Decay Rates and Probability Estimatesfor Massive Dirac Particlesin the Kerr-Newman Black Hole Geometry

NASA Astrophysics Data System (ADS)

Finster, F.; Kamran, N.; Smoller, J.; Yau, S.-T.

The Cauchy problem is considered for the massive Dirac equation in the non-extreme Kerr-Newman geometry, for smooth initial data with compact support outside the event horizon and bounded angular momentum. We prove that the Dirac wave function decays in L∞ {loc} at least at the rate t-5/6. For generic initial data, this rate of decay is sharp. We derive a formula for the probability p that the Dirac particle escapes to infinity. For various conditions on the initial data, we show that p = 0, 1 or 0 < p < 1. The proofs are based on a refined analysis of the Dirac propagator constructed in [4].

Explicit solutions for exit-only radioactive decay chains

NASA Astrophysics Data System (ADS)

Yuan, Ding; Kernan, Warnick

2007-05-01

In this study, we extended Bateman's [Proc. Cambridge Philos. Soc. 15, 423 (1910)] original work for solving radioactive decay chains and explicitly derived analytic solutions for generic exit-only radioactive decay problems under given initial conditions. Instead of using the conventional Laplace transform for solving Bateman's equations, we used a much simpler algebraic approach. Finally, we discuss methods of breaking down certain classes of large decay chains into collections of simpler chains for easy handling.

Generic versus branded medicines: An observational study among patients with chronic diseases attending a public hospital outpatient department

PubMed Central

Das, Manisha; Choudhury, Supriyo; Maity, Somnath; Hazra, Avijit; Pradhan, Tirthankar; Pal, Aishee; Roy, Ranendra Kumar

2017-01-01

Background: The concept of generic prescription is widely accepted in various parts of the world. Nevertheless, it has failed to gain popularity in India due to factors such as nonavailability and distrust on the product quality. However, since 2012, the Government of West Bengal, India, has initiated exclusive generic drug outlets called “fair price medicine shop” (FPMS) inside the government hospital premises in a “public-private-partnership” model. This study was undertaken to evaluate the experience and attitude of patients who were consuming generic drugs purchased from these FPMS. Materials and Methods: It was a questionnaire-based cross-sectional study where we have interviewed 100 patients each consuming generic and branded drugs, respectively. The perceived effectiveness, reported safety, medication adherence, cost of therapy, and availability of drugs was compared between two mentioned groups. Medication adherence was estimated through Drug Attitude Inventory-10. Results: 93% of generic and 87% branded drug users believed that their drugs were effective (P = 0.238) in controlling their ailments. No significant difference (9% generic, 10% branded drug users, P = 1.000) was observed in reported adverse effects between generic and branded drug users. 82% and 77% of patients were adherent generic and branded drugs, respectively (P = 0.289). As expected, a significantly lower cost of generic drugs was observed compared to its branded counterpart. Conclusion: The policy of FPMS implemented by the Government of West Bengal, India appeared to be promising in terms of perceived effectiveness, safety, and adherence of generic drugs from FPMS compared to drugs purchased from open market retailers. Therefore, this study might act as an impetus for the policy-makers to initiate similar models across the country. PMID:28250671

GeoSegmenter: A statistically learned Chinese word segmenter for the geoscience domain

NASA Astrophysics Data System (ADS)

Huang, Lan; Du, Youfu; Chen, Gongyang

2015-03-01

Unlike English, the Chinese language has no space between words. Segmenting texts into words, known as the Chinese word segmentation (CWS) problem, thus becomes a fundamental issue for processing Chinese documents and the first step in many text mining applications, including information retrieval, machine translation and knowledge acquisition. However, for the geoscience subject domain, the CWS problem remains unsolved. Although a generic segmenter can be applied to process geoscience documents, they lack the domain specific knowledge and consequently their segmentation accuracy drops dramatically. This motivated us to develop a segmenter specifically for the geoscience subject domain: the GeoSegmenter. We first proposed a generic two-step framework for domain specific CWS. Following this framework, we built GeoSegmenter using conditional random fields, a principled statistical framework for sequence learning. Specifically, GeoSegmenter first identifies general terms by using a generic baseline segmenter. Then it recognises geoscience terms by learning and applying a model that can transform the initial segmentation into the goal segmentation. Empirical experimental results on geoscience documents and benchmark datasets showed that GeoSegmenter could effectively recognise both geoscience terms and general terms.

The effect of an apparent change to a branded or generic medication on drug effectiveness and side effects.

PubMed

Faasse, Kate; Cundy, Tim; Gamble, Greg; Petrie, Keith J

2013-01-01

Generic medications are associated with reduced perceived effectiveness, increased perceived adverse effects, and increased rates of nonadherence compared with brand-name medications. This study examined the effect of an apparent medication formulation change on subjective and objective measures of medication effectiveness and medication side effects. Sixty-two university students participated in a study purportedly testing the effectiveness of fast-acting β-blocker medications in reducing preexamination anxiety. All tablets were placebos. In session 1, all participants received a yellow tablet ("Betaprol"). In session 2, participants were randomly allocated to receive Betaprol (no change condition) or a white tablet labeled either as "Novaprol" (branded change condition) or "Generic" (generic change condition). Blood pressure and state anxiety were measured before and after tablet ingestion. Side effects attributed to medication were assessed. The no change group showed significantly greater decreases in systolic blood pressure (mean [M] [standard deviation] = -7.72 mm Hg, standard error [SE] = 1.45) than the branded change (M = -2.75 mm Hg, SE = 1.44, p = .02) and generic change (M = -3.26 mm Hg, SE = 1.45, p = .03) groups. The no-change group showed significantly greater decreases in state anxiety (M = -1.53, SE = 0.33) than the branded change (M = -0.50, SE = 0.33, p = .03) and generic change (M = -0.52, SE = 0.33, p = .04) groups. Significantly more side effects were attributed to the medication in the generic change (M = 1.83, SE = 0.23) (but not the branded change) condition when compared with the no change condition (M = 0.87, SE = 0.31, p = .03). Medication formulation change, particularly to generic medication, seems to be associated with reduced subjective and objective measures of medication effectiveness and increased side effects.

Generic substitution of lamotrigine among medicaid patients with diverse indications: a cohort-crossover study.

PubMed

Hartung, Daniel M; Middleton, Luke; Svoboda, Leanne; McGregor, Jessina C

2012-08-01

Controversy exists about the safety of substituting generic antiepileptic drugs (AEDs). Lamotrigine, the prototypical newer AED, is often used for psychiatric and neurological conditions other than epilepsy. The safety of generic substitution of lamotrigine in diverse populations of AED users is unclear. The objective of this study was to evaluate potential associations between generic substitution of lamotrigine and adverse consequences in a population of diverse users of this drug. This study was a retrospective cohort-crossover design using state Medicaid claims data from July 2006 through June 2009. Subjects were included in the cohort if they converted from brand to generic lamotrigine and had 2 years of lamotrigine use prior to conversion. The frequency of emergency department (ED) visits, hospitalizations and condition-specific ED visits or hospitalizations were recorded in the 60 days immediately following the conversion to generic lamotrigine, then compared with the incidence of the same events during a randomly selected time period indexed to one of the patient's past refills of branded lamotrigine. Multivariate conditional logistic regression was used to quantify the association between generic conversion and health services utilization while controlling for changes in lamotrigine dose and concurrent drug use. Of the 616 unique subjects included in this analysis, epilepsy was the most common diagnosis (41%), followed by bipolar disorder (32%), pain (30%) and migraine (18%). Conversion to generic lamotrigine was not associated with a statistically significant increase in the odds of an ED visit (adjusted odds ratio [AOR] = 1.35; 95% confidence interval [CI] 0.92, 1.97), hospitalization (AOR = 1.21; 95% CI 0.60, 2.50) or condition-specific encounter (AOR 1.75; 95 CI 0.87, 3.51). A statistically significant increase in ED visits, hospitalizations or condition-specific encounters was not observed following the switch from brand to generic lamotrigine, although a type II error cannot be ruled out.

Model Development for VDE Computations in NIMROD

NASA Astrophysics Data System (ADS)

Bunkers, K. J.; Sovinec, C. R.

2017-10-01

Vertical displacement events (VDEs) and the disruptions associated with them have potential for causing considerable physical damage to ITER and other tokamak experiments. We report on simulations of generic axisymmetric VDEs and a vertically unstable case from Alcator C-MOD using the NIMROD code. Previous calculations have been done with closures for heat flux and viscous stress. Initial calculations show that halo current width is dependent on temperature boundary conditions, and so transport together with plasma-surface interaction may play a role in determining halo currents in experiments. The behavior of VDEs with Braginskii thermal conductivity and viscosity closures and Spitzer-like resistivity are investigated for both the generic axisymmetric VDE case and the C-MOD case. This effort is supported by the U.S. Dept. of Energy, Award Numbers DE-FG02-06ER54850 and DE-FC02-08ER54975.

The Role of Condition-Specific Preference-Based Measures in Health Technology Assessment.

PubMed

Rowen, Donna; Brazier, John; Ara, Roberta; Azzabi Zouraq, Ismail

2017-12-01

A condition-specific preference-based measure (CSPBM) is a measure of health-related quality of life (HRQOL) that is specific to a certain condition or disease and that can be used to obtain the quality adjustment weight of the quality-adjusted life-year (QALY) for use in economic models. This article provides an overview of the role and the development of CSPBMs, and presents a description of existing CSPBMs in the literature. The article also provides an overview of the psychometric properties of CSPBMs in comparison with generic preference-based measures (generic PBMs), and considers the advantages and disadvantages of CSPBMs in comparison with generic PBMs. CSPBMs typically include dimensions that are important for that condition but may not be important across all patient groups. There are a large number of CSPBMs across a wide range of conditions, and these vary from covering a wide range of dimensions to more symptomatic or uni-dimensional measures. Psychometric evidence is limited but suggests that CSPBMs offer an advantage in more accurate measurement of milder health states. The mean change and standard deviation can differ for CSPBMs and generic PBMs, and this may impact on incremental cost-effectiveness ratios. CSPBMs have a useful role in HTA where a generic PBM is not appropriate, sensitive or responsive. However, due to issues of comparability across different patient groups and interventions, their usage in health technology assessment is often limited to conditions where it is inappropriate to use a generic PBM or sensitivity analyses.

The experiences of implementing generic medicine policy in eight countries: A review and recommendations for a successful promotion of generic medicine use

PubMed Central

Hassali, Mohamed Azmi; Alrasheedy, Alian A.; McLachlan, Andrew; Nguyen, Tuan Anh; AL-Tamimi, Saleh Karamah; Ibrahim, Mohamed Izham Mohamed; Aljadhey, Hisham

2013-01-01

Generic medicines are clinically interchangeable with original brand medicines and have the same quality, efficacy and safety profiles. They are, nevertheless, much cheaper in price. Thus, while providing the same therapeutic outcomes, generic medicines lead to substantial savings for healthcare systems. Therefore, the quality use of generic medicines is promoted in many countries. In this paper, we reviewed the role of generic medicines in healthcare systems and the experiences of promoting the use of generic medicines in eight selected countries, namely the United States (US), the United Kingdom (UK), Sweden, Finland, Australia, Japan, Malaysia and Thailand. The review showed that there are different main policies adopted to promote generic medicines such as generic substitution in the US, generic prescribing in the UK and mandatory generic substitution in Sweden and Finland. To effectively and successfully implement the main policy, different complementary policies and initiatives were necessarily introduced. Barriers to generic medicine use varied between countries from negative perceptions about generic medicines to lack of a coherent generic medicine policy, while facilitators included availability of information about generic medicines to both healthcare professionals and patients, brand interchangeability guidelines, regulations that support generic substitution by pharmacists, and incentives to both healthcare professionals and patients. PMID:25561861

Modeling startle eyeblink electromyogram to assess fear learning.

PubMed

Khemka, Saurabh; Tzovara, Athina; Gerster, Samuel; Quednow, Boris B; Bach, Dominik R

2017-02-01

Pavlovian fear conditioning is widely used as a laboratory model of associative learning in human and nonhuman species. In this model, an organism is trained to predict an aversive unconditioned stimulus from initially neutral events (conditioned stimuli, CS). In humans, fear memory is typically measured via conditioned autonomic responses or fear-potentiated startle. For the latter, various analysis approaches have been developed, but a systematic comparison of competing methodologies is lacking. Here, we investigate the suitability of a model-based approach to startle eyeblink analysis for assessment of fear memory, and compare this to extant analysis strategies. First, we build a psychophysiological model (PsPM) on a generic startle response. Then, we optimize and validate this PsPM on three independent fear-conditioning data sets. We demonstrate that our model can robustly distinguish aversive (CS+) from nonaversive stimuli (CS-, i.e., has high predictive validity). Importantly, our model-based approach captures fear-potentiated startle during fear retention as well as fear acquisition. Our results establish a PsPM-based approach to assessment of fear-potentiated startle, and qualify previous peak-scoring methods. Our proposed model represents a generic startle response and can potentially be used beyond fear conditioning, for example, to quantify affective startle modulation or prepulse inhibition of the acoustic startle response. © 2016 The Authors. Psychophysiology published by Wiley Periodicals, Inc. on behalf of Society for Psychophysiological Research.

0-6733 : evaluation of generic and branded herbicides.

DOT National Transportation Integrated Search

2012-08-01

As with other products in the marketplace, : generic herbicides often have a lower initial : product cost than their brand-name : counterparts.Herbicide formulations are : patented for 17 years with proprietary rights for : name, formula, and product...

Select Generic Dry-Storage Pilot Plant Design for Safeguards and Security by Design (SSBD) per Used Fuel Campaign

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

Demuth, Scott Francis; Sprinkle, James K.

As preparation to the year-end deliverable (Provide SSBD Best Practices for Generic Dry-Storage Pilot Scale Plant) for the Work Package (FT-15LA040501–Safeguards and Security by Design for Extended Dry Storage), the initial step was to select a generic dry-storage pilot plant design for SSBD. To be consistent with other DOE-NE Fuel Cycle Research and Development (FCR&D) activities, the Used Fuel Campaign was engaged for the selection of a design for this deliverable. For the work Package FT-15LA040501–“Safeguards and Security by Design for Extended Dry Storage”, SSBD will be initiated for the Generic Dry-Storage Pilot Scale Plant described by the layout ofmore » Reference 2. SSBD will consider aspects of the design that are impacted by domestic material control and accounting (MC&A), domestic security, and international safeguards.« less

Impact of alternative interventions on changes in generic dispensing rates.

PubMed

O'Malley, A James; Frank, Richard G; Kaddis, Atheer; Rothenberg, Barbara M; McNeil, Barbara J

2006-10-01

To evaluate the effectiveness of four alternative interventions (member mailings, advertising campaigns, free generic drug samples to physicians, and physician financial incentives) used by a major health insurer to encourage its members to switch to generic drugs. Using claim-level data from Blue Cross Blue Shield of Michigan, we evaluated the success of four interventions implemented during 2000-2003 designed to increase the use of generic drugs among its members. Around 13 million claims involving seven important classes of drugs were used to assess the effectiveness of the interventions. For each intervention a control group was developed that most closely resembled the corresponding intervention group. Logistic regression models with interaction effects between the treatment group (intervention versus control) and the status of the intervention (active versus not active) were used to evaluate if the interventions had an effect on the generic dispensing rate (GDR). Because the mail order pharmacy was considered more aggressive at converting prescriptions to generics, separate generic purchasing models were fitted to retail and mail order claims. In secondary analyses separate models were also fitted to claims involving a new condition and claims refilled for preexisting conditions. The interventions did not appear to increase the market penetration of generic drugs for either retail or mail order claims, or for claims involving new or preexisting conditions. In addition, we found that the ratio of copayments for brand name to generic drugs had a large positive effect on the GDR. The interventions did not appear to directly influence the GDR. Financial incentives expressed to consumers through benefit designs have a large influence on their switching to generic drugs and on the less-costly mail-order mode of purchase.

Ontological approach for safe and effective polypharmacy prescription

PubMed Central

Grando, Adela; Farrish, Susan; Boyd, Cynthia; Boxwala, Aziz

2012-01-01

The intake of multiple medications in patients with various medical conditions challenges the delivery of medical care. Initial empirical studies and pilot implementations seem to indicate that generic safe and effective multi-drug prescription principles could be defined and reused to reduce adverse drug events and to support compliance with medical guidelines and drug formularies. Given that ontologies are known to provide well-principled, sharable, setting-independent and machine-interpretable declarative specification frameworks for modeling and reasoning on biomedical problems, we explore here their use in the context of multi-drug prescription. We propose an ontology for modeling drug-related knowledge and a repository of safe and effective generic prescription principles. To test the usability and the level of granularity of the developed ontology-based specification models and heuristic we implemented a tool that computes the complexity of multi-drug treatments, and a decision aid to check the safeness and effectiveness of prescribed multi-drug treatments. PMID:23304299

Generic lamotrigine versus brand-name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard.

PubMed

Ting, Tricia Y; Jiang, Wenlei; Lionberger, Robert; Wong, Jessica; Jones, Jace W; Kane, Maureen A; Krumholz, Allan; Temple, Robert; Polli, James E

2015-09-01

To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in "generic-brittle" patients with epilepsy under clinical use conditions. This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in "generic-brittle" patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax ), and minimum plasma concentration (Cmin ) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax , and Cmin for generic-versus-brand were 97.2-101.6%, 98.8-104.5%, and 93.4-101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand-to-generic switching. Bioequivalence results in "generic-brittle" patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Advertising and generic market entry.

PubMed

Königbauer, Ingrid

2007-03-01

The effect of purely persuasive advertising on generic market entry and social welfare is analysed. An incumbent has the possibility to invest in advertising which affects the prescribing physician's perceived relative qualities of the brand-name and the generic version of the drug. Advertising creates product differentiation and can induce generic market entry which is deterred without differentiation due to strong Bertrand competition. However, over-investment in advertising can deter generic market entry under certain conditions and reduces welfare as compared to accommodated market entry.

Similarity between generic and brand-name antihypertensive drugs for primary prevention of cardiovascular disease: evidence from a large population-based study.

PubMed

Corrao, Giovanni; Soranna, Davide; Merlino, Luca; Mancia, Giuseppe

2014-10-01

Although generic and earlier brand-name counterparts are bioequivalent, their equivalence in preventing relevant clinical outcomes is of concern. To compare effectiveness of generic and brand-name antihypertensive drugs for preventing the onset of cardiovascular (CV) outcomes. A population-based, nested case-control study was carried out by including the cohort of 78 520 patients from Lombardy (Italy) aged 18 years or older who were newly treated with antihypertensive drugs during 2005. Cases were the 2206 patients who experienced a hospitalization for CV disease from initial prescription until 2011. One control for each case was randomly selected from the same cohort that generated cases. Logistic regression was used to model the CV risk associated with starting on and/or continuing with generic or brand-name agents. There was no evidence that patients who started on generics experienced different CV risk than those on brand-name product (OR 0·86; 95% CI 0·63-1·17). Patients at whom generics were main dispensed had not significantly difference in CV outcomes than those mainly on brand-name agents (OR 1·19; 95% CI 0·86-1·63). Compared with patients who kept initial brand-name therapy, those who experienced brand-to-generic or generic-to-brand switches, and those always on generics, did not show differential CV risks, being the corresponding ORs (and 95% CIs), 1·18 (0·96-1·47), 0·87 (0·63-1·21) and 1·08 (0·80-1·46). Our findings do not support the notion that brand-name antihypertensive agents are superior to generics for preventing CV outcomes in the real-world clinical practice. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

Fourier phase retrieval with a single mask by Douglas-Rachford algorithms.

PubMed

Chen, Pengwen; Fannjiang, Albert

2018-05-01

The Fourier-domain Douglas-Rachford (FDR) algorithm is analyzed for phase retrieval with a single random mask. Since the uniqueness of phase retrieval solution requires more than a single oversampled coded diffraction pattern, the extra information is imposed in either of the following forms: 1) the sector condition on the object; 2) another oversampled diffraction pattern, coded or uncoded. For both settings, the uniqueness of projected fixed point is proved and for setting 2) the local, geometric convergence is derived with a rate given by a spectral gap condition. Numerical experiments demonstrate global, power-law convergence of FDR from arbitrary initialization for both settings as well as for 3 or more coded diffraction patterns without oversampling. In practice, the geometric convergence can be recovered from the power-law regime by a simple projection trick, resulting in highly accurate reconstruction from generic initialization.

Quantum no-scale regimes in string theory

NASA Astrophysics Data System (ADS)

Coudarchet, Thibaut; Fleming, Claude; Partouche, Hervé

2018-05-01

We show that in generic no-scale models in string theory, the flat, expanding cosmological evolutions found at the quantum level can be attracted to a "quantum no-scale regime", where the no-scale structure is restored asymptotically. In this regime, the quantum effective potential is dominated by the classical kinetic energies of the no-scale modulus and dilaton. We find that this natural preservation of the classical no-scale structure at the quantum level occurs when the initial conditions of the evolutions sit in a subcritical region of their space. On the contrary, supercritical initial conditions yield solutions that have no analogue at the classical level. The associated intrinsically quantum universes are sentenced to collapse and their histories last finite cosmic times. Our analysis is done at 1-loop, in perturbative heterotic string compactified on tori, with spontaneous supersymmetry breaking implemented by a stringy version of the Scherk-Schwarz mechanism.

Analysis of French generic medicines retail market: why the use of generic medicines is limited.

PubMed

Dylst, Pieter; Vulto, Arnold; Simoens, Steven

2014-12-01

The market share of generic medicines in France is low compared to other European countries. This perspective paper provides an overview of the generic medicines retail market in France and how the current policy environment may affect the long-term sustainability. Looking at the French generic medicines retail market and the surrounding regulatory framework, all conditions seem to be in place to create a healthy generic medicines market: the country has well-respected regulatory authorities, generic medicines enter the market in a timely manner and prices of generic medicines are competitive compared with other European countries. Despite the success of the demand-side policies targeted at pharmacists and patients, those targeted at physicians were less successful due to a lack of enforcement and a lack of trust in generic medicines by French physicians. Recommendations to increase the use of generic medicines in France round off this perspective paper.

77 FR 12089 - Proposed Generic Communication; Regulatory Issue Summary 2012-XX: Developing Inservice Testing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-28

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0048] Proposed Generic Communication; Regulatory Issue... CFR) Part 52, ``Licenses, Certifications, and Approvals for Nuclear Power Plants,'' to satisfy the... inservice testing programs during the initial 120-month program interval following nuclear power plant...

Generic Principles for Resolving Intergroup Conflict.

ERIC Educational Resources Information Center

Fisher, Ronald J.

1994-01-01

Provides an initial statement of generic principles deemed effective for addressing protracted social conflicts between identity groups. These principles are compatible with certain values for societal organization and approaches to social change, raising questions of value differences between intervenors and the host culture(s). Three case…

Review of ongoing initiatives to improve prescribing efficiency in China; angiotensin receptor blockers as a case history.

PubMed

Zeng, Wenjie; Gustafsson, Lars L; Bennie, Marion; Finlayson, Alexander E; Godman, Brian

2015-02-01

Pharmaceutical expenditure is rising by 16% per annum in China and is now 46% of total expenditure. Initiatives to moderate growth include drug pricing regulations and encouraging international non-proprietary name prescribing. However, there is no monitoring of physician prescribing quality and perverse incentives. Assess changes in angiotensin receptor blocker (ARB) utilization and expenditure as more generics become available; compare findings to Europe. Observational retrospective study of ARB utilization and expenditure between 2006 and 2012 in the largest hospital in Chongqing district. Variable and low use of generics versus originators with a maximum of 31% among single ARBs. Similar for fixed dose combinations. Prices typically reduced over time, greatest for generic telmisartan (-54%), mirroring price reductions in some European countries. However, no preferential increase in prescribing of lower cost generics. Accumulated savings of 33 million CNY for this large provider if they adopted European practices. Considerable opportunities to improve prescribing efficiency in China.

Rhyme and Word Placement in Storybooks Support High-Level Verb Mapping in 3- to 5-Year-Olds

PubMed Central

Read, Kirsten; Quirke, Jacqueline

2018-01-01

High-level verbs can be especially challenging for young children to initially map to meaning. This study manipulated the format of a storybook designed to support such verb learning from shared reading. We tested whether 3- to 5-year-olds (n = 38) could remember the referents of eight new verbs when presented as essential actions within a narrative story but with differences in placement. Children were randomly assigned to either a rhymed condition, in which target verbs were heard at the end of rhyming stanzas making them maximally appreciable, or a control condition, where the verbs were presented in the same story, but not in final position or within a rhymed stanza. After hearing the story, each child was given three sets of retention questions testing their identification, demonstration, and production of the target verbs. Children identified and successfully demonstrated more target verbs in the rhymed condition than the control condition, and only in the rhymed condition did children’s initial verb mappings exceed chance. No differences between conditions were found in children’s ability to produce the target verbs, in part because of how often they reverted to more generic terms to describe the actions in the story. Nonetheless, these findings support the hypothesis that giving children maximal support within a storybook reading context can facilitate an initial grasp on challenging verbs.

Different initiatives across Europe to enhance losartan utilization post generics: impact and implications.

PubMed

Moon, James C; Godman, Brian; Petzold, Max; Alvarez-Madrazo, Samantha; Bennett, Kathleen; Bishop, Iain; Bucsics, Anna; Hesse, Ulrik; Martin, Andrew; Simoens, Steven; Zara, Corinne; Malmström, Rickard E

2014-01-01

There is an urgent need for health authorities across Europe to fully realize potential savings from increased use of generics to sustain their healthcare systems. A variety of strategies were used across Europe following the availability of generic losartan, the first angiotensin receptor blocker (ARB) to be approved and marketed, to enhance its prescribing vs. single-sourced drugs in the class. Demand-side strategies ranged from 100% co-payment for single-sourced ARBs in Denmark to no specific measures. We hypothesized this heterogeneity of approaches would provide opportunities to explore prescribing in a class following patent expiry. Contrast the impact of the different approaches among European countries and regions to the availability of generic losartan to provide future guidance. Retrospective segmented regression analyses applying linear random coefficient models with country specific intercepts and slopes were used to assess the impact of the various initiatives across Europe following the availability of generic losartan. Utilization measured in defined daily doses (DDDs). Price reductions for generic losartan were also measured. Utilization of losartan was over 90% of all ARBs in Denmark by the study end. Multiple measures in Sweden and one English primary care group also appreciably enhanced losartan utilization. Losartan utilization actually fell in some countries with no specific demand-side measures. Considerable differences were seen in the prices of generic losartan. Delisting single-sourced ARBs produced the greatest increase in losartan utilization. Overall, multiple demand-side measures are needed to change physician prescribing habits to fully realize savings from generics. There is no apparent "spill over" effect from one class to another to influence future prescribing patterns even if these are closely related.

Different initiatives across Europe to enhance losartan utilization post generics: impact and implications

PubMed Central

Moon, James C.; Godman, Brian; Petzold, Max; Alvarez-Madrazo, Samantha; Bennett, Kathleen; Bishop, Iain; Bucsics, Anna; Hesse, Ulrik; Martin, Andrew; Simoens, Steven; Zara, Corinne; Malmström, Rickard E.

2014-01-01

Introduction: There is an urgent need for health authorities across Europe to fully realize potential savings from increased use of generics to sustain their healthcare systems. A variety of strategies were used across Europe following the availability of generic losartan, the first angiotensin receptor blocker (ARB) to be approved and marketed, to enhance its prescribing vs. single-sourced drugs in the class. Demand-side strategies ranged from 100% co-payment for single-sourced ARBs in Denmark to no specific measures. We hypothesized this heterogeneity of approaches would provide opportunities to explore prescribing in a class following patent expiry. Objective: Contrast the impact of the different approaches among European countries and regions to the availability of generic losartan to provide future guidance. Methodology: Retrospective segmented regression analyses applying linear random coefficient models with country specific intercepts and slopes were used to assess the impact of the various initiatives across Europe following the availability of generic losartan. Utilization measured in defined daily doses (DDDs). Price reductions for generic losartan were also measured. Results: Utilization of losartan was over 90% of all ARBs in Denmark by the study end. Multiple measures in Sweden and one English primary care group also appreciably enhanced losartan utilization. Losartan utilization actually fell in some countries with no specific demand-side measures. Considerable differences were seen in the prices of generic losartan. Conclusion: Delisting single-sourced ARBs produced the greatest increase in losartan utilization. Overall, multiple demand-side measures are needed to change physician prescribing habits to fully realize savings from generics. There is no apparent “spill over” effect from one class to another to influence future prescribing patterns even if these are closely related. PMID:25339902

Impaired health-related quality of life in children and adolescents with chronic conditions: a comparative analysis of 10 disease clusters and 33 disease categories/severities utilizing the PedsQL 4.0 Generic Core Scales.

PubMed

Varni, James W; Limbers, Christine A; Burwinkle, Tasha M

2007-07-16

Advances in biomedical science and technology have resulted in dramatic improvements in the healthcare of pediatric chronic conditions. With enhanced survival, health-related quality of life (HRQOL) issues have become more salient. The objectives of this study were to compare generic HRQOL across ten chronic disease clusters and 33 disease categories/severities from the perspectives of patients and parents. Comparisons were also benchmarked with healthy children data. The analyses were based on over 2,500 pediatric patients from 10 physician-diagnosed disease clusters and 33 disease categories/severities and over 9,500 healthy children utilizing the PedsQL 4.0 Generic Core Scales. Patients were recruited from general pediatric clinics, subspecialty clinics, and hospitals. Pediatric patients with diabetes, gastrointestinal conditions, cardiac conditions, asthma, obesity, end stage renal disease, psychiatric disorders, cancer, rheumatologic conditions, and cerebral palsy self-reported progressively more impaired overall HRQOL than healthy children, respectively, with medium to large effect sizes. Patients with cerebral palsy self-reported the most impaired HRQOL, while patients with diabetes self-reported the best HRQOL. Parent proxy-reports generally paralleled patient self-report, with several notable differences. The results demonstrate differential effects of pediatric chronic conditions on patient HRQOL across diseases clusters, categories, and severities utilizing the PedsQL 4.0 Generic Core Scales from the perspectives of pediatric patients and parents. The data contained within this study represents a larger and more diverse population of pediatric patients with chronic conditions than previously reported in the extant literature. The findings contribute important information on the differential effects of pediatric chronic conditions on generic HRQOL from the perspectives of children and parents utilizing the PedsQL 4.0 Generic Core Scales. These findings with the PedsQL have clinical implications for the healthcare services provided for children with chronic health conditions. Given the degree of reported impairment based on PedsQL scores across different pediatric chronic conditions, the need for more efficacious targeted treatments for those pediatric patients with more severely impaired HRQOL is clearly and urgently indicated.

Impaired health-related quality of life in children and adolescents with chronic conditions: a comparative analysis of 10 disease clusters and 33 disease categories/severities utilizing the PedsQL™ 4.0 Generic Core Scales

PubMed Central

Varni, James W; Limbers, Christine A; Burwinkle, Tasha M

2007-01-01

Background Advances in biomedical science and technology have resulted in dramatic improvements in the healthcare of pediatric chronic conditions. With enhanced survival, health-related quality of life (HRQOL) issues have become more salient. The objectives of this study were to compare generic HRQOL across ten chronic disease clusters and 33 disease categories/severities from the perspectives of patients and parents. Comparisons were also benchmarked with healthy children data. Methods The analyses were based on over 2,500 pediatric patients from 10 physician-diagnosed disease clusters and 33 disease categories/severities and over 9,500 healthy children utilizing the PedsQL™ 4.0 Generic Core Scales. Patients were recruited from general pediatric clinics, subspecialty clinics, and hospitals. Results Pediatric patients with diabetes, gastrointestinal conditions, cardiac conditions, asthma, obesity, end stage renal disease, psychiatric disorders, cancer, rheumatologic conditions, and cerebral palsy self-reported progressively more impaired overall HRQOL than healthy children, respectively, with medium to large effect sizes. Patients with cerebral palsy self-reported the most impaired HRQOL, while patients with diabetes self-reported the best HRQOL. Parent proxy-reports generally paralleled patient self-report, with several notable differences. Conclusion The results demonstrate differential effects of pediatric chronic conditions on patient HRQOL across diseases clusters, categories, and severities utilizing the PedsQL™ 4.0 Generic Core Scales from the perspectives of pediatric patients and parents. The data contained within this study represents a larger and more diverse population of pediatric patients with chronic conditions than previously reported in the extant literature. The findings contribute important information on the differential effects of pediatric chronic conditions on generic HRQOL from the perspectives of children and parents utilizing the PedsQL™ 4.0 Generic Core Scales. These findings with the PedsQL™ have clinical implications for the healthcare services provided for children with chronic health conditions. Given the degree of reported impairment based on PedsQL™ scores across different pediatric chronic conditions, the need for more efficacious targeted treatments for those pediatric patients with more severely impaired HRQOL is clearly and urgently indicated. PMID:17634123

Super NiCd Open-Circuit Storage and Low Earth Orbit (LEO) Life Test Evaluation

NASA Technical Reports Server (NTRS)

Baer, Jean Marie; Hwang, Warren C.; Ang, Valerie J.; Hayden, Jeff; Rao, Gopalakrishna; Day, John H. (Technical Monitor)

2002-01-01

This presentation discusses Air Force tests performed on super NiCd cells to measure their performance under conditions simulating Low Earth Orbit (LEO) conditions. Super NiCd cells offer potential advantages over existing NiCd cell designs including advanced cell design with improved separator material and electrode making processes, but handling and storage requires active charging. These tests conclude that the super NiCd cells support generic Air Force qualifications for conventional LEO missions (up to five years duration) and that handling and storage may not actually require active charging as previously assumed. Topics covered include: Test Plan, Initial Characterization Tests, Open-Circuit Storage Tests, and post storage capacities.

Generic medicines policies in the Asia Pacific region: ways forward.

PubMed

Nguyen, Tuan A; Hassali, Mohamed A A; McLachlan, Andrew

2013-01-01

Generic medicines are a key strategy used by governments and third-party payers to contain medicines costs and improve the access to essential medicines. This strategy represents an important opportunity provided by the global intellectual property regimes to discover and develop copies of original products marketed by innovator companies once the patent protection term is over. While there is an extensive experience regarding generic medicines policies in developed countries, this evidence may not translate to developing countries. The generic medicines policies workshop at the Asia Pacific Conference on National Medicines Policies 2012 provided an important opportunity to discuss and document country-specific initiatives for improving access to and the rational of use of generic medicines in the Asia Pacific region. Based on the identified barriers and enablers to implementation of generic medicines policies in the region, a set of future action plans and recommendations has been made.

Initial value formulation of dynamical Chern-Simons gravity

NASA Astrophysics Data System (ADS)

Delsate, Térence; Hilditch, David; Witek, Helvi

2015-01-01

We derive an initial value formulation for dynamical Chern-Simons gravity, a modification of general relativity involving parity-violating higher derivative terms. We investigate the structure of the resulting system of partial differential equations thinking about linearization around arbitrary backgrounds. This type of consideration is necessary if we are to establish well-posedness of the Cauchy problem. Treating the field equations as an effective field theory we find that weak necessary conditions for hyperbolicity are satisfied. For the full field equations we find that there are states from which subsequent evolution is not determined. Generically the evolution system closes, but is not hyperbolic in any sense that requires a first order pseudodifferential reduction. In a cursory mode analysis we find that the equations of motion contain terms that may cause ill-posedness of the initial value problem.

76 FR 60499 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

... supports initiatives designed to reduce the health and financial burden of tobacco use through prevention and cessation approaches. CDC requests OMB approval of a new, generic clearance mechanism to support...-needed basis, or in the context of a coordinated series of activities. A generic clearance is needed to...

The effect of generic competition on the price of brand-name drugs.

PubMed

Lexchin, Joel

2004-04-01

Literature from the US has shown that brand-name manufacturers do not compete on price once generic competitors become available. This study was undertaken to investigate if this is also true in Canada. Editions of the Ontario Drug Benefit Formulary were used to identify brand-name drugs that lacked generic competition in July 1990 but had acquired one or more generic competitors by December 1998. Prices of the brand-name drugs were compared before generic competition, at the point when generic competition started and subsequent to the initiation of competition. Price changes for 81 different products in 144 separate presentations were analysed. There was no statistically significant change in brand-name prices when generic competition started. The movement of brand-name prices was not influenced by whether the generic was made by the company producing the brand-name product or price freezes imposed by the Ontario government. When generics first became available having four or more generics was associated with a rise in the price of the brand-name drugs compared to having one, two or three generic competitor(s). The lack of price competition may lead to increased costs in the private market. Private insurance companies generally do not require generic substitution and some provinces do not require generic substitution for cash-paying customers. Maintaining higher prices on brand-name drugs impacts on the prices of new patented medications coming onto the Canadian market under the current pricing guidelines of the Patented Medicine Prices Review Board.

Generic Substitution of Orphan Drugs for the Treatment of Rare Diseases: Exploring the Potential Challenges.

PubMed

Di Paolo, Antonello; Arrigoni, Elena

2018-03-01

Generic drugs are important components of measures introduced by healthcare regulatory authorities to reduce treatment costs. In most patients and conditions the switch from a branded drug to its generic counterpart is performed with no major complications. However, evidence from complex diseases suggests that generic substitution requires careful evaluation in some settings and that current bioequivalence criteria may not always be adequate for establishing the interchangeability of branded and generic products. Rare diseases, also called orphan diseases, are a group of heterogeneous diseases that share important characteristics: in addition to their scarcity, most are severe, chronic, highly debilitating, and often present in early childhood. Finding a treatment for a rare disease is challenging. Thanks to incentives that encourage research and development programs in rare diseases, several orphan drugs are currently available. The elevated cost of orphan drugs is a highly debated issue and a cause of limited access to treatment for many patients. As patent protection and the exclusivity period of several orphan drugs will expire soon, generic versions of orphan drugs should reach the market shortly, with great expectations about their impact on the economic burden of rare diseases. However, consistent with other complex diseases, generic substitution may require thoughtful considerations and may be even contraindicated in some rare conditions. This article provides an overview of rare disease characteristics, reviews reports of problematic generic substitution, and discusses why generic substitution of orphan drugs may be challenging and should be undertaken carefully in rare disease patients.

Extreme throat initial data set and horizon area-angular momentum inequality for axisymmetric black holes

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

Dain, Sergio; Max Planck Institute for Gravitational Physics

2010-11-15

We present a formula that relates the variations of the area of extreme throat initial data with the variation of an appropriate defined mass functional. From this expression we deduce that the first variation, with fixed angular momentum, of the area is zero and the second variation is positive definite evaluated at the extreme Kerr throat initial data. This indicates that the area of the extreme Kerr throat initial data is a minimum among this class of data. And hence the area of generic throat initial data is bounded from below by the angular momentum. Also, this result strongly suggestsmore » that the inequality between area and angular momentum holds for generic asymptotically flat axially symmetric black holes. As an application, we prove this inequality in the nontrivial family of spinning Bowen-York initial data.« less

Gravitational clustering in the expanding universe - Controlled high-resolution studies in two dimensions

NASA Technical Reports Server (NTRS)

Beacom, John Francis; Dominik, Kurt G.; Melott, Adrian L.; Perkins, Sam P.; Shandarin, Sergei F.

1991-01-01

Results are presented from a series of gravitational clustering simulations in two dimensions. These simulations are a significant departure from previous work, since in two dimensions one can have large dynamic range in both length scale and mass using present computer technology. Controlled experiments were conducted by varying the slope of power-law initial density fluctuation spectra and varying cutoffs at large k, while holding constant the phases of individual Fourier components and the scale of nonlinearity. Filaments are found in many different simulations, even with pure power-law initial conditions. By direct comparison, filaments, called 'second-generation pancakes' are shown to arise as a consequence of mild nonlinearity on scales much larger than the correlation length and are not relics of an initial lattice or due to sparse sampling of the Fourier components. Bumps of low amplitude in the two-point correlation are found to be generic but usually only statistical fluctuations. Power spectra are much easier to relate to initial conditions, and seem to follow a simple triangular shape (on log-log plot) in the nonlinear regime. The rms density fluctuation with Gaussian smoothing is the most stable indicator of nonlinearity.

Competition Between Transients in the Rate of Approach to a Fixed Point

NASA Astrophysics Data System (ADS)

Day, Judy; Rubin, Jonathan E.; Chow, Carson C.

2009-01-01

The goal of this paper is to provide and apply tools for analyzing a specific aspect of transient dynamics not covered by previous theory. The question we address is whether one component of a perturbed solution to a system of differential equations can overtake the corresponding component of a reference solution as both converge to a stable node at the origin, given that the perturbed solution was initially farther away and that both solutions are nonnegative for all time. We call this phenomenon tolerance, for its relation to a biological effect. We show using geometric arguments that tolerance will exist in generic linear systems with a complete set of eigenvectors and in excitable nonlinear systems. We also define a notion of inhibition that may constrain the regions in phase space where the possibility of tolerance arises in general systems. However, these general existence theorems do not not yield an assessment of tolerance for specific initial conditions. To address that issue, we develop some analytical tools for determining if particular perturbed and reference solution initial conditions will exhibit tolerance.

THE FINAL SPIN FROM BINARY BLACK HOLES IN QUASI-CIRCULAR ORBITS

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

Hofmann, Fabian; Rezzolla, Luciano; Barausse, Enrico

2016-07-10

We revisit the problem of predicting the spin magnitude and direction of the black hole (BH) resulting from the merger of two BHs with arbitrary masses and spins inspiraling in quasi-circular orbits. We do this by analyzing a catalog of 619 recent numerical-relativity simulations collected from the literature and spanning a large variety of initial conditions. By combining information from the post-Newtonian approximation, the extreme mass-ratio limit, and perturbative calculations, we improve our previously proposed phenomenological formulae for the final remnant spin. In contrast with alternative suggestions in the literature, and in analogy with our previous expressions, the new formulamore » is a simple algebraic function of the initial system parameters and is not restricted to binaries with spins aligned/anti-aligned with the orbital angular momentum but can be employed for fully generic binaries. The accuracy of the new expression is significantly improved, especially for almost extremal progenitor spins and for small mass ratios, yielding an rms error σ ≈ 0.002 for aligned/anti-aligned binaries and σ ≈ 0.006 for generic binaries. Our new formula is suitable for cosmological applications and can be employed robustly in the analysis of the gravitational waveforms from advanced interferometric detectors.« less

On the local well-posedness of Lovelock and Horndeski theories

NASA Astrophysics Data System (ADS)

Papallo, Giuseppe; Reall, Harvey S.

2017-08-01

We investigate local well-posedness of the initial value problem for Lovelock and Horndeski theories of gravity. A necessary condition for local well-posedness is strong hyperbolicity of the equations of motion. Even weak hyperbolicity can fail for strong fields so we restrict to weak fields. The Einstein equation is known to be strongly hyperbolic in harmonic gauge so we study Lovelock theories in harmonic gauge. We show that the equation of motion is always weakly hyperbolic for weak fields but, in a generic weak-field background, it is not strongly hyperbolic. For Horndeski theories, we prove that, for weak fields, the equation of motion is always weakly hyperbolic in any generalized harmonic gauge. For some Horndeski theories there exists a generalized harmonic gauge for which the equation of motion is strongly hyperbolic in a weak-field background. This includes "k-essence" like theories. However, for more general Horndeski theories, there is no generalized harmonic gauge for which the equation of motion is strongly hyperbolic in a generic weak-field background. Our results show that the standard method used to establish local well-posedness of the Einstein equation does not extend to Lovelock or general Horndeski theories. This raises the possibility that these theories may not admit a well-posed initial value problem even for weak fields.

Informing the development of services supporting self-care for severe, long term mental health conditions: a mixed method study of community based mental health initiatives in England

PubMed Central

2012-01-01

Background Supporting self-care is being explored across health care systems internationally as an approach to improving care for long term conditions in the context of ageing populations and economic constraint. UK health policy advocates a range of approaches to supporting self-care, including the application of generic self-management type programmes across conditions. Within mental health, the scope of self-care remains poorly conceptualised and the existing evidence base for supporting self-care is correspondingly disparate. This paper aims to inform the development of support for self-care in mental health by considering how generic self-care policy guidance is implemented in the context of services supporting people with severe, long term mental health problems. Methods A mixed method study was undertaken comprising standardised psychosocial measures, questionnaires about health service use and qualitative interviews with 120 new referrals to three contrasting community based initiatives supporting self-care for severe, long term mental health problems, repeated nine months later. A framework approach was taken to qualitative analysis, an exploratory statistical analysis sought to identify possible associations between a range of independent variables and self-care outcomes, and a narrative synthesis brought these analyses together. Results Participants reported improvement in self-care outcomes (e.g. greater empowerment; less use of Accident and Emergency services). These changes were not associated with level of engagement with self-care support. Level of engagement was associated with positive collaboration with support staff. Qualitative data described the value of different models of supporting self-care and considered challenges. Synthesis of analyses suggested that timing support for self-care, giving service users control over when and how they accessed support, quality of service user-staff relationships and decision making around medication are important issues in supporting self-care in mental health. Conclusions Service delivery components – e.g. peer support groups, personal planning – advocated in generic self-care policy have value when implemented in a mental health context. Support for self-care in mental health should focus on core, mental health specific qualities; issues of control, enabling staff-service user relationships and shared decision making. The broad empirical basis of our research indicates the wider relevance of our findings across mental health settings. PMID:22769593

Thermalization and its mechanism for generic quantum isolated systems

NASA Astrophysics Data System (ADS)

Olshanii, Maxim; Dunjko, Vanja; Rigol, Marcos

2008-05-01

Time dynamics of isolated many-body quantum systems has long been an elusive subject, perhaps most urgently needed in the foundations of quantum statistical mechanics. In generic systems, one expects the nonequilibrium dynamics to lead to thermalization: a relaxation to states where the values of macroscopic quantities are stationary, universal with respect to widely differing initial conditions, and predictable through the time-tested recipe of statistical mechanics. The relaxation mechanism is not obvious, however; dynamical chaos cannot play the key role as it does in classical systems since quantum evolution is linear. Here we demonstrateootnotetextM. Rigol, V. Dunjko, and M. Olshanii, to appear in Nature (2008), using the results of an ab initio numerical experiment with 5 hard-core bosons moving in a 5x5 lattice, that in quantum systems thermalization happens not in course of time evolution but instead at the level of individual eigenstates, as first proposed by DeutschootnotetextJ. M. Deutsch, Phys.Rev. A 43, 2046 (1991) and SrednickiootnotetextM. Srednicki, Phys. Rev. E 50, 888 (1994).

Cost sharing and branded antidepressant initiation among patients treated with generics.

PubMed

Buxbaum, Jason D; Chernew, Michael E; Bonafede, Machaon; Vlahiotis, Anna; Walter, Deborah; Mucha, Lisa; Fendrick, A Mark

2018-04-01

To determine the relationship between consumer cost sharing for branded antidepressants and the initiation of branded therapy among patients with major depressive disorder (MDD) filling a prescription for generic MDD medication.  Retrospective cross-sectional analyses. Patients aged 18 to 64 years with MDD who filled a generic antidepressant were identified in commercial claims data for 2012 to 2014. For each year-specific analysis, an average cost-sharing index for branded antidepressants at the level of the plan was computed. Multivariable models were used to estimate the relationship between plan-level cost sharing for branded antidepressant medications and the filling of branded prescriptions, with demographic and clinical variables as covariates. For patients with MDD filling a generic prescription, increases in branded cost sharing were associated with significant decreases in the likelihood of filling a branded antidepressant in each year (P <.001). Results in 2012 imply that a shift from the 0th to 90th percentile in the branded cost-sharing index corresponded with a 9.5% decrease in the relative likelihood of a branded fill among patients receiving a generic antidepressant. The corresponding figures for 2013 and 2014 were 9.3% and 3.5%, respectively. In MDD, patients and clinicians who dutifully adhere to guidelines requiring a trial of first-line medication may ultimately require therapy with alternate agents to achieve adequate disease control. A "reward the good soldier" benefit design would lower cost sharing for higher-tier evidence-based therapies when clinically indicated. Results suggest that narrowing the gap in cost sharing between branded and generic medications following a trial of a generic agent might improve access to second-line treatment in MDD.

The Effectiveness of a Web-Based Computer-Tailored Intervention on Workplace Sitting: A Randomized Controlled Trial.

PubMed

De Cocker, Katrien; De Bourdeaudhuij, Ilse; Cardon, Greet; Vandelanotte, Corneel

2016-05-31

Effective interventions to influence workplace sitting are needed, as office-based workers demonstrate high levels of continued sitting, and sitting too much is associated with adverse health effects. Therefore, we developed a theory-driven, Web-based, interactive, computer-tailored intervention aimed at reducing and interrupting sitting at work. The objective of our study was to investigate the effects of this intervention on objectively measured sitting time, standing time, and breaks from sitting, as well as self-reported context-specific sitting among Flemish employees in a field-based approach. Employees (n=213) participated in a 3-group randomized controlled trial that assessed outcomes at baseline, 1-month follow-up, and 3-month follow-up through self-reports. A subsample (n=122) were willing to wear an activity monitor (activPAL) from Monday to Friday. The tailored group received an automated Web-based, computer-tailored intervention including personalized feedback and tips on how to reduce or interrupt workplace sitting. The generic group received an automated Web-based generic advice with tips. The control group was a wait-list control condition, initially receiving no intervention. Intervention effects were tested with repeated-measures multivariate analysis of variance. The tailored intervention was successful in decreasing self-reported total workday sitting (time × group: P<.001), sitting at work (time × group: P<.001), and leisure time sitting (time × group: P=.03), and in increasing objectively measured breaks at work (time × group: P=.07); this was not the case in the other conditions. The changes in self-reported total nonworkday sitting, sitting during transport, television viewing, and personal computer use, objectively measured total sitting time, and sitting and standing time at work did not differ between conditions. Our results point out the significance of computer tailoring for sedentary behavior and its potential use in public health promotion, as the effects of the tailored condition were superior to the generic and control conditions. Clinicaltrials.gov NCT02672215; http://clinicaltrials.gov/ct2/show/NCT02672215 (Archived by WebCite at http://www.webcitation.org/6glPFBLWv).

The Effectiveness of a Web-Based Computer-Tailored Intervention on Workplace Sitting: A Randomized Controlled Trial

PubMed Central

De Bourdeaudhuij, Ilse; Cardon, Greet; Vandelanotte, Corneel

2016-01-01

Background Effective interventions to influence workplace sitting are needed, as office-based workers demonstrate high levels of continued sitting, and sitting too much is associated with adverse health effects. Therefore, we developed a theory-driven, Web-based, interactive, computer-tailored intervention aimed at reducing and interrupting sitting at work. Objective The objective of our study was to investigate the effects of this intervention on objectively measured sitting time, standing time, and breaks from sitting, as well as self-reported context-specific sitting among Flemish employees in a field-based approach. Methods Employees (n=213) participated in a 3-group randomized controlled trial that assessed outcomes at baseline, 1-month follow-up, and 3-month follow-up through self-reports. A subsample (n=122) were willing to wear an activity monitor (activPAL) from Monday to Friday. The tailored group received an automated Web-based, computer-tailored intervention including personalized feedback and tips on how to reduce or interrupt workplace sitting. The generic group received an automated Web-based generic advice with tips. The control group was a wait-list control condition, initially receiving no intervention. Intervention effects were tested with repeated-measures multivariate analysis of variance. Results The tailored intervention was successful in decreasing self-reported total workday sitting (time × group: P<.001), sitting at work (time × group: P<.001), and leisure time sitting (time × group: P=.03), and in increasing objectively measured breaks at work (time × group: P=.07); this was not the case in the other conditions. The changes in self-reported total nonworkday sitting, sitting during transport, television viewing, and personal computer use, objectively measured total sitting time, and sitting and standing time at work did not differ between conditions. Conclusions Our results point out the significance of computer tailoring for sedentary behavior and its potential use in public health promotion, as the effects of the tailored condition were superior to the generic and control conditions. Trial Registration Clinicaltrials.gov NCT02672215; http://clinicaltrials.gov/ct2/show/NCT02672215 (Archived by WebCite at http://www.webcitation.org/6glPFBLWv) PMID:27245789

Need for multicriteria evaluation of generic drug policies.

PubMed

Kaló, Zoltán; Holtorf, Anke-Peggy; Alfonso-Cristancho, Rafael; Shen, Jie; Ágh, Tamás; Inotai, András; Brixner, Diana

2015-03-01

Policymakers tend to focus on improving patented drug policies because they are under pressure from patients, physicians, and manufacturers to increase access to novel therapies. The success of pharmaceutical innovation over the last few decades has led to the availability of many off-patent drugs to treat disease areas with the greatest public health need. Therefore, the success of public health programs in improving the health status of the total population is highly dependent on the efficiency of generic drug policies. The objective of this article was to explore factors influencing the true efficiency of generic prescription drug policies in supporting public health initiatives in the developed world. Health care decision makers often assess the efficiency of generic drug policies by the level of price erosion and market share of generics. Drug quality, bioequivalence, in some cases drug formulations, supply reliability, medical adherence and persistence, health outcomes, and nondrug costs, however, are also attributes of success for generic drug policies. Further methodological research is needed to measure and improve the efficiency of generic drug policies. This also requires extension of the evidence base of the impact of generic drugs, partly based on real-world evidence. Multicriteria decision analysis may assist policymakers and researchers to evaluate the true value of generic drugs. Copyright © 2015. Published by Elsevier Inc.

Skillful regional prediction of Arctic sea ice on seasonal timescales

NASA Astrophysics Data System (ADS)

Bushuk, Mitchell; Msadek, Rym; Winton, Michael; Vecchi, Gabriel A.; Gudgel, Rich; Rosati, Anthony; Yang, Xiaosong

2017-05-01

Recent Arctic sea ice seasonal prediction efforts and forecast skill assessments have primarily focused on pan-Arctic sea ice extent (SIE). In this work, we move toward stakeholder-relevant spatial scales, investigating the regional forecast skill of Arctic sea ice in a Geophysical Fluid Dynamics Laboratory (GFDL) seasonal prediction system. Using a suite of retrospective initialized forecasts spanning 1981-2015 made with a coupled atmosphere-ocean-sea ice-land model, we show that predictions of detrended regional SIE are skillful at lead times up to 11 months. Regional prediction skill is highly region and target month dependent and generically exceeds the skill of an anomaly persistence forecast. We show for the first time that initializing the ocean subsurface in a seasonal prediction system can yield significant regional skill for winter SIE. Similarly, as suggested by previous work, we find that sea ice thickness initial conditions provide a crucial source of skill for regional summer SIE.

Comparison between Utility of the Thai Pediatric Quality of Life Inventory 4.0 Generic Core Scales and 3.0 Cerebral Palsy Module

ERIC Educational Resources Information Center

Tantilipikorn, Pinailug; Watter, Pauline; Prasertsukdee, Saipin

2013-01-01

Health-related quality of life (HRQOL) is increasingly being considered in the management of patients with various conditions. HRQOL instruments can be broadly classified as generic or disease-specific measures. Several generic HRQOL instruments in different languages have been developed for paediatric populations including the Pediatric Quality…

Generic NICA-Donnan model parameters for metal-ion binding by humic substances.

PubMed

Milne, Christopher J; Kinniburgh, David G; van Riemsdijk, Willem H; Tipping, Edward

2003-03-01

A total of 171 datasets of literature and experimental data for metal-ion binding by fulvic and humic acids have been digitized and re-analyzed using the NICA-Donnan model. Generic parameter values have been derived that can be used for modeling in the absence of specific metalion binding measurements. These values complement the previously derived generic descriptions of proton binding. For ions where the ranges of pH, concentration, and ionic strength conditions are well covered by the available data,the generic parameters successfully describe the metalion binding behavior across a very wide range of conditions and for different humic and fulvic acids. Where published data for other metal ions are too sparse to constrain the model well, generic parameters have been estimated by interpolating trends observable in the parameter values of the well-defined data. Recommended generic NICA-Donnan model parameters are provided for 23 metal ions (Al, Am, Ba, Ca, Cd, Cm, Co, CrIII, Cu, Dy, Eu, FeII, FeIII, Hg, Mg, Mn, Ni, Pb, Sr, Thv, UVIO2, VIIIO, and Zn) for both fulvic and humic acids. These parameters probably represent the best NICA-Donnan description of metal-ion binding that can be achieved using existing data.

Influencers of generic drug utilization: A systematic review.

PubMed

Howard, Jennifer N; Harris, Ilene; Frank, Gavriella; Kiptanui, Zippora; Qian, Jingjing; Hansen, Richard

2017-08-04

With an increase in prescription drug spending and rising drug costs there is a need to encourage the use of generic prescription drugs. However, maximizing generic drug use is not possible without the public's positive perception and meeting their informational needs about generic drugs. Thus, improving the public's confidence in, and knowledge of generic drugs on the market is critical. The objective of this systematic review is to examine and evaluate the studies focusing on the nature and extent of key factors influencing generic drug use in the United States in order to help guide policy, education and practice interventions. Using multiple search engines and key word screening criteria, empirical studies published in English between January 1, 2005 and December 31, 2015 were identified. A qualitative synthesis of the evidence identified domains of key factors that influenced generic drug use across studies. Over 3000 citations met the key word screening criteria; 67 of these met inclusion criteria for the systematic review. Seven domains of factors that influence generic drug utilization were identified: 1) patient-related factors, 2) formulary management or cost containment, 3) healthcare policies, 4) promotional activities, 5) educational initiatives, 6) technology, and 7) physician-related factors. Patients, physicians, pharmacists, formulary managers, and policymakers play an important role in generic drug use. Understanding the factors influencing generic drug use can help guide future policy, education, and practice interventions to increase generic drug use. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative effectiveness and costs of generic and brand-name gabapentin and venlafaxine in patients with neuropathic pain or generalized anxiety disorder in Spain.

PubMed

Sicras-Mainar, Antoni; Rejas-Gutiérrez, Javier; Navarro-Artieda, Ruth

2015-01-01

To explore adherence/persistence with generic gabapentin/venlafaxine versus brand-name gabapentin/venlafaxine (Neurontin(®)/Vandral(®)) in peripheral neuropathic pain (pNP) or generalized anxiety disorder (GAD), respectively, and whether it is translated into different costs and patient outcomes in routine medical practice. A retrospective, new-user cohort study was designed. Electronic medical records (EMR) of patients included in the health plan of Badalona Serveis Assistencials SA, Barcelona, Spain were exhaustively extracted for analysis. Participants were beneficiaries aged 18+ years, followed between 2008 and 2012, with a pNP/GAD International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code, who initiated treatment with generic or brand-name gabapentin or venlafaxine. Assessments included 1-year treatment persistence and adherence (medication possession ratio), health care costs, and reduction in severity of pain and anxiety symptoms. A total of 2,210 EMR were analyzed; 1,369 on gabapentin (brand 400; generic 969) and 841 on venlafaxine (brand 370 and generic 471). Brand-name gabapentin and venlafaxine were both significantly associated with longer persistence than generic: 7.3 versus 6.3 months, P<0.001; and 8.8 versus 8.1 months, P<0.05, respectively. Brand-name was associated with higher adherence: 86.5% versus 81.3%, P<0.001; and 82.1% versus 79.0%, P<0.05, respectively. Adjusted average costs were higher with generic compared with brand: €1,277 versus €1,057 (difference of €220 per patient; P<0.001) for gabapentin; and €1,110 versus €928 (difference of €182 per patient; P=0.020) for venlafaxine, both because of more use of medical visits and concomitant medication. Compared with generic, brand-name was associated with higher reduction in pain (7.8%; P<0.001) and anxiety (13.2%; P<0.001). Patients initiating brand-name gabapentin or venlafaxine were more likely to adhere and persist on treatment of pNP or GAD, have lower health care costs, and show further reduction of pain and anxiety symptoms than with generic drugs in routine medical practice.

Generic antibiotic industries: Challenges and implied strategies with regulatory perspectives

PubMed Central

Venkatesh, M.; Bairavi, V. G.; Sasikumar, K. C.

2011-01-01

Ever since the discovery of antibiotics, the quality of human life greatly improved in the 20th century. The discovery of penicillin transformed the medicine industry and initiated a search for a better antibiotic every time resulting in several synthetic and semi-synthetic antibiotics. Beginning with the 1937 sulfa drug tragedy, the drug regulations had a parallel growth along with the antibiotics and the antibiotic-based generic Pharma industries. This review article is focused on the scenario depicting current global Pharma industries based on generic antibiotics. Several regulatory aspects involved with these industries have been discussed along with the complexity of the market, issues that could affect their growth, their struggle for quality, and their compliance with the tightened regulations. With the skyrocketing commercialization of antibiotics through generics and the leveraging technologic renaissance, generic industries are involved in providing maximum safer benefits for the welfare of the people, highlighting its need today.. PMID:21430959

Fingering patterns in Hele-Shaw flows are density shock wave solutions of dispersionless KdV hierarchy

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

Teodorescu, Razvan; Lee, S - Y; Wiegmann, P

We investigate the hydrodynamics of a Hele-Shaw flow as the free boundary evolves from smooth initial conditions into a generic cusp singularity (of local geometry type x{sup 3} {approx} y{sup 2}), and then into a density shock wave. This novel solution preserves the integrability of the dynamics and, unlike all the weak solutions proposed previously, is not underdetermined. The evolution of the shock is such that the net vorticity remains zero, as before the critical time, and the shock can be interpreted as a singular line distribution of fluid deficit.

Arcmancer: Geodesics and polarized radiative transfer library

NASA Astrophysics Data System (ADS)

Pihajoki, Pauli; Mannerkoski, Matias; Nättilä, Joonas; Johansson, Peter H.

2018-05-01

Arcmancer computes geodesics and performs polarized radiative transfer in user-specified spacetimes. The library supports Riemannian and semi-Riemannian spaces of any dimension and metric; it also supports multiple simultaneous coordinate charts, embedded geometric shapes, local coordinate systems, and automatic parallel propagation. Arcmancer can be used to solve various problems in numerical geometry, such as solving the curve equation of motion using adaptive integration with configurable tolerances and differential equations along precomputed curves. It also provides support for curves with an arbitrary acceleration term and generic tools for generating ray initial conditions and performing parallel computation over the image, among other tools.

Validation of an ocean shelf model for the prediction of mixed-layer properties in the Mediterranean Sea west of Sardinia

NASA Astrophysics Data System (ADS)

Onken, Reiner

2017-04-01

The Regional Ocean Modeling System (ROMS) has been employed to explore the sensitivity of the forecast skill of mixed-layer properties to initial conditions, boundary conditions, and vertical mixing parameterisations. The initial and lateral boundary conditions were provided by the Mediterranean Forecasting System (MFS) or by the MERCATOR global ocean circulation model via one-way nesting; the initial conditions were additionally updated through the assimilation of observations. Nowcasts and forecasts from the weather forecast models COSMO-ME and COSMO-IT, partly melded with observations, served as surface boundary conditions. The vertical mixing was parameterised by the GLS (generic length scale) scheme Umlauf and Burchard (2003) in four different set-ups. All ROMS forecasts were validated against the observations which were taken during the REP14-MED survey to the west of Sardinia. Nesting ROMS in MERCATOR and updating the initial conditions through data assimilation provided the best agreement of the predicted mixed-layer properties with the time series from a moored thermistor chain. Further improvement was obtained by the usage of COSMO-ME atmospheric forcing, which was melded with real observations, and by the application of the k-ω vertical mixing scheme with increased vertical eddy diffusivity. The predicted temporal variability of the mixed-layer temperature was reasonably well correlated with the observed variability, while the modelled variability of the mixed-layer depth exhibited only agreement with the observations near the diurnal frequency peak. For the forecasted horizontal variability, reasonable agreement was found with observations from a ScanFish section, but only for the mesoscale wave number band; the observed sub-mesoscale variability was not reproduced by ROMS.

Contemporary generic market in Japan - key conditions to successful evolution.

PubMed

Jakovljevic, Mihajlo B; Nakazono, Sanae; Ogura, Seiritsu

2014-04-01

The Japanese pharmaceutical market, the world's second largest, is traditionally renowned for the domination of patented drugs and the weakest generics share among major established economies. An in-depth observation of published evidence in Japanese/English language provided closer insight into current trends in Japanese domestic legislation and pharmaceutical market development. Recent governmental interventions have resulted in significant expansion of the generic medicines market size. Substantial savings due to generic substitution of patent-protected drugs have already been achieved and are likely to increase in future. Nationwide population aging threatening sustainable healthcare funding is contributing to the relevance of generic policy success. Serious long-term challenges to the modest Japanese generic manufacturing capacities will be posed by foreign pharmaceutical industries particularly the ones based in emerging BRIC economies.

A "Goldilocks" Approach to Hearing Aid Self-Fitting: Ear-Canal Output and Speech Intelligibility Index.

PubMed

Mackersie, Carol; Boothroyd, Arthur; Lithgow, Alexandra

2018-06-11

The objective was to determine self-adjusted output response and speech intelligibility index (SII) in individuals with mild to moderate hearing loss and to measure the effects of prior hearing aid experience. Thirteen hearing aid users and 13 nonusers, with similar group-mean pure-tone thresholds, listened to prerecorded and preprocessed sentences spoken by a man. Starting with a generic level and spectrum, participants adjusted (1) overall level, (2) high-frequency boost, and (3) low-frequency cut. Participants took a speech perception test after an initial adjustment before making a final adjustment. The three self-selected parameters, along with individual thresholds and real-ear-to-coupler differences, were used to compute output levels and SIIs for the starting and two self-adjusted conditions. The values were compared with an NAL second nonlinear threshold-based prescription (NAL-NL2) and, for the hearing aid users, performance of their existing hearing aids. All participants were able to complete the self-adjustment process. The generic starting condition provided outputs (between 2 and 8 kHz) and SIIs that were significantly below those prescribed by NAL-NL2. Both groups increased SII to values that were not significantly different from prescription. The hearing aid users, but not the nonusers, increased high-frequency output and SII significantly after taking the speech perception test. Seventeen of the 26 participants (65%) met an SII criterion of 60% under the generic starting condition. The proportion increased to 23 out of 26 (88%) after the final self-adjustment. Of the 13 hearing aid users, 8 (62%) met the 60% criterion with their existing hearing aids. With the final self-adjustment, 12 out of 13 (92%) met this criterion. The findings support the conclusion that user self-adjustment of basic amplification characteristics can be both feasible and effective with or without prior hearing aid experience.

Equivalence and interchangeability of narrow therapeutic index drugs in organ transplantation

PubMed Central

Johnston, Atholl

2013-01-01

The calcineurin inhibitors (CNIs), ciclosporin and tacrolimus, are the mainstay of immunosuppression in solid organ transplantation. Generic formulations of these drugs are now available. With increasing pressure on healthcare budgets and the consequent need to match health expectations to available resources, substitution with a generic product appears an attractive option to reduce costs. Approval of generic products differs from innovator drugs, and narrow therapeutic index drugs (NTIs; including CNIs) bring their own particular considerations. With NTIs, small variations in drug exposure could result in reduced immunosuppression or drug toxicity with potentially adverse effects on patient outcomes. NTIs are subject to stricter regulatory approval versus many other generic drugs. However, different generic formulations may still not necessarily be therapeutically equivalent in individuals, raising the possibility of significant differences in exposure between products. Although regional recommendations vary, many guidelines emphasise the need for NTI drug substitution to be initiated by the transplant physician, thus ensuring careful therapeutic monitoring and reduced negative patient impact. The need for therapeutic monitoring during generic substitution has important implications for the overall costs of generic treatment as these costs have to be factored in to the potential savings made from using generic formulations. The reduced acquisition costs of generic products may not necessarily translate into lower overall healthcare costs. This article examines the issue of equivalence and interchangeability of NTI drugs used in organ transplantation, the implications of the approval process for generic drugs on treatment efficacy and safety, and the effective management of substitutions between products. PMID:24089632

Patient empowerment: The need to consider it as a measurable patient-reported outcome for chronic conditions

PubMed Central

2012-01-01

Background Health policy in the UK and elsewhere is prioritising patient empowerment and patient evaluations of healthcare. Patient reported outcome measures now take centre-stage in implementing strategies to increase patient empowerment. This article argues for consideration of patient empowerment itself as a directly measurable patient reported outcome for chronic conditions, highlights some issues in adopting this approach, and outlines a research agenda to enable healthcare evaluation on the basis of patient empowerment. Discussion Patient empowerment is not a well-defined construct. A range of condition-specific and generic patient empowerment questionnaires have been developed; each captures a different construct e.g. personal control, self-efficacy/self-mastery, and each is informed by a different implicit or explicit theoretical framework. This makes it currently problematic to conduct comparative evaluations of healthcare services on the basis of patient empowerment. A case study (clinical genetics) is used to (1) illustrate that patient empowerment can be a valued healthcare outcome, even if patients do not obtain health status benefits, (2) provide a rationale for conducting work necessary to tighten up the patient empowerment construct (3) provide an exemplar to inform design of interventions to increase patient empowerment in chronic disease. Such initiatives could be evaluated on the basis of measurable changes in patient empowerment, if the construct were properly operationalised as a patient reported outcome measure. To facilitate this, research is needed to develop an appropriate and widely applicable generic theoretical framework of patient empowerment to inform (re)development of a generic measure. This research should include developing consensus between patients, clinicians and policymakers about the content and boundaries of the construct before operationalisation. This article also considers a number of issues for society and for healthcare providers raised by adopting the patient empowerment paradigm. Summary Healthcare policy is driving the need to consider patient empowerment as a measurable patient outcome from healthcare services. Research is needed to (1) tighten up the construct (2) develop consensus about what is important to include (3) (re)develop a generic measure of patient empowerment for use in evaluating healthcare (4) understand if/how people make trade-offs between empowerment and gain in health status. PMID:22694747

Medication persistence and the use of generic and brand-name blood pressure-lowering agents.

PubMed

Corrao, Giovanni; Soranna, Davide; La Vecchia, Carlo; Catapano, Alberico; Agabiti-Rosei, Enrico; Gensini, Gianfranco; Merlino, Luca; Mancia, Giuseppe

2014-05-01

Because of their lower cost, healthcare systems recommend physicians to prefer generic products, rather than brand-name medicaments. There is then considerable interest and debate concerning safety and effectiveness of generic products. Few studies have compared patients treated with brand-name and generic drugs for adherence to treatment, with somewhat inconsistent results. The primary objective of this study was to compare the risk of discontinuing antihypertensive drug therapy in patients treated with generic or brand-name agents. The 101,618 beneficiaries of the Healthcare system of Lombardy, Italy, aged 18 years or older who were newly treated on monotherapy with antihypertensive generic or brand-name drugs during 2008, were followed until the earliest date among those of the occurrence of treatment discontinuation to whatever antihypertensive drug therapy (outcome), or censoring (death, emigration, 12 months after treatment initiation). Hazard ratios of discontinuation associated with starting on generic or brand-name products (intention-to-treat analysis), and incidence rate ratio of discontinuation during periods on generic and brand-name products (as-treated analysis) were respectively estimated from a cohort and self-controlled case series analyses. Patients who started on generics did not experience a different risk of discontinuation compared with those starting on brand-name agents (hazard ratio: 1.00; 95% confidence interval 0.98-1.02). Discontinuation did not occur with different rates during periods covered by generics or brand-name agents (incidence rate ratio: 1.01; 95% confidence interval 0.96-1.11) within the same individuals. A number of sensitivity and subgroup analyses confirmed the robustness of these findings. Generic products are not responsible for the high rate of discontinuation from antihypertensive drug therapy. Assuming therapeutic equivalence, clinical implication is of prescribing generic drug therapies.

Routes to the past: neural substrates of direct and generative autobiographical memory retrieval.

PubMed

Addis, Donna Rose; Knapp, Katie; Roberts, Reece P; Schacter, Daniel L

2012-02-01

Models of autobiographical memory propose two routes to retrieval depending on cue specificity. When available cues are specific and personally-relevant, a memory can be directly accessed. However, when available cues are generic, one must engage a generative retrieval process to produce more specific cues to successfully access a relevant memory. The current study sought to characterize the neural bases of these retrieval processes. During functional magnetic resonance imaging (fMRI), participants were shown personally-relevant cues to elicit direct retrieval, or generic cues (nouns) to elicit generative retrieval. We used spatiotemporal partial least squares to characterize the spatial and temporal characteristics of the networks associated with direct and generative retrieval. Both retrieval tasks engaged regions comprising the autobiographical retrieval network, including hippocampus, and medial prefrontal and parietal cortices. However, some key neural differences emerged. Generative retrieval differentially recruited lateral prefrontal and temporal regions early on during the retrieval process, likely supporting the strategic search operations and initial recovery of generic autobiographical information. However, many regions were activated more strongly during direct versus generative retrieval, even when we time-locked the analysis to the successful recovery of events in both conditions. This result suggests that there may be fundamental differences between memories that are accessed directly and those that are recovered via the iterative search and retrieval process that characterizes generative retrieval. Copyright © 2011 Elsevier Inc. All rights reserved.

Routes to the past: Neural substrates of direct and generative autobiographical memory retrieval

PubMed Central

Addis, Donna Rose; Knapp, Katie; Roberts, Reece P.; Schacter, Daniel L.

2011-01-01

Models of autobiographical memory propose two routes to retrieval depending on cue specificity. When available cues are specific and personally-relevant, a memory can be directly accessed. However, when available cues are generic, one must engage a generative retrieval process to produce more specific cues to successfully access a relevant memory. The current study sought to characterize the neural bases of these retrieval processes. During functional magnetic resonance imaging (fMRI), participants were shown personally-relevant cues to elicit direct retrieval, or generic cues (nouns) to elicit generative retrieval. We used spatiotemporal partial least squares to characterize the spatial and temporal characteristics of the networks associated with direct and generative retrieval. Both retrieval tasks engaged regions comprising the autobiographical retrieval network, including hippocampus, and medial prefrontal and parietal cortices. However, some key neural differences emerged. Generative retrieval differentially recruited lateral prefrontal and temporal regions early on during the retrieval process, likely supporting the strategic search operations and initial recovery of generic autobiographical information. However, many regions were activated more strongly during direct versus generative retrieval, even when we time-locked the analysis to the successful recovery of events in both conditions. This result suggests that there may be fundamental differences between memories that are accessed directly and those that are recovered via the iterative search and retrieval process that characterizes generative retrieval. PMID:22001264

A Systematic Review of Physicians' and Pharmacists' Perspectives on Generic Drug Use: What are the Global Challenges?

PubMed

Toverud, Else-Lydia; Hartmann, Katrin; Håkonsen, Helle

2015-08-01

Generic substitution has been introduced in most countries in order to reduce costs and improve access to drugs. However, regulations and the generic drugs available vary between countries. It is the prescriber or dispenser of the drug who is the final decision maker. Nevertheless, physicians' and pharmacists' perceptions of generic drug use are not well documented to date. This study presents a systematic review of physicians' and pharmacists' perspectives on generic drug use worldwide. A systematic literature search was performed to retrieve all articles published between 2002 and 2012 regarding physicians' and/or pharmacists' experiences with generic drugs and generic substitution. Of 1322 publications initially identified, 24 were eligible for inclusion. Overall, the studies revealed that physicians and pharmacists were aware of the cost-saving function of generic drugs and their role in improving global access to drugs. Nevertheless, marked differences were observed between countries when studying physicians' and pharmacists' perceptions of the available generic drugs. In less mature healthcare systems, large variations regarding, for example, control routines, bioequivalence requirements, and manufacturer standards were reported. A lack of reliable information and mistrust in the efficacy and quality were also mentioned by these participants. In the most developed healthcare systems, the participants trusted the quality of the generic drugs and did not hesitate to offer them to all patients regardless of socioeconomic status. In general, pharmacists seemed to have better knowledge of the concept of bioequivalence and generic drug aspects than physicians. The present study indicates that physicians and pharmacists are aware of the role of generic drugs in the improvement of global access to drugs. However, there are marked differences regarding how these health professionals view the quality of generic drugs depending on the maturity of their country's healthcare system. This can be attributed to the fact that developed healthcare systems have more reliable public control routines for drugs in general as well as better bioequivalence requirements concerning generics in particular.

The development of an advanced generic solar dynamic heat receiver thermal model

NASA Technical Reports Server (NTRS)

Wu, Y. C.; Roschke, E. J.; Kohout, L.

1988-01-01

An advanced generic solar dynamic heat receiver thermal model under development which can analyze both orbital transient and orbital average conditions is discussed. This model can be used to study advanced receiver concepts, evaluate receiver concepts under development, analyze receiver thermal characteristics under various operational conditions, and evaluate solar dynamic system thermal performances in various orbit conditions. The model and the basic considerations that led to its creation are described, and results based on a set of baseline orbit, configuration, and operational conditions are presented to demonstrate the working of the receiver model.

A generic multibody simulation

NASA Technical Reports Server (NTRS)

Hopping, K. A.; Kohn, W.

1986-01-01

Described is a dynamic simulation package which can be configured for orbital test scenarios involving multiple bodies. The rotational and translational state integration methods are selectable for each individual body and may be changed during a run if necessary. Characteristics of the bodies are determined by assigning components consisting of mass properties, forces, and moments, which are the outputs of user-defined environmental models. Generic model implementation is facilitated by a transformation processor which performs coordinate frame inversions. Transformations are defined in the initialization file as part of the simulation configuration. The simulation package includes an initialization processor, which consists of a command line preprocessor, a general purpose grammar, and a syntax scanner. These permit specifications of the bodies, their interrelationships, and their initial states in a format that is not dependent on a particular test scenario.

Multimodal analysis of pretreated biomass species highlights generic markers of lignocellulose recalcitrance.

PubMed

Herbaut, Mickaël; Zoghlami, Aya; Habrant, Anouck; Falourd, Xavier; Foucat, Loïc; Chabbert, Brigitte; Paës, Gabriel

2018-01-01

Biomass recalcitrance to enzymatic hydrolysis has been assigned to several structural and chemical factors. However, their relative importance remains challenging to evaluate. Three representative biomass species (wheat straw, poplar and miscanthus) were submitted to four standard pretreatments (dilute acid, hot water, ionic liquid and sodium chlorite) in order to generate a set of contrasted samples. A large array of techniques, including wet chemistry analysis, porosity measurements using NMR spectroscopy, electron and fluorescence microscopy, were used in order to determine possible generic factors of biomass recalcitrance. The pretreatment conditions selected allowed obtaining samples displaying different susceptibility to enzymatic hydrolysis (from 3 up to 98% of the initial glucose content released after 96 h of saccharification). Generic correlation coefficients were calculated between the measured chemical and structural features and the final saccharification rates. Increases in porosity displayed overall strong positive correlations with saccharification efficiency, but different porosity ranges were concerned depending on the considered biomass. Lignin-related factors displayed highly negative coefficients for all biomasses. Lignin content, which is likely involved in the correlations observed for porosity, was less detrimental to enzymatic hydrolysis than lignin composition. Lignin influence was highlighted by the strong negative correlation with fluorescence intensity which mainly originates from monolignols in mature tissues. Our results provide a better understanding of the factors responsible for biomass recalcitrance that can reasonably be considered as generic. The correlations with specific porosity ranges are biomass species-dependent, meaning that enzymes cocktails with fitted enzyme size are likely to be needed to optimise saccharification depending on the biomass origin. Lignin composition, which probably influences its structure, is the most important parameter to overcome to enhance enzymes access to the polysaccharides. Accordingly, fluorescence intensity was found to be a rapid and simple method to assess recalcitrance after pretreatment.

Motion of discrete solitons assisted by nonlinearity management.

PubMed

Cuevas, Jesús; Malomed, Boris A; Kevrekidis, P G

2005-06-01

We demonstrate that time-periodic modulation of the nonlinearity coefficient in the discrete nonlinear Schrödinger equation strongly facilitates creation of traveling solitons in the lattice. We predict this possibility in a semi-qualitative form analytically, and test it in direct numerical simulations. Systematic computations reveal several generic dynamical regimes, depending on the amplitude and frequency of the time modulation, and on the initial thrust which sets the soliton in motion. These regimes include irregular motion of the soliton, regular motion of a decaying one, and regular motion of a stable soliton. The motion may occur in both the straight and reverse directions, relative to the initial thrust. In the case of stable motion, extremely long simulations in a lattice with periodic boundary conditions demonstrate that the soliton keeps moving indefinitely long without any visible loss. Velocities of moving stable solitons are in good agreement with the analytical prediction, which is based on requiring a resonance between the ac drive and motion of the soliton through the periodic lattice. The generic dynamical regimes are mapped in the model's parameter space. Collisions between moving stable solitons are briefly investigated too, with a conclusion that two different outcomes are possible: elastic bounce, or bounce with mass transfer from one soliton to the other. The model can be realized experimentally in a Bose-Einstein condensate trapped in a deep optical lattice.

Creating a Culture of Thinking in DCPS: A Generic Proposal for the District of Columbia Public Schools Board of Education

ERIC Educational Resources Information Center

Fluellen, Jerry E., Jr.

2006-01-01

Preparing students for college and work in the Knowledge Age. That is the mission of this generic proposal. A counterpoint to Industrial Age mindsets marking most initiatives in the District of Columbia Public schools and described in the "fifth discipline" works of Peter Senge, Creating a Culture of Thinking in DCPS proposes a project…

Technology to Enhance Mathematics and Science Instruction: Changes in Teacher Perceptions after Participating in a Yearlong Professional Development Program

ERIC Educational Resources Information Center

Kersaint, Gladis; Ritzhaupt, Albert D.; Liu, Feng

2014-01-01

The purpose of this study is to examine the extent to which teachers of mathematics or science who were engaged in a year-long initiative to help them integrate technological tools were (a) familiar with generic and mathematics- or science-specific technology, (b) comfortable integrating generic and content-specific technology, (c) believe that…

10 CFR 50.54 - Conditions of licenses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... to the licensee's facility; (iii) The use of generic organizational position titles that clearly...; (iv) The use of generic organizational charts to indicate functional relationships, authorities, and... which the licensee is committed; and (vi) Organizational revisions that ensure that persons and...

Evaluation of the clinical and economic impact of a brand name-to-generic warfarin sodium conversion program.

PubMed

Witt, Daniel M; Tillman, Donald J; Evans, Christy M; Plotkin, Tatyana V; Sadler, Melanie A

2003-03-01

Substitution of generic warfarin initially was discouraged because of concerns regarding therapeutic failure or toxicity. Although subsequent research with AB-rated (i.e., bioequivalent) warfarin did not confirm initial concerns, the issue is not settled for all clinicians. We sought to provide additional information regarding the clinical and economic impact of warfarin conversion by analyzing a real-life sample of patients receiving long-term anticoagulation therapy who were switched from brand name to generic warfarin. Patients who had been taking warfarin for at least 180 days and had received uninterrupted oral anticoagulation 90 days before and 90 days after switching to generic warfarin were included. The switch date was based on the first time generic warfarin was dispensed from our pharmacies. The primary end point was the calculated amount of time each patient's international normalized ratio (INR) values were within the patient-specific target INR range in the 90 days before and after the switch. Data regarding adverse events and medical resource utilization were also collected. Pharmacoeconomic analyses were performed. The analysis included 2299 patients. The overall difference in calculated time INR values were below (22.6% before vs 26.1% after switch, p<0.0001) and within (65.9% before vs 63.3% after switch, p=0.0002) the therapeutic INR range was statistically but not clinically significant. Only 28.0% of patients experienced a change in therapeutic INR control of 10% or less, 33.1% experienced INR control that improved by greater than 10%, and 38.9% experienced INR control that worsened by more than 10%. The difference in total treatment costs associated with brand name and generic warfarin was 3128 dollars/100 patient-years in favor of the generic product. Sensitivity analyses revealed that cost savings associated with warfarin conversion in this health care system were highly dependent on the difference between warfarin costs and cost of treating anticoagulation-related adverse events. Most of these patients were successfully switched from brand name to generic warfarin. However, supplemental INR monitoring is warranted when one warfarin product is substituted for another to allow timely detection of those patients who experience significant changes in anticoagulation response.

Encouraging the use of generic medicines: implications for transition economies.

PubMed

King, Derek R; Kanavos, Panos

2002-08-01

Generic drugs have a key role to play in the efficient allocation of financial resources for pharmaceutical medicines. Policies implemented in the countries with a high rate of generic drug use, such as Canada, Denmark, Germany, the Netherlands, the United Kingdom, and the United States, are reviewed, with consideration of the market structures that facilitate strong competition. Savings in these countries are realized through increases in the volume of generic drugs used and the frequently significant differences in the price between generic medicines and branded originator medicines. Their policy tools include the mix of supply-side measures and demand-side measures that are relevant for generic promotion and higher generic use. On the supply-side, key policy measures include generic drug marketing regulation that facilitates market entry soon after patent expiration, reference pricing, the pricing of branded originator products, and the degree of price competition in pharmaceutical markets. On the demand-side, measures typically encompass influencing prescribing and dispensing patterns as well as introducing a co-payment structure for consumers/patients that takes into consideration the difference in cost between branded and generic medicines. Quality of generic medicines is a pre-condition for all other measures discussed to take effect. The paper concludes by offering a list of policy options for decision-makers in Central and Eastern European economies in transition.

Generic Medicine Pricing Policies in Europe: Current Status and Impact

PubMed Central

Dylst, Pieter; Simoens, Steven

2010-01-01

Generic medicine pricing is an area of national responsibility of European Union countries. This article aims to present the current status and impact of generic medicine pricing policies in ambulatory care in Europe. The study conducts a literature review of policies relating to free-pricing systems, price-regulated systems, price differentiation, price competition and discounts, and tendering procedures; and a survey of European generic medicine pricing policies. Competition from Indian generic medicine manufacturers, European variation in generic medicine prices and competition between generic medicine manufacturers by discount suggest that the potential savings to health care payers and patients from generic medicines are not fully realized in Europe. One way of attaining these savings may be to move away from competition by discount to competition by price. Free-pricing systems may drive medicine prices downwards under specific conditions. In price-regulated systems, regulation may lower prices of originator and generic medicines, but may also remove incentives for additional price reductions beyond those imposed by regulation. To date, little is known about the current status and impact of tendering procedures for medicines in ambulatory care. In conclusion, the European experience suggests that there is not a single approach towards developing generic medicine pricing policies in Europe. PMID:27713264

Comparison between utility of the Thai Pediatric Quality of Life Inventory 4.0 Generic Core Scales and 3.0 Cerebral Palsy Module.

PubMed

Tantilipikorn, Pinailug; Watter, Pauline; Prasertsukdee, Saipin

2013-03-01

Health-related quality of life (HRQOL) is increasingly being considered in the management of patients with various conditions. HRQOL instruments can be broadly classified as generic or disease-specific measures. Several generic HRQOL instruments in different languages have been developed for paediatric populations including the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) Generic Core Scale. This tool and a condition-specific tool, PedsQL 3.0 Cerebral Palsy (CP) Module, are widely used in children with CP. No psychometric properties have been reported for Thai PedsQL 4.0. Therefore, this study aimed to explore the psychometric properties of the Thai version of the PedsQL 4.0 Generic Core Scales and compare these with the values for the Thai PedsQL 3.0 CP Module reported previously. Thai PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 CP Module were completed, respectively, by children with CP and their parents or caregivers twice within 2-4 weeks. Respondents were 97 parents or caregivers and 54 children. Minimal missing data were found in most scales. Acceptable internal consistency was supported, except for Emotional, Social, and School Functioning. Intraclass correlation coefficients for parent-proxy report and self-report were good to excellent (0.625-0.849). The feasibility and reliability of the Thai PedsQL 4.0 Generic Core Scales were supported. The Thai PedsQL 3.0 CP Module showed higher values for the psychometric properties. Low-to-good correlations were found among the scales between the PedsQL 4.0 Generic Core Scales and the 3.0 CP Module. Both instruments could be used to measure HRQOL for children with CP, and may provide different information.

Automated startup of the MIT research reactor

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

Kwok, K.S.

1992-01-01

This summary describes the development, implementation, and testing of a generic method for performing automated startups of nuclear reactors described by space-independent kinetics under conditions of closed-loop digital control. The technique entails first obtaining a reliable estimate of the reactor's initial degree of subcriticality and then substituting that estimate into a model-based control law so as to permit a power increase from subcritical on a demanded trajectory. The estimation of subcriticality is accomplished by application of the perturbed reactivity method. The shutdown reactor is perturbed by the insertion of reactivity at a known rate. Observation of the resulting period permitsmore » determination of the initial degree of subcriticality. A major advantage to this method is that repeated estimates are obtained of the same quantity. Hence, statistical methods can be applied to improve the quality of the calculation.« less

Geomechanical/Geochemical Modeling Studies Conducted within theInternational DECOVALEX Project

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

Birkholzer, J.T.; Rutqvist, J.; Sonnenthal, E.L.

2005-10-19

The DECOVALEX project is an international cooperative project initiated by SKI, the Swedish Nuclear Power Inspectorate, with participation of about 10 international organizations. The general goal of this project is to encourage multidisciplinary interactive and cooperative research on modeling coupled thermo-hydro-mechanical-chemical (THMC) processes in geologic formations in support of the performance assessment for underground storage of radioactive waste. One of the research tasks, initiated in 2004 by the U.S. Department of Energy (DOE), addresses the long-term impact of geomechanical and geochemical processes on the flow conditions near waste emplacement tunnels. Within this task, four international research teams conduct predictive analysismore » of the coupled processes in two generic repositories, using multiple approaches and different computer codes. Below, we give an overview of the research task and report its current status.« less

Geomechanical/ Geochemical Modeling Studies onducted Within the International DECOVALEX Project

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

J.T. Birkholzer; J. Rutqvist; E.L. Sonnenthal

2006-02-01

The DECOVALEX project is an international cooperative project initiated by SKI, the Swedish Nuclear Power Inspectorate, with participation of about 10 international organizations. The general goal of this project is to encourage multidisciplinary interactive and cooperative research on modeling coupled thermo-hydro-mechanical-chemical (THMC) processes in geologic formations in support of the performance assessment for underground storage of radioactive waste. One of the research tasks, initiated in 2004 by the U.S. Department of Energy (DOE), addresses the long-term impact of geomechanical and geochemical processes on the flow conditions near waste emplacement tunnels. Within this task, four international research teams conduct predictive analysismore » of the coupled processes in two generic repositories, using multiple approaches and different computer codes. Below, we give an overview of the research task and report its current status.« less

Role of angular momentum and cosmic censorship in (2+1)-dimensional rotating shell collapse

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

Mann, Robert B.; Oh, John J.; Park, Mu-In

2009-03-15

We study the gravitational collapse problem of rotating shells in three-dimensional Einstein gravity with and without a cosmological constant. Taking the exterior and interior metrics to be those of stationary metrics with asymptotically constant curvature, we solve the equations of motion for the shells from the Darmois-Israel junction conditions in the corotating frame. We study various collapse scenarios with arbitrary angular momentum for a variety of geometric configurations, including anti-de Sitter, de Sitter, and flat spaces. We find that the collapsing shells can form a BTZ black hole, a three-dimensional Kerr-dS spacetime, and an horizonless geometry of point masses undermore » certain initial conditions. For pressureless dust shells, the curvature singularity is not formed due to the angular momentum barrier near the origin. However when the shell pressure is nonvanishing, we find that for all types of shells with polytropic-type equations of state (including the perfect fluid and the generalized Chaplygin gas), collapse to a naked singularity is possible under generic initial conditions. We conclude that in three dimensions angular momentum does not in general guard against violation of cosmic censorship.« less

Two-rowed Hecke algebra representations at roots of unity

NASA Astrophysics Data System (ADS)

Welsh, Trevor Alan

1996-02-01

In this paper, we initiate a study into the explicit construction of irreducible representations of the Hecke algebraH n (q) of typeA n-1 in the non-generic case whereq is a root of unity. The approach is via the Specht modules ofH n (q) which are irreducible in the generic case, and possess a natural basis indexed by Young tableaux. The general framework in which the irreducible non-genericH n (q)-modules are to be constructed is set up and, in particular, the full set of modules corresponding to two-part partitions is described. Plentiful examples are given.

Power-on performance predictions for a complete generic hypersonic vehicle configuration

NASA Technical Reports Server (NTRS)

Bennett, Bradford C.

1991-01-01

The Compressible Navier-Stokes (CNS) code was developed to compute external hypersonic flow fields. It has been applied to various hypersonic external flow applications. Here, the CNS code was modified to compute hypersonic internal flow fields. Calculations were performed on a Mach 18 sidewall compression inlet and on the Lewis Mach 5 inlet. The use of the ARC3D diagonal algorithm was evaluated for internal flows on the Mach 5 inlet flow. The initial modifications to the CNS code involved generalization of the boundary conditions and the addition of viscous terms in the second crossflow direction and modifications to the Baldwin-Lomax turbulence model for corner flows.

Back from the Future: The Impact of Change on Airpower in the Decades Ahead

DTIC Science & Technology

2009-01-01

generic/story_generic.jsp?channel= awst &id=news/aw021108p2.xml&headline=Fate%20of%20F -22,%20C-17%20Lines%20Uncertain%20in%20Fiscal%202009; Pierre Sprey...second lot of low-rate initial production aircraft was announced on 22 May 2008 as $2.2 billion for 12 aircraft, and Maj Gen Charles R . Davis, USAF, the

Can authorities appreciably enhance the prescribing of oral generic risperidone to conserve resources? Findings from across Europe and their implications.

PubMed

Godman, Brian; Petzold, Max; Bennett, Kathleen; Bennie, Marion; Bucsics, Anna; Finlayson, Alexander E; Martin, Andrew; Persson, Marie; Piessnegger, Jutta; Raschi, Emanuel; Simoens, Steven; Zara, Corinne; Barbui, Corrado

2014-06-13

Generic atypical antipsychotic drugs offer health authorities opportunities for considerable savings. However, schizophrenia and bipolar disorders are complex diseases that require tailored treatments. Consequently, generally there have been limited demand-side measures by health authorities to encourage the preferential prescribing of generics. This is unlike the situation with hypertension, hypercholaesterolaemia or acid-related stomach disorders.The objectives of this study were to compare the effect of the limited demand-side measures in Western European countries and regions on the subsequent prescribing of risperidone following generics; to utilise the findings to provide future guidance to health authorities; and where possible, to investigate the utilisation of generic versus originator risperidone and the prices for generic risperidone. Principally, this was a segmented regression analysis of retrospective time-series data of the effect of the various initiatives in Belgium, Ireland, Scotland and Sweden following the introduction of generic risperidone. The study included patients prescribed at least one atypical antipsychotic drug up to 20 months before and up to 20 months after generic risperidone. In addition, retrospective observational studies were carried out in Austria and Spain (Catalonia) from 2005 to 2011 as well as one English primary care organisation (Bury Primary Care Trust (PCT)). There was a consistent steady reduction in risperidone as a percentage of total selected atypical antipsychotic utilisation following generics. A similar pattern was seen in Austria and Spain, with stable utilisation in one English PCT. However, there was considerable variation in the utilisation of generic risperidone, ranging from 98% of total risperidone in Scotland to only 14% in Ireland. Similarly, the price of generic risperidone varied considerably. In Scotland, generic risperidone was only 16% of pre-patent loss prices versus 72% in Ireland. Consistent findings of no increased prescribing of risperidone post generics with limited specific demand-side measures suggests no 'spillover' effect from one class to another encouraging the preferential prescribing of generic atypical antipsychotic drugs. This is exacerbated by the complexity of the disease area and differences in the side-effects between treatments. There appeared to be no clinical issues with generic risperidone, and prices inversely reflected measures to enhance their utilisation.

Evaluation of the cooperative multi-carrier delivery initiatives.

DOT National Transportation Integrated Search

2013-12-01

In the last several years there has been a surge of interest in fostering more sustainable logistical operations in : urban areas. Under the umbrella of the generic term City Logistics, these initiatives try to take advantage of : the coordinating po...

Establishing "abuse-deterrence equivalence" for generic abuse-deterrent opioid formulations: A proposed development framework.

PubMed

Setnik, Beatrice; Cone, Edward J

2016-01-01

Abuse-deterrent formulations are one strategy for mitigating the epidemic of prescription opioid abuse. Regulatory guidance documents describe the requirements for developing abuse-deterrent formulations of novel drugs and formulations; however, they do not address "abuse-deterrence equivalence" for generic formulations. As generics may be produced with different excipients and formulations compared to reference drugs, differences in their properties may impact their abuse-deterrent features. Currently, it is unclear what specific studies are needed to support generic abuse-deterrence claims. This commentary outlines several recommendations on the in vitro and in vivo testing required, including the conditions for conducting a human abuse potential study.

Explaining parent-child (dis)agreement in generic and short stature-specific health-related quality of life reports: do family and social relationships matter?

PubMed

Quitmann, Julia; Rohenkohl, Anja; Sommer, Rachel; Bullinger, Monika; Silva, Neuza

2016-10-21

In the context of health-related quality of life (HrQoL) assessment in pediatric short stature, the present study aimed to examine the levels of agreement/disagreement between parents' and children's reports of generic and condition-specific HrQoL, and to identify socio-demographic, clinical and psychosocial variables associated with the extent and direction of parent-child discrepancies. This study was part of the retest phase of the QoLISSY project, which was a multicenter study conducted simultaneously in France, Germany, Spain, Sweden and UK. The sample comprised 137 dyads of children/adolescents between 8 and 18 years of age, diagnosed with growth hormone deficiency (GHD) or idiopathic short stature (ISS), and one of their parents. The participants completed child- and parent-reported questionnaires on generic (KIDSCREEN-10 Index) and condition-specific HrQoL (QoLISSY Core Module). Children/adolescents also reported on social support (Oslo 3-items Social Support Scale) and parents assessed the parent-child relationships (Parental Role subscale of the Social Adjustment Scale) and burden of short stature on parents (QoLISSY- additional module). The parent-child agreement on reported HrQoL was strong (intraclass correlation coefficients between .59 and .80). The rates of parent-child discrepancies were 61.5 % for generic and 35.2 % for condition-specific HrQoL, with the parents being more prone to report lower generic (42.3 %) and condition-specific HrQoL (23.7 %) than their children. The extent of discrepancies was better explained by family and social relationships than by clinical and socio-demographic variables: poorer parent-child relationships and better children's social support were associated with larger discrepancies in generic HrQoL, while more parental burden was associated with larger discrepancies in condition-specific HrQoL reports. Regarding the direction of discrepancies, higher parental burden was significantly associated with parents' underrating, and better children's social support was significantly associated with parents' overrating of condition-specific HrQoL. Routine assessment of pediatric HrQoL in healthcare and research contexts should include child- and parent-reported data as complementary sources of information, and also consider the family and social context.

Generalized quantum theory of recollapsing homogeneous cosmologies

NASA Astrophysics Data System (ADS)

Craig, David; Hartle, James B.

2004-06-01

A sum-over-histories generalized quantum theory is developed for homogeneous minisuperspace type A Bianchi cosmological models, focusing on the particular example of the classically recollapsing Bianchi type-IX universe. The decoherence functional for such universes is exhibited. We show how the probabilities of decoherent sets of alternative, coarse-grained histories of these model universes can be calculated. We consider in particular the probabilities for classical evolution defined by a suitable coarse graining. For a restricted class of initial conditions and coarse grainings we exhibit the approximate decoherence of alternative histories in which the universe behaves classically and those in which it does not. For these situations we show that the probability is near unity for the universe to recontract classically if it expands classically. We also determine the relative probabilities of quasiclassical trajectories for initial states of WKB form, recovering for such states a precise form of the familiar heuristic “JṡdΣ” rule of quantum cosmology, as well as a generalization of this rule to generic initial states.

What is an integrable quench?

NASA Astrophysics Data System (ADS)

Piroli, Lorenzo; Pozsgay, Balázs; Vernier, Eric

2017-12-01

Inspired by classical results in integrable boundary quantum field theory, we propose a definition of integrable initial states for quantum quenches in lattice models. They are defined as the states which are annihilated by all local conserved charges that are odd under space reflection. We show that this class includes the states which can be related to integrable boundary conditions in an appropriate rotated channel, in loose analogy with the picture in quantum field theory. Furthermore, we provide an efficient method to test integrability of given initial states. We revisit the recent literature of global quenches in several models and show that, in all of the cases where closed-form analytical results could be obtained, the initial state is integrable according to our definition. In the prototypical example of the XXZ spin-s chains we show that integrable states include two-site product states but also larger families of matrix product states with arbitrary bond dimension. We argue that our results could be practically useful for the study of quantum quenches in generic integrable models.

Nonsingular cosmology with a scale-invariant spectrum of cosmological perturbations from Lee-Wick theory

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

Cai Yifu; Qiu Taotao; Brandenberger, Robert

2009-07-15

We study the cosmology of a Lee-Wick type scalar field theory. First, we consider homogeneous and isotropic background solutions and find that they are nonsingular, leading to cosmological bounces. Next, we analyze the spectrum of cosmological perturbations which result from this model. Unless either the potential of the Lee-Wick theory or the initial conditions are finely tuned, it is impossible to obtain background solutions which have a sufficiently long period of inflation after the bounce. More interestingly, however, we find that in the generic noninflationary bouncing cosmology, perturbations created from quantum vacuum fluctuations in the contracting phase have the correctmore » form to lead to a scale-invariant spectrum of metric inhomogeneities in the expanding phase. Since the background is nonsingular, the evolution of the fluctuations is defined unambiguously through the bounce. We also analyze the evolution of fluctuations which emerge from thermal initial conditions in the contracting phase. The spectrum of gravitational waves stemming from quantum vacuum fluctuations in the contracting phase is also scale-invariant, and the tensor to scalar ratio is not suppressed.« less

Droplet formation and scaling in dense suspensions

PubMed Central

Miskin, Marc Z.; Jaeger, Heinrich M.

2012-01-01

When a dense suspension is squeezed from a nozzle, droplet detachment can occur similar to that of pure liquids. While in pure liquids the process of droplet detachment is well characterized through self-similar profiles and known scaling laws, we show here the simple presence of particles causes suspensions to break up in a new fashion. Using high-speed imaging, we find that detachment of a suspension drop is described by a power law; specifically we find the neck minimum radius, rm, scales like near breakup at time τ = 0. We demonstrate data collapse in a variety of particle/liquid combinations, packing fractions, solvent viscosities, and initial conditions. We argue that this scaling is a consequence of particles deforming the neck surface, thereby creating a pressure that is balanced by inertia, and show how it emerges from topological constraints that relate particle configurations with macroscopic Gaussian curvature. This new type of scaling, uniquely enforced by geometry and regulated by the particles, displays memory of its initial conditions, fails to be self-similar, and has implications for the pressure given at generic suspension interfaces. PMID:22392979

Employability for Music Graduates: Malaysian Educational Reform and the Focus on Generic Skills

ERIC Educational Resources Information Center

Ghazali, Ghaziah; Bennett, Dawn

2017-01-01

In Malaysia, the demand for employable higher education graduates has resulted in a national strategy that outlines desirable graduate attributes including "hard," discipline-specific skills and "soft," generic skills. As a result, music programs are under pressure to become more relevant to the conditions and characteristics…

Asymmetric bubble collapse

NASA Astrophysics Data System (ADS)

Lai, Lipeng; Turitsyn, Konstantin S.; Zhang, Wendy W.

2008-11-01

Recent studies reveal that an inertial implosion, analogous to the collapse of a large cavity in water, governs how a submerged air bubble disconnects from a nozzle. For the bubble, slight asymmetries in the initial neck shape give rise to vibrations that grow pronounced over time. These results motivate our study of the final stage of asymmetric cavity collapse. We are particularly interested in the generic situation where the initial condition is sufficiently well-focused that a cavity can implode inwards energetically. Yet, because the initial condition is not perfectly symmetric, the implosion fails to condense all the energy. We consider cavity shapes in the slender-body limit, for which the collapse dynamics is quasi two-dimensional. In this limit, each cross-section of the cavity evolves as if it were a distorted void immersed in an inviscid and irrotational fluid. Simulations of a circular void distorted by an elongation-compression vibrational mode reveal that a variety of outcomes are possible in the 2D problem. Opposing sides of the void surface can curve inwards and contact smoothly in a finite amount of time. Depending on the phase of the vibration excited, the contact can be either north-south or east-west. Phase values that lie in the transition zone from one orientation to the other give rise to final shapes with large lengthscale separation. We show also that the final outcome varies non-monotonically with the initial amplitude of the vibrational mode.

Comparing Generic Drug Markets in Europe and the United States: Prices, Volumes, and Spending.

PubMed

Wouters, Olivier J; Kanavos, Panos G; McKEE, Martin

2017-09-01

Policy Points: Our study indicates that there are opportunities for cost savings in generic drug markets in Europe and the United States. Regulators should make it easier for generic drugs to reach the market. Regulators and payers should apply measures to stimulate price competition among generic drugmakers and to increase generic drug use. To meaningfully evaluate policy options, it is important to analyze historical context and understand why similar initiatives failed previously. Rising drug prices are putting pressure on health care budgets. Policymakers are assessing how they can save money through generic drugs. We compared generic drug prices and market shares in 13 European countries, using data from 2013, to assess the amount of variation that exists between countries. To place these results in context, we reviewed evidence from recent studies on the prices and use of generics in Europe and the United States. We also surveyed peer-reviewed studies, gray literature, and books published since 2000 to (1) outline existing generic drug policies in European countries and the United States; (2) identify ways to increase generic drug use and to promote price competition among generic drug companies; and (3) explore barriers to implementing reform of generic drug policies, using a historical example from the United States as a case study. The prices and market shares of generics vary widely across Europe. For example, prices charged by manufacturers in Switzerland are, on average, more than 2.5 times those in Germany and more than 6 times those in the United Kingdom, based on the results of a commonly used price index. The proportion of prescriptions filled with generics ranges from 17% in Switzerland to 83% in the United Kingdom. By comparison, the United States has historically had low generic drug prices and high rates of generic drug use (84% in 2013), but has in recent years experienced sharp price increases for some off-patent products. There are policy solutions to address issues in Europe and the United States, such as streamlining the generic drug approval process and requiring generic prescribing and substitution where such policies are not yet in place. The history of substitution laws in the United States provides insights into the economic, political, and cultural issues influencing the adoption of generic drug policies. Governments should apply coherent supply- and demand-side policies in generic drug markets. An immediate priority is to convince more physicians, pharmacists, and patients that generic drugs are bioequivalent to branded products. Special-interest groups continue to obstruct reform in Europe and the United States. © 2017 The Authors The Milbank Quarterly published by Wiley Periodicals, Inc. on behalf of The Millbank Memorial Fund.

Retailing policies for generic medicines.

PubMed

Narciso, Susana

2005-06-01

As there is general disagreement about the way generic medicines should be commercialized, two retailing policies are analyzed, taking into account their effects on the welfare of patients, government, pharmacies and physicians. In the first policy scenario, pharmacies are allowed to substitute generic medicines for branded ones, while in the second, substitution is forbidden. In both cases a pharmacies association is allowed to have a share in the production of generic medicines. The model predicts that under some conditions patients may prefer substitution by pharmacies but when doctors' decisions are binding, they are never "excessively bad". However, the policy choice belongs to the government, which prefers to allow for substitution more often than patients would like.

Helical vortices: Quasiequilibrium states and their time evolution

NASA Astrophysics Data System (ADS)

Selçuk, Can; Delbende, Ivan; Rossi, Maurice

2017-08-01

The time evolution of a viscous helical vortex is investigated by direct numerical simulations of the Navier-Stokes equations where helical symmetry is enforced. Using conservation laws in the framework of helical symmetry, we elaborate an initial condition consisting in a finite core vortex, the time evolution of which leads to a generic quasiequilibrium state independent of the initial core size. Numerical results at different helical pitch values provide an accurate characterization in time for such helical states, for which specific techniques have been introduced: helix radius, angular velocity, stream function-velocity-vorticity relationships, and core properties (size, self-similarity, and ellipticity). Viscosity is shown to be at the origin of a small helical velocity component, which we relate to the helical vorticity component. Finally, changes in time of the flow topology are studied using the helical stream function and three-dimensional Lagrangian orbits.

Burnishing of rotatory parts to improve surface quality

NASA Astrophysics Data System (ADS)

Celaya, A.; López de Lacalle, L. N.; Albizuri, J.; Alberdi, R.

2009-11-01

In this paper, the use of rolling burnishing process to improve the final quality of railway and automotive workpieces is studied. The results are focused on the improvement of the manufacturing processes of rotary workpieces used in railway and automotion industry, attending to generic target of achieving `maximum surface quality with minimal process time'. Burnishing is a finishing operation in which plastic deformation of surface irregularities occurs by applying pressure through a very hard element, a roller or a ceramic ball. This process gives additional advantages to the workpiece such as good surface roughness, increased hardness and high compressive residual stresses. The effect of the initial turning conditions on the final burnishing operation has also been studied. The results show that feeds used in the initial rough turning have little influence in the surface finish of the burnished workpieces. So, the process times of the combined turning and burnishing processes can be reduced, optimizing the shaft's machining process.

The recommendation of line-balancing improvement on MCM product line 1 using genetics algorithm and moodie young at XYZ Company, Co.

NASA Astrophysics Data System (ADS)

Sriwana, I. K.; Marie, I. A.; Mangala, D.

2017-12-01

Kencana Gemilang, Co. is one electronics industry engaging in the manufacture sector. This company manufactures and assembles household electronic products, such as rice cooker, fan, iron, blender, etc. The company deals with an issue of underachievement of an established production target on MCM products line 1. This study aimed to calculate line efficiencies, delay times, and initial line smoothness indexes. The research was carried out by means of depicting a precedence diagram and gathering time data of each work element followed by examination and calculation of standard time as well as line balancing using methods of Moodie Young and Generics Algorithm. Based on results of calculation, better line balancing than the existing initial conditions, i.e. improvement in the line efficiency by 18.39%, deterioration in balanced delay by 28.39%, and deterioration of a smoothness index by 23.85% was obtained.

A model of phytoplankton blooms.

PubMed

Huppert, Amit; Blasius, Bernd; Stone, Lewi

2002-02-01

A simple model that describes the dynamics of nutrient-driven phytoplankton blooms is presented. Apart from complicated simulation studies, very few models reported in the literature have taken this "bottom-up" approach. Yet, as discussed and justified from a theoretical standpoint, many blooms are strongly controlled by nutrients rather than by higher trophic levels. The analysis identifies an important threshold effect: a bloom will only be triggered when nutrients exceed a certain defined level. This threshold effect should be generic to both natural blooms and most simulation models. Furthermore, predictions are given as to how the peak of the bloom Pmax is determined by initial conditions. A number of counterintuitive results are found. In particular, it is shown that increasing initial nutrient or phytoplankton levels can act to decrease Pmax. Correct predictions require an understanding of such factors as the timing of the bloom and the period of nutrient buildup before the bloom.

SEACAS Theory Manuals: Part 1. Problem Formulation in Nonlinear Solid Mechancis

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

Attaway, S.W.; Laursen, T.A.; Zadoks, R.I.

1998-08-01

This report gives an introduction to the basic concepts and principles involved in the formulation of nonlinear problems in solid mechanics. By way of motivation, the discussion begins with a survey of some of the important sources of nonlinearity in solid mechanics applications, using wherever possible simple one dimensional idealizations to demonstrate the physical concepts. This discussion is then generalized by presenting generic statements of initial/boundary value problems in solid mechanics, using linear elasticity as a template and encompassing such ideas as strong and weak forms of boundary value problems, boundary and initial conditions, and dynamic and quasistatic idealizations. Themore » notational framework used for the linearized problem is then extended to account for finite deformation of possibly inelastic solids, providing the context for the descriptions of nonlinear continuum mechanics, constitutive modeling, and finite element technology given in three companion reports.« less

Numerical modelling of fault reactivation in carbonate rocks under fluid depletion conditions - 2D generic models with a small isolated fault

NASA Astrophysics Data System (ADS)

Zhang, Yanhua; Clennell, Michael B.; Delle Piane, Claudio; Ahmed, Shakil; Sarout, Joel

2016-12-01

This generic 2D elastic-plastic modelling investigated the reactivation of a small isolated and critically-stressed fault in carbonate rocks at a reservoir depth level for fluid depletion and normal-faulting stress conditions. The model properties and boundary conditions are based on field and laboratory experimental data from a carbonate reservoir. The results show that a pore pressure perturbation of -25 MPa by depletion can lead to the reactivation of the fault and parts of the surrounding damage zones, producing normal-faulting downthrows and strain localization. The mechanism triggering fault reactivation in a carbonate field is the increase of shear stresses with pore-pressure reduction, due to the decrease of the absolute horizontal stress, which leads to an expanded Mohr's circle and mechanical failure, consistent with the predictions of previous poroelastic models. Two scenarios for fault and damage-zone permeability development are explored: (1) large permeability enhancement of a sealing fault upon reactivation, and (2) fault and damage zone permeability development governed by effective mean stress. In the first scenario, the fault becomes highly permeable to across- and along-fault fluid transport, removing local pore pressure highs/lows arising from the presence of the initially sealing fault. In the second scenario, reactivation induces small permeability enhancement in the fault and parts of damage zones, followed by small post-reactivation permeability reduction. Such permeability changes do not appear to change the original flow capacity of the fault or modify the fluid flow velocity fields dramatically.

Generic particulate-monitoring system for retrofit to Hanford exhaust stacks

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

Camman, J.W.; Carbaugh, E.H.

1982-11-01

Evaluations of 72 sampling and monitoring systems were performed at Hanford as the initial phase of a program to upgrade such systems. Each evaluation included determination of theoretical sampling efficiencies for particle sizes ranging from 0.5 to 10 micrometers aerodynamic equivalent diameter, addressing anisokinetic bias, sample transport line losses, and collector device efficiency. Upgrades needed to meet current Department of Energy guidance for effluent sampling and monitoring were identified, and a cost for each upgrade was estimated. A relative priority for each system's upgrade was then established based on evaluation results, current operational status, and future plans for the facilitymore » being exhausted. Common system upgrade requirements lead to the development of a generic design for common components of an exhaust stack sampling and monitoring system for airborne radioactive particulates. The generic design consists of commercially available off-the-shelf components to the extent practical and will simplify future stack sampling and monitoring system design, fabrication, and installation efforts. Evaluation results and their significance to system upgrades are empasized. A brief discussion of the analytical models used and experience to date with the upgrade program is included. Development of the generic stack sampling and monitoring system design is outlined. Generic system design features and limitations are presented. Requirements for generic system retrofitting to existing exhaust stacks are defined and benefits derived from generic system application are discussed.« less

Generic phytosanitary irradiation treatments

NASA Astrophysics Data System (ADS)

Hallman, Guy J.

2012-07-01

The history of the development of generic phytosanitary irradiation (PI) treatments is discussed beginning with its initial proposal in 1986. Generic PI treatments in use today are 150 Gy for all hosts of Tephritidae, 250 Gy for all arthropods on mango and papaya shipped from Australia to New Zealand, 300 Gy for all arthropods on mango shipped from Australia to Malaysia, 350 Gy for all arthropods on lychee shipped from Australia to New Zealand and 400 Gy for all hosts of insects other than pupae and adult Lepidoptera shipped to the United States. Efforts to develop additional generic PI treatments and reduce the dose for the 400 Gy treatment are ongoing with a broad based 5-year, 12-nation cooperative research project coordinated by the joint Food and Agricultural Organization/International Atomic Energy Agency Program on Nuclear Techniques in Food and Agriculture. Key groups identified for further development of generic PI treatments are Lepidoptera (eggs and larvae), mealybugs and scale insects. A dose of 250 Gy may suffice for these three groups plus others, such as thrips, weevils and whiteflies.

Driver compliance to take-over requests with different auditory outputs in conditional automation.

PubMed

Forster, Yannick; Naujoks, Frederik; Neukum, Alexandra; Huestegge, Lynn

2017-12-01

Conditionally automated driving (CAD) systems are expected to improve traffic safety. Whenever the CAD system exceeds its limit of operation, designers of the system need to ensure a safe and timely enough transition from automated to manual mode. An existing visual Human-Machine Interface (HMI) was supplemented by different auditory outputs. The present work compares the effects of different auditory outputs in form of (1) a generic warning tone and (2) additional semantic speech output on driver behavior for the announcement of an upcoming take-over request (TOR). We expect the information carried by means of speech output to lead to faster reactions and better subjective evaluations by the drivers compared to generic auditory output. To test this assumption, N=17 drivers completed two simulator drives, once with a generic warning tone ('Generic') and once with additional speech output ('Speech+generic'), while they were working on a non-driving related task (NDRT; i.e., reading a magazine). Each drive incorporated one transition from automated to manual mode when yellow secondary lanes emerged. Different reaction time measures, relevant for the take-over process, were assessed. Furthermore, drivers evaluated the complete HMI regarding usefulness, ease of use and perceived visual workload just after experiencing the take-over. They gave comparative ratings on usability and acceptance at the end of the experiment. Results revealed that reaction times, reflecting information processing time (i.e., hands on the steering wheel, termination of NDRT), were shorter for 'Speech+generic' compared to 'Generic' while reaction time, reflecting allocation of attention (i.e., first glance ahead), did not show this difference. Subjective ratings were in favor of the system with additional speech output. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of the introduction of generic latanoprost on glaucoma medication adherence.

PubMed

Stein, Joshua D; Shekhawat, Nakul; Talwar, Nidhi; Balkrishnan, Rajesh

2015-04-01

To assess possible changes in medication adherence to prostaglandin analog (PGA) regimens among patients with open-angle glaucoma (OAG) after the initial introduction of generic PGAs. Longitudinal cohort analysis. Patients older than 40 years with OAG continuously enrolled in a nationwide managed-care network during 2009-2012 who used PGAs. Mean adherence rates were calculated for topical PGA use during the 18 months before the introduction of generic latanoprost (September 2009-February 2011) and the 18 months after generic latanoprost became available (July 2011-December 2012). The rates were compared between persons who continued to use brand-name PGAs once generic latanoprost became available and others who switched to generic latanoprost. Multivariable logistic regression identified variables associated with an improvement or worsening of adherence of ≥25%. Mean adherence rates and odds of 25% or more improved or worsened adherence (with 95% confidence intervals [CIs]). A total of 8427 patients met the study eligibility criteria. Compared with persons switching to generic latanoprost, patients who continued taking brand name PGAs were 28% less likely to have improved adherence (odds ratio [OR], 0.72; 95% CI, 0.55-0.94) and 39% more likely to have reduced adherence (OR, 1.39; 1.04-1.86) of ≥25%. Improved adherence after the generic drug's introduction was also associated with higher monthly medication copay in the pregeneric period (P = 0.02), lower copay after introduction of the generic drug (P < 0.0001), and black race (OR, 1.25; 95% CI, 1.04-1.50). Six-hundred twelve patients (7.3%) discontinued all antiglaucoma interventions when generic latanoprost became available. Given that cost can significantly deter adherence, switching patients to generic medications may help improve patients' drug-regimen adherence. A considerable number of patients discontinued glaucoma drug use altogether when generic latanoprost became available. Ophthalmologists should work with insurers and pharmacists to prevent such discontinuation of use as generic forms of other PGA agents become available. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Generic Drugs - Decreasing Costs and Room for Increased Number of Kidney Transplantations.

PubMed

Spasovski, Goce

2015-01-01

Kidney transplantation is the best treatment option in comparison to dialysis, although patients are obliged to receive life-long medical treatment with immunosuppressive drugs (ISDs) for prevention of the graft rejection. Such immunosuppressive treatment may be costly and associated with multiple adverse effects. Since costs are viewed as one of the major constraints for the increasing number of transplantation, the use of generic ISDs may decrease the overall cost of transplantation and raise the possibility for its further development. An ideal ISD should have the security margin between toxic and therapeutic dose, and prevent development of acute or chronic rejection of the transplanted kidney. This is particularly important for drugs with a "narrow therapeutical index" (NTI), where small differences in dose or concentration lead to dose and concentration-dependent, serious therapeutic failures and/or adverse drug reactions. The NTI generic drug is approved if within 90%-112% of the area under the curve of the original product the pharmacokinetics fulfills the strict criteria of pharmaceutical equivalence and bioequivalence. Every generic has to be proven to be bioequivalent to the innovator product, and not to other generic products because of the possible generic "drift". Thus, the generic ISDs may be economically attractive, but theoretically, they may pose a risk to transplant patients. Such risks may be reduced if a long-term clinical studies showing cost-effectiveness of generic ISDs in de novo and prevalent transplant patients for every new generic ISD are performed. In conclusion, the increased number of solid organ transplantation goes in line with the increased health care expenditure for ISDs. The generic immunosuppressants could be a possible solution if safely substituted for innovator products or other generic drug of choice. The substantial cost reduction needs to be redirected into organ donation initiatives so that more patients can benefit from the further increase in transplantation.

Generic Information Can Retrieve Known Biological Associations: Implications for Biomedical Knowledge Discovery

PubMed Central

van Haagen, Herman H. H. B. M.; 't Hoen, Peter A. C.; Mons, Barend; Schultes, Erik A.

2013-01-01

Motivation Weighted semantic networks built from text-mined literature can be used to retrieve known protein-protein or gene-disease associations, and have been shown to anticipate associations years before they are explicitly stated in the literature. Our text-mining system recognizes over 640,000 biomedical concepts: some are specific (i.e., names of genes or proteins) others generic (e.g., ‘Homo sapiens’). Generic concepts may play important roles in automated information retrieval, extraction, and inference but may also result in concept overload and confound retrieval and reasoning with low-relevance or even spurious links. Here, we attempted to optimize the retrieval performance for protein-protein interactions (PPI) by filtering generic concepts (node filtering) or links to generic concepts (edge filtering) from a weighted semantic network. First, we defined metrics based on network properties that quantify the specificity of concepts. Then using these metrics, we systematically filtered generic information from the network while monitoring retrieval performance of known protein-protein interactions. We also systematically filtered specific information from the network (inverse filtering), and assessed the retrieval performance of networks composed of generic information alone. Results Filtering generic or specific information induced a two-phase response in retrieval performance: initially the effects of filtering were minimal but beyond a critical threshold network performance suddenly drops. Contrary to expectations, networks composed exclusively of generic information demonstrated retrieval performance comparable to unfiltered networks that also contain specific concepts. Furthermore, an analysis using individual generic concepts demonstrated that they can effectively support the retrieval of known protein-protein interactions. For instance the concept “binding” is indicative for PPI retrieval and the concept “mutation abnormality” is indicative for gene-disease associations. Conclusion Generic concepts are important for information retrieval and cannot be removed from semantic networks without negative impact on retrieval performance. PMID:24260124

A possibility for standoff bomb detection

NASA Astrophysics Data System (ADS)

Akar Tarim, U.; Ozmutlu, E. N.; Gurler, O.; Yalcin, S.

2015-01-01

The response functions of backscattered photons, which are initially collimated with an energy of 662 keV, were obtained by a Monte Carlo method in an NaI(Tl) scintillation detector using a suitcase or briefcase full of paper, clothing, ammonium nitrate or other generic explosives, as these can be used for terrorism. The results show that characteristic response functions for ammonium nitrate and generic explosives may be found, and using this information, standoff detection of these materials may be possible.

Generic substitution of antihypertensive drugs: does it affect adherence?

PubMed

Van Wijk, Boris L G; Klungel, Olaf H; Heerdink, Eibert R; de Boer, Anthonius

2006-01-01

Generic substitution is an important opportunity to reduce the costs of pharmaceutical care. However, pharmacists and physicians often find that patients and brand-name manufacturers have doubt about the equivalence of the substituted drug. This may be reflected by decreased adherence to therapy. To assess the association between generic substitution and nonadherence to antihypertensive drugs. We conducted a matched cohort study between January 1, 1999, and December 31, 2002. Data were obtained from PHARMO, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 people in The Netherlands. Residents of 30 medium-sized cities who initiated antihypertensive drug therapy were potential subjects. Refill adherence with antihypertensive drugs after substitution was determined; those with refill adherence below 80% were considered nonadherent. Four hundred sixty-three patients with a substitution in therapy and 565 controls, matched on age, gender, therapy start date, duration of use, and generic product code, were identified. Of the patients who switched from brand-name to generic formulations ("substituted"), 13.6% were nonadherent, and of the non-substituted patients (those who did not switch to generic), 18.7% were nonadherent (OR 0.68; 95% CI 0.48 to 0.96). The association was absent in males. None of the patients discontinued the medication. No differences in hospitalizations for cardiovascular disease in the 6 months after the substitution were observed. Generic substitution of antihypertensive drugs does not lead to lower adherence or more discontinuation and cardiovascular disease-related hospitalizations compared with brand-name therapy. When a less-expensive antihypertensive generic equivalent becomes available, generic substitution should be considered to achieve economic benefits.

Comparison of measured and calculated composition of irradiated EBR-II blanket assemblies.

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

Grimm, K. N.

1998-07-13

In anticipation of processing irradiated EBR-II depleted uranium blanket subassemblies in the Fuel Conditioning Facility (FCF) at ANL-West, it has been possible to obtain a limited set of destructive chemical analyses of samples from a single EBR-II blanket subassembly. Comparison of calculated values with these measurements is being used to validate a depletion methodology based on a limited number of generic models of EBR-II to simulate the irradiation history of these subassemblies. Initial comparisons indicate these methods are adequate to meet the operations and material control and accountancy (MC and A) requirements for the FCF, but also indicate several shortcomingsmore » which may be corrected or improved.« less

Long-term stability of acyclovir in 0.9% NaCl infusion polyolefin bags at 5±3°C after freeze-thaw treatment: a generic product versus the brand name.

PubMed

Dewulf, J; Galanti, L; Godet, M; Gillet, P; Jamart, J; Hecq, J-D

2015-03-01

The aim of the study was to investigate the long-term stability of acyclovir 5 mg/mL (a generic product versus the brand name) in NaCl 0.9% after storage at 5±3°C and to evaluate the influence of initial freezing and microwave thawing on this stability. Five bags of Acyclovir® Hospira 5 mg/mL (A) and five bags of Zovirax® GSK 5 mg/mL (B) were prepared under aseptic conditions and stored 3 months at -20°C, then thawed and stored 30 days at 4°C. Five bags of Acyclovir® 5 mg/mL (C) and five bags of Zovirax® 5 mg/mL (D) were also prepared under aseptic conditions and stored 30 days at 5±3°C. Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCl 12 M and NaOH 5 M before and after heating at 100°C was also performed. The concentrations were measured by HPLC-PDA. The only one forced degradation test that yielded chromatograms with degradation products peak was the test with the acid solution heated at 100°C without interference with the native product. No significant change in pH values or optic densities were seen during the study for both products. No crystals were seen with the optic microscope during the study. Acyclovir® and Zovirax® solutions were stable for at least 21 days according to the FDA recommendations. Moreover, there was no statistical difference between regression lines of those two products and two storage conditions. Under the conditions of this study, Acyclovir® 5 mg/mL in 100 mL of NaCl 0.9% infusion remains stable at least for 21 days at 5±3°C with or without freezing at -20°C during the three previous months. There is no statistical difference between the brand name and a generic product. Acyclovir may be prepared in advanced by a centralized intravenous additive service, frozen in polyolefin bags and microwave thawed before storage under refrigeration until 21 days. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Pilot-in-the-Loop CFD Method Development

DTIC Science & Technology

2014-06-16

CFD analysis. Coupled simulations will be run at PSU on the COCOA -4 cluster, a high performance computing cluster. The CRUNCH CFD software has...been installed on the COCOA -4 servers and initial software tests are being conducted. Initial efforts will use the Generic Frigate Shape SFS-2 to

Impact on Bacterial Resistance of Therapeutically Nonequivalent Generics: The Case of Piperacillin-Tazobactam

PubMed Central

Rodriguez, Carlos A.; Agudelo, Maria; Aguilar, Yudy A.; Zuluaga, Andres F.

2016-01-01

Previous studies have demonstrated that pharmaceutical equivalence and pharmacokinetic equivalence of generic antibiotics are necessary but not sufficient conditions to guarantee therapeutic equivalence (better called pharmacodynamic equivalence). In addition, there is scientific evidence suggesting a direct link between pharmacodynamic nonequivalence of generic vancomycin and promotion of resistance in Staphylococcus aureus. To find out if even subtle deviations from the expected pharmacodynamic behavior with respect to the innovator could favor resistance, we studied a generic product of piperacillin-tazobactam characterized by pharmaceutical and pharmacokinetic equivalence but a faulty fit of Hill’s Emax sigmoid model that could be interpreted as pharmacodynamic nonequivalence. We determined the impact in vivo of this generic product on the resistance of a mixed Escherichia coli population composed of ∼99% susceptible cells (ATCC 35218 strain) and a ∼1% isogenic resistant subpopulation that overproduces TEM-1 β-lactamase. After only 24 hours of treatment in the neutropenic murine thigh infection model, the generic amplified the resistant subpopulation up to 20-times compared with the innovator, following an inverted-U dose-response relationship. These findings highlight the critical role of therapeutic nonequivalence of generic antibiotics as a key factor contributing to the global problem of bacterial resistance. PMID:27191163

The differences between the branded and generic medicines using solid dosage forms: In-vitro dissolution testing

PubMed Central

Al Ameri, Mubarak Nasser; Nayuni, Nanda; Anil Kumar, K.G.; Perrett, David; Tucker, Arthur; Johnston, Atholl

2011-01-01

Introduction Dissolution is the amount of substance that goes into solution per unit time under standardised conditions of liquid/solid interface, solvent composition and temperature. Dissolution is one of the most important tools to predict the in-vivo bioavailability and in some cases to determine bioequivalence and assure interchangeability. Aim To compare the differences in dissolution behaviour of solid dosage forms between innovators (reference products) and their generic counterparts (tested products). Methods Four replicates for each batch of 37 tested medicines was carried out using A PT-DT70 dissolution tester from Pharma Test. A total of 13 branded medicines and 24 generic counterparts were obtained locally and internationally to detect any differences in their dissolution behaviour. They were tested according to the British Pharmacopeia, European Pharmacopeia and the US Pharmacopeia with the rate of dissolution determined by ultra-violet Spectrophotometery. Results Most tested medicines complied with the pharmacopoeial specifications and achieved 85% dissolution in 60 min. However, some generic medicines showed significant differences in dissolution rate at 60 and 120 min. Many generic medicines showed a slower dissolution rate than their branded counterparts such as the generic forms of omeprazole 20 mg. Some showed an incomplete dissolution such as the generic form of nifedipine 10 mg. Other generics showed faster dissolution rate than their branded counterpart such as the generic forms of meloxicam 15 mg. Moreover, some generics from different batches of the same manufacturer showed significant differences in their dissolution rate such as the generic forms of meloxicam 7.5 mg. Nevertheless, some generic medicines violated the EMA and the FDA guidelines for industry when they failed to achieve 85% dissolution at 60 min, such as the generic form of diclofenac sodium 50 mg. Conclusion Most medicines in this study complied with the pharmacopeial limits. However, some generics dissolved differently than their branded counterparts. This can clearly question the interchangeability between the branded and its generic counterpart or even among generics. PMID:25755988

Analytical solutions for sequentially coupled one-dimensional reactive transport problems Part I: Mathematical derivations

NASA Astrophysics Data System (ADS)

Srinivasan, V.; Clement, T. P.

2008-02-01

Multi-species reactive transport equations coupled through sorption and sequential first-order reactions are commonly used to model sites contaminated with radioactive wastes, chlorinated solvents and nitrogenous species. Although researchers have been attempting to solve various forms of these reactive transport equations for over 50 years, a general closed-form analytical solution to this problem is not available in the published literature. In Part I of this two-part article, we derive a closed-form analytical solution to this problem for spatially-varying initial conditions. The proposed solution procedure employs a combination of Laplace and linear transform methods to uncouple and solve the system of partial differential equations. Two distinct solutions are derived for Dirichlet and Cauchy boundary conditions each with Bateman-type source terms. We organize and present the final solutions in a common format that represents the solutions to both boundary conditions. In addition, we provide the mathematical concepts for deriving the solution within a generic framework that can be used for solving similar transport problems.

Addition of generic medication vouchers to a pharmacist academic detailing program: effects on the generic dispensing ratio in a physician-hospital organization.

PubMed

Bhargava, Vinay; Greg, Mark E; Shields, Mark C

2010-01-01

Generic dispensing ratio (GDR) is an important measure of efficiency in pharmacy benefit management. A few studies have examined the effects of academic detailing or generic drug samples on GDR. On July 1, 2007, a physician-hospital organization (PHO) with a pay-for-performance incentive for generic utilization initiated a pilot generic medication voucher program that augmented its existing pharmacist-led academic detailing efforts. No published studies have examined the role of generic medication vouchers in promoting generic drug utilization. To determine if supplementing an existing academic detailing initiative in a PHO with a generic medication voucher program would be more effective in increasing the GDR compared with academic detailing alone. The intervention took place over the 9-month period from July 1, 2007, through March 31, 2008. Vouchers provided patients with the first fill of a 30-day supply of a generic drug at no cost to the patient for 8 specific generic medications obtained through a national community pharmacy chain. The study was conducted in a PHO composed of 7 hospitals and approximately 2,900 physicians (900 primary care providers [PCPs] and 2,000 specialists). Of the approximately 300 PCP practices, 21 practices with at least 2 physicians each were selected on the basis of high prescription volume (more than 500 pharmacy claims for the practice over a 12-month pre-baseline period) and low GDR (practice GDR less than 55% in the 12-month pre-baseline period). These 21 practices were then randomized to a control group of academic detailing alone or the intervention group that received academic detailing plus generic medication vouchers. One of 10 intervention groups declined to participate, and 2 of 11 control groups dropped out of the PHO. GDR was calculated monthly for all pharmacy claims including the 8 voucher medications. GDR was defined as the ratio of the total number of paid generic pharmacy claims divided by the total number of paid pharmacy claims for 108 prescriber identification numbers (Drug Enforcement Administration [DEA] or National Provider Identifier [NPI]) for 9 intervention groups [n = 53 PCPs] and 9 control groups [n = 55 PCPs]). For both intervention and control arms, the GDR for each month from July 2007 (start of 2007 Q3, intervention start date) through September 2008 (end of 2008 Q3, 6 months after intervention end date) was compared with the same month in the previous year. A descriptive analysis compared a 9-month baseline period from 2006 Q3 through 2007 Q1 with a 9-month voucher period from 2007 Q3 to 2008 Q1. A panel data regression analysis assessed GDR for 18 practices over 27 months (12 months pre-intervention and 15 months post-intervention). A total of 656 vouchers were redeemed over the 9-month voucher period from July 1, 2007, through March 31, 2008, for an average of about 12 vouchers per participating physician; approximately one-third of the redeemed vouchers were for generic simvastatin. The GDR increase for all drugs, including the 8 voucher drugs, was 7.4 points for the 9 PCP group practices with access to generic medication vouchers, from 53.4% in the 9-month baseline period to 60.8% in the 9-month voucher period, compared with a 6.2 point increase for the control group from 55.9% during baseline to 62.1% during the voucher period. The panel data regression model estimated that the medication voucher program was associated with a 1.77-point increase in overall GDR compared with academic detailing alone (P = 0.047). Compared with academic detailing alone, a generic medication voucher program providing a 30-day supply of 8 specific medications in addition to academic detailing in PCP groups with low GDR and high prescribing volume in an outpatient setting was associated with a small but statistically significant increase in adjusted overall GDR.

Separability and Entanglement in the Hilbert Space Reference Frames Related Through the Generic Unitary Transform for Four Level System

NASA Astrophysics Data System (ADS)

Man'ko, V. I.; Markovich, L. A.

2018-02-01

Quantum correlations in the state of four-level atom are investigated by using generic unitary transforms of the classical (diagonal) density matrix. Partial cases of pure state, X-state, Werner state are studied in details. The geometrical meaning of unitary Hilbert reference-frame rotations generating entanglement in the initially separable state is discussed. Characteristics of the entanglement in terms of concurrence, entropy and negativity are obtained as functions of the unitary matrix rotating the reference frame.

GMODWeb: a web framework for the generic model organism database

PubMed Central

O'Connor, Brian D; Day, Allen; Cain, Scott; Arnaiz, Olivier; Sperling, Linda; Stein, Lincoln D

2008-01-01

The Generic Model Organism Database (GMOD) initiative provides species-agnostic data models and software tools for representing curated model organism data. Here we describe GMODWeb, a GMOD project designed to speed the development of model organism database (MOD) websites. Sites created with GMODWeb provide integration with other GMOD tools and allow users to browse and search through a variety of data types. GMODWeb was built using the open source Turnkey web framework and is available from . PMID:18570664

Scattering transform for nonstationary Schroedinger equation with bidimensionally perturbed N-soliton potential

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

Boiti, M.; Pempinelli, F.; Pogrebkov, A. K.

2006-12-15

In the framework of the extended resolvent approach the direct and inverse scattering problems for the nonstationary Schroedinger equation with a potential being a perturbation of the N-soliton potential by means of a generic bidimensional smooth function decaying at large spaces are introduced and investigated. The initial value problem of the Kadomtsev-Petviashvili I equation for a solution describing N wave solitons on a generic smooth decaying background is then linearized, giving the time evolution of the spectral data.

Human life support during interplanetary travel and domicile. VI - Generic modular flow schematic for hybrid physical/chemical-biological life support systems

NASA Technical Reports Server (NTRS)

Ganapathi, Gani B.; Seshan, P. K.; Ferrall, Joseph; Rohatgi, Naresh

1992-01-01

An extension is proposed for the NASA Space Exploration Initiative's Generic Modular Flow Schematics for physical/chemical life support systems which involves the addition of biological processes. The new system architecture includes plant, microbial, and animal habitat, as well as the human habitat subsystem. Major Feedstock Production and Food Preparation and Packaging components have also been incorporated. Inedible plant, aquaculture, microbial, and animal solids are processed for recycling.

Imperative to consider multiple initiatives to maximize prescribing efficiency from generic availability: case history from Abu Dhabi.

PubMed

Abuelkhair, Mohammed; Abdu, Shajahan; Godman, Brian; Fahmy, Sahar; Malmström, Rickard E; Gustafsson, Lars L

2012-02-01

Pharmaceutical expenditure has risen rapidly in Abu Dhabi, resulting in policies surrounding generics. However, various circumstances will reduce potential savings, including pharmacists still being free to dispense either originator or branded generics and be fully reimbursed. To research the changes in utilization patterns of proton pump inhibitors (PPIs) and lipid-lowering drugs before and after combined reforms on generics; and subsequently, calculate potential savings based on 'best practices' among Western European countries. An uncontrolled before-and-after observational study of utilization and expenditure of PPIs, statins and ezetimibe between 2004 and 2010, as well as up to 12 months before the first generic policy, to 1 year after the second generic policy, was carried out. Utilization was converted to defined daily doses (DDDs; 2011 DDDs) and DDDs/1000 inhabitants per day. Expenditure/DDD was calculated for omeprazole and simvastatin. PPI utilization rose by 6.5-fold from 2004 to 2010, principally driven by increased utilization of patent-protected PPIs, although more recently stabilization in esomperazole utilization has occurred. Similar changes were seen for statins. Introduction of best practices would reduce PPI expenditure in 2010 by 32.8 million United Arab Emirates dirham (AED; €6.26 million) and statins by over 27 million AED (€5.15 million). Limited demand-side measures led to increased utilization of patent-protected products in Abu Dhabi following the generic reforms. Successful measures will release considerable resources.

Global strategies to reduce the price of antiretroviral medicines: evidence from transactional databases.

PubMed

Waning, Brenda; Kaplan, Warren; King, Alexis C; Lawrence, Danielle A; Leufkens, Hubert G; Fox, Matthew P

2009-07-01

To estimate the impact of global strategies, such as pooled procurement arrangements, third-party price negotiation and differential pricing, on reducing the price of antiretrovirals (ARVs), which currently hinders universal access to HIV/AIDS treatment. We estimated the impact of global strategies to reduce ARV prices using data on 7253 procurement transactions (July 2002-October 2007) from databases hosted by WHO and the Global Fund to Fight AIDS, Tuberculosis and Malaria. For 19 of 24 ARV dosage forms, we detected no association between price and volume purchased. For the other five ARVs, high-volume purchases were 4-21% less expensive than medium- or low-volume purchases. Nine of 13 generic ARVs were priced 6-36% lower when purchased under the Clinton Foundation HIV/AIDS Initiative (CHAI). Fifteen of 18 branded ARVs were priced 23-498% higher for differentially priced purchases compared with non-CHAI generic purchases. However, two branded, differentially priced ARVs were priced 63% and 73% lower, respectively, than generic non-CHAI equivalents. Large purchase volumes did not necessarily result in lower ARV prices. Although current plans for pooled procurement will further increase purchase volumes, savings are uncertain and should be balanced against programmatic costs. Third-party negotiation by CHAI resulted in lower generic ARV prices. Generics were less expensive than differentially priced branded ARVs, except where little generic competition exists. Alternative strategies for reducing ARV prices, such as streamlining financial management systems, improving demand forecasting and removing barriers to generics, should be explored.

Anomalous cooling and heating - the Mpemba effect and its inverse

NASA Astrophysics Data System (ADS)

Lu, Zhiyue; Raz, Oren

Under certain conditions, it takes a shorter time to cool a hot object than to cool the same object initiated at a lower temperature. This counter-intuitive phenomenon - the 'Mpemba Effect'\\x9D, has been observed in a variety of systems. So far, no generic mechanism was suggested to explain this effect. In the theoretical framework of non-equilibrium thermodynamics, we construct a model to describe this effect and illustrates the fundamental principles behind it. In addition, we predict and demonstrate an inverse Mpemba effect: it can take a shorter time to heat a cold object than a warmer one. We derive sufficient conditions for the occurrences of both the forward and the inverse Mpemba effects, and suggest experiments to further study the non-equilibrium nature of these effects. Z.L. acknowledges financial support from the NSF under Grant DMR-1206971. O.R. acknowledges financial support from the James S. McDonnell Foundation.

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

Venkatraman, A.; Walawender, W.P.; Fan, L.T.

The term, activated carbon, is a generic name for a family of carbonaceous materials with well-developed porosities and consequently, large adsorptive capacities. Activated carbons are increasingly being consumed worldwide for environmental applications such as separation of volatiles from bulk gases and purification of water and waste-water streams. The global annual production is estimated to be around 300 million kilograms, with a rate of increase of 7% each year. Activated carbons can be prepared from a variety of raw materials. Approximately, 60% of the activated carbons generated in the United States is produced from coal; 20%, from coconut shells; and themore » remaining 20% from wood and other sources of biomass. The pore structure and properties of activated carbons are influenced by the nature of the starting material and the initial physical and chemical conditioning as well as the process conditions involved in its manufacture. The porous structures of charcoals and activated carbons obtained by the carbonization of kernels have been characterized.« less

Evaluation of safety in clinical use of generic paclitaxel [NK] for injection.

PubMed

Tsukiyama, Ikuto; Hotta, Kazuo; Takeuchi, Masayuki; Onishi, Masahumi; Toyama, Yukio; Saito, Hiroko; Sai, Yoshimichi; Miyamoto, Ken-Ichi; Hasegawa, Takaaki

2012-04-01

The introduction of generic drugs is a favored strategy in reducing medical costs, but some clinicians are often reluctant to use them because of lack of information with regard to their side effects. Generic paclitaxel [NK] differs from the proprietary version, Taxol®, in containing added citric acid and a more pure form of castor oil. However, little information exists regarding the effects of these additives on adverse events such as vascular pain, phlebitis, hypersensitivity and hepatic dysfunction. To compensate for this lack of information and to validate the safety of using generic paclitaxel, we investigated adverse events in response to generic paclitaxel [NK]. Our investigation focused on patients treated with both the proprietary formulation (Taxol® for injection) and the generic version(paclitaxel [NK] for injection)sequentially from April 2008 to March 2009. Adverse events were investigated retrospectively. Incidence of vascular pain, phlebitis and hypersensitivity was similar to that with the original product. Although the expression of some liver enzymes was slightly increased and some gastrointestinal events were reduced following generic paclitaxel [NK] treatment there was no statistically significant difference. The profiles of other adverse events were not significantly different. Increased vascular pain and phlebitis, predicted due to low pH conditions caused by citric acid, were not observed. Similarly, the pure castor oil included in generic paclitaxel [NK] did not influence hypersensitivity and hepatic function. We found no significant differences in our study of proprietary and generic paclitaxel [NK]. Thus, clinicians have no reason for prejudice against using generic paclitaxel [NK] on the basis of increased risk of side effects.

Synthesizing Safety Conditions for Code Certification Using Meta-Level Programming

NASA Technical Reports Server (NTRS)

Eusterbrock, Jutta

2004-01-01

In code certification the code consumer publishes a safety policy and the code producer generates a proof that the produced code is in compliance with the published safety policy. In this paper, a novel viewpoint approach towards an implementational re-use oriented framework for code certification is taken. It adopts ingredients from Necula's approach for proof-carrying code, but in this work safety properties can be analyzed on a higher code level than assembly language instructions. It consists of three parts: (1) The specification language is extended to include generic pre-conditions that shall ensure safety at all states that can be reached during program execution. Actual safety requirements can be expressed by providing domain-specific definitions for the generic predicates which act as interface to the environment. (2) The Floyd-Hoare inductive assertion method is refined to obtain proof rules that allow the derivation of the proof obligations in terms of the generic safety predicates. (3) A meta-interpreter is designed and experimentally implemented that enables automatic synthesis of proof obligations for submitted programs by applying the modified Floyd-Hoare rules. The proof obligations have two separate conjuncts, one for functional correctness and another for the generic safety obligations. Proof of the generic obligations, having provided the actual safety definitions as context, ensures domain-specific safety of program execution in a particular environment and is simpler than full program verification.

Protein particulates: another generic form of protein aggregation?

PubMed

Krebs, Mark R H; Devlin, Glyn L; Donald, A M

2007-02-15

Protein aggregation is a problem with a multitude of consequences, ranging from affecting protein expression to its implication in many diseases. Of recent interest is the specific form of aggregation leading to the formation of amyloid fibrils, structures associated with diseases such as Alzheimer's disease. The ability to form amyloid fibrils is now regarded as a property generic to all polypeptide chains. Here we show that around the isoelectric point a different generic form of aggregation can also occur by studying seven widely different, nonrelated proteins that are also all known to form amyloid fibrils. Under these conditions gels consisting of relatively monodisperse spherical particulates are formed. Although these gels have been described before for beta-lactoglobulin, our results suggest that the formation of particulates in the regime where charge on the molecules is minimal is a common property of all proteins. Because the proteins used here also form amyloid fibrils, we further propose that protein misfolding into clearly defined aggregates is a generic process whose outcome depends solely on the general properties of the state the protein is in when aggregation occurs, rather than the specific amino acid sequence. Thus under conditions of high net charge, amyloid fibrils form, whereas under conditions of low net charge, particulates form. This observation furthermore suggests that the rules of soft matter physics apply to these systems.

[Measures to reduce costs for prescriptions in Vienna--preliminary analysis].

PubMed

Tönies, Hans

2009-01-01

To increase the rate of prescriptions for generic drugs in Vienna an information campaign was started in 2004 and quality circles for prescribing doctors were organized. Since the result of this initiative is not yet known publicly this report aims to present a preliminary analysis. The prescription statements kindly provided by the health insurance fund of Vienna could be analysed. Data from the Chamber of Viennese Physicians were used for compiling a report about the quality circles. A total of 17 quality circles with an average of 15 participants were formed; they met four times yearly. Participants were paid for their attendance. The rate of prescribed generic drugs in Vienna has continuously improved, with the major increase in the first year of the activities. In the year 2006 a rate of over 40% generic prescriptions was reached by 80% of general practitioners. This cooperation between the health insurance fund and doctors apparently resulted in both an increase in the rate of generic drugs prescribed and in a good acceptance among physicians.

Developing and Validating a Competence Framework for Secondary Mathematics Student Teachers through a Delphi Method

ERIC Educational Resources Information Center

Muñiz-Rodríguez, Laura; Alonso, Pedro; Rodríguez-Muñiz, Luis J.; Valcke, Martin

2017-01-01

Initial teacher education programmes provide student teachers with the desired competences to develop themselves as teachers. Although a generic framework for teaching competences is available covering all school subjects in Spain, the initial teacher education programmes curriculum does not specify which competences secondary mathematics student…

DNA condensation and size effects of DNA condensation agent

NASA Astrophysics Data System (ADS)

Liu, Yan-Hui; Jiang, Chong-Ming; Guo, Xin-Miao; Tang, Yan-Lin; Hu, Lin

2013-08-01

Based on the model of the strong correlation of counterions condensed on DNA molecule, by tailoring interaction potential, interduplex spacing and correlation spacing between condensed counterions on DNA molecule and interduplex spacing fluctuation strength, toroidal configuration, rod-like configuration and two-hole configurations are possible. The size effects of counterion structure on the toroidal structure can be detected by this model. The autocorrelation function of the tangent vectors is found as an effective way to detect the structure of toroidal conformations and the generic pathway of the process of DNA condensation. The generic pathway of all of the configurations involves an initial nucleation loop, and the next part of the DNA chain is folded on the top of the initial nucleation loop with different manners, in agreement with the recent experimental results.

Generic expansion of the Jastrow correlation factor in polynomials satisfying symmetry and cusp conditions

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

Lüchow, Arne, E-mail: luechow@rwth-aachen.de; Jülich Aachen Research Alliance; Sturm, Alexander

2015-02-28

Jastrow correlation factors play an important role in quantum Monte Carlo calculations. Together with an orbital based antisymmetric function, they allow the construction of highly accurate correlation wave functions. In this paper, a generic expansion of the Jastrow correlation function in terms of polynomials that satisfy both the electron exchange symmetry constraint and the cusp conditions is presented. In particular, an expansion of the three-body electron-electron-nucleus contribution in terms of cuspless homogeneous symmetric polynomials is proposed. The polynomials can be expressed in fairly arbitrary scaling function allowing a generic implementation of the Jastrow factor. It is demonstrated with a fewmore » examples that the new Jastrow factor achieves 85%–90% of the total correlation energy in a variational quantum Monte Carlo calculation and more than 90% of the diffusion Monte Carlo correlation energy.« less

Investigation of an alternative generic model for predicting pharmacokinetic changes during physiological stress.

PubMed

Peng, Henry T; Edginton, Andrea N; Cheung, Bob

2013-10-01

Physiologically based pharmacokinetic models were developed using MATLAB Simulink® and PK-Sim®. We compared the capability and usefulness of these two models by simulating pharmacokinetic changes of midazolam under exercise and heat stress to verify the usefulness of MATLAB Simulink® as a generic PBPK modeling software. Although both models show good agreement with experimental data obtained under resting condition, their predictions of pharmacokinetics changes are less accurate in the stressful conditions. However, MATLAB Simulink® may be more flexible to include physiologically based processes such as oral absorption and simulate various stress parameters such as stress intensity, duration and timing of drug administration to improve model performance. Further work will be conducted to modify algorithms in our generic model developed using MATLAB Simulink® and to investigate pharmacokinetics under other physiological stress such as trauma. © The Author(s) 2013.

The changing patterns of dispensing branded and generic drugs for the treatment of gastroesophageal reflux disease between 2006 and 2011 in Japan: a retrospective cohort study.

PubMed

Murata, Kyoko; Hinotsu, Shiro; Hamada, Shota; Ezoe, Yasumasa; Muto, Manabu; Kawakami, Koji

2015-02-27

Despite rising healthcare costs, generic drugs are less frequently dispensed in Japan compared with other developed countries. This study aimed to describe changes in dispensing of branded and generic drugs and to explore possible factors that promote the use of generic drugs. We conducted a retrospective cohort study using a Japanese medical and pharmacy claims database. All proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs) with indications for gastroesophageal reflux disease (GERD) described on Japanese labels were included. Patterns of dispensing branded and generic drugs for the treatment of GERD between 2006 and 2011 were analyzed. Multivariate logistic regression was applied to investigate factors associated with receiving generic drugs. The study cohort included 14,590 patients (male: 50.2%, mean age: 43.1 years). Branded drugs for GERD were still frequently dispensed despite an increase in the share of generic drugs. Only 4.3% of patients who initially received branded drugs switched to generic drugs. The percentage of patients who received only generic drugs increased over time (6.5% to 22.1%). The frequency of generic drug dispensing was the highest in the setting where both prescription and dispensing were implemented in clinics (43.3%), while the lowest in the setting where both prescription and dispensing were implemented in hospitals (11.5%). Factors associated with receiving generic drugs included year of dispensing (adjusted OR 2.22, 95% CI 1.94 to 2.55 for 2009-11 v 2006-8), prescription and dispensing setting (OR 1.81, 95% CI 1.44 to 2.26 for prescription in hospitals and dispensing in community pharmacies; OR 2.21, 95% CI 1.80 to 2.72 for prescription in clinics and dispensing in community pharmacies; and OR 4.55, 95% CI 3.68 to 5.62 for prescription and dispensing in clinics v prescription and dispensing in hospitals) and H2RAs (OR 1.64, 95% CI 1.49 to 1.81 compared to PPIs). The share of generic drugs for the treatment of GERD increased over time although branded drugs for GERD were still dispensed frequently. The use of generic drugs for GERD was influenced not only by government policies but also by changes in treatment approach and the setting of prescription and dispensing.

Firm- and drug-specific patterns of generic drug payments by US medicaid programs: 1991-2008.

PubMed

Kelton, Christina M L; Chang, Lenisa V; Guo, Jeff J; Yu, Yan; Berry, Edmund A; Bian, Boyang; Heaton, Pamela C

2014-04-01

The entry of generic drugs into markets previously monopolized by patented, branded drugs often represents large potential savings for healthcare payers in the USA. Our objectives were to describe and explain the trends in drug reimbursement by public Medicaid programmes post-generic entry for as many drug markets and for as long a time period as possible. The data were the Medicaid State Drug Utilization Data maintained by the Centers for Medicare and Medicaid Services. Quarterly utilization and expenditure data from 1991 to 2008 were extracted for 83 drugs, produced by 229 firms, that experienced initial generic entry between 1992 and 2004. A relative 'price' for a specific drug, firm and quarter was constructed as Medicaid reimbursement per unit (e.g. tablet, capsule or vial) divided by average reimbursement per unit for the branded drug the year before entry. Fixed-effects models controlling for time-, firm- and drug-specific differences were estimated to explain reimbursement. Twelve quarters after generic entry, 18 % of drugs had average per-unit reimbursement less than 50 % of the original branded-drug reimbursement. For each additional firm manufacturing the drug, reimbursement per unit, relative to the pre-generic-entry branded-drug reimbursement, was estimated to fall by 17 (p < 0.01) and 3 (p < 0.01) percentage points for generic and branded-drug companies, respectively. Each additional quarter post-generic entry brought a 2 (p < 0.01) percentage point drop in relative reimbursement. State Medicaid programmes generally have been able to obtain relief from high drug prices following patent expirations for many branded-drug medications by adjusting reimbursement following the expanded competition in the pharmaceutical market.

Group presence, category labels, and generic statements influence children to treat descriptive group regularities as prescriptive.

PubMed

Roberts, Steven O; Ho, Arnold K; Gelman, Susan A

2017-06-01

Children use descriptive regularities of social groups (what is) to generate prescriptive judgments (what should be). We examined whether this tendency held when the regularities were introduced through group presence, category labels, or generic statements. Children (ages 4-9years, N=203) were randomly assigned to one of four conditions that manipulated how descriptive group regularities were presented: group presence (e.g., "These ones [a group of three individuals] eat this kind of berry"), category labels (e.g., "This [individual] Hibble eats this kind of berry"), generic statements (e.g., [showing an individual] "Hibbles eat this kind of berry"), or control (e.g., "This one [individual] eats this kind of berry"). Then, children saw conforming and non-conforming individuals and were asked to evaluate their behavior. As predicted, children evaluated non-conformity negatively in all conditions except the control condition. Together, these results suggest that minimal perceptual and linguistic cues provoke children to treat social groups as having normative force. Copyright © 2016 Elsevier Inc. All rights reserved.

The UNITAID Patent Pool Initiative: Bringing Patents Together for the Common Good.

PubMed

Bermudez, Jorge; 't Hoen, Ellen

2010-01-19

Developing and delivering appropriate, affordable, well-adapted medicines for HIV/AIDS remains an urgent challenge: as first-line therapies fail, increasing numbers of people require costly second-line therapy; one-third of ARVs are not available in pediatric formulations; and certain key first- and second-line triple fixed-dose combinations do not exist or sufficient suppliers are lacking. UNITAID aims to help solve these problems through an innovative initiative for the collective management of intellectual property (IP) rights - a patent pool for HIV medicines. The idea behind a patent pool is that patent holders - companies, governments, researchers or universities - voluntarily offer, under certain conditions, the IP related to their inventions to the patent pool. Any company that wants to use the IP to produce or develop medicines can seek a license from the pool against the payment of royalties, and may then produce the medicines for use in developing countries (conditional upon meeting agreed quality standards). The patent pool will be a voluntary mechanism, meaning its success will largely depend on the willingness of pharmaceutical companies to participate and commit their IP to the pool. Generic producers must also be willing to cooperate. The pool has the potential to provide benefits to all.

Visuospatial and psychomotor aptitude predicts endovascular performance of inexperienced individuals on a virtual reality simulator.

PubMed

Van Herzeele, Isabelle; O'Donoghue, Kevin G L; Aggarwal, Rajesh; Vermassen, Frank; Darzi, Ara; Cheshire, Nicholas J W

2010-04-01

This study evaluated virtual reality (VR) simulation for endovascular training of medical students to determine whether innate perceptual, visuospatial, and psychomotor aptitude (VSA) can predict initial and plateau phase of technical endovascular skills acquisition. Twenty medical students received didactic and endovascular training on a commercially available VR simulator. Each student treated a series of 10 identical noncomplex renal artery stenoses endovascularly. The simulator recorded performance data instantly and objectively. An experienced interventionalist rated the performance at the initial and final sessions using generic (out of 40) and procedure-specific (out of 30) rating scales. VSA were tested with fine motor dexterity (FMD, Perdue Pegboard), psychomotor ability (minimally invasive virtual reality surgical trainer [MIST-VR]), image recall (Rey-Osterrieth), and organizational aptitude (map-planning). VSA performance scores were correlated with the assessment parameters of endovascular skills at commencement and completion of training. Medical students exhibited statistically significant learning curves from the initial to the plateau performance for contrast usage (medians, 28 vs 17 mL, P < .001), total procedure time (2120 vs 867 seconds, P < .001), and fluoroscopy time (993 vs. 507 seconds, P < .001). Scores on generic and procedure-specific rating scales improved significantly (10 vs 25, P < .001; 8 vs 17 P < .001). Significant correlations were noted for FMD with initial and plateau sessions for fluoroscopy time (r(s) = -0.564, P = .010; r(s) = -.449, P = .047). FMD correlated with procedure-specific scores at the initial session (r(s) = .607, P = .006). Image recall correlated with generic skills at the end of training (r(s) = .587, P = .006). Simulator-based training in endovascular skills improved performance in medical students. There were significant correlations between initial endovascular skill and fine motor dexterity as well as with image recall at end of the training period. In addition to current recruitment strategies, VSA may be a useful tool for predictive validity studies.

Ash deposits - Initiating the change from empiricism to generic engineering. Part 1: The generic approach

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

Wagoner, C.L.; Wessel, R.A.

1986-01-01

Empiricism has traditionally been used to relate laboratory and pilot-scale measurements of fuel characteristics with the design, performance, and the slagging and fouling behavior of steam generators. Currently, a new engineering approach is being evaluated. The goal is to develop and use calculations and measurements from several engineering disciplines that exceed the demonstrated limitations of present empirical techniques for predicting slagging/fouling behavior. In Part I of this paper, the generic approach to deposits and boiler performance is defined and a matrix of engineering concepts is described. General relationships are presented for assessing the effects of deposits and sootblowing on themore » real-time performance of heat transfer surfaces in pilot- and commercial-scale steam generators.« less

A Generic Ground Framework for Image Expertise Centres and Small-Sized Production Centres

NASA Astrophysics Data System (ADS)

Sellé, A.

2009-05-01

Initiated by the Pleiadas Earth Observation Program, the CNES (French Space Agency) has developed a generic collaborative framework for its image quality centre, highly customisable for any upcoming expertise centre. This collaborative framework has been design to be used by a group of experts or scientists that want to share data and processings and manage interfaces with external entities. Its flexible and scalable architecture complies with the core requirements: defining a user data model with no impact on the software (generic access data), integrating user processings with a GUI builder and built-in APIs, and offering a scalable architecture to fit any preformance requirement and accompany growing projects. The CNES jas given licensing grants for two software companies that will be able to redistribute this framework to any customer.

Framework for the rapid optimization of soluble protein expression in Escherichia coli combining microscale experiments and statistical experimental design.

PubMed

Islam, R S; Tisi, D; Levy, M S; Lye, G J

2007-01-01

A major bottleneck in drug discovery is the production of soluble human recombinant protein in sufficient quantities for analysis. This problem is compounded by the complex relationship between protein yield and the large number of variables which affect it. Here, we describe a generic framework for the rapid identification and optimization of factors affecting soluble protein yield in microwell plate fermentations as a prelude to the predictive and reliable scaleup of optimized culture conditions. Recombinant expression of firefly luciferase in Escherichia coli was used as a model system. Two rounds of statistical design of experiments (DoE) were employed to first screen (D-optimal design) and then optimize (central composite face design) the yield of soluble protein. Biological variables from the initial screening experiments included medium type and growth and induction conditions. To provide insight into the impact of the engineering environment on cell growth and expression, plate geometry, shaking speed, and liquid fill volume were included as factors since these strongly influence oxygen transfer into the wells. Compared to standard reference conditions, both the screening and optimization designs gave up to 3-fold increases in the soluble protein yield, i.e., a 9-fold increase overall. In general the highest protein yields were obtained when cells were induced at a relatively low biomass concentration and then allowed to grow slowly up to a high final biomass concentration, >8 g.L-1. Consideration and analysis of the model results showed 6 of the original 10 variables to be important at the screening stage and 3 after optimization. The latter included the microwell plate shaking speeds pre- and postinduction, indicating the importance of oxygen transfer into the microwells and identifying this as a critical parameter for subsequent scale translation studies. The optimization process, also known as response surface methodology (RSM), predicted there to be a distinct optimum set of conditions for protein expression which could be verified experimentally. This work provides a generic approach to protein expression optimization in which both biological and engineering variables are investigated from the initial screening stage. The application of DoE reduces the total number of experiments needed to be performed, while experimentation at the microwell scale increases experimental throughput and reduces cost.

Diffusion controlled initial recombination

NASA Astrophysics Data System (ADS)

Christen, T.; Büttiker, M.

1998-08-01

This work addresses nucleation rates in systems with strong initial recombination. Initial (or ``geminate'') recombination is a process where a dissociated structure (anion, vortex, kink, etc.) recombines with its twin brother (cation, antivortex, antikink) generated in the same nucleation event. Initial recombination is important if there is an asymptotically vanishing interaction force instead of a generic saddle-type activation barrier. At low temperatures, initial recombination strongly dominates homogeneous recombination. In a first part, we discuss the effect in one-, two-, and three-dimensional diffusion controlled systems with spherical symmetry. Since there is no well-defined saddle, we introduce a threshold which is to some extent arbitrary but which is restricted by physically reasonable conditions. We show that the dependence of the nucleation rate on the specific choice of this threshold is strongest for one-dimensional systems and decreases in higher dimensions. We also discuss the influence of a weak driving force, and show that the transport current is directly determined by the imbalance of the activation rate in the direction of the field and the rate against this direction. In a second part, we apply the results to the overdamped sine-Gordon system at equilibrium. It turns out that diffusive initial recombination is the essential mechanism which governs the equilibrium kink nucleation rate. We emphasize analogies between the single particle problem with initial recombination and the multidimensional kink-antikink nucleation problem.

Is it ethical to prescribe generic immunosuppressive drugs to renal transplant patients?

PubMed

Allard, Julie; Fortin, Marie-Chantal

2014-01-01

This review was conducted to determine the ethical acceptability of prescribing generic immunosuppressive drugs to renal transplant patients. The literature search was conducted using Pubmed and Google Scholar. The use of generic immunosuppressive drugs (ISDs) in transplantation is a controversial topic. There is a consensus among transplant societies that clinical data is lacking and that caution should be exercised. The reluctance to use generic ISDs in organ transplantation is partly related to the fact that most are "critical dose drugs", and that either low dosing or overdosing could have serious adverse consequences for both patients and society (i.e., the loss of scarce organs). In this paper, we examine the various ethical issues involved such as distributive justice, physician duties, risks versus benefits, conflict of interest, informed consent, and logistical and economic issues. Our analysis was limited by the paucity of clinical data on generic ISDs and the absence of health economics studies to quantify the benefits of prescribing generic ISDs. Our study led us to conclude that it would be ethical to prescribe generic ISDs provided certain conditions were met. These include regulatory safeguards to minimize the risks of substitution; education of patients; and further clinical and health economics studies to better inform clinicians, patients and society of the risks and costs related to drug substitution.

A cross-sectional survey of pharmacists to understand their personal preference of brand and generic over-the-counter medications used to treat common health conditions.

PubMed

Patel, Mira; Slack, Marion; Cooley, Janet; Bhattacharjee, Sandipan

2016-01-01

Consumers are hesitant in choosing generic medications as they are under the assumption that they are not as safe nor effective as brand medications. However, pharmacists do have the education and training to know that this is not the case. The aim of this study was to determine pharmacists' preference of generic versus brand over-the-counter (OTC) medication for their personal use as self-treatment for various health symptoms. A prospective, cross sectional study was conducted on 553 licensed pharmacists who were presumed to have expertise in the use of generic and brand name OTC medications. In a single Southwestern state in the United States, from December 2014 to January 2015, a web-based questionnaire was sent to pharmacists to explore their preference of brand and generic medications based on various health symptoms. Thirty-one brand-generic medication pairs were used to identify which medication type pharmacists preferred when asked about nine health symptoms. Frequency counts of pharmacists' preference of a brand medication or a generic OTC medication overall and for each of the nine health symptoms were determined. Chi-squared analyses and one-way ANOVA were conducted to determine if there were any differences between the preferences of brand and generic OTC medications across each symptom. The study overall showed that pharmacists preferred generic OTC medications to brand OTC medications (62 to 5 %, respectively). Based on an 11-point rating scale, pharmacists were likely to take OTC generic medications (as their choice of self-treatment) when presented with health symptoms (mean = 7.32 ± 2.88). In addition, pharmacists chose generic OTC medications over brand medications regardless of health symptoms (p < 0.001). Pharmacists who have expertise in medications were shown to prefer using generic OTC medications rather than brand name OTC medications for self-treating a variety of health symptoms. These study findings support the theory that expertise affects preference for generic versus brand name OTC medications. This information can be used to provide consumers the evidence needed to make well-informed choices when choosing between brand and generic medications.

Effects of generic language on category content and structure.

PubMed

Gelman, Susan A; Ware, Elizabeth A; Kleinberg, Felicia

2010-11-01

We hypothesized that generic noun phrases ("Bears climb trees") would provide important input to children's developing concepts. In three experiments, four-year-olds and adults learned a series of facts about a novel animal category, in one of three wording conditions: generic (e.g., "Zarpies hate ice cream"), specific-label (e.g., "This zarpie hates ice cream"), or no-label (e.g., "This hates ice cream"). Participants completed a battery of tasks assessing the extent to which they linked the category to the properties expressed, and the extent to which they treated the category as constituting an essentialized kind. As predicted, for adults, generics training resulted in tighter category-property links and more category essentialism than both the specific-label and no-label training. Children also showed effects of generic wording, though the effects were weaker and required more extensive input. We discuss the implications for language-thought relations, and for the acquisition of essentialized categories. Copyright 2010 Elsevier Inc. All rights reserved.

On the stabilizability of multivariable systems by minimum order compensation

NASA Technical Reports Server (NTRS)

Byrnes, C. I.; Anderson, B. D. O.

1983-01-01

In this paper, a derivation is provided of the necessary condition, mp equal to or greater than n, for stabilizability by constant gain feedback of the generic degree n, p x m system. This follows from another of the main results, which asserts that generic stabilizability is equivalent to generic solvability of a deadbeat control problem, provided mp equal to or less than n. Taken together, these conclusions make it possible to make some sharp statements concerning minimum order stabilization. The techniques are primarily drawn from decision algebra and classical algebraic geometry and have additional consequences for problems of stabilizability and pole-assignability. Among these are the decidability (by a Sturm test) of the equivalence of generic pole-assignability and generic stabilizability, the semi-algebraic nature of the minimum order, q, of a stabilizing compensator, and the nonexistence of formulae involving rational operations and extraction of square roots for pole-assigning gains when they exist, answering in the negative a question raised by Anderson, Bose, and Jury (1975).

Architecture design of a generic centralized adjudication module integrated in a web-based clinical trial management system.

PubMed

Zhao, Wenle; Pauls, Keith

2016-04-01

Centralized outcome adjudication has been used widely in multicenter clinical trials in order to prevent potential biases and to reduce variations in important safety and efficacy outcome assessments. Adjudication procedures could vary significantly among different studies. In practice, the coordination of outcome adjudication procedures in many multicenter clinical trials remains as a manual process with low efficiency and high risk of delay. Motivated by the demands from two large clinical trial networks, a generic outcome adjudication module has been developed by the network's data management center within a homegrown clinical trial management system. In this article, the system design strategy and database structure are presented. A generic database model was created to transfer different adjudication procedures into a unified set of sequential adjudication steps. Each adjudication step was defined by one activate condition, one lock condition, one to five categorical data items to capture adjudication results, and one free text field for general comments. Based on this model, a generic outcome adjudication user interface and a generic data processing program were developed within a homegrown clinical trial management system to provide automated coordination of outcome adjudication. By the end of 2014, this generic outcome adjudication module had been implemented in 10 multicenter trials. A total of 29 adjudication procedures were defined with the number of adjudication steps varying from 1 to 7. The implementation of a new adjudication procedure in this generic module took an experienced programmer 1 or 2 days. A total of 7336 outcome events had been adjudicated and 16,235 adjudication step activities had been recorded. In a multicenter trial, 1144 safety outcome event submissions went through a three-step adjudication procedure and reported a median of 3.95 days from safety event case report form submission to adjudication completion. In another trial, 277 clinical outcome events were adjudicated by a six-step procedure and took a median of 23.84 days from outcome event case report form submission to adjudication procedure completion. A generic outcome adjudication module integrated in the clinical trial management system made the automated coordination of efficacy and safety outcome adjudication a reality. © The Author(s) 2015.

Switching between phenytoin generics in patients with epilepsy may lead to increased risk of breakthrough seizure: chart analysis and practice recommendations.

PubMed

Shin, Jung-Won; Chu, Kon; Jung, Keun-Hwa; Lee, Soon-Tae; Moon, Jangsup; Lee, Sang Kun

2014-12-01

The Food and Drug Administration (FDA) only requires bioequivalence testing of generic substitutions in order for them to be deemed equivalen to the original product. There may be a large difference of bioavailability among the generic drugs that especially have a narrow therapeutic index, and this may affect clinical outcomes. We aimed to determine whether switching from generic-to-generic equivalent anti-epileptic drugs (AEDs) in patients with epilepsy is associated with clinical outcomes. We performed a retrospective study using the electronic medical records of a tertiary hospital. Adults with a history of epilepsy who used a generic phenytoin and whose therapy was switched to another generic phenytoin between January 2012 and June 2013 were included (n = 80). We compared the drug concentration of phenytoin and seizure events before and after the switch. After switching their generic phenytoin, 33 out of 80 patients (41%) suffered from increasing seizure events (pre-interchange period, 0.44 ± 0.97; post-interchange period, 1.24 ± 2.05; p < 0.0001). The number of medical visits for acute seizure significantly increased in the post-interchange period. The phenytoin serum concentration of all the patients was lesser in the post-interchange period than in the pre-interchange period. (pre-interchange period, 12.79 μg/mL; post-interchange period, 6.36 μg/mL; p < 0.0001). Among the patients with drug resistant epilepsy (DRE), 17 patients (84.2%) had increasing seizure events in the post-interchange period. We confirmed that there was a significant difference in bioavailability between generic phenytoin. Therefore, when using or switching generic anti-epileptic drugs, therapeutic drug monitoring must be done, and the patients' condition must be considered.

Global strategies to reduce the price of antiretroviral medicines: evidence from transactional databases

PubMed Central

Kaplan, Warren; King, Alexis C; Lawrence, Danielle A; Leufkens, Hubert G; Fox, Matthew P

2009-01-01

Abstract Objective To estimate the impact of global strategies, such as pooled procurement arrangements, third-party price negotiation and differential pricing, on reducing the price of antiretrovirals (ARVs), which currently hinders universal access to HIV/AIDS treatment. Methods We estimated the impact of global strategies to reduce ARV prices using data on 7253 procurement transactions (July 2002–October 2007) from databases hosted by WHO and the Global Fund to Fight AIDS, Tuberculosis and Malaria. Findings For 19 of 24 ARV dosage forms, we detected no association between price and volume purchased. For the other five ARVs, high-volume purchases were 4–21% less expensive than medium- or low-volume purchases. Nine of 13 generic ARVs were priced 6–36% lower when purchased under the Clinton Foundation HIV/AIDS Initiative (CHAI). Fifteen of 18 branded ARVs were priced 23–498% higher for differentially priced purchases compared with non-CHAI generic purchases. However, two branded, differentially priced ARVs were priced 63% and 73% lower, respectively, than generic non-CHAI equivalents. Conclusion Large purchase volumes did not necessarily result in lower ARV prices. Although current plans for pooled procurement will further increase purchase volumes, savings are uncertain and should be balanced against programmatic costs. Third-party negotiation by CHAI resulted in lower generic ARV prices. Generics were less expensive than differentially priced branded ARVs, except where little generic competition exists. Alternative strategies for reducing ARV prices, such as streamlining financial management systems, improving demand forecasting and removing barriers to generics, should be explored. PMID:19649366

Generic health/safety/environment cases

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

Kelland, A.N.; Primrose, M.; Pickles, J.C.

1996-12-31

A desire to implement HSE Management Systems including HSE Cases in all Shell companies operations prompted the development of a relational data base software package (THESIS) to provide a structured way of preparing an HSE Case. The software includes features which facilitate the management of {open_quotes}Keeping the Case Alive{close_quotes}, enabling the dissemination of tasks and hazard information to the workplace. During the software development it was recognized that a significant reduction could be made in the resources which would be required to prepare an HSE Case for each and every operation by the building of {open_quotes}Generic HSE Cases{close_quotes} addressing specificmore » activities which were repeated across the Company`s operations. This was recognized to be particularly valid for the smaller Single String Venture type of operations. The activities selected for the initial Generic HSE Case development include Land Drilling Operations, Land Seismic Acquisition, and Land Transport. To establish the Generic HSE Case, the THESIS data base is populated with data for a generic operation, identifying all the hazards and activities associated with that operation including all the associated controls, with established formats for the textual sections. In effect, the Generic Case defines the standards required for that type of operation. To generate an operation specific HSE Case, the Generic Case thereafter requires to be modified/adapted so that it represents the actual situation in the operation which it defines. This process includes itemization of all the operation specific details, and may involve the inclusion/deletion of any additional/existing activities or hazards together with their associated controls.« less

Even apparently insignificant chemical deviations among bioequivalent generic antibiotics can lead to therapeutic nonequivalence: the case of meropenem.

PubMed

Agudelo, M; Rodriguez, C A; Pelaez, C A; Vesga, O

2014-01-01

Several studies with animal models have demonstrated that bioequivalence of generic products of antibiotics like vancomycin, as currently defined, do not guarantee therapeutic equivalence. However, the amounts and characteristics of impurities and degradation products in these formulations do not violate the requirements of the U.S. Pharmacopeia (USP). Here, we provide experimental data with three generic products of meropenem that help in understanding how these apparently insignificant chemical differences affect the in vivo efficacy. Meropenem generics were compared with the innovator in vitro by microbiological assay, susceptibility testing, and liquid chromatography/mass spectrometry (LC/MS) analysis and in vivo with the neutropenic guinea pig soleus infection model (Pseudomonas aeruginosa) and the neutropenic mouse thigh (P. aeruginosa), brain (P. aeruginosa), and lung (Klebisella pneumoniae) infection models, adding the dihydropeptidase I (DHP-I) inhibitor cilastatin in different proportions to the carbapenem. We found that the concentration and potency of the active pharmaceutical ingredient, in vitro susceptibility testing, and mouse pharmacokinetics were identical for all products; however, two generics differed significantly from the innovator in the guinea pig and mouse models, while the third generic was therapeutically equivalent under all conditions. Trisodium adducts in a bioequivalent generic made it more susceptible to DHP-I hydrolysis and less stable at room temperature, explaining its therapeutic nonequivalence. We conclude that the therapeutic nonequivalence of generic products of meropenem is due to greater susceptibility to DHP-I hydrolysis. These failing generics are compliant with USP requirements and would remain undetectable under current regulations.

Inflation expels runaways

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

Bachlechner, Thomas C.

We argue that moduli stabilization generically restricts the evolution following transitions between weakly coupled de Sitter vacua and can induce a strong selection bias towards inflationary cosmologies. The energy density of domain walls between vacua typically destabilizes Kähler moduli and triggers a runaway towards large volume. This decompactification phase can collapse the new de Sitter region unless a minimum amount of inflation occurs after the transition. A stable vacuum transition is guaranteed only if the inflationary expansion generates overlapping past light cones for all observable modes originating from the reheating surface, which leads to an approximately flat and isotropic universe.more » High scale inflation is vastly favored. Finally, our results point towards a framework for studying parameter fine-tuning and inflationary initial conditions in flux compactifications.« less

Reheating-volume measure for random-walk inflation

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

Winitzki, Sergei; Yukawa Institute of Theoretical Physics, Kyoto University, Kyoto

2008-09-15

The recently proposed 'reheating-volume' (RV) measure promises to solve the long-standing problem of extracting probabilistic predictions from cosmological multiverse scenarios involving eternal inflation. I give a detailed description of the new measure and its applications to generic models of eternal inflation of random-walk type. For those models I derive a general formula for RV-regulated probability distributions that is suitable for numerical computations. I show that the results of the RV cutoff in random-walk type models are always gauge invariant and independent of the initial conditions at the beginning of inflation. In a toy model where equal-time cutoffs lead to themore » 'youngness paradox', the RV cutoff yields unbiased results that are distinct from previously proposed measures.« less

Analytical study of sandwich structures using Euler-Bernoulli beam equation

NASA Astrophysics Data System (ADS)

Xue, Hui; Khawaja, H.

2017-01-01

This paper presents an analytical study of sandwich structures. In this study, the Euler-Bernoulli beam equation is solved analytically for a four-point bending problem. Appropriate initial and boundary conditions are specified to enclose the problem. In addition, the balance coefficient is calculated and the Rule of Mixtures is applied. The focus of this study is to determine the effective material properties and geometric features such as the moment of inertia of a sandwich beam. The effective parameters help in the development of a generic analytical correlation for complex sandwich structures from the perspective of four-point bending calculations. The main outcomes of these analytical calculations are the lateral displacements and longitudinal stresses for each particular material in the sandwich structure.

Inflation expels runaways

NASA Astrophysics Data System (ADS)

Bachlechner, Thomas C.

2016-12-01

We argue that moduli stabilization generically restricts the evolution following transitions between weakly coupled de Sitter vacua and can induce a strong selection bias towards inflationary cosmologies. The energy density of domain walls between vacua typically destabilizes Kähler moduli and triggers a runaway towards large volume. This decompactification phase can collapse the new de Sitter region unless a minimum amount of inflation occurs after the transition. A stable vacuum transition is guaranteed only if the inflationary expansion generates overlapping past light cones for all observable modes originating from the reheating surface, which leads to an approximately flat and isotropic universe. High scale inflation is vastly favored. Our results point towards a framework for studying parameter fine-tuning and inflationary initial conditions in flux compactifications.

Inflation expels runaways

DOE PAGES

Bachlechner, Thomas C.

2016-12-30

We argue that moduli stabilization generically restricts the evolution following transitions between weakly coupled de Sitter vacua and can induce a strong selection bias towards inflationary cosmologies. The energy density of domain walls between vacua typically destabilizes Kähler moduli and triggers a runaway towards large volume. This decompactification phase can collapse the new de Sitter region unless a minimum amount of inflation occurs after the transition. A stable vacuum transition is guaranteed only if the inflationary expansion generates overlapping past light cones for all observable modes originating from the reheating surface, which leads to an approximately flat and isotropic universe.more » High scale inflation is vastly favored. Finally, our results point towards a framework for studying parameter fine-tuning and inflationary initial conditions in flux compactifications.« less

Position space analysis of the AdS (in)stability problem

NASA Astrophysics Data System (ADS)

Dimitrakopoulos, Fotios V.; Freivogel, Ben; Lippert, Matthew; Yang, I.-Sheng

2015-08-01

We investigate whether arbitrarily small perturbations in global AdS space are generically unstable and collapse into black holes on the time scale set by gravitational interactions. We argue that current evidence, combined with our analysis, strongly suggests that a set of nonzero measure in the space of initial conditions does not collapse on this time scale. We perform an analysis in position space to study this puzzle, and our formalism allows us to directly study the vanishing-amplitude limit. We show that gravitational self-interaction leads to tidal deformations which are equally likely to focus or defocus energy, and we sketch the phase diagram accordingly. We also clarify the connection between gravitational evolution in global AdS and holographic thermalization.

Initial Training for VET Teachers: A Portrait within a Larger Canvas

ERIC Educational Resources Information Center

Guthrie, Hugh; McNaughton, Alicen; Gamlin, Tracy

2011-01-01

This study focuses on a critical aspect of the vocational education and training (VET) workforce: initial VET teacher training. It has identified the generic teacher education courses offered both by the VET and higher education sectors, ranging from the Certificate IV in Training and Assessment (now the Certificate IV in Training and Education)…

Insensitive fuze train for high explosives

DOEpatents

Cutting, Jack L.; Lee, Ronald S.; Von Holle, William G.

1994-01-01

A generic insensitive fuze train to initiate insensitive high explosives, such as PBXW-124. The insensitive fuze train uses a slapper foil to initiate sub-gram quantities of an explosive, such as HNS-IV or PETN. This small amount of explosive drives a larger metal slapper onto a booster charge of an insensitive explosive, such as UF-TATB. The booster charge initiates a larger charge of an explosive, such as LX-17, which in turn, initiates the insensitive high explosive, such as PBXW-124.

Insensitive fuze train for high explosives

DOEpatents

Cutting, J.L.; Lee, R.S.; Von Holle, W.G.

1994-01-04

A generic insensitive fuze train to initiate insensitive high explosives, such as PBXW-124 is described. The insensitive fuze train uses a slapper foil to initiate sub-gram quantities of an explosive, such as HNS-IV or PETN. This small amount of explosive drives a larger metal slapper onto a booster charge of an insensitive explosive, such as UF-TATB. The booster charge initiates a larger charge of an explosive, such as LX-17, which in turn, initiates the insensitive high explosive, such as PBXW-124. 3 figures.

Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity

PubMed Central

Guo, Tianruo; Al Abed, Amr; Lovell, Nigel H.; Dokos, Socrates

2013-01-01

A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented. The model provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation. PMID:23710254

SP-100 initial startup and restart control strategy

NASA Astrophysics Data System (ADS)

Halfen, Frank J.; Wong, Kwok K.; Switick, Dennis M.; Shukla, Jaikaran N.

Startup control strategies for SP-100 are described. Revised control and operating strategies are discussed which have been developed and tested using the SP-100 dynamic simulation model Aries-GFS (Generic Flight System).

Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States.

PubMed

Padula, William V; Larson, Richard A; Dusetzina, Stacie B; Apperley, Jane F; Hehlmann, Rudiger; Baccarani, Michele; Eigendorff, Ekkehard; Guilhot, Joelle; Guilhot, Francois; Hehlmann, Rudiger; Mahon, Francois-Xavier; Martinelli, Giovanni; Mayer, Jiri; Müller, Martin C; Niederwieser, Dietger; Saussele, Susanne; Schiffer, Charles A; Silver, Richard T; Simonsson, Bengt; Conti, Rena M

2016-07-01

We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib's price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness ("imatinib-first") would be cost-effective compared with the current standard of care: "physicians' choice" of initiating treatment with any one of the three TKIs. We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician's choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models' clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven's MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study's conduct. Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician's choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses. When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP. © The Author 2016. Published by Oxford University Press.

Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States

PubMed Central

Padula, William V.; Larson, Richard A.; Dusetzina, Stacie B.; Apperley, Jane F.; Hehlmann, Rudiger; Baccarani, Michele; Eigendorff, Ekkehard; Guilhot, Joelle; Guilhot, Francois; Hehlmann, Rudiger; Mahon, Francois-Xavier; Martinelli, Giovanni; Mayer, Jiri; Müller, Martin C.; Niederwieser, Dietger; Saussele, Susanne; Schiffer, Charles A.; Silver, Richard T.; Simonsson, Bengt

2016-01-01

Background: We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib’s price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness (“imatinib-first”) would be cost-effective compared with the current standard of care: “physicians’ choice” of initiating treatment with any one of the three TKIs. Methods: We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician’s choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models’ clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven’s MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study’s conduct. Results: Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician’s choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses. Conclusion: When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP. PMID:26944912

Factorial invariance of child self-report across healthy and chronic health condition groups: a confirmatory factor analysis utilizing the PedsQLTM 4.0 Generic Core Scales.

PubMed

Limbers, Christine A; Newman, Daniel A; Varni, James W

2008-07-01

The objective of the present study was to examine the factorial invariance of the PedsQL 4.0 Generic Core Scales for child self-report across 11,433 children ages 5-18 with chronic health conditions and healthy children. Multigroup Confirmatory Factor Analysis was performed specifying a five-factor model. Two multigroup structural equation models, one with constrained parameters and the other with unconstrained parameters, were proposed in order to compare the factor loadings across children with chronic health conditions and healthy children. Metric invariance (i.e., equal factor loadings) was demonstrated based on stability of the Comparative Fit Index (CFI) between the two models, and several additional indices of practical fit including the root mean squared error of approximation, the Non-normed Fit Index, and the Parsimony Normed Fit Index. The findings support an equivalent five-factor structure on the PedsQL 4.0 Generic Core Scales across healthy and chronic health condition groups. These findings suggest that when differences are found across chronic health condition and healthy groups when utilizing the PedsQL, these differences are more likely real differences in self-perceived health-related quality of life, rather than differences in interpretation of the PedsQL items as a function of health status.

Multiple policies to enhance prescribing efficiency for established medicines in Europe with a particular focus on demand-side measures: findings and future implications.

PubMed

Godman, Brian; Wettermark, Bjorn; van Woerkom, Menno; Fraeyman, Jessica; Alvarez-Madrazo, Samantha; Berg, Christian; Bishop, Iain; Bucsics, Anna; Campbell, Stephen; Finlayson, Alexander E; Fürst, Jurij; Garuoliene, Kristina; Herholz, Harald; Kalaba, Marija; Laius, Ott; Piessnegger, Jutta; Sermet, Catherine; Schwabe, Ulrich; Vlahović-Palčevski, Vera V; Markovic-Pekovic, Vanda; Vončina, Luka; Malinowska, Kamila; Zara, Corinne; Gustafsson, Lars L

2014-01-01

The appreciable growth in pharmaceutical expenditure has resulted in multiple initiatives across Europe to lower generic prices and enhance their utilization. However, considerable variation in their use and prices. Assess the influence of multiple supply and demand-side initiatives across Europe for established medicines to enhance prescribing efficiency before a decision to prescribe a particular medicine. Subsequently utilize the findings to suggest potential future initiatives that countries could consider. An analysis of different methodologies involving cross national and single country retrospective observational studies on reimbursed use and expenditure of PPIs, statins, and renin-angiotensin inhibitor drugs among European countries. Nature and intensity of the various initiatives appreciably influenced prescribing behavior and expenditure, e.g., multiple measures resulted in reimbursed expenditure for PPIs in Scotland in 2010 56% below 2001 levels despite a 3-fold increase in utilization and in the Netherlands, PPI expenditure fell by 58% in 2010 vs. 2000 despite a 3-fold increase in utilization. A similar picture was seen with prescribing restrictions, i.e., (i) more aggressive follow-up of prescribing restrictions for patented statins and ARBs resulted in a greater reduction in the utilization of patented statins in Austria vs. Norway and lower utilization of patented ARBs vs. generic ACEIs in Croatia than Austria. However, limited impact of restrictions on esomeprazole in Norway with the first prescription or recommendation in hospital where restrictions do not apply. Similar findings when generic losartan became available in Western Europe. Multiple demand-side measures are needed to influence prescribing patterns. When combined with supply-side measures, activities can realize appreciable savings. Health authorities cannot rely on a "spill over" effect between classes to affect changes in prescribing.

Multiple policies to enhance prescribing efficiency for established medicines in Europe with a particular focus on demand-side measures: findings and future implications

PubMed Central

Godman, Brian; Wettermark, Bjorn; van Woerkom, Menno; Fraeyman, Jessica; Alvarez-Madrazo, Samantha; Berg, Christian; Bishop, Iain; Bucsics, Anna; Campbell, Stephen; Finlayson, Alexander E.; Fürst, Jurij; Garuoliene, Kristina; Herholz, Harald; Kalaba, Marija; Laius, Ott; Piessnegger, Jutta; Sermet, Catherine; Schwabe, Ulrich; Vlahović-Palčevski, Vera V.; Markovic-Pekovic, Vanda; Vončina, Luka; Malinowska, Kamila; Zara, Corinne; Gustafsson, Lars L.

2014-01-01

Introduction: The appreciable growth in pharmaceutical expenditure has resulted in multiple initiatives across Europe to lower generic prices and enhance their utilization. However, considerable variation in their use and prices. Objective: Assess the influence of multiple supply and demand-side initiatives across Europe for established medicines to enhance prescribing efficiency before a decision to prescribe a particular medicine. Subsequently utilize the findings to suggest potential future initiatives that countries could consider. Method: An analysis of different methodologies involving cross national and single country retrospective observational studies on reimbursed use and expenditure of PPIs, statins, and renin-angiotensin inhibitor drugs among European countries. Results: Nature and intensity of the various initiatives appreciably influenced prescribing behavior and expenditure, e.g., multiple measures resulted in reimbursed expenditure for PPIs in Scotland in 2010 56% below 2001 levels despite a 3-fold increase in utilization and in the Netherlands, PPI expenditure fell by 58% in 2010 vs. 2000 despite a 3-fold increase in utilization. A similar picture was seen with prescribing restrictions, i.e., (i) more aggressive follow-up of prescribing restrictions for patented statins and ARBs resulted in a greater reduction in the utilization of patented statins in Austria vs. Norway and lower utilization of patented ARBs vs. generic ACEIs in Croatia than Austria. However, limited impact of restrictions on esomeprazole in Norway with the first prescription or recommendation in hospital where restrictions do not apply. Similar findings when generic losartan became available in Western Europe. Conclusions: Multiple demand-side measures are needed to influence prescribing patterns. When combined with supply-side measures, activities can realize appreciable savings. Health authorities cannot rely on a “spill over” effect between classes to affect changes in prescribing. PMID:24987370

Comparing effectiveness of generic and disease-specific self-management interventions for people with diabetes in a practice context.

PubMed

Ghahari, Setareh; Packer, Tanya; Boldy, Duncan; Melling, Lauren; Parsons, Richard

2015-10-01

The effectiveness of self-management interventions has been demonstrated. However, the benefits of generic vs. disease-specific programs are unclear, and their efficacy within a practice setting has yet to be fully explored. To compare the outcomes of the diabetes-specific self-management program (Diabetes) and the generic chronic disease Self-management Program (Chronic Condition) and to explore whether program characteristics, evaluated using the Quality Self-Management Assessment Framework (Q-SAF), provide insight into the results of the outcome evaluation. A pragmatic pretest, post-test design with 12-week follow up was used to compare the 2 self-management interventions. Outcomes were quality of life, self-efficacy, loneliness, self-management skills, depression, and health behaviours. People with diabetes self-selected attendance at the Diabetes or Chronic Condition program offered as part of routine practice. Participants with diabetes in the 2 programs (Diabetes=200; Chronic Condition=90) differed significantly in almost all demographic and clinical characteristics. Both programs yielded positive outcomes. Controlling for baseline and demographic characteristics, random effects modelling showed an interaction between time and program for 1 outcome: self-efficacy (p=0.029). Participants in the Chronic Condition group experienced greater improvements over time than did those in the Diabetes group. The Q-SAF analysis showed differences in program content, delivery and workforce capacity. People with diabetes benefited from both programs, but participation in the generic program resulted in greater improvements in self-efficacy for participants who had self-selected that program. Both programs in routine care led to health-related improvements. The Q-SAF can be used to assess the quality of programs. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Pharmaceutical quality of seven generic Levodopa/Benserazide products compared with original Madopar® / Prolopa®.

PubMed

Gasser, Urs E; Fischer, Anton; Timmermans, Jan P; Arnet, Isabelle

2013-04-23

By definition, a generic product is considered interchangeable with the innovator brand product. Controversy exists about interchangeability, and attention is predominantly directed to contaminants. In particular for chronic, degenerative conditions such as in Parkinson's disease (PD) generic substitution remains debated among physicians, patients and pharmacists. The objective of this study was to compare the pharmaceutical quality of seven generic levodopa/benserazide hydrochloride combination products marketed in Germany with the original product (Madopar® / Prolopa® 125, Roche, Switzerland) in order to evaluate the potential impact of Madopar® generics versus branded products for PD patients and clinicians. Madopar® / Prolopa® 125 tablets and capsules were used as reference material. The generic products tested (all 100 mg/25 mg formulations) included four tablet and three capsule formulations. Colour, appearance of powder (capsules), disintegration and dissolution, mass of tablets and fill mass of capsules, content, identity and amounts of impurities were assessed along with standard physical and chemical laboratory tests developed and routinely practiced at Roche facilities. Results were compared to the original "shelf-life" specifications in use by Roche. Each of the seven generic products had one or two parameters outside the specifications. Deviations for the active ingredients ranged from +8.4% (benserazide) to -7.6% (levodopa) in two tablet formulations. Degradation products were measured in marked excess (+26.5%) in one capsule formulation. Disintegration time and dissolution for levodopa and benserazide hydrochloride at 30 min were within specifications for all seven generic samples analysed, however with some outliers. Deviations for the active ingredients may go unnoticed by a new user of the generic product, but may entail clinical consequences when switching from original to generic during a long-term therapy. Degradation products may pose a safety concern. Our results should prompt caution when prescribing a generic of Madopar®/Prolopa®, and also invite to further investigations in view of a more comprehensive approach, both pharmaceutical and clinical.

Attitudes of Slovene general practitioners towards generic drug prescribing and comparison with international studies.

PubMed

Kersnik, J; Peklar, J

2006-12-01

Over the recent years there has been a steady 7% yearly increase in prescribing costs, which accounts for 17% of the Slovene national health care budget. Substitution of branded products by generic equivalents can offer savings. General practitioners (GPs) are often concerned about the quality of generic products and possible legal liabilities associated with their use. We wanted to examine the attitudes of GPs in Slovenia towards generic drug prescribing. We conducted a postal survey of a random sample of 200 out of 800 GPs in Slovenia from the National Health Insurance Institute database. GPs were asked 21 questions regarding their knowledge on generic drugs, awareness of prescribing costs, prices of generic drugs relative to brand name drugs and their attitude towards use of generic drugs. The 117 (58.5%) replies we received represent 15% of the GP population in Slovenia. 66.1% of GPs considered rising costs of medicines to be a serious problem for the health care budget. Each week, over 50% of GPs experienced demands from patients for specific drugs and the majority of GPs usually met their patients' demands or requests from hospital consultants for branded products. 38.3% of GPs did not take price into consideration when prescribing drugs. The majority of GPs (88.9%) perceived generics to have the same effectiveness as branded drugs. One quarter of GPs would prescribe more generics if additional clinical trials were presented. 37.3% would follow advice of academic detailers and 30.3% expected the generics to be even cheaper than they were. Independent detailing was welcomed by 63.8% of GPs because of the big influence of the pharmaceutical industry on the prescribing habits. 15.5% thought that the industry had a tremendous impact on their prescribing patterns. Slovene GPs are aware of the cost of prescribed drugs. They are willing to accept independent academic detailing to improve their prescribing and are willing to increase generic drugs under certain conditions.

A multiplex PCR-based method to identify strongylid parasite larvae recovered from ovine faecal cultures and/or pasture samples.

PubMed

Bisset, S A; Knight, J S; Bouchet, C L G

2014-02-24

A multiplex PCR-based method was developed to overcome the limitations of microscopic examination as a means of identifying individual infective larvae from the wide range of strongylid parasite species commonly encountered in sheep in mixed sheep-cattle grazing situations in New Zealand. The strategy employed targets unique species-specific sequence markers in the second internal transcribed spacer (ITS-2) region of ribosomal DNA of the nematodes and utilises individual larval lysates as reaction templates. The basic assay involves two sets of reactions designed to target the ten strongylid species most often encountered in ovine faecal cultures under New Zealand conditions (viz. Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus, Cooperia curticei, Cooperia oncophora, Nematodirus spathiger, Chabertia ovina, and Oesophagostomum venulosum). Five species-specific primers, together with a pair of "generic" (conserved) primers, are used in each of the reactions. Two products are generally amplified, one by the generic primer pair regardless of species (providing a positive PCR control) and the other (whose size is indicative of the species present) by the appropriate species-specific primer in combination with one or other of the generic primers. If necessary, any larvae not identified by these reactions can subsequently be tested using primers designed specifically to detect those species less frequently encountered in ovine faecal cultures (viz. Ostertagia ostertagi, Ostertagia leptospicularis, Cooperia punctata, Nematodirus filicollis, and Bunostomum trigonocephalum). Results of assays undertaken on >5500 nematode larvae cultured from lambs on 16 different farms distributed throughout New Zealand indicated that positive identifications were initially obtained for 92.8% of them, while a further 4.4% of reactions gave a generic but no visible specific product and 2.8% gave no discernible PCR products (indicative of insufficient or poor quality DNA template). Of the reactions which yielded only generic products, 91% gave positive identifications in an assay re-run, resulting in a failure rate of just ∼ 0.4% for reactions containing amplifiable template. Although the method was developed primarily to provide a reliable way to identify individual strongylid larvae for downstream molecular applications, it potentially has a variety of other research and practical applications which are not readily achievable at present using other methods. Copyright © 2013 Elsevier B.V. All rights reserved.

Consumers' views on generic medicines: a review of the literature.

PubMed

Hassali, Mohamed A A; Shafie, Asrul A; Jamshed, Shazia; Ibrahim, Mohamed I M; Awaisu, Ahmed

2009-04-01

To review the literature on consumers' knowledge, attitudes and opinions of the use of generic medicines. A narrative review of studies conducted from 1970 to 2008 on consumers perceptions and views towards generic medicines was performed. An extensive literature search was undertaken using indexing services available at the authors' institution library. The following keywords were used for the search: brand, generic, multisource, medications, medicines, drugs, pharmaceuticals and consumers, customers, and patients. Electronic databases searched were Medline, Inside Web, ISI Web of Knowledge, Science Direct, Springer Link, JSTOR, Proquest, Ebsco Host and Google Scholar. These electronic databases were searched for full text papers published in English from 1970 to October 2008. Twenty studies were identified. Eleven were from the USA, four were from Europe, two were from Canada and one each was from Australia, Brazil and Malaysia. In general, consumers showed mixed reactions towards the use of generic medicines. This was evident from the divergence of views observed by country development level, consumers' socioeconomic characteristics, drug product characteristics, pharmaceutical reimbursement system, policy environment, contact with health care professionals, past experience with medications, and knowledge of the seriousness of a medical condition. Patient confidence and knowledge pertaining to generic medicines use have increased over the past four decades, especially in developed countries. Mass educational efforts, financial incentives, and greater communication among patients and health care professionals were seen as major drivers to the uptake of generic medicines among consumers.

The generic drug user fee amendments: an economic perspective

PubMed Central

Berndt, Ernst R; Murphy, Stephen J

2018-01-01

Abstract Since the vast majority of prescription drugs consumed by Americans are off patent (‘generic’), their regulation and supply is of wide interest. We describe events leading up to the US Congress's 2012 passage of the Generic Drug User Fee Amendments (GDUFA I) as part of the Food and Drug Administration Safety and Innovation Act (FDASIA). Under GDUFA I, generic manufacturers agreed to pay approximately $300 million in fees each year of the five-year program. In exchange, the US Food and Drug Administration (FDA) committed to performance goals. We describe GDUFA I’s FDA commitments, provisions, goals, and annual fee structure and compare it to that entailed in the authorization and implementation of GDUFA II on October 1, 2017. We explain how user fees required under GDUFA I erected barriers to entry and created scale and scope economies for incumbent manufacturers. Congress changed user fees under GDUFA II in part to lessen these incentives. In order to initiate and sustain user fees under GDUFA legislation, FDA requires the submission of self-reported data on generic manufacturers including domestic and foreign facilities. These data are public and our examination of them provides an unprecedented window into the recent organization of generic drug manufacturers supplying the US market. Our results suggest that generic drug manufacturing is increasingly concentrated and foreign. We discuss the implications of this observed market structure for GDUFA II’s implementation among other outcomes. PMID:29707218

Generic Ada code in the NASA space station command, control and communications environment

NASA Technical Reports Server (NTRS)

Mcdougall, D. P.; Vollman, T. E.

1986-01-01

The results of efforts to apply powerful Ada constructs to the formatted message handling process are described. The goal of these efforts was to extend the state-of-technology in message handling while at the same time producing production-quality, reusable code. The first effort was initiated in September, 1984 and delivered in April, 1985. That product, the Generic Message Handling Facility, met initial goals, was reused, and is available in the Ada Repository on ARPANET. However, it became apparent during its development that the initial approach to building a message handler template was not optimal. As a result of this initial effort, several alternate approaches were identified, and research is now on-going to identify an improved product. The ultimate goal is to be able to instantly build a message handling system for any message format given a specification of that message format. The problem lies in how to specify the message format, and one that is done, how to use that information to build the message handler. Message handling systems and message types are described. The initial efforts, its results and its shortcomings are detailed. The approach now being taken to build a system which will be significantly easier to implement, and once implemented, easier to use, is described. Finally, conclusions are offered.

Mechanical energy fluctuations in granular chains: the possibility of rogue fluctuations or waves.

PubMed

Han, Ding; Westley, Matthew; Sen, Surajit

2014-09-01

The existence of rogue or freak waves in the ocean has been known for some time. They have been reported in the context of optical lattices and the financial market. We ask whether such waves are generic to late time behavior in nonlinear systems. In that vein, we examine the dynamics of an alignment of spherical elastic beads held within fixed, rigid walls at zero precompression when they are subjected to sufficiently rich initial conditions. Here we define such waves generically as unusually large energy fluctuations that sustain for short periods of time. Our simulations suggest that such unusually large fluctuations ("hot spots") and occasional series of such fluctuations through space and time ("rogue fluctuations") are likely to exist in the late time dynamics of the granular chain system at zero dissipation. We show that while hot spots are common in late time evolution, rogue fluctuations are seen in purely nonlinear systems (i.e., no precompression) at late enough times. We next show that the number of such fluctuations grows exponentially with increasing nonlinearity whereas rogue fluctuations decrease superexponentially with increasing precompression. Dissipation-free granular alignment systems may be possible to realize as integrated circuits and hence our observations may potentially be testable in the laboratory.

Cost-effectiveness comparison of current proton-pump inhibitors to treat gastro-oesophageal reflux disease in the UK.

PubMed

Remák, E; Brown, R E; Yuen, C; Robinson, A

2005-10-01

Gastro-oesophageal reflux disease (GORD) is a recurring condition with many patients requiring long-term maintenance therapy. Therefore initial choice of treatment has long-term cost implications. The aim was to compare the costs and effectiveness of treatment of GORD the (unconfirmed by endoscopy) with seven proton pump inhibitors (PPIs: esomeprazole, lansoprazole (capsules and oro-dispersible tablets), omeprazole (generic and branded), pantoprazole and rabeprazole), over one year. A treatment model was developed of 13 interconnected Markov models incorporating acute treatment of symptoms, long-term therapy and subsequent decisions to undertake endoscopy to confirm diagnosis. Patients were allowed to stop treatment or to receive maintenance treatment either continuously or on-demand depending on response to therapy. Long-term dosing schedule (high dose or step-down dose) was based on current market data. Efficacy of treatments was based on clinical trials and follow-up studies, while resource use patterns were determined by a panel of physicians. The model predicts total expected annual costs, number of symptom-free days and quality-adjusted life-years (QALY). Generic omeprazole and rabeprazole dominated (i.e. cost less and resulted in more symptom-free days and higher QALY gains) the other PPIs. Rabeprazole had a favourable cost-effectiveness ratio of 3.42 pounds per symptom-free day and 8308 pounds/quality-adjusted life-year gained when compared with generic omeprazole. Rabeprazole remained cost-effective independent of choice of maintenance treatment (i.e. proportion of patients remaining on continuous treatment versus on-demand treatment). Economic models provide a useful framework to evaluate PPIs in realistic clinical scenarios. Our findings show that rabeprazole is cost-effective for the treatment of GORD.

Geographical scenario uncertainty in generic fate and exposure factors of toxic pollutants for life-cycle impact assessment

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

Huijbregts, Mark A.J.; Lundi, Sven; McKone, Thomas E.

In environmental life-cycle assessments (LCA), fate and exposure factors account for the general fate and exposure properties of chemicals under generic environmental conditions by means of 'evaluative' multi-media fate and exposure box models. To assess the effect of using different generic environmental conditions, fate and exposure factors of chemicals emitted under typical conditions of (1) Western Europe, (2) Australia and (3) the United States of America were compared with the multi-media fate and exposure box model USES-LCA. Comparing the results of the three evaluative environments, it was found that the uncertainty in fate and exposure factors for ecosystems and humansmore » due to choice of an evaluative environment, as represented by the ratio of the 97.5th and 50th percentile, is between a factor 2 and 10. Particularly, fate and exposure factors of emissions causing effects in fresh water ecosystems and effects on human health have relatively high uncertainty. This uncertainty i s mainly caused by the continental difference in the average soil erosion rate, the dimensions of the fresh water and agricultural soil compartment, and the fraction of drinking water coming from ground water.« less

Comparing recurrent antibiotic prescriptions in children treated with a brand name or a generic formulation.

PubMed

Piovani, Daniele; Clavenna, Antonio; Cartabia, Massimo; Bortolotti, Angela; Fortino, Ida; Merlino, Luca; Bonati, Maurizio

2015-02-01

The aim of this study was to investigate the rate of recurrent prescriptions and hospital admissions in children receiving a brand name or generic antibiotic prescription. The data source was a database of reimbursed prescriptions. Outpatient children/adolescents <18 years old (Lombardy Region, Italy) were included. The observational period was February-April 2010. A recurrence was defined as an antibiotic prescription occurring within 28 days after an index prescription. The rate of recurrent prescriptions and hospital admissions was calculated for generic/brand name formulations and for each age strata (0-5, 6-11, and 12-17 years old) for four antibiotics: amoxicillin, amoxicillin clavulanate, clarithromycin, and cefaclor. The percentage of therapy switches was calculated. Cochran-Mantel-Haenszel test was used to compare the age-adjusted outcomes. In all, 17.5% (57 346) of children received at least one recurrent prescription. The rate of recurrent prescriptions was slightly lower in children receiving any generic (OR 0.96; 95%CI 0.93-0.98), compared with any brand name, antibiotic. The percentage of hospital admissions occurring in children initially treated with a brand name (1.01%; 95%CI 0.98-1.08) or generic (1.03%; 0.96-1.06) antibiotic was not different (p = 0.43). For children receiving amoxicillin clavulanate, the hospital admission rate was slightly higher in the brand name group (p = 0.002), while no differences were found for the other active substances. Children treated with generic antibiotics had no worse safety and effectiveness outcomes when compared with those receiving brand name ones. These results provide additional evidence on the safety of generic antibiotics. Copyright © 2014 John Wiley & Sons, Ltd.

Impacts of generic competition and benefit management practices on spending for prescription drugs: evidence from Medicare's Part D benefit.

PubMed

Sheingold, Steven; Nguyen, Nguyen Xuan

2014-01-01

This study estimates the effects of generic competition, increased cost-sharing, and benefit practices on utilization and spending for prescription drugs. We examined changes in Medicare price and utilization from 2007 to 2009 of all drugs in 28 therapeutic classes. The classes accounted for 80% of Medicare Part D spending in 2009 and included the 6 protected classes and 6 classes with practically no generic competition. All variables were constructed to measure each drug relative to its class at a specific plan sponsor. We estimated that the shift toward generic utilization had cut in half the rate of increase in the price of a prescription during 2007-2009. Specifically, the results showed that (1) rapid generic penetration had significantly held down costs per prescription, (2) copayment and other benefit practices shifted utilization to generics and favored brands, and (3) price increases were generally greater in less competitive classes of drugs. In many ways, Part D was implemented at a fortuitous time; since 2006, there have been relatively few new blockbuster drugs introduced, and many existing high-volume drugs used by beneficiaries were in therapeutic classes with multiple brands and generic alternatives. Under these conditions, our paper showed that plan sponsors have been able to contain costs by encouraging use of generics or drugs offering greater value within therapeutic classes. It is less clear what will happen to future Part D costs if a number of new and effective drugs for beneficiaries enter the market with no real competitors.

Reducing orbital eccentricity of precessing black-hole binaries

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

Buonanno, Alessandra; Taracchini, Andrea; Kidder, Lawrence E.

2011-05-15

Building initial conditions for generic binary black-hole evolutions which are not affected by initial spurious eccentricity remains a challenge for numerical-relativity simulations. This problem can be overcome by applying an eccentricity-removal procedure which consists of evolving the binary black hole for a couple of orbits, estimating the resulting eccentricity, and then restarting the simulation with corrected initial conditions. The presence of spins can complicate this procedure. As predicted by post-Newtonian theory, spin-spin interactions and precession prevent the binary from moving along an adiabatic sequence of spherical orbits, inducing oscillations in the radial separation and in the orbital frequency. For single-spinmore » binary black holes these oscillations are a direct consequence of monopole-quadrupole interactions. However, spin-induced oscillations occur at approximately twice the orbital frequency, and therefore can be distinguished and disentangled from the initial spurious eccentricity which occurs at approximately the orbital frequency. Taking this into account, we develop a new eccentricity-removal procedure based on the derivative of the orbital frequency and find that it is rather successful in reducing the eccentricity measured in the orbital frequency to values less than 10{sup -4} when moderate spins are present. We test this new procedure using numerical-relativity simulations of binary black holes with mass ratios 1.5 and 3, spin magnitude 0.5, and various spin orientations. The numerical simulations exhibit spin-induced oscillations in the dynamics at approximately twice the orbital frequency. Oscillations of similar frequency are also visible in the gravitational-wave phase and frequency of the dominant l=2, m=2 mode.« less

Early Impact Of The Affordable Care Act On Oral Contraceptive Cost Sharing, Discontinuation, And Nonadherence.

PubMed

Pace, Lydia E; Dusetzina, Stacie B; Keating, Nancy L

2016-09-01

The oral contraceptive pill is the contraceptive method most commonly used by US women, but inconsistent use of the pill is a contributor to high rates of unintended pregnancy. The relationship between consumer cost sharing and consistent use of the pill is not well understood, and the impact of the elimination of cost sharing for oral contraceptive pills in a mandate in the Affordable Care Act (ACA) is not yet known. We analyzed insurance claims for 635,075 women with employer-sponsored insurance who were initiating use of the pill, to examine rates of discontinuation and nonadherence, their relationship with cost sharing, and trends before and during the first year after implementation of the ACA mandate. We found that cost sharing for oral contraceptives decreased markedly following implementation, more significantly for generic than for brand-name versions. Higher copays were associated with greater discontinuation of and nonadherence to generic pills than was the case with zero copayments. Discontinuation of the use of generic or brand-name pills decreased slightly but significantly following ACA implementation, as did nonadherence to brand-name pills. Our findings suggest a modest early impact of the ACA on improving consistent use of oral contraceptives among women initiating their use. Project HOPE—The People-to-People Health Foundation, Inc.

A longitudinal examination of generic and occupational specific job demands, and work-related social support associated with burnout among nurses in Sweden.

PubMed

Sundin, L; Hochwälder, J; Lisspers, J

2011-01-01

Burnout is a familiar problem within nursing. This longitudinal study was designed to examine the roles that generic and occupational specific job demands (i.e. "pain and death", "patient and relative needs", "threats and violence", "professional worries"), and various work-related sources of support play in association with burnout in a sample of registered nurses in Sweden. A questionnaire was completed on two different occasions, by the same group of nurses from three hospitals and two primary health care centers. Nurses with initial low and moderate scores on emotional exhaustion (n=585) and depersonalization (n=631) were included in the logistic regression analyses. Initial scores, as well as four categories examining change over time in the predictors (unchanged low, improved, impaired, unchanged high), were associated with burnout approximately one year later. In the multivariate analyses, quantitative job demands and professional worries were associated with emotional exhaustion. Poor co-worker support was associated with depersonalization over time. This study suggests an association between generic as well as occupational specific job demands and emotional exhaustion. Furthermore, an association between poor co-worker support and depersonalization was suggested. Implications of these findings and recommended directions for future research are discussed.

Comparison of Informed Consent Preferences for Multiplex Genetic Carrier Screening among a Diverse Population.

PubMed

Reeves, Ashley; Trepanier, Angela

2016-02-01

Multiplex genetic carrier screening is increasingly being integrated into reproductive care. Obtaining informed consent becomes more challenging as the number of screened conditions increases. Implementing a model of generic informed consent may facilitate informed decision-making. Current Wayne State University students and staff were invited to complete a web-based survey by blast email solicitation. Participants were asked to determine which of two generic informed consent scenarios they preferred: a brief versus a detailed consent. They were asked to rank the importance of different informational components in making an informed decision and to provide demographic information. Comparisons between informational preferences, demographic variables and scenario preferences were made. Six hundred ninety three participants completed the survey. When evaluating these generic consents, the majority preferred the more detailed consent (74.5%), and agreed that it provided enough information to make an informed decision (89.5%). Those who thought it would be more important to know the severity of the conditions being screened (p = .002) and range of symptoms (p = .000) were more likely to prefer the more detailed consent. There were no significant associations between scenario preferences and demographic variables. A generic consent was perceived to provide sufficient information for informed decision making regarding multiplex carrier screening with most preferring a more detailed version of the consent. Individual attitudes rather than demographic variables influenced preferences regarding the amount of information that should be included in the generic consent. The findings have implications for how clinicians approach providing tailored informed consent.

Unsteady Pressures on a Generic Capsule Shape

NASA Technical Reports Server (NTRS)

Burnside, Nathan; Ross, James C.

2015-01-01

While developing the aerodynamic database for the Orion spacecraft, the low-speed flight regime (transonic and below) proved to be the most difficult to predict and measure accurately. The flow over the capsule heat shield in descent flight was particularly troublesome for both computational and experimental efforts due to its unsteady nature and uncertainty about the boundary layer state. The data described here were acquired as part of a study to improve the understanding of the overall flow around a generic capsule. The unsteady pressure measurements acquired on a generic capsule shape are presented along with a discussion about the effects of various flight conditions and heat-shield surface roughness on the resulting pressure fluctuations.

Patient adherence to generic versus brand statin therapy after acute myocardial infarction: Insights from the Can Rapid Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines Registry.

PubMed

O'Brien, Emily C; McCoy, Lisa A; Thomas, Laine; Peterson, Eric D; Wang, Tracy Y

2015-07-01

Statins reduce mortality after acute myocardial infarction, but up to half of patients discontinue statin use within 1 year of therapy initiation. Although cost may influence medication adherence, it is unknown whether use of generic versus brand statins influences adherence. We linked detailed inhospital clinical data for 1421 non-ST-segment elevation myocardial infarction patients discharged on a statin in 2006 to Medicare Part D medication claims records to examine postdischarge medication use. One-year statin adherence was defined using the proportion of days covered with optimal adherence ≥80%. We examined the association of brand versus generic statin prescription and 1-year adherence after adjusting for demographics, clinical factors, predischarge lipid values, prior statin use, and socioeconomic status. Overall, 65.5% of statin fills were for brand-name statins. There were few baseline differences in demographics and clinical factors among generic versus brand users. Patient copay amounts were higher for brand versus generic statins (median = $25 vs $5, P < .001), yet the mean proportion of days covered over 1 year was similar (71.5% vs 68.9%; P = .97; unadjusted odds ratio 1.15 [95% CI 0.96-1.37]). Proportion of days covered ≥80% was low for both generic (56.2%) and brand statins (55.9%; P = .93). Statin adherence rates remained similar between generic and brand users after adjusting for demographics, clinical risk factors, lipid value, prior statin use, and socioeconomic status. In a cohort of older non-ST-segment elevation myocardial infarction patients, we found no evidence that use of generic versus brand drug was associated with higher adherence to statins at 1 year after hospital discharge. Copyright © 2015 Elsevier Inc. All rights reserved.

Cost variability of suggested generic treatment alternatives under the Medicare Part D benefit.

PubMed

Patel, Rajul A; Walberg, Mark P; Tong, Emily; Tan, Florence; Rummel, Ashley E; Woelfel, Joseph A; Carr-Lopez, Sian M; Galal, Suzanne M

2014-03-01

The substitution of generic treatment alternatives for brand-name drugs is a strategy that can help lower Medicare beneficiary out-of-pocket costs. Beginning in 2011, Medicare beneficiaries reaching the coverage gap received a 50% discount on the full drug cost of brand-name medications and a 7% discount on generic medications filled during the gap. This discount will increase until 2020, when beneficiaries will be responsible for 25% of total drug costs during the coverage gap. To examine the cost variability of brand and generic drugs within 4 therapeutic classes before and during the coverage gap for each 2011 California stand-alone prescription drug plan (PDP) and prospective coverage gap costs in 2020 to determine the effects on beneficiary out-of-pocket drug costs. Equivalent doses of brand and generic drugs in the following 4 pharmacological classes were examined: angiotensin II receptor blockers (ARBs), bisphosphonates, HMG-CoA reductase inhibitors (statins), and proton pump inhibitors (PPIs). The full drug cost and patient copay/coinsurance amounts during initial coverage and the coverage gap of each drug was recorded based on information retrieved from the Medicare website. These drug cost data were recorded for 28 California PDPs. The highest cost difference between a brand medication and a Centers for Medicare Medicaid Services (CMS)-suggested generic treatment alternative varied between $110.53 and $195.49 at full cost and between $51.37 and $82.35 in the coverage gap. The lowest cost difference varied between $38.45 and $76.93 at full cost and between -$4.11 and $18.52 during the gap. Medicare beneficiaries can realize significant out-of-pocket cost savings for their drugs by taking CMS-suggested generic treatment alternatives. However, due to larger discounts on brand medications made available through recent changes reducing the coverage gap, the potential dollar savings by taking suggested generic treatment alternatives during the gap is less compelling and will decrease as subsidies increase.

Mathematical Analysis of a Coarsening Model with Local Interactions

NASA Astrophysics Data System (ADS)

Helmers, Michael; Niethammer, Barbara; Velázquez, Juan J. L.

2016-10-01

We consider particles on a one-dimensional lattice whose evolution is governed by nearest-neighbor interactions where particles that have reached size zero are removed from the system. Concentrating on configurations with infinitely many particles, we prove existence of solutions under a reasonable density assumption on the initial data and show that the vanishing of particles and the localized interactions can lead to non-uniqueness. Moreover, we provide a rigorous upper coarsening estimate and discuss generic statistical properties as well as some non-generic behavior of the evolution by means of heuristic arguments and numerical observations.

Architecture design of a generic centralized adjudication module integrated in a web-based clinical trial management system

PubMed Central

Zhao, Wenle; Pauls, Keith

2015-01-01

Background Centralized outcome adjudication has been used widely in multi-center clinical trials in order to prevent potential biases and to reduce variations in important safety and efficacy outcome assessments. Adjudication procedures could vary significantly among different studies. In practice, the coordination of outcome adjudication procedures in many multicenter clinical trials remains as a manual process with low efficiency and high risk of delay. Motivated by the demands from two large clinical trial networks, a generic outcome adjudication module has been developed by the network’s data management center within a homegrown clinical trial management system. In this paper, the system design strategy and database structure are presented. Methods A generic database model was created to transfer different adjudication procedures into a unified set of sequential adjudication steps. Each adjudication step was defined by one activate condition, one lock condition, one to five categorical data items to capture adjudication results, and one free text field for general comments. Based on this model, a generic outcome adjudication user interface and a generic data processing program were developed within a homegrown clinical trial management system to provide automated coordination of outcome adjudication. Results By the end of 2014, this generic outcome adjudication module had been implemented in 10 multicenter trials. A total of 29 adjudication procedures were defined with the number of adjudication steps varying from 1 to 7. The implementation of a new adjudication procedure in this generic module took an experienced programmer one or two days. A total of 7,336 outcome events had been adjudicated and 16,235 adjudication step activities had been recorded. In a multicenter trial, 1144 safety outcome event submissions went through a three-step adjudication procedure and reported a median of 3.95 days from safety event case report form submission to adjudication completion. In another trial, 277 clinical outcome events were adjudicated by a six-step procedure and took a median of 23.84 days from outcome event case report form submission to adjudication procedure completion. Conclusions A generic outcome adjudication module integrated in the clinical trial management system made the automated coordination of efficacy and safety outcome adjudication a reality. PMID:26464429

Launch Condition Deviations of Reusable Launch Vehicle Simulations in Exo-Atmospheric Zoom Climbs

NASA Technical Reports Server (NTRS)

Urschel, Peter H.; Cox, Timothy H.

2003-01-01

The Defense Advanced Research Projects Agency has proposed a two-stage system to deliver a small payload to orbit. The proposal calls for an airplane to perform an exo-atmospheric zoom climb maneuver, from which a second-stage rocket is launched carrying the payload into orbit. The NASA Dryden Flight Research Center has conducted an in-house generic simulation study to determine how accurately a human-piloted airplane can deliver a second-stage rocket to a desired exo-atmospheric launch condition. A high-performance, fighter-type, fixed-base, real-time, pilot-in-the-loop airplane simulation has been modified to perform exo-atmospheric zoom climb maneuvers. Four research pilots tracked a reference trajectory in the presence of winds, initial offsets, and degraded engine thrust to a second-stage launch condition. These launch conditions have been compared to the reference launch condition to characterize the expected deviation. At each launch condition, a speed change was applied to the second-stage rocket to insert the payload onto a transfer orbit to the desired operational orbit. The most sensitive of the test cases was the degraded thrust case, yielding second-stage launch energies that were too low to achieve the radius of the desired operational orbit. The handling qualities of the airplane, as a first-stage vehicle, have also been investigated.

"Hi Mommy": Parental Preferences of Greetings by Medical Staff.

PubMed

Wilks-Gallo, Lisa; Aron, Chaim Zev; Messina, Catherine R

2018-04-01

The therapeutic alliance between pediatricians and parents begins at the initial encounter. The manner in which pediatricians greet family members influences this relationship. This study evaluated whether parents are addressed using generic titles and investigated perceptions of parents regarding how they are addressed by medical staff. Written surveys of 137 parents of pediatric inpatients collected opinions about greetings during medical encounters. Parents were asked if they have been addressed as Mom/Dad/Mommy/Daddy during past medical encounters and which generic titles they would prefer. Using a Likert-type scale, the parents' perceptions of various salutations were assessed and compared. In this sample, 86% of parents were previously called Mom/Dad/Mommy/Daddy. Parents preferred to be addressed as Mom or Dad over other generic titles. Many disliked being addressed as Mommy/Daddy, Ma'am/Sir, or without a name, suggesting that providers should avoid the use of these salutations.

Conception of an Expert Advisory Board for the European Reference Network for Rare Respiratory Diseases.

PubMed

Walther, Désirée; Steinmann, Olivia; Schaefer, Johanna; Wagner, Thomas O F; Storf, Holger

2018-01-01

Due to low prevalence of rare diseases and lack of expertise, patients suffering rare diseases are challenged with finding experts that are specialized and experienced in treating their conditions and get qualified answers. To address this issue, the approach of an interactive platform was made, which should allow affected patients or physicians the possibility to ask experts their specific questions to gather and improve their knowledge about their condition. This paper introduces the pan-European Internet platform EXABO, an Expert Advisory Board, which is developed within the framework of the European Reference Network for rare respiratory diseases (ERN-LUNG). The purpose of establishing this platform is initially dedicated to rare respiratory diseases in whole Europe, whilst the set-up is however, planned to be a generic tool for additional diseases or groups of diseases. This paper gives an overview of the concept and planning of the EXABO platform and shows how the platform is to be implemented.

Unnatural selection: talent identification and development in sport.

PubMed

Abbott, Angela; Button, Chris; Pepping, Gert-Jan; Collins, Dave

2005-01-01

The early identification of talented individuals has become increasingly important across many performance domains. Current talent identification (TI) schemes in sport typically select on the basis of discrete, unidimensional measures at unstable periods in the athlete's development. In this article, the concept of talent is revised as a complex, dynamical system in which future behaviors emerge from an interaction of key performance determinants such as psychological behaviors, motor abilities, and physical characteristics. Key nonlinear dynamics concepts are related to TI approaches such as sensitivity to initial conditions, transitions, and exponential behavioral distributions. It is concluded that many TI models place an overemphasis on early identification rather than the development of potentially talented performers. A generic model of talent identification and development is proposed that addresses these issues and provides direction for future research.

Evidence for self-refraction in a convergence zone: NPE (Nonlinear progressive wave equation) model results

NASA Technical Reports Server (NTRS)

Mcdonald, B. Edward; Plante, Daniel R.

1989-01-01

The nonlinear progressive wave equation (NPE) model was developed by the Naval Ocean Research and Development Activity during 1982 to 1987 to study nonlinear effects in long range oceanic propagation of finite amplitude acoustic waves, including weak shocks. The NPE model was applied to propagation of a generic shock wave (initial condition provided by Sandia Division 1533) in a few illustrative environments. The following consequences of nonlinearity are seen by comparing linear and nonlinear NPE results: (1) a decrease in shock strength versus range (a well-known result of entropy increases at the shock front); (2) an increase in the convergence zone range; and (3) a vertical meandering of the energy path about the corresponding linear ray path. Items (2) and (3) are manifestations of self-refraction.

Geometrical shock dynamics, formation of singularities and topological bifurcations of converging shock fronts

NASA Astrophysics Data System (ADS)

Suramlishvili, Nugzar; Eggers, Jens; Fontelos, Marco

2014-11-01

We are concerned with singularities of the shock fronts of converging perturbed shock waves. Our considerations are based on Whitham's theory of geometrical shock dynamics. The recently developed method of local analysis is applied in order to determine generic singularities. In this case the solutions of partial differential equations describing the geometry of the shock fronts are presented as families of smooth maps with state variables and the set of control parameters dependent on Mach number, time and initial conditions. The space of control parameters of the singularities is analysed, the unfoldings describing the deformations of the canonical germs of shock front singularities are found and corresponding bifurcation diagrams are constructed. Research is supported by the Leverhulme Trust, Grant Number RPG-2012-568.

Entanglement concentration for two-mode Gaussian states in non-inertial frames

NASA Astrophysics Data System (ADS)

Di Noia, Maurizio; Giraldi, Filippo; Petruccione, Francesco

2017-04-01

Entanglement creation and concentration by means of a beam splitter (BS) is analysed for a generic two-mode bipartite Gaussian state in a relativistic framework. The total correlations, the purity and the entanglement in terms of logarithmic negativity are analytically studied for observers in an inertial state and in a non-inertial state of uniform acceleration. The dependence of entanglement on the BS transmissivity due to the Unruh effect is analysed in the case when one or both observers undergo uniform acceleration. Due to the Unruh effect, depending on the initial Gaussian state parameters and observed accelerations, the best condition for entanglement generation limited to the two modes of the observers in their regions is not always a balanced beam splitter, as it is for the inertial case.

Phonological universals constrain the processing of nonspeech stimuli.

PubMed

Berent, Iris; Balaban, Evan; Lennertz, Tracy; Vaknin-Nusbaum, Vered

2010-08-01

Domain-specific systems are hypothetically specialized with respect to the outputs they compute and the inputs they allow (Fodor, 1983). Here, we examine whether these 2 conditions for specialization are dissociable. An initial experiment suggests that English speakers could extend a putatively universal phonological restriction to inputs identified as nonspeech. A subsequent comparison of English and Russian participants indicates that the processing of nonspeech inputs is modulated by linguistic experience. Striking, qualitative differences between English and Russian participants suggest that they rely on linguistic principles, both universal and language-particular, rather than generic auditory processing strategies. Thus, the computation of idiosyncratic linguistic outputs is apparently not restricted to speech inputs. This conclusion presents various challenges to both domain-specific and domain-general accounts of cognition. 2010 APA, all rights reserved

The investigation of tethered satellite system dynamics

NASA Technical Reports Server (NTRS)

Lorenzini, E.

1985-01-01

Progress in tethered satellite system dynamics research is reported. A retrieval rate control law with no angular feedback to investigate the system's dynamic response was studied. The initial conditions for the computer code which simulates the satellite's rotational dynamics were extended to a generic orbit. The model of the satellite thrusters was modified to simulate a pulsed thrust, by making the SKYHOOK integrator suitable for dealing with delta functions without loosing computational efficiency. Tether breaks were simulated with the high resolution computer code SLACK3. Shuttle's maneuvers were tested. The electric potential around a severed conductive tether with insulator, in the case of a tether breakage at 20 km from the Shuttle, was computed. The electrodynamic hazards due to the breakage of the TSS electrodynamic tether in a plasma are evaluated.

Initial Computations of Vertical Displacement Events with NIMROD

NASA Astrophysics Data System (ADS)

Bunkers, Kyle; Sovinec, C. R.

2014-10-01

Disruptions associated with vertical displacement events (VDEs) have potential for causing considerable physical damage to ITER and other tokamak experiments. We report on initial computations of generic axisymmetric VDEs using the NIMROD code [Sovinec et al., JCP 195, 355 (2004)]. An implicit thin-wall computation has been implemented to couple separate internal and external regions without numerical stability limitations. A simple rectangular cross-section domain generated with the NIMEQ code [Howell and Sovinec, CPC (2014)] modified to use a symmetry condition at the midplane is used to test linear and nonlinear axisymmetric VDE computation. As current in simulated external coils for large- R / a cases is varied, there is a clear n = 0 stability threshold which lies below the decay-index criterion for the current-loop model of a tokamak to model VDEs [Mukhovatov and Shafranov, Nucl. Fusion 11, 605 (1971)]; a scan of wall distance indicates the offset is due to the influence of the conducting wall. Results with a vacuum region surrounding a resistive wall will also be presented. Initial nonlinear computations show large vertical displacement of an intact simulated tokamak. This effort is supported by U.S. Department of Energy Grant DE-FG02-06ER54850.

The UNITAID Patent Pool Initiative: Bringing Patents Together for the Common Good

PubMed Central

Bermudez, Jorge; 't Hoen, Ellen

2010-01-01

Developing and delivering appropriate, affordable, well-adapted medicines for HIV/AIDS remains an urgent challenge: as first-line therapies fail, increasing numbers of people require costly second-line therapy; one-third of ARVs are not available in pediatric formulations; and certain key first- and second-line triple fixed-dose combinations do not exist or sufficient suppliers are lacking. UNITAID aims to help solve these problems through an innovative initiative for the collective management of intellectual property (IP) rights – a patent pool for HIV medicines. The idea behind a patent pool is that patent holders - companies, governments, researchers or universities - voluntarily offer, under certain conditions, the IP related to their inventions to the patent pool. Any company that wants to use the IP to produce or develop medicines can seek a license from the pool against the payment of royalties, and may then produce the medicines for use in developing countries (conditional upon meeting agreed quality standards). The patent pool will be a voluntary mechanism, meaning its success will largely depend on the willingness of pharmaceutical companies to participate and commit their IP to the pool. Generic producers must also be willing to cooperate. The pool has the potential to provide benefits to all. PMID:20309404

An Evaluation of Health Service Impacts Consequent to Switching from Brand to Generic Venlafaxine in New Zealand under Conditions of Price Neutrality.

PubMed

Lessing, Charon; Ashton, Toni; Davis, Peter

2015-07-01

To study the health impact on adult New Zealand patients who switch from originator brand to generic venlafaxine. The national pharmacy database was used to select patients using venlafaxine for at least 6 months. Switchers and nonswitchers were identified, and switch behavior was compared for a 12-month follow-up period. Change in health service use following switching was also compared between switchers and nonswitchers including use of the emergency department, hospital, and specialist outpatient services over the same period. Approximately 12% of all originator brand users switched to generic venlafaxine, at least half of whom continued to use the generic throughout the follow-up period to August 1, 2012. Almost 60% of new users of the generic venlafaxine, however, switched to using the originator brand. Aside from a slight reduction in the use of outpatient services among switchers, there were no significant differences in health services use between switchers and nonswitchers for either existing or new venlafaxine users. Although both products remain fully subsidized and available, there is little incentive for prescribers, pharmacists, or patients to switch to the less expensive generic brand. If savings to the national New Zealand budget are to be realized, additional policy measures should be implemented to minimize incentives for multiple and reverse switching, and prescribers, as key opinion leaders, could take the lead in promoting generics to their patients. Copyright © 2015. Published by Elsevier Inc.

Determination of an Optimal Control Strategy for a Generic Surface Vehicle

DTIC Science & Technology

2014-06-18

paragraphs uses the numerical procedure in MATLAB’s BVP (bvp4c) algorithm using the continuation method. The goal is to find a solution to the set of...solution. Solving the BVP problem using bvp4c requires an initial guess for the solution. Note that the algorithm is very sensitive to the particular...form of the initial guess. The quality of the initial guess is paramount in convergence speed of the BVP algorithm and often determines if the

Initial data sets and the topology of closed three-manifolds in general relativity

NASA Astrophysics Data System (ADS)

Carfora, M.

1983-10-01

The interaction between the matter content of a closed physical space associated with a generic gravitational configuration and the topology of the underlying closed three-manifold is discussed. Within the context of the conformal approach to the initial value problem, it is shown that the presence of enough matter and radiation favors the three-sphere topology or the worm-hole topology. It is argued that such topologies leave more room for possible gravitational initial data sets for the field equations.

Dirac perturbations on Schwarzschild-anti-de Sitter spacetimes: Generic boundary conditions and new quasinormal modes

NASA Astrophysics Data System (ADS)

Wang, Mengjie; Herdeiro, Carlos; Jing, Jiliang

2017-11-01

We study Dirac quasinormal modes of Schwarzschild-anti-de Sitter (Schwarzschild-AdS) black holes, following the generic principle for allowed boundary conditions proposed in [M. Wang, C. Herdeiro, and M. O. P. Sampaio, Phys. Rev. D 92, 124006 (2015)., 10.1103/PhysRevD.92.124006]. After deriving the equations of motion for Dirac fields on the aforementioned background, we impose vanishing energy flux boundary conditions to solve these equations. We find a set of two Robin boundary conditions are allowed. These two boundary conditions are used to calculate Dirac normal modes on empty AdS and quasinormal modes on Schwarzschild-AdS black holes. In the former case, we recover the known normal modes of empty AdS; in the latter case, the two sets of Robin boundary conditions lead to two different branches of quasinormal modes. The impact on these modes of the black hole size, the angular momentum quantum number and the overtone number are discussed. Our results show that vanishing energy flux boundary conditions are a robust principle, applicable not only to bosonic fields but also to fermionic fields.

Pharmaceutical quality of seven generic Levodopa/Benserazide products compared with original Madopar® / Prolopa®

PubMed Central

2013-01-01

Background By definition, a generic product is considered interchangeable with the innovator brand product. Controversy exists about interchangeability, and attention is predominantly directed to contaminants. In particular for chronic, degenerative conditions such as in Parkinson’s disease (PD) generic substitution remains debated among physicians, patients and pharmacists. The objective of this study was to compare the pharmaceutical quality of seven generic levodopa/benserazide hydrochloride combination products marketed in Germany with the original product (Madopar® / Prolopa® 125, Roche, Switzerland) in order to evaluate the potential impact of Madopar® generics versus branded products for PD patients and clinicians. Methods Madopar® / Prolopa® 125 tablets and capsules were used as reference material. The generic products tested (all 100 mg/25 mg formulations) included four tablet and three capsule formulations. Colour, appearance of powder (capsules), disintegration and dissolution, mass of tablets and fill mass of capsules, content, identity and amounts of impurities were assessed along with standard physical and chemical laboratory tests developed and routinely practiced at Roche facilities. Results were compared to the original “shelf-life” specifications in use by Roche. Results Each of the seven generic products had one or two parameters outside the specifications. Deviations for the active ingredients ranged from +8.4% (benserazide) to −7.6% (levodopa) in two tablet formulations. Degradation products were measured in marked excess (+26.5%) in one capsule formulation. Disintegration time and dissolution for levodopa and benserazide hydrochloride at 30 min were within specifications for all seven generic samples analysed, however with some outliers. Conclusions Deviations for the active ingredients may go unnoticed by a new user of the generic product, but may entail clinical consequences when switching from original to generic during a long-term therapy. Degradation products may pose a safety concern. Our results should prompt caution when prescribing a generic of Madopar®/Prolopa®, and also invite to further investigations in view of a more comprehensive approach, both pharmaceutical and clinical. PMID:23617953

Quench dynamics in superconducting nanojunctions: Metastability and dynamical Yang-Lee zeros

NASA Astrophysics Data System (ADS)

Souto, R. Seoane; Martín-Rodero, A.; Yeyati, A. Levy

2017-10-01

We study the charge transfer dynamics following the formation of a phase or voltage biased superconducting nanojunction using a full counting statistics analysis. We demonstrate that the evolution of the zeros of the generating function allows one to identify the population of different many body states much in the same way as the accumulation of Yang-Lee zeros of the partition function in equilibrium statistical mechanics is connected to phase transitions. We give an exact expression connecting the dynamical zeros to the charge transfer cumulants and discuss when an approximation based on "dominant" zeros is valid. We show that, for generic values of the parameters, the system gets trapped into a metastable state characterized by a nonequilibrium population of the many body states which is dependent on the initial conditions. We study in particular the effect of the switching rates in the dynamics showing that, in contrast to intuition, the deviation from thermal equilibrium increases for the slower rates. In the voltage biased case the steady state is reached independent of the initial conditions. Our method allows us to obtain accurate results for the steady state current and noise in quantitative agreement with steady state methods developed to describe the multiple Andreev reflections regime. Finally, we discuss the system dynamics after a sudden voltage drop showing the possibility of tuning the many body states population by an appropriate choice of the initial voltage, providing a feasible experimental way to access the quench dynamics and control the state of the system.

Conditional bistability, a generic cellular mnemonic mechanism for robust and flexible working memory computations.

PubMed

Rodriguez, Guillaume; Sarazin, Matthieu; Clemente, Alexandra; Holden, Stephanie; Paz, Jeanne T; Delord, Bruno

2018-04-30

Persistent neural activity, the substrate of working memory, is thought to emerge from synaptic reverberation within recurrent networks. However, reverberation models do not robustly explain fundamental dynamics of persistent activity, including high-spiking irregularity, large intertrial variability, and state transitions. While cellular bistability may contribute to persistent activity, its rigidity appears incompatible with persistent activity labile characteristics. Here, we unravel in a cellular model a form of spike-mediated conditional bistability that is robust, generic and provides a rich repertoire of mnemonic computations. Under asynchronous synaptic inputs of the awakened state, conditional bistability generates spiking/bursting episodes, accounting for the irregularity, variability and state transitions characterizing persistent activity. This mechanism has likely been overlooked because of the sub-threshold input it requires and we predict how to assess it experimentally. Our results suggest a reexamination of the role of intrinsic properties in the collective network dynamics responsible for flexible working memory. SIGNIFICANCE STATEMENT This study unravels a novel form of intrinsic neuronal property, i.e. conditional bistability. We show that, thanks of its conditional character, conditional bistability favors the emergence of flexible and robust forms of persistent activity in PFC neural networks, in opposition to previously studied classical forms of absolute bistability. Specifically, we demonstrate for the first time that conditional bistability 1) is a generic biophysical spike-dependent mechanism of layer V pyramidal neurons in the PFC and that 2) it accounts for essential neurodynamical features for the organisation and flexibility of PFC persistent activity (the large irregularity and intertrial variability of the discharge and its organization under discrete stable states), which remain unexplained in a robust fashion by current models. Copyright © 2018 the authors.

Unsteady Aerodynamic Modeling in Roll for the NASA Generic Transport Model

NASA Technical Reports Server (NTRS)

Murphy, Patrick C.; Klein, Vladislav; Frink, Neal T.

2012-01-01

Reducing the impact of loss-of-control conditions on commercial transport aircraft is a primary goal of the NASA Aviation Safety Program. One aspect in developing the supporting technologies is to improve the aerodynamic models that represent these adverse conditions. Aerodynamic models appropriate for loss of control conditions require a more general mathematical representation to predict nonlinear unsteady behaviors. In this paper, a more general mathematical model is proposed for the subscale NASA Generic Transport Model (GTM) that covers both low and high angles of attack. Particular attention is devoted to the stall region where full-scale transports have demonstrated a tendency for roll instability. The complete aerodynamic model was estimated from dynamic wind-tunnel data. Advanced computational methods are used to improve understanding and visualize the flow physics within the region where roll instability is a factor.

A Generic Evaluation Model for Semantic Web Services

NASA Astrophysics Data System (ADS)

Shafiq, Omair

Semantic Web Services research has gained momentum over the last few Years and by now several realizations exist. They are being used in a number of industrial use-cases. Soon software developers will be expected to use this infrastructure to build their B2B applications requiring dynamic integration. However, there is still a lack of guidelines for the evaluation of tools developed to realize Semantic Web Services and applications built on top of them. In normal software engineering practice such guidelines can already be found for traditional component-based systems. Also some efforts are being made to build performance models for servicebased systems. Drawing on these related efforts in component-oriented and servicebased systems, we identified the need for a generic evaluation model for Semantic Web Services applicable to any realization. The generic evaluation model will help users and customers to orient their systems and solutions towards using Semantic Web Services. In this chapter, we have presented the requirements for the generic evaluation model for Semantic Web Services and further discussed the initial steps that we took to sketch such a model. Finally, we discuss related activities for evaluating semantic technologies.

Performance degradation of a model helicopter rotor with a generic ice shape

NASA Technical Reports Server (NTRS)

Korkan, K. D.; Cross, E. J., Jr.; Miller, T. L.

1984-01-01

An experimental program using a commercially available remotely controlled model helicopter in the Texas A&M University (TAMU) subsonic wind tunnel has been conducted to investigate the performance degradation resulting from the simulated formation of ice on the leading edge of the main rotor blades in both hover and forward flight. The rotor blades utilized a NACA 0012 airfoil with a 2.5-in. constant chord. A generic ice shape derived from a predetermined natural ice condition was applied to the 53.375-in.-diameter main rotor, and thrust and torque coefficients were measured for the main rotor as functions of velocity, main rotor rpm, fuselage angle of incidence, collective pitch angle, and spanwise extent of icing. The model helicopter test exhibited significant performance degradation of the main rotor when generic ice was added. An increase of approximately 150 percent in torque coefficient to maintain a constant thrust coefficient was noted when generic ice had been applied to the 85 percent rotor radial location. Also, considerable additional degradation occurred when generic ice was applied to the 100 percent rotor radial location, as compared with the 85 percent simulated ice performance values, indicating the sensitivity of the rotor tip region.

Recent results on output feedback problems

NASA Technical Reports Server (NTRS)

Byrnes, C. I.

1980-01-01

Given a real linear system sigma = (A, B, C) with m inputs, p outputs and degree n, the problem of generic pole placement by output feedback is studied, which is to compute the constant C(m,p) such that the inequality C(m,p) not less than n is necessary and sufficient for generically positioning the poles of the generic linear system by constant output feedback. A constant C prime (m,p) is determined, which gives a sufficient condition for generic pole placement and which, to the best of the author's knowledge, is at least as good an estimate of C(m,p) as any in the literature. Some results on the construction of solutions in case mp = n are announced, based on the degree formula of Brockett and Byrnes and the Galois theory. In particular, a question raised by Anderson, Bose, and Jury, on the existence of a rational procedure for computing the feedback law from the desired characteristic polynomial is answered.

Development of Multi-physics (Multiphase CFD + MCNP) simulation for generic solution vessel power calculation

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

Kim, Seung Jun; Buechler, Cynthia Eileen

The current study aims to predict the steady state power of a generic solution vessel and to develop a corresponding heat transfer coefficient correlation for a Moly99 production facility by conducting a fully coupled multi-physics simulation. A prediction of steady state power for the current application is inherently interconnected between thermal hydraulic characteristics (i.e. Multiphase computational fluid dynamics solved by ANSYS-Fluent 17.2) and the corresponding neutronic behavior (i.e. particle transport solved by MCNP6.2) in the solution vessel. Thus, the development of a coupling methodology is vital to understand the system behavior at a variety of system design and postulated operatingmore » scenarios. In this study, we report on the k-effective (keff) calculation for the baseline solution vessel configuration with a selected solution concentration using MCNP K-code modeling. The associated correlation of thermal properties (e.g. density, viscosity, thermal conductivity, specific heat) at the selected solution concentration are developed based on existing experimental measurements in the open literature. The numerical coupling methodology between multiphase CFD and MCNP is successfully demonstrated, and the detailed coupling procedure is documented. In addition, improved coupling methods capturing realistic physics in the solution vessel thermal-neutronic dynamics are proposed and tested further (i.e. dynamic height adjustment, mull-cell approach). As a key outcome of the current study, a multi-physics coupling methodology between MCFD and MCNP is demonstrated and tested for four different operating conditions. Those different operating conditions are determined based on the neutron source strength at a fixed geometry condition. The steady state powers for the generic solution vessel at various operating conditions are reported, and a generalized correlation of the heat transfer coefficient for the current application is discussed. The assessment of multi-physics methodology and preliminary results from various coupled calculations (power prediction and heat transfer coefficient) can be further utilized for the system code validation and generic solution vessel design improvement.« less

Positional Differences in External On-Field Load During Specific Drill Classifications Over a Professional Rugby League Preseason.

PubMed

Cummins, Cloe; McLean, Blake; Halaki, Mark; Orr, Rhonda

2017-07-01

To quantify the external training loads of positional groups in preseason training drills. Thirty-three elite rugby league players were categorized into 1 of 4 positional groups: outside backs (n = 9), adjustables (n = 9), wide-running forwards (n = 9), and hit-up forwards (n = 6). Data for 8 preseason weeks were collected using microtechnology devices. Training drills were classified based on drill focus: speed and agility, conditioning, and generic and positional skills. Total, high-speed, and very-high-speed distance decreased across the preseason in speed and agility (moderate, small, and small, respectively), conditioning (large, large, and small) and generic skills (large, large, and large). The duration of speed and generic skills also decreased (77% and 48%, respectively). This was matched by a concomitant increase in total distance (small), high-speed running (small), very-high-speed running (moderate), and 2-dimensional (2D) BodyLoad (small) demands in positional skills. In positional skills, hit-up forwards (1240 ± 386 m) completed less very-high-speed running than outside backs (2570 ± 1331 m) and adjustables (2121 ± 1163 m). Hit-up forwards (674 ± 253 AU) experienced greater 2D BodyLoad demands than outside backs (432 ± 230 AU, P = .034). In positional drills, hit-up forwards experienced greater relative 2D BodyLoad demands than outside backs (P = .015). Conversely, outside backs experienced greater relative high- (P = .007) and very-high-speed-running (P < .001) demands than hit-up forwards. Significant differences were observed in training loads between positional groups during positional skills but not in speed and agility, conditioning, and generic skills. This work also highlights the importance of different external-load parameters to adequately quantify workload across different positional groups.

Individualized Health Care Plans: Supporting Children With Chronic Conditions in the Classroom

ERIC Educational Resources Information Center

Hopkins, Amanda F.; Hughes, Mary-alayne

2016-01-01

Due to the major advances in technology and the sciences, advances in the medical treatment options for children with chronic conditions are being made at an astonishing rate. In the health care field, "children with chronic conditions" is a generic phrase that typically refers to children with physical, developmental, behavioral, or…

On macroeconomic characteristics of pharmaceutical generics and the potential for manufacturing and consumption under fuzzy conditions.

PubMed

Gascón, Fernando; de la Fuente, David; Puente, Javier; Lozano, Jesús

2007-11-01

The aim of this paper is to develop a methodology that is useful for analyzing, from a macroeconomic perspective, the aggregate demand and the aggregate supply features of the market of pharmaceutical generics. In order to determine the potential consumption and the potential production of pharmaceutical generics in different countries, two fuzzy decision support systems are proposed. Two fuzzy decision support systems, both based on the Mamdani model, were applied in this paper. These systems, generated by Matlab Toolbox 'Fuzzy' (v. 2.0), are able to determine the potential of a country for the manufacturing or the consumption of pharmaceutical generics. The systems make use of three macroeconomic input variables. In an empirical application of our proposed methodology, the potential towards consumption and manufacturing in Holland, Sweden, Italy and Spain has been estimated from national indicators. Cross-country comparisons are made and graphical surfaces are analyzed in order to interpret the results. The main contribution of this work is the development of a methodology that is useful for analyzing aggregate demand and aggregate supply characteristics of pharmaceutical generics. The methodology is valid for carrying out a systematic analysis of the potential generics have at a macrolevel in different countries. The main advantages of the use of fuzzy decision support systems in the context of pharmaceutical generics are the flexibility in the construction of the system, the speed in interpreting the results offered by the inference and surface maps and the ease with which a sensitivity analysis of the potential behavior of a given country may be performed.

Use of the International Classification of Functioning, Disability and Health Generic-30 Set for the characterization of outpatients: Italian Society of Physical and Rehabilitative Medicine Residents Section Project.

PubMed

Gimigliano, Francesca; De Sire, Alessandro; Gastaldo, Marco; Maghini, Irene; Paoletta, Marco; Pasquini, Andrea; Boldrini, Paolo; Selb, Melissa; Prodinger, Birgit

2018-06-11

The International Classification of Functioning, Disability and Health (ICF) Generic- 30 Set (previously referred to as Rehabilitation Set) is a minimal set of ICF categories for reporting and assessing functioning and disability in clinical populations with different health conditions along the continuum of care. Recently, the Italian Society of Physical and Rehabilitation Medicine (SIMFER) developed an Italian modification of the simple and intuitive descriptions (SID) of these categories. This study was the first one to implement the use of the SID in practice. 1) To implement the use of the ICF in clinical practice and research among Italian Residents in PRM. 2) To verify if the SID made the application of ICF Generic 30 Set more user-friendly than the original descriptions. 3) To examine the prevalence of functioning problems of patients accessing Rehabilitation Services to serve as reference for the development of an ICF-based clinical data collection tool. Multicenter cross-sectional study. Italian Physical Medicine and Rehabilitation (PRM) outpatient rehabilitation services. Patients referring to Italian PRM outpatient rehabilitation services and Italian Residents in PRM. Each School of Specialization involved, randomly, received the ICF Generic-30 Set with the original descriptions or with the SID. Residents collected over a 4-month period (April-July 2016) patients data related to the ICF Generic-30 Set categories. Moreover, the residents self- assessed their difficulty in using the ICF Generic-30 Set with the original descriptions or with the SID, through a Numeric Rating Scale (NRS). Ninety-three residents collected functioning data of 864 patients (mean aged 57.7±19.3) with ICF Generic-30 Set: 304 with the original descriptions and 560 with SID. The difficulty in using the ICF Generic-30 Set with SID was rated as lower than using the original descriptions (NRS = 2.8±2.5 vs 3.5±3.1; p<0.001). The most common disease was the back pain (9.6%) and the most common altered ICF categories were b280 (76.3%) and b710 (72.9%). This multicenter cross-sectional study shown that the ICF Generic-30 Set is a valuable instrument for reporting and assessing functioning and disability in clinical populations with different health conditions and along the continuum of care and that SID facilitate the understanding of the ICF categories and therefore their use in clinical practice. This National survey, improving the knowledge of ICF among Italian PRM residents, represents an important step towards the system-wide implementation of ICF in the healthcare system.

Generic Friedberg-Lee symmetry of Dirac neutrinos

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

Luo Shu; Xing Zhizhong; Li Xin

2008-12-01

We write out the generic Dirac neutrino mass operator which possesses the Friedberg-Lee symmetry and find that its corresponding neutrino mass matrix is asymmetric. Following a simple way to break the Friedberg-Lee symmetry, we calculate the neutrino mass eigenvalues and show that the resultant neutrino mixing pattern is nearly tri-bimaximal. Imposing the Hermitian condition on the neutrino mass matrix, we also show that the simplified ansatz is consistent with current experimental data and favors the normal neutrino mass hierarchy.

Phase I Experimental Testing of a Generic Submarine Model in the DSTO Low Speed Wind Tunnel

DTIC Science & Technology

2012-07-01

used during the tests , along with the test methodology . A sub-set of the data gathered is also presented and briefly discussed. Overall, the force...total pressure probe when positioned close to the model. 4. Results Selected results from the testing of the generic submarine model in the...Appendix B summaries the test conditions. 4.3.1 Smoke Generator and Probe An Aerotech smoke generator and probe were used for visualisation of

On the relevance of modeling viscoelastic bending behavior in finite element forming simulation of continuously fiber reinforced thermoplastics

NASA Astrophysics Data System (ADS)

Dörr, Dominik; Schirmaier, Fabian J.; Henning, Frank; Kärger, Luise

2017-10-01

Finite Element (FE) forming simulation offers the possibility of a detailed analysis of the deformation behavior of multilayered thermoplastic blanks during forming, considering material behavior and process conditions. Rate-dependent bending behavior is a material characteristic, which is so far not considered in FE forming simulation of pre-impregnated, continuously fiber reinforced polymers (CFRPs). Therefore, an approach for modeling viscoelastic bending behavior in FE composite forming simulation is presented in this work. The presented approach accounts for the distinct rate-dependent bending behavior of e.g. thermoplastic CFRPs at process conditions. The approach is based on a Voigt-Kelvin (VK) and a generalized Maxwell (GM) approach, implemented within a FE forming simulation framework implemented in several user-subroutines of the commercially available FE solver Abaqus. The VK, GM, as well as purely elastic bending modeling approaches are parameterized according to dynamic bending characterization results for a PA6-CF UD-tape. It is found that only the GM approach is capable to represent the bending deformation characteristic for all of the considered bending deformation rates. The parameterized bending modeling approaches are applied to a hemisphere test and to a generic geometry. A comparison of the forming simulation results of the generic geometry to experimental tests show a good agreement between simulation and experiments. Furthermore, the simulation results reveal that especially a correct modeling of the initial bending stiffness is relevant for the prediction of wrinkling behavior, as a similar onset of wrinkles is observed for the GM, the VK and an elastic approach, fitted to the stiffness observed in the dynamic rheometer test for low curvatures. Hence, characterization and modeling of rate-dependent bending behavior is crucial for FE forming simulation of thermoplastic CFRPs.

Establishment of a broadband radiometric ground station on the South African east coast

NASA Astrophysics Data System (ADS)

Brooks, Michael J.; Roberts, Lance W.

2009-08-01

A radiometric monitoring program for solar irradiance has been initiated on the Howard College campus of the University of KwaZulu-Natal (UKZN) in Durban, South Africa. This paper describes the establishment of the broadband ground station which employs conventional radiometers and a new type of pyranometer shadow band. The ZEBRA (Zonal Exposure to Broadband RAdiation) band consists of a perforated metal strip that permits the separation of direct normal and diffuse irradiance from global data with a single pyranometer. In this paper a time-based model of the new band's shading mask is described. The model is derived from a ray tracing exercise that accounts for ZEBRA geometry and solar position throughout a generic 365-day year. The UKZN facility lies at 29.9° South latitude and is part of a larger test initiative for the new shadow band that includes the NREL Solar Radiation Research Laboratory in Colorado. Data from northern and southern hemisphere test sites are to be used to characterize performance of the band under a range of conditions and for comparison with output from the newly developed model.

Medicine prices, availability and affordability in Sri Lanka

PubMed Central

Senarathna, S.M.D.K. Ganga; Mannapperuma, Uthpali; Fernandopulle, B.M. Rohini

2011-01-01

Background: No pricing formula has been implemented from November 2002 to date in Sri Lanka. Therefore, we initiated a study in 2003 to determine the prices, availability and affordability of medicines in the private sector of Sri Lanka in the absence of a price control. Materials and Methods: The World Health Organization/Health Action International methodology was used. The study was conducted in retail pharmacies (Rajya Osu Sala) of State Pharmaceuticals Corporation (semigovernment) and privately owned retail pharmacies (n = 15) in 2003, 2006 and 2009 in a geographical area. Essential medicines (n = 28) were studied and, for each medicine, innovator, most sold generic and cheapest generic were monitored. The medicine’s median price was compared with the international reference prices (IRP) to obtain the median price ratio. The daily wage of the lowest-paid government worker was used to calculate affordability. Results: Innovators were five to six-times the IRP at privately owned pharmacies and four to seven-times at the Rajya Osu Sala. The prices of generics were ≤1 the IRP during 6 years in privately owned and Rajya Osu Sala pharmacies. Cheapest generics were high in availability (>80%) throughout the study period. Innovators cost more than a day’s wage of the lowest-paid government worker; in contrast, generics were always less than one day’s wage. There seems to be no difference in affordability between privately owned or semigovernment pharmacies. Conclusion: In Sri Lanka, generic medicines have effective pricing and are available and affordable. No drastic changes in prices of medicine in the private sector were observed over the 6 years despite removal of price control. PMID:21455424

Evaluation of the Crystallization Tendency of Commercially Available Amorphous Tacrolimus Formulations Exposed to Different Stress Conditions.

PubMed

Trasi, Niraj S; Purohit, Hitesh S; Taylor, Lynne S

2017-10-01

Tacrolimus, an immunosuppressant, is a poorly water soluble compound whereby the commercially available capsule formulations contain the drug in amorphous form. The goal of this study was to evaluate the robustness of the innovator product and five generic formulations to crystallization following storage at stress conditions. Products were purchased from a pharmacy and stored at 40°C/75% relative humidity (RH), open dish conditions. Crystallinity was determined using X-ray diffraction. The quantity of the ingredients in the formulations were determined using different approaches and the various factors that might cause instability in the formulations were studied. After 4 weeks of open dish storage at 40°C/75% RH, one of the generic formulations showed evidence of tacrolimus crystallization. Further investigations revealed batch-to-batch variations in crystallization tendency with the extent of crystallinity varying between 50 and 100% for different batches. Crystallization was also observed at lower storage temperatures (30°C) when the RH was maintained at 75%. It was found that crystallization could be induced in a model formulation by wet granulating an ethanolic solution of the drug with lactose and drying at 60-70°C followed by exposure to stress conditions. It seems probable that the generic that was susceptible to crystallization contains amorphous drug physically mixed with polymeric excipients, rather than as an amorphous solid dispersion. This study highlights the importance of considering the manufacturing process on the stability of the resultant amorphous product.

Myopic and Forward Looking Behavior in Branded Oral Anti-Diabetic Medication Consumption: An Example from Medicare Part D.

PubMed

Sacks, Naomi C; Burgess, James F; Cabral, Howard J; Pizer, Steven D

2017-06-01

We evaluate consumption responses to the non-linear Medicare Part D prescription drug benefit. We compare propensity-matched older patients with diabetes and Part D Standard or low-income-subsidy (LIS) coverage. We evaluate monthly adherence to branded oral anti-diabetics, with high end-of-year donut hole prices (>$200) for Standard patients and consistent, low (≤$6) prices for LIS. As an additional control, we examine adherence to generic anti-diabetics, with relatively low, consistent prices for Standard patients. If Standard patients are forward looking, they will reduce branded adherence in January, and LIS-Standard differences will be constant through the year. Contrary to this expectation, branded adherence is lower for Standard patients in January and diverges from LIS as the coverage year progresses. Standard-LIS generic adherence differences are minimal. Our findings suggest that seniors with chronic conditions respond myopically to the nonlinear Part D benefit, reducing consumption in response to high deductible, initial coverage and gap prices. Thus, when the gap is fully phased out in 2020, cost-related nonadherence will likely remain in the face of higher spot prices for more costly branded medications. These results contribute to studies of Part D plan choice and medication adherence that suggest that seniors may not make optimal healthcare decisions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

DEFLECTION OF A HETEROGENEOUS WIDE-BEAM UNDER UNIFORM PRESSURE LOAD

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

T. V. Holschuh; T. K. Howard; W. R. Marcum

2014-07-01

Oregon State University (OSU) and the Idaho National Laboratory (INL) are currently collaborating on a test program which entails hydro-mechanical testing of a generic plate type fuel element, or generic test plate assembly (GTPA), for the purpose of qualitatively demonstrating mechanical integrity of uranium-molybdenum monolithic plates as compared to that of uranium aluminum dispersion, and aluminum fuel plates onset by hydraulic forces. This test program supports ongoing work conducted for/by the Global Threat Reduction Initiative (GTRI) Fuels Development Program. This study’s focus supports the ongoing collaborative effort by detailing the derivation of an analytic solution for deflection of a heterogeneousmore » plate under a uniform, distributed load in order to predict the deflection of test plates in the GTPA. The resulting analytical solutions for three specific boundary condition sets are then presented against several test cases of a homogeneous plate. In all test cases considered, the results for both homogeneous and heterogeneous plates are numerically identical to one another, demonstrating correct derivation of the heterogeneous solution. Two additional problems are presents herein that provide a representative deflection profile for the plates under consideration within the GTPA. Furthermore, qualitative observations are made about the influence of a more-rigid internal fuel-meat region and its influence on the overall deflection profile of a plate. Present work is being directed to experimentally confirm the analytical solution’s results using select materials.« less

Vortex lattices and defect-mediated viscosity reduction in active liquids

NASA Astrophysics Data System (ADS)

Slomka, Jonasz; Dunkel, Jorn

2016-11-01

Generic pattern-formation and viscosity-reduction mechanisms in active fluids are investigated using a generalized Navier-Stokes model that captures the experimentally observed bulk vortex dynamics in microbial suspensions. We present exact analytical solutions including stress-free vortex lattices and introduce a computational framework that allows the efficient treatment of previously intractable higher-order shear boundary conditions. Large-scale parameter scans identify the conditions for spontaneous flow symmetry breaking, defect-mediated low-viscosity phases and negative-viscosity states amenable to energy harvesting in confined suspensions. The theory uses only generic assumptions about the symmetries and long-wavelength structure of active stress tensors, suggesting that inviscid phases may be achievable in a broad class of non-equilibrium fluids by tuning confinement geometry and pattern scale selection.

Longitudinal factorial invariance of the PedsQL 4.0 Generic Core Scales child self-report Version: one year prospective evidence from the California State Children's Health Insurance Program (SCHIP).

PubMed

Varni, James W; Limbers, Christine A; Newman, Daniel A; Seid, Michael

2008-11-01

The measurement of health-related quality of life (HRQOL) in pediatric medicine and health services research has grown significantly over the past decade. The paradigm shift toward patient-reported outcomes (PROs) has provided the opportunity to emphasize the value and critical need for pediatric patient self-report. In order for changes in HRQOL/PRO outcomes to be meaningful over time, it is essential to demonstrate longitudinal factorial invariance. This study examined the longitudinal factor structure of the PedsQL 4.0 Generic Core Scales over a one-year period for child self-report ages 5-17 in 2,887 children from a statewide evaluation of the California State Children's Health Insurance Program (SCHIP) utilizing a structural equation modeling framework. Specifying four- and five-factor measurement models, longitudinal structural equation modeling was used to compare factor structures over a one-year interval on the PedsQL 4.0 Generic Core Scales. While the four-factor conceptually-derived measurement model for the PedsQL 4.0 Generic Core Scales produced an acceptable fit, the five-factor empirically-derived measurement model from the initial field test of the PedsQL 4.0 Generic Core Scales produced a marginally superior fit in comparison to the four-factor model. For the five-factor measurement model, the best fitting model, strict factorial invariance of the PedsQL 4.0 Generic Core Scales across the two measurement occasions was supported by the stability of the comparative fit index between the unconstrained and constrained models, and several additional indices of practical fit including the root mean squared error of approximation, the non-normed fit index, and the parsimony normed fit index. The findings support an equivalent factor structure on the PedsQL 4.0 Generic Core Scales over time. Based on these data, it can be concluded that over a one-year period children in our study interpreted items on the PedsQL 4.0 Generic Core Scales in a similar manner.

Generic and therapeutic statin switches and disruptions in therapy.

PubMed

Chapman, Richard H; Benner, Joshua S; Girase, Prafulla; Benigno, Michael; Axelsen, Kirsten; Liu, Larry Z; Nichol, Michael B

2009-05-01

The study objective was to compare dose-equivalence, adherence and subsequent switch rates among patients recently switched from a branded to generic version of the same statin (generic substitution, GS) vs. those switched from branded statin to generic version of a different statin (therapeutic substitution, TS). In a retrospective cohort analysis among adult enrollees in over 90 US health plans, the authors identified adult patients who switched from a branded to generic statin from July-December 2006 (simvastatin became generic in June 2006). Patients were classified by type of statin switch: GS (e.g., branded simvastatin --> generic simvastatin), and TS (e.g., branded atorvastatin --> generic simvastatin). Demographic and clinical data were collected from claims before switch through 6 months follow-up. Separate outcomes of interest included proportion of patients that switched to a less potent daily dose, that switched back to previous branded statin after switch, and that were at least 80% adherent during the 6 months after initial switch. Significant predictors of each clinical outcome were identified using multivariable logistic regression models, adjusting for differences between groups in covariates and potential confounders. The 6-month TS (n = 3807) and GS (n = 40,165) groups were generally similar demographically. Compared to GS, TS patients were significantly more likely to be switched to a less potent dose (26.2% vs. 0.5%, adjusted odds ratio [AOR] in patients with high-potency index medication = 83.4, p < 0.0001); 33% less likely to be adherent in the 6 months after switch (67.7% vs. 75.9%, AOR in patients with no switch in first 6 months follow-up = 0.67, p < 0.0001); and four times more likely to switch back to previous branded statin (11.3% vs. 2.9%, AOR = 4.1, p < 0.0001). This study did not account for co-payment changes, lipid measurements, or changes in pill burden. While this study did not have data on why patients had TS (e.g., for cost or clinical reasons), TS was more likely to involve a subsequent disruption to statin therapy than GS. TS could potentially lead to adverse impacts on patients' outcomes, and should be studied further.

Generic quality of life in persons with hearing loss: a systematic literature review.

PubMed

Nordvik, Øyvind; Laugen Heggdal, Peder O; Brännström, Jonas; Vassbotn, Flemming; Aarstad, Anne Kari; Aarstad, Hans Jørgen

2018-01-01

To the best of our knowledge, no empirically based consensus has been reached as to if, and to what extent, persons with hearing loss (HL) have reduced generic Quality of life (QoL). There seems to be limited knowledge regarding to what extent a hearing aid (HA) would improve QoL. The main aim of the present study was to review studies about the relationship between HL and QoL. A supporting aim was to study the association between distress and HL. Literature databases (Cinahl, Pub Med and Web of Science) were searched to identify relevant journal articles published in the period from January 2000 to March 17, 2016. We performed a primary search pertaining to the relationship between HL, HA and QoL (search number one) followed by a supporting search pertaining to the relationship between distress/mood/anxiety and HL (search number two). After checking for duplications and screening the titles of the papers, we read the abstracts of the remaining papers. The most relevant papers were read thoroughly, leaving us with the journal articles that met the inclusion criteria. Twenty journal articles were included in the present review: 13 were found in the primary search (HL and QoL), and seven in the supporting search (HL and distress). The literature yields equivocal findings regarding the association between generic QoL and HL. A strong association between distress and HL was shown, where distressed persons tend to have a lowered generic QoL. It is suggested that QoL is lowered among HL patients. Some studies suggest an increased generic QoL following the use of HA, especially during the first few months after initiation of treatment. Other studies suggest that HA use is one of several possible factors that contribute to improve generic QoL. The majority of the studies suggest that HL is associated with reduced generic QoL. Using hearing aids seem to improve general QoL at follow-up within the first year. HL is a risk factor for distress. Further research is needed to explore the relationship between HL and generic QoL, in addition to the importance of influencing variables on this relationship.

Investigation of Aerodynamics Scale Effects for a Generic Fighter Configuration in the National Transonic Facility (Invited)

NASA Technical Reports Server (NTRS)

Tomek, W. G.; Wahls, R. A.; Owens, L. R.; Burner, A. B.; Graves, S. S.; Luckring, J. M.

2003-01-01

Two wind tunnel tests of a generic fighter configuration have been completed in the National Transonic Facility. The primary purpose of the tests was to assess Reynolds number scale effects on a thin-wing, fighter-type configuration up to full-scale flight conditions (that is, Reynolds numbers of the order of 60 million). The tests included longitudinal and lateral/directional studies at subsonic and transonic conditions across a range of Reynolds numbers from that available in conventional wind tunnels to flight conditions. Results are presented for three Mach numbers (0.6, 0.8, and 0.9) and three configurations: 1) Fuselage / Wing, 2) Fuselage / Wing / Centerline Vertical Tail / Horizontal Tail, and 3) Fuselage / Wing / Trailing-Edge Extension / Twin Vertical Tails. Reynolds number effects on the lateral-directional aerodynamic characteristics are presented herein, along with longitudinal data demonstrating the effects of fixing the boundary layer transition location for low Reynolds number conditions. In addition, an improved model videogrammetry system and results are discussed.

Load-Flow in Multiphase Distribution Networks: Existence, Uniqueness, Non-Singularity, and Linear Models

DOE PAGES

Bernstein, Andrey; Wang, Cong; Dall'Anese, Emiliano; ...

2018-01-01

This paper considers unbalanced multiphase distribution systems with generic topology and different load models, and extends the Z-bus iterative load-flow algorithm based on a fixed-point interpretation of the AC load-flow equations. Explicit conditions for existence and uniqueness of load-flow solutions are presented. These conditions also guarantee convergence of the load-flow algorithm to the unique solution. The proposed methodology is applicable to generic systems featuring (i) wye connections; (ii) ungrounded delta connections; (iii) a combination of wye-connected and delta-connected sources/loads; and, (iv) a combination of line-to-line and line-to-grounded-neutral devices at the secondary of distribution transformers. Further, a sufficient condition for themore » non-singularity of the load-flow Jacobian is proposed. Finally, linear load-flow models are derived, and their approximation accuracy is analyzed. Theoretical results are corroborated through experiments on IEEE test feeders.« less

Investigation of Reynolds Number Effects on a Generic Fighter Configuration in the National Transonic Facility

NASA Technical Reports Server (NTRS)

Tomek, W. G.; Hall, R. M.; Wahls, R. A.; Luckring, J. M.; Owens, L. R.

2002-01-01

A wind tunnel test of a generic fighter configuration was tested in the National Transonic Facility through a cooperative agreement between NASA Langley Research Center and McDonnell Douglas. The primary purpose of the test was to assess Reynolds number scale effects on a thin-wing, fighter-type configuration up to full-scale flight conditions (that is, Reynolds numbers of the order of 60 million). The test included longitudinal and lateral/directional studies at subsonic and transonic conditions across a range of Reynolds numbers from that available in conventional wind tunnels to flight conditions. Results are presented for three Mach numbers (0.6, 0.8, and 0.9) and three configurations: (1) Fuselage/Wing; (2) Fuselage/Wing/Centerline Vertical Tail/Horizontal Tail; and (3) Fuselage/Wing/Trailing-Edge Extension/Twin Vertical Tails. Reynolds number effects on the longitudinal aerodynamic characteristics are presented herein.

Load-Flow in Multiphase Distribution Networks: Existence, Uniqueness, Non-Singularity, and Linear Models

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

Bernstein, Andrey; Wang, Cong; Dall'Anese, Emiliano

This paper considers unbalanced multiphase distribution systems with generic topology and different load models, and extends the Z-bus iterative load-flow algorithm based on a fixed-point interpretation of the AC load-flow equations. Explicit conditions for existence and uniqueness of load-flow solutions are presented. These conditions also guarantee convergence of the load-flow algorithm to the unique solution. The proposed methodology is applicable to generic systems featuring (i) wye connections; (ii) ungrounded delta connections; (iii) a combination of wye-connected and delta-connected sources/loads; and, (iv) a combination of line-to-line and line-to-grounded-neutral devices at the secondary of distribution transformers. Further, a sufficient condition for themore » non-singularity of the load-flow Jacobian is proposed. Finally, linear load-flow models are derived, and their approximation accuracy is analyzed. Theoretical results are corroborated through experiments on IEEE test feeders.« less

Scramjet mixing establishment times for a pulse facility

NASA Technical Reports Server (NTRS)

Rogers, R. Clayton; Weidner, Elizabeth H.

1991-01-01

A numerical simulation of the temporally developing flow through a generic scramjet combustor duct is presented for stagnation conditions typical of flight at Mach 13 as produced by a shock tunnel pulse facility. The particular focus is to examine the start up transients and to determine the time required for certain flow parameters to become established. The calculations were made with a Navier-Stokes solver SPARK with temporally relaxing inflow conditions derived from operation of the T4 shock tunnel at the University of Queensland in Australia. Calculations at nominal steady inflow conditions were made for comparison. The generic combustor geometry includes the injection of hydrogen fuel from the base of a centrally located strut. In both cases, the flow was assumed laminar and fuel combustion was not included. The establishment process is presented for viscous parameters in the boundary layer and for parameters related to the fuel mixing.

Opening up the QCD axion window

NASA Astrophysics Data System (ADS)

Agrawal, Prateek; Marques-Tavares, Gustavo; Xue, Wei

2018-03-01

We present a new mechanism to deplete the energy density of the QCD axion, making decay constants as high as f a ≃ 1017 GeV viable for generic initial conditions. In our setup, the axion couples to a massless dark photon with a coupling that is moderately stronger than the axion coupling to gluons. Dark photons are produced copiously through a tachyonic instability when the axion field starts oscillating, and an exponential suppression of the axion density can be achieved. For a large part of the parameter space this dark radiation component of the universe can be observable in upcoming CMB experiments. Such dynamical depletion of the axion density ameliorates the isocurvature bound on the scale of inflation. The depletion also amplifies the power spectrum at scales that enter the horizon before particle production begins, potentially leading to axion miniclusters.

Mathematical simulations for bioanalytical assay development: the (un-)necessity and (im-)possibility of free drug quantification.

PubMed

Staack, Roland F; Jordan, Gregor; Heinrich, Julia

2012-02-01

For every drug development program it needs to be discussed whether discrimination between free and total drug concentrations is required to accurately describe its pharmacokinetic behavior. This perspective describes the application of mathematical simulation approaches to guide this initial decision based on available knowledge about target biology, binding kinetics and expected drug concentrations. We provide generic calculations that can be used to estimate the necessity of free drug quantification for different drug molecules. In addition, mathematical approaches are used to simulate various assay conditions in bioanalytical ligand-binding assays: it is demonstrated that due to the noncovalent interaction between the binding partners and typical assay-related interferences in the equilibrium, a correct quantification of the free drug concentration is highly challenging and requires careful design of different assay procedure steps.

Using Dynamic Simulation to Evaluate Attemperator Operation in a Natural Gas Combined Cycle With Duct Burners in the Heat Recovery Steam Generator

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

Liese, Eric; Zitney, Stephen E.

A generic training simulator of a natural gas combined cycle was modified to match operations at a real plant. The objective was to use the simulator to analyze cycling operations of the plant. Initial operation of the simulator revealed the potential for saturation conditions in the final high pressure superheater as the attemperator tried to control temperature at the superheater outlet during gas turbine loading and unloading. Subsequent plant operational data confirmed simulation results. Multiple simulations were performed during loading and unloading of the gas turbine to determine operational strategies that prevented saturation and increased the approach to saturation temperature.more » The solutions included changes to the attemperator temperature control setpoints and strategic control of the steam turbine inlet pressure control valve.« less

Analysis of capillary drainage from a flat solid strip

NASA Astrophysics Data System (ADS)

Ramé, Enrique; Zimmerli, Gregory A.

2014-06-01

A long and narrow solid strip coated with a thin liquid layer is used as a model of a generic fluid mass probe in a spacecraft propellant tank just after a small thruster firing. The drainage dynamics of the initial coating layer into the settled bulk fluid affects the interpretation of probe measurements as the sensors' signal depends strongly on whether a sensor is in contact with vapor or with liquid. We analyze the drainage under various conditions of zero-gravity (i.e., capillary drainage) and with gravity aligned with the strip length, corresponding to the thruster acceleration. Long-time analytical solutions are found for zero and non-zero gravity. In the case with gravity, an approximate solution is found using matched asymptotics. Estimates show that a thrust of 10-3g0 significantly reduces drainage times.

Parametric study of the dynamic JWL-EOS for detonation products

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

Urtiew, P.A.; Hayes, B.

1990-03-01

The JWL equation of state describing the adiabatic expansion of detonation products is revisited to complete the description of the principal eigenvalue, to reset the secondary eigenvalue to produce a well-behaved adiabatic gamma profile, and to normalize the characteristic equation of state in terms of conventional parameters having a clear experimental interpretation. This is accomplished by interjecting a dynamic flow condition concerning the value of the relative specific volume when the particle velocity of the detonation products is zero. In addition, a set of generic parameters based on the statistical distribution of the primary explosives making up the available datamore » base is presented. Unlike theoretical and statistical mechanical models, the adiabatic gamma function for these materials is seen to have a positive initial slope in accord with experimental findings. 10 refs., 4 figs.« less

Cooperative mission execution and planning

NASA Astrophysics Data System (ADS)

Flann, Nicholas S.; Saunders, Kevin S.; Pells, Larry

1998-08-01

Utilizing multiple cooperating autonomous vehicles to perform tasks enhances robustness and efficiency over the use of a single vehicle. Furthermore, because autonomous vehicles can be controlled precisely and their status known accurately in real time, new types of cooperative behaviors are possible. This paper presents a working system called MEPS that plans and executes missions for multiple autonomous vehicles in large structured environments. Two generic spatial tasks are supported, to sweep an area and to visit a location while activating on-board equipment. Tasks can be entered both initially by the user and dynamically during mission execution by both users and vehicles. Sensor data and task achievement data is shared among the vehicles enabling them to cooperatively adapt to changing environmental, vehicle and tasks conditions. The system has been successfully applied to control ATV and micro-robotic vehicles in precision agriculture and waste-site characterization environments.

Non-minimal gravitational reheating during kination

NASA Astrophysics Data System (ADS)

Dimopoulos, Konstantinos; Markkanen, Tommi

2018-06-01

A new mechanism is presented which can reheat the Universe in non-oscillatory models of inflation, where the inflation period is followed by a period dominated by the kinetic density for the inflaton field (kination). The mechanism considers an auxiliary field non-minimally coupled to gravity. The auxiliary field is a spectator during inflation, rendered heavy by the non-minimal coupling to gravity. During kination however, the non-minimal coupling generates a tachyonic mass, which displaces the field, until its bare mass becomes important, leading to coherent oscillations. Then, the field decays into the radiation bath of the hot big bang. The model is generic and predictive, in that the resulting reheating temperature is a function only of the model parameters (masses and couplings) and not of initial conditions. It is shown that reheating can be very efficient also when considering only the Standard Model.

Conventional curing practices reduce generic Escherichia coli and Salmonella spp. on dry bulb onions produced with contaminated irrigation water.

PubMed

Emch, Alexander W; Waite-Cusic, Joy G

2016-02-01

Food Safety Modernization Act (FSMA) has emphasized microbial risks associated with irrigation water. Treasure Valley (eastern Oregon/western Idaho) has the highest yield of dry bulb onions in the country; however, their irrigation water is often non-compliant with current industry and proposed federal standards for fresh produce. Conventional curing practices may provide a mechanism to mitigate irrigation water quality to comply with FSMA regulations. Dry bulb onions were grown in Owyhee silt loam and Semiahmoo muck soils in greenhouses and irrigated with water containing a cocktail of rifampicin-resistant generic Escherichia coli and Salmonella spp. (4.80 log CFU/ml). To mimic conventional practices, mature onions remained undisturbed in soil without irrigation for 12 days prior to being lifted and cured for 16 additional days. Surviving generic E. coli and Salmonella spp. were selectively enumerated on using standard plating (Hektoen Enteric Agar with rifampicin; HE + rif) or most probable number (lactose broth with rifampicin; HE + rif) methods. Generic E. coli and Salmonella spp. on onions decreased 0.19-0.26 log CFU/g·d during the initial 12 days of finishing. At lifting, generic E. coli and Salmonella spp. had been reduced to <1 CFU/g and persisted through the end of curing. This study demonstrates conventional curing practices as an effective mitigation strategy for dry bulb onions produced with water of poor microbiological quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bioequivalence of generic alendronate sodium tablets (70 mg) to Fosamax® tablets (70 mg) in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

PubMed Central

Zhang, Yifan; Chen, Xiaoyan; Tang, Yunbiao; Lu, Youming; Guo, Lixia; Zhong, Dafang

2017-01-01

Purpose The aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax® 70 mg tablet. Materials and methods A single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg). Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) reference-scaled average bioequivalence (RSABE) methods. Results The average maximum concentrations (Cmax) of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration–time curves from time 0 to the last timepoint (AUC0–t) were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h⋅ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product (sWR) for Cmax and AUC0–t were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were −0.16 and −0.17 for Cmax and AUC0–t, respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for Cmax and AUC0–t were 90.35%–129.04% and 85.31%–117.15%, respectively, which were within the limits of the EMA for the bioequivalence of 69.84%–143.19% and 80.00%–125.00%. Conclusion The generic product was bioequivalent to the reference product in terms of the rate and extent of alendronate absorption after a single 70 mg oral dose under fasting conditions. PMID:28744102

The Generic Spacecraft Analyst Assistant (gensaa): a Tool for Developing Graphical Expert Systems

NASA Technical Reports Server (NTRS)

Hughes, Peter M.

1993-01-01

During numerous contacts with a satellite each day, spacecraft analysts must closely monitor real-time data. The analysts must watch for combinations of telemetry parameter values, trends, and other indications that may signify a problem or failure. As the satellites become more complex and the number of data items increases, this task is becoming increasingly difficult for humans to perform at acceptable performance levels. At NASA GSFC, fault-isolation expert systems are in operation supporting this data monitoring task. Based on the lessons learned during these initial efforts in expert system automation, a new domain-specific expert system development tool named the Generic Spacecraft Analyst Assistant (GenSAA) is being developed to facilitate the rapid development and reuse of real-time expert systems to serve as fault-isolation assistants for spacecraft analysts. Although initially domain-specific in nature, this powerful tool will readily support the development of highly graphical expert systems for data monitoring purposes throughout the space and commercial industry.

The generic danger and the idiosyncratic support

NASA Astrophysics Data System (ADS)

Temme, Arnaud; Nijp, Jelmer; van der Meij, Marijn; Samia, Jalal; Masselink, Rens

2016-04-01

This contribution argues two main points. First, that generic landscapes used in some modelling studies sometimes have properties or cause simulation results that are unrealistic. Such initially flat or straight-sloped landscapes, sometimes with minor random perturbations, e.g. form the backdrop for ecological simulations of vegetation growth and competition that predict catastrophic shifts. Exploratory results for semi-arid systems suggest that the results based on these generic landscapes are end-members from a distribution of results, rather than an unbiased, typical outcome. Apparently, the desire to avoid idiosyncrasy has unintended consequences. Second, we argue and illustrate that in fact new insights often come from close inspection of idiosyncratic case studies. Our examples from landslide systems, connectivity and soil formation show how a central role for the case study - either in empirical work or to provide model targets - has advanced our understanding. Both points contribute to the conclusion that it is dangerous to forget about annoying, small-scale, idiosyncratic and, indeed, perhaps bad-ass case studies in Earth Sciences.

SEL Ada reuse analysis and representations

NASA Technical Reports Server (NTRS)

Kester, Rush

1990-01-01

Overall, it was revealed that the pattern of Ada reuse has evolved from initial reuse of utility components into reuse of generalized application architectures. Utility components were both domain-independent utilities, such as queues and stacks, and domain-specific utilities, such as those that implement spacecraft orbit and attitude mathematical functions and physics or astronomical models. The level of reuse was significantly increased with the development of a generalized telemetry simulator architecture. The use of Ada generics significantly increased the level of verbatum reuse, which is due to the ability, using Ada generics, to parameterize the aspects of design that are configurable during reuse. A key factor in implementing generalized architectures was the ability to use generic subprogram parameters to tailor parts of the algorithm embedded within the architecture. The use of object oriented design (in which objects model real world entities) significantly improved the modularity for reuse. Encapsulating into packages the data and operations associated with common real world entities creates natural building blocks for reuse.

Operationally Efficient Propulsion System Study (OEPSS) data book. Volume 1: Generic ground operations data

NASA Technical Reports Server (NTRS)

Byrd, Raymond J.

1990-01-01

This study was initiated to identify operations problems and cost drivers for current propulsion systems and to identify technology and design approaches to increase the operational efficiency and reduce operations costs for future propulsion systems. To provide readily usable data for the Advance Launch System (ALS) program, the results of the Operationally Efficient Propulsion System Study (OEPSS) were organized into a series of OEPSS Data Books as follows: Volume 1, Generic Ground Operations Data; Volume 2, Ground Operations Problems; Volume 3, Operations Technology; Volume 4, OEPSS Design Concepts; and Volume 5, OEPSS Final Review Briefing, which summarizes the activities and results of the study. This volume presents ground processing data for a generic LOX/LH2 booster and core propulsion system based on current STS experience. The data presented includes: top logic diagram, process flow, activities bar-chart, loaded timelines, manpower requirements in terms of duration, headcount and skill mix per operations and maintenance instruction (OMI), and critical path tasks and durations.

Overview of NASA Lewis Research Center free-piston Stirling engine activities

NASA Technical Reports Server (NTRS)

Slaby, J. G.

1984-01-01

A generic free-piston Stirling technology project is being conducted to develop technologies generic to both space power and terrestrial heat pump applications in a cooperative, cost-shared effort. The generic technology effort includes extensive parametric testing of a 1 kW free-piston Stirling engine (RE-1000), development of a free-piston Stirling performance computer code, design and fabrication under contract of a hydraulic output modification for RE-1000 engine tests, and a 1000-hour endurance test, under contract, of a 3 kWe free-piston Stirling/alternator engine. A newly initiated space power technology feasibility demonstration effort addresses the capability of scaling a free-piston Stirling/alternator system to about 25 kWe; developing thermodynamic cycle efficiency or equal to 70 percent of Carnot at temperature ratios in the order of 1.5 to 2.0; achieving a power conversion unit specific weight of 6 kg/kWe; operating with noncontacting gas bearings; and dynamically balancing the system. Planned engine and component design and test efforts are described.

An Approach to Detect and Mitigate Ice Particle Accretion in Aircraft Engine Compression Systems

NASA Technical Reports Server (NTRS)

May, Ryan D.; Guo, Ten-Huei; Simon, Donald L.

2013-01-01

The accretion of ice in the compression system of commercial gas turbine engines operating in high ice water content conditions is a safety issue being studied by the aviation sector. While most of the research focuses on the underlying physics of ice accretion and the meteorological conditions in which accretion can occur, a systems-level perspective on the topic lends itself to potential near-term operational improvements. This work focuses on developing an accurate and reliable algorithm for detecting the accretion of ice in the low pressure compressor of a generic 40,000 lbf thrust class engine. The algorithm uses only the two shaft speed sensors and works regardless of engine age, operating condition, and power level. In a 10,000-case Monte Carlo simulation, the detection approach was found to have excellent capability at determining ice accretion from sensor noise with detection occurring when ice blocks an average of 6.8 percent of the low pressure compressor area. Finally, an initial study highlights a potential mitigation strategy that uses the existing engine actuators to raise the temperature in the low pressure compressor in an effort to reduce the rate at which ice accretes.

An Approach to Detect and Mitigate Ice Particle Accretion in Aircraft Engine Compression Systems

NASA Technical Reports Server (NTRS)

May, Ryan D.; Guo, Ten-Huei; Simon, Donald L.

2013-01-01

The accretion of ice in the compression system of commercial gas turbine engines operating in high ice water content conditions is a safety issue being studied by the aviation sector. While most of the research focuses on the underlying physics of ice accretion and the meteorological conditions in which accretion can occur, a systems-level perspective on the topic lends itself to potential near-term operational improvements. This work focuses on developing an accurate and reliable algorithm for detecting the accretion of ice in the low pressure compressor of a generic 40,000 lbf thrust class engine. The algorithm uses only the two shaft speed sensors and works regardless of engine age, operating condition, and power level. In a 10,000-case Monte Carlo simulation, the detection approach was found to have excellent capability at determining ice accretion from sensor noise with detection occurring when ice blocks an average of 6.8% of the low pressure compressor area. Finally, an initial study highlights a potential mitigation strategy that uses the existing engine actuators to raise the temperature in the low pressure compressor in an effort to reduce the rate at which ice accretes.

A Systems-Level Perspective on Engine Ice Accretion

NASA Technical Reports Server (NTRS)

May, Ryan D.; Guo, Ten-Huei; Simon, Donald L.

2013-01-01

The accretion of ice in the compression system of commercial gas turbine engines operating in high ice water content conditions is a safety issue being studied by the aviation sector. While most of the research focuses on the underlying physics of ice accretion and the meteorological conditions in which accretion can occur, a systems-level perspective on the topic lends itself to potential near-term operational improvements. This work focuses on developing an accurate and reliable algorithm for detecting the accretion of ice in the low pressure compressor of a generic 40,000 lbf thrust class engine. The algorithm uses only the two shaft speed sensors and works regardless of engine age, operating condition, and power level. In a 10,000-case Monte Carlo simulation, the detection approach was found to have excellent capability at determining ice accretion from sensor noise with detection occurring when ice blocks an average of 6.8% of the low pressure compressor area. Finally, an initial study highlights a potential mitigation strategy that uses the existing engine actuators to raise the temperature in the low pressure compressor in an effort to reduce the rate at which ice accretes.

Numerical and experimental study of the thermal degradation process during the atmospheric re-entry of a TiAl6V4 tank

NASA Astrophysics Data System (ADS)

Prévereaud, Y.; Vérant, J.-L.; Balat-Pichelin, M.; Moschetta, J.-M.

2016-05-01

To answer the question of space debris survivability during atmospheric entry ONERA uses its software named MUSIC/FAST. So, the first part of this paper is dedicated to the presentation of the ONERA tool and its validation by comparison with flight data and CFD computations. However, the influence of oxidation on the thermal degradation process and material properties in atmospheric entry conditions is still unknown. A second step is then devoted to the presentation of an experimental campaign investigating TA6V oxidation in atmospheric entry conditions, as the most of the debris found on ground are made of this material. Experiments have been realized using the MESOX facility implemented at the 6 kW solar furnace in PROMES-CNRS laboratory. Finally, an application of MUSIC/FAST is proposed on the atmospheric re-entry of a generic TA6V tank. Aiming at degradation assessment, a sensitive study to initial conditions is conducted. To complete computational analysis regarding degradation process by melting, a numerical analysis of the influence of oxidation on the thermal wall degradation during the tank atmospheric re-entry is presented as well.

Complete set of homogeneous isotropic analytic solutions in scalar-tensor cosmology with radiation and curvature

NASA Astrophysics Data System (ADS)

Bars, Itzhak; Chen, Shih-Hung; Steinhardt, Paul J.; Turok, Neil

2012-10-01

We study a model of a scalar field minimally coupled to gravity, with a specific potential energy for the scalar field, and include curvature and radiation as two additional parameters. Our goal is to obtain analytically the complete set of configurations of a homogeneous and isotropic universe as a function of time. This leads to a geodesically complete description of the Universe, including the passage through the cosmological singularities, at the classical level. We give all the solutions analytically without any restrictions on the parameter space of the model or initial values of the fields. We find that for generic solutions the Universe goes through a singular (zero-size) bounce by entering a period of antigravity at each big crunch and exiting from it at the following big bang. This happens cyclically again and again without violating the null-energy condition. There is a special subset of geodesically complete nongeneric solutions which perform zero-size bounces without ever entering the antigravity regime in all cycles. For these, initial values of the fields are synchronized and quantized but the parameters of the model are not restricted. There is also a subset of spatial curvature-induced solutions that have finite-size bounces in the gravity regime and never enter the antigravity phase. These exist only within a small continuous domain of parameter space without fine-tuning the initial conditions. To obtain these results, we identified 25 regions of a 6-parameter space in which the complete set of analytic solutions are explicitly obtained.

Development of utility generic functional requirements for electronic work packages and computer-based procedures

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

Oxstrand, Johanna

The Nuclear Electronic Work Packages - Enterprise Requirements (NEWPER) initiative is a step toward a vision of implementing an eWP framework that includes many types of eWPs. This will enable immediate paper-related cost savings in work management and provide a path to future labor efficiency gains through enhanced integration and process improvement in support of the Nuclear Promise (Nuclear Energy Institute 2016). The NEWPER initiative was organized by the Nuclear Information Technology Strategic Leadership (NITSL) group, which is an organization that brings together leaders from the nuclear utility industry and regulatory agencies to address issues involved with information technology usedmore » in nuclear-power utilities. NITSL strives to maintain awareness of industry information technology-related initiatives and events and communicates those events to its membership. NITSL and LWRS Program researchers have been coordinating activities, including joint organization of NEWPER-related meetings and report development. The main goal of the NEWPER initiative was to develop a set of utility generic functional requirements for eWP systems. This set of requirements will support each utility in their process of identifying plant-specific functional and non-functional requirements. The NEWPER initiative has 140 members where the largest group of members consists of 19 commercial U.S. nuclear utilities and eleven of the most prominent vendors of eWP solutions. Through the NEWPER initiative two sets of functional requirements were developed; functional requirements for electronic work packages and functional requirements for computer-based procedures. This paper will describe the development process as well as a summary of the requirements.« less

A Coordinated Initialization Process for the Distributed Space Exploration Simulation (DSES)

NASA Technical Reports Server (NTRS)

Phillips, Robert; Dexter, Dan; Hasan, David; Crues, Edwin Z.

2007-01-01

This document describes the federate initialization process that was developed at the NASA Johnson Space Center with the HIIA Transfer Vehicle Flight Controller Trainer (HTV FCT) simulations and refined in the Distributed Space Exploration Simulation (DSES). These simulations use the High Level Architecture (HLA) IEEE 1516 to provide the communication and coordination between the distributed parts of the simulation. The purpose of the paper is to describe a generic initialization sequence that can be used to create a federate that can: 1. Properly initialize all HLA objects, object instances, interactions, and time management 2. Check for the presence of all federates 3. Coordinate startup with other federates 4. Robustly initialize and share initial object instance data with other federates.

Dynamic stability and bifurcation analysis in fractional thermodynamics

NASA Astrophysics Data System (ADS)

Béda, Péter B.

2018-02-01

In mechanics, viscoelasticity was the first field of applications in studying geomaterials. Further possibilities arise in spatial non-locality. Non-local materials were already studied in the 1960s by several authors as a part of continuum mechanics and are still in focus of interest because of the rising importance of materials with internal micro- and nano-structure. When material instability gained more interest, non-local behavior appeared in a different aspect. The problem was concerned to numerical analysis, because then instability zones exhibited singular properties for local constitutive equations. In dynamic stability analysis, mathematical aspects of non-locality were studied by using the theory of dynamic systems. There the basic set of equations describing the behavior of continua was transformed to an abstract dynamic system consisting of differential operators acting on the perturbation field variables. Such functions should satisfy homogeneous boundary conditions and act as indicators of stability of a selected state of the body under consideration. Dynamic systems approach results in conditions for cases, when the differential operators have critical eigenvalues of zero real parts (dynamic stability or instability conditions). When the critical eigenvalues have non-trivial eigenspace, the way of loss of stability is classified as a typical (or generic) bifurcation. Our experiences show that material non-locality and the generic nature of bifurcation at instability are connected, and the basic functions of the non-trivial eigenspace can be used to determine internal length quantities of non-local mechanics. Fractional calculus is already successfully used in thermo-elasticity. In the paper, non-locality is introduced via fractional strain into the constitutive relations of various conventional types. Then, by defining dynamic systems, stability and bifurcation are studied for states of thermo-mechanical solids. Stability conditions and genericity conditions are presented for constitutive relations under consideration.

Thermal Modeling and Analysis of a Cryogenic Tank Design Exposed to Extreme Heating Profiles

NASA Technical Reports Server (NTRS)

Stephens, Craig A.; Hanna, Gregory J.

1991-01-01

A cryogenic test article, the Generic Research Cryogenic Tank, was designed to qualitatively simulate the thermal response of transatmospheric vehicle fuel tanks exposed to the environment of hypersonic flight. One-dimensional and two-dimensional finite-difference thermal models were developed to simulate the thermal response and assist in the design of the Generic Research Cryogenic Tank. The one-dimensional thermal analysis determined the required insulation thickness to meet the thermal design criteria and located the purge jacket to eliminate the liquefaction of air. The two-dimensional thermal analysis predicted the temperature gradients developed within the pressure-vessel wall, estimated the cryogen boiloff, and showed the effects the ullage condition has on pressure-vessel temperatures. The degree of ullage mixing, location of the applied high-temperature profile, and the purge gas influence on insulation thermal conductivity had significant effects on the thermal behavior of the Generic Research Cryogenic Tank. In addition to analysis results, a description of the Generic Research Cryogenic Tank and the role it will play in future thermal structures and transatmospheric vehicle research at the NASA Dryden Flight Research Facility is presented.

Regulatory and clinical aspects of psychotropic medicinal products bioequivalence.

PubMed

Bałkowiec-Iskra, Ewa; Cessak, Grzegorz; Kuzawińska, Olga; Sejbuk-Rozbicka, Katarzyna; Rokita, Konrad; Mirowska-Guzel, Dagmara

2015-07-01

Introduction of generic medicinal products to the market has increased access to modern therapies but also enabled significant reduction in their cost, leading to containment of public expenditures on medicinal products reimbursement. The critical assessment of bioequivalence of any reference medicinal product and its counterpart is based on comparison of their rate and extent of absorption. It is assumed that two medicinal products are bioequivalent when their rate and extent of absorption do not show significant differences when administered at the same dose under similar experimental conditions. Bioequivalent medicinal products are declared to be also therapeutically equivalent and can be used interchangeably. However, despite regulatory declaration, switching from reference to generic drugs is often associated with concerns of healthcare providers about decreased treatment effectiveness or occurrence of adverse drug reactions. The aim of this article is to provide a description of rules that guide registration of generic medicinal products in the European Union and to analyze specific examples from the scientific literature concerning therapeutic equivalence of reference and generic antidepressant and antipsychotic medicinal products. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Stem geometry changes initial femoral fixation stability of a revised press-fit hip prosthesis: A finite element study.

PubMed

Russell, Robert D; Huo, Michael H; Rodrigues, Danieli C; Kosmopoulos, Victor

2016-11-14

Stable femoral fixation during uncemented total hip arthroplasty is critical to allow for subsequent osseointegration of the prosthesis. Varying stem designs provide surgeons with multiple options to gain femoral fixation. The purpose of this study was to compare the initial fixation stability of cylindrical and tapered stem implants using two different underreaming techniques (press-fit conditions) for revision total hip arthroplasty (THA). A finite element femur model was created from three-dimensional computed tomography images simulating a trabecular bone defect commonly observed in revision THA. Two 18-mm generic femoral hip implants were modeled using the same geometry, differing only in that one had a cylindrical stem and the other had a 2 degree tapered stem. Surgery was simulated using a 0.05-mm and 0.01-mm press-fit and tested with a physiologically relevant loading protocol. Mean contact pressure was influenced more by the surgical technique than by the stem geometry. The 0.05-mm press-fit condition resulted in the highest contact pressures for both the cylindrical (27.35 MPa) and tapered (20.99 MPa) stems. Changing the press-fit to 0.01-mm greatly decreased the contact pressure by 79.8% and 78.5% for the cylindrical (5.53 MPa) and tapered (4.52 MPa) models, respectively. The cylindrical stem geometry consistently showed less relative micromotion at all the cross-sections sampled as compared to the tapered stem regardless of press-fit condition. This finite element analysis study demonstrates that tapered stem results in lower average contact pressure and greater micromotion at the implant-bone interface than a cylindrical stem geometry. More studies are needed to establish how these different stem geometries perform in such non-ideal conditions encountered in revision THA cases where less bone stock is available.

Toward Optimizing VEMP: Calculating VEMP Inhibition Depth With a Generic Template.

PubMed

Noij, Kimberley S; van Tilburg, Mark J; Herrmann, Barbara S; Marciniak, Piotr; Rauch, Steven D; Guinan, John J

2018-04-05

Cervical vestibular evoked myogenic potentials (cVEMP) indirectly reveal the response of the saccule to acoustic stimuli through the inhibition of sternocleidomastoid muscle electromyographic response. VEMP inhibition depth (VEMPid) is a recently developed metric that estimates the percentage of saccular inhibition. VEMPid provides both normalization and better accuracy at low response levels than amplitude-normalized cVEMPs. Hopefully, VEMPid will aid in the clinical assessment of patients with vestibulopatholgy. To calculate VEMPid a template is needed. In the original method, a subject's own cVEMP was used as the template, but this method can be problematic in patients who do not have robust cVEMP responses. We hypothesize that a "generic" template, created by assembling cVEMPs from healthy subjects, can be used to compute VEMPid, which would facilitate the use of VEMPid in subjects with pathological conditions. A generic template was created by averaging cVEMP responses from 6 normal subjects. To compare VEMPid calculations using a generic versus a subject-specific template, cVEMPs were obtained in 40 healthy subjects using 500, 750, and 1000 Hz tonebursts at sound levels ranging from 98 to 123 dB peSPL. VEMPids were calculated both with the generic template and with the subject's own template. The ability of both templates to determine whether a cVEMP was present or not was compared with receiver operating characteristic curves. No significant differences were found between VEMPid calculations using a generic template versus using a subject-specific template for all frequencies and sound levels. Based on the receiver operating characteristic curves, the subject-specific and generic template did an equally good job at determining threshold. Within limits, the shape of the generic template did not affect these results. A generic template can be used instead of a subject-specific template to calculate VEMPid. Compared with cVEMP normalized by electromyographic amplitudes, VEMPid is advantageous because it averages zero when there is no sound stimulus and it allows the accumulating VEMPid value to be shown during data acquisition as a guide to deciding when enough data has been collected.

The Role of Geographical Indication in Supporting Food Safety: A not Taken for Granted Nexus

PubMed Central

2014-01-01

The paper focuses on the role of geographical indication in supporting strategies of food safety. Starting from the distinction between generic and specific quality, the article analyses the main factors influencing food safety in cases of geographical indication products, by stressing the importance of traceability systems and biodiversity in securing generic and specific quality. In the second part, the paper investigates the coordination problems behind a designation of origin and conditions to foster an effective collective action, a prerequisite to grant food safety through geographical indications. PMID:27800417

Survival and distribution of Escherichia coli on diverse fresh-cut baby leafy greens under preharvest through postharvest conditions.

PubMed

Tomás-Callejas, Alejandro; López-Velasco, Gabriela; Camacho, Alex B; Artés, Francisco; Artés-Hernández, Francisco; Suslow, Trevor V

2011-12-02

Escherichia coli O157:H7 has been associated in multiple outbreaks linked to the consumption of whole produce and fresh-cut leafy vegetables. However, plant-based foods had not been traditionally recognized as a host for enteric pathogens until the elevated incidence of produce-related outbreaks became apparent. The survival dynamics of two cocktails of generic E. coli (environmental water, plant and soil isolates) and E. coli O157:H7 within the phyllosphere of Mizuna, Red Chard and Tatsoi during their production, harvest, minimal processing, packaging and storage over two greenhouse production cycles were studied. Genotyping of applied generic E. coli strains to evaluate their comparative survival and relative abundance in the phyllosphere by REP-PCR is also reported. The Mizuna, Red Chard and Tatsoi shoots were grown under standard greenhouse conditions and fertility management. Both E. coli cocktails were spray-inoculated separately and determined to result in an initial mean population density of log 4.2 CFU/cm². Leaves were harvested as mini-greens approximating commercial maturity, minimally processed in a model washing system treated with 3 mg/L of ClO₂ and stored for 7 days at 5 °C. Rapid decline of generic E. coli and E. coli O157:H7 populations was observed for all plant types regardless of the leaf age at the time of inoculation and the irrigation type across both seasonal growth cycle trials. The decline rate of the surviving populations for the fall season was slower than for the summer season. The minimal processing with 3 mg/L of ClO₂ was not sufficient to fully disinfect the inoculated leaves prior to packaging and refrigerated storage. Viable populations of E. coli and E. coli O157:H7 were confirmed throughout storage, including the final time point at the end of acceptable visual leaf quality. In this study, the ability of low populations of E. coli to survive during production and postharvest operations in selected mini-greens has been demonstrated. However, further field-based trials are needed to expand understanding of the post-contamination fate of enteric bacterial pathogens on leafy vegetables. In summary, this research work provides baseline data upon which to develop food safety preventive control guidance during the production and minimal processing of these crops. Copyright © 2011 Elsevier B.V. All rights reserved.

An Exploratory Study on Using Principal-Component Analysis and Confirmatory Factor Analysis to Identify Bolt-On Dimensions: The EQ-5D Case Study.

PubMed

Finch, Aureliano Paolo; Brazier, John Edward; Mukuria, Clara; Bjorner, Jakob Bue

2017-12-01

Generic preference-based measures such as the EuroQol five-dimensional questionnaire (EQ-5D) are used in economic evaluation, but may not be appropriate for all conditions. When this happens, a possible solution is adding bolt-ons to expand their descriptive systems. Using review-based methods, studies published to date claimed the relevance of bolt-ons in the presence of poor psychometric results. This approach does not identify the specific dimensions missing from the Generic preference-based measure core descriptive system, and is inappropriate for identifying dimensions that might improve the measure generically. This study explores the use of principal-component analysis (PCA) and confirmatory factor analysis (CFA) for bolt-on identification in the EQ-5D. Data were drawn from the international Multi-Instrument Comparison study, which is an online survey on health and well-being measures in five countries. Analysis was based on a pool of 92 items from nine instruments. Initial content analysis provided a theoretical framework for PCA results interpretation and CFA model development. PCA was used to investigate the underlining dimensional structure and whether EQ-5D items were represented in the identified constructs. CFA was used to confirm the structure. CFA was cross-validated in random halves of the sample. PCA suggested a nine-component solution, which was confirmed by CFA. This included psychological symptoms, physical functioning, and pain, which were covered by the EQ-5D, and satisfaction, speech/cognition,relationships, hearing, vision, and energy/sleep which were not. These latter factors may represent relevant candidate bolt-ons. PCA and CFA appear useful methods for identifying potential bolt-ons dimensions for an instrument such as the EQ-5D. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Exact solutions for discrete breathers in a forced-damped chain.

PubMed

Gendelman, O V

2013-06-01

Exact solutions for symmetric on-site discrete breathers (DBs) are obtained in a forced-damped linear chain with on-site vibro-impact constraints. The damping in the system is caused by inelastic impacts; the forcing functions should satisfy conditions of periodicity and antisymmetry. Global conditions for existence and stability of the DBs are established by a combination of analytic and numeric methods. The DB can lose its stability through either pitchfork, or Neimark-Sacker bifurcations. The pitchfork bifurcation is related to the internal dynamics of each individual oscillator. It is revealed that the coupling can suppress this type of instability. To the contrary, the Neimark-Sacker bifurcation occurs for relatively large values of the coupling, presumably due to closeness of the excitation frequency to a boundary of the propagation zone of the chain. Both bifurcation mechanisms seem to be generic for the considered type of forced-damped lattices. Some unusual phenomena, like nonmonotonous dependence of the stability boundary on the forcing amplitude, are revealed analytically for the initial system and illustrated numerically for small periodic lattices.

Development of an integrated BEM approach for hot fluid structure interaction

NASA Technical Reports Server (NTRS)

Dargush, Gary F.; Banerjee, Prasanta K.; Honkala, Keith A.

1991-01-01

The development of a boundary element formulation for the study of hot fluid-structure interaction in earth-to-orbit engine hot section components is described. The initial primary thrust of the program to date was directed quite naturally toward the examination of fluid flow, since boundary element methods for fluids are at a much less developed state. This required the development of integral formulations for both the solid and fluid, and some preliminary infrastructural enhancements to a boundary element code to permit coupling of the fluid-structure problem. Boundary element formulations are implemented in two dimensions for both the solid and the fluid. The solid is modeled as an uncoupled thermoelastic medium under plane strain conditions, while several formulations are investigated for the fluid. For example, both vorticity and primitive variable approaches are implemented for viscous, incompressible flow, and a compressible version is developed. All of the above boundary element implementations are incorporated in a general purpose two-dimensional code. Thus, problems involving intricate geometry, multiple generic modeling regions, and arbitrary boundary conditions are all supported.

Community-Based Prevention Specialist. Trainer Manual.

ERIC Educational Resources Information Center

University Research Corp., Bethesda, MD.

This trainer manual is designed to assist facilitators in the design of entry-level courses and programs for substance abuse prevention specialists. The manual initially concentrates on a basic, generic approach to community work, and introduces the knowledge and skills needed to implement substance abuse prevention programs by using the community…

Development and Validation of an Internet Use Attitude Scale

ERIC Educational Resources Information Center

Zhang, Yixin

2007-01-01

This paper describes the development and validation of a new 40-item Internet Attitude Scale (IAS), a one-dimensional inventory for measuring the Internet attitudes. The first experiment initiated a generic Internet attitude questionnaire, ensured construct validity, and examined factorial validity and reliability. The second experiment further…

Information Services at the Nuclear Safety Analysis Center.

ERIC Educational Resources Information Center

Simard, Ronald

This paper describes the operations of the Nuclear Safety Analysis Center. Established soon after an accident at the Three Mile Island nuclear power plant near Harrisburg, Pennsylvania, its efforts were initially directed towards a detailed analysis of the accident. Continuing functions include: (1) the analysis of generic nuclear safety issues,…

Budget impact analysis of 8 hormonal contraceptive options.

PubMed

Crespi, Simone; Kerrigan, Matthew; Sood, Vipan

2013-07-01

To develop a model comparing costs of 8 hormonal contraceptives and determine whether acquisition costs for implants and intrauterine devices (IUDs) were offset by decreased pregnancy-related costs over a 3-year time horizon from a managed care perspective. A model was developed to assess the budget impact of branded or generic oral contraceptives (OCs), quarterly intramuscular depot medroxyprogesterone, etonogestrel/ethinyl estradiol vaginal ring, etonogestrel implant, levonorgestrel IUD, norelgestromin/ethinyl estradiol transdermal contraceptive, and ethinyl estradiol/levonorgestrel extended-cycle OC. Major variables included drug costs, typical use failure rates, discontinuation rates, and pregnancy costs. The base case assessed costs for 1000 women initiating each of the hormonal contraceptives. The etonogestrel implant and levonorgestrel IUD resulted in the fewest pregnancies, 63 and 85, respectively, and the least cost, $1.75 million and $2.0 million, respectively. In comparison, generic OC users accounted for a total of 243 pregnancies and $3.4 million in costs. At the end of year 1, costs for the etonogestrel implant ($800,471) and levonorgestrel IUD ($949,721) were already lower than those for generic OCs ($1,146,890). Sensitivity analysis showed that the cost of pregnancies, not product acquisition cost, was the primary cost driver. Higher initial acquisition costs for the etonogestrel implant and levonorgestrel IUD were offset within 1 year by lower contraceptive failure rates and consequent pregnancy costs. Thus, after accounting for typical use failure rates of contraceptive products, the etonogestrel implant and levonorgestrel IUD emerged as the least expensive hormonal contraceptives.

Differential effect of a patient-education transition intervention in adolescents with IBD vs. diabetes.

PubMed

Schmidt, Silke; Markwart, Henriette; Bomba, Franziska; Muehlan, Holger; Findeisen, Annette; Kohl, Martina; Menrath, Ingo; Thyen, Ute

2018-04-01

Patient education programs (PEPs) to improve disease management are part of standard and regular treatment in adolescents with diabetes. In Germany, youth with inflammatory bowel disease (IBD) receive individual counseling but not PEPs in group settings. Generic PEPs have been developed in order to improve transition from child-centered to adolescent health services. The aim of the study was to investigate the effects of a transition-oriented PEP on quality of life (QoL) and self-management in young patients with IBD (PEP naive), compared to patients with diabetes (familiar with PEPs). A 2-day transition workshop was oriented at improving psychosocial skills and addressed both generic as well as specific aspects of the condition. A controlled trial on the outcomes of a generic transition-oriented PEP was conducted in 14- to 20-year-old patients with IBD (n = 99) and diabetes (n = 153). Transition competence and QoL were assessed at baseline and 6-month follow-up. Results show that the intervention lead to a significant increase in QoL only in patients with IBD. The PEP significantly improved transition competence in both groups, however to a higher extent in subjects with IBD. Transition-oriented PEPs can have differential effects in different patient groups. However, this needs further longitudinal investigations. What is Known: • To date, evidence has accumulated concerning the effectiveness of patient education programs (PEPs) in pediatric health care for chronic conditions such as type 1 diabetes, asthma, atopic dermatitis, or obesity but is less documented in inflammatory bowel disease (IBD). In particular, PEPs in the transition period have not been investigated in youth with IBD. • The current study focuses on evaluating a PEP for transition preparation and management designed to be generically used across different chronic conditions since many aspects of managing chronic conditions share commonalities across conditions. The 2-day workshop included condition-specific modules adapted to the specific medical needs but was otherwise similar in quality and organization among different conditions. What is New: • The transition-oriented PEP was effective in enhancing self-management and transition management skills in both patients with IBD and diabetes; however, effects were higher in youth with IBD. A significant impact of the intervention on patients' QoL compared to the control group was only identified in youth with IBD. • We recommend that patients with IBD have access to PEP as a standard treatment as well as to a transition program during the course of illness.

Long-term Stability of Vancomycin Hydrochloride in Glucose 5% Polyolefin Bags: The Brand Name Versus a Generic Product.

PubMed

Huvelle, Sophie; Godet, Marie; Hecq, Jean-Daniel; Gillet, Patricia; Jamart, Jacques; Galanti, Laurence M

2016-01-01

The objectives of this study were to determine if the preparation of vancomycin hydrochloride in advance of infusion could improve the quality of the drug, time management of drug delivery, cost savings of drug delivery, and to investigate the long-term stability of vancomycin hydrochloride (brand name Vancocin®) infusion in glucose 5% polyolefin bags versus the generic (Vancomycine®) at 5°C ± 3°C. Five bags of each infusion 1 g/100 mL vancomycin hydrochloride in 5% glucose (Vancocin ® and Vancomycine®) were stored up to 57 days at 5°C ± 3°C. A visual inspection and pH measurement were performed periodically during the storage, and the concentrations were measured by high-performance liquid chromatography-diode array detection. No color change or precipitation in the solution was observed throughout the study period. As recommended by the U.S. Food and Drug Administration, the lower confidence limit at 95% of the concentration for the solutions remained superior to 90% of the initial concentration up to 43 days for the brand vancomycin (Vancocin®) infusion (96% ± 2%) and up to 57 days for the generic (Vancomycine®) (95% ± 4%). The solutions prepared either from brand or generic vancomycin hydrochloride were chemically stable more than one month (43 days for the brand and 57 days for the generic solution) and could be prepared in advance in a centralized intravenous additive service facility. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Artificial neural network modelling for organic and total nitrogen removal of aerobic granulation under steady-state condition.

PubMed

Gong, H; Pishgar, R; Tay, J H

2018-04-27

Aerobic granulation is a recent technology with high level of complexity and sensitivity to environmental and operational conditions. Artificial neural networks (ANNs), computational tools capable of describing complex non-linear systems, are the best fit to simulate aerobic granular bioreactors. In this study, two feedforward backpropagation ANN models were developed to predict chemical oxygen demand (Model I) and total nitrogen removal efficiencies (Model II) of aerobic granulation technology under steady-state condition. Fundamentals of ANN models and the steps to create them were briefly reviewed. The models were respectively fed with 205 and 136 data points collected from laboratory-, pilot-, and full-scale studies on aerobic granulation technology reported in the literature. Initially, 60%, 20%, and 20%, and 80%, 10%, and 10% of the points in the corresponding datasets were randomly chosen and used for training, testing, and validation of Model I, and Model II, respectively. Overall coefficient of determination (R 2 ) value and mean squared error (MSE) of the two models were initially 0.49 and 15.5, and 0.37 and 408, respectively. To improve the model performance, two data division methods were used. While one method is generic and potentially applicable to other fields, the other can only be applied to modelling the performance of aerobic granular reactors. R 2 value and MSE were improved to 0.90 and 2.54, and 0.81 and 121.56, respectively, after applying the new data division methods. The results demonstrated that ANN-based models were capable simulation approach to predict a complicated process like aerobic granulation.

Objectivity in a Noisy Photonic Environment through Quantum State Information Broadcasting

NASA Astrophysics Data System (ADS)

Korbicz, J. K.; Horodecki, P.; Horodecki, R.

2014-03-01

Recently, the emergence of classical objectivity as a property of a quantum state has been explicitly derived for a small object embedded in a photonic environment in terms of a spectrum broadcast form—a specific classically correlated state, redundantly encoding information about the preferred states of the object in the environment. However, the environment was in a pure state and the fundamental problem was how generic and robust is the conclusion. Here, we prove that despite the initial environmental noise, the emergence of the broadcast structure still holds, leading to the perceived objectivity of the state of the object. We also show how this leads to a quantum Darwinism-type condition, reflecting the classicality of proliferated information in terms of a limit behavior of the mutual information. Quite surprisingly, we find "singular points" of the decoherence, which can be used to faithfully broadcast a specific classical message through the noisy environment.

Nanodisc-Tm: Rapid functional assessment of nanodisc reconstituted membrane proteins by CPM assay.

PubMed

Ashok, Yashwanth; Jaakola, Veli-Pekka

2016-01-01

Membrane proteins are generally unstable in detergents. Therefore, biochemical and biophysical studies of membrane proteins in lipidic environments provides a near native-like environment suitable for membrane proteins. However, manipulation of proteins embedded in lipid bilayer has remained difficult. Methods such as nanodiscs and lipid cubic phase have been developed for easy manipulation of membrane proteins and have yielded significant insights into membrane proteins. Traditionally functional reconstitution of receptors in nanodiscs has been studied with radioligands. We present a simple and faster method for studying the functionality of reconstituted membrane proteins for routine characterization of protein batches after initial optimization of suitable conditions using radioligands. The benefits of the method are •Faster and generic method to assess functional reconstitution of membrane proteins.•Adaptable in high throughput format (≥96 well format).•Stability measurement in near-native lipid environment and lipid dependent melting temperatures.

No elliptic islands for the universal area-preserving map

NASA Astrophysics Data System (ADS)

Johnson, Tomas

2011-07-01

A renormalization approach has been used in Eckmann et al (1982) and Eckmann et al (1984) to prove the existence of a universal area-preserving map, a map with hyperbolic orbits of all binary periods. The existence of a horseshoe, with positive Hausdorff dimension, in its domain was demonstrated in Gaidashev and Johnson (2009a). In this paper the coexistence problem is studied, and a computer-aided proof is given that no elliptic islands with period less than 18 exist in the domain. It is also shown that less than 1.5% of the measure of the domain consists of elliptic islands. This is proven by showing that the measure of initial conditions that escape to infinity is at least 98.5% of the measure of the domain, and we conjecture that the escaping set has full measure. This is highly unexpected, since generically it is believed that for conservative systems hyperbolicity and ellipticity coexist.

Mass inflation followed by Belinskii-Khalatnikov-Lifshitz collapse inside accreting, rotating black holes

NASA Astrophysics Data System (ADS)

Hamilton, Andrew J. S.

2017-10-01

Numerical evidence is presented that the Poisson-Israel mass inflation instability at the inner horizon of an accreting, rotating black hole is generically followed by Belinskii-Khalatnikov-Lifshitz oscillatory collapse to a spacelike singularity. The computation involves following all 6 degrees of freedom of the gravitational field. To simplify the problem, the computation takes as initial conditions the conformally separable solutions of Andrew J. S. Hamilton and Gavin Polhemus [Interior structure of rotating black holes. I. Concise derivation, Phys. Rev. D 84, 124055 (2011), 10.1103/PhysRevD.84.124055] and Andrew J. S. Hamilton [Interior structure of rotating black holes. II. Uncharged black holes, Phys. Rev. D 84, 124056 (2011), 10.1103/PhysRevD.84.124056] just above the inner horizon of a slowly accreting, rotating black hole and integrates the equations inward along single latitudes.

Bioequivalence of generic and branded amoxicillin capsules in healthy human volunteers

PubMed Central

Pathak, Priyanka; Pandit, Vijaya A.; Dhande, Priti P.

2017-01-01

CONTEXT: The Medical Council of India urges doctors to prescribe generic drugs as far as possible. The Indian Medical Association had responded earlier saying that it requires guarantees on the quality of generic forms of drugs. Although no published scientific reports are available on the issue of therapeutic inequivalence, unconfirmed clinician accounts and newspaper reports of therapeutic inequivalence exist. AIM: This study was planned to ascertain whether bioequivalence of branded and generic amoxicillin capsule is comparable. SETTINGS AND DESIGN: An open-label, randomized, single-dose, two-treatment, two-sequence, two-period crossover oral bioequivalence study was conducted in 12 healthy, adult human subjects under fasting condition. MATERIALS AND METHODS: Serum samples, collected at 8 time points, were analyzed by a validated ultraviolet spectrophotometer method. Pharmacokinetic (PK) parameters such as area under the curve (AUC)0–t, AUC0–∞, Cmax, and Tmax were determined along with time above minimum inhibitory concentration (MIC). STATISTICAL ANALYSIS USED: The log-transformed PK parameters (Cmax, AUC0–t, AUC0–∞) were analyzed using a Two One-Sided Test ANOVA in SAS for each parameter. Tmax and MIC were analyzed by Wilcoxon rank-sum test in GraphPad Prism. RESULTS: Geometric mean ratio of Cmax fell within bioequivalence criteria. The upper and lower confidence limits of both AUC0–t and AUC0–∞ geometric mean ratio fell below bioequivalence criteria. Time above MIC of generic preparation was significantly lower than that of branded version. CONCLUSIONS: The generic capsule was not bioequivalent to the branded amoxicillin capsule. PMID:28706331

Generic patches containing fentanyl: In vitro equivalence and abuse deterrent evaluation according to EMA and FDA guidelines.

PubMed

Padula, Cristina; Pescina, Silvia; Nicoli, Sara; Santi, Patrizia

2018-02-15

The aim of this work was to characterize in vitro and ex vivo the performances of Durogesic and of two bioequivalent generic products, by evaluating: (a) fentanyl release; (b) fentanyl permeation across porcine skin and (c) fentanyl ease of extraction. Additional characteristics studied are the effect of temperature and skin integrity, applied individually or combined, to check a possible synergism. The two generic patches resulted equivalent to the originator according to the new Guideline. Nevertheless, the same data reported in a different way, i.e. considering the total amount of drug permeated from the whole patch over the application time, highlight differences among the patches. The additional tests performed showed that skin integrity does not represent a barrier for fentanyl permeation across the skin, regardless of the type and complexity of the patch. The effect of temperature resulted critical for two out of three patches, probably due to the different composition and to the different structure. The combination of skin damage and elevated temperature did not produce a synergistic effect. Fentanyl extraction was different for the different products and variable according to the conditions used. The results reported in the present work underline the influence of patch composition and complexity on fentanyl extraction, release and skin permeation, in particular in conditions that can be critical, such as elevated temperature. In particular, the effect of critical variables, such as skin integrity and temperature, should be addressed to in the development of a new or new generic patch and new discriminant tests should be developed. Copyright © 2017 Elsevier B.V. All rights reserved.

A comment on Baxter condition for commutativity of transfer matrices

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

Gutkin, E.

1986-07-01

Let T..nu.. and T'..nu.. be the transfer matrices of two vertex models corresponding to two sets of Boltzmann weights. The Baxter condition on Boltzmann weights was known to be sufficient for commutativity of T..nu.. and T'..nu.. for all ..nu... We show that generically it is also necessary.

A generic double-curvature piezoelectric shell energy harvester: Linear/nonlinear theory and applications

NASA Astrophysics Data System (ADS)

Zhang, X. F.; Hu, S. D.; Tzou, H. S.

2014-12-01

Converting vibration energy to useful electric energy has attracted much attention in recent years. Based on the electromechanical coupling of piezoelectricity, distributed piezoelectric zero-curvature type (e.g., beams and plates) energy harvesters have been proposed and evaluated. The objective of this study is to develop a generic linear and nonlinear piezoelectric shell energy harvesting theory based on a double-curvature shell. The generic piezoelectric shell energy harvester consists of an elastic double-curvature shell and piezoelectric patches laminated on its surface(s). With a current model in the closed-circuit condition, output voltages and energies across a resistive load are evaluated when the shell is subjected to harmonic excitations. Steady-state voltage and power outputs across the resistive load are calculated at resonance for each shell mode. The piezoelectric shell energy harvesting mechanism can be simplified to shell (e.g., cylindrical, conical, spherical, paraboloidal, etc.) and non-shell (beam, plate, ring, arch, etc.) distributed harvesters using two Lamé parameters and two curvature radii of the selected harvester geometry. To demonstrate the utility and simplification procedures, the generic linear/nonlinear shell energy harvester mechanism is simplified to three specific structures, i.e., a cantilever beam case, a circular ring case and a conical shell case. Results show the versatility of the generic linear/nonlinear shell energy harvesting mechanism and the validity of the simplification procedures.

The development of a post-test diagnostic system for rocket engines

NASA Technical Reports Server (NTRS)

Zakrajsek, June F.

1991-01-01

An effort was undertaken by NASA to develop an automated post-test, post-flight diagnostic system for rocket engines. The automated system is designed to be generic and to automate the rocket engine data review process. A modular, distributed architecture with a generic software core was chosen to meet the design requirements. The diagnostic system is initially being applied to the Space Shuttle Main Engine data review process. The system modules currently under development are the session/message manager, and portions of the applications section, the component analysis section, and the intelligent knowledge server. An overview is presented of a rocket engine data review process, the design requirements and guidelines, the architecture and modules, and the projected benefits of the automated diagnostic system.

Initiation of rotors by fast propagation regions in excitable media: A theoretical study

NASA Astrophysics Data System (ADS)

Gao, Xiang; Krekhov, Alexei; Zykov, Vladimir; Bodenschatz, Eberhard

2018-02-01

We study the effect of geometry of a fast propagation region (FPR) in an excitable medium on the rotor initiation using a generic two-dimensional reaction-diffusion model. We find that, while the flat boundary of a rectangularly shaped FPR may block the propagation of the excitation wave, a large local curvature at the rounded corners of the FPR would prevent the blockage and thus initiate a rotor. Our simulations demonstrate that the prerequisites for the rotor initiation are the degree of the heterogeneity, its shape and size. These results may explain the incidence of arrhythmias by local heterogeneities induced, for example, by a cardiac tissue remodeling.

Generic Raman-based calibration models enabling real-time monitoring of cell culture bioreactors.

PubMed

Mehdizadeh, Hamidreza; Lauri, David; Karry, Krizia M; Moshgbar, Mojgan; Procopio-Melino, Renee; Drapeau, Denis

2015-01-01

Raman-based multivariate calibration models have been developed for real-time in situ monitoring of multiple process parameters within cell culture bioreactors. Developed models are generic, in the sense that they are applicable to various products, media, and cell lines based on Chinese Hamster Ovarian (CHO) host cells, and are scalable to large pilot and manufacturing scales. Several batches using different CHO-based cell lines and corresponding proprietary media and process conditions have been used to generate calibration datasets, and models have been validated using independent datasets from separate batch runs. All models have been validated to be generic and capable of predicting process parameters with acceptable accuracy. The developed models allow monitoring multiple key bioprocess metabolic variables, and hence can be utilized as an important enabling tool for Quality by Design approaches which are strongly supported by the U.S. Food and Drug Administration. © 2015 American Institute of Chemical Engineers.

Anamorphic quasiperiodic universes in modified and Einstein gravity with loop quantum gravity corrections

NASA Astrophysics Data System (ADS)

Amaral, Marcelo M.; Aschheim, Raymond; Bubuianu, Laurenţiu; Irwin, Klee; Vacaru, Sergiu I.; Woolridge, Daniel

2017-09-01

The goal of this work is to elaborate on new geometric methods of constructing exact and parametric quasiperiodic solutions for anamorphic cosmology models in modified gravity theories, MGTs, and general relativity, GR. There exist previously studied generic off-diagonal and diagonalizable cosmological metrics encoding gravitational and matter fields with quasicrystal like structures, QC, and holonomy corrections from loop quantum gravity, LQG. We apply the anholonomic frame deformation method, AFDM, in order to decouple the (modified) gravitational and matter field equations in general form. This allows us to find integral varieties of cosmological solutions determined by generating functions, effective sources, integration functions and constants. The coefficients of metrics and connections for such cosmological configurations depend, in general, on all spacetime coordinates and can be chosen to generate observable (quasi)-periodic/aperiodic/fractal/stochastic/(super) cluster/filament/polymer like (continuous, stochastic, fractal and/or discrete structures) in MGTs and/or GR. In this work, we study new classes of solutions for anamorphic cosmology with LQG holonomy corrections. Such solutions are characterized by nonlinear symmetries of generating functions for generic off-diagonal cosmological metrics and generalized connections, with possible nonholonomic constraints to Levi-Civita configurations and diagonalizable metrics depending only on a time like coordinate. We argue that anamorphic quasiperiodic cosmological models integrate the concept of quantum discrete spacetime, with certain gravitational QC-like vacuum and nonvacuum structures. And, that of a contracting universe that homogenizes, isotropizes and flattens without introducing initial conditions or multiverse problems.

Eochrysis, a new replacement name for the fossil Protochrysis Bischoff, 1916 (Insecta: Hymenoptera: Chrysididae) nec Pascher, 1911 (Protista: Cryptomonada).

PubMed

Doweld, Alexander B

2015-12-18

The genus Protochrysis (type species P. succinalis Bischoff, 1916, by monotypy) was established by Bischoff (1916: 139) for distinctive fossil insect remains of Eocene (Lutetian) age from the former Königsberg outskirts of East Prussia (now Kalinigrad, Russian Federation), referred at present to the Chrysididae (Hymenoptera) (Brues 1933; Carpenter 1985, 1992). However, an identical generic name Protochrysis had previously been proposed by Pascher (1911: 191) for a living protist (Cryptomonada). Bischoff's (1916) name is therefore an invalid junior homonym. Carpenter (1985: 577) proposed a new replacement name for the fossil genus, but overlooked the fact that his newly proposed generic name Protochrysidis was also preoccupied, again by the name of another protist genus, Protochrysidis [Protista: Chrysomonada] described by Skvortzov (1969: 346) from Harbin (China). In fact, the protistan genus Protochrysidis had initially been published as chrysophyte algae following the International Code of Nomenclature for Algae, Fungi, and Plants (McNeill et al. 2012) by Skvortzov (1961: 4) who had failed to designate holotype of the species, but later fulfilled all conditions for valid publication in 1969 by providing necessary typification and reference to formerly published description and illustrations. At present chrysophyte algae are still maintained as Chrysomonada in protozoology due to a continued somewhat archaic tradition (Preisig & Anderson 2002). Protochrysidis Skvortzov, 1969 remained little studied since the time of its first description and is currently treated as an incertae sedis protistan taxon.

Longitudinal aerodynamic characteristics of a generic fighter model with a wing designed for sustained transonic maneuver conditions

NASA Technical Reports Server (NTRS)

Ferris, J. C.

1986-01-01

A wind-tunnel investigation was made to determine the longitudinal aerodynamic characteristics of a fixed-wing generic fighter model with a wing designed for sustained transonic maneuver conditions. The airfoil sections on the wing were designed with a two-dimensional nonlinear computer code, and the root and tip section were modified with a three-dimensional code. The wing geometric characteristics were as follows: a leading-edge sweep of 45 degrees, a taper ratio of 0.2141, an aspect ratio of 3.30, and a thickness ratio of 0.044. The model was investigated at Mach numbers from 0.600 to 1.200, at Reynolds numbers, based on the model reference length, from 2,560,000 to 3,970,000, and through a model angle-of-attack range from -5 to +18 degrees.

Approaches to Foster Transfer of Formal Principles: Which Route to Take?

PubMed

Schalk, Lennart; Saalbach, Henrik; Stern, Elsbeth

2016-01-01

Enabling learners to transfer knowledge about formal principles to new problems is a major aim of science and mathematics education, which, however, is notoriously difficult to reach. Previous research advocates different approaches of how to introduce principles to foster the transfer of knowledge about formal principles. One approach suggests teaching a generic formalism of the principles. Another approach suggests presenting (at least) two concrete cases instantiating the principle. A third approach suggests presenting a generic formalism accompanied by a case. As yet, though, empirical results regarding the transfer potential of these approaches are mixed and difficult to integrate as the three approaches have rarely been tested competitively. Furthermore, the approaches have been evaluated in relation to different control conditions, and they have been assessed using varying transfer measures. In the present experiment, we introduced undergraduates to the formal principles of propositional logic with the aim to systematically compare the transfer potential of the different approaches in relation to each other and to a common control condition by using various learning and transfer tasks. Results indicate that all approaches supported successful learning and transfer of the principles, but also caused systematic differences in the magnitude of transfer. Results indicate that the combination of a generic formalism with a case was surprisingly unsuccessful while learners who compared two cases outperformed the control condition. We discuss how the simultaneous assessment of the different approaches allows to more precisely capture the underlying learning mechanisms and to advance theory on how these mechanisms contribute to transfer performance.

Generic and Brand-Name l-Thyroxine Are Not Bioequivalent for Children With Severe Congenital Hypothyroidism

PubMed Central

Carswell, Jeremi M.; Gordon, Joshua H.; Popovsky, Erica; Hale, Andrea

2013-01-01

Context: In the United States, generic substitution of levothyroxine (l-T4) by pharmacists is permitted if the formulations are deemed to be bioequivalent by the Federal Drug Administration, but there is widespread concern that the pharmacokinetic standard used is too insensitive. Objective: We aimed to evaluate the bioequivalence of a brand-name l-T4 (Synthroid) and an AB-rated generic formulation (Sandoz, Princeton, NJ) in children with severe hypothyroidism. Design: This was a prospective randomized crossover study in which patients received 8 weeks of one l-T4 formulation followed by 8 weeks of the other. Setting: The setting was an academic medical center. Patients: Of 31 children with an initial serum TSH concentration >100 mU/L, 20 had congenital hypothyroidism (CH), and 11 had autoimmune thyroiditis. Main Outcome Measures: The primary endpoint was the serum TSH concentration. Secondary endpoints were the free T4 and total T3 concentrations. Results: The serum TSH concentration was significantly lower after 8 weeks of Synthroid than after generic drug (P = .002), but thyroid hormone levels did not differ significantly. Subgroup analysis revealed that the difference in TSH was restricted to patients with CH (P = .0005). Patients with CH required a higher l-T4 dose (P < .0004) and were younger (P = .003) but were not resistant to thyroid hormone; 15 of 16 CH patients had severe thyroid dysgenesis or agenesis on imaging. The response to generic vs brand-name preparation remained significant when adjusted for age. Conclusions: Synthroid and an AB-rated generic l-T4 are not bioequivalent for patients with severe hypothyroidism due to CH, probably because of diminished thyroid reserve. It would therefore seem prudent not to substitute l-T4 formulations in patients with severe CH, particularly in those <3 yr of age. Our results may have important implications for other severely hypothyroid patients in whom precise titration of l-T4 is necessary. PMID:23264396

A portable MPI-based parallel vector template library

NASA Technical Reports Server (NTRS)

Sheffler, Thomas J.

1995-01-01

This paper discusses the design and implementation of a polymorphic collection library for distributed address-space parallel computers. The library provides a data-parallel programming model for C++ by providing three main components: a single generic collection class, generic algorithms over collections, and generic algebraic combining functions. Collection elements are the fourth component of a program written using the library and may be either of the built-in types of C or of user-defined types. Many ideas are borrowed from the Standard Template Library (STL) of C++, although a restricted programming model is proposed because of the distributed address-space memory model assumed. Whereas the STL provides standard collections and implementations of algorithms for uniprocessors, this paper advocates standardizing interfaces that may be customized for different parallel computers. Just as the STL attempts to increase programmer productivity through code reuse, a similar standard for parallel computers could provide programmers with a standard set of algorithms portable across many different architectures. The efficacy of this approach is verified by examining performance data collected from an initial implementation of the library running on an IBM SP-2 and an Intel Paragon.

A Portable MPI-Based Parallel Vector Template Library

NASA Technical Reports Server (NTRS)

Sheffler, Thomas J.

1995-01-01

This paper discusses the design and implementation of a polymorphic collection library for distributed address-space parallel computers. The library provides a data-parallel programming model for C + + by providing three main components: a single generic collection class, generic algorithms over collections, and generic algebraic combining functions. Collection elements are the fourth component of a program written using the library and may be either of the built-in types of c or of user-defined types. Many ideas are borrowed from the Standard Template Library (STL) of C++, although a restricted programming model is proposed because of the distributed address-space memory model assumed. Whereas the STL provides standard collections and implementations of algorithms for uniprocessors, this paper advocates standardizing interfaces that may be customized for different parallel computers. Just as the STL attempts to increase programmer productivity through code reuse, a similar standard for parallel computers could provide programmers with a standard set of algorithms portable across many different architectures. The efficacy of this approach is verified by examining performance data collected from an initial implementation of the library running on an IBM SP-2 and an Intel Paragon.

Defining interdisciplinary competencies for audiological rehabilitation: findings from a modified Delphi study.

PubMed

Xue, Lina; Le Bot, Gaëlle; Van Petegem, Wim; van Wieringen, Astrid

2018-02-01

The aim of this study is to derive a consensus on an interdisciplinary competency framework regarding a holistic approach for audiological rehabilitation (AR), which includes disciplines from medicine, engineering, social sciences and humanities. We employed a modified Delphi method. In the first round survey, experts were asked to rate an initial list of 28 generic interdisciplinary competencies and to propose specific knowledge areas for AR. In the second round, experts were asked to reconsider their answers in light of the group answers of the first round. An international panel of 27 experts from different disciplines in AR completed the first round. Twenty-two of them completed the second round. We developed a competency framework consisting of 21 generic interdisciplinary competencies grouped in five domains and nine specific competencies (knowledge areas) in three clusters. Suggestions for the implementation of the generic competencies in interdisciplinary programmes were identified. This study reveals insights into the interdisciplinary competencies that are unique for AR. The framework will be useful for educators in developing interdisciplinary programmes as well as for professionals in considering their lifelong training needs in AR.

A Conditions Data Management System for HEP Experiments

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

Laycock, P. J.; Dykstra, D.; Formica, A.

Conditions data infrastructure for both ATLAS and CMS have to deal with the management of several Terabytes of data. Distributed computing access to this data requires particular care and attention to manage request-rates of up to several tens of kHz. Thanks to the large overlap in use cases and requirements, ATLAS and CMS have worked towards a common solution for conditions data management with the aim of using this design for data-taking in Run 3. In the meantime other experiments, including NA62, have expressed an interest in this cross- experiment initiative. For experiments with a smaller payload volume and complexity,more » there is particular interest in simplifying the payload storage. The conditions data management model is implemented in a small set of relational database tables. A prototype access toolkit consisting of an intermediate web server has been implemented, using standard technologies available in the Java community. Access is provided through a set of REST services for which the API has been described in a generic way using standard Open API specications, implemented in Swagger. Such a solution allows the automatic generation of client code and server stubs and further allows changes in the backend technology transparently. An important advantage of using a REST API for conditions access is the possibility of caching identical URLs, addressing one of the biggest challenges that large distributed computing solutions impose on conditions data access, avoiding direct DB access by means of standard web proxy solutions.« less

78 FR 37783 - Proposed Information Collection; Comment Request; Generic Clearance for Internet Nonprobability...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

... design of a survey or a release of a Census Bureau data dissemination product with a feedback mechanism... encompass both methodological and subject matter research questions that can be tested on a medium-scale... comments to determine optimal interface designs and to obtain feedback from respondents. For the initial...

The Potential of Teaching Schools in Enabling Student Teacher Learning for the Teaching Profession

ERIC Educational Resources Information Center

Ramsaroop, Sarita; Gravett, Sarah

2017-01-01

In 2011 the Integrated Strategic Planning Framework for Teacher Education and Development in South Africa was promulgated. This framework proposes the establishment of teaching schools to strengthen pre-service teacher education. This study arises from this initiative. A generic qualitative study was undertaken to explore the views of research…

Health Promotion Using Life Skills Education Approach for Adolescents in Schools--Development of a Model

ERIC Educational Resources Information Center

Bharath, Srikala; Kumar, K. V. Kishore

2008-01-01

Life Skills Education (LSE) is a novel promotional program that teaches generic life skills through participatory learning methods of games, debates, role-plays, and group discussion. Conceptual understanding and practicing of the skills occurs through experiential learning in a non-threatening setting. Such initiatives provide the adolescent with…

The Unique Roles of Intrapersonal and Social Factors in Adolescent Smoking Development

ERIC Educational Resources Information Center

Defoe, Ivy N.; Semon Dubas, Judith; Somerville, Leah H.; Lugtig, Peter; van Aken, Marcel A. G.

2016-01-01

Adolescence is a vulnerable period for the initiation and peak of many harmful risk-taking behaviors such as smoking, which is among the most addictive and deadliest behaviors. Generic metatheories like the theory of triadic influence (TTI) suggest that interrelated risk factors across multiple domains (i.e., intrapersonal and…

Cognitive-Operative Model of Intelligent Learning Systems Behavior

ERIC Educational Resources Information Center

Laureano-Cruces, Ana Lilia; Ramirez-Rodriguez, Javier; Mora-Torres, Martha; de Arriaga, Fernando; Escarela-Perez, Rafael

2010-01-01

In this paper behavior during the teaching-learning process is modeled by means of a fuzzy cognitive map. The elements used to model such behavior are part of a generic didactic model, which emphasizes the use of cognitive and operative strategies as part of the student-tutor interaction. Examples of possible initial scenarios for the…

PelePhysics

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

2017-05-17

PelePhysics is a suite of physics packages that provides functionality of use to reacting hydrodynamics CFD codes. The initial release includes an interface to reaction rate mechanism evaluation, transport coefficient evaluation, and a generalized equation of state (EOS) facility. Both generic evaluators and interfaces to code from externally available tools (Fuego for chemical rates, EGLib for transport coefficients) are provided.

78 FR 64413 - Proposed Waste Confidence Rule and Draft Generic Environmental Impact Statement

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-29

... rescheduled the Waste Confidence public meetings it initially planned to hold in San Luis Obispo and Carlsbad... Confidence public meeting in San Luis Obispo will now be held on November 20, 2013. The rescheduled meetings... rescheduled Waste Confidence public meeting in San Luis Obispo, California, on November 20, 2013. This...

Reconstruction of genome-scale human metabolic models using omics data.

PubMed

Ryu, Jae Yong; Kim, Hyun Uk; Lee, Sang Yup

2015-08-01

The impact of genome-scale human metabolic models on human systems biology and medical sciences is becoming greater, thanks to increasing volumes of model building platforms and publicly available omics data. The genome-scale human metabolic models started with Recon 1 in 2007, and have since been used to describe metabolic phenotypes of healthy and diseased human tissues and cells, and to predict therapeutic targets. Here we review recent trends in genome-scale human metabolic modeling, including various generic and tissue/cell type-specific human metabolic models developed to date, and methods, databases and platforms used to construct them. For generic human metabolic models, we pay attention to Recon 2 and HMR 2.0 with emphasis on data sources used to construct them. Draft and high-quality tissue/cell type-specific human metabolic models have been generated using these generic human metabolic models. Integration of tissue/cell type-specific omics data with the generic human metabolic models is the key step, and we discuss omics data and their integration methods to achieve this task. The initial version of the tissue/cell type-specific human metabolic models can further be computationally refined through gap filling, reaction directionality assignment and the subcellular localization of metabolic reactions. We review relevant tools for this model refinement procedure as well. Finally, we suggest the direction of further studies on reconstructing an improved human metabolic model.

Rigidity of complete generic shrinking Ricci solitons

NASA Astrophysics Data System (ADS)

Chu, Yawei; Zhou, Jundong; Wang, Xue

2018-01-01

Let (Mn , g , X) be a complete generic shrinking Ricci soliton of dimension n ≥ 3. In this paper, by employing curvature inequalities, the formula of X-Laplacian for the norm square of the trace-free curvature tensor, the weak maximum principle and the estimate of the scalar curvature of (Mn , g) , we prove some rigidity results for (Mn , g , X) . In particular, it is showed that (Mn , g , X) is isometric to Rn or a finite quotient of Sn under a pointwise pinching condition. Moreover, we establish several optimal inequalities and classify those shrinking solitons for equalities.

Implementation and Evaluation of Multiple Adaptive Control Technologies for a Generic Transport Aircraft Simulation

NASA Technical Reports Server (NTRS)

Campbell, Stefan F.; Kaneshige, John T.; Nguyen, Nhan T.; Krishakumar, Kalmanje S.

2010-01-01

Presented here is the evaluation of multiple adaptive control technologies for a generic transport aircraft simulation. For this study, seven model reference adaptive control (MRAC) based technologies were considered. Each technology was integrated into an identical dynamic-inversion control architecture and tuned using a methodology based on metrics and specific design requirements. Simulation tests were then performed to evaluate each technology s sensitivity to time-delay, flight condition, model uncertainty, and artificially induced cross-coupling. The resulting robustness and performance characteristics were used to identify potential strengths, weaknesses, and integration challenges of the individual adaptive control technologies

MOD silver metallization for photovoltaics

NASA Technical Reports Server (NTRS)

Vest, G. M.; Vest, R. W.

1984-01-01

The development of flat plate solar arrays is reported. Photovoltaic cells require back side metallization and a collector grid system on the front surface. Metallo-organic decomposition (MOD) silver films can eliminate most of the present problems with silver conductors. The objectives are to: (1) identify and characterize suitable MO compounds; (2) develop generic synthesis procedures for the MO compounds; (3) develop generic fabrication procedures to screen printable MOD silver inks; (4) optimize processing conditions to produce grid patterns and photovoltaic cells; and (5) develop a model which describes the adhesion between the fired silver film and the silicon surface.

Entry decisions in the generic pharmaceutical industry.

PubMed

Morton, F M

1999-01-01

Data on all generic drug entries in the period 1984-1994 are used to estimate which markets heterogeneous potential entrants will decide to enter. I find that organizational experience predicts entry. Firms tend to enter markets with supply and demand characteristics similar to the firm's existing drugs. Larger revenue markets, markets with more hospital sales, and products that treat chronic conditions attract more entry. The simultaneous nature of entry leads to an additional interpretation: specialization is profitable because of the severe risk to profits when a market is "overentered." However, I am unable to make any conclusions about the efficiency of entry decisions.

Computations of ideal and real gas high altitude plume flows

NASA Technical Reports Server (NTRS)

Feiereisen, William J.; Venkatapathy, Ethiraj

1988-01-01

In the present work, complete flow fields around generic space vehicles in supersonic and hypersonic flight regimes are studied numerically. Numerical simulation is performed with a flux-split, time asymptotic viscous flow solver that incorporates a generalized equilibrium chemistry model. Solutions to generic problems at various altitude and flight conditions show the complexity of the flow, the equilibrium chemical dissociation and its effect on the overall flow field. Viscous ideal gas solutions are compared against equilibrium gas solutions to illustrate the effect of equilibrium chemistry. Improved solution accuracy is achieved through adaptive grid refinement.

The disruption of multiplanet systems through resonance with a binary orbit.

PubMed

Touma, Jihad R; Sridhar, S

2015-08-27

Most exoplanetary systems in binary stars are of S-type, and consist of one or more planets orbiting a primary star with a wide binary stellar companion. Planetary eccentricities and mutual inclinations can be large, perhaps forced gravitationally by the binary companion. Earlier work on single planet systems appealed to the Kozai-Lidov instability wherein a sufficiently inclined binary orbit excites large-amplitude oscillations in the planet's eccentricity and inclination. The instability, however, can be quenched by many agents that induce fast orbital precession, including mutual gravitational forces in a multiplanet system. Here we report that orbital precession, which inhibits Kozai-Lidov cycling in a multiplanet system, can become fast enough to resonate with the orbital motion of a distant binary companion. Resonant binary forcing results in dramatic outcomes ranging from the excitation of large planetary eccentricities and mutual inclinations to total disruption. Processes such as planetary migration can bring an initially non-resonant system into resonance. As it does not require special physical or initial conditions, binary resonant driving is generic and may have altered the architecture of many multiplanet systems. It can also weaken the multiplanet occurrence rate in wide binaries, and affect planet formation in close binaries.

Reheating-volume measure in the string theory landscape

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

Winitzki, Sergei

2008-12-15

I recently proposed the ''reheating-volume'' (RV) prescription as a possible solution to the measure problem in ''multiverse'' cosmology. The goal of this work is to extend the RV measure to scenarios involving bubble nucleation, such as the string theory landscape. In the spirit of the RV prescription, I propose to calculate the distribution of observable quantities in a landscape that is conditioned in probability to nucleate a finite total number of bubbles to the future of an initial bubble. A general formula for the relative number of bubbles of different types can be derived. I show that the RV measuremore » is well defined and independent of the choice of the initial bubble type, as long as that type supports further bubble nucleation. Applying the RV measure to a generic landscape, I find that the abundance of Boltzmann brains is always negligibly small compared with the abundance of ordinary observers in the bubbles of the same type. As an illustration, I present explicit results for a toy landscape containing four vacuum states, and for landscapes with a single high-energy vacuum and a large number of low-energy vacua.« less

How likely are constituent quanta to initiate inflation?

DOE PAGES

Berezhiani, Lasha; Trodden, Mark

2015-08-06

In this study, we propose an intuitive framework for studying the problem of initial conditions in slow-roll inflation. In particular, we consider a universe at high, but sub-Planckian energy density and analyze the circumstances under which it is plausible for it to become dominated by inflated patches at late times, without appealing to the idea of self-reproduction. Our approach is based on defining a prior probability distribution for the constituent quanta of the pre-inflationary universe. To test the idea that inflation can begin under very generic circumstances, we make specific – yet quite general and well grounded – assumptions onmore » the prior distribution. As a result, we are led to the conclusion that the probability for a given region to ignite inflation at sub-Planckian densities is extremely small. Furthermore, if one chooses to use the enormous volume factor that inflation yields as an appropriate measure, we find that the regions of the universe which started inflating at densities below the self-reproductive threshold nevertheless occupy a negligible physical volume in the present universe as compared to those domains that have never inflated.« less

Fractionation of the component processes underlying successful episodic encoding: a combined fMRI and divided-attention study.

PubMed

Uncapher, Melina R; Rugg, Michael D

2008-02-01

Considerable evidence suggests that attentional resources are necessary for the encoding of episodic memories, but the nature of the relationship between attention and neural correlates of encoding is unclear. Here we address this question using functional magnetic resonance imaging and a divided-attention paradigm in which competition for different types of attentional resources was manipulated. Fifteen volunteers were scanned while making animacy judgments to visually presented words and concurrently performing one of three tasks on auditorily presented words: male/female voice discrimination (control task), 1-back voice comparison (1-back task), or indoor/outdoor judgment (semantic task). The 1-back and semantic tasks were designed to compete for task-generic and task-specific attentional resources, respectively. Using the "remember/know" procedure, memory for the study words was assessed after 15 min. In the control condition, subsequent memory effects associated with later recollection were identified in the left dorsal inferior frontal gyrus and in the left hippocampus. These effects were differentially attenuated in the two more difficult divided-attention conditions. The effects of divided attention seem, therefore, to reflect impairments due to limitations at both task-generic and task-specific levels. Additionally, each of the two more difficult divided-attention conditions was associated with subsequent memory effects in regions distinct from those showing effects in the control condition. These findings suggest the engagement of alternative encoding processes to those engaged in the control task. The overall pattern of findings suggests that divided attention can impact later memory in different ways, and accordingly, that different attentional resources, including task-generic and task-specific resources, make distinct contributions to successful episodic encoding.

Assessing health-related quality of life in Japanese children with a chronic condition: validation of the DISABKIDS chronic generic module.

PubMed

Sasaki, Hatoko; Kakee, Naoko; Morisaki, Naho; Mori, Rintaro; Ravens-Sieberer, Ulrike; Bullinger, Monika

2018-05-02

This study examined the reliability and validity of the Japanese versions of the DISABKIDS-37 generic modules, a tool for assessing the health-related quality of life (HRQOL) of children and adolescents with a chronic condition. The study was conducted using a sample of 123 children/adolescents with a chronic medical condition, aged 8-18 years, and their parents. Focus interviews were performed to ensure content validity after translation. The classical psychometric tests were used to assess reliability and scale intercorrelations. The factor structure was examined with confirmatory factor analysis (CFA). Convergent validity was assessed by the correlation between the total score and the sub-scales of DISABKIDS-37 as well as the total score of KIDSCREEN-10. Both the children/adolescent and parent versions of the score showed good to high internal consistency, and the test-retest reliability correlations were r = 0.91 or above. The CFA revealed that the modified models for all domains were better fit than the original 37 item scale model for both self-report and proxy-report. Moderate to high positive correlations were found for the associations within DISABKIDS-37 sub-scales and between the subscales and total score, except for the treatment sub-scale, which correlated weakly with the remaining sub-scales. The total score of the child-reported version of KIDSCREEN-10 correlated significantly and positively with the total score and all the sub-scales of the child-reported version of DISABKIDS-37 except the Treatment sub-scale in adolescents. The modified models of Japanese version of DISABKIDS generic module were psychometrically robust enough to assess the HRQOL of children with a chronic condition.

The effects of thiopental and generic and nongeneric propofol on respiratory resistance during anesthetic induction in patients with reactive airways.

PubMed

Arain, Shahbaz R; Navani, Annu; Ebert, Thomas J

2002-06-01

To demonstrate a favorable effect of propofol on respiratory system resistance during anesthetic induction, and to determine if generic propofol causes adverse effects on respiratory resistance. Randomized pilot study. Anesthetic induction for elective surgery. 27 consenting ASA physical status II and III patients with reactive airways (positive smoking history or chronic obstructive pulmonary disease), but not receiving bronchodilator therapy. Patients were randomized equally to one of three anesthetic induction (and maintenance) drugs: sodium thiopental, 5 mg/kg (25 microg/kg/min), generic or nongeneric propofol, 1.25 mg/kg (50 microg/kg/min). They received preinduction midazolam and fentanyl (2 mg and 150 microg) and intravenous lidocaine (0.5 mg/kg). After anesthetic induction, tracheal intubation was established, and predetermined settings for mechanical ventilation were initiated. Immediately after intubation, a sensor was placed on the 8-mm endotracheal tube to detect baseline airway pressure and flow. During maintenance, repeat measurements of pressure and flow were obtained at 2.5-minute intervals for 10 minutes. Respiratory system resistance was derived off-line using the isovolumetric technique. Patients were similar across groups. The respiratory resistance measured after anesthetic induction did not differ among groups. During the maintenance infusion of thiopental or propofol, respiratory resistance increased gradually across all groups. There was no difference in the response of respiratory resistance either at induction or during the 10-minute maintenance between the generic and the nongeneric propofol groups. In contrast to earlier reports, this pilot study was unable to document a difference in the respiratory resistance in patients induced with thiopental or propofol. In addition, we were unable to demonstrate any different respiratory responses between generic propofol, containing sodium metabisulfite preservative, and nongeneric propofol.

Forecasting the (un)productivity of the 2014 M 6.0 South Napa aftershock sequence

USGS Publications Warehouse

Llenos, Andrea L.; Michael, Andrew J.

2017-01-01

The 24 August 2014 Mw 6.0 South Napa mainshock produced fewer aftershocks than expected for a California earthquake of its magnitude. In the first 4.5 days, only 59 M≥1.8 aftershocks occurred, the largest of which was an M 3.9 that happened a little over two days after the mainshock. We investigate the aftershock productivity of the South Napa sequence and compare it with other M≥5.5 California strike‐slip mainshock–aftershock sequences. While the productivity of the South Napa sequence is among the lowest, northern California mainshocks generally have fewer aftershocks than mainshocks further south, although the productivities vary widely in both regions. An epidemic‐type aftershock sequence (ETAS) model (Ogata, 1988) fit to Napa seismicity from 1980 to 23 August 2014 fits the sequence well and suggests that low‐productivity sequences are typical of this area. Utilizing regional variations in productivity could improve operational earthquake forecasting (OEF) by improving the model used immediately after the mainshock. We show this by comparing the daily rate of M≥2 aftershocks to forecasts made with the generic California model (Reasenberg and Jones, 1989; hereafter, RJ89), RJ89 models with productivity updated daily, a generic California ETAS model, an ETAS model based on premainshock seismicity, and ETAS models updated daily following the mainshock. RJ89 models for which only the productivity is updated provide better forecasts than the generic RJ89 California model, and the Napa‐specific ETAS models forecast the aftershock rates more accurately than either generic model. Therefore, forecasts that use localized initial parameters and that rapidly update the productivity may be better for OEF than using a generic model and/or updating all parameters.

Cross-cultural adaptation, reliability and validity of the Spanish version of the Quality of Life in Adult Cancer Survivors (QLACS) questionnaire: application in a sample of short-term survivors.

PubMed

Escobar, Antonio; Trujillo-Martín, Maria del Mar; Rueda, Antonio; Pérez-Ruiz, Elisabeth; Avis, Nancy E; Bilbao, Amaia

2015-11-16

The aim of this study was to validate the Quality of Life in Adult Cancer Survivors (QLACS) in short-term Spanish cancer survivor's patients. Patients with breast, colorectal or prostate cancer that had finished their initial cancer treatment 3 years before the beginning of this study completed QLACS, WHOQOL, Short Form-36, Hospital Anxiety and Depression Scale, EORTC-QLQ-BR23 and EQ-5D. Cultural adaptation was made based on established guidelines. Reliability was evaluated using internal consistency and test-retest. Convergent validity was studied by mean of Pearson's correlation coefficient. Structural validity was determined by a second-order confirmatory factor analysis (CFA) and Rasch analysis was used to assess the unidimensionality of the Generic and Cancer-specific scales. Cronbach's alpha were above 0.7 in all domains and summary scales. Test-retest coefficients were 0.88 for Generic and 0.82 for Cancer-specific summary scales. QLACS generic summary scale was correlated with other generic criterion measures, SF-36 MCS (r = - 0.74) and EQ-VAS (r = - 0.63). QLACS cancer-specific scale had lower values with the same constructs. CFA provided satisfactory fit indices in all cases. The RMSEA value was 0.061 and CFI and TLI values were 0.929 and 0.925, respectively. All factor loadings were higher than 0.40 and statistically significant (P < 0.001). Generic summary scale had eight misfitting items. In the remaining 20 items, the unidimensionality was supported. Cancer Specific summary scale showed four misfitting items, the remaining showed unidimensionality. The findings support the validity and reliability of QLACS questionnaire to be used in short-term cancer survivors.

Validity and reliability of the Iranian version of the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™) Generic Core Scales in children

PubMed Central

2012-01-01

Background This study aimed to investigate the reliability and validity of the Iranian version of the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™ 4.0) Generic Core Scales in children. Methods A standard forward and backward translation procedure was used to translate the US English version of the PedsQL™ 4.0 Generic Core Scales for children into the Iranian language (Persian). The Iranian version of the PedsQL™ 4.0 Generic Core Scales was completed by 503 healthy and 22 chronically ill children aged 8-12 years and their parents. The reliability was evaluated using internal consistency. Known-groups discriminant comparisons were made, and exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted. Results The internal consistency, as measured by Cronbach's alpha coefficients, exceeded the minimum reliability standard of 0.70. All monotrait-multimethod correlations were higher than multitrait-multimethod correlations. The intraclass correlation coefficients (ICC) between the children self-report and parent proxy-reports showed moderate to high agreement. Exploratory factor analysis extracted six factors from the PedsQL™ 4.0 for both self and proxy reports, accounting for 47.9% and 54.8% of total variance, respectively. The results of the confirmatory factor analysis for 6-factor models for both self-report and proxy-report indicated acceptable fit for the proposed models. Regarding health status, as hypothesized from previous studies, healthy children reported significantly higher health-related quality of life than those with chronic illnesses. Conclusions The findings support the initial reliability and validity of the Iranian version of the PedsQL™ 4.0 as a generic instrument to measure health-related quality of life of children in Iran. PMID:22221765

Validity and reliability of the Iranian version of the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™) Generic Core Scales in children.

PubMed

Amiri, Parisa; Eslamian, Ghazaleh; Mirmiran, Parvin; Shiva, Niloofar; Jafarabadi, Mohammad Asghari; Azizi, Fereidoun

2012-01-05

This study aimed to investigate the reliability and validity of the Iranian version of the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™ 4.0) Generic Core Scales in children. A standard forward and backward translation procedure was used to translate the US English version of the PedsQL™ 4.0 Generic Core Scales for children into the Iranian language (Persian). The Iranian version of the PedsQL™ 4.0 Generic Core Scales was completed by 503 healthy and 22 chronically ill children aged 8-12 years and their parents. The reliability was evaluated using internal consistency. Known-groups discriminant comparisons were made, and exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted. The internal consistency, as measured by Cronbach's alpha coefficients, exceeded the minimum reliability standard of 0.70. All monotrait-multimethod correlations were higher than multitrait-multimethod correlations. The intraclass correlation coefficients (ICC) between the children self-report and parent proxy-reports showed moderate to high agreement. Exploratory factor analysis extracted six factors from the PedsQL™ 4.0 for both self and proxy reports, accounting for 47.9% and 54.8% of total variance, respectively. The results of the confirmatory factor analysis for 6-factor models for both self-report and proxy-report indicated acceptable fit for the proposed models. Regarding health status, as hypothesized from previous studies, healthy children reported significantly higher health-related quality of life than those with chronic illnesses. The findings support the initial reliability and validity of the Iranian version of the PedsQL™ 4.0 as a generic instrument to measure health-related quality of life of children in Iran.

Viscoplastic crack initiation and propagation in crosslinked UHMWPE from clinically relevant notches up to 0.5mm radius.

PubMed

Sirimamilla, P Abhiram; Rimnac, Clare M; Furmanski, Jevan

2018-01-01

Highly crosslinked UHMWPE is now the material of choice for hard-on-soft bearing couples in total joint replacements. However, the fracture resistance of the polymer remains a design concern for increased longevity of the components in vivo. Fracture research utilizing the traditional linear elastic fracture mechanics (LEFM) or elastic plastic fracture mechanics (EPFM) approach has not yielded a definite failure criterion for UHMWPE. Therefore, an advanced viscous fracture model has been applied to various notched compact tension specimen geometries to estimate the fracture resistance of the polymer. Two generic crosslinked UHMWPE formulations (remelted 65kGy and remelted 100kGy) were analyzed in this study using notched test specimens with three different notch radii under static loading conditions. The results suggest that the viscous fracture model can be applied to crosslinked UHMWPE and a single value of critical energy governs crack initiation and propagation in the material. To our knowledge, this is one of the first studies to implement a mechanistic approach to study crack initiation and propagation in UHMWPE for a range of clinically relevant stress-concentration geometries. It is believed that a combination of structural analysis of components and material parameter quantification is a path to effective failure prediction in UHMWPE total joint replacement components, though additional testing is needed to verify the rigor of this approach. Copyright © 2017 Elsevier Ltd. All rights reserved.

78 FR 25418 - Initiation of Antidumping and Countervailing Duty Administrative Reviews and Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-01

... Create-Bio Engineering Co. Ltd. Ningbo Generic Chemical Co. Qingdao Samin Chemical Co., Ltd. Paras... CHINA: Certain Tissue Paper 3/1/12-2/28/13 Products,\\8\\ A-570-894 AR Printing & Packaging (India) Pvt... does not qualify for a separate rate, all other exporters of Tissue Paper Products from the PRC who...

Transforming Space Missions into Service Oriented Architectures

NASA Technical Reports Server (NTRS)

Mandl, Dan; Frye, Stuart; Cappelaere, Pat

2006-01-01

This viewgraph presentation reviews the vision of the sensor web enablement via a Service Oriented Architecture (SOA). An generic example is given of a user finding a service through the Web, and initiating a request for the desired observation. The parts that comprise this system and how they interact are reviewed. The advantages of the use of SOA are reviewed.

Adopting a Strategy for Enhancing Generic Skills in Engineering Education

ERIC Educational Resources Information Center

Krassadaki, Evangelia; Lakiotaki, Kleanthi; Matsatsinis, Nilolaos F.

2014-01-01

It is remarkable how often academic staff discover students' weaknesses in expressing their thoughts in written and oral contexts, and in team working. To examine these weaknesses, a study was conducted in 2009-2010 and 2010-2011 of students taking an engineering course. Students self-reported an initial high level of weakness in both…

Building a Dangerous Outpost in the Green Mountain State: A Case Study of Educator Preparation Policymaking

ERIC Educational Resources Information Center

McGough, David J.; Bedell, Claudine; Tinkler, Barri

2018-01-01

Poised at a bifurcation, the educator preparation community in Vermont faced either the adoption of a generic product for the assessment of initial educator licensure candidates or the comprehensive revision of a longstanding state-based assessment portfolio. Using a case study approach and narrative methods, specifically the Narrative Policy…

Toddler Autism Screening Questionnaire: Development and Potential Clinical Validity

ERIC Educational Resources Information Center

Tsai, Wen-Che; Soong, Wei-Tsuen; Shyu, Yea-Ing Lotus

2012-01-01

No feasible screening instrument is available for early detection of children with autism in Taiwan. The existing instruments may not be appropriate for use in Taiwan due to different health care systems and child-rearing cultures. The purpose of this study was to develop and test a screening questionnaire for generic autism. The initial 18-item…

Automated subsystems control development. [for life support systems of space station

NASA Technical Reports Server (NTRS)

Block, R. F.; Heppner, D. B.; Samonski, F. H., Jr.; Lance, N., Jr.

1985-01-01

NASA has the objective to launch a Space Station in the 1990s. It has been found that the success of the Space Station engineering development, the achievement of initial operational capability (IOC), and the operation of a productive Space Station will depend heavily on the implementation of an effective automation and control approach. For the development of technology needed to implement the required automation and control function, a contract entitled 'Automated Subsystems Control for Life Support Systems' (ASCLSS) was awarded to two American companies. The present paper provides a description of the ASCLSS program. Attention is given to an automation and control architecture study, a generic automation and control approach for hardware demonstration, a standard software approach, application of Air Revitalization Group (ARG) process simulators, and a generic man-machine interface.

Linear Transformation Method for Multinuclide Decay Calculation

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

Ding Yuan

2010-12-29

A linear transformation method for generic multinuclide decay calculations is presented together with its properties and implications. The method takes advantage of the linear form of the decay solution N(t) = F(t)N{sub 0}, where N(t) is a column vector that represents the numbers of atoms of the radioactive nuclides in the decay chain, N{sub 0} is the initial value vector of N(t), and F(t) is a lower triangular matrix whose time-dependent elements are independent of the initial values of the system.

Master Logic Diagram: method for hazard and initiating event identification in process plants.

PubMed

Papazoglou, I A; Aneziris, O N

2003-02-28

Master Logic Diagram (MLD), a method for identifying events initiating accidents in chemical installations, is presented. MLD is a logic diagram that resembles a fault tree but without the formal mathematical properties of the latter. MLD starts with a Top Event "Loss of Containment" and decomposes it into simpler contributing events. A generic MLD has been developed which may be applied to all chemical installations storing toxic and/or flammable substances. The method is exemplified through its application to an ammonia storage facility.

Differences in Adverse Event Reporting Rates of Therapeutic Failure Between Two Once-daily Extended-release Methylphenidate Medications in Canada: Analysis of Spontaneous Adverse Event Reporting Databases.

PubMed

Park-Wyllie, Laura; van Stralen, Judy; Castillon, Genaro; Sherman, Stephen E; Almagor, Doron

2017-10-01

Our study evaluated adverse events of therapeutic failure (and specifically reduced duration of action) with the use of a branded product, Osmotic Release Oral System (OROS) methylphenidate, which is approved for the treatment of attention deficit/hyperactivity disorder, and a generic product (methylphenidate, methylphenidate ER-C), which was approved for marketing in Canada based on bioequivalence to OROS methylphenidate. This study was initiated following reports that some US-marketed generic methylphenidate ER products had substantially higher reporting rates of therapeutic failure than did the referenced brands. Through methodology similar to that used by the US Food and Drug Administration to investigate the issue with the US-marketed generic, reporting rates were calculated from cases of therapeutic failure identified in the Canadian Vigilance Adverse Reaction Online database for a 1-year period beginning 8 months after each product launch. Corresponding population exposure was estimated from the number of tablets dispensed. An in-depth analysis of narratives of individual case safety reports (ICSRs) with the use of the generic product was conducted in duplicate by 2 physicians to assess causality and to characterize the potential safety risk and clinical pattern of therapeutic failure. Similar secondary analyses were conducted on the US-marketed products. Reporting rates of therapeutic failure with the use of methylphenidate ER-C (generic) and OROS methylphenidate (brand name) were 411.5 and 37.5 cases per 100,000 patient-years, respectively (reporting rate ratio, 10.99; 95% CI, 5.93-22.21). In-depth analysis of narratives of 230 ICSRs of therapeutic failure with the Canadian-marketed generic determined that all ICSRs were either probably (60 [26%]) or possibly (170 [74%]) causally related to methylphenidate ER-C. Clinical symptoms suggestive of overdose were present in 31 reports of loss of efficacy (13.5%) and occurred primarily in the morning, and premature loss of efficacy (shorter duration of action) was described in 98 cases (42.6%) and occurred primarily in the afternoon. Impacts on social functioning, such as disruption in work or school performance or adverse social behaviors, were found in 51 cases (22.2%). The ~10-fold higher reporting rate of therapeutic failure with the generic product relative to its reference product in the present Canadian study resembles findings with US-marketed generic products. While these results should be interpreted with caution due to the limitations of spontaneous adverse event reporting, which may confound comparisons across products, similar findings nonetheless led the US Food and Drug Administration to declare in 2014 that 2 methylphenidate ER generic products in the United States were neither bioequivalent nor interchangeable with OROS methylphenidate-their reference product. Our results indicate a potential safety issue with the Canadian-marketed generic and suggest a need for further investigation by Health Canada. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Prediction of Flows about Forebodies at High-Angle-of-Attack Dynamic Conditions

NASA Technical Reports Server (NTRS)

Fremaux, C. M.; vanDam, C. P.; Saephan, S.; DalBello, T.

2003-01-01

A Reynolds-average Navier Stokes method developed for rotorcraft type of flow problems is applied for predicting the forces and moments of forebody models at high-angle-of-attack dynamic conditions and for providing insight into the flow characteristics at these conditions. Wind-tunnel results from rotary testing on generic forebody models conducted by NASA Langley and DERA are used for comparison. This paper focuses on the steady-state flow problem.

Can increases in CHIP copayments reduce program expenditures on prescription drugs?

PubMed

Sen, Bisakha; Blackburn, Justin; Morrisey, Michael; Becker, David; Kilgore, Meredith; Caldwell, Cathy; Menachemi, Nir

2014-01-01

The primary aim is to explore whether prescription drug expenditures by enrollees changed in Alabama's CHIP program, ALL Kids, after copayment increases in fiscal year 2004. The subsidiary aim is to explore whether non-pharmaceutical expenditures also changed. Data on ALL Kids enrollees between 1999-2007, obtained from claims files and the state's administrative database. We used data on children who were enrolled between one and three years both before and after the changes to the copayment schedule, and estimate regression models with individual-level fixed effects to control for time-invariant heterogeneity at the child level. This allows an accurate estimate of how program expenditures change for the same individual following copayment changes. Primary outcomes of interest are expenditures for prescription drugs by class and brand-name and generic versions. We estimate models for the likelihood of any use of prescription drugs and expenditure level conditional on use. Following the copayment increase, the probability of any expenditure decline by 5.8%, brand name drugs by 6.9%, generic drugs by 7.4%. Conditional on any use, program expenditures decline by 7.9% for all drugs, by 9.6% for brand name drugs, and 6.2% for generic drugs. The largest declines are for antihistamine drugs; the least declines are for Central Nervous System agents. Declines are smaller and statistically weaker for children with chronic health conditions. Concurrent declines are also seen for non-pharmaceutical medical expenditures. Copayment increases appear to reduce program expenditures on prescription drugs per enrollee and may be a useful tool for controlling program costs.

Composite load spectra for select space propulsion structural components

NASA Technical Reports Server (NTRS)

Newell, J. F.; Ho, H. W.; Kurth, R. E.

1991-01-01

The work performed to develop composite load spectra (CLS) for the Space Shuttle Main Engine (SSME) using probabilistic methods. The three methods were implemented to be the engine system influence model. RASCAL was chosen to be the principal method as most component load models were implemented with the method. Validation of RASCAL was performed. High accuracy comparable to the Monte Carlo method can be obtained if a large enough bin size is used. Generic probabilistic models were developed and implemented for load calculations using the probabilistic methods discussed above. Each engine mission, either a real fighter or a test, has three mission phases: the engine start transient phase, the steady state phase, and the engine cut off transient phase. Power level and engine operating inlet conditions change during a mission. The load calculation module provides the steady-state and quasi-steady state calculation procedures with duty-cycle-data option. The quasi-steady state procedure is for engine transient phase calculations. In addition, a few generic probabilistic load models were also developed for specific conditions. These include the fixed transient spike model, the poison arrival transient spike model, and the rare event model. These generic probabilistic load models provide sufficient latitude for simulating loads with specific conditions. For SSME components, turbine blades, transfer ducts, LOX post, and the high pressure oxidizer turbopump (HPOTP) discharge duct were selected for application of the CLS program. They include static pressure loads and dynamic pressure loads for all four components, centrifugal force for the turbine blade, temperatures of thermal loads for all four components, and structural vibration loads for the ducts and LOX posts.

Approaches to Foster Transfer of Formal Principles: Which Route to Take?

PubMed Central

Schalk, Lennart; Saalbach, Henrik; Stern, Elsbeth

2016-01-01

Enabling learners to transfer knowledge about formal principles to new problems is a major aim of science and mathematics education, which, however, is notoriously difficult to reach. Previous research advocates different approaches of how to introduce principles to foster the transfer of knowledge about formal principles. One approach suggests teaching a generic formalism of the principles. Another approach suggests presenting (at least) two concrete cases instantiating the principle. A third approach suggests presenting a generic formalism accompanied by a case. As yet, though, empirical results regarding the transfer potential of these approaches are mixed and difficult to integrate as the three approaches have rarely been tested competitively. Furthermore, the approaches have been evaluated in relation to different control conditions, and they have been assessed using varying transfer measures. In the present experiment, we introduced undergraduates to the formal principles of propositional logic with the aim to systematically compare the transfer potential of the different approaches in relation to each other and to a common control condition by using various learning and transfer tasks. Results indicate that all approaches supported successful learning and transfer of the principles, but also caused systematic differences in the magnitude of transfer. Results indicate that the combination of a generic formalism with a case was surprisingly unsuccessful while learners who compared two cases outperformed the control condition. We discuss how the simultaneous assessment of the different approaches allows to more precisely capture the underlying learning mechanisms and to advance theory on how these mechanisms contribute to transfer performance. PMID:26871902

A structure-preserving method for a class of nonlinear dissipative wave equations with Riesz space-fractional derivatives

NASA Astrophysics Data System (ADS)

Macías-Díaz, J. E.

2017-12-01

In this manuscript, we consider an initial-boundary-value problem governed by a (1 + 1)-dimensional hyperbolic partial differential equation with constant damping that generalizes many nonlinear wave equations from mathematical physics. The model considers the presence of a spatial Laplacian of fractional order which is defined in terms of Riesz fractional derivatives, as well as the inclusion of a generic continuously differentiable potential. It is known that the undamped regime has an associated positive energy functional, and we show here that it is preserved throughout time under suitable boundary conditions. To approximate the solutions of this model, we propose a finite-difference discretization based on fractional centered differences. Some discrete quantities are proposed in this work to estimate the energy functional, and we show that the numerical method is capable of conserving the discrete energy under the same boundary conditions for which the continuous model is conservative. Moreover, we establish suitable computational constraints under which the discrete energy of the system is positive. The method is consistent of second order, and is both stable and convergent. The numerical simulations shown here illustrate the most important features of our numerical methodology.

Nonlinear rotordynamics analysis. [Space Shuttle Main Engine turbopumps

NASA Technical Reports Server (NTRS)

Noah, Sherif T.

1991-01-01

Effective analysis tools were developed for predicting the nonlinear rotordynamic behavior of the Space Shuttle Main Engine (SSME) turbopumps under steady and transient operating conditions. Using these methods, preliminary parametric studies were conducted on both generic and actual HPOTP (high pressure oxygen turbopump) models. In particular, a novel modified harmonic balance/alternating Fourier transform (HB/AFT) method was developed and used to conduct a preliminary study of the effects of fluid, bearing and seal forces on the unbalanced response of a multi-disk rotor in the presence of bearing clearances. The method makes it possible to determine periodic, sub-, super-synchronous and chaotic responses of a rotor system. The method also yields information about the stability of the obtained response, thus allowing bifurcation analyses. This provides a more effective capability for predicting the response under transient conditions by searching in proximity of resonance peaks. Preliminary results were also obtained for the nonlinear transient response of an actual HPOTP model using an efficient, newly developed numerical method based on convolution integration. Currently, the HB/AFT is being extended for determining the aperiodic response of nonlinear systems. Initial results show the method to be promising.

The knowledge-based framework for a nuclear power plant operator advisor

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

Miller, D.W.; Hajek, B.K.

1989-01-01

An important facet in the design, development, and evaluation of aids for complex systems is the identification of the tasks performed by the operator. Operator aids utilizing artificial intelligence, or more specifically knowledge-based systems, require identification of these tasks in the context of a knowledge-based framework. In this context, the operator responses to the plant behavior are to monitor and comprehend the state of the plant, identify normal and abnormal plant conditions, diagnose abnormal plant conditions, predict plant response to specific control actions, and select the best available control action, implement a feasible control action, monitor system response to themore » control action, and correct for any inappropriate responses. These tasks have been identified to formulate a knowledge-based framework for an operator advisor under development at Ohio State University that utilizes the generic task methodology proposed by Chandrasekaran. The paper lays the foundation to identify the responses as a knowledge-based set of tasks in accordance with the expected human operator responses during an event. Initial evaluation of the expert system indicates the potential for an operator aid that will improve the operator's ability to respond to both anticipated and unanticipated events.« less

Hi-alpha forebody design. Part 2: Determination of body shapes for positive directional stability

NASA Technical Reports Server (NTRS)

Ravi, R.; Mason, William H.

1991-01-01

Computational Fluid Dynamics (CFD) has been used to study aircraft forebody flowfields at low speed high angle-of-attack conditions with sideslip. The purpose is to define forebody geometries which provide good directional stability characteristics under these conditions. The flows of the F-5A forebody and Erickson forebody were recomputed with better and refined grids. The results were obtained using a modified version of cfl3d to solve either the Euler equations or the Reynolds equations employing a form of the Baldwin-Lomax turbulence model. Based on those results, we conclude that current CFD methods can be used to investigate the aerodynamic characteristics of forebodies to achieve desirable high angle-of-attack characteristics. An analytically defined generic forebody model is described, and a systematic study of forebody shapes was then conducted to determine which shapes promote a positive contribution to directional stability at high angle-of-attack. A novel way of presenting the results is used to illustrate how the positive contribution arises. Based on the results of this initial parametric study, some guidelines for aerodynamic design to promote positive directional stability are presented.

Comparison of response rates and cost-effectiveness for a community-based survey: postal, internet and telephone modes with generic or personalised recruitment approaches

PubMed Central

2012-01-01

Background Epidemiological research often requires collection of data from a representative sample of the community or recruitment of specific groups through broad community approaches. The population coverage of traditional survey methods such as mail-outs to residential addresses, and telephone contact via public directories or random-digit-dialing is declining and survey response rates are falling. There is a need to explore new sampling frames and consider multiple response modes including those offered by changes in telecommunications and internet technology. Methods We evaluated response rates and cost-effectiveness for three modes of survey administration (postal invitation/postal survey, postal invitation/internet survey and postal invitation/telephone survey) and two styles of contact approach (personalised and generic) in a community survey of greywater use. Potential respondents were contacted only once, with no follow up of non-responders. Results The telephone survey produced the highest adjusted response rate (30.2%), followed by the personalised postal survey (10.5%), generic postal survey (7.5%) and then the internet survey (4.7% for the personalised approach and 2.2% for the generic approach). There were some differences in household characteristics and greywater use rates between respondents to different survey modes, and between respondents to personalised and generic approaches. These may be attributable to the differing levels of motivations needed for a response, and varying levels of interest in the survey topic among greywater users and non-users. The generic postal survey had the lowest costs per valid survey received (Australian $22.93), followed by the personalised postal survey ($24.75). Conclusions Our findings suggest that postal surveys currently remain the most economic option for population-based studies, with similar costs for personalised and generic approaches. Internet surveys may be effective for specialised groups where email lists are available for initial contact, but barriers other than household internet access still exist for community-based surveys. Given the increasing recruitment challenges facing community-based studies, there is an imperative to gather contemporary comparative data on different survey modes and recruitment approaches in order to determine their strengths, limitations and costs. Researchers also need to document and report on the potential biases in the target and respondent populations and how this may affect the data collected. PMID:22938205

Comparison of Outcomes Following a Switch From a Brand to an Authorized Versus Independent Generic Drug.

PubMed

Hansen, R A; Qian, J; Berg, R L; Linneman, J G; Seoane-Vazquez, E; Dutcher, S; Raofi, S; Page, C D; Peissig, P L

2018-02-01

Authorized generics are identical in formulation to brand drugs, manufactured by the brand company but marketed as a generic. Generics, marketed by generic manufacturers, are required to demonstrate pharmaceutical and bioequivalence to the brand drug, but repetition of clinical trials is not required. This retrospective cohort study compared outcomes for generics and authorized generics, which serves as a generic vs. brand proxy that minimizes bias against generics. For the seven drugs studied between 1999 and 2014, 5,234 unique patients were on brand drugs prior to generic entry and 4,900 (93.6%) switched to a generic. During the 12 months following the brand-to-generic switch, patients using generics vs. authorized generics were similar in terms of outpatient visits, urgent care visits, hospitalizations, and medication discontinuation. The likelihood of emergency department (ED) visits was slightly higher for authorized generics compared with generics. These data suggest that generics were clinically no worse than their proxy brand comparators. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Decision validity should determine whether a generic or condition-specific HRQOL measure is used in health care decisions.

PubMed

Dowie, Jack

2002-01-01

When a HRQOL measure is needed in health care decision making should it be a generic measure (a GEN), intended to cover the entire domain of health, a condition-specific measure (a CSM) intended to embrace those aspects of health associated with the condition concerned, or both? This paper proposes that it will never be appropriate to use both a CSM and a GEN for the same decision; that a GEN alone will probably be the appropriate measure in the majority of decisions; that a CSM alone will sometimes be appropriate; and that whether it is a GEN alone or a CSM alone that is appropriate depends entirely on the structure of the decision. The argument rests on the distinction between knowledge validity and decision validity. But it has a supplementary basis in rejection of the widespread (but unjustifiable) belief that CSMs are more "sensitive" or "responsive" than GENs and hence can detect "small but important changes" that GENs always or often miss. Copyright 2002 John Wiley & Sons, Ltd.

The importance of patient-reported outcome measures in reconstructive urology.

PubMed

Jackson, Matthew J; N'Dow, James; Pickard, Rob

2010-11-01

Patient-reported outcome measures (PROMs) are now recognised as the most appropriate instruments to assess the effectiveness of healthcare interventions from the patient's perspective. The purpose of this review was to identify recent publications describing the use of PROMs following reconstructive urological surgery. A wide systematic search identified only three original articles published in the last 2 years that prospectively assessed effectiveness using a patient-completed condition-specific or generic health-related quality of life (HRQoL) instrument. These publications illustrate the need to administer PROMs at a postoperative interval relevant to the anticipated recovery phase of individual procedures. They also highlight the difference in responsiveness of generic HRQoL instruments to symptomatic improvement between straightforward conditions such as pelviureteric junction obstruction and complex multidimensional conditions such as meningomyelocele. PROMs uptake and awareness is increasing in reconstructive urology but more work is required to demonstrate the effectiveness of surgical procedures for patients and healthcare funders alike. Healthcare policy-makers now rely on these measures to determine whether specific treatments are worth financing and to compare outcomes between institutions.

Development of the Transport Class Model (TCM) Aircraft Simulation From a Sub-Scale Generic Transport Model (GTM) Simulation

NASA Technical Reports Server (NTRS)

Hueschen, Richard M.

2011-01-01

A six degree-of-freedom, flat-earth dynamics, non-linear, and non-proprietary aircraft simulation was developed that is representative of a generic mid-sized twin-jet transport aircraft. The simulation was developed from a non-proprietary, publicly available, subscale twin-jet transport aircraft simulation using scaling relationships and a modified aerodynamic database. The simulation has an extended aerodynamics database with aero data outside the normal transport-operating envelope (large angle-of-attack and sideslip values). The simulation has representative transport aircraft surface actuator models with variable rate-limits and generally fixed position limits. The simulation contains a generic 40,000 lb sea level thrust engine model. The engine model is a first order dynamic model with a variable time constant that changes according to simulation conditions. The simulation provides a means for interfacing a flight control system to use the simulation sensor variables and to command the surface actuators and throttle position of the engine model.

Automatically producing tailored web materials for public administration

NASA Astrophysics Data System (ADS)

Colineau, Nathalie; Paris, Cécile; Vander Linden, Keith

2013-06-01

Public administration organizations commonly produce citizen-focused, informational materials describing public programs and the conditions under which citizens or citizen groups are eligible for these programs. The organizations write these materials for generic audiences because of the excessive human resource costs that would be required to produce personalized materials for everyone. Unfortunately, generic materials tend to be longer and harder to understand than materials tailored for particular citizens. Our work explores the feasibility and effectiveness of automatically producing tailored materials. We have developed an adaptive hypermedia application system that automatically produces tailored informational materials and have evaluated it in a series of studies. The studies demonstrate that: (1) subjects prefer tailored materials over generic materials, even if the tailoring requires answering a set of demographic questions first; (2) tailored materials are more effective at supporting subjects in their task of learning about public programs; and (3) the time required to specify the demographic information on which the tailoring is based does not significantly slow down the subjects in their information seeking task.

Pre-Big-Bang bubbles from the gravitational instability of generic string vacua

NASA Astrophysics Data System (ADS)

Buonanno, A.; Damour, T.; Veneziano, G.

1999-03-01

We formulate the basic postulate of pre-Big-Bang cosmology as one of ``asymptotic past triviality", by which we mean that the initial state is a generic perturbative solution of the tree-level low-energy effective action. Such a past-trivial ``string vacuum'' is made of an arbitrary ensemble of incoming gravitational and dilatonic waves, and is generically prone to gravitational instability, leading to the possible formation of many black holes hiding singular space-like hypersurfaces. Each such singular space-like hypersurface of gravitational collapse becomes, in the string-frame metric, the usual Big-Bang t=0 hypersurface, i.e. the place of birth of a baby Friedmann universe after a period of dilaton-driven inflation. Specializing to the spherically symmetric case, we review and reinterpret previous work on the subject, and propose a simple, scale-invariant criterion for collapse/inflation in terms of asymptotic data at past null infinity. Those data should determine whether, when, and where collapse/inflation occurs, and, when it does, fix its characteristics, including anisotropies on the Big-Bang hypersurface whose imprint could have survived till now. Using Bayesian probability concepts, we finally attempt to answer some fine-tuning objections recently moved to the pre-Big-Bang scenario.

Greek Physicians' Perceptions on Generic Drugs in the Era of Austerity

PubMed Central

Labiris, Georgios; Fanariotis, Michael; Kastanioti, Catherine; Alexias, Georgios; Protopapas, Adonis; Karampitsakos, Theodoros; Niakas, Dimitris

2015-01-01

Purpose. To assess the beliefs and preferences of Greek physicians, regarding generic drugs, in the years of financial crisis. Setting. Multicentered, nationwide survey. Material and Methods. A custom questionnaire based on former similar studies was developed and administered to Greek physicians. The variable “perception on generics” was constructed after an exploratory study and the instrument was validated by conventional and Rasch analysis methods. 22 items formed 5 subscales that constructed the variable in question. Results. 908 physicians successfully participated in the study (response rate: 80%). Mean total scores to the instrument were 60.63 ± 12.12 for men and significantly less (58.24 ± 11.73) for women (p = 0.04). Greek physicians were not persuaded on the potential economic gain (45.79 ± 10.53); moreover they identified that Greek authorities cannot address the increased pharmacovigilance mandates. Physicians working in Athens and those working in surgical units demonstrated significantly worse scores than their colleagues from the rest of Greece and those working in Internal Medicine wards (p = 0.03).  Conclusion. Our results suggest an overall poor acceptance of the national initiative on generic drugs by Greek physicians. This trial is registered with Clinicaltrials.gov identifier: NCT01855802. PMID:26457225

Extracting recurrent scenarios from narrative texts using a Bayesian network: application to serious occupational accidents with movement disturbance.

PubMed

Abdat, F; Leclercq, S; Cuny, X; Tissot, C

2014-09-01

A probabilistic approach has been developed to extract recurrent serious Occupational Accident with Movement Disturbance (OAMD) scenarios from narrative texts within a prevention framework. Relevant data extracted from 143 accounts was initially coded as logical combinations of generic accident factors. A Bayesian Network (BN)-based model was then built for OAMDs using these data and expert knowledge. A data clustering process was subsequently performed to group the OAMDs into similar classes from generic factor occurrence and pattern standpoints. Finally, the Most Probable Explanation (MPE) was evaluated and identified as the associated recurrent scenario for each class. Using this approach, 8 scenarios were extracted to describe 143 OAMDs in the construction and metallurgy sectors. Their recurrent nature is discussed. Probable generic factor combinations provide a fair representation of particularly serious OAMDs, as described in narrative texts. This work represents a real contribution to raising company awareness of the variety of circumstances, in which these accidents occur, to progressing in the prevention of such accidents and to developing an analysis framework dedicated to this kind of accident. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthesis and identification of three-dimensional faces from image(s) and three-dimensional generic models

NASA Astrophysics Data System (ADS)

Liu, Zexi; Cohen, Fernand

2017-11-01

We describe an approach for synthesizing a three-dimensional (3-D) face structure from an image or images of a human face taken at a priori unknown poses using gender and ethnicity specific 3-D generic models. The synthesis process starts with a generic model, which is personalized as images of the person become available using preselected landmark points that are tessellated to form a high-resolution triangular mesh. From a single image, two of the three coordinates of the model are reconstructed in accordance with the given image of the person, while the third coordinate is sampled from the generic model, and the appearance is made in accordance with the image. With multiple images, all coordinates and appearance are reconstructed in accordance with the observed images. This method allows for accurate pose estimation as well as face identification in 3-D rendering of a difficult two-dimensional (2-D) face recognition problem into a much simpler 3-D surface matching problem. The estimation of the unknown pose is achieved using the Levenberg-Marquardt optimization process. Encouraging experimental results are obtained in a controlled environment with high-resolution images under a good illumination condition, as well as for images taken in an uncontrolled environment under arbitrary illumination with low-resolution cameras.

Cost effectiveness of letrozole versus anastrozole in postmenopausal women with HR+ early-stage breast cancer.

PubMed

Lipsitz, Michael; Delea, Thomas E; Guo, Amy

2010-10-01

The Breast International Group (BIG) 1-98 and Arimidex, Tamoxifen Alone or in Combination (ATAC) trials demonstrated that, in postmenopausal women with hormone receptor positive (HR+) early-stage breast cancer, 5 years of initial adjuvant endocrine therapy with letrozole or anastrozole is superior to tamoxifen. With expected generic availability of anastrozole in July 2010 and letrozole in June 2011, there may be financial pressures prior to letrozole's generic availability to start treatment-naïve patients on anastrozole vs. letrozole or to switch patients already receiving letrozole to anastrozole. A Markov model was used to estimate cost per quality-adjusted life-year (QALY) gained with letrozole vs. anastrozole from the US healthcare system perspective. Cost effectiveness was examined separately in treatment-naïve patients and in patients already receiving letrozole. For the latter, cost effectiveness of continued letrozole vs. therapeutic substitution (TS) to generic anastrozole was evaluated separately in cohorts defined on years of endocrine therapy remaining. TS to generic anastrozole was assumed to result in an additional 5% of patients discontinuing endocrine therapy. Probabilities of distant recurrence and death were taken from reports of BIG 1-98, ATAC, the Early Breast Cancer Trialists' Collaborative Group meta-analysis of tamoxifen, and other published sources. Carry-over effects of aromatase inhibitors were assumed to be proportional to treatment duration. Costs of aromatase inhibitors were assumed to decline by 75% with generic availability. In treatment-naïve patients, total expected lifetime costs are $3916 greater with letrozole vs. anastrozole. However, initiation of treatment with letrozole results in a gain of 0.15 QALYs. Cost per QALY gained with letrozole vs. anastrozole is $25,846. In patients already receiving letrozole, the increase in total expected lifetime costs with continued letrozole vs. TS to anastrozole is between $4200 and $4500 in all cohorts. QALYs gained with letrozole range from 0.21 in those with 4 years of endocrine therapy remaining to 0.13 in those with 1 year of therapy remaining. Cost per QALY gained ranges from $20,276 to $34,356. For postmenopausal women with HR+ early-stage breast cancer, letrozole is more likely to be cost effective vs. anastrozole in treatment-naïve patients and in patients already receiving letrozole. Limitations of the study include a lack of direct evidence comparing letrozole and anastrozole and lack of data on rates of discontinuation due to therapeutic substitution with aromatase inhibitors.

Exponential Sensitivity and its Cost in Quantum Physics

PubMed Central

Gilyén, András; Kiss, Tamás; Jex, Igor

2016-01-01

State selective protocols, like entanglement purification, lead to an essentially non-linear quantum evolution, unusual in naturally occurring quantum processes. Sensitivity to initial states in quantum systems, stemming from such non-linear dynamics, is a promising perspective for applications. Here we demonstrate that chaotic behaviour is a rather generic feature in state selective protocols: exponential sensitivity can exist for all initial states in an experimentally realisable optical scheme. Moreover, any complex rational polynomial map, including the example of the Mandelbrot set, can be directly realised. In state selective protocols, one needs an ensemble of initial states, the size of which decreases with each iteration. We prove that exponential sensitivity to initial states in any quantum system has to be related to downsizing the initial ensemble also exponentially. Our results show that magnifying initial differences of quantum states (a Schrödinger microscope) is possible; however, there is a strict bound on the number of copies needed. PMID:26861076

Exponential Sensitivity and its Cost in Quantum Physics.

PubMed

Gilyén, András; Kiss, Tamás; Jex, Igor

2016-02-10

State selective protocols, like entanglement purification, lead to an essentially non-linear quantum evolution, unusual in naturally occurring quantum processes. Sensitivity to initial states in quantum systems, stemming from such non-linear dynamics, is a promising perspective for applications. Here we demonstrate that chaotic behaviour is a rather generic feature in state selective protocols: exponential sensitivity can exist for all initial states in an experimentally realisable optical scheme. Moreover, any complex rational polynomial map, including the example of the Mandelbrot set, can be directly realised. In state selective protocols, one needs an ensemble of initial states, the size of which decreases with each iteration. We prove that exponential sensitivity to initial states in any quantum system has to be related to downsizing the initial ensemble also exponentially. Our results show that magnifying initial differences of quantum states (a Schrödinger microscope) is possible; however, there is a strict bound on the number of copies needed.

Policies to Enhance Prescribing Efficiency in Europe: Findings and Future Implications

PubMed Central

Godman, Brian; Shrank, William; Andersen, Morten; Berg, Christian; Bishop, Iain; Burkhardt, Thomas; Garuoliene, Kristina; Herholz, Harald; Joppi, Roberta; Kalaba, Marija; Laius, Ott; Lonsdale, Julie; Malmström, Rickard E.; Martikainen, Jaana E.; Samaluk, Vita; Sermet, Catherine; Schwabe, Ulrich; Teixeira, Inês; Tilson, Lesley; Tulunay, F. Cankat; Vlahović-Palčevski, Vera; Wendykowska, Kamila; Wettermark, Bjorn; Zara, Corinne; Gustafsson, Lars L.

2010-01-01

Introduction: European countries need to learn from each other to address unsustainable increases in pharmaceutical expenditures. Objective: To assess the influence of the many supply and demand-side initiatives introduced across Europe to enhance prescribing efficiency in ambulatory care. As a result provide future guidance to countries. Methods: Cross national retrospective observational study of utilization (DDDs – defined daily doses) and expenditure (Euros and local currency) of proton pump inhibitors (PPIs) and statins among 19 European countries and regions principally from 2001 to 2007. Demand-side measures categorized under the “4Es” – education engineering, economics, and enforcement. Results: Instigating supply side initiatives to lower the price of generics combined with demand-side measures to enhance their prescribing is important to maximize prescribing efficiency. Just addressing one component will limit potential efficiency gains. The influence of demand-side reforms appears additive, with multiple initiatives typically having a greater influence on increasing prescribing efficiency than single measures apart from potentially “enforcement.” There are also appreciable differences in expenditure (€/1000 inhabitants/year) between countries. Countries that have not introduced multiple demand side measures to counteract commercial pressures to enhance the prescribing of generics have seen considerably higher expenditures than those that have instigated a range of measures. Conclusions: There are considerable opportunities for European countries to enhance their prescribing efficiency, with countries already learning from each other. The 4E methodology allows European countries to concisely capture the range of current demand-side measures and plan for the future knowing that initiatives can be additive to further enhance their prescribing efficiency. PMID:21833180

Bright is the New Black - Multi-Year Performance of Generic High-Albedo Roofs in an Urban Climate

NASA Technical Reports Server (NTRS)

Gaffin, S. R.; Imhoff, M.; Rosenzweig, C.; Khanbilvardi, R.; Pasqualini, A.; Kong, A. Y. Y.; Grillo, D.; Freed, A.; Hillel, D.; Hartung, E.

2012-01-01

High-albedo white and cool roofing membranes are recognized as a fundamental strategy that dense urban areas can deploy on a large scale, at low cost, to mitigate the urban heat island effect. We are monitoring three generic white membranes within New York City that represent a cross-section of the dominant white membrane options for U.S. flat roofs: (1) an ethylene propylene diene monomer (EPDM) rubber membrane; (2) a thermoplastic polyolefin (TPO) membrane and; (3) an asphaltic multi-ply built-up membrane coated with white elastomeric acrylic paint. The paint product is being used by New York City s government for the first major urban albedo enhancement program in its history. We report on the temperature and related albedo performance of these three membranes at three different sites over a multi-year period. The results indicate that the professionally installed white membranes are maintaining their temperature control effectively and are meeting the Energy Star Cool Roofing performance standards requiring a three-year aged albedo above 0.50. The EPDM membrane however shows evidence of low emissivity. The painted asphaltic surface shows high emissivity but lost about half of its initial albedo within two years after installation. Given that the acrylic approach is an important "do-it-yourself," low-cost, retrofit technique, and, as such, offers the most rapid technique for increasing urban albedo, further product performance research is recommended to identify conditions that optimize its long-term albedo control. Even so, its current multi-year performance still represents a significant albedo enhancement for urban heat island mitigation.

A predator-prey model with generic birth and death rates for the predator.

PubMed

Terry, Alan J

2014-02-01

We propose and study a predator-prey model in which the predator has a Holling type II functional response and generic per capita birth and death rates. Given that prey consumption provides the energy for predator activity, and that the predator functional response represents the prey consumption rate per predator, we assume that the per capita birth and death rates for the predator are, respectively, increasing and decreasing functions of the predator functional response. These functions are monotonic, but not necessarily strictly monotonic, for all values of the argument. In particular, we allow the possibility that the predator birth rate is zero for all sufficiently small values of the predator functional response, reflecting the idea that a certain level of energy intake is needed before a predator can reproduce. Our analysis reveals that the model exhibits the behaviours typically found in predator-prey models - extinction of the predator population, convergence to a periodic orbit, or convergence to a co-existence fixed point. For a specific example, in which the predator birth and death rates are constant for all sufficiently small or large values of the predator functional response, we corroborate our analysis with numerical simulations. In the unlikely case where these birth and death rates equal the same constant for all sufficiently large values of the predator functional response, the model is capable of structurally unstable behaviour, with a small change in the initial conditions leading to a more pronounced change in the long-term dynamics. Copyright © 2013 Elsevier Inc. All rights reserved.

Generic versus disorder specific cognitive behavior therapy for social anxiety disorder in youth: A randomized controlled trial using internet delivery.

PubMed

Spence, Susan H; Donovan, Caroline L; March, Sonja; Kenardy, Justin A; Hearn, Cate S

2017-03-01

The study examined whether the efficacy of cognitive behavioral treatment for Social Anxiety Disorder for children and adolescents is increased if intervention addresses specific cognitive and behavioral factors linked to the development and maintenance of SAD in young people, over and above the traditional generic CBT approach. Participants were 125 youth, aged 8-17 years, with a primary diagnosis of SAD, who were randomly assigned to generic CBT (CBT-GEN), social anxiety specific CBT (CBT-SAD) or a wait list control (WLC). Intervention was delivered using a therapist-supported online program. After 12-weeks, participants who received treatment (CBT-SAD or CBT-GEN) showed significantly greater reduction in social anxiety and post-event processing, and greater improvement in global functioning than the WLC but there was no significant difference between CBT-SAD and CBT-GEN on any outcome variable at 12-weeks or 6-month follow-up. Despite significant reductions in anxiety, the majority in both treatment conditions continued to meet diagnostic criteria for SAD at 6-month follow-up. Decreases in social anxiety were associated with decreases in post-event processing. Future research should continue to investigate disorder-specific interventions for SAD in young people, drawing on evidence regarding causal or maintaining factors, in order to enhance treatment outcomes for this debilitating condition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effective-one-body model for black-hole binaries with generic mass ratios and spins

NASA Astrophysics Data System (ADS)

Taracchini, Andrea; Buonanno, Alessandra; Pan, Yi; Hinderer, Tanja; Boyle, Michael; Hemberger, Daniel A.; Kidder, Lawrence E.; Lovelace, Geoffrey; Mroué, Abdul H.; Pfeiffer, Harald P.; Scheel, Mark A.; Szilágyi, Béla; Taylor, Nicholas W.; Zenginoglu, Anil

2014-03-01

Gravitational waves emitted by black-hole binary systems have the highest signal-to-noise ratio in LIGO and Virgo detectors when black-hole spins are aligned with the orbital angular momentum and extremal. For such systems, we extend the effective-one-body inspiral-merger-ringdown waveforms to generic mass ratios and spins calibrating them to 38 numerical-relativity nonprecessing waveforms produced by the SXS Collaboration. The numerical-relativity simulations span mass ratios from 1 to 8, spin magnitudes up to 98% of extremality, and last for 40 to 60 gravitational-wave cycles. When the total mass of the binary is between 20 and 200M⊙, the effective-one-body nonprecessing (dominant mode) waveforms have overlap above 99% (using the advanced-LIGO design noise spectral density) with all of the 38 nonprecessing numerical waveforms, when maximizing only on initial phase and time. This implies a negligible loss in event rate due to modeling. We also show that—without further calibration— the precessing effective-one-body (dominant mode) waveforms have overlap above 97% with two very long, strongly precessing numerical-relativity waveforms, when maximizing only on the initial phase and time.

Differences in the availability of medicines for chronic and acute conditions in the public and private sectors of developing countries.

PubMed

Cameron, Alexandra; Roubos, Ilse; Ewen, Margaret; Mantel-Teeuwisse, Aukje K; Leufkens, Hubertus G M; Laing, Richard O

2011-06-01

To investigate potential differences in the availability of medicines for chronic and acute conditions in low- and middle-income countries. Data on the availability of 30 commonly-surveyed medicines - 15 for acute and 15 for chronic conditions - were obtained from facility-based surveys conducted in 40 developing countries. Results were aggregated by World Bank country income group and World Health Organization region. The availability of medicines for both acute and chronic conditions was suboptimal across countries, particularly in the public sector. Generic medicines for chronic conditions were significantly less available than generic medicines for acute conditions in both the public sector (36.0% availability versus 53.5%; P = 0.001) and the private sector (54.7% versus 66.2%; P = 0.007). Antiasthmatics, antiepileptics and antidepressants, followed by antihypertensives, were the drivers of the observed differences. An inverse association was found between country income level and the availability gap between groups of medicines, particularly in the public sector. In low- and lower-middle income countries, drugs for acute conditions were 33.9% and 12.9% more available, respectively, in the public sector than medicines for chronic conditions. Differences in availability were smaller in the private sector than in the public sector in all country income groups. Current disease patterns do not explain the significant gaps observed in the availability of medicines for chronic and acute conditions. Measures are needed to better respond to the epidemiological transition towards chronic conditions in developing countries alongside current efforts to scale up treatment for communicable diseases.

Preparing Adolescents With Chronic Disease for Transition to Adult Care: A Technology Program

PubMed Central

Terrones, Laura; Tompane, Trevor; Dillon, Lindsay; Pian, Mark; Gottschalk, Michael; Norman, Gregory J.; Bartholomew, L. Kay

2014-01-01

BACKGROUND: Adolescents with chronic disease (ACD) must develop independent disease self-management and learn to communicate effectively with their health care team to transition from pediatric to adult-oriented health care systems. Disease-specific interventions have been implemented to aid specific ACD groups through transition. A generic approach might be effective and cost-saving. METHODS: Eighty-one ACD, aged 12 to 20 years, were recruited for a randomized clinical trial evaluating an 8-month transition intervention (MD2Me). MD2Me recipients received a 2-month intensive Web-based and text-delivered disease management and skill-based intervention followed by a 6-month review period. MD2Me recipients also had access to a texting algorithm for disease assessment and health care team contact. The intervention was applicable to adolescents with diverse chronic illnesses. Controls received mailed materials on general health topics. Disease management, health-related self-efficacy, and health assessments were performed at baseline and at 2 and 8 months. Frequency of patient-initiated communications was recorded over the study period. Outcomes were analyzed according to assigned treatment group over time. RESULTS: MD2Me recipients demonstrated significant improvements in performance of disease management tasks, health-related self-efficacy, and patient-initiated communications compared with controls. CONCLUSIONS: Outcomes in ACD improved significantly among recipients of a generic, technology-based intervention. Technology can deliver transition interventions to adolescents with diverse chronic illnesses, and a generic approach offers a cost-effective means of positively influencing transition outcomes. Further research is needed to determine whether improved short-term outcomes translate into an improved transition for ACD. PMID:24843066

Adherence to thyroid hormone replacement therapy: a retrospective, claims database analysis.

PubMed

Hepp, Zsolt; Wyne, Kathleen; Manthena, Shivaji R; Wang, Siting; Gossain, Ved

2018-06-25

The objective of this analysis was to compare adherence at 6 months and 12 months across levothyroxine formulations for patients with hypothyroidism. This retrospective analysis utilized insurance claims data from a commercially insured population from January 1, 2000 through March 31, 2016. Patients were included if they were diagnosed with hypothyroidism and initiated treatment with generic levothyroxine, Levoxyl, Synthroid, Unithroid, or Tirosint. Patients were excluded if they were younger than age 18, were diagnosed with thyroid cancer, received a prescription for liothyronine, or did not have continuous insurance coverage over the study period. Adherence, defined by the proportion of days covered (PDC) ≥ 80%, was examined using multivariable analyses for both 6 and 12 months post-initiation on therapy Results: The study identified 580,331 patients who fit the study criteria. At 6 months, 40.3% of patients were found to be non-adherent, while 51.9% were non-adherent at 12 months. Synthroid was associated with significantly higher adherence compared to all other levothyroxine formulations at both 6 and 12 months. Compared to generic levothyroxine, the likelihood of being adherent at 12 months was highest for Synthroid (OR = 1.44; 95% CI = 1.43-1.46), followed by Levoxyl (OR = 1.20 95% CI = 1.17-1.23). Tirosint and Unithroid were associated with significantly lower adherence at 12 months compared to generic levothyroxine (OR = 0.65; 95% CI = 0.57-0.75 and OR = 0.79; 95% CI = 0.71-0.89, respectively). This large, retrospective real-world study demonstrated that adherence to levothyroxine remains a concern among patients with hypothyroidism, and that differences in adherence may exist across levothyroxine formulations.

Preparing adolescents with chronic disease for transition to adult care: a technology program.

PubMed

Huang, Jeannie S; Terrones, Laura; Tompane, Trevor; Dillon, Lindsay; Pian, Mark; Gottschalk, Michael; Norman, Gregory J; Bartholomew, L Kay

2014-06-01

Adolescents with chronic disease (ACD) must develop independent disease self-management and learn to communicate effectively with their health care team to transition from pediatric to adult-oriented health care systems. Disease-specific interventions have been implemented to aid specific ACD groups through transition. A generic approach might be effective and cost-saving. Eighty-one ACD, aged 12 to 20 years, were recruited for a randomized clinical trial evaluating an 8-month transition intervention (MD2Me). MD2Me recipients received a 2-month intensive Web-based and text-delivered disease management and skill-based intervention followed by a 6-month review period. MD2Me recipients also had access to a texting algorithm for disease assessment and health care team contact. The intervention was applicable to adolescents with diverse chronic illnesses. Controls received mailed materials on general health topics. Disease management, health-related self-efficacy, and health assessments were performed at baseline and at 2 and 8 months. Frequency of patient-initiated communications was recorded over the study period. Outcomes were analyzed according to assigned treatment group over time. MD2Me recipients demonstrated significant improvements in performance of disease management tasks, health-related self-efficacy, and patient-initiated communications compared with controls. Outcomes in ACD improved significantly among recipients of a generic, technology-based intervention. Technology can deliver transition interventions to adolescents with diverse chronic illnesses, and a generic approach offers a cost-effective means of positively influencing transition outcomes. Further research is needed to determine whether improved short-term outcomes translate into an improved transition for ACD. Copyright © 2014 by the American Academy of Pediatrics.

Comparison of generic-to-brand switchback patterns for generic and authorized generic drugs

PubMed Central

Hansen, Richard A.; Qian, Jingjing; Berg, Richard; Linneman, James; Seoane-Vazquez, Enrique; Dutcher, Sarah K.; Raofi, Saeid; Page, C. David; Peissig, Peggy

2018-01-01

Background While generic drugs are therapeutically equivalent to brand drugs, some patients and healthcare providers remain uncertain about whether they produce identical outcomes. Authorized generics, which are identical in formulation to corresponding brand drugs but marketed as a generic, provide a unique post-marketing opportunity to study whether utilization patterns are influenced by perceptions of generic drugs. Objectives To compare generic-to-brand switchback rates between generics and authorized generics. Methods A retrospective cohort study was conducted using claims and electronic health records data from a regional U.S. healthcare system. Ten drugs with authorized generics and generics marketed between 1999 and 2014 were evaluated. Eligible adult patients received a brand drug during the 6 months preceding generic entry, and then switched to a generic or authorized generic. Patients in this cohort were followed for up to 30 months from the index switch date to evaluate occurrence of generic-to-brand switchbacks. Switchback rates were compared between patients on authorized generics versus generics using Kaplan-Meier curves and Cox proportional hazards models, controlling for individual drug effects, age, sex, Charlson comorbidity score, pre-index drug use characteristics, and pre-index healthcare utilization. Results Among 5,542 unique patients that switched from brand-to-generic or brand-to-authorized generic, 264 (4.8%) switched back to the brand drug. Overall switchback rates were similar for authorized generics compared with generics (HR=0.86; 95% CI 0.65-1.15). The likelihood of switchback was higher for alendronate (HR=1.64; 95% CI 1.20-2.23) and simvastatin (HR=1.81; 95% CI 1.30-2.54) and lower for amlodipine (HR=0.27; 95% CI 0.17-0.42) compared with other drugs in the cohort. Conclusions Overall switchback rates were similar between authorized generic and generic drug users, indirectly supporting similar efficacy and tolerability profiles for brand and generic drugs. Reasons for differences in switchback rates among specific products need to be further explored. PMID:28152215

Generic pure quantum states as steady states of quasi-local dissipative dynamics

NASA Astrophysics Data System (ADS)

Karuvade, Salini; Johnson, Peter D.; Ticozzi, Francesco; Viola, Lorenza

2018-04-01

We investigate whether a generic pure state on a multipartite quantum system can be the unique asymptotic steady state of locality-constrained purely dissipative Markovian dynamics. In the tripartite setting, we show that the problem is equivalent to characterizing the solution space of a set of linear equations and establish that the set of pure states obeying the above property has either measure zero or measure one, solely depending on the subsystems’ dimension. A complete analytical characterization is given when the central subsystem is a qubit. In the N-partite case, we provide conditions on the subsystems’ size and the nature of the locality constraint, under which random pure states cannot be quasi-locally stabilized generically. Also, allowing for the possibility to approximately stabilize entangled pure states that cannot be exact steady states in settings where stabilizability is generic, our results offer insights into the extent to which random pure states may arise as unique ground states of frustration-free parent Hamiltonians. We further argue that, to a high probability, pure quantum states sampled from a t-design enjoy the same stabilizability properties of Haar-random ones as long as suitable dimension constraints are obeyed and t is sufficiently large. Lastly, we demonstrate a connection between the tasks of quasi-local state stabilization and unique state reconstruction from local tomographic information, and provide a constructive procedure for determining a generic N-partite pure state based only on knowledge of the support of any two of the reduced density matrices of about half the parties, improving over existing results.

Drug substitution associated with a hospital stay in Belgium: a retrospective analysis of a claims database.

PubMed

Simoens, Steven; Dubois, Cécile; Spinewine, Anne; Foulon, Veerle; Paulus, Dominique

2014-04-01

This study measures the extent of drug substitution associated with a hospital stay in Belgium. Data were extracted from the 2006-2007 dataset of the Belgian Agency of Health Insurance Funds on drug use of patients hospitalized in acute hospitals. Reimbursed drugs received in ambulatory care during the 3 months prior to hospitalization were compared with drugs received during the 3 months following hospital discharge. Both a narrow definition and a broad definition were used for drug substitution. Narrow substitution (switches between generic and originator drugs) was computed for 14 drug classes for chronic conditions with the highest public expenditure. Broad substitution (changes between chemical substances within the drug class at ATC level 4, changes in brand name) was calculated for statins and proton-pump inhibitors only. The database included 17 764 patients (mean age 66 ± 17 years; 60% female). In 71% of cases an originator drug was received prior to and following hospitalization. A generic drug was received prior to and following hospitalization in 25% of cases. Some form of narrow substitution occurred in 4% of cases: a generic drug was replaced by an originator drug in 2% of cases and an originator drug was replaced by a generic drug in 2% of cases. Some form of broad substitution occurred in 25% of cases for proton-pump inhibitors and 13% of cases for statins. Hospitalization was not a trigger for changes between originator and generic versions of a drug. Broad substitution associated with a hospital stay was relatively limited for statins and proton-pump inhibitors. © 2013 Royal Pharmaceutical Society.

Analysis of generic reentry vehicle flight dynamics

NASA Astrophysics Data System (ADS)

Metsker, Yu.; Weinand, K.; Geulen, G.; Haidn, O. J.

2018-06-01

The knowledge of reentry vehicles (RV) flight characteristics regarding geometrical shape, dimensions, and mechanical properties is essential for precise prediction of their flight trajectory, impact point, and possible deviations according to simulation uncertainties. The flight characteristic estimations of existing RV require both body dimensions and mechanical properties of the objects. Due to comparatively simple and reliable methods of specifying the vehicle outer dimensions, e. g., photos and videomaterials, the estimation of mechanical properties is a subject of higher uncertainties. Within this study, a generic medium range ballistic missile (MRBM) RV was examined for several modifications such as center of gravity (CoG) position, weight moment of inertia, and initial reentry flight states. Combinations of these variables with constant aerodynamic properties for maximal lateral accelerations will be determined. Basing on these, potential evasion maneuver capabilities of the RV will be described.

Measuring Access to Medicines: A Survey of Prices, Availability and Affordability in Shaanxi Province of China

PubMed Central

Jiang, Minghuan; Yang, Shimin; Yan, Kangkang; Liu, Jun; Zhao, Jun; Fang, Yu

2013-01-01

Objective To measure the prices and availability of selected medicines in Shaanxi Province after the implementation of new healthcare reform in 2009. Methods Data on the prices and availability of 47 medicines were collected from 50 public and 36 private sector medicine outlets in six regions of Shaanxi Province, Western China using a standardized methodology developed by the World Health Organization and Health Action International from September to October 2010. Medicine prices were compared with international reference prices to obtain a median price ratio. Affordability was measured as the number of days’ wages required for the lowest-paid unskilled government worker to purchase standard treatments for common conditions. Findings The mean availabilities of originator brands and lowest-priced generics were 8.9% and 26.5% in the public sector, and 18.1% and 43.6% in the private sector, respectively. The public sector procured generics and originator brands at median price ratios of 0.75 and 8.49, respectively, while patients paid 0.97 and 10.16. Final patient prices for lowest-priced generics and originator brands in the private sector were about 1.53 and 8.36 times their international retail prices, respectively. Public sector vendors applied high markups of 30.4% to generics, and 19.6% to originator brands. In the private sector, originator brands cost 390.7% more, on average, than their generic equivalents. Generic medicines were priced 17.3% higher in the private sector than the public sector. The lowest-paid government worker would need 0.1 day’s wages to purchase captopril for lowest-priced generics from private sector, while 6.6 days’ wages for losartan. For originator brands, the costs rise to 1.2 days’ wages for salbutamol inhaler and 15.6 days’ wages for omeprazole. Conclusions The prices, availability and affordability of medicines in China should be improved to ensure equitable access to basic medical treatments, especially for the poor. This requires multi-faceted interventions, as well as the review and refocusing of policies, regulations and educational interventions. PMID:23936471

Measuring access to medicines: a survey of prices, availability and affordability in Shaanxi province of China.

PubMed

Jiang, Minghuan; Yang, Shimin; Yan, Kangkang; Liu, Jun; Zhao, Jun; Fang, Yu

2013-01-01

To measure the prices and availability of selected medicines in Shaanxi Province after the implementation of new healthcare reform in 2009. Data on the prices and availability of 47 medicines were collected from 50 public and 36 private sector medicine outlets in six regions of Shaanxi Province, Western China using a standardized methodology developed by the World Health Organization and Health Action International from September to October 2010. Medicine prices were compared with international reference prices to obtain a median price ratio. Affordability was measured as the number of days' wages required for the lowest-paid unskilled government worker to purchase standard treatments for common conditions. The mean availabilities of originator brands and lowest-priced generics were 8.9% and 26.5% in the public sector, and 18.1% and 43.6% in the private sector, respectively. The public sector procured generics and originator brands at median price ratios of 0.75 and 8.49, respectively, while patients paid 0.97 and 10.16. Final patient prices for lowest-priced generics and originator brands in the private sector were about 1.53 and 8.36 times their international retail prices, respectively. Public sector vendors applied high markups of 30.4% to generics, and 19.6% to originator brands. In the private sector, originator brands cost 390.7% more, on average, than their generic equivalents. Generic medicines were priced 17.3% higher in the private sector than the public sector. The lowest-paid government worker would need 0.1 day's wages to purchase captopril for lowest-priced generics from private sector, while 6.6 days' wages for losartan. For originator brands, the costs rise to 1.2 days' wages for salbutamol inhaler and 15.6 days' wages for omeprazole. The prices, availability and affordability of medicines in China should be improved to ensure equitable access to basic medical treatments, especially for the poor. This requires multi-faceted interventions, as well as the review and refocusing of policies, regulations and educational interventions.

Generic Vehicle Speed Models Based On Traffic Simulation: Development and Application (Revision #1)

DOT National Transportation Integrated Search

1994-12-15

The findings of a research project to develop new methods of estimating speeds for inclusion in the Highway Performance Monitoring System (HPMS) Analytical Process are summarized. The paper focuses on the effects of traffic conditions excluding incid...

ENVIRONMENTAL TECHNOLOGY VERIFICATION--GENERIC VERIFICATION PROTOCOL FOR BIOLOGICAL AND AEROSOL TESTING OF GENERAL VENTILATION AIR CLEANERS

EPA Science Inventory

Under EPA's Environmental Technology Verification Program, Research Triangle Institute (RTI) will operate the Air Pollution Control Technology Center to verify the filtration efficiency and bioaerosol inactivation efficiency of heating, ventilation and air conditioning air cleane...

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

Kobayashi, Tsutomu; Yamaguchi, Masahide; Yokoyama, Jun’ichi

It has been pointed out that the null energy condition can be violated stably in some non-canonical scalar-field theories. This allows us to consider the Galilean Genesis scenario in which the universe starts expanding from Minkowski spacetime and hence is free from the initial singularity. We use this scenario to study the early-time completion of inflation, pushing forward the recent idea of Pirtskhalava et al. We present a generic form of the Lagrangian governing the background and perturbation dynamics in the Genesis phase, the subsequent inflationary phase, and the graceful exit from inflation, as opposed to employing the effective fieldmore » theory approach. Our Lagrangian belongs to a more general class of scalar-tensor theories than the Horndeski theory and Gleyzes-Langlois-Piazza-Vernizzi generalization, but still has the same number of the propagating degrees of freedom, and thus can avoid Ostrogradski instabilities. We investigate the generation and evolution of primordial perturbations in this scenario and show that one can indeed construct a stable model of inflation preceded by (generalized) Galilean Genesis.« less

Anomalous Transient Amplification of Waves in Non-normal Photonic Media

NASA Astrophysics Data System (ADS)

Makris, K. G.; Ge, L.; Türeci, H. E.

2014-10-01

Dissipation is a ubiquitous phenomenon in dynamical systems encountered in nature because no finite system is fully isolated from its environment. In optical systems, a key challenge facing any technological application has traditionally been the mitigation of optical losses. Recent work has shown that a new class of optical materials that consist of a precisely balanced distribution of loss and gain can be exploited to engineer novel functionalities for propagating and filtering electromagnetic radiation. Here we show a generic property of optical systems that feature an unbalanced distribution of loss and gain, described by non-normal operators, namely, that an overall lossy optical system can transiently amplify certain input signals by several orders of magnitude. We present a mathematical framework to analyze the dynamics of wave propagation in media with an arbitrary distribution of loss and gain, and we construct the initial conditions to engineer such non-normal power amplifiers. Our results point to a new design space for engineered optical systems employed in photonics and quantum optics.

Constraints upon the spectral indices of relic gravitational waves by LIGO S5

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

Zhang, Y.; Tong, M. L.; Fu, Z. W.

With LIGO having achieved its design sensitivity and the LIGO S5 strain data being available, constraints on the relic gravitational waves (RGWs) become realistic. The analytical spectrum of RGWs generated during inflation depends sensitively on the initial condition, which is generically described by the index {beta}, the running index {alpha}{sub t}, and the tensor-to-scalar ratio r. By the LIGO S5 data of the cross-correlated two detectors, we obtain constraints on the parameters ({beta},{alpha}{sub t},r). As a main result, we have computed the theoretical signal-to-noise ratio of RGWs for various values of ({beta},{alpha}{sub t},r), using the cross-correlation for the given pairmore » of LIGO detectors. The constraints by the indirect bound on the energy density of RGWs by big bang nucleosynthesis and cosmic microwave background have been obtained, which turn out to be still more stringent than LIGO S5.« less

An introduction to patient-reported outcome measures (PROMs) in physiotherapy.

PubMed

Kyte, D G; Calvert, M; van der Wees, P J; ten Hove, R; Tolan, S; Hill, J C

2015-06-01

The use of patient-reported outcome measures (PROMs) is set to rise in physiotherapy. PROMs provide additional 'patient-centred' data which is unique in capturing the patient's own opinion on the impact of their disease or disorder, and its treatment, on their life. Thus, PROMs are increasingly used by clinicians to guide routine patient care, or for the purposes of audit, and are already firmly embedded in clinical research. This article seeks to summarise the key aspects of PROM use for physiotherapists, both in routine clinical practice and in the research setting, and highlights recent developments in the field. Generic and condition-specific PROMs are defined and examples of commonly used measures are provided. The selection of appropriate PROMs, and their effective use in the clinical and research settings is discussed. Finally, existing barriers to PROM use in practice are identified and recent physiotherapy PROM initiatives, led by the Royal Dutch Society for Physical Therapy are explored. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cracking the chocolate egg problem: polymeric films coated on curved substrates

NASA Astrophysics Data System (ADS)

Brun, Pierre-Thomas; Lee, Anna; Marthelot, Joel; Balestra, Gioele; Gallaire, François; Reis, Pedro

2015-11-01

Inspired by the traditional chocolate egg recipe, we show that pouring a polymeric solution onto spherical molds yields a simple and robust path of fabrication of thin elastic curved shells. The drainage dynamics naturally leads to uniform coatings frozen in time as the polymer cures, which are subsequently peeled off their mold. We show how the polymer curing affects the drainage dynamics and eventually selects the shell thickness and sets its uniformity. To this end, we perform coating experiments using silicon based elastomers, Vinylpolysiloxane (VPS) and Polydimethylsiloxane (PDMS). These results are rationalized combining numerical simulations of the lubrication flow field to a theoretical model of the dynamics yielding an analytical prediction of the formed shell characteristics. In particular, the robustness of the coating technique and its flexibility, two critical features for providing a generic framework for future studies, are shown to be an inherent consequence of the flow field (memory loss). The shell structure is both independent of initial conditions and tailorable by changing a single experimental parameter.

Application of Electro Chemical Machining for materials used in extreme conditions

NASA Astrophysics Data System (ADS)

Pandilov, Z.

2018-03-01

Electro-Chemical Machining (ECM) is the generic term for a variety of electrochemical processes. ECM is used to machine work pieces from metal and metal alloys irrespective of their hardness, strength or thermal properties, through the anodic dissolution, in aerospace, automotive, construction, medical equipment, micro-systems and power supply industries. The Electro Chemical Machining is extremely suitable for machining of materials used in extreme conditions. General overview of the Electro-Chemical Machining and its application for different materials used in extreme conditions is presented.

Generic analysis of kinetically driven inflation

NASA Astrophysics Data System (ADS)

Saitou, Rio

2018-04-01

We perform a model-independent analysis of kinetically driven inflation (KDI) which (partially) includes generalized G-inflation and ghost inflation. We evaluate the background evolution splitting into the inflationary attractor and the perturbation around it. We also consider the quantum fluctuation of the scalar mode with a usual scaling and derive the spectral index, ignoring the contribution from the second-order products of slow-roll parameters. Using these formalisms, we find that within our generic framework the models of KDI which possess the shift symmetry of scalar field cannot create the quantum fluctuation consistent with the observation. Breaking the shift symmetry, we obtain a few essential conditions for viable models of KDI associated with the graceful exit.

An efficient fully unsupervised video object segmentation scheme using an adaptive neural-network classifier architecture.

PubMed

Doulamis, A; Doulamis, N; Ntalianis, K; Kollias, S

2003-01-01

In this paper, an unsupervised video object (VO) segmentation and tracking algorithm is proposed based on an adaptable neural-network architecture. The proposed scheme comprises: 1) a VO tracking module and 2) an initial VO estimation module. Object tracking is handled as a classification problem and implemented through an adaptive network classifier, which provides better results compared to conventional motion-based tracking algorithms. Network adaptation is accomplished through an efficient and cost effective weight updating algorithm, providing a minimum degradation of the previous network knowledge and taking into account the current content conditions. A retraining set is constructed and used for this purpose based on initial VO estimation results. Two different scenarios are investigated. The first concerns extraction of human entities in video conferencing applications, while the second exploits depth information to identify generic VOs in stereoscopic video sequences. Human face/ body detection based on Gaussian distributions is accomplished in the first scenario, while segmentation fusion is obtained using color and depth information in the second scenario. A decision mechanism is also incorporated to detect time instances for weight updating. Experimental results and comparisons indicate the good performance of the proposed scheme even in sequences with complicated content (object bending, occlusion).

Fuel-optimal low-thrust formation reconfiguration via Radau pseudospectral method

NASA Astrophysics Data System (ADS)

Li, Jing

2016-07-01

This paper investigates fuel-optimal low-thrust formation reconfiguration near circular orbit. Based on the Clohessy-Wiltshire equations, first-order necessary optimality conditions are derived from the Pontryagin's maximum principle. The fuel-optimal impulsive solution is utilized to divide the low-thrust trajectory into thrust and coast arcs. By introducing the switching times as optimization variables, the fuel-optimal low-thrust formation reconfiguration is posed as a nonlinear programming problem (NLP) via direct transcription using multiple-phase Radau pseudospectral method (RPM), which is then solved by a sparse nonlinear optimization software SNOPT. To facilitate optimality verification and, if necessary, further refinement of the optimized solution of the NLP, formulas for mass costate estimation and initial costates scaling are presented. Numerical examples are given to show the application of the proposed optimization method. To fix the problem, generic fuel-optimal low-thrust formation reconfiguration can be simplified as reconfiguration without any initial and terminal coast arcs, whose optimal solutions can be efficiently obtained from the multiple-phase RPM at the cost of a slight fuel increment. Finally, influence of the specific impulse and maximum thrust magnitude on the fuel-optimal low-thrust formation reconfiguration is analyzed. Numerical results shown the links and differences between the fuel-optimal impulsive and low-thrust solutions.

A high-throughput assay of membrane protein stability.

PubMed

Postis, Vincent L G; Deacon, Sarah E; Roach, Peter C J; Wright, Gareth S A; Xia, Xiaobing; Ingram, Jean C; Hadden, Jonathan M; Henderson, Peter J F; Phillips, Simon E V; McPherson, Michael J; Baldwin, Stephen A

2008-12-01

The preparation of purified, detergent-solubilized membrane proteins in a monodisperse and stable form is usually a prerequisite for investigation not only of their function but also for structural studies by X-ray crystallography and other approaches. Typically, it is necessary to explore a wide range of conditions, including detergent type, buffer pH, and the presence of additives such as glycerol, in order to identify those optimal for stability. Given the difficulty of expressing and purifying membrane proteins in large amounts, such explorations must ideally be performed on as small a scale as practicable. To achieve this objective in the UK Membrane Protein Structure Initiative, we have developed a rapid, economical, light-scattering assay of membrane protein aggregation that allows the testing of 48 buffer conditions in parallel on 6 protein targets, requiring less than 2 mg protein for each target. Testing of the assay on a number of unrelated membrane transporters has shown that it is of generic applicability. Proteins of sufficient purity for this plate-based assay are first rapidly prepared using simple affinity purification procedures performed in batch mode. Samples are then transferred by microdialysis into each of the conditions to be tested. Finally, attenuance at 340 nm is monitored in a 384-well plate using a plate reader. Optimal conditions for protein stability identified in the assay can then be exploited for the tailored purification of individual targets in as stable a form as possible.

Clinical Outcomes of Plavix and Generic Clopidogrel for Patients Hospitalized With an Acute Coronary Syndrome.

PubMed

Ko, Dennis T; Krumholz, Harlan M; Tu, Jack V; Austin, Peter C; Stukel, Therese A; Koh, Maria; Chong, Alice; de Melo, Jose Francisco; Jackevicius, Cynthia A

2018-03-01

Clopidogrel is one of the most commonly prescribed medications because of its ability to improve clinical outcomes for a broad range of cardiovascular conditions. After patent protection expired for Plavix in 2012, many healthcare systems adopted generic clopidogrel as a strategy to reduce healthcare costs. We conducted a population-based observational study to determine whether generic clopidogrel was noninferior to Plavix. Patients who were hospitalized with an acute coronary syndrome (ACS) from 2009 to 2014 in Ontario, Canada, >65 years, survived ≥7 days after discharge, were eligible for inclusion. The primary outcome was a composite of death and recurrent ACS at 1 year. The noninferiority margin was prespecified at a relative hazard difference of 10%. Inverse propensity of treatment weighting of the propensity score was used to account for differences in baseline characteristics between the treatment groups. The effect of clopidogrel on the hazard of clinical outcomes was estimated using a Cox proportional hazards model within the propensity-weighted cohort using Plavix as a reference. Our study included 24 530 patients with ACS, 12 643 were prescribed Plavix and 11  887 were prescribed generic clopidogrel at hospital discharge. The mean age was 77 years, 57% were men, and 21% had an ST-segment-elevation myocardial infarction. At 1 year, 17.6% of patients prescribed Plavix and 17.9% of patients prescribed clopidogrel experienced the primary outcome (hazard ratio, 1.02; 95% confidence interval, 0.96-1.08; P =0.005 for noninferiority). No significant differences between rates of death, all-cause readmission, ACS, stroke or transient ischemic attack, or bleeding were observed. Generic clopidogrel was noninferior to Plavix with respect to the composite end point of death and recurrent hospitalization for ACS at 1 year among adults >65 years after an ACS hospitalization. Our findings support generic clopidogrel in ACS, which could lead to substantial healthcare cost savings. © 2018 American Heart Association, Inc.

Affordability of adult HIV/AIDS treatment in developing countries: modelling price determinants for a better insight of the market functioning.

PubMed

Sagaon-Teyssier, Luis; Singh, Sauman; Dongmo-Nguimfack, Boniface; Moatti, Jean-Paul

2016-01-01

This study aims to provide a landscape of the global antiretroviral (ARV) market by analyzing the transactional data on donor-funded ARV procurement between 2003 and 2015, and the ARV price determinants. The data were obtained from the Global Price Reporting Mechanism (GPRM) managed by the AIDS Medicines and Diagnostics Service of the WHO, and it consists of information that covers approximately 80% of the total donor-funded adult ARV transactions procurement. ExWorks prices and procured quantities were standardized according to the guidelines in terms of yearly doses. Descriptive statistics on quantities and prices show the main trends of the ARV market. Ordinary least squares estimation was carried out for the whole sample, then stratified according to the type of supplier (originator and generic) and controlled for time and geographical fixed-effects. Given that analyses were carried out on a public dataset on ARV transactional prices from the GPRM, ethics are respected and consent was not necessary. Originator medicines are on average the least expensive in the sub-Saharan Africa region, where at the same time, generic medicines are on average the most expensive. By contrast, originator medicines are the most expensive in Europe and Central Asia, and generic medicines are the least expensive. In fact, the data suggest mixed strategies by ARV suppliers to exploit opportunities for profit maximization and to adapt to the specific conditions of market competition in each region. Our results also suggest that the expiration of patents is not sufficient to boost additional developments in generic competition (at least in the ARV market) and that formal or informal agreements between generic firms may de facto slow down or even reverse long-term trends towards price decreases. Our findings provide an improved understanding of the ARV market that can help countries strengthen policy measures to increase their bargaining power in price negotiations and the use of TRIPS flexibilities, with a special emphasis on negotiations with generic manufacturers.

Authorized generic drugs, price competition, and consumers' welfare.

PubMed

Berndt, Ernst R; Mortimer, Richard; Bhattacharjya, Ashoke; Parece, Andrew; Tuttle, Edward

2007-01-01

The growing frequency of authorized generics has important implications for the welfare of prescription drug consumers. Authorized generic entry could affect the timing of generic entry, brand-name and generic prices, and generic penetration. We reviewed 1999-2003 data and found that generic entry in the absence of short-run exclusivity restrictions benefits consumers through lower short-run prices. We suggest that these benefits likely also result from authorized generics. We posit that long-run prices and shares are likely essentially unaffected by authorized generics and that potential costs to consumers from any delayed generic entry are likely small.

Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial

PubMed Central

Vinks, Alexander A.; Fukuda, Tsuyoshi; King, Eileen C.; Zou, Yuanshu; Jiang, Wenlei; Klawitter, Jelena; Christians, Uwe

2017-01-01

Background Although the generic drug approval process has a long-term successful track record, concerns remain for approval of narrow therapeutic index generic immunosuppressants, such as tacrolimus, in transplant recipients. Several professional transplant societies and publications have generated skepticism of the generic approval process. Three major areas of concern are that the pharmacokinetic properties of generic products and the innovator (that is, “brand”) product in healthy volunteers may not reflect those in transplant recipients, bioequivalence between generic and innovator may not ensure bioequivalence between generics, and high-risk patients may have specific bioequivalence concerns. Such concerns have been fueled by anecdotal observations and retrospective and uncontrolled published studies, while well-designed, controlled prospective studies testing the validity of the regulatory bioequivalence testing approach for narrow therapeutic index immunosuppressants in transplant recipients have been lacking. Thus, the present study prospectively assesses bioequivalence between innovator tacrolimus and 2 generics in individuals with a kidney or liver transplant. Methods and findings From December 2013 through October 2014, a prospective, replicate dosing, partially blinded, randomized, 3-treatment, 6-period crossover bioequivalence study was conducted at the University of Cincinnati in individuals with a kidney (n = 35) or liver transplant (n = 36). Abbreviated New Drug Applications (ANDA) data that included manufacturing and healthy individual pharmacokinetic data for all generics were evaluated to select the 2 most disparate generics from innovator, and these were named Generic Hi and Generic Lo. During the 8-week study period, pharmacokinetic studies assessed the bioequivalence of Generic Hi and Generic Lo with the Innovator tacrolimus and with each other. Bioequivalence of the major tacrolimus metabolite was also assessed. All products fell within the US Food and Drug Administration (FDA) average bioequivalence (ABE) acceptance criteria of a 90% confidence interval contained within the confidence limits of 80.00% and 125.00%. Within-subject variability was similar for the area under the curve (AUC) (range 12.11–15.81) and the concentration maximum (Cmax) (range 17.96–24.72) for all products. The within-subject variability was utilized to calculate the scaled average bioequivalence (SCABE) 90% confidence interval. The calculated SCABE 90% confidence interval was 84.65%–118.13% and 80.00%–125.00% for AUC and Cmax, respectively. The more stringent SCABE acceptance criteria were met for all product comparisons for AUC and Cmax in both individuals with a kidney transplant and those with a liver transplant. European Medicines Agency (EMA) acceptance criteria for narrow therapeutic index drugs were also met, with the only exception being in the case of Brand versus Generic Lo, in which the upper limits of the 90% confidence intervals were 111.30% (kidney) and 112.12% (liver). These were only slightly above the upper EMA acceptance criteria limit for an AUC of 111.11%. SCABE criteria were also met for the major tacrolimus metabolite 13-O-desmethyl tacrolimus for AUC, but it failed the EMA criterion. No acute rejections, no differences in renal function in all individuals, and no differences in liver function were observed in individuals with a liver transplant using the Tukey honest significant difference (HSD) test for multiple comparisons. Fifty-two percent and 65% of all individuals with a kidney or liver transplant, respectively, reported an adverse event. The Exact McNemar test for paired categorical data with adjustments for multiple comparisons was used to compare adverse event rates among the products. No statistically significant differences among any pairs of products were found for any adverse event code or for adverse events overall. Limitations of this study include that the observations were made under strictly controlled conditions that did not allow for the impact of nonadherence or feeding on the possible pharmacokinetic differences. Generic Hi and Lo were selected based upon bioequivalence data in healthy volunteers because no pharmacokinetic data in recipients were available for all products. The safety data should be interpreted in light of the small number of participants and the short observation periods. Lastly, only the 1 mg tacrolimus strength was utilized in this study. Conclusions Using an innovative, controlled bioequivalence study design, we observed equivalence between tacrolimus innovator and 2 generic products as well as between 2 generic products in individuals after kidney or liver transplantation following current FDA bioequivalence metrics. These results support the position that bioequivalence for the narrow therapeutic index drug tacrolimus translates from healthy volunteers to individuals receiving a kidney or liver transplant and provides evidence that generic products that are bioequivalent with the innovator product are also bioequivalent to each other. Trial registration ClinicalTrials.gov NCT01889758. PMID:29135993

Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial.

PubMed

Alloway, Rita R; Vinks, Alexander A; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; King, Eileen C; Zou, Yuanshu; Jiang, Wenlei; Woodle, E Steve; Tremblay, Simon; Klawitter, Jelena; Klawitter, Jost; Christians, Uwe

2017-11-01

Although the generic drug approval process has a long-term successful track record, concerns remain for approval of narrow therapeutic index generic immunosuppressants, such as tacrolimus, in transplant recipients. Several professional transplant societies and publications have generated skepticism of the generic approval process. Three major areas of concern are that the pharmacokinetic properties of generic products and the innovator (that is, "brand") product in healthy volunteers may not reflect those in transplant recipients, bioequivalence between generic and innovator may not ensure bioequivalence between generics, and high-risk patients may have specific bioequivalence concerns. Such concerns have been fueled by anecdotal observations and retrospective and uncontrolled published studies, while well-designed, controlled prospective studies testing the validity of the regulatory bioequivalence testing approach for narrow therapeutic index immunosuppressants in transplant recipients have been lacking. Thus, the present study prospectively assesses bioequivalence between innovator tacrolimus and 2 generics in individuals with a kidney or liver transplant. From December 2013 through October 2014, a prospective, replicate dosing, partially blinded, randomized, 3-treatment, 6-period crossover bioequivalence study was conducted at the University of Cincinnati in individuals with a kidney (n = 35) or liver transplant (n = 36). Abbreviated New Drug Applications (ANDA) data that included manufacturing and healthy individual pharmacokinetic data for all generics were evaluated to select the 2 most disparate generics from innovator, and these were named Generic Hi and Generic Lo. During the 8-week study period, pharmacokinetic studies assessed the bioequivalence of Generic Hi and Generic Lo with the Innovator tacrolimus and with each other. Bioequivalence of the major tacrolimus metabolite was also assessed. All products fell within the US Food and Drug Administration (FDA) average bioequivalence (ABE) acceptance criteria of a 90% confidence interval contained within the confidence limits of 80.00% and 125.00%. Within-subject variability was similar for the area under the curve (AUC) (range 12.11-15.81) and the concentration maximum (Cmax) (range 17.96-24.72) for all products. The within-subject variability was utilized to calculate the scaled average bioequivalence (SCABE) 90% confidence interval. The calculated SCABE 90% confidence interval was 84.65%-118.13% and 80.00%-125.00% for AUC and Cmax, respectively. The more stringent SCABE acceptance criteria were met for all product comparisons for AUC and Cmax in both individuals with a kidney transplant and those with a liver transplant. European Medicines Agency (EMA) acceptance criteria for narrow therapeutic index drugs were also met, with the only exception being in the case of Brand versus Generic Lo, in which the upper limits of the 90% confidence intervals were 111.30% (kidney) and 112.12% (liver). These were only slightly above the upper EMA acceptance criteria limit for an AUC of 111.11%. SCABE criteria were also met for the major tacrolimus metabolite 13-O-desmethyl tacrolimus for AUC, but it failed the EMA criterion. No acute rejections, no differences in renal function in all individuals, and no differences in liver function were observed in individuals with a liver transplant using the Tukey honest significant difference (HSD) test for multiple comparisons. Fifty-two percent and 65% of all individuals with a kidney or liver transplant, respectively, reported an adverse event. The Exact McNemar test for paired categorical data with adjustments for multiple comparisons was used to compare adverse event rates among the products. No statistically significant differences among any pairs of products were found for any adverse event code or for adverse events overall. Limitations of this study include that the observations were made under strictly controlled conditions that did not allow for the impact of nonadherence or feeding on the possible pharmacokinetic differences. Generic Hi and Lo were selected based upon bioequivalence data in healthy volunteers because no pharmacokinetic data in recipients were available for all products. The safety data should be interpreted in light of the small number of participants and the short observation periods. Lastly, only the 1 mg tacrolimus strength was utilized in this study. Using an innovative, controlled bioequivalence study design, we observed equivalence between tacrolimus innovator and 2 generic products as well as between 2 generic products in individuals after kidney or liver transplantation following current FDA bioequivalence metrics. These results support the position that bioequivalence for the narrow therapeutic index drug tacrolimus translates from healthy volunteers to individuals receiving a kidney or liver transplant and provides evidence that generic products that are bioequivalent with the innovator product are also bioequivalent to each other. ClinicalTrials.gov NCT01889758.

Cost-effectiveness of hepatitis C treatment using generic direct-acting antivirals available in India

PubMed Central

Aggarwal, Rakesh; Chen, Qiushi; Goel, Amit; Seguy, Nicole; Pendse, Razia; Ayer, Turgay

2017-01-01

Background & aims Availability of directly-acting antivirals (DAAs) has changed the treatment landscape of hepatitis C virus (HCV) infection. The high price of DAAs has restricted their use in several countries. However, in some countries such as India, generic DAAs are available at much cheaper price. This study examined whether generic DAAs could be cost-saving and how long it would take for the treatment to become cost-saving/effective. Methods A previously-validated, mathematical model was adapted to the HCV-infected population in India to compare the outcomes of no treatment versus treatment with DAAs. Model parameters were estimated from published studies. Cost-effectiveness of HCV treatment using available DAAs was calculated, using a payer’s perspective. We estimated quality-adjusted life years (QALYs), disability-adjusted life years (DALYs), total costs, and incremental cost-effectiveness ratio of DAAs versus no treatment. One-way and probabilistic sensitivity analyses were conducted. Results Compared with no treatment, the use of generic DAAs in Indian HCV patients would increase the life expectancy by 8.02 years, increase QALYs by 3.89, avert 19.07 DALYs, and reduce the lifetime healthcare costs by $1,309 per-person treated. Treatment became cost-effective within 2 years, and cost-saving within 10 years of its initiation overall and within 5 years in persons with cirrhosis. Treating 10,000 HCV-infected persons could prevent 3400–3850 decompensated cirrhosis, 1800–2500 HCC, and 4000–4550 liver-related deaths. The results were sensitive to the costs of DAAs, pre- and post-treatment diagnostic tests and management of cirrhosis, and quality of life after sustained virologic response. Conclusions Treatment with generic DAAs available in India will improve patient outcomes, provide a good value for money within 2 years, and be ultimately cost-saving. Therefore, in this and similar settings, HCV treatment should be a priority from a public health as well an economic perspective. PMID:28520728

Cost-effectiveness of hepatitis C treatment using generic direct-acting antivirals available in India.

PubMed

Aggarwal, Rakesh; Chen, Qiushi; Goel, Amit; Seguy, Nicole; Pendse, Razia; Ayer, Turgay; Chhatwal, Jagpreet

2017-01-01

Availability of directly-acting antivirals (DAAs) has changed the treatment landscape of hepatitis C virus (HCV) infection. The high price of DAAs has restricted their use in several countries. However, in some countries such as India, generic DAAs are available at much cheaper price. This study examined whether generic DAAs could be cost-saving and how long it would take for the treatment to become cost-saving/effective. A previously-validated, mathematical model was adapted to the HCV-infected population in India to compare the outcomes of no treatment versus treatment with DAAs. Model parameters were estimated from published studies. Cost-effectiveness of HCV treatment using available DAAs was calculated, using a payer's perspective. We estimated quality-adjusted life years (QALYs), disability-adjusted life years (DALYs), total costs, and incremental cost-effectiveness ratio of DAAs versus no treatment. One-way and probabilistic sensitivity analyses were conducted. Compared with no treatment, the use of generic DAAs in Indian HCV patients would increase the life expectancy by 8.02 years, increase QALYs by 3.89, avert 19.07 DALYs, and reduce the lifetime healthcare costs by $1,309 per-person treated. Treatment became cost-effective within 2 years, and cost-saving within 10 years of its initiation overall and within 5 years in persons with cirrhosis. Treating 10,000 HCV-infected persons could prevent 3400-3850 decompensated cirrhosis, 1800-2500 HCC, and 4000-4550 liver-related deaths. The results were sensitive to the costs of DAAs, pre- and post-treatment diagnostic tests and management of cirrhosis, and quality of life after sustained virologic response. Treatment with generic DAAs available in India will improve patient outcomes, provide a good value for money within 2 years, and be ultimately cost-saving. Therefore, in this and similar settings, HCV treatment should be a priority from a public health as well an economic perspective.

Application of Gene Expression Trajectories Initiated from ErbB Receptor Activation Highlights the Dynamics of Divergent Promoter Usage.

PubMed

Carbajo, Daniel; Magi, Shigeyuki; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Arner, Erik; Forrest, Alistair R R; Carninci, Piero; Hayashizaki, Yoshihide; Daub, Carsten O; Okada-Hatakeyama, Mariko; Mar, Jessica C

2015-01-01

Understanding how cells use complex transcriptional programs to alter their fate in response to specific stimuli is an important question in biology. For the MCF-7 human breast cancer cell line, we applied gene expression trajectory models to identify the genes involved in driving cell fate transitions. We modified trajectory models to account for the scenario where cells were exposed to different stimuli, in this case epidermal growth factor and heregulin, to arrive at different cell fates, i.e. proliferation and differentiation respectively. Using genome-wide CAGE time series data collected from the FANTOM5 consortium, we identified the sets of promoters that were involved in the transition of MCF-7 cells to their specific fates versus those with expression changes that were generic to both stimuli. Of the 1,552 promoters identified, 1,091 had stimulus-specific expression while 461 promoters had generic expression profiles over the time course surveyed. Many of these stimulus-specific promoters mapped to key regulators of the ERK (extracellular signal-regulated kinases) signaling pathway such as FHL2 (four and a half LIM domains 2). We observed that in general, generic promoters peaked in their expression early on in the time course, while stimulus-specific promoters tended to show activation of their expression at a later stage. The genes that mapped to stimulus-specific promoters were enriched for pathways that control focal adhesion, p53 signaling and MAPK signaling while generic promoters were enriched for cell death, transcription and the cell cycle. We identified 162 genes that were controlled by an alternative promoter during the time course where a subset of 37 genes had separate promoters that were classified as stimulus-specific and generic. The results of our study highlighted the degree of complexity involved in regulating a cell fate transition where multiple promoters mapping to the same gene can demonstrate quite divergent expression profiles.

Might generic OCs create contraceptive price war?

PubMed

1987-02-01

Genora 1/35 and 1/50, the 1st generic oral contraceptives (OCs) in the world, are now being marketed in the US. Clinicians interviewed by "Contraceptive Technology Update" (CTU) offer differing opinions as to what this new OC may mean in the marketplace. Products of Rugby Laboratories, the pills are copy products of Ortho Pharmaceutical's ON 1/35 and ON 1/50 formulations. Most clinicians believe that Genora's success or failure in the OC market depends on its eventual retail price. The price difference of $3-$4 may be sufficiently substantial for retailers to charge less for the generic OCs. If that is the case, many doctors may prescribe a pill which will save their patients $4/month. Dr. Mildred Hanson, a Minneapolis gynecologist/obstetrician, feels any cost savings from Genora will have a significant impact on the OC market. She suggests that the less expensive OCs will catch the attention of health maintenance organizations (HMOs) and the business of women who participate in such health plans. Yet James Burns, director of family planning services for the Hartford City Health Department, thinks that even a full-scale retail price war won't have much effect from a clinic standpoint. He reports that clinics are able to obtain contraceptive supplies rather inexpensively through the contracting system. Hanson also expressed doubt over the potential popularity of Genora 1/50 as clinical concerns about the effects of combined OCs on serum lipid levels and carbohydrate metabolism have resulted in a nationwide push toward OCs containing less than 50 micrograms of estrogen. He indicated concern that declines in pharmaceutical house products from pricing competition with generic pills might have a negative impact on contraceptive research and development. Dick Haskitt, director of business planning for Syntex Laboratories, Inc., who will produce the OCs for Rugby, reports that their market research shows that people are very interested in having a generic OC available. Initially, Genora will be marketed only to retail pharmacies, wholesalers, and drug chains.

Application of process mapping to understand integration of high risk medicine care bundles within community pharmacy practice.

PubMed

Weir, Natalie M; Newham, Rosemary; Corcoran, Emma D; Ali Atallah Al-Gethami, Ashwag; Mohammed Abd Alridha, Ali; Bowie, Paul; Watson, Anne; Bennie, Marion

2017-11-21

The Scottish Patient Safety Programme - Pharmacy in Primary Care collaborative is a quality improvement initiative adopting the Institute of Healthcare Improvement Breakthrough Series collaborative approach. The programme developed and piloted High Risk Medicine (HRM) Care Bundles (CB), focused on warfarin and non-steroidal anti-inflammatories (NSAIDs), within 27 community pharmacies over 4 NHS Regions. Each CB involves clinical assessment and patient education, although the CB content varies between regions. To support national implementation, this study aims to understand how the pilot pharmacies integrated the HRM CBs into routine practice to inform the development of a generic HRM CB process map. Regional process maps were developed in 4 pharmacies through simulation of the CB process, staff interviews and documentation of resources. Commonalities were collated to develop a process map for each HRM, which were used to explore variation at a national event. A single, generic process map was developed which underwent validation by case study testing. The findings allowed development of a generic process map applicable to warfarin and NSAID CB implementation. Five steps were identified as required for successful CB delivery: patient identification; clinical assessment; pharmacy CB prompt; CB delivery; and documentation. The generic HRM CB process map encompasses the staff and patients' journey and the CB's integration into routine community pharmacy practice. Pharmacist involvement was required only for clinical assessment, indicating suitability for whole-team involvement. Understanding CB integration into routine practice has positive implications for successful implementation. The generic process map can be used to develop targeted resources, and/or be disseminated to facilitate CB delivery and foster whole team involvement. Similar methods could be utilised within other settings, to allow those developing novel services to distil the key processes and consider their integration within routine workflows to effect maximal, efficient implementation and benefit to patient care. Copyright © 2017 Elsevier Inc. All rights reserved.

Should the Gross Motor Function Classification System be used for children who do not have cerebral palsy?

PubMed

Towns, Megan; Rosenbaum, Peter; Palisano, Robert; Wright, F Virginia

2018-02-01

This literature review addressed four questions. (1) In which populations other than cerebral palsy (CP) has the Gross Motor Function Classification System (GMFCS) been applied? (2) In what types of study, and why was it used? (3) How was it modified to facilitate these applications? (4) What justifications and evidence of psychometric adequacy were used to support its application? A search of PubMed, MEDLINE, and Embase databases (January 1997 to April 2017) using the terms: 'GMFCS' OR 'Gross Motor Function Classification System' yielded 2499 articles. 118 met inclusion criteria and reported children/adults with 133 health conditions/clinical descriptions other than CP. Three broad GMFCS applications were observed: as a categorization tool, independent variable, or outcome measure. While the GMFCS is widely used for children with health conditions/clinical description other than CP, researchers rarely provided adequate justification for these uses. We offer recommendations for development/validation of other condition-specific classification systems and discuss the potential need for a generic gross motor function classification system. The Gross Motor Function Classification System should not be used outside cerebral palsy or as an outcome measure. The authors provide recommendations for development and validation of condition-specific or generic classification systems. © 2017 Mac Keith Press.

How should we build a generic open-source water management simulator?

NASA Astrophysics Data System (ADS)

Khadem, M.; Meier, P.; Rheinheimer, D. E.; Padula, S.; Matrosov, E.; Selby, P. D.; Knox, S.; Harou, J. J.

2014-12-01

Increasing water needs for agriculture, industry and cities mean effective and flexible water resource system management tools will remain in high demand. Currently many regions or countries use simulators that have been adapted over time to their unique system properties and water management rules and realities. Most regions operate with a preferred short-list of water management and planning decision support systems. Is there scope for a simulator, shared within the water management community, that could be adapted to different contexts, integrate community contributions, and connect to generic data and model management software? What role could open-source play in such a project? How could a genericuser-interface and data/model management software sustainably be attached to this model or suite of models? Finally, how could such a system effectively leverage existing model formulations, modeling technologies and software? These questions are addressed by the initial work presented here. We introduce a generic water resource simulation formulation that enables and integrates both rule-based and optimization driven technologies. We suggest how it could be linked to other sub-models allowing for detailed agent-based simulation of water management behaviours. An early formulation is applied as an example to the Thames water resource system in the UK. The model uses centralised optimisation to calculate allocations but allows for rule-based operations as well in an effort to represent observed behaviours and rules with fidelity. The model is linked through import/export commands to a generic network model platform named Hydra. Benefits and limitations of the approach are discussed and planned work and potential use cases are outlined.

A randomized comparison of platelet reactivity in patients after treatment with various commercial clopidogrel preparations: the CLO-CLO trial.

PubMed

Oberhänsli, Markus; Lehner, Cédric; Puricel, Serban; Lehmann, Sonja; Togni, Mario; Stauffer, Jean-Christophe; Baeriswyl, Gérard; Goy, Jean-Jacques; Cook, Stéphane

2012-11-01

The salt linked to the clopidogrel molecule in generic preparations is suspected to affect its clinical efficacy. There is a lack of information about inhibition of platelet reactivity by generic preparations. To compare the effect of original clopidogrel (clopidogrel bisulphate [Plavix(®)]), generic clopidogrel preparations (clopidogrel hydrochloride [Clopidogrel-Mepha(®)]; clopidogrel besylate [Clopidogrel Sandoz(®)]) and prasugrel (Efient(®)) on platelet reactivity in patients with coronary artery disease. Patients with coronary artery disease treated with stents received, in a random sequence, original clopidogrel bisulphate, clopidogrel hydrochloride and clopidogrel besylate. Platelet function was assessed with the Multiplate analyser after an initial loading dose (600 mg) and at day 10 after each treatment period. Prasugrel was given for another 10 days. An adenosine diphosphate (ADP) test value<46 antiaggregation units (U) was defined as therapeutic platelet inhibition. Sixty patients (mean age 69 ± 10 years; 50 men) were randomized. Original clopidogrel bisulphate, clopidogrel hydrochloride and clopidogrel besylate provided similar inhibition of platelet reactivity with values of 31 ± 25, 33 ± 28 and 28 ± 23 U, respectively (P not significant). Prasugrel provided better inhibition of platelet function (10 ± 11 vs. 31 ± 25 U for clopidogrel bisulphate; P<0.001). An ADP test value>46 U was measured in 11 patients (18%) with clopidogrel bisulphate, 13 (22%) with clopidogrel besylate and 13 (22%) with clopidogrel hydrochloride compared with only one (2%) with prasugrel. Generic clopidogrel preparations provided similar inhibition of platelet reactivity to original clopidogrel bisulphate, although prasugrel was more efficient. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Distributed sensor for water and pH measurements using fiber optics and swellable polymeric systems

NASA Astrophysics Data System (ADS)

Michie, W. C.; Culshaw, B.; McKenzie, I.; Konstantakis, M.; Graham, N. B.; Moran, C.; Santos, F.; Bergqvist, E.; Carlstrom, B.

1995-01-01

We report on the design, construction and test of a generic form of sensor for making distributed measurements of a range of chemical parameters. The technique combines optical time-domain reflectometry with chemically sensitive water-swellable polymers (hydrogels). Initial experiments have concentrated on demonstrating a distributed water detector; however, gels have been developed that enable this sensor to be

Unmanned Ground Vehicle

DTIC Science & Technology

2001-11-01

Systems ( JAUGS ). JAUGS is a JRP technology initiative under the cognizance of the Aviation and Missile Command Research, Development and Engineering Center...AMRDEC). The JAUGS focus is on developing a high-level command and control architecture for UGVs. As defined in the JRP Glossary, “ JAUGS is an upper...vehicle platforms and missions. JAUGS uses the Society of Automotive Engineers Generic Open Architecture framework to classify UGV interfaces and

Exploring Strategic Thinking: Insights to Assess, Develop, and Retain Strategic Thinkers

DTIC Science & Technology

2013-02-01

rise even as goal difficulty increases (Nisan, 1972). Individual time perspective is associated with the ability to perform professional... initial association with things military, strategy has assumed other more generic meanings that people use broadly and commonly. To mention just a...quantitative methods. Even within the holistic or systemic approach to design there are times when such methods are useful , particularly when

The generalized pole assignment problem. [dynamic output feedback problems

NASA Technical Reports Server (NTRS)

Djaferis, T. E.; Mitter, S. K.

1979-01-01

Two dynamic output feedback problems for a linear, strictly proper system are considered, along with their interrelationships. The problems are formulated in the frequency domain and investigated in terms of linear equations over rings of polynomials. Necessary and sufficient conditions are expressed using genericity.

42 CFR 423.871 - Contract terms and conditions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... not permitted to market or brand fallback prescription drug plans. Notwithstanding any other... entity contains costs to the Medicare Prescription Drug Account and to Part D eligible individuals enrolled in a fallback prescription drug plan offered by the entity through mechanisms such as generic...

Qualitative analysis of Kantowski-Sachs metric in a generic class of f(R) models

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

Leon, Genly; Roque, Armando A., E-mail: genly.leon@ucv.cl, E-mail: arestrada@ucf.edu.cu

2014-05-01

In this paper we investigate, from the dynamical systems perspective, the evolution of a Kantowski-Sachs metric in a generic class of f(R) models. We present conditions (i.e., differentiability conditions, existence of minima, monotony intervals, etc.) for a free input function related to the f(R), that guarantee the asymptotic stability of well-motivated physical solutions, specially, self-accelerated solutions, allowing to describe both inflationary- and late-time acceleration stages of the cosmic evolution. We discuss which f(R) theories allows for a cosmic evolution with an acceptable matter era, in correspondence to the modern cosmological paradigm. We find a very rich behavior, and amongst othersmore » the universe can result in isotropized solutions with observables in agreement with observations, such as de Sitter, quintessence-like, or phantom solutions. Additionally, we find that a cosmological bounce and turnaround are realized in a part of the parameter-space as a consequence of the metric choice.« less

Closed form expressions for ABER and capacity over EGK fading channel in presence of CCI

NASA Astrophysics Data System (ADS)

Singh, S. Pratap; Kumar, Sanjay

2017-03-01

Goal of next generation wireless communication system is to achieve very high data rate. Femto-cell is one of the possibilities to achieve the above target. However, co-channel interference (CCI) is the important concern in femto-cell. This paper presents closed form expressions for average bit error rate (ABER) and capacity for different adaptive schemes under extended generalised-K (EGK) fading channel in the presence of CCI. A novel conditional unified expression (CUE) is derived, which results different conditional error probability and normalised average capacity. Using CUE, a generic expression for ABER is obtained. In addition, closed form expressions for ABER for different modulation schemes under EGK fading channel in presence of CCI are also derived. Further, it is shown that generic ABER expression results into ABER of different modulation schemes. Besides, the closed form expressions of capacity for different adaptive schemes under EGK in presence of CCI are derived. Finally, analytical and simulated results are obtained with excellent agreement.

Computational analysis of forebody tangential slot blowing

NASA Technical Reports Server (NTRS)

Gee, Ken; Agosta-Greenman, Roxana M.; Rizk, Yehia M.; Schiff, Lewis B.; Cummings, Russell M.

1994-01-01

An overview of the computational effort to analyze forebody tangential slot blowing is presented. Tangential slot blowing generates side force and yawing moment which may be used to control an aircraft flying at high-angle-of-attack. Two different geometries are used in the analysis: (1) The High Alpha Research Vehicle; and (2) a generic chined forebody. Computations using the isolated F/A-18 forebody are obtained at full-scale wind tunnel test conditions for direct comparison with available experimental data. The effects of over- and under-blowing on force and moment production are analyzed. Time-accurate solutions using the isolated forebody are obtained to study the force onset timelag of tangential slot blowing. Computations using the generic chined forebody are obtained at experimental wind tunnel conditions, and the results compared with available experimental data. This computational analysis compliments the experimental results and provides a detailed understanding of the effects of tangential slot blowing on the flow field about simple and complex geometries.

Modification of porous silicon rugate filters through thiol-yne photochemistry

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

Soeriyadi, Alexander H., E-mail: alexander.soeriyadi@unsw.edu.au; Zhu, Ying, E-mail: alexander.soeriyadi@unsw.edu.au; Gooding, J. Justin, E-mail: justin.gooding@unsw.edu.au

2014-02-24

Porous silicon (PSi) has a considerable potential as biosensor platform. In particular, the ability to modify the surface chemistry of porous silicon is of interest. Here we present a generic method to modify the surface of porous silicon through thiol-yne photochemistry initiated by a radical initiator. Firstly, a freshly etched porous silicon substrate is modified through thermal hydrosilylation with 1,8-nonadiyne to passivate the surface and introduce alkyne functionalities. The alkyne functional surface could then be further reacted with thiol species in the presence of a radical initiator and UV light. Functionalization of the PSi rugate filter is followed with opticalmore » reflectivity measurements as well as high resolution X-ray photoelectron spectroscopy (XPS)« less

A Yang-Mills field on the extremal Reissner-Nordström black hole

NASA Astrophysics Data System (ADS)

Bizoń, Piotr; Kahl, Michał

2016-09-01

We consider a spherically symmetric (magnetic) SU(2) Yang-Mills field propagating on the exterior of the extremal Reissner-Nordström black hole. Taking advantage of the conformal symmetry, we reduce the problem to the study of the Yang-Mills equation in a geodesically complete spacetime with two asymptotically flat ends. We prove the existence of infinitely many static solutions (two of which are found in closed form) and determine the spectrum of their linear perturbations and quasinormal modes. Finally, using the hyperboloidal approach to the initial value problem, we describe the process of relaxation to the static endstates of evolution, both stable (for generic initial data) and unstable (for codimension-one initial data).

Generic medicines and generic substitution: contrasting perspectives of stakeholders in Ireland.

PubMed

O'Leary, A; Usher, C; Lynch, M; Hall, M; Hemeryk, L; Spillane, S; Gallagher, P; Barry, M

2015-12-15

The Health (Pricing and Supply of Medical Goods) Act 2013 passed into law in July 2013 and legislated for generic substitution in Ireland. The aim of the study was to ascertain the knowledge and perceptions of stakeholders i.e. patients, pharmacists and prescribers, of generic medicines and to generic substitution with the passing of legislation. Three stakeholder specific questionnaires were developed to assess knowledge of and perceptions to generic medicines and generic substitution. Purposive samples of patients, prescribers and pharmacists were analysed. Descriptive quantitative and qualitative analyses were undertaken. A total of 762 healthcare professionals and 353 patients were recruited. The study highlighted that over 84% of patients were familiar with generic medicines and are supportive of the concept of generic substitution. Approximately 74% of prescribers and 84% of pharmacists were supportive of generic substitution in most cases. The main areas of concern highlighted by the healthcare professionals that might impact on the successful implementation of the policy, were the issue of bioequivalence with generic medicines, the computer software systems used at present in general practitioner (GP) surgeries and the availability of branded generics. The findings from this study identify a high baseline rate of acceptance to generic medicines and generic substitution among patients, prescribers and pharmacists in the Irish setting. The concerns of the main stakeholders provide a valuable insight into the potential difficulties that may arise in its implementation, and the need for on-going reassurance and proactive dissemination of the impact of the generic substitution policy. The existing positive attitude to generic medicines and generic substitution among key stakeholders in Ireland to generic substitution, combined with appropriate support and collaboration should result in the desired increase in rates of prescribing, dispensing and use of generic medicines.

Is there a relationship between patient beliefs or communication about generic drugs and medication utilization?

PubMed

Shrank, William H; Cadarette, Suzanne M; Cox, Emily; Fischer, Michael A; Mehta, Jyotsna; Brookhart, Alan M; Avorn, Jerry; Choudhry, Niteesh K

2009-03-01

Insurers and policymakers strive to stimulate more cost-effective prescribing and, increasingly, are educating beneficiaries about generics. To evaluate the relationship between patient beliefs and communication about generic drugs and actual drug use. We performed a national mailed survey of a random sample of 2500 commercially-insured adults. Patient responses were linked to pharmacy claims data to assess actual generic medication use. We used factor analysis to develop 5 multi-item scales from patient survey responses that measured: (1) general preferences for generics, (2) generic safety/effectiveness, (3) generic cost/value, (4) comfort with generic substitution, and (5) communication with providers about generics. The relationship between each scale and the proportion of prescriptions filled for generics was assessed using linear regression, controlling for demographic, health, and insurance characteristics. Separate models were created for each scale and then all 5 scales were included simultaneously in a fully-adjusted model. The usable response rate was 48%. When evaluated independently, a 1 SD increase in each of the 5 scales was associated with a 3.1% to 6.3% increase in generic drug use (P < 0.05 for each). In the fully adjusted model, only 2 scales were significantly associated with generic drug use: comfort with generic substitution (P = 0.021) and communication with providers about generic drugs (P = 0.012). Generic drug use is most closely associated with the 2 actionable items we evaluated: communication with providers about generics and comfort with generic substitution. Educational campaigns that focus on these 2 domains may be most effective at influencing generic drug use.

Differences in the availability of medicines for chronic and acute conditions in the public and private sectors of developing countries

PubMed Central

Roubos, Ilse; Ewen, Margaret; Mantel-Teeuwisse, Aukje K; Leufkens, Hubertus GM; Laing, Richard O

2011-01-01

Abstract Objective To investigate potential differences in the availability of medicines for chronic and acute conditions in low- and middle-income countries. Methods Data on the availability of 30 commonly-surveyed medicines – 15 for acute and 15 for chronic conditions – were obtained from facility-based surveys conducted in 40 developing countries. Results were aggregated by World Bank country income group and World Health Organization region. Findings The availability of medicines for both acute and chronic conditions was suboptimal across countries, particularly in the public sector. Generic medicines for chronic conditions were significantly less available than generic medicines for acute conditions in both the public sector (36.0% availability versus 53.5%; P = 0.001) and the private sector (54.7% versus 66.2%; P = 0.007). Antiasthmatics, antiepileptics and antidepressants, followed by antihypertensives, were the drivers of the observed differences. An inverse association was found between country income level and the availability gap between groups of medicines, particularly in the public sector. In low- and lower-middle income countries, drugs for acute conditions were 33.9% and 12.9% more available, respectively, in the public sector than medicines for chronic conditions. Differences in availability were smaller in the private sector than in the public sector in all country income groups. Conclusion Current disease patterns do not explain the significant gaps observed in the availability of medicines for chronic and acute conditions. Measures are needed to better respond to the epidemiological transition towards chronic conditions in developing countries alongside current efforts to scale up treatment for communicable diseases. PMID:21673857

Generic evolution of mixing in heterogeneous media

NASA Astrophysics Data System (ADS)

De Dreuzy, J.; Carrera, J.; Dentz, M.; Le Borgne, T.

2011-12-01

Mixing in heterogeneous media results from the competition bewteen flow fluctuations and local scale diffusion. Flow fluctuations quickly create concentration contrasts and thus heterogeneity of the concentration field, which is slowly homogenized by local scale diffusion. Mixing first deviates from Gaussian mixing, which represents the potential mixing induced by spreading before approaching it. This deviation fundamentally expresses the evolution of the interaction between spreading and local scale diffusion. We characterize it by the ratio γ of the non-Gaussian to the Gaussian mixing states. We define the Gaussian mixing state as the integrated squared concentration of the Gaussian plume that has the same longitudinal dispersion as the real plume. The non-Gaussian mixing state is the difference between the overall mixing state defined as the integrated squared concentration and the Gaussian mixing state. The main advantage of this definition is to use the full knowledge previously acquired on dispersion for characterizing mixing even when the solute concentration field is highly non Gaussian. Using high precision numerical simulations, we show that γ quickly increases, peaks and slowly decreases. γ can be derived from two scales characterizing spreading and local mixing, at least for large flux-weighted solute injection conditions into classically log-normal Gaussian correlated permeability fields. The spreading scale is directly related to the longitudinal dispersion. The local mixing scale is the largest scale over which solute concentrations can be considered locally uniform. More generally, beyond the characteristics of its maximum, γ turns out to have a highly generic scaling form. Its fast increase and slow decrease depend neither on the heterogeneity level, nor on the ratio of diffusion to advection, nor on the injection conditions. They might even not depend on the particularities of the flow fields as the same generic features also prevail for Taylor dispersion. This generic characterization of mixing can offer new ways to set up transport equations that honor not only advection and spreading (dispersion), but also mixing.

Cross-cultural adaptation and validation of the Korean version of the EQ-5D in patients with rheumatic diseases.

PubMed

Kim, Myoung-Hee; Cho, Young-Shin; Uhm, Wan-Sik; Kim, Sehyun; Bae, Sang-Cheol

2005-06-01

This study aimed to determine the cross-cultural adaptation and validation of the Korean version of the EQ-5D in rheumatic conditions. Translation, back-translation and cognitive debriefing were performed according to the EuroQol group's guidelines. For validity, 508 patients were recruited and administered the EQ-5D, Short-Form 36 and condition-specific measures. Construct validity and sensitivity were evaluated by testing a-priori hypotheses. For reliability, another 57 patients repeated the EQ-5D at 1-week interval, and intra-class correlations (ICC) and kappa statistics were estimated. For responsiveness, another 60 patients repeated it at 12-week interval within the context of clinical trial, and standardized response mean(SRM) were calculated. The cross-cultural adaptation produced no major modifications in the scale. The associations of the EQ-5D with the generic- and condition-specific measures were observed as expected in hypotheses: the higher EQ-5Dindex and EQ-5D(VAS) scores, the better health status by generic- or condition-specific measures, and the better functional class. The ICCs were 0.751 and 0.767, respectively, and kappa ranged from 0.455 to 0.772. The SRM were 0.649 and 0.410, respectively. The Korean EQ-5D exhibits good validity and sensitivity in various rheumatic conditions. Although its reliability and responsiveness were not excellent, it seems acceptable if condition-specific measures are applied together.

Generic Procedure for Coupling the PHREEQC Geochemical Modeling Framework with Flow and Solute Transport Simulators

NASA Astrophysics Data System (ADS)

Wissmeier, L. C.; Barry, D. A.

2009-12-01

Computer simulations of water availability and quality play an important role in state-of-the-art water resources management. However, many of the most utilized software programs focus either on physical flow and transport phenomena (e.g., MODFLOW, MT3DMS, FEFLOW, HYDRUS) or on geochemical reactions (e.g., MINTEQ, PHREEQC, CHESS, ORCHESTRA). In recent years, several couplings between both genres of programs evolved in order to consider interactions between flow and biogeochemical reactivity (e.g., HP1, PHWAT). Software coupling procedures can be categorized as ‘close couplings’, where programs pass information via the memory stack at runtime, and ‘remote couplings’, where the information is exchanged at each time step via input/output files. The former generally involves modifications of software codes and therefore expert programming skills are required. We present a generic recipe for remotely coupling the PHREEQC geochemical modeling framework and flow and solute transport (FST) simulators. The iterative scheme relies on operator splitting with continuous re-initialization of PHREEQC and the FST of choice at each time step. Since PHREEQC calculates the geochemistry of aqueous solutions in contact with soil minerals, the procedure is primarily designed for couplings to FST’s for liquid phase flow in natural environments. It requires the accessibility of initial conditions and numerical parameters such as time and space discretization in the input text file for the FST and control of the FST via commands to the operating system (batch on Windows; bash/shell on Unix/Linux). The coupling procedure is based on PHREEQC’s capability to save the state of a simulation with all solid, liquid and gaseous species as a PHREEQC input file by making use of the dump file option in the TRANSPORT keyword. The output from one reaction calculation step is therefore reused as input for the following reaction step where changes in element amounts due to advection/dispersion are introduced as irreversible reactions. An example for the coupling of PHREEQC and MATLAB for the solution of unsaturated flow and transport is provided.

Concerns about the safety of obesity agents from a manufacturing perspective.

PubMed

Kanfer, Isadore

2008-07-01

Salt derivatives of active pharmaceutical ingredients (API), such as hydrochloride and mesylate salts, are frequently used during drug product development. Compared with the underivatized API, salt derivatives are often associated with beneficial properties, including improved solubility and better absorption. Although the obesity agent sibutramine was initially approved as the hydrochloride salt, it has also been formulated as a mesylate salt (sibutramine mesylate). In order to qualify as interchangeable, generic products generally must be both pharmaceutically equivalent and bioequivalent to an approved reference product. Because generic versions of hydrochloride salt formulations that have been reformulated as mesylate salts are not pharmaceutically equivalent to the approved reference products, they would not be interchangeable, even if bioequivalent. The safety of APIs and drug products manufactured outside the United States in non-Food and Drug Administration-regulated facilities are of concern, particularly agents that may contain harmful impurities, such as obesity products formulated as mesylate salts.

Telerobotic system performance measurement - Motivation and methods

NASA Technical Reports Server (NTRS)

Kondraske, George V.; Khoury, George J.

1992-01-01

A systems performance-based strategy for modeling and conducting experiments relevant to the design and performance characterization of telerobotic systems is described. A developmental testbed consisting of a distributed telerobotics network and initial efforts to implement the strategy described is presented. Consideration is given to the general systems performance theory (GSPT) to tackle human performance problems as a basis for: measurement of overall telerobotic system (TRS) performance; task decomposition; development of a generic TRS model; and the characterization of performance of subsystems comprising the generic model. GSPT employs a resource construct to model performance and resource economic principles to govern the interface of systems to tasks. It provides a comprehensive modeling/measurement strategy applicable to complex systems including both human and artificial components. Application is presented within the framework of a distributed telerobotics network as a testbed. Insight into the design of test protocols which elicit application-independent data is described.

Potential impact of policy regulation and generic competition on sales of cholesterol lowering medication, antidepressants and acid blocking agents in Belgium.

PubMed

Fraeyman, J; Van Hal, G; De Loof, H; Remmen, R; De Meyer, G R Y; Beutels, P

2012-01-01

Pharmaceutical expenditures are increasing as a proportion of health expenditures in most rich countries. Antidepressants, acid blocking agents and cholesterol lowering medication are major contributors to medicine sales around the globe. We aimed to document the possible impact of policy regulations and generic market penetration on the evolution of sales volume and average cost per unit (Defined Daily Doses and packages) of antidepressants, acid blocking agents and cholesterol lowering medication. We extracted data from the IMS health database regarding the public price and sales volume of the antidepressants (selective serotonin reuptake inhibitors (SSRI's), monoamine oxidase inhibitors (MAOl's) and tricyclic and remaining antidepressants (TCA's)), acid blocking agents (proton pump inhibitors (PPl's) and H2 receptor antagonists) and cholesterol lowering medication (statins and fibrates) in Belgium between 1995 and 2009. We describe these sales data in relation to various national policy measures which were systematically searched in official records. Our analysis suggests that particular policy regulations have had immediate impact on sales figures and expenditures on pharmaceuticals in Belgium: changes in reimbursement conditions, a public tender and entry of generic competitors in a reference pricing system. However, possible sustainable effects seem to be counteracted by other mechanisms such as marketing strategies, prescribing behaviour, brand loyalty and the entry of pseudogenerics. It is likely that demand-side measures have a more sustainable impact on expenditure. Compared with other European countries, generic penetration in Belgium remains low. Alternative policy regulations aimed at enlarging the generic market and influencing pharmaceutical expenditures deserve consideration. This should include policies aiming to influence physicians' prescribing and a shared responsibility of pharmacists, physicians and patients towards expenditures.

Association of authorized generic marketing with prescription drug spending on antidepressants from 2000 to 2011.

PubMed

Cheng, Ning; Banerjee, Tannista; Qian, Jingjing; Hansen, Richard A

Prior research suggests that authorized generic drugs increase competition and decrease prices, but little empirical evidence supports this conclusion. This study evaluated the impact of authorized generic marketing on brand and generic prices. Longitudinal analysis of the household component of the Medical Expenditure Panel Survey. Interview panels over 12 years, with a new panel each year. For each panel, 5 rounds of household interviews were conducted over 30 months. Nationally representative sample of the U.S. civilian noninstitutionalized population, focusing on people using 1 of 5 antidepressant drugs that became generically available between 2000 to 2011. Drugs and dose/formulations with versus without an authorized generic drug marketed. Multiple linear regression models with lagged variables evaluated the effect of an authorized generic on average inflation-adjusted brand and generic price, adjusting for payment sources, generic entry time, competitor price, and year. During 2000-2011, annual brand antidepressant utilization decreased from 51.47 to 7.52 million prescriptions, and generic antidepressant utilization increased from 0 to 88.83 million prescriptions. Over time, payment per prescription for brand prescriptions increased 25% overall, and generic payments decreased 70% for all payer types. With unadjusted data, after generic entry the average brand price decreased $0.59 per year with and $3.62 per year without an authorized generic in the market. Average generic prices decreased $10.30 per year with and $8.47 per year without an authorized generic in the market. In multiple regression models with lagged variables adjusted for heteroscedasticity, payer source, time since generic entry, competitor price, and year, authorized generics significantly reduced average payment for generic (-$3.03) and brand (-$60.64) prescriptions, and over time this price change slowly diminished. Availability of an authorized generic was associated with reduced average generic and brand price in the antidepressant market, supporting prior evidences. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

42 CFR 423.871 - Contract terms and conditions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... contains costs to the Medicare Prescription Drug Account and to Part D eligible individuals enrolled in a fallback prescription drug plan offered by the entity through mechanisms such as generic substitution and... permitted to market or brand fallback prescription drug plans. Notwithstanding any other provisions of this...

Potential of select intermediate-volatility organic compounds and consumer products for secondary organic aerosol and ozone formation under relevant urban conditions

NASA Astrophysics Data System (ADS)

Li, Weihua; Li, Lijie; Chen, Chia-li; Kacarab, Mary; Peng, Weihan; Price, Derek; Xu, Jin; Cocker, David R.

2018-04-01

Emissions of certain low vapor pressure-volatile organic compounds (LVP-VOCs) are considered exempt to volatile organic compounds (VOC) regulations due to their low evaporation rates. However, these compounds may still play a role in ambient secondary organic aerosol (SOA) and ozone formation. The LVP-VOCs selected for this work are categorized as intermediate-volatility organic compounds (IVOCs) according to their vapor pressures and molecular formulas. In this study, the evaporation rates of 14 select IVOCs are investigated with half of them losing more than 95% of their mass in less than one month. Further, SOA and ozone formation are presented from 11 select IVOCs and 5 IVOC-containing generic consumer products under atmospherically relevant conditions using varying radical sources (NOx and/or H2O2) and a surrogate reactive organic gas (ROG) mixture. Benzyl alcohol (0.41), n-heptadecane (0.38), and diethylene glycol monobutyl ether (0.16) are determined to have SOA yields greater than 0.1 in the presence of NOx and a surrogate urban hydrocarbon mixture. IVOCs also influence ozone formation from the surrogate urban mixture by impacting radical levels and NOx availability. The addition of lab created generic consumer products has a weak influence on ozone formation from the surrogate mixture but strongly affects SOA formation. The overall SOA and ozone formation of the generic consumer products could not be explained solely by the results of the pure IVOC experiments.

The Communicative Participation Item Bank (CPIB): Item bank calibration and development of a disorder-generic short form

PubMed Central

Baylor, Carolyn; Yorkston, Kathryn; Eadie, Tanya; Kim, Jiseon; Chung, Hyewon; Amtmann, Dagmar

2015-01-01

Purpose The purpose of this study was to calibrate the items for the Communicative Participation Item Bank (CPIB) using Item Response Theory (IRT). One overriding objective was to examine if the IRT item parameters would be consistent across different diagnostic groups, thereby allowing creation of a disorder-generic instrument. The intended outcomes were the final item bank and a short form ready for clinical and research applications. Methods Self-report data were collected from 701 individuals representing four diagnoses: multiple sclerosis, Parkinson’s disease, amyotrophic lateral sclerosis and head and neck cancer. Participants completed the CPIB and additional self-report questionnaires. CPIB data were analyzed using the IRT Graded Response Model (GRM). Results The initial set of 94 candidate CPIB items were reduced to an item bank of 46 items demonstrating unidimensionality, local independence, good item fit, and good measurement precision. Differential item function (DIF) analyses detected no meaningful differences across diagnostic groups. A 10-item, disorder-generic short form was generated. Conclusions The CPIB provides speech-language pathologists with a unidimensional, self-report outcomes measurement instrument dedicated to the construct of communicative participation. This instrument may be useful to clinicians and researchers wanting to implement measures of communicative participation in their work. PMID:23816661

Scaling Limits and Generic Bounds for Exploration Processes

NASA Astrophysics Data System (ADS)

Bermolen, Paola; Jonckheere, Matthieu; Sanders, Jaron

2017-12-01

We consider exploration algorithms of the random sequential adsorption type both for homogeneous random graphs and random geometric graphs based on spatial Poisson processes. At each step, a vertex of the graph becomes active and its neighboring nodes become blocked. Given an initial number of vertices N growing to infinity, we study statistical properties of the proportion of explored (active or blocked) nodes in time using scaling limits. We obtain exact limits for homogeneous graphs and prove an explicit central limit theorem for the final proportion of active nodes, known as the jamming constant, through a diffusion approximation for the exploration process which can be described as a unidimensional process. We then focus on bounding the trajectories of such exploration processes on random geometric graphs, i.e., random sequential adsorption. As opposed to exploration processes on homogeneous random graphs, these do not allow for such a dimensional reduction. Instead we derive a fundamental relationship between the number of explored nodes and the discovered volume in the spatial process, and we obtain generic bounds for the fluid limit and jamming constant: bounds that are independent of the dimension of space and the detailed shape of the volume associated to the discovered node. Lastly, using coupling techinques, we give trajectorial interpretations of the generic bounds.

Refinement and evaluation of helicopter real-time self-adaptive active vibration controller algorithms

NASA Technical Reports Server (NTRS)

Davis, M. W.

1984-01-01

A Real-Time Self-Adaptive (RTSA) active vibration controller was used as the framework in developing a computer program for a generic controller that can be used to alleviate helicopter vibration. Based upon on-line identification of system parameters, the generic controller minimizes vibration in the fuselage by closed-loop implementation of higher harmonic control in the main rotor system. The new generic controller incorporates a set of improved algorithms that gives the capability to readily define many different configurations by selecting one of three different controller types (deterministic, cautious, and dual), one of two linear system models (local and global), and one or more of several methods of applying limits on control inputs (external and/or internal limits on higher harmonic pitch amplitude and rate). A helicopter rotor simulation analysis was used to evaluate the algorithms associated with the alternative controller types as applied to the four-bladed H-34 rotor mounted on the NASA Ames Rotor Test Apparatus (RTA) which represents the fuselage. After proper tuning all three controllers provide more effective vibration reduction and converge more quickly and smoothly with smaller control inputs than the initial RTSA controller (deterministic with external pitch-rate limiting). It is demonstrated that internal limiting of the control inputs a significantly improves the overall performance of the deterministic controller.

Is There a Relationship Between Patient Beliefs or Communication About Generic Drugs and Medication Utilization?

PubMed Central

Shrank, William H.; Cadarette, Suzanne M.; Cox, Emily; Fischer, Michael A.; Mehta, Jyotsna; Brookhart, Alan M.; Avorn, Jerry; Choudhry, Niteesh K.

2009-01-01

Background Insurers and policymakers strive to stimulate more cost-effective prescribing and, increasingly, are educating beneficiaries about generics. Objectives To evaluate the relationship between patient beliefs and communication about generic drugs and actual drug use. Research Design and Subjects We performed a national mailed survey of a random sample of 2500 commercially-insured adults. Patient responses were linked to pharmacy claims data to assess actual generic medication use. Measures We used factor analysis to develop 5 multi-item scales from patient survey responses that measured: (1) general preferences for generics, (2) generic safety/effectiveness, (3) generic cost/value, (4) comfort with generic substitution, and (5) communication with providers about generics. The relationship between each scale and the proportion of prescriptions filled for generics was assessed using linear regression, controlling for demographic, health, and insurance characteristics. Separate models were created for each scale and then all 5 scales were included simultaneously in a fully-adjusted model. Results The usable response rate was 48%. When evaluated independently, a 1 SD increase in each of the 5 scales was associated with a 3.1% to 6.3% increase in generic drug use (P < 0.05 for each). In the fully adjusted model, only 2 scales were significantly associated with generic drug use: comfort with generic substitution (P = 0.021) and communication with providers about generic drugs (P = 0.012). Conclusions Generic drug use is most closely associated with the 2 actionable items we evaluated: communication with providers about generics and comfort with generic substitution. Educational campaigns that focus on these 2 domains may be most effective at influencing generic drug use. PMID:19194329

The Market Dynamics of Generic Medicines in the Private Sector of 19 Low and Middle Income Countries between 2001 and 2011: A Descriptive Time Series Analysis

PubMed Central

Kaplan, Warren A.; Wirtz, Veronika J.; Stephens, Peter

2013-01-01

This observational study investigates the private sector, retail pharmaceutical market of 19 low and middle income countries (LMICs) in Latin America, Asia and the Middle East/South Africa analyzing the relationships between volume market share of generic and originator medicines over a time series from 2001 to 2011. Over 5000 individual pharmaceutical substances were divided into generic (unbranded generic, branded generic medicines) and originator categories for each country, including the United States as a comparator. In 9 selected LMICs, the market share of those originator substances with the largest decrease over time was compared to the market share of their counterpart generic versions. Generic medicines (branded generic plus unbranded generic) represent between 70 and 80% of market share in the private sector of these LMICs which exceeds that of most European countries. Branded generic medicine market share is higher than that of unbranded generics in all three regions and this is in contrast to the U.S. Although switching from an originator to its generic counterpart can save money, this narrative in reality is complex at the level of individual medicines. In some countries, the market behavior of some originator medicines that showed the most temporal decrease, showed switching to their generic counterpart. In other countries such as in the Middle East/South Africa and Asia, the loss of these originators was not accompanied by any change at all in market share of the equivalent generic version. For those countries with a significant increase in generic medicines market share and/or with evidence of comprehensive “switching” to generic versions, notably in Latin America, it would be worthwhile to establish cause-effect relationships between pharmaceutical policies and uptake of generic medicines. The absence of change in the generic medicines market share in other countries suggests that, at a minimum, generic medicines have not been strongly promoted. PMID:24098644

The market dynamics of generic medicines in the private sector of 19 low and middle income countries between 2001 and 2011: a descriptive time series analysis.

PubMed

Kaplan, Warren A; Wirtz, Veronika J; Stephens, Peter

2013-01-01

This observational study investigates the private sector, retail pharmaceutical market of 19 low and middle income countries (LMICs) in Latin America, Asia and the Middle East/South Africa analyzing the relationships between volume market share of generic and originator medicines over a time series from 2001 to 2011. Over 5000 individual pharmaceutical substances were divided into generic (unbranded generic, branded generic medicines) and originator categories for each country, including the United States as a comparator. In 9 selected LMICs, the market share of those originator substances with the largest decrease over time was compared to the market share of their counterpart generic versions. Generic medicines (branded generic plus unbranded generic) represent between 70 and 80% of market share in the private sector of these LMICs which exceeds that of most European countries. Branded generic medicine market share is higher than that of unbranded generics in all three regions and this is in contrast to the U.S. Although switching from an originator to its generic counterpart can save money, this narrative in reality is complex at the level of individual medicines. In some countries, the market behavior of some originator medicines that showed the most temporal decrease, showed switching to their generic counterpart. In other countries such as in the Middle East/South Africa and Asia, the loss of these originators was not accompanied by any change at all in market share of the equivalent generic version. For those countries with a significant increase in generic medicines market share and/or with evidence of comprehensive "switching" to generic versions, notably in Latin America, it would be worthwhile to establish cause-effect relationships between pharmaceutical policies and uptake of generic medicines. The absence of change in the generic medicines market share in other countries suggests that, at a minimum, generic medicines have not been strongly promoted.

Passive Sun seeker/tracker and a thermally activated power module

NASA Technical Reports Server (NTRS)

Siebert, C. J.; Morris, F. A.

1984-01-01

Development and testing of two mechanisms using a shape memory alloy metal (NITINOL) as the power source are described. The two mechanisms developed are a passive Sun Seeker/Tracker and a generic type power module. These mechanisms use NITINOL wire initially strained in pure torsion which provides the greatest mechanical work capacity upon recovery, as compared to other deformation modes (i.e., tension, helical springs, and bending).

Health-Related Quality of Life and Cognitive Functioning from the Perspective of Parents of School-Aged Children with Asperger's Syndrome Utilizing the PedsQL[TM

ERIC Educational Resources Information Center

Limbers, Christine A.; Heffer, Robert W.; Varni, James W.

2009-01-01

HRQOL as a multidimensional construct has not been previously investigated in children with Asperger's Syndrome. The objective of the present study was to examine the initial feasibility, reliability, and validity of the PedsQL[TM] 4.0 Generic Core Scales and PedsQL[TM] Cognitive Functioning Scale parent proxy-report versions in school-aged…

Generics, Supergenerics and Patent Strategies--SMi's 13th Annual Meeting.

PubMed

Edwards, Catherine

2010-07-01

SMi's 13th Annual Meeting on Generics, Supergenerics and Patent Strategies, held in London, included topics covering new trends in the generics field, the difficulties faced by companies in entering the generics market and recent developments in IP. This conference report highlights selected presentations on generics in India, protecting pharmaceutical products in China, changes in generics law and litigation in the US and Europe, challenges for market selection and entry for generics companies, the influence of changes in the healthcare market on the generics industry, supergenerics, and biosimilars.

A generic model for evaluating payor net cost savings from a disease management program.

PubMed

McKay, Niccie L

2006-01-01

Private and public payors increasingly are turning to disease management programs as a means of improving the quality of care provided and controlling expenditures for individuals with specific medical conditions. This article presents a generic model that can be adapted to evaluate payor net cost savings from a variety of types of disease management programs, with net cost savings taking into account both changes in expenditures resulting from the program and the costs of setting up and operating the program. The model specifies the required data, describes the data collection process, and shows how to calculate the net cost savings in a spreadsheet format. An accompanying hypothetical example illustrates how to use the model.

Generic instabilities in a fluid membrane coupled to a thin layer of ordered active polar fluid.

PubMed

Sarkar, Niladri; Basu, Abhik

2013-08-01

We develop an effective two-dimensional coarse-grained description for the coupled system of a planar fluid membrane anchored to a thin layer of polar ordered active fluid below. The macroscopic orientation of the active fluid layer is assumed to be perpendicular to the attached membrane. We demonstrate that activity or nonequilibrium drive of the active fluid makes such a system generically linearly unstable for either signature of a model parameter [Formula: see text] [Formula: see text] that characterises the strength of activity. Depending upon boundary conditions and within a range of the model parameters, underdamped propagating waves may be present in our model. We discuss the phenomenological significance of our results.

PRISM, a Novel Visual Metaphor Measuring Personally Salient Appraisals, Attitudes and Decision-Making: Qualitative Evidence Synthesis.

PubMed

Sensky, Tom; Büchi, Stefan

2016-01-01

PRISM (the Pictorial Representation of Illness and Self Measure) is a novel, simple visual instrument. Its utility was initially discovered serendipitously, but has been validated as a quantitative measure of suffering. Recently, new applications for different purposes, even in non-health settings, have encouraged further exploration of how PRISM works, and how it might be applied. This review will summarise the results to date from applications of PRISM and propose a generic conceptualisation of how PRISM works which is consistent with all these applications. A systematic review, in the form of a qualitative evidence synthesis, was carried out of all available published data on PRISM. Fifty-two publications were identified, with a total of 8254 participants. Facilitated by simple instructions, PRISM has been used with patient groups in a variety of settings and cultures. As a measure of suffering, PRISM has, with few exceptions, behaved as expected according to Eric Cassell's seminal conceptualisation of suffering. PRISM has also been used to assess beliefs about or attitudes to stressful working conditions, interpersonal relations, alcohol consumption, and suicide, amongst others. This review supports PRISM behaving as a visual metaphor of the relationship of objects (eg 'my illness') to a subject (eg 'myself') in a defined context (eg 'my life at the moment'). As a visual metaphor, it is quick to complete and yields personally salient information. PRISM is likely to have wide applications in assessing beliefs, attitudes, and decision-making, because of its properties, and because it yields both quantitative and qualitative data. In medicine, it can serve as a generic patient-reported outcome measure. It can serve as a tool for representational guidance, can be applied to developing strategies visually, and is likely to have applications in coaching, psychological assessment and therapeutic interventions.

Dynamics and Adaptive Control for Stability Recovery of Damaged Aircraft

NASA Technical Reports Server (NTRS)

Nguyen, Nhan; Krishnakumar, Kalmanje; Kaneshige, John; Nespeca, Pascal

2006-01-01

This paper presents a recent study of a damaged generic transport model as part of a NASA research project to investigate adaptive control methods for stability recovery of damaged aircraft operating in off-nominal flight conditions under damage and or failures. Aerodynamic modeling of damage effects is performed using an aerodynamic code to assess changes in the stability and control derivatives of a generic transport aircraft. Certain types of damage such as damage to one of the wings or horizontal stabilizers can cause the aircraft to become asymmetric, thus resulting in a coupling between the longitudinal and lateral motions. Flight dynamics for a general asymmetric aircraft is derived to account for changes in the center of gravity that can compromise the stability of the damaged aircraft. An iterative trim analysis for the translational motion is developed to refine the trim procedure by accounting for the effects of the control surface deflection. A hybrid direct-indirect neural network, adaptive flight control is proposed as an adaptive law for stabilizing the rotational motion of the damaged aircraft. The indirect adaptation is designed to estimate the plant dynamics of the damaged aircraft in conjunction with the direct adaptation that computes the control augmentation. Two approaches are presented 1) an adaptive law derived from the Lyapunov stability theory to ensure that the signals are bounded, and 2) a recursive least-square method for parameter identification. A hardware-in-the-loop simulation is conducted and demonstrates the effectiveness of the direct neural network adaptive flight control in the stability recovery of the damaged aircraft. A preliminary simulation of the hybrid adaptive flight control has been performed and initial data have shown the effectiveness of the proposed hybrid approach. Future work will include further investigations and high-fidelity simulations of the proposed hybrid adaptive Bight control approach.

Challenges of therapeutic substitution of drugs for economic reasons: focus on CVD prevention.

PubMed

Johnston, Atholl

2010-04-01

Healthcare systems throughout the world are under increasing pressure to control and minimise costs. The substitution of initially-prescribed drugs with cheaper equivalents is an obvious option which presents a rapid and visible means to reduce these costs. Whether the substitution improves patient and/or population outcomes must be appraised and this paper highlights the conditions under which therapeutic substitution may require additional thought and consideration. In this paper, some of the medical evidence and the regulatory environment for and against the three types of therapeutic substitution - generic, within-class and between-class - are discussed. This article is not an exhaustive review of the literature, but captures some of the key clinical, pharmacological, economic, policy and ethical issues regarding generic and therapeutic substitution. Search criteria of the most commonly used terms, i.e. therapeutic substitution, switching, interchange, and bioequivalence, were applied to Embase, PubMed and Google Scholar to identify relevant publications. Although population studies support therapeutic substitution in principle, there is evidence that substitution may not always result in therapeutic equivalence in individual patients, with the consequent potential for greater risks of decreased efficacy and/or increased safety concerns. Factors such as patient choice and therapeutic equivalence also play an important role in the effectiveness of the treatment and overall management of the patient. The pan-European regulatory environment provides another contradiction, encouraging widespread cost containment through reduction in drug acquisition costs, while simultaneously promoting an increased role for patients in defining and managing their own treatment. There is a strong rationale for careful management in some patients with cardiovascular disease. Treatment decisions should be transparent and based on strong clinical evidence. If not, drug substitution on economic grounds alone cannot be considered to be in the individual patient's interest and is therefore unethical.

Brand vs generic adverse event reporting patterns: An authorized generic-controlled evaluation of cardiovascular medications.

PubMed

Alatawi, Y; Rahman, Md M; Cheng, N; Qian, J; Peissig, P L; Berg, R L; Page, C D; Hansen, R A

2018-06-01

Some public scepticism exists about generics in terms of whether brand and generic drugs produce identical outcomes. This study explores whether adverse event (AE) reporting patterns are similar between brand and generic drugs, using authorized generics (AGs) as a control for possible generic drug perception biases. Events reported to the FDA Adverse Event Reporting System from the years 2004-2015 were analysed. Drugs were classified as brand, AG or generic based on drug and manufacturer names. Reports were included if amlodipine, losartan, metoprolol extended release (ER) or simvastatin were listed as primary or secondary suspect drugs. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting labelled AEs compared to reporting these AEs with all other drugs. The Breslow-Day test compared RORs across brand, AG and generic. Interrupted time series analysis evaluated the impact of generic entry on reporting trends. Generics accounted for significant percentages of total U.S. reports, but AGs accounted for smaller percentages of reports, including for amlodipine (14.26%), losartan (1.48%), metoprolol ER (0.35%) and simvastatin (0.70%). Whereas the RORs were significantly different for multiple brand vs generic comparisons, the AG vs generic comparisons yielded fewer statistically significant findings. Namely, only the ROR for AG differed from generic for amlodipine with peripheral oedema (P < .01). Inconsistent reporting patterns were observed more between brand and generic compared with AG and generic. Use of AGs as a control for perception biases against generics is useful, but this approach can be limited by small AG report numbers. Requiring the manufacturer name to be printed on the prescription bottle or packaging could improve the accuracy of assignment for products being reported. © 2017 John Wiley & Sons Ltd.

A Meta-Analysis of Reliability Coefficients in Second Language Research

ERIC Educational Resources Information Center

Plonsky, Luke; Derrick, Deirdre J.

2016-01-01

Ensuring internal validity in quantitative research requires, among other conditions, reliable instrumentation. Unfortunately, however, second language (L2) researchers often fail to report and even more often fail to interpret reliability estimates beyond generic benchmarks for acceptability. As a means to guide interpretations of such estimates,…

42 CFR 423.871 - Contract terms and conditions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... following: (i) Costs. The entity contains costs to the Medicare Prescription Drug Account and to Part D... such as generic substitution and price discounts. (ii) Quality programs. The entity provides the... a fallback entity includes terms for payment for— (1) The actual costs of covered Part D drugs...

42 CFR 423.871 - Contract terms and conditions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... following: (i) Costs. The entity contains costs to the Medicare Prescription Drug Account and to Part D... such as generic substitution and price discounts. (ii) Quality programs. The entity provides the... a fallback entity includes terms for payment for— (1) The actual costs of covered Part D drugs...

In-Service Training of Teachers as Behavior Modifiers: Review and Analysis.

ERIC Educational Resources Information Center

Eachus, Herbert Todd

The basic principles of operant and classical conditioning are presented, and their applications for the in-service training of teachers are discussed. Certain classroom behaviors are analyzed and applied to the classic stimulus-response paradigm. Activities are generically classified as positive or negative reinforcers and these reinforcers, in…

Generic weak isolated horizons

NASA Astrophysics Data System (ADS)

Chatterjee, Ayan; Ghosh, Amit

2006-12-01

Weak isolated horizon boundary conditions have been relaxed supposedly to their weakest form so that both zeroth and first laws of black hole mechanics hold. This makes the formulation more amenable for applications in both analytic and numerical relativities. It also unifies the phase spaces of non-extremal and extremal black holes.

The Hawking-Penrose Singularity Theorem for C 1,1-Lorentzian Metrics

NASA Astrophysics Data System (ADS)

Graf, Melanie; Grant, James D. E.; Kunzinger, Michael; Steinbauer, Roland

2018-06-01

We show that the Hawking-Penrose singularity theorem, and the generalisation of this theorem due to Galloway and Senovilla, continue to hold for Lorentzian metrics that are of C 1,1-regularity. We formulate appropriate weak versions of the strong energy condition and genericity condition for C 1,1-metrics, and of C 0-trapped submanifolds. By regularisation, we show that, under these weak conditions, causal geodesics necessarily become non-maximising. This requires a detailed analysis of the matrix Riccati equation for the approximating metrics, which may be of independent interest.

Weyl consistency conditions in non-relativistic quantum field theory

DOE PAGES

Pal, Sridip; Grinstein, Benjamín

2016-12-05

Weyl consistency conditions have been used in unitary relativistic quantum field theory to impose constraints on the renormalization group flow of certain quantities. We classify the Weyl anomalies and their renormalization scheme ambiguities for generic non-relativistic theories in 2 + 1 dimensions with anisotropic scaling exponent z = 2; the extension to other values of z are discussed as well. We give the consistency conditions among these anomalies. As an application we find several candidates for a C-theorem. Here, we comment on possible candidates for a C-theorem in higher dimensions.

Intervening in global markets to improve access to HIV/AIDS treatment: an analysis of international policies and the dynamics of global antiretroviral medicines markets

PubMed Central

2010-01-01

Background Universal access to antiretroviral therapy (ART) in low- and middle-income countries faces numerous challenges: increasing numbers of people needing ART, new guidelines recommending more expensive antiretroviral (ARV) medicines, limited financing, and few fixed-dose combination (FDC) products. Global initiatives aim to promote efficient global ARV markets, yet little is known about market dynamics and the impact of global policy interventions. Methods We utilize several data sources, including 12,958 donor-funded, adult first-line ARV purchase transactions, to describe the market from 2002-2008. We examine relationships between market trends and: World Health Organization (WHO) HIV/AIDS treatment guidelines; WHO Prequalification Programme (WHO Prequal) and United States (US) Food and Drug Administration (FDA) approvals; and procurement policies of the Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM), US President's Emergency Plan for AIDS Relief (PEPFAR) and UNITAID. Results WHO recommended 7, 4, 24, and 6 first-line regimens in 2002, 2003, 2006 and 2009 guidelines, respectively. 2009 guidelines replaced a stavudine-based regimen ($88/person/year) with more expensive zidovudine- ($154-260/person/year) or tenofovir-based ($244-465/person/year) regimens. Purchase volumes for ARVs newly-recommended in 2006 (emtricitabine, tenofovir) increased >15-fold from 2006 to 2008. Twenty-four generic FDCs were quality-approved for older regimens but only four for newer regimens. Generic FDCs were available to GFATM recipients in 2004 but to PEPFAR recipients only after FDA approval in 2006. Price trends for single-component generic medicines mirrored generic FDC prices. Two large-scale purchasers, PEPFAR and UNITAID, together accounted for 53%, 84%, and 77% of market volume for abacavir, emtricitabine, and tenofovir, respectively, in 2008. PEPFAR and UNITAID purchases were often split across two manufacturers. Conclusions Global initiatives facilitated the creation of fairly efficient markets for older ARVs, but markets for newer ARVs are less competitive and slower to evolve. WHO guidelines shape demand, and their complexity may help or hinder achievement of economies of scale in pharmaceutical manufacturing. Certification programs assure ARV quality but can delay uptake of new formulations. Large-scale procurement policies may decrease the numbers of buyers and sellers, rendering the market less competitive in the longer-term. Global policies must be developed with consideration for their short- and long-term impact on market dynamics. PMID:20500827

Comparison of Generic-to-Brand Switchback Rates Between Generic and Authorized Generic Drugs.

PubMed

Hansen, Richard A; Qian, Jingjing; Berg, Richard; Linneman, James; Seoane-Vazquez, Enrique; Dutcher, Sarah K; Raofi, Saeid; Page, C David; Peissig, Peggy

2017-04-01

Generic drugs contain identical active ingredients as their corresponding brand drugs and are pharmaceutically equivalent and bioequivalent, whereas authorized generic drugs (AGs) contain both identical active and inactive ingredients as their corresponding brand drugs but are marketed as generics. This study compares generic-to-brand switchback rates between generic and AGs. Retrospective cohort study. Claims and electronic health record data from a regional U.S. health care system. The full cohort consisted of 5542 unique patients who received select branded drugs during the 6 months prior to their generic drug market availability (between 1999 and 2014) and then were switched to an AG or generic drug within 30 months of generic drug entry. For these patients, 5929 unique patient-drug combinations (867 with AGs and 5062 with generic drugs) were evaluated. Ten drugs with AGs and generics marketed between 1999 and 2014 were evaluated. The date of the first generic prescription was considered the index date for each drug, and it marked the beginning of follow-up to evaluate the occurrence of generic-to-brand switchback patterns over the subsequent 30 months. Switchback rates were compared between patients receiving AGs versus those receiving generics using multivariable Cox proportional hazards models, controlling for individual drug effects, age, sex, Charlson Comorbidity Score, pre-index drug use characteristics, and pre-index health care utilization. Among the 5542 unique patients who switched from brand to generic or brand to AG, 264 (4.8%) switched back to the brand drug. Overall switchback rates were similar for AGs compared with generics (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65-1.15). The likelihood of switchback was higher for alendronate (HR 1.64, 95% CI 1.20-2.23) and simvastatin (HR 1.81, 95% CI 1.30-2.54) and lower for amlodipine (HR 0.27, 95% CI 0.17-0.42) compared with the other drugs evaluated. Overall switchback rates were similar between AG and generic drug users, indirectly supporting similar efficacy and tolerability profiles for brand and generic drugs. Reasons for differences in switchback rates among specific products need to be explored further. © 2017 Pharmacotherapy Publications, Inc.

A computational examination of directional stability for smooth and chined forebodies at high-alpha

NASA Technical Reports Server (NTRS)

Ravi, Ramakrishnan; Mason, William H.

1992-01-01

Computational Fluid Dynamics (CFD) has been used to study aircraft forebody flowfields at low-speed, angle-of-attack conditions with sideslip. The purpose is to define forebody geometries which provide good directional stability characteristics under these conditions. The flows over the experimentally investigated F-5A forebody and chine type configuration, previously computed by the authors, were recomputed with better grid topology and resolution. The results were obtained using a modified version of CFL3D (developed at NASA Langley) to solve either the Euler equations or the Reynolds equations employing the Baldwin-Lomax turbulence model with the Degani-Schiff modification to account for massive crossflow separation. Based on the results, it is concluded that current CFD methods can be used to investigate the aerodynamic characteristics of forebodies to achieve desirable high angle-of-attack characteristics. An analytically defined generic forebody model is described, and a parametric study of various forebody shapes was then conducted to determine which shapes promote a positive contribution to directional stability at high angle-of-attack. An unconventional approach for presenting the results is used to illustrate how the positive contribution arises. Based on the results of this initial parametric study, some guidelines for aerodynamic design to promote positive directional stability are presented.

Development of the Lens Antenna Deployment Demonstration (LADD) shuttle-attached flight experiment

NASA Technical Reports Server (NTRS)

Hill, H.; Johnston, D.; Frauenberger, H.

1986-01-01

The primary objective of the LADD Program is to develop a technology demonstration test article that can be used for both ground and flight tests to demonstrate the structural and mechanical feasibility and reliability of the single-axis roll-out space based radar (SBR) approach. As designed, the LADD will essentially be a generic strucutural experiment which incorporates all critical technology elements of the operational satellite and is applicable to a number of future antenna systems. However, to fully determine its design integrity for meeting the lens flatness and constant geometry requirements in a zero g environment under extreme thermal conditions, the LADD must be space flight tested. By accurately surveying the structure under varying conditions the membrane tolerance-holding capabilities of the structure will be demonstrated. The flight test will provide data to verify analytical tools used to predict thermal and structural behavior. Most important, the experiment will provide an initial indication of structural damping in a zero g vacuum environment. The recently completed Solar Array Flight Experiment (SAFE) showed orbital damping greater than that experienced during ground testing. From the experience and the information obtained from LADD it is hoped that designs can be confidently extrapolated to operational satellites with apertures in the 20 m by 60 m size range.

Amyloid Formation by Human Carboxypeptidase D Transthyretin-like Domain under Physiological Conditions*

PubMed Central

Garcia-Pardo, Javier; Graña-Montes, Ricardo; Fernandez-Mendez, Marc; Ruyra, Angels; Roher, Nerea; Aviles, Francesc X.; Lorenzo, Julia; Ventura, Salvador

2014-01-01

Protein aggregation is linked to a growing list of diseases, but it is also an intrinsic property of polypeptides, because the formation of functional globular proteins comes at the expense of an inherent aggregation propensity. Certain proteins can access aggregation-prone states from native-like conformations without the need to cross the energy barrier for unfolding. This is the case of transthyretin (TTR), a homotetrameric protein whose dissociation into its monomers initiates the aggregation cascade. Domains with structural homology to TTR exist in a number of proteins, including the M14B subfamily carboxypeptidases. We show here that the monomeric transthyretin-like domain of human carboxypeptidase D aggregates under close to physiological conditions into amyloid structures, with the population of folded but aggregation-prone states being controlled by the conformational stability of the domain. We thus confirm that the TTR fold keeps a generic residual aggregation propensity upon folding, resulting from the presence of preformed amyloidogenic β-strands in the native state. These structural elements should serve for functional/structural purposes, because they have not been purged out by evolution, but at the same time they put proteins like carboxypeptidase D at risk of aggregation in biological environments and thus can potentially lead to deposition diseases. PMID:25294878

Faint blue counts from formation of dwarf galaxies at z approximately equals 1

NASA Technical Reports Server (NTRS)

Babul, Arif; Rees, Martin J.

1993-01-01

The nature of faint blue objects (FBO's) has been a source of much speculation since their detection in deep CCD images of the sky. Their high surface density argues against them being progenitors of present-day bright galaxies and since they are only weakly clustered on small scales, they cannot be entities that merged together to form present-day galaxies. Babul & Rees (1992) have suggested that the observed faint blue counts may be due to dwarf elliptical galaxies undergoing their initial starburst at z is approximately equal to 1. In generic hierarchical clustering scenarios, however, dwarf galaxy halos (M is approximately 10(exp 9) solar mass) are expected to form at an earlier epoch; for example, typical 10(exp 9) solar mass halos will virialize at z is approximately equal to 2.3 if the power-spectrum for the density fluctuations is that of the standard b = 2 cold dark matter (CDM) model. Under 'ordinary conditions' the gas would rapidly cool, collect in the cores, and undergo star-formation. Conditions at high redshifts are far from 'ordinary'. The intense UV background will prevent the gas in the dwarf halos from cooling, the halos being released from their suspended state only when the UV flux has diminished sufficiently.

Encouraging generic use can yield significant savings.

PubMed

Zimmerman, Christina

2012-11-01

Key findings. (1) Zero copayment for generic drugs is the greatest influencer of generic statin utilization. (2) Both higher copayments for generic drugs and lower copayments for competing brands are associated with a decreased probability of using generic statins. (3) Prior authorization and step therapy requirements for brand-name statins are associated with an increased use of generic drugs. (4) Greater use of generic statins should reduce costs for patients, plans, and Medicare.

Medicaid prescription limits: policy trends and comparative impact on utilization.

PubMed

Lieberman, Daniel A; Polinski, Jennifer M; Choudhry, Niteesh K; Avorn, Jerry; Fischer, Michael A

2016-01-15

Medicaid programs face growing pressure to control spending. Despite evidence of clinical harms, states continue to impose policies limiting the number of reimbursable prescriptions (caps). We examined the recent use of prescription caps by Medicaid programs and the impact of policy implementation on prescription utilization. We identified Medicaid cap policies from 2001-2010. We classified caps as applying to all prescriptions (overall caps) or only branded prescriptions (brand caps). Using state-level, aggregate prescription data, we developed interrupted time-series analyses to evaluate the impact of implementing overall caps and brand caps in a subset of states with data available before and after cap initiation. For overall caps, we examined the use of essential medications, which were classified as preventive or as providing symptomatic benefit. For brand caps, we examined the use of all branded drugs as well as branded and generic medications among classes with available generic replacements. The number of states with caps increased from 12 in 2001 to 20 in 2010. Overall cap implementation (n = 3) led to a 0.52% (p < 0.001) annual decrease in the proportion of essential prescriptions but no change in cost. For preventive essential medications, overall caps led to a 1.12% (p = 0.001) annual decrease in prescriptions (246,000 prescriptions annually) and a 1.20% (p < 0.001) decrease in spending (-$12.2 million annually), but no decrease in symptomatic essential medication use. Brand cap implementation (n = 6) led to an immediate 2.29% (p = 0.16) decrease in branded prescriptions and 1.26% (p = 0.025) decrease in spending. For medication classes with generic replacements, the decrease in branded prescriptions (0.74%, p = 0.003) approximately equaled the increase in generics (0.79%, p = 0.009), with estimated savings of $17.4 million. An increasing number of states are using prescription caps, with mixed results. Overall caps decreased the use of preventive but not symptomatic essential medications, suggesting that patients assign higher priority to agents providing symptomatic benefit when faced with reimbursement limits. Among medications with generic replacements, brand caps shifted usage from branded drugs to generics, with considerable savings. Future research should analyze the patient-level impact of these policies to measure clinical outcomes associated with these changes.

An analysis of volumes, prices and pricing trends of the pediatric antiretroviral market in developing countries from 2004 to 2012.

PubMed

Lee, Janice Soo Fern; Sagaon Teyssier, Luis; Dongmo Nguimfack, Boniface; Collins, Intira Jeannie; Lallemant, Marc; Perriens, Joseph; Moatti, Jean-Paul

2016-03-15

The pediatric antiretroviral (ARV) market is poorly described in the literature, resulting in gaps in understanding treatment access. We analyzed the pediatric ARV market from 2004 to 2012 and assessed pricing trends and associated factors. Data on donor funded procurements of pediatric ARV formulations reported to the Global Price Reporting Mechanism database from 2004 to 2012 were analyzed. Outcomes of interest were the volume and mean price per patient-year ARV formulation based on WHO ARV dosing recommendations for a 10 kg child. Factors associated with the price of formulations were assessed using linear regression; potential predictors included: country income classification, geographical region, market segment (originator versus generic ARVs), and number of manufacturers per formulation. All analyses were adjusted for type of formulations (single, dual or triple fixed-dose combinations (FDCs)) Data from 111 countries from 2004 to 2012 were included, with procurement of 33 formulations at a total value of USD 204 million. Use of dual and triple FDC formulations increased substantially over time, but with limited changes in price. Upon multivariate analysis, prices of originator formulations were found to be on average 72 % higher than generics (p < 0.001). A 10 % increase in procurement volume was associated with a 1 % decrease (p < 0.001) in both originator and generic prices. The entry of one additional manufacturer producing a formulation was associated with a decrease in prices of 2 % (p < 0.001) and 8 % (p < 0.001) for originator and generic formulations, respectively. The mean generic ARV price did not differ by country income level. Prices of originator ARVs were 48 % (p < 0.001) and 14 % (p < 0.001) higher in upper-middle income and lower-middle income countries compared to low income countries respectively, with the exception of South Africa, which had lower prices despite being an upper-middle income country. The donor funded pediatric ARV market as represented by the GPRM database is small, and lacks price competition. It is dominated by generic drugs due to the lower prices offered and the practicality of FDC formulations. This market requires continued donor support and the current initiatives to protect it are important to ensure market viability, especially if new formulations are to be introduced in the future.

High rates of regimen change due to drug toxicity among a cohort of South Indian adults with HIV infection initiated on generic, first-line antiretroviral treatment.

PubMed

Sivadasan, Ajith; Abraham, O C; Rupali, Priscilla; Pulimood, Susanne A; Rajan, Joyce; Rajkumar, S; Zachariah, Anand; Kannangai, Rajesh; Kandathil, Abraham Joseph; Sridharan, G; Mathai, Dilip

2009-05-01

To determine the rates, reasons and predictors of treatment change of the initial antiretroviral treatment (ART) regimen in HIV-infected south Indian adults. In this prospective cohort study, ART-naive adults initiated on generic, fixed dose combination ART as per the National AIDS Control Organization guidelines were followed up at an academic medical center. Treatment change was defined as any event which necessitated a change in or discontinuation of the initial ART regimen. Two hundred and thirty persons with HIV infection (males 74.8% and median age 37 years) were followed up for median duration of 48 weeks. The majority (98.7%) had acquired HIV infection through the heterosexual route. Most (70.4%) had advanced IV infection (WHO clinical stage 3 or 4) and 78% had CD4+ T-lymphocyte counts below 200 cells/microL. The initial ART regimens used were: Lamivudine (3TC) with Stavudine (d4T) (in 76%) or Azidothymidine (AZT) and Nevirapine (NVP) (in 86%) or Efavirenz (EFV). The cumulative incidence of treatment change was 39.6% (91 patients). Drug toxicity (WHO grade 3 or 4) was the reason for treatment change among 62 (27%) (incidence rate 35.9/100 person-years). The most common toxicities were attributable to the thymidine analogue nucleoside reverse transcriptase inhibitors (NRTIs), d4T and AZT [lactic acidosis (8.7%), anemia (7%) and peripheral neuropathy (5.2%)]. The other toxicities were rash (3.9%) and hepatitis (1.3%) due to NVP. The mortality (4.6/100 person-years) and disease progression rates (4.1/100 person-years) were low. The ART regimens used in this study were effective in decreasing disease progression and death. However, they were associated with high rates of drug toxicities, particularly those attributable to thymidine analogue NRTI. As efforts are made to improve access to ART, treatment regimens chosen should not only be potent, but also safe.

27 CFR 4.24 - Generic, semi-generic, and non-generic designations of geographic significance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Generic, semi-generic, and non-generic designations of geographic significance. 4.24 Section 4.24 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND...

Generic drugs in Brazil: known by many, used by few.

PubMed

Bertoldi, Andréa D; Barros, Aluísio J D; Hallal, Pedro C

2005-01-01

This study evaluated knowledge and use of generic drugs in a population-based sample of adults from a southern Brazilian city. The outcomes were: the proportion of generics in total medicines used; theoretical and practical knowledge about generics; and strategies used to buy medicines on medical prescriptions. The recall period for drug utilization was 15 days. The proportion of generics in total medicines was 3.9%. While 86.0% knew that generics cost less and 70.0% that the quality is similar to brand name medicines, only 57.0% knew any packaging characteristics that distinguish generics from other medicines. The highest proportion of generic drug utilization was in the antimicrobial pharmacological group. A brand name medicine (with a brand similar to the generic name) was mistakenly classified as a generic through photos by 48.0% of the interviewees. Among subjects who bought medicines in the 15-day period, 18.9% reported buying a generic, but this result should be interpreted with caution, because the population frequently fails to differentiate between generics and other medicines.

Comparison of brand versus generic antiepileptic drug adverse event reporting rates in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

PubMed

Rahman, Md Motiur; Alatawi, Yasser; Cheng, Ning; Qian, Jingjing; Plotkina, Annya V; Peissig, Peggy L; Berg, Richard L; Page, David; Hansen, Richard A

2017-09-01

Despite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics. Events reported to the U.S. Food and Drug Administration Adverse Event Reporting System between January 2004 to March 2015 with lamotrigine, carbamazepine, and oxcarbazepine listed as primary or secondary suspect were classified as brand, generic, or AG based on the manufacturer. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting of labeled AEs compared to reporting these events with all other drugs. The Breslow-Day statistic compared RORs across brand, AG, and other generics using a Bonferroni-corrected P<0.01. A total of 27,150 events with lamotrigine, 13,950 events with carbamazepine, and 5077 events with oxcarbazepine were reported, with generics accounting for 27%, 41%, and 32% of reports, respectively. Although RORs for the majority of known AEs were different between brand and generics for all three drugs of interest (Breslow-Day P<0.001), RORs generally were similar for AG and generic comparisons. Generic lamotrigine and carbamazepine were more commonly involved in reports of suicide or suicidal ideation compared with the respective AGs based on a multiple comparison-adjusted P<0.01. Similar AED reporting rates were observed for the AG and generic comparisons for most outcomes and drugs, suggesting that brands and generics have similar reporting rates after accounting for generic perception biases. Disproportional suicide reporting was observed for generics compared with AGs and brand, although this finding needs further study. Copyright © 2017 Elsevier B.V. All rights reserved.

Knowledge, perceptions and use of generic drugs: a cross sectional study

PubMed Central

de Lira, Claudio Andre Barbosa; Oliveira, Jéssica Nathalia Soares; Andrade, Marília dos Santos; Vancini-Campanharo, Cássia Regina; Vancini, Rodrigo Luiz

2014-01-01

Objective To assess the level of knowledge, perceptions and usage profile for generic drugs among laypersons. Methods A cross-sectional study was conducted with 278 volunteers (180 women and 98 men, aged 37.1±15.8 years). A questionnaire was drawn up with questions on their use, perceptions and knowledge of generic drugs. Results Most respondents (99.6%) knew that generic drugs exist, but only 48.6% were able to define them correctly, while 78.8% of the respondents had some information about generics. This information was obtained mainly through television (49.3%). In terms of generic drug characteristics, 79.1% stated that they were confident about their efficacy, 74.8% believed that generic drugs have the same effect as branded medications, 88.8% said that generics were priced lower than branded medications, and 80.2% stated that they bought generic drugs because of price. With regard to drugs prescribed by medical practitioners, 17.6% of the participants said that their doctors never prescribed generics and only 7.5% confirmed that their doctors always prescribed generics. Conclusion For the lay public, the sample in this study has sufficient knowledge of generic drugs in terms of definition, efficacy and cost. Consequently, the volunteers interviewed are very likely to use generics. Furthermore, the results of this study indicate that programs should be implemented in order to boost generic drug prescriptions by medical practitioners. PMID:25295444

The PedsQL Multidimensional Fatigue Scale in pediatric rheumatology: reliability and validity.

PubMed

Varni, James W; Burwinkle, Tasha M; Szer, Ilona S

2004-12-01

. The PedsQL (Pediatric Quality of Life Inventory) is a modular instrument designed to measure health related quality of life (HRQOL) in children and adolescents ages 2-18 years. The recently developed 18-item PedsQL Multidimensional Fatigue Scale was designed to measure fatigue in pediatric patients and comprises the General Fatigue Scale (6 items), Sleep/Rest Fatigue Scale (6 items), and Cognitive Fatigue Scale (6 items). The PedsQL 4.0 Generic Core Scales were developed as the generic core measure to be integrated with the PedsQL Disease-Specific Modules. The PedsQL 3.0 Rheumatology Module was designed to measure pediatric rheumatology-specific HRQOL. Methods. The PedsQL Multidimensional Fatigue Scale, Generic Core Scales, and Rheumatology Module were administered to 163 children and 154 parents (183 families accrued overall) recruited from a pediatric rheumatology clinic. Results. Internal consistency reliability for the PedsQL Multidimensional Fatigue Scale Total Score (a = 0.95 child, 0.95 parent report), General Fatigue Scale (a = 0.93 child, 0.92 parent), Sleep/Rest Fatigue Scale (a = 0.88 child, 0.90 parent), and Cognitive Fatigue Scale (a = 0.93 child, 0.96 parent) were excellent for group and individual comparisons. The validity of the PedsQL Multidimensional Fatigue Scale was confirmed through hypothesized intercorrelations with dimensions of generic and rheumatology-specific HRQOL. The PedsQL Multidimensional Fatigue Scale distinguished between healthy children and children with rheumatic diseases as a group, and was associated with greater disease severity. Children with fibromyalgia manifested greater fatigue than children with other rheumatic diseases. The results confirm the initial reliability and validity of the PedsQL Multidimensional Fatigue Scale in pediatric rheumatology.

What use is generic prescribing?

PubMed Central

Archer, Michael

1985-01-01

The dispensing of generic preparations at four dispensing chemist shops was investigated by means of a questionnaire. Certain generic prescriptions result in the dispensing of proprietary products despite the existence of generic preparations, and the pharmacist may be reimbursed for the cost of the proprietary drug which has been dispensed. Not all generic prescriptions result in the dispensing of cheaper drugs because of the methods of payment to chemists. If doctors write more generic prescriptions there will ultimately be more dispensing of generic products. Even in the case of drugs still under patent, prescribing by generic name should be encouraged. The savings achieved by generic prescribing are to some extent at the cost of the dispensing chemists. The method and scale of payments for dispensing requires urgent review. PMID:4032358

Impact of medicare part D plan features on use of generic drugs.

PubMed

Tang, Yan; Gellad, Walid F; Men, Aiju; Donohue, Julie M

2014-06-01

Little is known about how Medicare Part D plan features influence choice of generic versus brand drugs. To examine the association between Part D plan features and generic medication use. Data from a 2009 random sample of 1.6 million fee-for-service, Part D enrollees aged 65 years and above, who were not dually eligible or receiving low-income subsidies, were used to examine the association between plan features (generic cost-sharing, difference in brand and generic copay, prior authorization, step therapy) and choice of generic antidepressants, antidiabetics, and statins. Logistic regression models accounting for plan-level clustering were adjusted for sociodemographic and health status. Generic cost-sharing ranged from $0 to $9 for antidepressants and statins, and from $0 to $8 for antidiabetics (across 5th-95th percentiles). Brand-generic cost-sharing differences were smallest for statins (5th-95th percentiles: $16-$37) and largest for antidepressants ($16-$64) across plans. Beneficiaries with higher generic cost-sharing had lower generic use [adjusted odds ratio (OR)=0.97, 95% confidence interval (CI), 0.95-0.98 for antidepressants; OR=0.97, 95% CI, 0.96-0.98 for antidiabetics; OR=0.94, 95% CI, 0.92-0.95 for statins]. Larger brand-generic cost-sharing differences and prior authorization were significantly associated with greater generic use in all categories. Plans could increase generic use by 5-12 percentage points by reducing generic cost-sharing from the 75th ($7) to 25th percentiles ($4-$5), increasing brand-generic cost-sharing differences from the 25th ($25-$26) to 75th ($32-$33) percentiles, and using prior authorization and step therapy. Cost-sharing features and utilization management tools were significantly associated with generic use in 3 commonly used medication categories.

Do higher-priced generic medicines enjoy a competitive advantage under reference pricing?

PubMed

Puig-Junoy, Jaume

2012-11-01

In many countries with generic reference pricing, generic producers and distributors compete by means of undisclosed discounts offered to pharmacies in order to reduce acquisition costs and to induce them to dispense their generic to patients in preference over others. The objective of this article is to test the hypothesis that under prevailing reference pricing systems for generic medicines, those medicines sold at a higher consumer price may enjoy a competitive advantage. Real transaction prices for 179 generic medicines acquired by pharmacies in Spain have been used to calculate the discount rate on acquisition versus reimbursed costs to pharmacies. Two empirical hypotheses are tested: the discount rate at which pharmacies acquire generic medicines is higher for those pharmaceutical presentations for which there are more generic competitors; and, the discount rate at which pharmacies acquire generic medicines is higher for those pharmaceutical forms for which the consumer price has declined less in relation to the consumer price of the brand drug before generic entry (higher-priced generic medicines). An average discount rate of 39.3% on acquisition versus reimbursed costs to pharmacies has been observed. The magnitude of the discount positively depends on the number of competitors in the market. The higher the ratio of the consumer price of the generic to that of the brand drug prior to generic entry (i.e. the smaller the price reduction of the generic in relation to the brand drug), the larger the discount rate. Under reference pricing there is intense price competition among generic firms in the form of unusually high discounts to pharmacies on official ex-factory prices reimbursed to pharmacies. However, this effect is highly distorting because it favours those medicines with a higher relative price in relation to the brand price before generic entry.

Questionnaire on the awareness of generic drugs among outpatients and medical staff.

PubMed

Hoshi, S; Kimura, H

2008-06-01

Generic drugs are not as widely used in Japan as they are in the West. The objective of this study was to survey the awareness of generic drugs among outpatients and medical staff and propose methods of promoting the use of generic drugs. Our survey showed that 86.7% of respondents were aware of generic drugs. This is a higher awareness rate than that in a survey of other groups conducted last year. One reason to explain this higher awareness is the recent increase in generic drug advertisements both in newspapers and on television. However, a point of note is that generic drug usage has not increased. Our survey also showed that generic drug awareness was differed widely among age groups, as younger respondents were much more aware of generic drugs than older respondents. Still, about 40% of respondents who were aware of generic drugs did not realize that they were less expensive than name-brand drugs ? including 30% of medical staff. In addition to continuing advertisement of generic drugs in the media, medical doctors and pharmacists should also be encouraged to endorse the use of generic drugs. Furthermore a new system allowing for substitution prescriptions started in April 2008 and consequently pharmacists can now play an important role in promoting the use of generic drugs.

Holographic thermalization with initial long range correlation

DOE PAGES

Lin, Shu

2016-01-19

Here, we studied the evolution of the Wightman correlator in a thermalizing state modeled by AdS 3-Vaidya background. A prescription was given for calculating the Wightman correlator in coordinate space without using any approximation. For equal-time correlator , we obtained an enhancement factor v 2 due to long range correlation present in the initial state. This was missed by previous studies based on geodesic approximation. Moreover, we found that the long range correlation in initial state does not lead to significant modification to thermalization time as compared to known results with generic initial state. We also studied the spatially integratedmore » Wightman correlator and showed evidence on the distinction between long distance and small momentum physics for an out-of-equilibrium state. We also calculated the radiation spectrum of particles weakly coupled to O and found that lower frequency mode approaches thermal spectrum faster than high frequency mode.« less

Perception of Generic Prescription Drugs and Utilization of Generic Drug Discount Programs

PubMed Central

Omojasola, Anthony; Hernandez, Mike; Sansgiry, Sujit; Jones, Lovell

2012-01-01

Objective Our study aimed to assess patient’s perceptions of generic drugs and utilization of generic drug discount programs. Design, Setting and Participants A survey was administered to adult participants at community health centers and community-based organizations in Houston, Texas, USA (n=525). Main Outcome Measures Multivariate logistic regression was used to quantify the strength of association between generic drug perception and utilization of generic drug discount programs. Results Respondents who agreed that “Generic prescription drugs are as effective as brand name prescription drugs,” were 3 times as likely to utilize generic drug discount programs (AOR: 3.0, 95% CI: 1.8–4.8, P<.001). Compared to non-Hispanic Whites, African Americans (OR: 10.2; 95% CI: 1.4–76.4) and Hispanics (OR: 10.3; 95% CI: 1.3–79.4) were 10 times as likely to agree that generic drugs have more side effects than brand name drugs. Conclusion Race/ethnicity had no impact in utilization of generic drug discount programs, despite racial disparities in perception toward generic drugs’ side effects and generic drugs being inferior to brand name drugs. PMID:23140080

The Portuguese generic medicines market: a policy analysis

PubMed Central

Simoens, Steven

2008-01-01

Objectives: This study aims to conduct a descriptive analysis of the policy environment surrounding the generic medicines retail market in Portugal. The policy analysis focuses on supply-side measures (i.e. market access, pricing, reference-pricing and reimbursement of generic medicines) and demand-side measures (i.e. incentives for physicians to prescribe, for pharmacists to dispense and for patients to use generic medicines). Methods: The policy analysis was based on an international literature review. Also, a simulation exercise was carried out to compute potential savings from substituting generic for originator medicines in Portugal using IMS Health data. Results: Portugal has developed a successful generic medicines market by increasing reimbursement of generic medicines (until October 2005), by introducing a reference-pricing system, by encouraging physicians to prescribe by international non-proprietary name (INN), and by allowing generic substitution by pharmacists. However, the development of the generic medicines market has been hindered by the existence of copies, pricing regulation, certain features of the reference-pricing system, weak incentives for physicians to prescribe generic medicines and a financial disincentive for pharmacists to dispense generic medicines. Increased generic substitution would be expected to reduce public expenditure on originator medicines by 45%. Conclusions: The development of the Portuguese generic medicines market has mainly been fuelled by supply-side measures. To support the further expansion of the market, policy makers need to strengthen demand-side measures inciting physicians to prescribe, pharmacists to dispense and patients to use generic medicines. PMID:25152781

A Case Study of Pharmaceutical Pricing in China: Setting the Price for Off-Patent Originators.

PubMed

Hu, Shanlian; Zhang, Yabing; He, Jiangjiang; Du, Lixia; Xu, Mingfei; Xie, Chunyan; Peng, Ying; Wang, Linan

2015-08-01

This article aims to define a value-based approach to pricing and reimbursement for off-patent originators using a multiple criteria decision analysis (MCDA) approach centered on a systematic analysis of current pricing and reimbursement policies in China. A drug price policy review was combined with a quantitative analysis of China's drug purchasing database. Policy preferences were identified through a MCDA performed by interviewing well-known academic experts and industry stakeholders. The study findings indicate that the current Chinese price policy includes cost-based pricing and the establishment of maximum retail prices and premiums for off-patent originators, whereas reference pricing may be adopted in the future. The literature review revealed significant differences in the dissolution profiles between originators and generics; therefore, dissolution profiles need to be improved. Market data analysis showed that the overall price ratio of generics and off-patent originators was around 0.54-0.59 in 2002-2011, with a 40% price difference, on average. Ten differentiating value attributes were identified and MCDA was applied to test the impact of three pricing policy scenarios. With the condition of implementing quality consistency regulations and controls, a reduction in the price gap between high-quality off-patent products (including originator and generics) seemed to be the preferred policy. Patents of many drugs will expire within the next 10 years; thus, pricing will be an issue of importance for off-patent originators and generic alternatives.

Generic superweak chaos induced by Hall effect

NASA Astrophysics Data System (ADS)

Ben-Harush, Moti; Dana, Itzhack

2016-05-01

We introduce and study the "kicked Hall system" (KHS), i.e., charged particles periodically kicked in the presence of uniform magnetic (B ) and electric (E ) fields that are perpendicular to each other and to the kicking direction. We show that for resonant values of B and E and in the weak-chaos regime of sufficiently small nonintegrability parameter κ (the kicking strength), there exists a generic family of periodic kicking potentials for which the Hall effect from B and E significantly suppresses the weak chaos, replacing it by "superweak" chaos (SWC). This means that the system behaves as if the kicking strength were κ2 rather than κ . For E =0 , SWC is known to be a classical fingerprint of quantum antiresonance, but it occurs under much less generic conditions, in particular only for very special kicking potentials. Manifestations of SWC are a decrease in the instability of periodic orbits and a narrowing of the chaotic layers, relative to the ordinary weak-chaos case. Also, for global SWC, taking place on an infinite "stochastic web" in phase space, the chaotic diffusion on the web is much slower than the weak-chaos one. Thus, the Hall effect can be relatively stabilizing for small κ . In some special cases, the effect is shown to cause ballistic motion for almost all parameter values. The generic global SWC on stochastic webs in the KHS appears to be the two-dimensional closest analog to the Arnol'd web in higher dimensional systems.

The theory-practice relationship: reflective skills and theoretical knowledge as key factors in bridging the gap between theory and practice in initial nursing education.

PubMed

Hatlevik, Ida Katrine Riksaasen

2012-04-01

This paper is a report of a correlational study of the relations of nursing students' acquired reflective skills, practical skills and theoretical knowledge on their perception of coherence between theory and practice. Reflection is considered a key factor in bridging the gap between theory and practice. However, it is not evident whether reflective skills are primarily generic in nature or whether they develop from a theoretical knowledge base or the acquisition of practical skills. This study is a secondary analysis of existing data. The data are part of a student survey that was conducted among third-year nursing students in Norway during the spring of 2007. A total of 446 nursing students participated in this study and the response rate was 71%. Structural equation modelling analyses were performed. The results indicate that students' perception of coherence between theory and practice during initial nursing education is directly influenced by reflective skills and theoretical knowledge. The results also reveal that reflective skills have mediating effects and that practical skills have a fully mediated and theoretical knowledge a partially mediated influence on students' perception of coherence. The findings imply that helping students perceive coherence between theory and practice in nursing education, developing students' reflective skills and strengthening the theoretical components of the initial nursing education programme might be beneficial. The results suggest that reflective thinking is not merely a generic skill but rather a skill that depends on the acquisition of relevant professional knowledge and experience. © 2011 Blackwell Publishing Ltd.

Functional and Topological Conditions for Explosive Synchronization Develop in Human Brain Networks with the Onset of Anesthetic-Induced Unconsciousness

PubMed Central

Kim, Minkyung; Mashour, George A.; Moraes, Stefanie-Blain; Vanini, Giancarlo; Tarnal, Vijay; Janke, Ellen; Hudetz, Anthony G.; Lee, Uncheol

2016-01-01

Sleep, anesthesia, and coma share a number of neural features but the recovery profiles are radically different. To understand the mechanisms of reversibility of unconsciousness at the network level, we studied the conditions for gradual and abrupt transitions in conscious and anesthetized states. We hypothesized that the conditions for explosive synchronization (ES) in human brain networks would be present in the anesthetized brain just over the threshold of unconsciousness. To test this hypothesis, functional brain networks were constructed from multi-channel electroencephalogram (EEG) recordings in seven healthy subjects across conscious, unconscious, and recovery states. We analyzed four variables that are involved in facilitating ES in generic, non-biological networks: (1) correlation between node degree and frequency, (2) disassortativity (i.e., the tendency of highly-connected nodes to link with less-connected nodes, or vice versa), (3) frequency difference of coupled nodes, and (4) an inequality relationship between local and global network properties, which is referred to as the suppressive rule. We observed that the four network conditions for ES were satisfied in the unconscious state. Conditions for ES in the human brain suggest a potential mechanism for rapid recovery from the lightly-anesthetized state. This study demonstrates for the first time that the network conditions for ES, formerly shown in generic networks only, are present in empirically-derived functional brain networks. Further investigations with deep anesthesia, sleep, and coma could provide insight into the underlying causes of variability in recovery profiles of these unconscious states. PMID:26834616

Functional and Topological Conditions for Explosive Synchronization Develop in Human Brain Networks with the Onset of Anesthetic-Induced Unconsciousness.

PubMed

Kim, Minkyung; Mashour, George A; Moraes, Stefanie-Blain; Vanini, Giancarlo; Tarnal, Vijay; Janke, Ellen; Hudetz, Anthony G; Lee, Uncheol

2016-01-01

Sleep, anesthesia, and coma share a number of neural features but the recovery profiles are radically different. To understand the mechanisms of reversibility of unconsciousness at the network level, we studied the conditions for gradual and abrupt transitions in conscious and anesthetized states. We hypothesized that the conditions for explosive synchronization (ES) in human brain networks would be present in the anesthetized brain just over the threshold of unconsciousness. To test this hypothesis, functional brain networks were constructed from multi-channel electroencephalogram (EEG) recordings in seven healthy subjects across conscious, unconscious, and recovery states. We analyzed four variables that are involved in facilitating ES in generic, non-biological networks: (1) correlation between node degree and frequency, (2) disassortativity (i.e., the tendency of highly-connected nodes to link with less-connected nodes, or vice versa), (3) frequency difference of coupled nodes, and (4) an inequality relationship between local and global network properties, which is referred to as the suppressive rule. We observed that the four network conditions for ES were satisfied in the unconscious state. Conditions for ES in the human brain suggest a potential mechanism for rapid recovery from the lightly-anesthetized state. This study demonstrates for the first time that the network conditions for ES, formerly shown in generic networks only, are present in empirically-derived functional brain networks. Further investigations with deep anesthesia, sleep, and coma could provide insight into the underlying causes of variability in recovery profiles of these unconscious states.

Automated analysis in generic groups

NASA Astrophysics Data System (ADS)

Fagerholm, Edvard

This thesis studies automated methods for analyzing hardness assumptions in generic group models, following ideas of symbolic cryptography. We define a broad class of generic and symbolic group models for different settings---symmetric or asymmetric (leveled) k-linear groups --- and prove ''computational soundness'' theorems for the symbolic models. Based on this result, we formulate a master theorem that relates the hardness of an assumption to solving problems in polynomial algebra. We systematically analyze these problems identifying different classes of assumptions and obtain decidability and undecidability results. Then, we develop automated procedures for verifying the conditions of our master theorems, and thus the validity of hardness assumptions in generic group models. The concrete outcome is an automated tool, the Generic Group Analyzer, which takes as input the statement of an assumption, and outputs either a proof of its generic hardness or shows an algebraic attack against the assumption. Structure-preserving signatures are signature schemes defined over bilinear groups in which messages, public keys and signatures are group elements, and the verification algorithm consists of evaluating ''pairing-product equations''. Recent work on structure-preserving signatures studies optimality of these schemes in terms of the number of group elements needed in the verification key and the signature, and the number of pairing-product equations in the verification algorithm. While the size of keys and signatures is crucial for many applications, another aspect of performance is the time it takes to verify a signature. The most expensive operation during verification is the computation of pairings. However, the concrete number of pairings is not captured by the number of pairing-product equations considered in earlier work. We consider the question of what is the minimal number of pairing computations needed to verify structure-preserving signatures. We build an automated tool to search for structure-preserving signatures matching a template. Through exhaustive search we conjecture lower bounds for the number of pairings required in the Type~II setting and prove our conjecture to be true. Finally, our tool exhibits examples of structure-preserving signatures matching the lower bounds, which proves tightness of our bounds, as well as improves on previously known structure-preserving signature schemes.

Affordability of adult HIV/AIDS treatment in developing countries: modelling price determinants for a better insight of the market functioning

PubMed Central

Sagaon-Teyssier, Luis; Singh, Sauman; Dongmo-Nguimfack, Boniface; Moatti, Jean-Paul

2016-01-01

Introduction This study aims to provide a landscape of the global antiretroviral (ARV) market by analyzing the transactional data on donor-funded ARV procurement between 2003 and 2015, and the ARV price determinants. Design The data were obtained from the Global Price Reporting Mechanism (GPRM) managed by the AIDS Medicines and Diagnostics Service of the WHO, and it consists of information that covers approximately 80% of the total donor-funded adult ARV transactions procurement. Methods ExWorks prices and procured quantities were standardized according to the guidelines in terms of yearly doses. Descriptive statistics on quantities and prices show the main trends of the ARV market. Ordinary least squares estimation was carried out for the whole sample, then stratified according to the type of supplier (originator and generic) and controlled for time and geographical fixed-effects. Given that analyses were carried out on a public dataset on ARV transactional prices from the GPRM, ethics are respected and consent was not necessary. Results Originator medicines are on average the least expensive in the sub-Saharan Africa region, where at the same time, generic medicines are on average the most expensive. By contrast, originator medicines are the most expensive in Europe and Central Asia, and generic medicines are the least expensive. In fact, the data suggest mixed strategies by ARV suppliers to exploit opportunities for profit maximization and to adapt to the specific conditions of market competition in each region. Our results also suggest that the expiration of patents is not sufficient to boost additional developments in generic competition (at least in the ARV market) and that formal or informal agreements between generic firms may de facto slow down or even reverse long-term trends towards price decreases. Conclusions Our findings provide an improved understanding of the ARV market that can help countries strengthen policy measures to increase their bargaining power in price negotiations and the use of TRIPS flexibilities, with a special emphasis on negotiations with generic manufacturers. PMID:27765142

Hierarchical Architectural Considerations in Econometric Modeling of Manufacturing Systems

DTIC Science & Technology

1981-06-01

behavioral factors must also be considered. A proposed economic model, to be aligned with ICAM program intentions, should be generic and have the... relevant to the effort and to identify contractors, if any, involved in economic model development. Due to the nature of involvement of other con...tractors with the ICAM program office, information which was thought relevant to the initiation of the current effort was in a lag-time and was

Measuring performance in off-patent drug markets: a methodological framework and empirical evidence from twelve EU Member States.

PubMed

Kanavos, Panos

2014-11-01

This paper develops a methodological framework to help evaluate the performance of generic pharmaceutical policies post-patent expiry or after loss of exclusivity in non-tendering settings, comprising five indicators (generic availability, time delay to and speed of generic entry, number of generic competitors, price developments, and generic volume share evolution) and proposes a series of metrics to evaluate performance. The paper subsequently tests this framework across twelve EU Member States (MS) by using IMS data on 101 patent expired molecules over the 1998-2010 period. Results indicate that significant variation exists in generic market entry, price competition and generic penetration across the study countries. Size of a geographical market is not a predictor of generic market entry intensity or price decline. Regardless of geographic or product market size, many off patent molecules lack generic competitors two years after loss of exclusivity. The ranges in each of the five proposed indicators suggest, first, that there are numerous factors--including institutional ones--contributing to the success of generic entry, price decline and market penetration and, second, MS should seek a combination of supply and demand-side policies in order to maximise cost-savings from generics. Overall, there seems to be considerable potential for faster generic entry, uptake and greater generic competition, particularly for molecules at the lower end of the market. Copyright © 2014. Published by Elsevier Ireland Ltd.

Predictors of generic substitution: The role of psychological, sociodemographic, and contextual factors.

PubMed

Drozdowska, Aleksandra; Hermanowski, Tomasz

2016-01-01

Escalating pharmaceutical costs have become a global challenge for both governments and patients. Generic substitution is one way of decreasing these costs. The aim of this study was to investigate factors associated with patients' choice between generic drugs and innovator drugs. The survey was conducted in June 2013, 1000 people from across Poland were chosen as a representative population sample. The outcome (a preference for generics/a preference for innovator pharmaceuticals/no preference) was modeled by multinomial logistic regression, adjusted for several variables describing patients' sensitivity to selected generic features (price, brand, and country of origin), to third-party opinions about generics (information on generics in the mass media, opinions of health professionals (i.e. physicians, pharmacists), relatives/friends), as well as patients' personal experiences and income per household. The results supported the predictive capacity of most independent variables (except for patient sensitivity to the country of origin and to the information on generics in the mass media), denoting patients' preferences toward generic substitution. Patient sensitivity to recommendations by physicians, generic brand, and household income were the strongest predictors of the choice between generic and innovator pharmaceuticals (P < 0.001). The probability of choosing generics over innovator drugs was significantly higher among respondents with the lowest income levels, in those who were indifferent to generic brand or their physician's opinion, as well as in respondents who were sensitive to recommendations by pharmacists or attached a greater value to a past experience with generics (their own experience or that of relatives/friends). In consideration of the foregoing, awareness-raising campaigns may be recommended, supported by a variety of systemic solutions and tools to encourage generic substitution. Copyright © 2016 Elsevier Inc. All rights reserved.

40 CFR Appendix B to Part 72 - Methodology for Conversion of Emissions Limits

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Methodology for Conversion of... Conversion of Emissions Limits For the purposes of the Acid Rain Program, all emissions limits must be... conditions. Generic conversions for these limits are based on the assumed average energy contents listed in...

40 CFR Appendix B to Part 72 - Methodology for Conversion of Emissions Limits

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Methodology for Conversion of... Conversion of Emissions Limits For the purposes of the Acid Rain Program, all emissions limits must be... conditions. Generic conversions for these limits are based on the assumed average energy contents listed in...

Universal absolute quantification of biomolecules using element mass spectrometry and generic standards.

PubMed

Calderón-Celis, Francisco; Sanz-Medel, Alfredo; Encinar, Jorge Ruiz

2018-01-23

We present a novel and highly sensitive ICP-MS approach for absolute quantification of all important target biomolecule containing P, S, Se, As, Br, and/or I (e.g., proteins and phosphoproteins, metabolites, pesticides, drugs), under the same simple instrumental conditions and without requiring any specific and/or isotopically enriched standard.

[Generic drugs: good or bad? Physician's knowledge of generic drugs and prescribing habits].

PubMed

García, A J; Martos, F; Leiva, F; Sánchez de la Cuesta, F

2003-01-01

In this article we analyze the responses of 1220 Spanish physicians who participated in a survery about generic drugs. A previously validated questionnaire was sent to physicians through the Spanish Medical Councils of the different provinces. Four items were analyzed: what doctors know about generic drugs (knowledge); physicians' prescribing habits concerning these drugs (attitude and professional competence); how prescription of generic drugs effects pharmaceutical costs amd, finally, what doctors believe a generic drug should be. The influence of physician-related variables (age, type of contract, specialty, workload, etc.) on prescribing of generic drugs was also analyzed. In view of the results, we believe that to rationalize expenditure through and appropriate policy on generic drugs Spanish health authorities should offer more and better training and information (clear and independent) about what generic drugs are.

Effectiveness and safety of generic fixed-dose combination of tenofovir/emtricitabine/efavirenz in HIV-1-infected patients in Western India.

PubMed

Pujari, Sanjay; Dravid, Ameet; Gupte, Nikhil; Joshi, Kedar; Bele, Vivek

2008-01-01

To assess effectiveness and safety of a generic fixed-dose combination of tenofovir (TDF)/emtricitabine (FTC)/efavirenz (EFV) among HIV-1-infected patients in Western India. Antiretroviral (ARV)-naive and experienced (thymidine analog nucleoside reverse transcriptase inhibitor [tNRTI] replaced by TDF) patients were started on a regimen of 1 TDF/FTC/EFV pill once a day. They were followed clinically on a periodic basis, and viral loads and CD4 counts were measured at 6 and 12 months. Creatinine clearance was calculated at baseline and at 6 months and/or as clinically indicated. Effectiveness was defined as not having to discontinue the regimen due to failure or toxicity. One hundred forty-one patients who started TDF/FTC/EFV before 1 June 2007 were eligible. Of these, 130 (92.2%) and 44 (31.2%) had 6- and 12-months follow-up, respectively. Thirty-five percent of the patients were ARV-naive. Eleven patients discontinued treatment (4 for virologic failure, 1 for grade 3-4 central nervous system disturbances, 4 for grade 3-4 renal toxicity, and 2 for cost). Ninety-six percent of patients were virologically suppressed at 6 months. Frequency of TDF-associated grade 3-4 renal toxicity was 2.8%; however, 3 of these patients had comorbid conditions associated with renal dysfunction. A fixed-dose combination of generic TDF/FTC/EFV is effective in ARV-naive and experienced patients. Although frequency of severe renal toxicity was higher than has been reported in the literature, it was safe in patients with no comorbid renal conditions.

Effectiveness and Safety of Generic Fixed-Dose Combination of Tenofovir/Emtricitabine/Efavirenz in HIV-1-Infected Patients in Western India.

PubMed

Pujari, Sanjay; Dravid, Ameet; Gupte, Nikhil; Joshix, Kedar; Bele, Vivek

2008-08-20

To assess effectiveness and safety of a generic fixed-dose combination of tenofovir (TDF)/emtricitabine (FTC)/efavirenz (EFV) among HIV-1-infected patients in Western India. Antiretroviral (ARV)-naive and experienced (thymidine analog nucleoside reverse transcriptase inhibitor [tNRTI] replaced by TDF) patients were started on a regimen of 1 TDF/FTC/EFV pill once a day. They were followed clinically on a periodic basis, and viral loads and CD4 counts were measured at 6 and 12 months. Creatinine clearance was calculated at baseline and at 6 months and/or as clinically indicated. Effectiveness was defined as not having to discontinue the regimen due to failure or toxicity. One hundred forty-one patients who started TDF/FTC/EFV before 1 June 2007 were eligible. Of these, 130 (92.2%) and 44 (31.2%) had 6- and 12-months follow-up, respectively. Thirty-five percent of the patients were ARV-naive. Eleven patients discontinued treatment (4 for virologic failure, 1 for grade 3-4 central nervous system disturbances, 4 for grade 3-4 renal toxicity, and 2 for cost). Ninety-six percent of patients were virologically suppressed at 6 months. Frequency of TDF-associated grade 3-4 renal toxicity was 2.8%; however, 3 of these patients had comorbid conditions associated with renal dysfunction. A fixed-dose combination of generic TDF/FTC/EFV is effective in ARV-naive and experienced patients. Although frequency of severe renal toxicity was higher than has been reported in the literature, it was safe in patients with no comorbid renal conditions.

Network Mechanisms Generating Abnormal and Normal Hippocampal High-Frequency Oscillations: A Computational Analysis1,2,3

PubMed Central

Catoni, Nicholas

2015-01-01

Abstract High-frequency oscillations (HFOs) are an intriguing potential biomarker for epilepsy, typically categorized according to peak frequency as either ripples (100–250 Hz) or fast ripples (>250 Hz). In the hippocampus, fast ripples were originally thought to be more specific to epileptic tissue, but it is still very difficult to distinguish which HFOs are caused by normal versus pathological brain activity. In this study, we use a computational model of hippocampus to investigate possible network mechanisms underpinning normal ripples, pathological ripples, and fast ripples. Our results unify several prior findings regarding HFO mechanisms, and also make several new predictions regarding abnormal HFOs. We show that HFOs are generic, emergent phenomena whose characteristics reflect a wide range of connectivity and network input. Although produced by different mechanisms, both normal and abnormal HFOs generate similar ripple frequencies, underscoring that peak frequency is unable to distinguish the two. Abnormal ripples are generic phenomena that arise when input to pyramidal cells overcomes network inhibition, resulting in high-frequency, uncoordinated firing. In addition, fast ripples transiently and sporadically arise from the precise conditions that produce abnormal ripples. Lastly, we show that such abnormal conditions do not require any specific network structure to produce coherent HFOs, as even completely asynchronous activity is capable of producing abnormal ripples and fast ripples in this manner. These results provide a generic, network-based explanation for the link between pathological ripples and fast ripples, and a unifying description for the entire spectrum from normal ripples to pathological fast ripples. PMID:26146658

On-board autonomous attitude maneuver planning for planetary spacecraft using genetic algorithms

NASA Technical Reports Server (NTRS)

Kornfeld, Richard P.

2003-01-01

A key enabling technology that leads to greater spacecraft autonomy is the capability to autonomously and optimally slew the spacecraft from and to different attitudes while operating under a number of celestial and dynamic constraints. The task of finding an attitude trajectory that meets all the constraints is a formidable one, in particular for orbiting or fly-by spacecraft where the constraints and initial and final conditions are of time-varying nature. This paper presents an approach for attitude path planning that makes full use of a priori constraint knowledge and is computationally tractable enough to be executed on-board a spacecraft. The approach is based on incorporating the constraints into a cost function and using a Genetic Algorithm to iteratively search for and optimize the solution. This results in a directed random search that explores a large part of the solution space while maintaining the knowledge of good solutions from iteration to iteration. A solution obtained this way may be used 'as is' or as an initial solution to initialize additional deterministic optimization algorithms. A number of example simulations are presented including the case examples of a generic Europa Orbiter spacecraft in cruise as well as in orbit around Europa. The search times are typically on the order of minutes, thus demonstrating the viability of the presented approach. The results are applicable to all future deep space missions where greater spacecraft autonomy is required. In addition, onboard autonomous attitude planning greatly facilitates navigation and science observation planning, benefiting thus all missions to planet Earth as well.

Unruh effect for general trajectories

NASA Astrophysics Data System (ADS)

Obadia, N.; Milgrom, M.

2007-03-01

We consider two-level detectors coupled to a scalar field and moving on arbitrary trajectories in Minkowski space-time. We first derive a generic expression for the response function using a (novel) regularization procedure based on the Feynman prescription that is explicitly causal, and we compare it to other expressions used in the literature. We then use this expression to study, analytically and numerically, the time dependence of the response function in various nonstationarity situations. We show that, generically, the response function decreases like a power in the detector’s level spacing, E, for high E. It is only for stationary worldlines that the response function decays faster than any power law, in keeping with the known exponential behavior for some stationary cases. Under some conditions the (time-dependent) response function for a nonstationary worldline is well approximated by the value of the response function for a stationary worldline having the same instantaneous acceleration, torsion, and hypertorsion. While we cannot offer general conditions for this to apply, we discuss special cases; in particular, the low-energy limit for linear space trajectories.

Current utilization, interpretation, and recommendations: the musculoskeletal function assessments (MFA/SMFA).

PubMed

Barei, David P; Agel, Julie; Swiontkowski, Marc F

2007-01-01

The development of patient-oriented health status measurements has resulted in the emergence of several generic condition-specific and anatomic-specific instruments. These instruments are generally designed to measure the function of the individual as a whole from the individual's own point of view. They are not intended to replace traditional physician-oriented clinical outcome measures, such as complication rates, ranges of motion, or time to fracture union; instead, they are an attempt to measure the results of a treatment or condition from the patient's perspective. Over the past decade, the Musculoskeletal Function Assessment (MFA) instrument has been developed and used as one of the primary generic musculoskeletal functional assessment tools, in part because of its validity, reliability, and responsiveness. Despite the numerous publications reporting the MFA/SMFA, we are unaware of any publications that have used those results to subsequently affect patient care. We hope that this special interest article highlights the current underutilization of the available data and encourages the orthopedic community to maximize the clinical and research potential of the MFA/SMFA (Short Musculoskeletal Function Assessment).

76 FR 17182 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-28

... Activities: Proposed Collection; Comment Request; Generic Clearance for the Collection of Qualitative... Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service...: Title: Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery. Abstract...

Generic Example Proving Criteria for All

ERIC Educational Resources Information Center

Yopp, David; Ely, Rob; Johnson­-Leung, Jennifer

2015-01-01

We review literature that discusses generic example proving and highlight ambiguities that pervade our research community's discourse about generic example arguments. We distinguish between pedagogical advice for choosing good examples that can serve as generic examples when teaching and advice for developing generic example arguments. We provide…

Estimating the gravitational-wave content of initial-data sets for numerical relativity using the Beetle--Burko scalar

NASA Astrophysics Data System (ADS)

Burko, Lior M.

2006-04-01

The Beetle--Burko radiation scalar is a gauge independent, tetrad independent, and background independent quantity that depends only on the radiative degrees of freedom where the notion of radiation is incontrovertible, and can be computed from spatial data as is typical in numerical relativity simulations even for strongly dynamical spacetimes. We show that the Beetle--Burko radiation scalar can be used for estimating the graviational-wave content of initial-data sets in numerical relativity, and can thus be useful for the construction of physically meaningful ones, and the identification of ``junk'' data on the intial value surface. We apply this method for the case of a momentarily stationary black hole binary, and demonstrate how the Beetle-- Burko scalar distinguishes between Misner and Brill--Lindquist initial data. The method, however, is robust, and is applicable to generic initial data sets. In addition to initial data sets, the Beetle--Burko radiation scalar is equally applicable also for evolution data.

Significance of groundwater flux on contaminant concentration and mass discharge in the nonaqueous phase liquid (NAPL) contaminated zone.

PubMed

Zhu, Jianting; Sun, Dongmin

2016-09-01

Groundwater flowing through residual nonaqueous phase liquid (NAPL) source zone will cause NAPL dissolution and generate large contaminant plume. The use of contaminant mass discharge (CMD) measurements in addition to NAPL aqueous phase concentration to characterize site conditions and assess remediation performance is becoming popular. In this study, we developed new and generic numerical models to investigate the significance of groundwater flux temporal variations on the NAPL source dynamics. The developed models can accommodate any temporal variations of groundwater flux in the source zone. We examined the various features of groundwater flux using a few selected functional forms of linear increase/decrease, gradual smooth increase/decrease, and periodic fluctuations with a general trend. Groundwater flux temporal variations have more pronounced effects on the contaminant mass discharge dynamics than the aqueous concentration. If the groundwater flux initially increases, then the reduction in contaminant mass discharge (CMDR) vs. NAPL mass reduction (MR) relationship is mainly downward concave. If the groundwater flux initially decreases, then CMDR vs. MR relationship is mainly upward convex. If the groundwater flux variations are periodic, the CMDR vs. MR relationship tends to also have periodic variations ranging from upward convex to downward concave. Eventually, however, the CMDR vs. MR relationship approaches 1:1 when majority of the NAPL mass becomes depleted. Copyright © 2016 Elsevier B.V. All rights reserved.

Life prediction and constitutive models for engine hot section anisotropic materials program

NASA Technical Reports Server (NTRS)

Nissley, D. M.; Meyer, T. G.

1992-01-01

This report presents the results from a 35 month period of a program designed to develop generic constitutive and life prediction approaches and models for nickel-based single crystal gas turbine airfoils. The program is composed of a base program and an optional program. The base program addresses the high temperature coated single crystal regime above the airfoil root platform. The optional program investigates the low temperature uncoated single crystal regime below the airfoil root platform including the notched conditions of the airfoil attachment. Both base and option programs involve experimental and analytical efforts. Results from uniaxial constitutive and fatigue life experiments of coated and uncoated PWA 1480 single crystal material form the basis for the analytical modeling effort. Four single crystal primary orientations were used in the experiments: (001), (011), (111), and (213). Specific secondary orientations were also selected for the notched experiments in the optional program. Constitutive models for an overlay coating and PWA 1480 single crystal material were developed based on isothermal hysteresis loop data and verified using thermomechanical (TMF) hysteresis loop data. A fatigue life approach and life models were selected for TMF crack initiation of coated PWA 1480. An initial life model used to correlate smooth and notched fatigue data obtained in the option program shows promise. Computer software incorporating the overlay coating and PWA 1480 constitutive models was developed.

Perspectives of physicians practicing in low and middle income countries towards generic medicines: a narrative review.

PubMed

Hassali, Mohamed Azmi; Wong, Zhi Yen; Alrasheedy, Alian A; Saleem, Fahad; Mohamad Yahaya, Abdul Haniff; Aljadhey, Hisham

2014-09-01

This review was conducted to document published literature related to physicians' knowledge, attitudes, and perceptions of generic medicines in low- and middle-income countries (LMICs) and to compare the findings with high-income countries. A systematic search of articles published in peer-reviewed journals from January 2001 to February 2013 was performed. The search comprised nine electronic databases. The search strategy involved using Boolean operators for combinations of the following terms: generic medicines, generic medications, generic drugs, generic, generic substitution, generic prescribing, international non-proprietary, prescribers, doctors, general practitioners, physicians, and specialists. Sixteen articles were included in this review. The majority (n=11) were from high income countries and five from LMICs. The main difference between high income countries and LMICs is that physicians from high income countries generally have positive views whereas those from LMICs tend to have mixed views regarding generic medicines. Few similarities were identified among different country income groups namely low level of physicians' knowledge of the basis of bioequivalence testing, cost of generic medicines as an encouraging factor for generic medicine prescribing, physicians' concerns towards safety and quality of generic medicines and effect of pharmaceutical sales representative on generic medicine prescribing. The present literature review revealed that physicians from LMICs tend to have mixed views regarding generic medicines. This may be due to differences in the health care system and pharmaceutical funding system, medicine policies, the level of educational interventions, and drug information sources in countries of different income levels. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Assessing bioequivalence of generic antiepilepsy drugs.

PubMed

Krauss, Gregory L; Caffo, Brian; Chang, Yi-Ting; Hendrix, Craig W; Chuang, Kelly

2011-08-01

Patients with epilepsy are often concerned that switching between brand-name and generic formulations of antiepilepsy drugs (AEDs) may cause clinically significant changes in plasma drug concentrations. We assessed bioequivalence (BE) studies for approved generic AEDs to evaluate US Food and Drug Administration claims that: (1) generic AEDs are accurate copies of reference formulations; (2) delivery of reference formulations may be as variable as generic AEDs and so provide no increased benefit; and (3) switches between generic AED formulations are safe and effective. We determined differences in 90% confidence interval limits for total drug exposure (AUC(0-t) ) and peak concentration (Cmax) ratios of generic and reference formulations during fasting and fed BE studies. We simulated BE between generic formulations after adjusting for reference values. AUC(0-t) values of approved reference and generic formulations differed by <15% in 99% of BE studies; Cmax differed by <15% in 89% of studies. Food affected variability of Cmax but not AUC(0-t) . Intersubject variability in Cmax and AUC(0-t) was small and similar for reference and generic products. In simulated switches between 595 pairs of generic AED formulations, estimated AUC(0-t) differed by >15% for 17% of pairs; estimated Cmax differed by >15% for 39%. AEDs with low bioavailability and solubility (eg, oxcarbazepine) had the greatest variability in BE. Most generic AED products provide total drug delivery (AUC) similar to reference products; differences in peak concentrations between formulations are more common. Switches between generic AED products may cause greater changes in plasma drug concentrations than generic substitutions of reference products. Copyright © 2011 American Neurological Association.

The risks and costs of multiple-generic substitution of topiramate.

PubMed

Duh, M S; Paradis, P E; Latrémouille-Viau, D; Greenberg, P E; Lee, S P; Durkin, M B; Wan, G J; Rupnow, M F T; LeLorier, J

2009-06-16

To investigate clinical and economic consequences following generic substitution of one vs multiple generics of topiramate (Topamax; Ortho-McNeil Neurologics, Titusville, NJ). Medical and pharmacy claims data of Régie de l'Assurance-Maladie du Québec from January 2006 to October 2007 were used. Patients with epilepsy treated with topiramate were selected. An open-cohort design was used to classify the observation period into periods of brand, single-generic, and multiple-generic use. One-year generic-switch and switchback-to-brand rates were estimated using Kaplan-Meier methodology. Medical resource utilization and costs were compared among the three periods using multivariate regression analysis. In total, 948 patients were observed during 1,105 person-years of brand use, 233 person-years of single-generic use, and 92 person-years of multiple-generic use. A total of 23% of generic users received at least two different generic versions. Compared to brand use, multiple-generic use was associated with higher utilization of other prescription drugs (incidence rate ratio [IRR] = 1.27, 95% confidence interval [CI] = 1.24-1.31), higher hospitalization rates (0.48 vs 0.83 visit/person-year, IRR = 1.65, 95% CI = 1.28-2.13), and longer hospital stays (2.6 vs 3.9 days/person-year, IRR = 1.43, 95% CI = 1.27-1.60), but the effect was less pronounced in single-generic use (hospitalization: IRR = 1.08, 95% CI = 0.88-1.34, length of stay: IRR = 1.12, 95% CI = 1.03-1.23). The risk of head injury or fracture was nearly three times higher (hazard ratio = 2.84, 95% CI = 1.24-6.48) following a generic-to-generic switch compared to brand use. The total annualized health care cost per patient was higher in the multiple-generic than brand periods by C$1,716 (cost ratio = 1.21, p = 0.0420). Multiple-generic substitution of topiramate was significantly associated with negative outcomes, such as hospitalizations and injuries, and increased health care costs.

Alternative Test Methods for Electronic Parts

NASA Technical Reports Server (NTRS)

Plante, Jeannette

2004-01-01

It is common practice within NASA to test electronic parts at the manufacturing lot level to demonstrate, statistically, that parts from the lot tested will not fail in service using generic application conditions. The test methods and the generic application conditions used have been developed over the years through cooperation between NASA, DoD, and industry in order to establish a common set of standard practices. These common practices, found in MIL-STD-883, MIL-STD-750, military part specifications, EEE-INST-002, and other guidelines are preferred because they are considered to be effective and repeatable and their results are usually straightforward to interpret. These practices can sometimes be unavailable to some NASA projects due to special application conditions that must be addressed, such as schedule constraints, cost constraints, logistical constraints, or advances in the technology that make the historical standards an inappropriate choice for establishing part performance and reliability. Alternate methods have begun to emerge and to be used by NASA programs to test parts individually or as part of a system, especially when standard lot tests cannot be applied. Four alternate screening methods will be discussed in this paper: Highly accelerated life test (HALT), forward voltage drop tests for evaluating wire-bond integrity, burn-in options during or after highly accelerated stress test (HAST), and board-level qualification.

Advanced life support control/monitor instrumentation concepts for flight application

NASA Technical Reports Server (NTRS)

Heppner, D. B.; Dahlhausen, M. J.; Fell, R. B.

1986-01-01

Development of regenerative Environmental Control/Life Support Systems requires instrumentation characteristics which evolve with successive development phases. As the development phase moves toward flight hardware, the system availability becomes an important design aspect which requires high reliability and maintainability. This program was directed toward instrumentation designs which incorporate features compatible with anticipated flight requirements. The first task consisted of the design, fabrication and test of a Performance Diagnostic Unit. In interfacing with a subsystem's instrumentation, the Performance Diagnostic Unit is capable of determining faulty operation and components within a subsystem, perform on-line diagnostics of what maintenance is needed and accept historical status on subsystem performance as such information is retained in the memory of a subsystem's computerized controller. The second focus was development and demonstration of analog signal conditioning concepts which reduce the weight, power, volume, cost and maintenance and improve the reliability of this key assembly of advanced life support instrumentation. The approach was to develop a generic set of signal conditioning elements or cards which can be configured to fit various subsystems. Four generic sensor signal conditioning cards were identified as being required to handle more than 90 percent of the sensors encountered in life support systems. Under company funding, these were detail designed, built and successfully tested.

76 FR 39893 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-07

...; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery... (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery.... SUPPLEMENTARY INFORMATION: Title: Generic Clearance for the Collection of Qualitative Feedback on Agency Service...

76 FR 19359 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-07

... Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery AGENCY... Information Collection Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback...: Title: Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery. Abstract...

The Full Kostant-Toda Hierarchy on the Positive Flag Variety

NASA Astrophysics Data System (ADS)

Kodama, Yuji; Williams, Lauren

2015-04-01

We study some geometric and combinatorial aspects of the solution to the full Kostant-Toda (f-KT) hierarchy, when the initial data is given by an arbitrary point on the totally non-negative (tnn) flag variety of . The f-KT flows on the tnn flag variety are complete, and we show that their asymptotics are completely determined by the cell decomposition of the tnn flag variety given by Rietsch (Total positivity and real flag varieties. Ph.D. Thesis, Massachusetts Institute of Technology, Cambridge, 1998). Our results represent the first results on the asymptotics of the f-KT hierarchy (and even the f-KT lattice); moreover, our results are not confined to the generic flow, but cover non-generic flows as well. We define the f-KT flow on the weight space via the moment map, and show that the closure of each f-KT flow forms an interesting convex polytope which we call a Bruhat interval polytope. In particular, the Bruhat interval polytope for the generic flow is the permutohedron of the symmetric group . We also prove analogous results for the full symmetric Toda hierarchy, by mapping our f-KT solutions to those of the full symmetric Toda hierarchy. In the appendix we show that Bruhat interval polytopes are generalized permutohedra, in the sense of Postnikov (Int. Math. Res. Not. IMRN (6):1026-1106, 2009).

Computational study of generic hypersonic vehicle flow fields

NASA Technical Reports Server (NTRS)

Narayan, Johnny R.

1994-01-01

The geometric data of the generic hypersonic vehicle configuration included body definitions and preliminary grids for the forebody (nose cone excluded), midsection (propulsion system excluded), and afterbody sections. This data was to be augmented by the nose section geometry (blunt conical section mated with the noncircular cross section of the forebody initial plane) along with a grid and a detailed supersonic combustion ramjet (scramjet) geometry (inlet and combustor) which should be merged with the nozzle portion of the afterbody geometry. The solutions were to be obtained by using a Navier-Stokes (NS) code such as TUFF for the nose portion, a parabolized Navier-Stokes (PNS) solver such as the UPS and STUFF codes for the forebody, a NS solver with finite rate hydrogen-air chemistry capability such as TUFF and SPARK for the scramjet and a suitable solver (NS or PNS) for the afterbody and external nozzle flows. The numerical simulation of the hypersonic propulsion system for the generic hypersonic vehicle is the major focus of this entire work. Supersonic combustion ramjet is such a propulsion system, hence the main thrust of the present task has been to establish a solution procedure for the scramjet flow. The scramjet flow is compressible, turbulent, and reacting. The fuel used is hydrogen and the combustion process proceeds at a finite rate. As a result, the solution procedure must be capable of addressing such flows.