50-300 mg/day) monotherapy in elderly (≥66 years) patients (n=338) with MDD were carried out. Outcomes included randomization to week 9 change in Montgomery Åsberg Depression Rating Scale (MADRS) score and week 9 response (≥50% MADRS score reduction) rates. Post-hoc analyses were carried out to assess subgroups of patients with MDD according to baseline levels in terms of the following: higher or lower anxiety (Hamilton Rating Scale for Anxiety total score≥20 or Depression sleep disturbance factor (items 4+5+6) score≥5 or anxiety (least squares mean change -17.8 vs. -8.5; Panxiety (-14.8 vs. -8.8; Pdepressive symptoms in elderly patients with MDD, irrespective of baseline levels of anxiety, sleep disturbance, and pain.

  12. Healthy volunteers can be phenotyped using cutaneous sensitization pain models.

    Directory of Open Access Journals (Sweden)

    Mads U Werner

    Full Text Available BACKGROUND: Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models. METHODS: We performed post-hoc analyses of 10 completed healthy volunteer studies (n = 342 [409 repeated measurements]. Three different models were used to induce secondary hyperalgesia to monofilament stimulation: the heat/capsaicin sensitization (H/C, the brief thermal sensitization (BTS, and the burn injury (BI models. Three studies included both the H/C and BTS models. RESULTS: Within-subject compared to between-subject variability was low, and there was substantial strength of agreement between repeated induction-sessions in most studies. The intraclass correlation coefficient (ICC improved little with repeated testing beyond two sessions. There was good agreement in categorizing subjects into 'small area' (1(st quartile [75%] responders: 56-76% of subjects consistently fell into same 'small-area' or 'large-area' category on two consecutive study days. There was moderate to substantial agreement between the areas of secondary hyperalgesia induced on the same day using the H/C (forearm and BTS (thigh models. CONCLUSION: Secondary hyperalgesia induced by experimental heat pain models seem a consistent measure of sensitization in pharmacodynamic and physiological research. The analysis indicates that healthy volunteers can be phenotyped based on their pattern of sensitization by the heat [and heat plus capsaicin] pain models.

  13. Structural Equation Modeling with Mplus Basic Concepts, Applications, and Programming

    CERN Document Server

    Byrne, Barbara M

    2011-01-01

    Modeled after Barbara Byrne's other best-selling structural equation modeling (SEM) books, this practical guide reviews the basic concepts and applications of SEM using Mplus Versions 5 & 6. The author reviews SEM applications based on actual data taken from her own research. Using non-mathematical language, it is written for the novice SEM user. With each application chapter, the author "walks" the reader through all steps involved in testing the SEM model including: an explanation of the issues addressed illustrated and annotated testing of the hypothesized and post hoc models expl

  14. Analyses of Methods and Algorithms for Modelling and Optimization of Biotechnological Processes

    Directory of Open Access Journals (Sweden)

    Stoyan Stoyanov

    2009-08-01

    Full Text Available A review of the problems in modeling, optimization and control of biotechnological processes and systems is given in this paper. An analysis of existing and some new practical optimization methods for searching global optimum based on various advanced strategies - heuristic, stochastic, genetic and combined are presented in the paper. Methods based on the sensitivity theory, stochastic and mix strategies for optimization with partial knowledge about kinetic, technical and economic parameters in optimization problems are discussed. Several approaches for the multi-criteria optimization tasks are analyzed. The problems concerning optimal controls of biotechnological systems are also discussed.

  15. Using Rasch Modeling to Re-Evaluate Rapid Malaria Diagnosis Test Analyses

    Directory of Open Access Journals (Sweden)

    Dawit G. Ayele

    2014-06-01

    Full Text Available The objective of this study was to demonstrate the use of the Rasch model by assessing the appropriateness of the demographic, social-economic and geographic factors in providing a total score in malaria RDT in accordance with the model’s expectations. The baseline malaria indicator survey was conducted in Amhara, Oromiya and Southern Nation Nationalities and People (SNNP regions of Ethiopia by The Carter Center in 2007. The result shows high reliability and little disordering of thresholds with no evidence of differential item functioning.

  16. Fiskeoppdrett og verdsettelse : en analyse av resultatjustering og modeller for identifikasjon av slik aktivitet

    OpenAIRE

    Aaker, Harald

    2005-01-01

    Regnskapsinformasjon skal være relevant og pålitelig, men det vil alltid være skjønn forbundet med verdsettelsen.Usaklig skjønn omtales som resultatjustering (”Earnings management”) og regnskaps-manipulasjon. Det er store metodeproblemer innen ”earnings management” – forskningen, da den aktive tilpasningen i stor grad er skjult. I de senere år har ulike modeller for estimering av unormale tidsavgrensninger (”discretionary accruals”) dominert. Problemet er i å estimere de normale tidsavgrensni...

  17. Incorporating Measurement Error from Modeled Air Pollution Exposures into Epidemiological Analyses.

    Science.gov (United States)

    Samoli, Evangelia; Butland, Barbara K

    2017-12-01

    Outdoor air pollution exposures used in epidemiological studies are commonly predicted from spatiotemporal models incorporating limited measurements, temporal factors, geographic information system variables, and/or satellite data. Measurement error in these exposure estimates leads to imprecise estimation of health effects and their standard errors. We reviewed methods for measurement error correction that have been applied in epidemiological studies that use model-derived air pollution data. We identified seven cohort studies and one panel study that have employed measurement error correction methods. These methods included regression calibration, risk set regression calibration, regression calibration with instrumental variables, the simulation extrapolation approach (SIMEX), and methods under the non-parametric or parameter bootstrap. Corrections resulted in small increases in the absolute magnitude of the health effect estimate and its standard error under most scenarios. Limited application of measurement error correction methods in air pollution studies may be attributed to the absence of exposure validation data and the methodological complexity of the proposed methods. Future epidemiological studies should consider in their design phase the requirements for the measurement error correction method to be later applied, while methodological advances are needed under the multi-pollutants setting.

  18. ANALYSING POST-SEISMIC DEFORMATION OF IZMIT EARTHQUAKE WITH INSAR, GNSS AND COULOMB STRESS MODELLING

    Directory of Open Access Journals (Sweden)

    R. A. Barut

    2016-06-01

    Full Text Available On August 17th 1999, a Mw 7.4 earthquake struck the city of Izmit in the north-west of Turkey. This event was one of the most devastating earthquakes of the twentieth century. The epicentre of the Izmit earthquake was on the North Anatolian Fault (NAF which is one of the most active right-lateral strike-slip faults on earth. However, this earthquake offers an opportunity to study how strain is accommodated in an inter-segment region of a large strike slip fault. In order to determine the Izmit earthquake post-seismic effects, the authors modelled Coulomb stress changes of the aftershocks, as well as using the deformation measurement techniques of Interferometric Synthetic Aperture Radar (InSAR and Global Navigation Satellite System (GNSS. The authors have shown that InSAR and GNSS observations over a time period of three months after the earthquake combined with Coulomb Stress Change Modelling can explain the fault zone expansion, as well as the deformation of the northern region of the NAF. It was also found that there is a strong agreement between the InSAR and GNSS results for the post-seismic phases of investigation, with differences less than 2mm, and the standard deviation of the differences is less than 1mm.

  19. Subchannel and Computational Fluid Dynamic Analyses of a Model Pin Bundle

    Energy Technology Data Exchange (ETDEWEB)

    Gairola, A.; Arif, M.; Suh, K. Y. [Seoul National Univ., Seoul (Korea, Republic of)

    2014-05-15

    The current study showed that the simplistic approach of subchannel analysis code MATRA was not good in capturing the physical behavior of the coolant inside the rod bundle. With the incorporation of more detailed geometry of the grid spacer in the CFX code it was possible to approach the experimental values. However, it is vital to incorporate more advanced turbulence mixing models to more realistically simulate behavior of the liquid metal coolant inside the model pin bundle in parallel with the incorporation of the bottom and top grid structures. In the framework of the 11{sup th} international meeting of International Association for Hydraulic Research and Engineering (IAHR) working group on the advanced reactor thermal hydraulics a standard problem was conducted. The quintessence of the problem was to check on the hydraulics and heat transfer in a novel pin bundle with different pitch to rod diameter ratio and heat flux cooled by liquid metal. The standard problem stems from the field of nuclear safety research with the idea of validating and checking the performances of computer codes against the experimental results. Comprehensive checks between the two will succor in improving the dependability and exactness of the codes used for accident simulations.

  20. Integration of 3d Models and Diagnostic Analyses Through a Conservation-Oriented Information System

    Science.gov (United States)

    Mandelli, A.; Achille, C.; Tommasi, C.; Fassi, F.

    2017-08-01

    In the recent years, mature technologies for producing high quality virtual 3D replicas of Cultural Heritage (CH) artefacts has grown thanks to the progress of Information Technologies (IT) tools. These methods are an efficient way to present digital models that can be used with several scopes: heritage managing, support to conservation, virtual restoration, reconstruction and colouring, art cataloguing and visual communication. The work presented is an emblematic case of study oriented to the preventive conservation through monitoring activities, using different acquisition methods and instruments. It was developed inside a project founded by Lombardy Region, Italy, called "Smart Culture", which was aimed to realise a platform that gave the users the possibility to easily access to the CH artefacts, using as an example a very famous statue. The final product is a 3D reality-based model that contains a lot of information inside it, and that can be consulted through a common web browser. In the end, it was possible to define the general strategies oriented to the maintenance and the valorisation of CH artefacts, which, in this specific case, must consider the integration of different techniques and competencies, to obtain a complete, accurate and continuative monitoring of the statue.

  1. INTEGRATION OF 3D MODELS AND DIAGNOSTIC ANALYSES THROUGH A CONSERVATION-ORIENTED INFORMATION SYSTEM

    Directory of Open Access Journals (Sweden)

    A. Mandelli

    2017-08-01

    Full Text Available In the recent years, mature technologies for producing high quality virtual 3D replicas of Cultural Heritage (CH artefacts has grown thanks to the progress of Information Technologies (IT tools. These methods are an efficient way to present digital models that can be used with several scopes: heritage managing, support to conservation, virtual restoration, reconstruction and colouring, art cataloguing and visual communication. The work presented is an emblematic case of study oriented to the preventive conservation through monitoring activities, using different acquisition methods and instruments. It was developed inside a project founded by Lombardy Region, Italy, called “Smart Culture”, which was aimed to realise a platform that gave the users the possibility to easily access to the CH artefacts, using as an example a very famous statue. The final product is a 3D reality-based model that contains a lot of information inside it, and that can be consulted through a common web browser. In the end, it was possible to define the general strategies oriented to the maintenance and the valorisation of CH artefacts, which, in this specific case, must consider the integration of different techniques and competencies, to obtain a complete, accurate and continuative monitoring of the statue.

  2. Analysing and combining atmospheric general circulation model simulations forced by prescribed SST: northern extratropical response

    Directory of Open Access Journals (Sweden)

    K. Maynard

    2001-06-01

    Full Text Available The ECHAM 3.2 (T21, ECHAM 4 (T30 and LMD (version 6, grid-point resolution with 96 longitudes × 72 latitudes atmospheric general circulation models were integrated through the period 1961 to 1993 forced with the same observed Sea Surface Temperatures (SSTs as compiled at the Hadley Centre. Three runs were made for each model starting from different initial conditions. The mid-latitude circulation pattern which maximises the covariance between the simulation and the observations, i.e. the most skilful mode, and the one which maximises the covariance amongst the runs, i.e. the most reproducible mode, is calculated as the leading mode of a Singular Value Decomposition (SVD analysis of observed and simulated Sea Level Pressure (SLP and geopotential height at 500 hPa (Z500 seasonal anomalies. A common response amongst the different models, having different resolution and parametrization should be considered as a more robust atmospheric response to SST than the same response obtained with only one model. A robust skilful mode is found mainly in December-February (DJF, and in June-August (JJA. In DJF, this mode is close to the SST-forced pattern found by Straus and Shukla (2000 over the North Pacific and North America with a wavy out-of-phase between the NE Pacific and the SE US on the one hand and the NE North America on the other. This pattern evolves in a NAO-like pattern over the North Atlantic and Europe (SLP and in a more N-S tripole on the Atlantic and European sector with an out-of-phase between the middle Europe on the one hand and the northern and southern parts on the other (Z500. There are almost no spatial shifts between either field around North America (just a slight eastward shift of the highest absolute heterogeneous correlations for SLP relative to the Z500 ones. The time evolution of the SST-forced mode is moderatly to strongly related to the ENSO/LNSO events but the spread amongst the ensemble of runs is not systematically related

  3. Innovative three-dimensional neutronics analyses directly coupled with cad models of geometrically complex fusion systems

    International Nuclear Information System (INIS)

    Sawan, M.; Wilson, P.; El-Guebaly, L.; Henderson, D.; Sviatoslavsky, G.; Bohm, T.; Kiedrowski, B.; Ibrahim, A.; Smith, B.; Slaybaugh, R.; Tautges, T.

    2007-01-01

    Fusion systems are, in general, geometrically complex requiring detailed three-dimensional (3-D) nuclear analysis. This analysis is required to address tritium self-sufficiency, nuclear heating, radiation damage, shielding, and radiation streaming issues. To facilitate such calculations, we developed an innovative computational tool that is based on the continuous energy Monte Carlo code MCNP and permits the direct use of CAD-based solid models in the ray-tracing. This allows performing the neutronics calculations in a model that preserves the geometrical details without any simplification, eliminates possible human error in modeling the geometry for MCNP, and allows faster design iterations. In addition to improving the work flow for simulating complex 3- D geometries, it allows a richer representation of the geometry compared to the standard 2nd order polynomial representation. This newly developed tool has been successfully tested for a detailed 40 degree sector benchmark of the International Thermonuclear Experimental Reactor (ITER). The calculations included determining the poloidal variation of the neutron wall loading, flux and nuclear heating in the divertor components, nuclear heating in toroidal field coils, and radiation streaming in the mid-plane port. The tool has been applied to perform 3-D nuclear analysis for several fusion designs including the ARIES Compact Stellarator (ARIES-CS), the High Average Power Laser (HAPL) inertial fusion power plant, and ITER first wall/shield (FWS) modules. The ARIES-CS stellarator has a first wall shape and a plasma profile that varies toroidally within each field period compared to the uniform toroidal shape in tokamaks. Such variation cannot be modeled analytically in the standard MCNP code. The impact of the complex helical geometry and the non-uniform blanket and divertor on the overall tritium breeding ratio and total nuclear heating was determined. In addition, we calculated the neutron wall loading variation in

  4. A review on design of experiments and surrogate models in aircraft real-time and many-query aerodynamic analyses

    Science.gov (United States)

    Yondo, Raul; Andrés, Esther; Valero, Eusebio

    2018-01-01

    Full scale aerodynamic wind tunnel testing, numerical simulation of high dimensional (full-order) aerodynamic models or flight testing are some of the fundamental but complex steps in the various design phases of recent civil transport aircrafts. Current aircraft aerodynamic designs have increase in complexity (multidisciplinary, multi-objective or multi-fidelity) and need to address the challenges posed by the nonlinearity of the objective functions and constraints, uncertainty quantification in aerodynamic problems or the restrained computational budgets. With the aim to reduce the computational burden and generate low-cost but accurate models that mimic those full order models at different values of the design variables, Recent progresses have witnessed the introduction, in real-time and many-query analyses, of surrogate-based approaches as rapid and cheaper to simulate models. In this paper, a comprehensive and state-of-the art survey on common surrogate modeling techniques and surrogate-based optimization methods is given, with an emphasis on models selection and validation, dimensionality reduction, sensitivity analyses, constraints handling or infill and stopping criteria. Benefits, drawbacks and comparative discussions in applying those methods are described. Furthermore, the paper familiarizes the readers with surrogate models that have been successfully applied to the general field of fluid dynamics, but not yet in the aerospace industry. Additionally, the review revisits the most popular sampling strategies used in conducting physical and simulation-based experiments in aircraft aerodynamic design. Attractive or smart designs infrequently used in the field and discussions on advanced sampling methodologies are presented, to give a glance on the various efficient possibilities to a priori sample the parameter space. Closing remarks foster on future perspectives, challenges and shortcomings associated with the use of surrogate models by aircraft industrial

  5. A model using marginal efficiency of investment to analyse carbon and nitrogen interactions in forested ecosystems

    Science.gov (United States)

    Thomas, R. Q.; Williams, M.

    2014-12-01

    Carbon (C) and nitrogen (N) cycles are coupled in terrestrial ecosystems through multiple processes including photosynthesis, tissue allocation, respiration, N fixation, N uptake, and decomposition of litter and soil organic matter. Capturing the constraint of N on terrestrial C uptake and storage has been a focus of the Earth System modelling community. Here we explore the trade-offs and sensitivities of allocating C and N to different tissues in order to optimize the productivity of plants using a new, simple model of ecosystem C-N cycling and interactions (ACONITE). ACONITE builds on theory related to plant economics in order to predict key ecosystem properties (leaf area index, leaf C:N, N fixation, and plant C use efficiency) based on the optimization of the marginal change in net C or N uptake associated with a change in allocation of C or N to plant tissues. We simulated and evaluated steady-state and transient ecosystem stocks and fluxes in three different forest ecosystems types (tropical evergreen, temperate deciduous, and temperate evergreen). Leaf C:N differed among the three ecosystem types (temperate deciduous plant traits. Gross primary productivity (GPP) and net primary productivity (NPP) estimates compared well to observed fluxes at the simulation sites. A sensitivity analysis revealed that parameterization of the relationship between leaf N and leaf respiration had the largest influence on leaf area index and leaf C:N. Also, a widely used linear leaf N-respiration relationship did not yield a realistic leaf C:N, while a more recently reported non-linear relationship simulated leaf C:N that compared better to the global trait database than the linear relationship. Overall, our ability to constrain leaf area index and allow spatially and temporally variable leaf C:N can help address challenges simulating these properties in ecosystem and Earth System models. Furthermore, the simple approach with emergent properties based on coupled C-N dynamics has

  6. Analysing Time to Event Data in Dementia Prevention Trials: The Example of the GuidAge Study of EGb761.

    Science.gov (United States)

    Scherrer, B; Andrieu, S; Ousset, P J; Berrut, G; Dartigues, J F; Dubois, B; Pasquier, F; Piette, F; Robert, P; Touchon, J; Garnier, P; Mathiex-Fortunet, H; Vellas, B

    2015-12-01

    Time-to-event analysis is frequently used in medical research to investigate potential disease-modifying treatments in neurodegenerative diseases. Potential treatment effects are generally evaluated using the logrank test, which has optimal power and sensitivity when the treatment effect (hazard ratio) is constant over time. However, there is generally no prior information as to how the hazard ratio for the event of interest actually evolves. In these cases, the logrank test is not necessarily the most appropriate to use. When the hazard ratio is expected to decrease or increase over time, alternative statistical tests such as the Fleming-Harrington test, provide a better sensitivity. An example of this comes from a large, five-year randomised, placebo-controlled prevention trial (GuidAge) in 2854 community-based subjects making spontaneous memory complaints to their family physicians, which evaluated whether treatment with EGb761 can modify the risk of developing AD. The primary outcome measure was the time to conversion from memory complaint to Alzheimer's type dementia. Although there was no significant difference in the hazard function of conversion between the two treatment groups according to the preplanned logrank test, a significant treatment-by-time interaction for the incidence of AD was observed in a protocol-specified subgroup analysis, suggesting that the hazard ratio is not constant over time. For this reason, additional post hoc analyses were performed using the Fleming-Harrington test to evaluate whether there was a signal of a late effect of EGb761. Applying the Fleming-Harrington test, the hazard function for conversion to dementia in the placebo group was significantly different from that in the EGb761 treatment group (p = 0.0054), suggesting a late effect of EGb761. Since this was a post hoc analysis, no definitive conclusions can be drawn as to the effectiveness of the treatment. This post hoc analysis illustrates the interest of performing

  7. Use of model analysis to analyse Thai students’ attitudes and approaches to physics problem solving

    Science.gov (United States)

    Rakkapao, S.; Prasitpong, S.

    2018-03-01

    This study applies the model analysis technique to explore the distribution of Thai students’ attitudes and approaches to physics problem solving and how those attitudes and approaches change as a result of different experiences in physics learning. We administered the Attitudes and Approaches to Problem Solving (AAPS) survey to over 700 Thai university students from five different levels, namely students entering science, first-year science students, and second-, third- and fourth-year physics students. We found that their inferred mental states were generally mixed. The largest gap between physics experts and all levels of the students was about the role of equations and formulas in physics problem solving, and in views towards difficult problems. Most participants of all levels believed that being able to handle the mathematics is the most important part of physics problem solving. Most students’ views did not change even though they gained experiences in physics learning.

  8. Statistical Analyses and Modeling of the Implementation of Agile Manufacturing Tactics in Industrial Firms

    Directory of Open Access Journals (Sweden)

    Mohammad D. AL-Tahat

    2012-01-01

    Full Text Available This paper provides a review and introduction on agile manufacturing. Tactics of agile manufacturing are mapped into different production areas (eight-construct latent: manufacturing equipment and technology, processes technology and know-how, quality and productivity improvement, production planning and control, shop floor management, product design and development, supplier relationship management, and customer relationship management. The implementation level of agile manufacturing tactics is investigated in each area. A structural equation model is proposed. Hypotheses are formulated. Feedback from 456 firms is collected using five-point-Likert-scale questionnaire. Statistical analysis is carried out using IBM SPSS and AMOS. Multicollinearity, content validity, consistency, construct validity, ANOVA analysis, and relationships between agile components are tested. The results of this study prove that the agile manufacturing tactics have positive effect on the overall agility level. This conclusion can be used by manufacturing firms to manage challenges when trying to be agile.

  9. Use of CFD modelling for analysing air parameters in auditorium halls

    Science.gov (United States)

    Cichowicz, Robert

    2017-11-01

    Modelling with the use of numerical methods is currently the most popular method of solving scientific as well as engineering problems. Thanks to the use of computer methods it is possible for example to comprehensively describe the conditions in a given room and to determine thermal comfort, which is a complex issue including subjective sensations of the persons in a given room. The article presents the results of measurements and numerical computing that enabled carrying out the assessment of environment parameters, taking into consideration microclimate, temperature comfort, speeds in the zone of human presence and dustiness in auditory halls. For this purpose measurements of temperature, relative humidity and dustiness were made with the use of a digital microclimate meter and a laser dust particles counter. Thanks to the above by using the application DesignBuilder numerical computing was performed and the obtained results enabled determining PMV comfort indicator in selected rooms.

  10. Statistical modelling of measurement errors in gas chromatographic analyses of blood alcohol content.

    Science.gov (United States)

    Moroni, Rossana; Blomstedt, Paul; Wilhelm, Lars; Reinikainen, Tapani; Sippola, Erkki; Corander, Jukka

    2010-10-10

    Headspace gas chromatographic measurements of ethanol content in blood specimens from suspect drunk drivers are routinely carried out in forensic laboratories. In the widely established standard statistical framework, measurement errors in such data are represented by Gaussian distributions for the population of blood specimens at any given level of ethanol content. It is known that the variance of measurement errors increases as a function of the level of ethanol content and the standard statistical approach addresses this issue by replacing the unknown population variances by estimates derived from large sample using a linear regression model. Appropriate statistical analysis of the systematic and random components in the measurement errors is necessary in order to guarantee legally sound security corrections reported to the police authority. Here we address this issue by developing a novel statistical approach that takes into account any potential non-linearity in the relationship between the level of ethanol content and the variability of measurement errors. Our method is based on standard non-parametric kernel techniques for density estimation using a large database of laboratory measurements for blood specimens. Furthermore, we address also the issue of systematic errors in the measurement process by a statistical model that incorporates the sign of the error term in the security correction calculations. Analysis of a set of certified reference materials (CRMs) blood samples demonstrates the importance of explicitly handling the direction of the systematic errors in establishing the statistical uncertainty about the true level of ethanol content. Use of our statistical framework to aid quality control in the laboratory is also discussed. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Comparative ultrastructural analyses of platelets and fibrin networks using the murine model of asthma.

    Science.gov (United States)

    Pretorius, E; Ekpo, O E; Smit, E

    2007-10-01

    The murine Balb/c asthma model has been used successfully for a number of in vivo immunological applications and for testing novel therapeutics, and it is a reliable, clinically relevant facsimile of the human disease. Here we investigate whether this model can be used to study other components of the human body, e.g. ultrastructure. In particular, we investigate the effect of the phytomedicine Euphorbia hirta (used to treat asthma), on the ultrastructure of fibrin as well as platelets, cellular structures that both play an important role in the coagulation process. Hydrocortisone is used as positive control. Ultrastructure of the fibrin networks and platelets of control mice were compared to mice that were asthmatic, treated with two concentrations of hydrocortisone and one concentration of the plant material. Results indicate control mice possess major, thick fibers and minor thin fibers as well as tight round platelet aggregates with typical pseudopodia formation. Minor fibers of asthmatic mice have a netlike appearance covering the major fibers, while the platelets seem to form loosely connected, granular aggregates. Both concentrations of hydrocortisone make the fibrin more fragile and that platelet morphology changes form a tight platelet aggregate to a more granular aggregate not closely fused to each other. We conclude that E. hirta does not impact on the fragility of the fibrin and that it prevents the minor fibers to form the dense netlike layer over the major fibers, as is seen in untreated asthmatic mice. This ultrastructural morphology might give us better insight into asthma and the possible new treatment regimes.

  12. On Deriving Requirements for the Surface Mass Balance forcing of a Greenland Ice Sheet Model using Uncertainty Analyses

    Science.gov (United States)

    Schlegel, N.; Larour, E. Y.; Box, J. E.

    2015-12-01

    During July of 2012, the percentage of the Greenland surface exposed to melt was the largest in recorded history. And, even though evidence of increased melt rates had been captured by remote sensing observations throughout the last decade, this particular event took the community by surprise. How Greenland ice flow will respond to such an event or to increased frequencies of extreme melt events in the future is unclear, as it requires detailed comprehension of Greenland surface climate and the ice sheet's sensitivity to associated uncertainties. With established uncertainty quantification (UQ) tools embedded within the Ice Sheet System Model (ISSM), we conduct decadal-scale forward modeling experiments to 1) quantify the spatial resolution needed to effectively force surface mass balance (SMB) in various regions of the ice sheet and 2) determine the dynamic response of Greenland outlet glaciers to variations in SMB. First, we perform sensitivity analyses to determine how perturbations in SMB affect model output; results allow us to investigate the locations where variations most significantly affect ice flow, and on what spatial scales. Next, we apply Monte-Carlo style sampling analyses to determine how errors in SMB propagate through the model as uncertainties in estimates of Greenland ice discharge and regional mass balance. This work is performed at the California Institute of Technology's Jet Propulsion Laboratory under a contract with the National Aeronautics and Space Administration's Cryosphere Program.

  13. Analyses and optimization of Lee propagation model for LoRa 868 MHz network deployments in urban areas

    Directory of Open Access Journals (Sweden)

    Dobrilović Dalibor

    2017-01-01

    Full Text Available In the recent period, fast ICT expansion and rapid appearance of new technologies raised the importance of fast and accurate planning and deployment of emerging communication technologies, especially wireless ones. In this paper is analyzed possible usage of Lee propagation model for planning, design and management of networks based on LoRa 868MHz technology. LoRa is wireless technology which can be deployed in various Internet of Things and Smart City scenarios in urban areas. The analyses are based on comparison of field measurements with model calculations. Besides the analyses of Lee propagation model usability, the possible optimization of the model is discussed as well. The research results can be used for accurate design, planning and for preparation of high-performance wireless resource management of various Internet of Things and Smart City applications in urban areas based on LoRa or similar wireless technology. The equipment used for measurements is based on open-source hardware.

  14. Parametric analyses of DEMO Divertor using two dimensional transient thermal hydraulic modelling

    Science.gov (United States)

    Domalapally, Phani; Di Caro, Marco

    2017-11-01

    Among the options considered for cooling of the Plasma facing components of the DEMO reactor, water cooling is a conservative option because of its high heat removal capability. In this work a two-dimensional transient thermal hydraulic code is developed to support the design of the divertor for the projected DEMO reactor with water as a coolant. The mathematical model accounts for transient 2D heat conduction in the divertor section. Temperature-dependent properties are used for more accurate analysis. Correlations for single phase flow forced convection, partially developed subcooled nucleate boiling, fully developed subcooled nucleate boiling and film boiling are used to calculate the heat transfer coefficients on the channel side considering the swirl flow, wherein different correlations found in the literature are compared against each other. Correlation for the Critical Heat Flux is used to estimate its limit for a given flow conditions. This paper then investigates the results of the parametric analysis performed, whereby flow velocity, diameter of the coolant channel, thickness of the coolant pipe, thickness of the armor material, inlet temperature and operating pressure affect the behavior of the divertor under steady or transient heat fluxes. This code will help in understanding the basic parameterś effect on the behavior of the divertor, to achieve a better design from a thermal hydraulic point of view.

  15. Modelling and Analysing Deadlock in Flexible Manufacturing System using Timed Petri Net

    Directory of Open Access Journals (Sweden)

    Assem Hatem Taha

    2017-03-01

    Full Text Available Flexible manufacturing system (FMS has several advantages compared to conventional systems such as higher machine utilization, higher efficiency, less inventory, and less production time. On the other hand, FMS is expensive and complicated. One of the main problems that may happen is the deadlock. Deadlock is a case that happens when one operation or more are unable to complete their tasks because of waiting of resources that are used by other processes. This may occur due to inappropriate sharing of the resources or improper resource allocation logic which may lead to deadlock occurrence due to the complexity of assigning shared resources to different tasks in an efficient way. One of the most effective tools to model and detect the deadlocks is the petri net. In this research the Matlab software has been used to detect the deadlock in two parallel lines with one shared machines. The analysis shows that deadlock exists at transition with high utilization and place with high waiting time

  16. Alpins and thibos vectorial astigmatism analyses: proposal of a linear regression model between methods

    Directory of Open Access Journals (Sweden)

    Giuliano de Oliveira Freitas

    2013-10-01

    Full Text Available PURPOSE: To determine linear regression models between Alpins descriptive indices and Thibos astigmatic power vectors (APV, assessing the validity and strength of such correlations. METHODS: This case series prospectively assessed 62 eyes of 31 consecutive cataract patients with preoperative corneal astigmatism between 0.75 and 2.50 diopters in both eyes. Patients were randomly assorted among two phacoemulsification groups: one assigned to receive AcrySof®Toric intraocular lens (IOL in both eyes and another assigned to have AcrySof Natural IOL associated with limbal relaxing incisions, also in both eyes. All patients were reevaluated postoperatively at 6 months, when refractive astigmatism analysis was performed using both Alpins and Thibos methods. The ratio between Thibos postoperative APV and preoperative APV (APVratio and its linear regression to Alpins percentage of success of astigmatic surgery, percentage of astigmatism corrected and percentage of astigmatism reduction at the intended axis were assessed. RESULTS: Significant negative correlation between the ratio of post- and preoperative Thibos APVratio and Alpins percentage of success (%Success was found (Spearman's ρ=-0.93; linear regression is given by the following equation: %Success = (-APVratio + 1.00x100. CONCLUSION: The linear regression we found between APVratio and %Success permits a validated mathematical inference concerning the overall success of astigmatic surgery.

  17. Modelling and optimization of combined cycle power plant based on exergoeconomic and environmental analyses

    International Nuclear Information System (INIS)

    Ganjehkaviri, A.; Mohd Jaafar, M.N.; Ahmadi, P.; Barzegaravval, H.

    2014-01-01

    This research paper presents a study on a comprehensive thermodynamic modelling of a combined cycle power plant (CCPP). The effects of economic strategies and design parameters on the plant optimization are also studied. Exergoeconomic analysis is conducted in order to determine the cost of electricity and cost of exergy destruction. In addition, a comprehensive optimization study is performed to determine the optimal design parameters of the power plant. Next, the effects of economic parameters variations on the sustainability, carbon dioxide emission and fuel consumption of the plant are investigated and are presented for a typical combined cycle power plant. Therefore, the changes in economic parameters caused the balance between cash flows and fix costs of the plant changes at optimum point. Moreover, economic strategies greatly limited the maximum reasonable carbon emission and fuel consumption reduction. The results showed that by using the optimum values, the exergy efficiency increases for about 6%, while CO 2 emission decreases by 5.63%. However, the variation in the cost was less than 1% due to the fact that a cost constraint was implemented. In addition, the sensitivity analysis for the optimization study was curtailed to be carried out; therefore, the optimization process and results to two important parameters are presented and discussed.

  18. Microarray and bioinformatic analyses suggest models for carbon metabolism in the autotroph Acidithiobacillus ferrooxidans

    Energy Technology Data Exchange (ETDEWEB)

    C. Appia-ayme; R. Quatrini; Y. Denis; F. Denizot; S. Silver; F. Roberto; F. Veloso; J. Valdes; J. P. Cardenas; M. Esparza; O. Orellana; E. Jedlicki; V. Bonnefoy; D. Holmes

    2006-09-01

    Acidithiobacillus ferrooxidans is a chemolithoautotrophic bacterium that uses iron or sulfur as an energy and electron source. Bioinformatic analysis was used to identify putative genes and potential metabolic pathways involved in CO2 fixation, 2P-glycolate detoxification, carboxysome formation and glycogen utilization in At. ferrooxidans. Microarray transcript profiling was carried out to compare the relative expression of the predicted genes of these pathways when the microorganism was grown in the presence of iron versus sulfur. Several gene expression patterns were confirmed by real-time PCR. Genes for each of the above predicted pathways were found to be organized into discrete clusters. Clusters exhibited differential gene expression depending on the presence of iron or sulfur in the medium. Concordance of gene expression within each cluster, suggested that they are operons Most notably, clusters of genes predicted to be involved in CO2 fixation, carboxysome formation, 2P-glycolate detoxification and glycogen biosynthesis were up-regulated in sulfur medium, whereas genes involved in glycogen utilization were preferentially expressed in iron medium. These results can be explained in terms of models of gene regulation that suggest how A. ferrooxidans can adjust its central carbon management to respond to changing environmental conditions.

  19. Analysing hydro-mechanical behaviour of reinforced slopes through centrifuge modelling

    Science.gov (United States)

    Veenhof, Rick; Wu, Wei

    2017-04-01

    Every year, slope instability is causing casualties and damage to properties and the environment. The behaviour of slopes during and after these kind of events is complex and depends on meteorological conditions, slope geometry, hydro-mechanical soil properties, boundary conditions and the initial state of the soils. This study describes the effects of adding reinforcement, consisting of randomly distributed polyolefin monofilament fibres or Ryegrass (Lolium), on the behaviour of medium-fine sand in loose and medium dense conditions. Direct shear tests were performed on sand specimens with different void ratios, water content and fibre or root density, respectively. To simulate the stress state of real scale field situations, centrifuge model tests were conducted on sand specimens with different slope angles, thickness of the reinforced layer, fibre density, void ratio and water content. An increase in peak shear strength is observed in all reinforced cases. Centrifuge tests show that for slopes that are reinforced the period until failure is extended. The location of shear band formation and patch displacement behaviour indicate that the design of slope reinforcement has a significant effect on the failure behaviour. Future research will focus on the effect of plant water uptake on soil cohesion.

  20. Fungal-Induced Deterioration of Mural Paintings: In Situ and Mock-Model Microscopy Analyses.

    Science.gov (United States)

    Unković, Nikola; Grbić, Milica Ljaljević; Stupar, Miloš; Savković, Željko; Jelikić, Aleksa; Stanojević, Dragan; Vukojević, Jelena

    2016-04-01

    Fungal deterioration of frescoes was studied in situ on a selected Serbian church, and on a laboratory model, utilizing standard and newly implemented microscopy techniques. Scanning electron microscopy (SEM) with energy-dispersive X-ray confirmed the limestone components of the plaster. Pigments used were identified as carbon black, green earth, iron oxide, ocher, and an ocher/cinnabar mixture. In situ microscopy, applied via a portable microscope ShuttlePix P-400R, proved very useful for detection of invisible micro-impairments and hidden, symptomless, microbial growth. SEM and optical microscopy established that observed deterioration symptoms, predominantly discoloration and pulverization of painted layers, were due to bacterial filaments and fungal hyphal penetration, and formation of a wide range of fungal structures (i.e., melanized hyphae, chlamydospores, microcolonial clusters, Cladosporium-like conidia, and Chaetomium perithecia and ascospores). The all year-round monitoring of spontaneous and induced fungal colonization of a "mock painting" in controlled laboratory conditions confirmed the decisive role of humidity level (70.18±6.91% RH) in efficient colonization of painted surfaces, as well as demonstrated increased bioreceptivity of painted surfaces to fungal colonization when plant-based adhesives (ilinocopie, murdent), compared with organic adhesives of animal origin (bone glue, egg white), are used for pigment sizing.

  1. Modeling and Analysing of Air Filter in Air Intake System in Automobile Engine

    Directory of Open Access Journals (Sweden)

    R. Manikantan

    2013-01-01

    Full Text Available As the legislations on the emission and performance of automobiles are being made more stringent, the expected performance of all the subsystems of an internal combustion engine is also becoming crucial. Nowadays the engines are downsized, and their power increased the demand on the air intake system that has increased phenomenally. Hence, an analysis was carried on a typical air filter fitted into the intake system to determine its flow characteristics. In the present investigation, a CAD model of an existing air filter was designed, and CFD analysis was done pertaining to various operating regimes of an internal combustion engine. The numerical results were validated with the experimental data. From the postprocessed result, we can see that there is a deficit in the design of the present filter, as the bottom portion of the filter is preventing the upward movement of air. Hence, the intake passage can be rearranged to provide an upward tangential motion, which can enhance the removal of larger dust and soot particles effectively by the inertial action of air alone.

  2. Analysing movements in investor’s risk aversion using the Heston volatility model

    Directory of Open Access Journals (Sweden)

    Alexie ALUPOAIEI

    2013-03-01

    Full Text Available In this paper we intend to identify and analyze, if it is the case, an “epidemiological” relationship between forecasts of professional investors and short-term developments in the EUR/RON exchange rate. Even that we don’t call a typical epidemiological model as those ones used in biology fields of research, we investigated the hypothesis according to which after the Lehman Brothers crash and implicit the generation of the current financial crisis, the forecasts of professional investors pose a significant explanatory power on the futures short-run movements of EUR/RON. How does it work this mechanism? Firstly, the professional forecasters account for the current macro, financial and political states, then they elaborate forecasts. Secondly, based on that forecasts they get positions in the Romanian exchange market for hedging and/or speculation purposes. But their positions incorporate in addition different degrees of uncertainty. In parallel, a part of their anticipations are disseminated to the public via media channels. Since some important movements are viewed within macro, financial or political fields, the positions of professsional investors from FX derivative market are activated. The current study represents a first step in that direction of analysis for Romanian case. For the above formulated objectives, in this paper different measures of EUR/RON rate volatility have been estimated and compared with implied volatilities. In a second timeframe we called the co-integration and dynamic correlation based tools in order to investigate the relationship between implied volatility and daily returns of EUR/RON exchange rate.

  3. Computational Modeling of Oxygen Transport in the Microcirculation: From an Experiment-Based Model to Theoretical Analyses

    OpenAIRE

    Lücker, Adrien

    2017-01-01

    Oxygen supply to cells by the cardiovascular system involves multiple physical and chemical processes that aim to satisfy fluctuating metabolic demand. Regulation mechanisms range from increased heart rate to minute adaptations in the microvasculature. The challenges and limitations of experimental studies in vivo make computational models an invaluable complement. In this thesis, oxygen transport from capillaries to tissue is investigated using a new numerical model that is tailored for vali...

  4. Pathophysiologic and transcriptomic analyses of viscerotropic yellow fever in a rhesus macaque model.

    Science.gov (United States)

    Engelmann, Flora; Josset, Laurence; Girke, Thomas; Park, Byung; Barron, Alex; Dewane, Jesse; Hammarlund, Erika; Lewis, Anne; Axthelm, Michael K; Slifka, Mark K; Messaoudi, Ilhem

    2014-01-01

    Infection with yellow fever virus (YFV), an explosively replicating flavivirus, results in viral hemorrhagic disease characterized by cardiovascular shock and multi-organ failure. Unvaccinated populations experience 20 to 50% fatality. Few studies have examined the pathophysiological changes that occur in humans during YFV infection due to the sporadic nature and remote locations of outbreaks. Rhesus macaques are highly susceptible to YFV infection, providing a robust animal model to investigate host-pathogen interactions. In this study, we characterized disease progression as well as alterations in immune system homeostasis, cytokine production and gene expression in rhesus macaques infected with the virulent YFV strain DakH1279 (YFV-DakH1279). Following infection, YFV-DakH1279 replicated to high titers resulting in viscerotropic disease with ∼72% mortality. Data presented in this manuscript demonstrate for the first time that lethal YFV infection results in profound lymphopenia that precedes the hallmark changes in liver enzymes and that although tissue damage was noted in liver, kidneys, and lymphoid tissues, viral antigen was only detected in the liver. These observations suggest that additional tissue damage could be due to indirect effects of viral replication. Indeed, circulating levels of several cytokines peaked shortly before euthanasia. Our study also includes the first description of YFV-DakH1279-induced changes in gene expression within peripheral blood mononuclear cells 3 days post-infection prior to any clinical signs. These data show that infection with wild type YFV-DakH1279 or live-attenuated vaccine strain YFV-17D, resulted in 765 and 46 differentially expressed genes (DEGs), respectively. DEGs detected after YFV-17D infection were mostly associated with innate immunity, whereas YFV-DakH1279 infection resulted in dysregulation of genes associated with the development of immune response, ion metabolism, and apoptosis. Therefore, WT-YFV infection

  5. Model-based performance and energy analyses of reverse osmosis to reuse wastewater in a PVC production site.

    Science.gov (United States)

    Hu, Kang; Fiedler, Thorsten; Blanco, Laura; Geissen, Sven-Uwe; Zander, Simon; Prieto, David; Blanco, Angeles; Negro, Carlos; Swinnen, Nathalie

    2017-11-10

    A pilot-scale reverse osmosis (RO) followed behind a membrane bioreactor (MBR) was developed for the desalination to reuse wastewater in a PVC production site. The solution-diffusion-film model (SDFM) based on the solution-diffusion model (SDM) and the film theory was proposed to describe rejections of electrolyte mixtures in the MBR effluent which consists of dominant ions (Na + and Cl - ) and several trace ions (Ca 2+ , Mg 2+ , K + and SO 4 2- ). The universal global optimisation method was used to estimate the ion permeability coefficients (B) and mass transfer coefficients (K) in SDFM. Then, the membrane performance was evaluated based on the estimated parameters which demonstrated that the theoretical simulations were in line with the experimental results for the dominant ions. Moreover, an energy analysis model with the consideration of limitation imposed by the thermodynamic restriction was proposed to analyse the specific energy consumption of the pilot-scale RO system in various scenarios.

  6. An assessment of the wind re-analyses in the modelling of an extreme sea state in the Black Sea

    Science.gov (United States)

    Akpinar, Adem; Ponce de León, S.

    2016-03-01

    This study aims at an assessment of wind re-analyses for modelling storms in the Black Sea. A wind-wave modelling system (Simulating WAve Nearshore, SWAN) is applied to the Black Sea basin and calibrated with buoy data for three recent re-analysis wind sources, namely the European Centre for Medium-Range Weather Forecasts Reanalysis-Interim (ERA-Interim), Climate Forecast System Reanalysis (CFSR), and Modern Era Retrospective Analysis for Research and Applications (MERRA) during an extreme wave condition that occurred in the north eastern part of the Black Sea. The SWAN model simulations are carried out for default and tuning settings for deep water source terms, especially whitecapping. Performances of the best model configurations based on calibration with buoy data are discussed using data from the JASON2, TOPEX-Poseidon, ENVISAT and GFO satellites. The SWAN model calibration shows that the best configuration is obtained with Janssen and Komen formulations with whitecapping coefficient (Cds) equal to 1.8e-5 for wave generation by wind and whitecapping dissipation using ERA-Interim. In addition, from the collocated SWAN results against the satellite records, the best configuration is determined to be the SWAN using the CFSR winds. Numerical results, thus show that the accuracy of a wave forecast will depend on the quality of the wind field and the ability of the SWAN model to simulate the waves under extreme wind conditions in fetch limited wave conditions.

  7. Gamma-ray pulsar physics: gap-model populations and light-curve analyses in the Fermi era

    International Nuclear Information System (INIS)

    Pierbattista, M.

    2010-01-01

    This thesis research focusses on the study of the young and energetic isolated ordinary pulsar population detected by the Fermi gamma-ray space telescope. We compared the model expectations of four emission models and the LAT data. We found that all the models fail to reproduce the LAT detections, in particular the large number of high E objects observed. This inconsistency is not model dependent. A discrepancy between the radio-loud/radio-quiet objects ratio was also found between the observed and predicted samples. The L γ α E 0.5 relation is robustly confirmed by all the assumed models with particular agreement in the slot gap (SG) case. On luminosity bases, the intermediate altitude emission of the two pole caustic SG model is favoured. The beaming factor f Ω shows an E dependency that is slightly visible in the SG case. Estimates of the pulsar orientations have been obtained to explain the simultaneous gamma and radio light-curves. By analysing the solutions we found a relation between the observed energy cutoff and the width of the emission slot gap. This relation has been theoretically predicted. A possible magnetic obliquity α alignment with time is rejected -for all the models- on timescale of the order of 10 6 years. The light-curve morphology study shows that the outer magnetosphere gap emission (OGs) are favoured to explain the observed radio-gamma lag. The light curve moment studies (symmetry and sharpness) on the contrary favour a two pole caustic SG emission. All the model predictions suggest a different magnetic field layout with an hybrid two pole caustic and intermediate altitude emission to explain both the pulsar luminosity and light curve morphology. The low magnetosphere emission mechanism of the polar cap model, is systematically rejected by all the tests done. (author) [fr

  8. Modeling and stress analyses of a normal foot-ankle and a prosthetic foot-ankle complex.

    Science.gov (United States)

    Ozen, Mustafa; Sayman, Onur; Havitcioglu, Hasan

    2013-01-01

    Total ankle replacement (TAR) is a relatively new concept and is becoming more popular for treatment of ankle arthritis and fractures. Because of the high costs and difficulties of experimental studies, the developments of TAR prostheses are progressing very slowly. For this reason, the medical imaging techniques such as CT, and MR have become more and more useful. The finite element method (FEM) is a widely used technique to estimate the mechanical behaviors of materials and structures in engineering applications. FEM has also been increasingly applied to biomechanical analyses of human bones, tissues and organs, thanks to the development of both the computing capabilities and the medical imaging techniques. 3-D finite element models of the human foot and ankle from reconstruction of MR and CT images have been investigated by some authors. In this study, data of geometries (used in modeling) of a normal and a prosthetic foot and ankle were obtained from a 3D reconstruction of CT images. The segmentation software, MIMICS was used to generate the 3D images of the bony structures, soft tissues and components of prosthesis of normal and prosthetic ankle-foot complex. Except the spaces between the adjacent surface of the phalanges fused, metatarsals, cuneiforms, cuboid, navicular, talus and calcaneus bones, soft tissues and components of prosthesis were independently developed to form foot and ankle complex. SOLIDWORKS program was used to form the boundary surfaces of all model components and then the solid models were obtained from these boundary surfaces. Finite element analyses software, ABAQUS was used to perform the numerical stress analyses of these models for balanced standing position. Plantar pressure and von Mises stress distributions of the normal and prosthetic ankles were compared with each other. There was a peak pressure increase at the 4th metatarsal, first metatarsal and talus bones and a decrease at the intermediate cuneiform and calcaneus bones, in

  9. Genetic analyses using GGE model and a mixed linear model approach, and stability analyses using AMMI bi-plot for late-maturity alpha-amylase activity in bread wheat genotypes.

    Science.gov (United States)

    Rasul, Golam; Glover, Karl D; Krishnan, Padmanaban G; Wu, Jixiang; Berzonsky, William A; Fofana, Bourlaye

    2017-06-01

    Low falling number and discounting grain when it is downgraded in class are the consequences of excessive late-maturity α-amylase activity (LMAA) in bread wheat (Triticum aestivum L.). Grain expressing high LMAA produces poorer quality bread products. To effectively breed for low LMAA, it is necessary to understand what genes control it and how they are expressed, particularly when genotypes are grown in different environments. In this study, an International Collection (IC) of 18 spring wheat genotypes and another set of 15 spring wheat cultivars adapted to South Dakota (SD), USA were assessed to characterize the genetic component of LMAA over 5 and 13 environments, respectively. The data were analysed using a GGE model with a mixed linear model approach and stability analysis was presented using an AMMI bi-plot on R software. All estimated variance components and their proportions to the total phenotypic variance were highly significant for both sets of genotypes, which were validated by the AMMI model analysis. Broad-sense heritability for LMAA was higher in SD adapted cultivars (53%) compared to that in IC (49%). Significant genetic effects and stability analyses showed some genotypes, e.g. 'Lancer', 'Chester' and 'LoSprout' from IC, and 'Alsen', 'Traverse' and 'Forefront' from SD cultivars could be used as parents to develop new cultivars expressing low levels of LMAA. Stability analysis using an AMMI bi-plot revealed that 'Chester', 'Lancer' and 'Advance' were the most stable across environments, while in contrast, 'Kinsman', 'Lerma52' and 'Traverse' exhibited the lowest stability for LMAA across environments.

  10. ATOP - The Advanced Taiwan Ocean Prediction System Based on the mpiPOM. Part 1: Model Descriptions, Analyses and Results

    Directory of Open Access Journals (Sweden)

    Leo Oey

    2013-01-01

    Full Text Available A data-assimilated Taiwan Ocean Prediction (ATOP system is being developed at the National Central University, Taiwan. The model simulates sea-surface height, three-dimensional currents, temperature and salinity and turbulent mixing. The model has options for tracer and particle-tracking algorithms, as well as for wave-induced Stokes drift and wave-enhanced mixing and bottom drag. Two different forecast domains have been tested: a large-grid domain that encompasses the entire North Pacific Ocean at 0.1° × 0.1° horizontal resolution and 41 vertical sigma levels, and a smaller western North Pacific domain which at present also has the same horizontal resolution. In both domains, 25-year spin-up runs from 1988 - 2011 were first conducted, forced by six-hourly Cross-Calibrated Multi-Platform (CCMP and NCEP reanalysis Global Forecast System (GSF winds. The results are then used as initial conditions to conduct ocean analyses from January 2012 through February 2012, when updated hindcasts and real-time forecasts begin using the GFS winds. This paper describes the ATOP system and compares the forecast results against satellite altimetry data for assessing model skills. The model results are also shown to compare well with observations of (i the Kuroshio intrusion in the northern South China Sea, and (ii subtropical counter current. Review and comparison with other models in the literature of ¡§(i¡¨ are also given.

  11. A regional tidal/subtidal circulation model of the southeastern Bering Sea: development, sensitivity analyses and hindcasting

    Science.gov (United States)

    Hermann, Albert J.; Stabeno, Phyllis J.; Haidvogel, Dale B.; Musgrave, David L.

    2002-12-01

    A regional eddy-resolving primitive equation circulation model was used to simulate circulation on the southeastern Bering Sea (SEBS) shelf and basin. This model resolves the dominant observed mean currents, eddies and meanders in the region, and simultaneously includes both tidal and subtidal dynamics. Circulation, temperature, and salinity fields for years 1995 and 1997 were hindcast, using daily wind and buoyancy flux estimates, and tidal forcing derived from a global model. This paper describes the development of the regional model, a comparison of model results with available Eulerian and Lagrangian data, a comparison of results between the two hindcast years, and a sensitivity analysis. Based on these hindcasts and sensitivity analyses, we suggest the following: (1) The Bering Slope Current is a primary source of large ( ˜100 km diameter) eddies in the SEBS basin. Smaller meanders are also formed along the 100 m isobath on the southeastern shelf, and along the 200-m isobath near the shelf break. (2) There is substantial interannual variability in the statistics of eddies within the basin, driven by variability in the strength of the ANSC. (3) The mean flow on the shelf is not strongly sensitive to changes in the imposed strength of the ANSC; rather, it is strongly sensitive to the local wind forcing. (4) Vertical mixing in the SEBS is strongly affected by both tidal and subtidal dynamics. Strongest mixing in the SEBS may in fact occur between the 100- and 400-m isobaths, near the Pribilof Islands, and in Unimak Pass.

  12. One size does not fit all: On how Markov model order dictates performance of genomic sequence analyses

    Science.gov (United States)

    Narlikar, Leelavati; Mehta, Nidhi; Galande, Sanjeev; Arjunwadkar, Mihir

    2013-01-01

    The structural simplicity and ability to capture serial correlations make Markov models a popular modeling choice in several genomic analyses, such as identification of motifs, genes and regulatory elements. A critical, yet relatively unexplored, issue is the determination of the order of the Markov model. Most biological applications use a predetermined order for all data sets indiscriminately. Here, we show the vast variation in the performance of such applications with the order. To identify the ‘optimal’ order, we investigated two model selection criteria: Akaike information criterion and Bayesian information criterion (BIC). The BIC optimal order delivers the best performance for mammalian phylogeny reconstruction and motif discovery. Importantly, this order is different from orders typically used by many tools, suggesting that a simple additional step determining this order can significantly improve results. Further, we describe a novel classification approach based on BIC optimal Markov models to predict functionality of tissue-specific promoters. Our classifier discriminates between promoters active across 12 different tissues with remarkable accuracy, yielding 3 times the precision expected by chance. Application to the metagenomics problem of identifying the taxum from a short DNA fragment yields accuracies at least as high as the more complex mainstream methodologies, while retaining conceptual and computational simplicity. PMID:23267010

  13. Advances in global sensitivity analyses of demographic-based species distribution models to address uncertainties in dynamic landscapes

    Directory of Open Access Journals (Sweden)

    Ilona Naujokaitis-Lewis

    2016-07-01

    Full Text Available Developing a rigorous understanding of multiple global threats to species persistence requires the use of integrated modeling methods that capture processes which influence species distributions. Species distribution models (SDMs coupled with population dynamics models can incorporate relationships between changing environments and demographics and are increasingly used to quantify relative extinction risks associated with climate and land-use changes. Despite their appeal, uncertainties associated with complex models can undermine their usefulness for advancing predictive ecology and informing conservation management decisions. We developed a computationally-efficient and freely available tool (GRIP 2.0 that implements and automates a global sensitivity analysis of coupled SDM-population dynamics models for comparing the relative influence of demographic parameters and habitat attributes on predicted extinction risk. Advances over previous global sensitivity analyses include the ability to vary habitat suitability across gradients, as well as habitat amount and configuration of spatially-explicit suitability maps of real and simulated landscapes. Using GRIP 2.0, we carried out a multi-model global sensitivity analysis of a coupled SDM-population dynamics model of whitebark pine (Pinus albicaulis in Mount Rainier National Park as a case study and quantified the relative influence of input parameters and their interactions on model predictions. Our results differed from the one-at-time analyses used in the original study, and we found that the most influential parameters included the total amount of suitable habitat within the landscape, survival rates, and effects of a prevalent disease, white pine blister rust. Strong interactions between habitat amount and survival rates of older trees suggests the importance of habitat in mediating the negative influences of white pine blister rust. Our results underscore the importance of considering habitat

  14. Data Assimilation Tools for CO2 Reservoir Model Development – A Review of Key Data Types, Analyses, and Selected Software

    Energy Technology Data Exchange (ETDEWEB)

    Rockhold, Mark L.; Sullivan, E. C.; Murray, Christopher J.; Last, George V.; Black, Gary D.

    2009-09-30

    Pacific Northwest National Laboratory (PNNL) has embarked on an initiative to develop world-class capabilities for performing experimental and computational analyses associated with geologic sequestration of carbon dioxide. The ultimate goal of this initiative is to provide science-based solutions for helping to mitigate the adverse effects of greenhouse gas emissions. This Laboratory-Directed Research and Development (LDRD) initiative currently has two primary focus areas—advanced experimental methods and computational analysis. The experimental methods focus area involves the development of new experimental capabilities, supported in part by the U.S. Department of Energy’s (DOE) Environmental Molecular Science Laboratory (EMSL) housed at PNNL, for quantifying mineral reaction kinetics with CO2 under high temperature and pressure (supercritical) conditions. The computational analysis focus area involves numerical simulation of coupled, multi-scale processes associated with CO2 sequestration in geologic media, and the development of software to facilitate building and parameterizing conceptual and numerical models of subsurface reservoirs that represent geologic repositories for injected CO2. This report describes work in support of the computational analysis focus area. The computational analysis focus area currently consists of several collaborative research projects. These are all geared towards the development and application of conceptual and numerical models for geologic sequestration of CO2. The software being developed for this focus area is referred to as the Geologic Sequestration Software Suite or GS3. A wiki-based software framework is being developed to support GS3. This report summarizes work performed in FY09 on one of the LDRD projects in the computational analysis focus area. The title of this project is Data Assimilation Tools for CO2 Reservoir Model Development. Some key objectives of this project in FY09 were to assess the current state

  15. Perspectives on econometric modelling to inform policy: a UK qualitative case study of minimum unit pricing of alcohol.

    Science.gov (United States)

    Katikireddi, Srinivasa V; Bond, Lyndal; Hilton, Shona

    2014-06-01

    Novel policy interventions may lack evaluation-based evidence. Considerations to introduce minimum unit pricing (MUP) of alcohol in the UK were informed by econometric modelling (the 'Sheffield model'). We aim to investigate policy stakeholders' views of the utility of modelling studies for public health policy. In-depth qualitative interviews with 36 individuals involved in MUP policy debates (purposively sampled to include civil servants, politicians, academics, advocates and industry-related actors) were conducted and thematically analysed. Interviewees felt familiar with modelling studies and often displayed detailed understandings of the Sheffield model. Despite this, many were uneasy about the extent to which the Sheffield model could be relied on for informing policymaking and preferred traditional evaluations. A tension was identified between this preference for post hoc evaluations and a desire for evidence derived from local data, with modelling seen to offer high external validity. MUP critics expressed concern that the Sheffield model did not adequately capture the 'real life' world of the alcohol market, which was conceptualized as a complex and, to some extent, inherently unpredictable system. Communication of modelling results was considered intrinsically difficult but presenting an appropriate picture of the uncertainties inherent in modelling was viewed as desirable. There was general enthusiasm for increased use of econometric modelling to inform future policymaking but an appreciation that such evidence should only form one input into the process. Modelling studies are valued by policymakers as they provide contextually relevant evidence for novel policies, but tensions exist with views of traditional evaluation-based evidence. © The Author 2013. Published by Oxford University Press on behalf of the European Public Health Association.

  16. A systematic review of approaches to modelling lower limb muscle forces during gait: Applicability to clinical gait analyses.

    Science.gov (United States)

    Trinler, Ursula; Hollands, Kristen; Jones, Richard; Baker, Richard

    2018-03-01

    Computational methods to estimate muscle forces during walking are becoming more common in biomechanical research but not yet in clinical gait analysis. This systematic review aims to identify the current state-of-the-art, examine the differences between approaches, and consider applicability of the current approaches in clinical gait analysis. A systematic database search identified studies including estimated muscle force profiles of the lower limb during healthy walking. These were rated for quality and the muscle force profiles digitised for comparison. From 13.449 identified studies, 22 were finally included which used four modelling approaches: static optimisation, enhanced static optimisation, forward dynamics and EMG-driven. These used a range of different musculoskeletal models, muscle-tendon characteristics and cost functions. There is visually broad agreement between and within approaches about when muscles are active throughout the gait cycle. There remain, considerable differences (CV 7%-151%, range of timing of peak forces in gait cycle 1%-31%) in patterns and magnitudes of force between and within modelling approaches. The main source of this variability is not clear. Different musculoskeletal models, experimental protocols, and modelling approaches will clearly have an effect as will the variability of joint kinetics between healthy individuals. Limited validation of modelling approaches, particularly at the level of individual participants, makes it difficult to conclude if any of the approaches give consistently better estimates than others. While muscle force modelling has clear potential to enhance clinical gait analyses future research is needed to improve validation, accuracy and feasibility of implementation in clinical practice. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Using plant growth modeling to analyse C source-sink relations under drought: inter and intra specific comparison

    Directory of Open Access Journals (Sweden)

    Benoit ePallas

    2013-11-01

    Full Text Available The ability to assimilate C and allocate NSC (non structural carbohydrates to the most appropriate organs is crucial to maximize plant ecological or agronomic performance. Such C source and sink activities are differentially affected by environmental constraints. Under drought, plant growth is generally more sink than source limited as organ expansion or appearance rate is earlier and stronger affected than C assimilation. This favors plant survival and recovery but not always agronomic performance as NSC are stored rather than used for growth due to a modified metabolism in source and sink leaves. Such interactions between plant C and water balance are complex and plant modeling can help analyzing their impact on plant phenotype. This paper addresses the impact of trade-offs between C sink and source activities and plant production under drought, combining experimental and modeling approaches. Two contrasted monocotyledonous species (rice, oil palm were studied. Experimentally, the sink limitation of plant growth under moderate drought was confirmed as well as the modifications in NSC metabolism in source and sink organs. Under severe stress, when C source became limiting, plant NSC concentration decreased. Two plant models dedicated to oil palm and rice morphogenesis were used to perform a sensitivity analysis and further explore how to optimize C sink and source drought sensitivity to maximize plant growth. Modeling results highlighted that optimal drought sensitivity depends both on drought type and species and that modeling is a great opportunity to analyse such complex processes. Further modeling needs and more generally the challenge of using models to support complex trait breeding are discussed.

  18. Comparative sequence and structural analyses of G-protein-coupled receptor crystal structures and implications for molecular models.

    Directory of Open Access Journals (Sweden)

    Catherine L Worth

    Full Text Available BACKGROUND: Up until recently the only available experimental (high resolution structure of a G-protein-coupled receptor (GPCR was that of bovine rhodopsin. In the past few years the determination of GPCR structures has accelerated with three new receptors, as well as squid rhodopsin, being successfully crystallized. All share a common molecular architecture of seven transmembrane helices and can therefore serve as templates for building molecular models of homologous GPCRs. However, despite the common general architecture of these structures key differences do exist between them. The choice of which experimental GPCR structure(s to use for building a comparative model of a particular GPCR is unclear and without detailed structural and sequence analyses, could be arbitrary. The aim of this study is therefore to perform a systematic and detailed analysis of sequence-structure relationships of known GPCR structures. METHODOLOGY: We analyzed in detail conserved and unique sequence motifs and structural features in experimentally-determined GPCR structures. Deeper insight into specific and important structural features of GPCRs as well as valuable information for template selection has been gained. Using key features a workflow has been formulated for identifying the most appropriate template(s for building homology models of GPCRs of unknown structure. This workflow was applied to a set of 14 human family A GPCRs suggesting for each the most appropriate template(s for building a comparative molecular model. CONCLUSIONS: The available crystal structures represent only a subset of all possible structural variation in family A GPCRs. Some GPCRs have structural features that are distributed over different crystal structures or which are not present in the templates suggesting that homology models should be built using multiple templates. This study provides a systematic analysis of GPCR crystal structures and a consistent method for identifying

  19. Comparative sequence and structural analyses of G-protein-coupled receptor crystal structures and implications for molecular models.

    Science.gov (United States)

    Worth, Catherine L; Kleinau, Gunnar; Krause, Gerd

    2009-09-16

    Up until recently the only available experimental (high resolution) structure of a G-protein-coupled receptor (GPCR) was that of bovine rhodopsin. In the past few years the determination of GPCR structures has accelerated with three new receptors, as well as squid rhodopsin, being successfully crystallized. All share a common molecular architecture of seven transmembrane helices and can therefore serve as templates for building molecular models of homologous GPCRs. However, despite the common general architecture of these structures key differences do exist between them. The choice of which experimental GPCR structure(s) to use for building a comparative model of a particular GPCR is unclear and without detailed structural and sequence analyses, could be arbitrary. The aim of this study is therefore to perform a systematic and detailed analysis of sequence-structure relationships of known GPCR structures. We analyzed in detail conserved and unique sequence motifs and structural features in experimentally-determined GPCR structures. Deeper insight into specific and important structural features of GPCRs as well as valuable information for template selection has been gained. Using key features a workflow has been formulated for identifying the most appropriate template(s) for building homology models of GPCRs of unknown structure. This workflow was applied to a set of 14 human family A GPCRs suggesting for each the most appropriate template(s) for building a comparative molecular model. The available crystal structures represent only a subset of all possible structural variation in family A GPCRs. Some GPCRs have structural features that are distributed over different crystal structures or which are not present in the templates suggesting that homology models should be built using multiple templates. This study provides a systematic analysis of GPCR crystal structures and a consistent method for identifying suitable templates for GPCR homology modelling that will

  20. Perspectives on econometric modelling to inform policy: a UK qualitative case study of minimum unit pricing of alcohol

    Science.gov (United States)

    Bond, Lyndal; Hilton, Shona

    2014-01-01

    Background: Novel policy interventions may lack evaluation-based evidence. Considerations to introduce minimum unit pricing (MUP) of alcohol in the UK were informed by econometric modelling (the ‘Sheffield model’). We aim to investigate policy stakeholders’ views of the utility of modelling studies for public health policy. Methods: In-depth qualitative interviews with 36 individuals involved in MUP policy debates (purposively sampled to include civil servants, politicians, academics, advocates and industry-related actors) were conducted and thematically analysed. Results: Interviewees felt familiar with modelling studies and often displayed detailed understandings of the Sheffield model. Despite this, many were uneasy about the extent to which the Sheffield model could be relied on for informing policymaking and preferred traditional evaluations. A tension was identified between this preference for post hoc evaluations and a desire for evidence derived from local data, with modelling seen to offer high external validity. MUP critics expressed concern that the Sheffield model did not adequately capture the ‘real life’ world of the alcohol market, which was conceptualized as a complex and, to some extent, inherently unpredictable system. Communication of modelling results was considered intrinsically difficult but presenting an appropriate picture of the uncertainties inherent in modelling was viewed as desirable. There was general enthusiasm for increased use of econometric modelling to inform future policymaking but an appreciation that such evidence should only form one input into the process. Conclusion: Modelling studies are valued by policymakers as they provide contextually relevant evidence for novel policies, but tensions exist with views of traditional evaluation-based evidence. PMID:24367068

  1. Static and free-vibration analyses of dental prosthesis and atherosclerotic human artery by refined finite element models.

    Science.gov (United States)

    Carrera, E; Guarnera, D; Pagani, A

    2018-04-01

    Static and modal responses of representative biomechanical structures are investigated in this paper by employing higher-order theories of structures and finite element approximations. Refined models are implemented in the domain of the Carrera unified formulation (CUF), according to which low- to high-order kinematics can be postulated as arbitrary and, eventually, hierarchical expansions of the generalized displacement unknowns. By using CUF along with the principle of virtual work, the governing equations are expressed in terms of fundamental nuclei of finite element arrays. The fundamental nuclei are invariant of the theory approximation order and can be opportunely employed to implement variable kinematics theories of bio-structures. In this work, static and free-vibration analyses of an atherosclerotic plaque of a human artery and a dental prosthesis are discussed. The results from the proposed methodologies highlight a number of advantages of CUF models with respect to already established theories and commercial software tools. Namely, (i) CUF models can represent correctly the higher-order phenomena related to complex stress/strain field distributions and coupled mode shapes; (ii) bio-structures can be modeled in a component-wise sense by only employing the physical boundaries of the problem domain and without making any geometrical simplification. This latter aspect, in particular, can be currently accomplished only by using three-dimensional analysis, which may be computationally unbearable as complex bio-systems are considered.

  2. A multinomial logit model-Bayesian network hybrid approach for driver injury severity analyses in rear-end crashes.

    Science.gov (United States)

    Chen, Cong; Zhang, Guohui; Tarefder, Rafiqul; Ma, Jianming; Wei, Heng; Guan, Hongzhi

    2015-07-01

    Rear-end crash is one of the most common types of traffic crashes in the U.S. A good understanding of its characteristics and contributing factors is of practical importance. Previously, both multinomial Logit models and Bayesian network methods have been used in crash modeling and analysis, respectively, although each of them has its own application restrictions and limitations. In this study, a hybrid approach is developed to combine multinomial logit models and Bayesian network methods for comprehensively analyzing driver injury severities in rear-end crashes based on state-wide crash data collected in New Mexico from 2010 to 2011. A multinomial logit model is developed to investigate and identify significant contributing factors for rear-end crash driver injury severities classified into three categories: no injury, injury, and fatality. Then, the identified significant factors are utilized to establish a Bayesian network to explicitly formulate statistical associations between injury severity outcomes and explanatory attributes, including driver behavior, demographic features, vehicle factors, geometric and environmental characteristics, etc. The test results demonstrate that the proposed hybrid approach performs reasonably well. The Bayesian network reference analyses indicate that the factors including truck-involvement, inferior lighting conditions, windy weather conditions, the number of vehicles involved, etc. could significantly increase driver injury severities in rear-end crashes. The developed methodology and estimation results provide insights for developing effective countermeasures to reduce rear-end crash injury severities and improve traffic system safety performance. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Comparative analyses reveal potential uses of Brachypodium distachyon as a model for cold stress responses in temperate grasses

    Directory of Open Access Journals (Sweden)

    Li Chuan

    2012-05-01

    Full Text Available Abstract Background Little is known about the potential of Brachypodium distachyon as a model for low temperature stress responses in Pooideae. The ice recrystallization inhibition protein (IRIP genes, fructosyltransferase (FST genes, and many C-repeat binding factor (CBF genes are Pooideae specific and important in low temperature responses. Here we used comparative analyses to study conservation and evolution of these gene families in B. distachyon to better understand its potential as a model species for agriculturally important temperate grasses. Results Brachypodium distachyon contains cold responsive IRIP genes which have evolved through Brachypodium specific gene family expansions. A large cold responsive CBF3 subfamily was identified in B. distachyon, while CBF4 homologs are absent from the genome. No B. distachyon FST gene homologs encode typical core Pooideae FST-motifs and low temperature induced fructan accumulation was dramatically different in B. distachyon compared to core Pooideae species. Conclusions We conclude that B. distachyon can serve as an interesting model for specific molecular mechanisms involved in low temperature responses in core Pooideae species. However, the evolutionary history of key genes involved in low temperature responses has been different in Brachypodium and core Pooideae species. These differences limit the use of B. distachyon as a model for holistic studies relevant for agricultural core Pooideae species.

  4. Assessing models of speciation under different biogeographic scenarios; An empirical study using multi-locus and RNA-seq analyses

    Science.gov (United States)

    Edwards, Taylor; Tollis, Marc; Hsieh, PingHsun; Gutenkunst, Ryan N.; Liu, Zhen; Kusumi, Kenro; Culver, Melanie; Murphy, Robert W.

    2016-01-01

    Evolutionary biology often seeks to decipher the drivers of speciation, and much debate persists over the relative importance of isolation and gene flow in the formation of new species. Genetic studies of closely related species can assess if gene flow was present during speciation, because signatures of past introgression often persist in the genome. We test hypotheses on which mechanisms of speciation drove diversity among three distinct lineages of desert tortoise in the genus Gopherus. These lineages offer a powerful system to study speciation, because different biogeographic patterns (physical vs. ecological segregation) are observed at opposing ends of their distributions. We use 82 samples collected from 38 sites, representing the entire species' distribution and generate sequence data for mtDNA and four nuclear loci. A multilocus phylogenetic analysis in *BEAST estimates the species tree. RNA-seq data yield 20,126 synonymous variants from 7665 contigs from two individuals of each of the three lineages. Analyses of these data using the demographic inference package ∂a∂i serve to test the null hypothesis of no gene flow during divergence. The best-fit demographic model for the three taxa is concordant with the *BEAST species tree, and the ∂a∂i analysis does not indicate gene flow among any of the three lineages during their divergence. These analyses suggest that divergence among the lineages occurred in the absence of gene flow and in this scenario the genetic signature of ecological isolation (parapatric model) cannot be differentiated from geographic isolation (allopatric model).

  5. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses

    Directory of Open Access Journals (Sweden)

    Lisette J. A. Kogelman

    2014-07-01

    Full Text Available Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome investigations focusing on single genetic variants have achieved limited success, and the importance of including genetic interactions is becoming evident. Here, the aim was to perform an integrative genomic analysis in an F2 pig resource population that was constructed with an aim to maximize genetic variation of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation of haplotype blocks. We built Weighted Interaction SNP Hub (WISH and differentially wired (DW networks using genotypic correlations amongst obesity-associated SNPs resulting from GWA analysis. GWA results and SNP modules detected by WISH and DW analyses were further investigated by functional enrichment analyses. The functional annotation of SNPs revealed several genes associated with obesity, e.g. NPC2 and OR4D10. Moreover, gene enrichment analyses identified several significantly associated pathways, over and above the GWA study results, that may influence obesity and obesity related diseases, e.g. metabolic processes. WISH networks based on genotypic correlations allowed further identification of various gene ontology terms and pathways related to obesity and related traits, which were not identified by the GWA study. In conclusion, this is the first study to develop a (genetic obesity index and employ systems genetics in a porcine model to provide important insights into the complex genetic architecture associated with obesity and many biological pathways

  6. Clustering structures of large proteins using multifractal analyses based on a 6-letter model and hydrophobicity scale of amino acids

    International Nuclear Information System (INIS)

    Yang Jianyi; Yu Zuguo; Anh, Vo

    2009-01-01

    The Schneider and Wrede hydrophobicity scale of amino acids and the 6-letter model of protein are proposed to study the relationship between the primary structure and the secondary structural classification of proteins. Two kinds of multifractal analyses are performed on the two measures obtained from these two kinds of data on large proteins. Nine parameters from the multifractal analyses are considered to construct the parameter spaces. Each protein is represented by one point in these spaces. A procedure is proposed to separate large proteins in the α, β, α + β and α/β structural classes in these parameter spaces. Fisher's linear discriminant algorithm is used to assess our clustering accuracy on the 49 selected large proteins. Numerical results indicate that the discriminant accuracies are satisfactory. In particular, they reach 100.00% and 84.21% in separating the α proteins from the {β, α + β, α/β} proteins in a parameter space; 92.86% and 86.96% in separating the β proteins from the {α + β, α/β} proteins in another parameter space; 91.67% and 83.33% in separating the α/β proteins from the α + β proteins in the last parameter space.

  7. Nonlinear Modeling and Dynamic Simulation Using Bifurcation and Stability Analyses of Regenerative Chatter of Ball-End Milling Process

    Directory of Open Access Journals (Sweden)

    Jeehyun Jung

    2016-01-01

    Full Text Available A dynamic model for a ball-end milling process that includes the consideration of cutting force nonlinearities and regenerative chatter effects is presented. The nonlinear cutting force is approximated using a Fourier series and then expanded into a Taylor series up to the third order. A series of nonlinear analyses was performed to investigate the nonlinear dynamic behavior of a ball-end milling system, and the differences between the nonlinear analysis approach and its linear counterpart were examined. A bifurcation analysis of points near the critical equilibrium points was performed using the method of multiple scales (MMS and the method of harmonic balance (MHB to analyse the local chatter behaviors of the system. The bifurcation analysis was conducted at two subcritical Hopf bifurcation points. It was also found that a ball-end milling system with nonlinear cutting forces near its critical equilibrium points is conditionally stable. The analysis and simulation results were compared with experimental data reported in the literature, and the physical significance of the results is discussed.

  8. Civil engineering: EDF needs for concrete modelling; Genie civile: analyse des besoins EDF en modelisation du comportement des betons

    Energy Technology Data Exchange (ETDEWEB)

    Didry, O.; Gerard, B.; Bui, D. [Electricite de France (EDF), Direction des Etudes et Recherches, 92 - Clamart (France)

    1997-12-31

    Concrete structures which are encountered at EDF, like all civil engineering structures, age. In order to adapt the maintenance conditions of these structures, particularly to extend their service life, and also to prepare constructions of future structures, tools for predicting the behaviour of these structures in their environment should be available. For EDF the technical risks are high and consequently very appropriate R and D actions are required. In this context the Direction des Etudes et Recherches (DER) has developed a methodology for analysing concrete structure behaviour modelling. This approach has several aims: - making a distinction between the problems which refer to the existing models and those which require R and D; - displaying disciplinary links between different problems encountered on EDF structures (non-linear mechanical, chemical - hydraulic - mechanical coupling, etc); - listing of the existing tools and positioning the DER `Aster` finite element code among them. This document is a state of the art of scientific knowledge intended to shed light on the fields in which one should be involved when there is, on one part a strong requirement on the side of structure operators, and on the other one, the present tools do not allow this requirement to be satisfactorily met. The analysis has been done on 12 scientific subjects: 1) Hydration of concrete at early ages: exothermicity, hardening, autogenous shrinkage; 2) Drying and drying shrinkage; 3) Alkali-silica reaction and bulky stage formation; 4) Long term deterioration by leaching; 5) Ionic diffusion and associated attacks: the chlorides case; 6) Permeability / tightness of concrete; 7) Concretes -nonlinear behaviour and cracking (I): contribution of the plasticity models; 8) Concretes - nonlinear behaviour and cracking (II): contribution of the damage models; 9) Concretes - nonlinear behaviour and cracking (III): the contribution of the probabilistic analysis model; 10) Delayed behaviour of

  9. A permutation test to analyse systematic bias and random measurement errors of medical devices via boosting location and scale models.

    Science.gov (United States)

    Mayr, Andreas; Schmid, Matthias; Pfahlberg, Annette; Uter, Wolfgang; Gefeller, Olaf

    2017-06-01

    Measurement errors of medico-technical devices can be separated into systematic bias and random error. We propose a new method to address both simultaneously via generalized additive models for location, scale and shape (GAMLSS) in combination with permutation tests. More precisely, we extend a recently proposed boosting algorithm for GAMLSS to provide a test procedure to analyse potential device effects on the measurements. We carried out a large-scale simulation study to provide empirical evidence that our method is able to identify possible sources of systematic bias as well as random error under different conditions. Finally, we apply our approach to compare measurements of skin pigmentation from two different devices in an epidemiological study.

  10. Using niche-modelling and species-specific cost analyses to determine a multispecies corridor in a fragmented landscape

    Science.gov (United States)

    Zurano, Juan Pablo; Selleski, Nicole; Schneider, Rosio G.

    2017-01-01

    types independent of the degree of legal protection. These data used with multifocal GIS analyses balance the varying degree of overlap and unique properties among them allowing for comprehensive conservation strategies to be developed relatively rapidly. Our comprehensive approach serves as a model to other regions faced with habitat loss and lack of data. The five carnivores focused on in our study have wide ranges, so the results from this study can be expanded and combined with surrounding countries, with analyses at the species or community level. PMID:28841692

  11. Spatially quantitative models for vulnerability analyses and resilience measures in flood risk management: Case study Rafina, Greece

    Science.gov (United States)

    Karagiorgos, Konstantinos; Chiari, Michael; Hübl, Johannes; Maris, Fotis; Thaler, Thomas; Fuchs, Sven

    2013-04-01

    We will address spatially quantitative models for vulnerability analyses in flood risk management in the catchment of Rafina, 25 km east of Athens, Greece; and potential measures to reduce damage costs. The evaluation of flood damage losses is relatively advanced. Nevertheless, major problems arise since there are no market prices for the evaluation process available. Moreover, there is particular gap in quantifying the damages and necessary expenditures for the implementation of mitigation measures with respect to flash floods. The key issue is to develop prototypes for assessing flood losses and the impact of mitigation measures on flood resilience by adjusting a vulnerability model and to further develop the method in a Mediterranean region influenced by both, mountain and coastal characteristics of land development. The objective of this study is to create a spatial and temporal analysis of the vulnerability factors based on a method combining spatially explicit loss data, data on the value of exposed elements at risk, and data on flood intensities. In this contribution, a methodology for the development of a flood damage assessment as a function of the process intensity and the degree of loss is presented. It is shown that (1) such relationships for defined object categories are dependent on site-specific and process-specific characteristics, but there is a correlation between process types that have similar characteristics; (2) existing semi-quantitative approaches of vulnerability assessment for elements at risk can be improved based on the proposed quantitative method; and (3) the concept of risk can be enhanced with respect to a standardised and comprehensive implementation by applying the vulnerability functions to be developed within the proposed research. Therefore, loss data were collected from responsible administrative bodies and analysed on an object level. The used model is based on a basin scale approach as well as data on elements at risk exposed

  12. Computational modeling and statistical analyses on individual contact rate and exposure to disease in complex and confined transportation hubs

    Science.gov (United States)

    Wang, W. L.; Tsui, K. L.; Lo, S. M.; Liu, S. B.

    2018-01-01

    Crowded transportation hubs such as metro stations are thought as ideal places for the development and spread of epidemics. However, for the special features of complex spatial layout, confined environment with a large number of highly mobile individuals, it is difficult to quantify human contacts in such environments, wherein disease spreading dynamics were less explored in the previous studies. Due to the heterogeneity and dynamic nature of human interactions, increasing studies proved the importance of contact distance and length of contact in transmission probabilities. In this study, we show how detailed information on contact and exposure patterns can be obtained by statistical analyses on microscopic crowd simulation data. To be specific, a pedestrian simulation model-CityFlow was employed to reproduce individuals' movements in a metro station based on site survey data, values and distributions of individual contact rate and exposure in different simulation cases were obtained and analyzed. It is interesting that Weibull distribution fitted the histogram values of individual-based exposure in each case very well. Moreover, we found both individual contact rate and exposure had linear relationship with the average crowd densities of the environments. The results obtained in this paper can provide reference to epidemic study in complex and confined transportation hubs and refine the existing disease spreading models.

  13. Control volume analyses of glottal flow using a fully-coupled numerical fluid-structure interaction model

    Science.gov (United States)

    Yang, Jubiao; Krane, Michael; Zhang, Lucy

    2013-11-01

    Vocal fold vibrations and the glottal jet are successfully simulated using the modified Immersed Finite Element method (mIFEM), a fully coupled dynamics approach to model fluid-structure interactions. A self-sustained and steady vocal fold vibration is captured given a constant pressure input at the glottal entrance. The flow rates at different axial locations in the glottis are calculated, showing small variations among them due to the vocal fold motion and deformation. To further facilitate the understanding of the phonation process, two control volume analyses, specifically with Bernoulli's equation and Newton's 2nd law, are carried out for the glottal flow based on the simulation results. A generalized Bernoulli's equation is derived to interpret the correlations between the velocity and pressure temporally and spatially along the center line which is a streamline using a half-space model with symmetry boundary condition. A specialized Newton's 2nd law equation is developed and divided into terms to help understand the driving mechanism of the glottal flow.

  14. Bayesian salamanders: analysing the demography of an underground population of the European plethodontid Speleomantes strinatii with state-space modelling

    Directory of Open Access Journals (Sweden)

    Salvidio Sebastiano

    2010-02-01

    Full Text Available Abstract Background It has been suggested that Plethodontid salamanders are excellent candidates for indicating ecosystem health. However, detailed, long-term data sets of their populations are rare, limiting our understanding of the demographic processes underlying their population fluctuations. Here we present a demographic analysis based on a 1996 - 2008 data set on an underground population of Speleomantes strinatii (Aellen in NW Italy. We utilised a Bayesian state-space approach allowing us to parameterise a stage-structured Lefkovitch model. We used all the available population data from annual temporary removal experiments to provide us with the baseline data on the numbers of juveniles, subadults and adult males and females present at any given time. Results Sampling the posterior chains of the converged state-space model gives us the likelihood distributions of the state-specific demographic rates and the associated uncertainty of these estimates. Analysing the resulting parameterised Lefkovitch matrices shows that the population growth is very close to 1, and that at population equilibrium we expect half of the individuals present to be adults of reproductive age which is what we also observe in the data. Elasticity analysis shows that adult survival is the key determinant for population growth. Conclusion This analysis demonstrates how an understanding of population demography can be gained from structured population data even in a case where following marked individuals over their whole lifespan is not practical.

  15. Time Headway Modelling of Motorcycle-Dominated Traffic to Analyse Traffic Safety Performance and Road Link Capacity of Single Carriageways

    Directory of Open Access Journals (Sweden)

    D. M. Priyantha Wedagama

    2017-04-01

    Full Text Available This study aims to develop time headway distribution models to analyse traffic safety performance and road link capacities for motorcycle-dominated traffic in Denpasar, Bali. Three road links selected as the case study are Jl. Hayam Wuruk, Jl.Hang Tuah, and Jl. Padma. Data analysis showed that between 55%-80% of motorists in Denpasar during morning and evening peak hours paid less attention to the safe distance with the vehicles in front. The study found that Lognormal distribution models are best to fit time headway data during morning peak hours while either Weibull (3P or Pearson III distributions is for evening peak hours. Road link capacities for mixed traffic predominantly motorcycles are apparently affected by the behaviour of motorists in keeping safe distance with the vehicles in front. Theoretical road link capacities for Jl. Hayam Wuruk, Jl. Hang Tuah and Jl. Padma are 3,186 vehicles/hour, 3,077 vehicles/hour and 1935 vehicles/hour respectively.

  16. Round-robin pretest analyses of a 1:6-scale reinforced concrete containment model subject to static internal pressurization

    International Nuclear Information System (INIS)

    Clauss, D.B.

    1987-05-01

    Analyses of a 1:6-scale reinforced concrete containment model that will be tested to failure at Sandia National Laboratories in the spring of 1987 were conducted by the following organizations in the United States and Europe: Sandia National Laboratories (USA), Argonne National Laboratory (USA), Electric Power Research Institute (USA), Commissariat a L'Energie Atomique (France), HM Nuclear Installations Inspectorate (UK), Comitato Nazionale per la ricerca e per lo sviluppo dell'Energia Nucleare e delle Energie Alternative (Italy), UK Atomic Energy Authority, Safety and Reliability Directorate (UK), Gesellschaft fuer Reaktorsicherheit (FRG), Brookhaven National Laboratory (USA), and Central Electricity Generating Board (UK). Each organization was supplied with a standard information package, which included construction drawings and actual material properties for most of the materials used in the model. Each organization worked independently using their own analytical methods. This report includes descriptions of the various analytical approaches and pretest predictions submitted by each organization. Significant milestones that occur with increasing pressure, such as damage to the concrete (cracking and crushing) and yielding of the steel components, and the failure pressure (capacity) and failure mechanism are described. Analytical predictions for pressure histories of strain in the liner and rebar and displacements are compared at locations where experimental results will be available after the test. Thus, these predictions can be compared to one another and to experimental results after the test

  17. Heart rate is a prognostic risk factor for myocardial infarction: a post hoc analysis in the PERFORM (Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack) study population.

    Science.gov (United States)

    Fox, Kim; Bousser, Marie-Germaine; Amarenco, Pierre; Chamorro, Angel; Fisher, Marc; Ford, Ian; Hennerici, Michael G; Mattle, Heinrich P; Rothwell, Peter M

    2013-10-09

    Elevated resting heart rate is known to be detrimental to morbidity and mortality in cardiovascular disease, though its effect in patients with ischemic stroke is unclear. We analyzed the effect of baseline resting heart rate on myocardial infarction (MI) in patients with a recent noncardioembolic cerebral ischemic event participating in PERFORM. We compared fatal or nonfatal MI using adjusted Cox proportional hazards models for PERFORM patients with baseline heart rate heart rate was analyzed as a continuous variable. Other cerebrovascular and cardiovascular outcomes were also explored. Heart rate ≥70 bpm was associated with increased relative risk for fatal or nonfatal MI (HR 1.32, 95% CI 1.03-1.69, P=0.029). For every 5-bpm increase in heart rate, there was an increase in relative risk for fatal and nonfatal MI (11.3%, P=0.0002). Heart rate ≥70 bpm was also associated with increased relative risk for a composite of fatal or nonfatal ischemic stroke, fatal or nonfatal MI, or other vascular death (excluding hemorrhagic death) (Pheart rate, there were increases in relative risk for fatal or nonfatal ischemic stroke, fatal or nonfatal MI, or other vascular death (4.7%, Pheart rate ≥70 bpm places patients with a noncardioembolic cerebral ischemic event at increased risk for MI. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. On groundwater flow modelling in safety analyses of spent fuel disposal. A comparative study with emphasis on boundary conditions

    Energy Technology Data Exchange (ETDEWEB)

    Jussila, P

    1999-11-01

    Modelling groundwater flow is an essential part of the safety assessment of spent fuel disposal because moving groundwater makes a physical connection between a geological repository and the biosphere. Some of the common approaches to model groundwater flow in bedrock are equivalent porous continuum (EC), stochastic continuum and various fracture network concepts. The actual flow system is complex and measuring data are limited. Multiple distinct approaches and models, alternative scenarios as well as calibration and sensitivity analyses are used to give confidence on the results of the calculations. The correctness and orders of magnitude of results of such complex research can be assessed by comparing them to the results of simplified and robust approaches. The first part of this study is a survey of the objects, contents and methods of the groundwater flow modelling performed in the safety assessment of the spent fuel disposal in Finland and Sweden. The most apparent difference of the Swedish studies compared to the Finnish ones is the approach of using more different models, which is enabled by the more resources available in Sweden. The results of more comprehensive approaches provided by international co-operation are very useful to give perspective to the results obtained in Finland. In the second part of this study, the influence of boundary conditions on the flow fields of a simple 2D model is examined. The assumptions and simplifications in this approach include e.g. the following: (1) the EC model is used, in which the 2-dimensional domain is considered a continuum of equivalent properties without fractures present, (2) the calculations are done for stationary fields, without sources or sinks present in the domain and with a constant density of the groundwater, (3) the repository is represented by an isotropic plate, the hydraulic conductivity of which is given fictitious values, (4) the hydraulic conductivity of rock is supposed to have an exponential

  19. Water flow experiments and analyses on the cross-flow type mercury target model with the flow guide plates

    CERN Document Server

    Haga, K; Kaminaga, M; Hino, R

    2001-01-01

    A mercury target is used in the spallation neutron source driven by a high-intensity proton accelerator. In this study, the effectiveness of the cross-flow type mercury target structure was evaluated experimentally and analytically. Prior to the experiment, the mercury flow field and the temperature distribution in the target container were analyzed assuming a proton beam energy and power of 1.5 GeV and 5 MW, respectively, and the feasibility of the cross-flow type target was evaluated. Then the average water flow velocity field in the target mock-up model, which was fabricated from Plexiglass for a water experiment, was measured at room temperature using the PIV technique. Water flow analyses were conducted and the analytical results were compared with the experimental results. The experimental results showed that the cross-flow could be realized in most of the proton beam path area and the analytical result of the water flow velocity field showed good correspondence to the experimental results in the case w...

  20. Modeling Acequia Irrigation Systems Using System Dynamics: Model Development, Evaluation, and Sensitivity Analyses to Investigate Effects of Socio-Economic and Biophysical Feedbacks

    Directory of Open Access Journals (Sweden)

    Benjamin L. Turner

    2016-10-01

    Full Text Available Agriculture-based irrigation communities of northern New Mexico have survived for centuries despite the arid environment in which they reside. These irrigation communities are threatened by regional population growth, urbanization, a changing demographic profile, economic development, climate change, and other factors. Within this context, we investigated the extent to which community resource management practices centering on shared resources (e.g., water for agricultural in the floodplains and grazing resources in the uplands and mutualism (i.e., shared responsibility of local residents to maintaining traditional irrigation policies and upholding cultural and spiritual observances embedded within the community structure influence acequia function. We used a system dynamics modeling approach as an interdisciplinary platform to integrate these systems, specifically the relationship between community structure and resource management. In this paper we describe the background and context of acequia communities in northern New Mexico and the challenges they face. We formulate a Dynamic Hypothesis capturing the endogenous feedbacks driving acequia community vitality. Development of the model centered on major stock-and-flow components, including linkages for hydrology, ecology, community, and economics. Calibration metrics were used for model evaluation, including statistical correlation of observed and predicted values and Theil inequality statistics. Results indicated that the model reproduced trends exhibited by the observed system. Sensitivity analyses of socio-cultural processes identified absentee decisions, cumulative income effect on time in agriculture, and land use preference due to time allocation, community demographic effect, effect of employment on participation, and farm size effect as key determinants of system behavior and response. Sensitivity analyses of biophysical parameters revealed that several key parameters (e.g., acres per

  1. Automated post-hoc noise cancellation tool for audio recordings acquired in an MRI scanner

    NARCIS (Netherlands)

    Cusack, R.; Cumming, N.; Bor, D.; Norris, D.; Lijzenga, J.

    2005-01-01

    There are several types of experiment in which it is useful to have subjects speak overtly in a magnetic resonance imaging (MRI) scanner, including those studying the articulatory apparatus and the neural basis of speech production, and fMRI experiments in which speech is used as a response

  2. Discontinuation of continuous renal replacement therapy: A post hoc analysis of a prospective multicenter observational study

    NARCIS (Netherlands)

    Uchino, Shigehiko; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Oudemans-van Straaten, Heleen; Ronco, Claudio; Kellum, John A.

    2009-01-01

    Objectives: To describe current practice for the discontinuation of continuous renal replacement therapy in a multinational setting and to identify variables associated with successful discontinuation. The approach to discontinue continuous renal replacement therapy may affect patient outcomes.

  3. A-priori and post-hoc segmentation in the design of healthy eating campaigns

    DEFF Research Database (Denmark)

    Kazbare, Laura; van Trijp, Hans C. M.; Eskildsen, Jacob Kjær

    2010-01-01

    Nutrition-oriented public health campaigns - both communication and intervention initiatives - often target particular demographic groups, for example schoolchildren, adults at workplaces, older women, presuming that the members of these groups are homogenous with respect to healthy eating....... Although such practice may be justifiable from the practical point of view, it is unclear how effective these implicit segmentations are. In this study the authors argue that  it is important to transcend demographic boundaries and to further segment demographic groups. A study with 13-15-year...

  4. Correlation of pain relief with physical function in hand osteoarthritis: randomized controlled trial post hoc analysis.

    Science.gov (United States)

    Barthel, H Richard; Peniston, John H; Clark, Michael B; Gold, Morris S; Altman, Roy D

    2010-01-01

    Nonsteroidal anti-inflammatory drugs are recommended for the relief of pain associated with hand osteoarthritis (OA) but do not alter the underlying structural changes that contribute to impaired physical function. The current analysis examined the relationship of pain relief with measures of function and global rating of disease in patients with hand OA. This was a combined analysis of 2 prospective, randomized, double-blind, 8-week, multicenter, parallel-group studies comparing diclofenac sodium 1% gel with placebo gel (vehicle) in patients with radiographically confirmed mild to moderate hand OA. Patients (n = 783) aged > or = 40 years applied diclofenac sodium 1% gel (2 g) or vehicle to each hand 4 times daily for 8 weeks. Outcome measures included pain intensity assessed on a 100-mm Visual Analog Scale (VAS); the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) subscales for pain, stiffness, and physical function (100-mm VAS); and a global rating of disease (100-mm VAS). Change in VAS pain intensity from baseline to week 8 was categorized ( or = 70%) without regard to treatment and compared in each category with the mean change from baseline in each AUSCAN subindex and the global rating of disease. Pearson correlations between changes in outcome measures from baseline to week 8 were calculated. Changes in VAS pain intensity were accompanied by similar changes in AUSCAN scores and global rating of disease. Pearson correlations confirmed significant associations (P < 0.001) between change in VAS pain intensity and changes in AUSCAN pain (correlation coefficient [r] = 0.81), AUSCAN function (r = 0.75), AUSCAN stiffness (r = 0.66), and global rating of disease (r = 0.76). Pain relief correlated with improvements in physical function, stiffness, and global rating of disease in patients with hand OA, irrespective of treatment. This suggests that pain or anticipation of pain inhibits physical function and influences patient perception of disease severity in hand OA. These results also suggest that any intervention to relieve the pain of hand OA may improve function and patient perception of disease severity, despite the absence of a disease-modifying mechanism of action. Clinicaltrials.gov NCT00171652, NCT00171665.

  5. Prophylactic Azithromycin Therapy After Lung Transplantation: Post hoc Analysis of a Randomized Controlled Trial.

    Science.gov (United States)

    Ruttens, D; Verleden, S E; Vandermeulen, E; Bellon, H; Vanaudenaerde, B M; Somers, J; Schoonis, A; Schaevers, V; Van Raemdonck, D E; Neyrinck, A; Dupont, L J; Yserbyt, J; Verleden, G M; Vos, R

    2016-01-01

    Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome (BOS) 2 years after lung transplantation (LTx). In the current study, we re-evaluated the long-term effects of this prophylactic approach in view of the updated classification system for chronic lung allograft dysfunction (CLAD). A retrospective, intention-to-treat analysis of a randomized controlled trial comparing prophylactic treatment with placebo (n = 43) versus azithromycin (n = 40) after LTx was performed. Graft dysfunction (CLAD), graft loss (retransplantation, mortality), evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject. Following LTx, 22/43 (51%) patients of the placebo group and 11/40 (28%) patients of the azithromycin group ever developed CLAD (p = 0.043). CLAD-free survival was significantly longer in the azithromycin group (p = 0.024). No difference was present in proportion of obstructive versus restrictive CLAD between both groups. Graft loss was similar in both groups: 23/43 (53%) versus 16/40 (40%) patients (p = 0.27). Long-term pulmonary function and functional exercise capacity were significantly better in the azithromycin group (p azithromycin therapy reduces long-term CLAD prevalence and improves CLAD-free survival, pulmonary function, and functional exercise capacity after LTx. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  6. [Volumetric analysis of vascularized pigment epithelium detachment in AMD: post hoc analysis of the RECOVER study].

    Science.gov (United States)

    Clemens, C R; Alten, F; Heiduschka, P; Gamulescu, M A; Wolf, A; Eter, N

    2017-10-20

    The ratio of choroidal neovascularization (CNV) and pigment epithelium detachment (PED) represents an important parameter regarding the risk of developing a tear of the retinal pigment epithelium (RPE) in patients with vascularized PED due to age-related macular degeneration (AMD). Within the framework of the RECOVER study a total of 29 treatment-naive patients with vascularized PED underwent fluorescein angiography (FA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) volume scans. The CNV-PED ratio was evaluated retrospectively by two independent graders in three ways: 1) manually based on the en face image of the FA late phase and 2) manually based on the en face image of the ICGA late phase. 3) In every OCT scan encompassing the PED, the area between the RPE and Bruch's membrane and the CNV area was measured and multiplied by the distance between OCT scans in order to determine volumetric data of CNV, PED and the serous cavity. The FA and ICGA showed a mean serous area of 6.14 ± 4.21 mm 2 (ICGA 5.94 ± 4.13 mm 2 ), a mean CNV area of 3.25 ± 1.79 mm 2 (ICGA 2.84 ± 1.68 mm 2 ) and a mean PED area of 9.39 ± 4.27 mm 2 (ICGA 8.79 ± 4.23 mm 2 ) resulting in a mean two-dimensional morphological ratio of 0.35 ± 0.21 (ICGA 0.32 ± 0.22). The volumetric measurement revealed a mean CNV volume of 0.63 ± 0.67 mm 3 , a mean serous volume of 3.61 ± 3.83 mm 3 and a mean total PED volume of 4.25 ± 3.68 mm 3 . The mean three-dimensional morphological ratio was 0.15 ± 0.29. The difference between the two-dimensional ratios of FA (p < 0.0001) and ICGA (p = 0.0004) was significant compared to the three-dimensional OCT ratio. Assessment of the CNV-PED ratio using volumetric OCT measurements is an additional tool to the en face modalities FA and ICGA. This seems to be clinically relevant regarding the risk stratification of RPE tear development in PED patients and for the planning of the treatment regimen.

  7. Reducing consumption of confectionery foods: A post-hoc segmentation analysis using a social cognition approach.

    Science.gov (United States)

    Naughton, Paul; McCarthy, Mary; McCarthy, Sinéad

    2017-10-01

    Considering confectionary consumption behaviour this cross-sectional study used social cognition variables to identify distinct segments in terms of their motivation and efforts to decrease their consumption of such foods with the aim of informing targeted social marketing campaigns. Using Latent Class analysis on a sample of 500 adults four segments were identified: unmotivated, triers, successful actors, and thrivers. The unmotivated and triers segments reported low levels of perceived need and perceived behavioural control (PBC) in addition to high levels of habit and hedonic hunger with regards their consumption of confectionery foods. Being a younger adult was associated with higher odds of being in the unmotivated and triers segments and being female was associated with higher odds of being in the triers and successful actors segments. The findings indicate that in the absence of strong commitment to eating low amounts of confectionery foods (i.e. perceived need) people will continue to overconsume free sugars regardless of motivation to change. It is therefore necessary to identify relevant messages or 'triggers' related to sugar consumption that resonate with young adults in particular. For those motivated to change, counteracting unhealthy eating habits and the effects of hedonic hunger may necessitate changes to food environments in order to make the healthy choice more appealing and accessible. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. A-priori and post-hoc segmentation in the design of healthy eating campaigns

    NARCIS (Netherlands)

    Kazbare, L.; Trijp, van J.C.M.; Eskildsen, J.K.

    2010-01-01

    Nutrition-oriented public health campaigns – both communication and intervention initiatives – often target particular demographic groups, for example schoolchildren, adults at workplaces, older women, presuming that the members of these groups are homogenous with respect to healthy eating. Although

  9. Early induction of hypothermia for evacuated intracranial hematomas: a post hoc analysis of two clinical trials.

    Science.gov (United States)

    Clifton, Guy L; Coffey, Christopher S; Fourwinds, Sierra; Zygun, David; Valadka, Alex; Smith, Kenneth R; Frisby, Melisa L; Bucholz, Richard D; Wilde, Elisabeth A; Levin, Harvey S; Okonkwo, David O

    2012-10-01

    The authors hypothesized that cooling before evacuation of traumatic intracranial hematomas protects the brain from reperfusion injury and, if so, further hypothesized that hypothermia induction before or soon after craniotomy should be associated with improved outcomes. The National Acute Brain Injury Study: Hypothermia I (NABIS:H I) was a randomized multicenter clinical trial of 392 patients with severe brain injury treated using normothermia or hypothermia for 48 hours with patients reaching 33°C at 8.4 ± 3 hours after injury. The National Acute Brain Injury Study: Hypothermia II (NABIS:H II) was a randomized, multicenter clinical trial of 97 patients with severe brain injury treated with normothermia or hypothermia for 48 hours with patients reaching 35°C within 2.6 ± 1.2 hours and 33°C within 4.4 ± 1.5 hours of injury. Entry and exclusion criteria, management, and outcome measures in the 2 trials were similar. In NABIS:H II among the patients with evacuated intracranial hematomas, outcome was poor (severe disability, vegetative state, or death) in 5 of 15 patients in the hypothermia group and in 9 of 13 patients in the normothermia group (relative risk 0.44, 95% CI 0.22-0.88; p = 0.02). All patients randomized to hypothermia reached 35°C within 1.5 hours after surgery start and 33°C within 5.55 hours. Applying these criteria to NABIS:H I, 31 of 54 hypothermia-treated patients reached a temperature of 35°C or lower within 1.5 hours after surgery start time, and the remaining 23 patients reached 35°C at later time points. Outcome was poor in 14 (45%) of 31 patients reaching 35°C within 1.5 hours of surgery, in 14 (61%) of 23 patients reaching 35°C more than 1.5 hours of surgery, and in 35 (60%) of 58 patients in the normothermia group (relative risk 0.74, 95%, CI 0.49-1.13; p = 0.16). A meta-analysis of 46 patients with hematomas in both trials who reached 35°C within 1.5 hours of surgery start showed a significantly reduced rate of poor outcomes (41%) compared with 94 patients treated with hypothermia who did not reach 35°C within that time and patients treated at normothermia (62%, p = 0.009). Induction of hypothermia to 35°C before or soon after craniotomy with maintenance at 33°C for 48 hours thereafter may improve outcome of patients with hematomas and severe traumatic brain injury. Clinical trial registration no.: NCT00178711.

  10. Epidemiology of HPV 16 and cervical cancer in Finland and the potential impact of vaccination: mathematical modelling analyses.

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    Ruanne V Barnabas

    2006-05-01

    Full Text Available BACKGROUND: Candidate human papillomavirus (HPV vaccines have demonstrated almost 90%-100% efficacy in preventing persistent, type-specific HPV infection over 18 mo in clinical trials. If these vaccines go on to demonstrate prevention of precancerous lesions in phase III clinical trials, they will be licensed for public use in the near future. How these vaccines will be used in countries with national cervical cancer screening programmes is an important question. METHODS AND FINDINGS: We developed a transmission model of HPV 16 infection and progression to cervical cancer and calibrated it to Finnish HPV 16 seroprevalence over time. The model was used to estimate the transmission probability of the virus, to look at the effect of changes in patterns of sexual behaviour and smoking on age-specific trends in cancer incidence, and to explore the impact of HPV 16 vaccination. We estimated a high per-partnership transmission probability of HPV 16, of 0.6. The modelling analyses showed that changes in sexual behaviour and smoking accounted, in part, for the increase seen in cervical cancer incidence in 35- to 39-y-old women from 1990 to 1999. At both low (10% in opportunistic immunisation and high (90% in a national immunisation programme coverage of the adolescent population, vaccinating women and men had little benefit over vaccinating women alone. We estimate that vaccinating 90% of young women before sexual debut has the potential to decrease HPV type-specific (e.g., type 16 cervical cancer incidence by 91%. If older women are more likely to have persistent infections and progress to cancer, then vaccination with a duration of protection of less than 15 y could result in an older susceptible cohort and no decrease in cancer incidence. While vaccination has the potential to significantly reduce type-specific cancer incidence, its combination with screening further improves cancer prevention. CONCLUSIONS: HPV vaccination has the potential to

  11. Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder

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    Cardozo Linda

    2010-08-01

    Full Text Available Abstract Background Fesoterodine is an antimuscarinic for the treatment of overactive bladder, a syndrome of urgency, with or without urgency urinary incontinence (UUI, usually with increased daytime frequency and nocturia. Our objective was to develop predictive models to describe the dose response of fesoterodine. Methods Data from subjects enrolled in double-blind, placebo-controlled phase II and III trials were used for developing longitudinal dose-response models. Results The models predicted that clinically significant and near-maximum treatment effects would be seen within 3 to 4 weeks after treatment initiation. For a typical patient with 11 micturitions per 24 hours at baseline, predicted change was -1.2, -1.7, and -2.2 micturitions for placebo and fesoterodine 4 mg and 8 mg, respectively. For a typical patient with 2 UUI episodes per 24 hours at baseline, predicted change was -1.05, -1.26, and -1.43 UUI episodes for placebo and fesoterodine 4 mg and 8 mg, respectively. Increase in mean voided volume was estimated at 9.7 mL for placebo, with an additional 14.2 mL and 28.4 mL for fesoterodine 4 mg and 8 mg, respectively. Conclusions A consistent dose response for fesoterodine was demonstrated for bladder diary endpoints in subjects with overactive bladder, a result that supports the greater efficacy seen with fesoterodine 8 mg in post hoc analyses of clinical trial data. The dose-response models can be used to predict outcomes for doses not studied or for patient subgroups underrepresented in clinical trials. Trial Registration The phase III trials used in this analysis have been registered at ClinicalTrials.gov (NCT00220363 and NCT00138723.

  12. Intercomparison and analyses of the climatology of the West African monsoon in the West African monsoon modeling and evaluation project (WAMME) first model intercomparison experiment

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    Xue, Yongkang; Sales, Fernando De [University of California, Los Angeles, CA (United States); Lau, W.K.M.; Schubert, Siegfried D.; Wu, Man-Li C. [NASA, Goddard Space Flight Center, Greenbelt, MD (United States); Boone, Aaron [Centre National de Recherches Meteorologiques, Meteo-France Toulouse, Toulouse (France); Feng, Jinming [University of California, Los Angeles, CA (United States); Chinese Academy of Sciences, Institute of Atmospheric Physics, Beijing (China); Dirmeyer, Paul; Guo, Zhichang [Center for Ocean-Land-Atmosphere Interactions, Calverton, MD (United States); Kim, Kyu-Myong [University of Maryland Baltimore County, Baltimore, MD (United States); Kitoh, Akio [Meteorological Research Institute, Tsukuba (Japan); Kumar, Vadlamani [National Center for Environmental Prediction, Camp Springs, MD (United States); Wyle Information Systems, Gaithersburg, MD (United States); Poccard-Leclercq, Isabelle [Universite de Bourgogne, Centre de Recherches de Climatologie UMR5210 CNRS, Dijon (France); Mahowald, Natalie [Cornell University, Ithaca, NY (United States); Moufouma-Okia, Wilfran; Rowell, David P. [Met Office Hadley Centre, Exeter (United Kingdom); Pegion, Phillip [NASA, Goddard Space Flight Center, Greenbelt, MD (United States); National Center for Environmental Prediction, Camp Springs, MD (United States); Schemm, Jae; Thiaw, Wassila M. [National Center for Environmental Prediction, Camp Springs, MD (United States); Sealy, Andrea [The Caribbean Institute for Meteorology and Hydrology, St. James (Barbados); Vintzileos, Augustin [National Center for Environmental Prediction, Camp Springs, MD (United States); Science Applications International Corporation, Camp Springs, MD (United States); Williams, Steven F. [National Center for Atmospheric Research, Boulder, CO (United States)

    2010-07-15

    This paper briefly presents the West African monsoon (WAM) modeling and evaluation project (WAMME) and evaluates WAMME general circulation models' (GCM) performances in simulating variability of WAM precipitation, surface temperature, and major circulation features at seasonal and intraseasonal scales in the first WAMME experiment. The analyses indicate that models with specified sea surface temperature generally have reasonable simulations of the pattern of spatial distribution of WAM seasonal mean precipitation and surface temperature as well as the averaged zonal wind in latitude-height cross-section and low level circulation. But there are large differences among models in simulating spatial correlation, intensity, and variance of precipitation compared with observations. Furthermore, the majority of models fail to produce proper intensities of the African Easterly Jet (AEJ) and the tropical easterly jet. AMMA Land Surface Model Intercomparison Project (ALMIP) data are used to analyze the association between simulated surface processes and the WAM and to investigate the WAM mechanism. It has been identified that the spatial distributions of surface sensible heat flux, surface temperature, and moisture convergence are closely associated with the simulated spatial distribution of precipitation; while surface latent heat flux is closely associated with the AEJ and contributes to divergence in AEJ simulation. Common empirical orthogonal functions (CEOF) analysis is applied to characterize the WAM precipitation evolution and has identified a major WAM precipitation mode and two temperature modes (Sahara mode and Sahel mode). Results indicate that the WAMME models produce reasonable temporal evolutions of major CEOF modes but have deficiencies/uncertainties in producing variances explained by major modes. Furthermore, the CEOF analysis shows that WAM precipitation evolution is closely related to the enhanced Sahara mode and the weakened Sahel mode, supporting

  13. A second-generation device for automated training and quantitative behavior analyses of molecularly-tractable model organisms.

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    Douglas Blackiston

    2010-12-01

    Full Text Available A deep understanding of cognitive processes requires functional, quantitative analyses of the steps leading from genetics and the development of nervous system structure to behavior. Molecularly-tractable model systems such as Xenopus laevis and planaria offer an unprecedented opportunity to dissect the mechanisms determining the complex structure of the brain and CNS. A standardized platform that facilitated quantitative analysis of behavior would make a significant impact on evolutionary ethology, neuropharmacology, and cognitive science. While some animal tracking systems exist, the available systems do not allow automated training (feedback to individual subjects in real time, which is necessary for operant conditioning assays. The lack of standardization in the field, and the numerous technical challenges that face the development of a versatile system with the necessary capabilities, comprise a significant barrier keeping molecular developmental biology labs from integrating behavior analysis endpoints into their pharmacological and genetic perturbations. Here we report the development of a second-generation system that is a highly flexible, powerful machine vision and environmental control platform. In order to enable multidisciplinary studies aimed at understanding the roles of genes in brain function and behavior, and aid other laboratories that do not have the facilities to undergo complex engineering development, we describe the device and the problems that it overcomes. We also present sample data using frog tadpoles and flatworms to illustrate its use. Having solved significant engineering challenges in its construction, the resulting design is a relatively inexpensive instrument of wide relevance for several fields, and will accelerate interdisciplinary discovery in pharmacology, neurobiology, regenerative medicine, and cognitive science.

  14. Transcriptomics and proteomics analyses of the PACAP38 influenced ischemic brain in permanent middle cerebral artery occlusion model mice

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    Hori Motohide

    2012-11-01

    Full Text Available Abstract Introduction The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP is considered to be a potential therapeutic agent for prevention of cerebral ischemia. Ischemia is a most common cause of death after heart attack and cancer causing major negative social and economic consequences. This study was designed to investigate the effect of PACAP38 injection intracerebroventrically in a mouse model of permanent middle cerebral artery occlusion (PMCAO along with corresponding SHAM control that used 0.9% saline injection. Methods Ischemic and non-ischemic brain tissues were sampled at 6 and 24 hours post-treatment. Following behavioral