Network meta-analysis using R: a review of currently available automated packages.

PubMed

Neupane, Binod; Richer, Danielle; Bonner, Ashley Joel; Kibret, Taddele; Beyene, Joseph

2014-01-01

Network meta-analysis (NMA)--a statistical technique that allows comparison of multiple treatments in the same meta-analysis simultaneously--has become increasingly popular in the medical literature in recent years. The statistical methodology underpinning this technique and software tools for implementing the methods are evolving. Both commercial and freely available statistical software packages have been developed to facilitate the statistical computations using NMA with varying degrees of functionality and ease of use. This paper aims to introduce the reader to three R packages, namely, gemtc, pcnetmeta, and netmeta, which are freely available software tools implemented in R. Each automates the process of performing NMA so that users can perform the analysis with minimal computational effort. We present, compare and contrast the availability and functionality of different important features of NMA in these three packages so that clinical investigators and researchers can determine which R packages to implement depending on their analysis needs. Four summary tables detailing (i) data input and network plotting, (ii) modeling options, (iii) assumption checking and diagnostic testing, and (iv) inference and reporting tools, are provided, along with an analysis of a previously published dataset to illustrate the outputs available from each package. We demonstrate that each of the three packages provides a useful set of tools, and combined provide users with nearly all functionality that might be desired when conducting a NMA.

Diagnostics for generalized linear hierarchical models in network meta-analysis.

PubMed

Zhao, Hong; Hodges, James S; Carlin, Bradley P

2017-09-01

Network meta-analysis (NMA) combines direct and indirect evidence comparing more than 2 treatments. Inconsistency arises when these 2 information sources differ. Previous work focuses on inconsistency detection, but little has been done on how to proceed after identifying inconsistency. The key issue is whether inconsistency changes an NMA's substantive conclusions. In this paper, we examine such discrepancies from a diagnostic point of view. Our methods seek to detect influential and outlying observations in NMA at a trial-by-arm level. These observations may have a large effect on the parameter estimates in NMA, or they may deviate markedly from other observations. We develop formal diagnostics for a Bayesian hierarchical model to check the effect of deleting any observation. Diagnostics are specified for generalized linear hierarchical NMA models and investigated for both published and simulated datasets. Results from our example dataset using either contrast- or arm-based models and from the simulated datasets indicate that the sources of inconsistency in NMA tend not to be influential, though results from the example dataset suggest that they are likely to be outliers. This mimics a familiar result from linear model theory, in which outliers with low leverage are not influential. Future extensions include incorporating baseline covariates and individual-level patient data. Copyright © 2017 John Wiley & Sons, Ltd.

Theory and Normal Mode Analysis of Change in Protein Vibrational Dynamics on Ligand Binding

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

Mortisugu, Kei; Njunda, Brigitte; Smith, Jeremy C

2009-12-01

The change of protein vibrations on ligand binding is of functional and thermodynamic importance. Here, this process is characterized using a simple analytical 'ball-and-spring' model and all-atom normal-mode analysis (NMA) of the binding of the cancer drug, methotrexate (MTX) to its target, dihydrofolate reductase (DHFR). The analytical model predicts that the coupling between protein vibrations and ligand external motion generates entropy-rich, low-frequency vibrations in the complex. This is consistent with the atomistic NMA which reveals vibrational softening in forming the DHFR-MTX complex, a result also in qualitative agreement with neutron-scattering experiments. Energy minimization of the atomistic bound-state (B) structure whilemore » gradually decreasing the ligand interaction to zero allows the generation of a hypothetical 'intermediate' (I) state, without the ligand force field but with a structure similar to that of B. In going from I to B, it is found that the vibrational entropies of both the protein and MTX decrease while the complex structure becomes enthalpically stabilized. However, the relatively weak DHFR:MTX interaction energy results in the net entropy gain arising from coupling between the protein and MTX external motion being larger than the loss of vibrational entropy on complex formation. This, together with the I structure being more flexible than the unbound structure, results in the observed vibrational softening on ligand binding.« less

Continuously updated network meta-analysis and statistical monitoring for timely decision-making

PubMed Central

Nikolakopoulou, Adriani; Mavridis, Dimitris; Egger, Matthias; Salanti, Georgia

2016-01-01

Pairwise and network meta-analysis (NMA) are traditionally used retrospectively to assess existing evidence. However, the current evidence often undergoes several updates as new studies become available. In each update recommendations about the conclusiveness of the evidence and the need of future studies need to be made. In the context of prospective meta-analysis future studies are planned as part of the accumulation of the evidence. In this setting, multiple testing issues need to be taken into account when the meta-analysis results are interpreted. We extend ideas of sequential monitoring of meta-analysis to provide a methodological framework for updating NMAs. Based on the z-score for each network estimate (the ratio of effect size to its standard error) and the respective information gained after each study enters NMA we construct efficacy and futility stopping boundaries. A NMA treatment effect is considered conclusive when it crosses an appended stopping boundary. The methods are illustrated using a recently published NMA where we show that evidence about a particular comparison can become conclusive via indirect evidence even if no further trials address this comparison. PMID:27587588

A Bayesian network meta-analysis for binary outcome: how to do it.

PubMed

Greco, Teresa; Landoni, Giovanni; Biondi-Zoccai, Giuseppe; D'Ascenzo, Fabrizio; Zangrillo, Alberto

2016-10-01

This study presents an overview of conceptual and practical issues of a network meta-analysis (NMA), particularly focusing on its application to randomised controlled trials with a binary outcome of interest. We start from general considerations on NMA to specifically appraise how to collect study data, structure the analytical network and specify the requirements for different models and parameter interpretations, with the ultimate goal of providing physicians and clinician-investigators a practical tool to understand pros and cons of NMA. Specifically, we outline the key steps, from the literature search to sensitivity analysis, necessary to perform a valid NMA of binomial data, exploiting Markov Chain Monte Carlo approaches. We also apply this analytical approach to a case study on the beneficial effects of volatile agents compared to total intravenous anaesthetics for surgery to further clarify the statistical details of the models, diagnostics and computations. Finally, datasets and models for the freeware WinBUGS package are presented for the anaesthetic agent example. © The Author(s) 2013.

Novel presentational approaches were developed for reporting network meta-analysis.

PubMed

Tan, Sze Huey; Cooper, Nicola J; Bujkiewicz, Sylwia; Welton, Nicky J; Caldwell, Deborah M; Sutton, Alexander J

2014-06-01

To present graphical tools for reporting network meta-analysis (NMA) results aiming to increase the accessibility, transparency, interpretability, and acceptability of NMA analyses. The key components of NMA results were identified based on recommendations by agencies such as the National Institute for Health and Care Excellence (United Kingdom). Three novel graphs were designed to amalgamate the identified components using familiar graphical tools such as the bar, line, or pie charts and adhering to good graphical design principles. Three key components for presentation of NMA results were identified, namely relative effects and their uncertainty, probability of an intervention being best, and between-study heterogeneity. Two of the three graphs developed present results (for each pairwise comparison of interventions in the network) obtained from both NMA and standard pairwise meta-analysis for easy comparison. They also include options to display the probability best, ranking statistics, heterogeneity, and prediction intervals. The third graph presents rankings of interventions in terms of their effectiveness to enable clinicians to easily identify "top-ranking" interventions. The graphical tools presented can display results tailored to the research question of interest, and targeted at a whole spectrum of users from the technical analyst to the nontechnical clinician. Copyright © 2014 Elsevier Inc. All rights reserved.

A process for assessing the feasibility of a network meta-analysis: a case study of everolimus in combination with hormonal therapy versus chemotherapy for advanced breast cancer.

PubMed

Cope, Shannon; Zhang, Jie; Saletan, Stephen; Smiechowski, Brielan; Jansen, Jeroen P; Schmid, Peter

2014-06-05

The aim of this study is to outline a general process for assessing the feasibility of performing a valid network meta-analysis (NMA) of randomized controlled trials (RCTs) to synthesize direct and indirect evidence for alternative treatments for a specific disease population. Several steps to assess the feasibility of an NMA are proposed based on existing recommendations. Next, a case study is used to illustrate this NMA feasibility assessment process in order to compare everolimus in combination with hormonal therapy to alternative chemotherapies in terms of progression-free survival for women with advanced breast cancer. A general process for assessing the feasibility of an NMA is outlined that incorporates explicit steps to visualize the heterogeneity in terms of treatment and outcome characteristics (Part A) as well as the study and patient characteristics (Part B). Additionally, steps are performed to illustrate differences within and across different types of direct comparisons in terms of baseline risk (Part C) and observed treatment effects (Part D) since there is a risk that the treatment effect modifiers identified may not explain the observed heterogeneity or inconsistency in the results due to unexpected, unreported or unmeasured differences. Depending on the data available, alternative approaches are suggested: list assumptions, perform a meta-regression analysis, subgroup analysis, sensitivity analyses, or summarize why an NMA is not feasible. The process outlined to assess the feasibility of an NMA provides a stepwise framework that will help to ensure that the underlying assumptions are systematically explored and that the risks (and benefits) of pooling and indirectly comparing treatment effects from RCTs for a particular research question are transparent.

Adjustment for reporting bias in network meta-analysis of antidepressant trials

PubMed Central

2012-01-01

Background Network meta-analysis (NMA), a generalization of conventional MA, allows for assessing the relative effectiveness of multiple interventions. Reporting bias is a major threat to the validity of MA and NMA. Numerous methods are available to assess the robustness of MA results to reporting bias. We aimed to extend such methods to NMA. Methods We introduced 2 adjustment models for Bayesian NMA. First, we extended a meta-regression model that allows the effect size to depend on its standard error. Second, we used a selection model that estimates the propensity of trial results being published and in which trials with lower propensity are weighted up in the NMA model. Both models rely on the assumption that biases are exchangeable across the network. We applied the models to 2 networks of placebo-controlled trials of 12 antidepressants, with 74 trials in the US Food and Drug Administration (FDA) database but only 51 with published results. NMA and adjustment models were used to estimate the effects of the 12 drugs relative to placebo, the 66 effect sizes for all possible pair-wise comparisons between drugs, probabilities of being the best drug and ranking of drugs. We compared the results from the 2 adjustment models applied to published data and NMAs of published data and NMAs of FDA data, considered as representing the totality of the data. Results Both adjustment models showed reduced estimated effects for the 12 drugs relative to the placebo as compared with NMA of published data. Pair-wise effect sizes between drugs, probabilities of being the best drug and ranking of drugs were modified. Estimated drug effects relative to the placebo from both adjustment models were corrected (i.e., similar to those from NMA of FDA data) for some drugs but not others, which resulted in differences in pair-wise effect sizes between drugs and ranking. Conclusions In this case study, adjustment models showed that NMA of published data was not robust to reporting bias and provided estimates closer to that of NMA of FDA data, although not optimal. The validity of such methods depends on the number of trials in the network and the assumption that conventional MAs in the network share a common mean bias mechanism. PMID:23016799

Exploring the molecular mechanism of trimethylamine-N-oxide's ability to counteract the protein denaturing effects of urea.

PubMed

Sarma, Rahul; Paul, Sandip

2013-05-09

Protein denaturation in highly concentrated urea solution is a well-known phenomenon. The counteracting effect of a naturally occurring osmolyte, trimethylamine-N-oxide (TMAO), against urea-conferred protein denaturation is also well-established. However, what is largely unknown is the mechanism by which TMAO counteracts this denaturation. To provide a molecular level understanding of how TMAO protects proteins in highly concentrated urea solution, we report here the structural, energetic, and dynamical properties of N-methylacetamide (NMA) solutions that also contain urea and/or TMAO. The solute NMA is of interest mainly because it contains the peptide linkage in addition to hydrophobic sites and represents the typical solvent-exposed state of proteins. Molecular dynamics computer simulation technique is employed in this study. Analysis of solvation characteristics reveals dehydration of NMA and reduction in hydrogen bond number between NMA oxygen and water upon addition of TMAO. The effect of TMAO on NMA-urea interaction is found to be insignificant. Because TMAO cannot donate its hydrogen to NMA oxygen, the total number of hydrogen bonds formed by NMA oxygen with solution species decreases in the presence of TMAO. In solution, TMAO is found to interact strongly with water and urea. Solvation of TMAO makes the water hydrogen bonding network relatively stronger and reduces relaxation of urea-water hydrogen bonds. Implications of these results for counteracting mechanism of TMAO are discussed.

The Importance of Considering Differences in Study Design in Network Meta-analysis: An Application Using Anti-Tumor Necrosis Factor Drugs for Ulcerative Colitis.

PubMed

Cameron, Chris; Ewara, Emmanuel; Wilson, Florence R; Varu, Abhishek; Dyrda, Peter; Hutton, Brian; Ingham, Michael

2017-11-01

Adaptive trial designs present a methodological challenge when performing network meta-analysis (NMA), as data from such adaptive trial designs differ from conventional parallel design randomized controlled trials (RCTs). We aim to illustrate the importance of considering study design when conducting an NMA. Three NMAs comparing anti-tumor necrosis factor drugs for ulcerative colitis were compared and the analyses replicated using Bayesian NMA. The NMA comprised 3 RCTs comparing 4 treatments (adalimumab 40 mg, golimumab 50 mg, golimumab 100 mg, infliximab 5 mg/kg) and placebo. We investigated the impact of incorporating differences in the study design among the 3 RCTs and presented 3 alternative methods on how to convert outcome data derived from one form of adaptive design to more conventional parallel RCTs. Combining RCT results without considering variations in study design resulted in effect estimates that were biased against golimumab. In contrast, using the 3 alternative methods to convert outcome data from one form of adaptive design to a format more consistent with conventional parallel RCTs facilitated more transparent consideration of differences in study design. This approach is more likely to yield appropriate estimates of comparative efficacy when conducting an NMA, which includes treatments that use an alternative study design. RCTs based on adaptive study designs should not be combined with traditional parallel RCT designs in NMA. We have presented potential approaches to convert data from one form of adaptive design to more conventional parallel RCTs to facilitate transparent and less-biased comparisons.

GetReal in network meta-analysis: a review of the methodology.

PubMed

Efthimiou, Orestis; Debray, Thomas P A; van Valkenhoef, Gert; Trelle, Sven; Panayidou, Klea; Moons, Karel G M; Reitsma, Johannes B; Shang, Aijing; Salanti, Georgia

2016-09-01

Pairwise meta-analysis is an established statistical tool for synthesizing evidence from multiple trials, but it is informative only about the relative efficacy of two specific interventions. The usefulness of pairwise meta-analysis is thus limited in real-life medical practice, where many competing interventions may be available for a certain condition and studies informing some of the pairwise comparisons may be lacking. This commonly encountered scenario has led to the development of network meta-analysis (NMA). In the last decade, several applications, methodological developments, and empirical studies in NMA have been published, and the area is thriving as its relevance to public health is increasingly recognized. This article presents a review of the relevant literature on NMA methodology aiming to pinpoint the developments that have appeared in the field. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Similar and Promising Outcomes in Lymphoma Patients Treated with Myeloablative or Nonmyeloablative Conditioning and Allogeneic Hematopoietic Cell Transplantation

PubMed Central

Tomblyn, Marcie; Brunstein, Claudio; Burns, Linda J.; Miller, Jeffrey S.; MacMillan, Margaret; DeFor, Todd E.; Weisdorf, Daniel J.

2008-01-01

We compared the outcomes of 141 consecutive patients who received allogeneic transplantation with either myeloablative (MA) or nonmyeloablative/reduced intensity (NMA) conditioning for non-Hodgkin and Hodgkin lymphoma at the University of Minnesota. All patients were transplanted between 1997 and 2004. NMA transplant recipients were older and received umbilical cord blood grafts more frequently (MA: 6 [9%]; NMA: 33 [43%], P < .001). NMA patients had more advanced disease and 30 (39%) patients had undergone prior autologous transplantation. The 4-year overall survival (OS) (MA: 46% versus NMA: 49%; p = .34) and the 3-year progression-free survival (PFS) (MA: 44% versus NMA: 31%; P = 0.82) were similar after MA or NMA conditioning. However, MA conditioning resulted in significantly higher 1-year treatment-related mortality (TRM) (MA: 43% versus NMA: 17%; P < .01) but a lower risk of relapse at 3 years (MA: 11% versus NMA: 36%; P < .01). We conclude that similar transplant outcomes are achieved after allogeneic hematopoietic stem cell transplantation using MA conditioning in younger patients and NMA conditioning in older patients or those with prior autologous transplantation not eligible for MA conditioning. Modifications to refine patient assignment to the preferred conditioning intensity and reduce relapse risks with NMA approaches are needed. PMID:18410896

Aberrant Expression of Calretinin, D2-40 and Mesothelin in Mucinous and Non-Mucinous Colorectal Carcinomas and Relation to Clinicopathological Features and Prognosis.

PubMed

Foda, Abd AlRahman Mohammad; El-Hawary, Amira Kamal; Hamed, Hazem

2016-10-01

CRC is a heterogeneous disease in terms of morphology, invasive behavior, metastatic capacity, and clinical outcome. Recently, many so-called mesothelial markers, including calretinin, D2-40, WT1, thrombomodulin, mesothelin, and others, have been certified. The aim of this study was to assess the immunohistochemical expression of calretinin and other mesothelial markers (D2-40 and mesothelin) in colorectal mucinous adenocarcinoma (MA) and non mucinous adenocarcinoma (NMA) specimens and relation to clinicopathological features and prognosis using manual tissue microarray technique. We studied tumor tissue specimens from 150 patients with colorectal MA and NMA who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using Calretinin, D2-40 and mesothelin expressions. We found that NMA showed significantly more calretinin and D2-40 expression than MA In contrast, no statistically significant difference between NMA and MA was detected in mesothelin expression. There were no statistically significant relations between any of the clinicopathological or histological parameters and any of the three markers. In a univariate analysis, neither calretinin nor D2-40 expressions showed any significant relations to DFS or OS. However, mesothelin luminal expression was significantly associated with worse DFS. Multivariate Cox regression analysis proved that luminal mesothelin expression was an independent negative prognostic factor in NMA. In conclusion, Calretinin, D2-40 and mesothelin are aberrantly expressed in a proportion of CRC cases with more expression in NMA than MA. Aberrant expression of these mesothelial markers was not associated with clinicopathological or histological features of CRCs. Only mesothelin expression appears to be a strong predictor of adverse prognosis.

Three-dimensional evidence network plot system: covariate imbalances and effects in network meta-analysis explored using a new software tool.

PubMed

Batson, Sarah; Score, Robert; Sutton, Alex J

2017-06-01

The aim of the study was to develop the three-dimensional (3D) evidence network plot system-a novel web-based interactive 3D tool to facilitate the visualization and exploration of covariate distributions and imbalances across evidence networks for network meta-analysis (NMA). We developed the 3D evidence network plot system within an AngularJS environment using a third party JavaScript library (Three.js) to create the 3D element of the application. Data used to enable the creation of the 3D element for a particular topic are inputted via a Microsoft Excel template spreadsheet that has been specifically formatted to hold these data. We display and discuss the findings of applying the tool to two NMA examples considering multiple covariates. These two examples have been previously identified as having potentially important covariate effects and allow us to document the various features of the tool while illustrating how it can be used. The 3D evidence network plot system provides an immediate, intuitive, and accessible way to assess the similarity and differences between the values of covariates for individual studies within and between each treatment contrast in an evidence network. In this way, differences between the studies, which may invalidate the usual assumptions of an NMA, can be identified for further scrutiny. Hence, the tool facilitates NMA feasibility/validity assessments and aids in the interpretation of NMA results. The 3D evidence network plot system is the first tool designed specifically to visualize covariate distributions and imbalances across evidence networks in 3D. This will be of primary interest to systematic review and meta-analysis researchers and, more generally, those assessing the validity and robustness of an NMA to inform reimbursement decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

Enhanced conformational sampling technique provides an energy landscape view of large-scale protein conformational transitions.

PubMed

Shao, Qiang

2016-10-26

Large-scale conformational changes in proteins are important for their functions. Tracking the conformational change in real time at the level of a single protein molecule, however, remains a great challenge. In this article, we present a novel in silico approach with the combination of normal mode analysis and integrated-tempering-sampling molecular simulation (NMA-ITS) to give quantitative data for exploring the conformational transition pathway in multi-dimensional energy landscapes starting only from the knowledge of the two endpoint structures of the protein. The open-to-closed transitions of three proteins, including nCaM, AdK, and HIV-1 PR, were investigated using NMA-ITS simulations. The three proteins have varied structural flexibilities and domain communications in their respective conformational changes. The transition state structure in the conformational change of nCaM and the associated free-energy barrier are in agreement with those measured in a standard explicit-solvent REMD simulation. The experimentally measured transition intermediate structures of the intrinsically flexible AdK are captured by the conformational transition pathway measured here. The dominant transition pathways between the closed and fully open states of HIV-1 PR are very similar to those observed in recent REMD simulations. Finally, the evaluated relaxation times of the conformational transitions of three proteins are roughly at the same level as reported experimental data. Therefore, the NMA-ITS method is applicable for a variety of cases, providing both qualitative and quantitative insights into the conformational changes associated with the real functions of proteins.

Chemoradiotherapy enhanced the efficacy of radiotherapy in nasopharyngeal carcinoma patients: a network meta-analysis

PubMed Central

He, Jian; Wu, Ping; Tang, Yaoyun; Liu, Sulai; Xie, Chubo; Luo, Shi; Zeng, Junfeng; Xu, Jing; Zhao, Suping

2017-01-01

Object A Bayesian network meta-analysis (NMA) was conducted to estimate the overall survival (OS) and complete response (CR) performance in nasopharyngeal carcinoma (NPC) patients who have been given the treatment of radiotherapy, concurrent chemoradiotherapy (C), adjuvant chemotherapy (A), neoadjuvant chemotherapy (N), concurrent chemoradiotherapy with adjuvant chemotherapy (C+A), concurrent chemoradiotherapy with neoadjuvant chemotherapy (C+N) and neoadjuvant chemotherapy with adjuvant chemotherapy (N+A). Methods Literature search was conducted in electronic databases. Hazard ratios (HRs) accompanied their 95% confidence intervals (95%CIs) or 95% credible intervals (95%CrIs) were applied to measure the relative survival benefit between two comparators. Meanwhile odd ratios (ORs) with their 95% CIs or CrIs were given to present CR data from individual studies. RESULTS Totally 52 qualified studies with 10,081 patients were included in this NMA. In conventional meta-analysis (MA), patients with N+C exhibited an average increase of 9% in the 3-year OS in relation to those with C+A. As for the NMA results, five therapies were associated with a significantly reduced HR when compared with the control group when concerning 5-year OS. C, C+A and N+A also presented a decreased HR compared with A. There was continuity among 1-year, 3-year and 5-year OS status. Cluster analysis suggested that the three chemoradiotherapy appeared to be divided into the most compete group which is located in the upper right corner of the cluster plot. Conclusion In view of survival rate and complete response, the NMA results revealed that C, C+A and C+N showed excellent efficacy. As a result, these 3 therapies were supposed to be considered as the first-line treatment according to this NMA. PMID:28418901

Relation of glypican-3 and E-cadherin expressions to clinicopathological features and prognosis of mucinous and non-mucinous colorectal adenocarcinoma.

PubMed

Foda, Abd Al-Rahman Mohammad; Mohammad, Mie Ali; Abdel-Aziz, Azza; El-Hawary, Amira Kamal

2015-06-01

Glypican-3 (GPC3) is a member of the membrane-bound heparin sulfate proteoglycans. E-cadherin is an adhesive receptor that is believed to act as a tumor suppressor gene. Many studies had investigated E-cadherin expressions in colorectal carcinoma (CRC) while only one study had investigated GPC3 expression in CRC. This study aims to investigate expression of GCP3 and E-cadherin in colorectal mucinous carcinoma (MA) and non-mucinous adenocarcinoma (NMA) using manual tissue microarray technique. Tumor tissue specimens are collected from 75 cases of MC and 75 cases of NMA who underwent radical surgery from Jan 2007 to Jan 2012 at the Gastroenterology Centre, Mansoura University, Egypt. Their clinicopathological parameters and survival data were revised and analyzed using established statistical methodologies. High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique and immunohistochemistry for GPC3 and E-cadherin was done. NMA showed higher expression of GPC3 than MA with no statistically significant relation. NMA showed a significantly higher E-cadherin expression than MA. GPC3 and E-cadherin positivity rates were significantly interrelated in NMA, but not in MA, group. In NMA group, there was no significant relation between either GPC3 or E-cadherin expression and the clinicopathological features. In a univariate analysis, neither GPC3 nor E-cadherin expression showed a significant impact on disease-free survival (DFS) or overall survival (OS). GPC3 and E-cadherin expressions are not independent prognostic factors in CRC. However, expressions of both are significantly interrelated in NMA patients, suggesting an excellent interplay between both, in contrast to MA. Further molecular studies are needed to further explore the relationship between GCP3 and E-cadherin in colorectal carcinogenesis.

The rank-heat plot is a novel way to present the results from a network meta-analysis including multiple outcomes.

PubMed

Veroniki, Areti Angeliki; Straus, Sharon E; Fyraridis, Alexandros; Tricco, Andrea C

2016-08-01

To present a novel and simple graphical approach to improve the presentation of the treatment ranking in a network meta-analysis (NMA) including multiple outcomes. NMA simultaneously compares many relevant interventions for a clinical condition from a network of trials, and allows ranking of the effectiveness and/or safety of each intervention. There are numerous ways to present the NMA results, which can challenge their interpretation by research users. The rank-heat plot is a novel graph that can be used to quickly recognize which interventions are most likely the best or worst interventions with respect to their effectiveness and/or safety for a single or multiple outcome(s) and may increase interpretability. Using empirical NMAs, we show that the need for a concise and informative presentation of results is imperative, particularly as the number of competing treatments and outcomes in an NMA increases. The rank-heat plot is an efficient way to present the results of ranking statistics, particularly when a large amount of data is available, and it is targeted to users from various backgrounds. Copyright © 2016 Elsevier Inc. All rights reserved.

Automated Illustration of Molecular Flexibility.

PubMed

Bryden, A; Phillips, George N; Gleicher, M

2012-01-01

In this paper, we present an approach to creating illustrations of molecular flexibility using normal mode analysis (NMA). The output of NMA is a collection of points corresponding to the locations of atoms and associated motion vectors, where a vector for each point is known. Our approach abstracts the complex object and its motion by grouping the points, models the motion of each group as an affine velocity, and depicts the motion of each group by automatically choosing glyphs such as arrows. Affine exponentials allow the extrapolation of nonlinear effects such as near rotations and spirals from the linear velocities. Our approach automatically groups points by finding sets of neighboring points whose motions fit the motion model. The geometry and motion models for each group are used to determine glyphs that depict the motion, with various aspects of the motion mapped to each glyph. We evaluated the utility of our system in real work done by structural biologists both by utilizing it in our own structural biology work and quantitatively measuring its usefulness on a set of known protein conformation changes. Additionally, in order to allow ourselves and our collaborators to effectively use our techniques we integrated our system with commonly used tools for molecular visualization.

[Basic concepts for network meta-analysis].

PubMed

Catalá-López, Ferrán; Tobías, Aurelio; Roqué, Marta

2014-12-01

Systematic reviews and meta-analyses have long been fundamental tools for evidence-based clinical practice. Initially, meta-analyses were proposed as a technique that could improve the accuracy and the statistical power of previous research from individual studies with small sample size. However, one of its main limitations has been the fact of being able to compare no more than two treatments in an analysis, even when the clinical research question necessitates that we compare multiple interventions. Network meta-analysis (NMA) uses novel statistical methods that incorporate information from both direct and indirect treatment comparisons in a network of studies examining the effects of various competing treatments, estimating comparisons between many treatments in a single analysis. Despite its potential limitations, NMA applications in clinical epidemiology can be of great value in situations where there are several treatments that have been compared against a common comparator. Also, NMA can be relevant to a research or clinical question when many treatments must be considered or when there is a mix of both direct and indirect information in the body of evidence. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Mucinous Colorectal Adenocarcinoma: Influence of EGFR and E-Cadherin Expression on Clinicopathologic Features and Prognosis.

PubMed

Foda, Abd AlRahman M; AbdelAziz, Azza; El-Hawary, Amira K; Hosni, Ali; Zalata, Khalid R; Gado, Asmaa I

2015-08-01

Previous studies have shown conflicting results on epidermal growth factor receptor (EGFR) and E-cadherin expression in colorectal carcinoma and their prognostic significance. To the best of our knowledge, this study is the first to investigate EGFR and E-cadherin expression, interrelation and relation to clinicopathologic, histologic parameters, and survival in rare colorectal mucinous adenocarcinoma (MA). In this study, we studied tumor tissue specimens from 150 patients with colorectal MA and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tips technique, and immunohistochemistry for EGFR and E-cadherin was performed. All relations were analyzed using established statistical methodologies. NMA expressed EGFR and E-cadherin in significantly higher rates with significant heterogenous pattern than MA. EGFR and E-cadherin positivity rates were significantly interrelated in both NMA and MA groups. In the NMA group, high EGFR expression was associated with old age, male sex, multiplicity of tumors, lack of mucinous component, and association with schistosomiasis. However, in the MA group, high EGFR expression was associated only with old age and MA subtype rather than signet ring carcinoma subtype. Conversely, high E-cadherin expression in MA cases was associated with old age, fungating tumor configuration, MA subtype, and negative intratumoral lymphocytic response. However, in the NMA cases, none of these factors was statistically significant. In a univariate analysis, neither EGFR nor E-cadherin expression showed a significant impact on disease-free or overall survival. Targeted therapy against EGFR and E-cadherin may not be useful in patients with MA. Neither EGFR nor E-cadherin is an independent prognostic factor in NMA or MA.

Testing moderation in network meta-analysis with individual participant data.

PubMed

Dagne, Getachew A; Brown, C Hendricks; Howe, George; Kellam, Sheppard G; Liu, Lei

2016-07-10

Meta-analytic methods for combining data from multiple intervention trials are commonly used to estimate the effectiveness of an intervention. They can also be extended to study comparative effectiveness, testing which of several alternative interventions is expected to have the strongest effect. This often requires network meta-analysis (NMA), which combines trials involving direct comparison of two interventions within the same trial and indirect comparisons across trials. In this paper, we extend existing network methods for main effects to examining moderator effects, allowing for tests of whether intervention effects vary for different populations or when employed in different contexts. In addition, we study how the use of individual participant data may increase the sensitivity of NMA for detecting moderator effects, as compared with aggregate data NMA that employs study-level effect sizes in a meta-regression framework. A new NMA diagram is proposed. We also develop a generalized multilevel model for NMA that takes into account within-trial and between-trial heterogeneity and can include participant-level covariates. Within this framework, we present definitions of homogeneity and consistency across trials. A simulation study based on this model is used to assess effects on power to detect both main and moderator effects. Results show that power to detect moderation is substantially greater when applied to individual participant data as compared with study-level effects. We illustrate the use of this method by applying it to data from a classroom-based randomized study that involved two sub-trials, each comparing interventions that were contrasted with separate control groups. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Comparative efficacy and safety of antibiotics used to treat acute bacterial skin and skin structure infections: Results of a network meta-analysis.

PubMed

Guest, Julian F; Esteban, Jaime; Manganelli, Anton G; Novelli, Andrea; Rizzardini, Giuliano; Serra, Miquel

2017-01-01

This NMA compared the efficacy and safety between IV antibiotics that are used in the current standard of care for managing adult patients (≥18 years of age) with ABSSSI. Comparators were chosen on the basis that both direct and indirect comparisons between the interventions of interest could be performed. Outcomes of the analysis were selected on the basis that they are frequently measured and reported in trials involving ABSSSI patients, and only published randomised control trials of any size and duration and with any blinding status were eligible for inclusion in the analysis. The NMA was performed using both a fixed-effect and random-effect model. Efficacy-related endpoints were (1) clinical treatment success and (2) microbiological success at TOC visit. Safety-related endpoints were (1) number of discontinuations due to AEs/SAEs, (2) patients experiencing AEs, (3) patients experiencing SAEs and (4) all-cause mortality. Study interventions included daptomycin, dalbavancin, linezolid and tigecycline. Vancomycin was the comparator in all studies, except in two where it was linezolid and teicoplanin. The NMA showed that irrespective of patient subgroup, the likelihood of clinical and microbiological success with dalbavancin was statistically similar to the comparators studied. No statistically significant differences were observed between dalbavancin and any of the comparators in the discontinuation rate due to AEs/SAEs. In contrast, dalbavancin was associated with a significantly lower likelihood of experiencing an AE than linezolid, a significantly lower likelihood of experiencing a SAE than vancomycin and daptomycin, and a significantly lower risk of all-cause mortality than vancomycin, linezolid and tigecycline. Dalbavancin affords a promising, new alternative IV antimicrobial agent which is as effective as traditional therapies, but with the added benefit of enabling clinicians to treat patients with ABSSSI in different organisational settings. Notwithstanding, any introduction of an effective treatment with a differential mode of administration into healthcare systems must be followed by a change in clinical practice and patient management in order to fully achieve desirable economic outcomes.

Comparative efficacy and safety of antibiotics used to treat acute bacterial skin and skin structure infections: Results of a network meta-analysis

PubMed Central

Esteban, Jaime; Manganelli, Anton G.; Novelli, Andrea; Rizzardini, Giuliano; Serra, Miquel

2017-01-01

Objective This NMA compared the efficacy and safety between IV antibiotics that are used in the current standard of care for managing adult patients (≥18 years of age) with ABSSSI. Methods Comparators were chosen on the basis that both direct and indirect comparisons between the interventions of interest could be performed. Outcomes of the analysis were selected on the basis that they are frequently measured and reported in trials involving ABSSSI patients, and only published randomised control trials of any size and duration and with any blinding status were eligible for inclusion in the analysis. The NMA was performed using both a fixed-effect and random-effect model. Efficacy-related endpoints were (1) clinical treatment success and (2) microbiological success at TOC visit. Safety-related endpoints were (1) number of discontinuations due to AEs/SAEs, (2) patients experiencing AEs, (3) patients experiencing SAEs and (4) all-cause mortality. Results Study interventions included daptomycin, dalbavancin, linezolid and tigecycline. Vancomycin was the comparator in all studies, except in two where it was linezolid and teicoplanin. The NMA showed that irrespective of patient subgroup, the likelihood of clinical and microbiological success with dalbavancin was statistically similar to the comparators studied. No statistically significant differences were observed between dalbavancin and any of the comparators in the discontinuation rate due to AEs/SAEs. In contrast, dalbavancin was associated with a significantly lower likelihood of experiencing an AE than linezolid, a significantly lower likelihood of experiencing a SAE than vancomycin and daptomycin, and a significantly lower risk of all-cause mortality than vancomycin, linezolid and tigecycline. Conclusion Dalbavancin affords a promising, new alternative IV antimicrobial agent which is as effective as traditional therapies, but with the added benefit of enabling clinicians to treat patients with ABSSSI in different organisational settings. Notwithstanding, any introduction of an effective treatment with a differential mode of administration into healthcare systems must be followed by a change in clinical practice and patient management in order to fully achieve desirable economic outcomes. PMID:29136035

Exploring the Counteracting Mechanism of Trehalose on Urea Conferred Protein Denaturation: A Molecular Dynamics Simulation Study.

PubMed

Paul, Subrata; Paul, Sandip

2015-07-30

To provide the underlying mechanism of the inhibiting effect of trehalose on the urea denatured protein, we perform classical molecular dynamics simulations of N-methylacetamide (NMA) in aqueous urea and/or trehalose solution. The site-site radial distribution functions and hydrogen bond properties indicate in binary urea solution the replacement of NMA-water hydrogen bonds by NMA-urea hydrogen bonds. On the other hand, in ternary urea and trehalose solution, trehalose does not replace the NMA-urea hydrogen bonds significantly; rather, it forms hydrogen bonds with the NMA molecule. The calculation of a preferential interaction parameter shows that, at the NMA surface, trehalose molecules are preferred and the preference for urea decreases slightly in ternary solution with respect to the binary solution. The exclusion of urea molecules in the ternary urea-NMA-trehalose system causes alleviation in van der Waals interaction energy between urea and NMA molecules. Our findings also reveal the following: (a) trehalose and urea induced second shell collapse of water structure, (b) a reduction in the mean trehalose cluster size in ternary solution, and (c) slowing down of translational motion of solution species in the presence of osmolytes. Implications of these results for the molecular explanations of the counteracting mechanism of trehalose on urea induced protein denaturation are discussed.

Nma111p, the pro-apoptotic HtrA-like nuclear serine protease in Saccharomyces cerevisiae: a short survey.

PubMed

Fahrenkrog, Birthe

2011-10-01

The baker's yeast, Saccharomyces cerevisiae, is also capable of undergoing programmed cell death or apoptosis, for example in response to viral infection as well as during chronological and replicative aging. Intrinsically, programmed cell death in yeast can be induced by, for example, H2O2, acetic acid or the mating-type pheromone. A number of evolutionarily conserved apoptosis-regulatory proteins have been identified in yeast, one of which is the HtrA (high-temperature requirement A)-like serine protease Nma111p (Nma is nuclear mediator of apoptosis). Nma111p is a nuclear serine protease of the HtrA family, which targets Bir1p, the only known inhibitor-of-apoptosis protein in yeast. Nma111p mediates apoptosis in a serine-protease-dependent manner and exhibits its activity exclusively in the nucleus. How the activity of Nma111p is regulated has remained largely elusive, but some evidence points to a control by phosphorylation. Current knowledge of Nma111p's function in apoptosis will be discussed in the present review.

Hybrid statistical testing for nuclear material accounting data and/or process monitoring data in nuclear safeguards

DOE PAGES

Burr, Tom; Hamada, Michael S.; Ticknor, Larry; ...

2015-01-01

The aim of nuclear safeguards is to ensure that special nuclear material is used for peaceful purposes. Historically, nuclear material accounting (NMA) has provided the quantitative basis for monitoring for nuclear material loss or diversion, and process monitoring (PM) data is collected by the operator to monitor the process. PM data typically support NMA in various ways, often by providing a basis to estimate some of the in-process nuclear material inventory. We develop options for combining PM residuals and NMA residuals (residual = measurement - prediction), using a hybrid of period-driven and data-driven hypothesis testing. The modified statistical tests canmore » be used on time series of NMA residuals (the NMA residual is the familiar material balance), or on a combination of PM and NMA residuals. The PM residuals can be generated on a fixed time schedule or as events occur.« less

Antithrombotic therapy in patients receiving saphenous vein coronary artery bypass grafts: a protocol for a systematic review and network meta-analysis

PubMed Central

Solo, Karla; Martin, Janet; Lavi, Shahar; Kabali, Conrad; John-Baptiste, Ava; Nevis, Immaculate F; Choudhury, Tawfiq; Mamas, Mamas A

2018-01-01

Introduction The current evidence for the prevention of saphenous vein graft failure (SVGF) after coronary artery bypass graft (CABG) surgery consists of direct head-to-head comparison of treatments (including placebo) in randomised-controlled trials (RCTs) and observational studies. However, summarising the evidence using traditional pairwise meta-analyses does not allow the inclusion of data from treatments that have not been compared head to head. Exclusion of such comparisons could impact the precision of pooled estimates in a meta-analysis. Hence, to address the challenge of whether aspirin alone or in addition to another antithrombotic agent is a more effective regimen to improve SVG patency, a network meta-analysis (NMA) is necessary. The objectives of this study are to synthesise the available evidence on antithrombotic agents (or their combination) and estimate the treatment effects among direct and indirect treatment comparisons on SVGF and major adverse cardiovascular events, and to generate a treatment ranking according to their efficacy and safety outcomes. Methods We will perform a systematic review of RCTs evaluating antithrombotic agents in patients undergoing CABG. A comprehensive English literature search will be conducted using electronic databases and grey literature resources to identify published and unpublished articles. Two individuals will independently and in duplicate screen potential studies, assess the eligibility of potential studies and extract data. Risk of bias and quality of evidence will also be evaluated independently and in duplicate. We will investigate the data to ensure its suitability for NMA, including adequacy of the outcome data and transitivity of treatment effects. We plan to estimate the pooled direct, indirect and the mixed effects for all antithrombotic agents using a NMA. Ethics and dissemination Due to the nature of the study, there are no ethical concerns nor informed consent required. We anticipate that this NMA will be the first to simultaneously assess the relative effects of multiple antithrombotic agents in patients undergoing CABG. The results of this NMA will inform clinicians, patients and guideline developers the best available evidence on comparative effects benefits of antithrombotic agents after CABG while considering the side effect profile to support future clinical decision-making. We will disseminate the results of our systematic review and NMA through a peer-reviewed journal. PROSPERO registration number CRD42017065678. PMID:29627809

Comparative safety and effectiveness of long-acting inhaled agents for treating chronic obstructive pulmonary disease: a systematic review and network meta-analysis.

PubMed

Tricco, Andrea C; Strifler, Lisa; Veroniki, Areti-Angeliki; Yazdi, Fatemeh; Khan, Paul A; Scott, Alistair; Ng, Carmen; Antony, Jesmin; Mrklas, Kelly; D'Souza, Jennifer; Cardoso, Roberta; Straus, Sharon E

2015-10-26

To compare the safety and effectiveness of long-acting β-antagonists (LABA), long-acting antimuscarinic agents (LAMA) and inhaled corticosteroids (ICS) for managing chronic obstructive pulmonary disease (COPD). Systematic review and network meta-analysis (NMA). 208 randomised clinical trials (RCTs) including 134,692 adults with COPD. LABA, LAMA and/or ICS, alone or in combination, versus each other or placebo. The proportion of patients with moderate-to-severe exacerbations. The number of patients experiencing mortality, pneumonia, serious arrhythmia and cardiovascular-related mortality (CVM) were secondary outcomes. NMA was conducted including 20 RCTs for moderate-to-severe exacerbations for 26,141 patients with an exacerbation in the past year. 32 treatments were effective versus placebo including: tiotropium, budesonide/formoterol, salmeterol, indacaterol, fluticasone/salmeterol, indacaterol/glycopyrronium, tiotropium/fluticasone/salmeterol and tiotropium/budesonide/formoterol. Tiotropium/budesonide/formoterol was most effective (99.2% probability of being the most effective according to the Surface Under the Cumulative RAnking (SUCRA) curve). NMA was conducted on mortality (88 RCTs, 97 526 patients); fluticasone/salmeterol was more effective in reducing mortality than placebo, formoterol and fluticasone alone, and was the most effective (SUCRA=71%). NMA was conducted on CVM (37 RCTs, 55,156 patients) and the following were safest: salmeterol versus each OF placebo, tiotropium and tiotropium (Soft Mist Inhaler (SMR)); fluticasone versus tiotropium (SMR); and salmeterol/fluticasone versus tiotropium and tiotropium (SMR). Triamcinolone acetonide was the most harmful (SUCRA=81%). NMA was conducted on pneumonia occurrence (54 RCTs, 61 551 patients). 24 treatments were more harmful, including 2 that increased risk of pneumonia versus placebo; fluticasone and fluticasone/salmeterol. The most harmful agent was fluticasone/salmeterol (SUCRA=89%). NMA was conducted for arrhythmia; no statistically significant differences between agents were identified. Many inhaled agents are available for COPD, some are safer and more effective than others. Our results can be used by patients and physicians to tailor administration of these agents. PROSPERO # CRD42013006725. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Live cumulative network meta-analysis: protocol for second-line treatments in advanced non-small-cell lung cancer with wild-type or unknown status for epidermal growth factor receptor.

PubMed

Créquit, Perrine; Trinquart, Ludovic; Ravaud, Philippe

2016-08-03

Many second-line treatments for advanced non-small-cell lung cancer (NSCLC) have been assessed in randomised controlled trials, but which treatments work the best remains unclear. Novel treatments are being rapidly developed. We need a comprehensive up-to-date evidence synthesis of all these treatments. We present the protocol for a live cumulative network meta-analysis (NMA) to address this need. We will consider trials of second-line treatments in patients with advanced NSCLC with wild-type or unknown epidermal growth factor receptor status. We will consider any single agent of cytotoxic chemotherapy, targeted therapy, combination of cytotoxic chemotherapy and targeted therapy and any combination of targeted therapies. The primary outcomes will be overall survival and progression-free survival. The live cumulative NMA will be initiated with a NMA and then iterations will be repeated at regular intervals to keep the NMA up-to-date over time. We have defined the update frequency as 4 months, based on an assessment of the pace of evidence production on this topic. Each iteration will consist of six methodological steps: adaptive search for treatments and trials, screening of reports and selection of trials, data extraction, assessment of risk of bias, update of the network of trials and synthesis, and dissemination. We will set up a research community in lung cancer, with different groups of contributors of different skills. We will distribute tasks through online crowdsourcing. This proof-of-concept study in second-line treatments of advanced NSCLC will allow one for assessing the feasibility of live cumulative NMA and opening the path for this new form of synthesis. Ethical approval is not required because our study will not include confidential participant data and interventions. The description of all the steps and the results of this live cumulative NMA will be available online. CRD42015017592. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Ensemble of Transition State Structures for the Cis-Trans Isomerization of N-Methylacetamide

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

Mantz, Yves A.; Branduardi, Davide; Bussi, Giovanni

2009-09-17

The cis-trans isomerization of N-methylacetamide (NMA), a model peptidic fragment, is studied theoretically in vacuo and in explicit water solvent at 300 K using the metadynamics technique. The computed cis-trans free energy difference is very similar for NMA(g) and NMA(aq), in agreement with experimental measurements of population ratios and theoretical studies at 0 K. By exploiting the flexibility in the definition of a pair of recently introduced collective variables (Branduardi, D.; Gervasio, F. L.; Parrinello, M. J. Chem. Phys. 2007, 126, 054103), an ensemble of transition state structures is generated at finite temperature for both NMA(g) and NMA(aq), as verifiedmore » by computing committor distribution functions. Ensemble members of NMA(g) are shown to have correlated values of the backbone dihedral angle and a second dihedral angle involving the amide hydrogen atom. The dynamical character of these structures is preserved in the presence of solvent, whose influence on the committor functions can be modeled using effective friction/noise terms.« less

Testing moderation in network meta-analysis with individual participant data

PubMed Central

Dagne, Getachew A.; Brown, C. Hendricks; Howe, George; Kellam, Sheppard G.; Liu, Lei

2016-01-01

Summary Meta-analytic methods for combining data from multiple intervention trials are commonly used to estimate the effectiveness of an intervention. They can also be extended to study comparative effectiveness, testing which of several alternative interventions is expected to have the strongest effect. This often requires network meta-analysis (NMA), which combines trials involving direct comparison of two interventions within the same trial and indirect comparisons across trials. In this paper, we extend existing network methods for main effects to examining moderator effects, allowing for tests of whether intervention effects vary for different populations or when employed in different contexts. In addition, we study how the use of individual participant data (IPD) may increase the sensitivity of NMA for detecting moderator effects, as compared to aggregate data NMA that employs study-level effect sizes in a meta-regression framework. A new network meta-analysis diagram is proposed. We also develop a generalized multilevel model for NMA that takes into account within- and between-trial heterogeneity, and can include participant-level covariates. Within this framework we present definitions of homogeneity and consistency across trials. A simulation study based on this model is used to assess effects on power to detect both main and moderator effects. Results show that power to detect moderation is substantially greater when applied to IPD as compared to study-level effects. We illustrate the use of this method by applying it to data from a classroom-based randomized study that involved two sub-trials, each comparing interventions that were contrasted with separate control groups. PMID:26841367

Computational analysis of a novel mutation in ETFDH gene highlights its long-range effects on the FAD-binding motif.

PubMed

Er, Tze-Kiong; Chen, Chih-Chieh; Liu, Yen-Yi; Chang, Hui-Chiu; Chien, Yin-Hsiu; Chang, Jan-Gowth; Hwang, Jenn-Kang; Jong, Yuh-Jyh

2011-10-21

Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is an autosomal recessive disease caused by the defects in the mitochondrial electron transfer system and the metabolism of fatty acids. Recently, mutations in electron transfer flavoprotein dehydrogenase (ETFDH) gene, encoding electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) have been reported to be the major causes of riboflavin-responsive MADD. To date, no studies have been performed to explore the functional impact of these mutations or their mechanism of disrupting enzyme activity. High resolution melting (HRM) analysis and sequencing of the entire ETFDH gene revealed a novel mutation (p.Phe128Ser) and the hotspot mutation (p.Ala84Thr) from a patient with MADD. According to the predicted 3D structure of ETF:QO, the two mutations are located within the flavin adenine dinucleotide (FAD) binding domain; however, the two residues do not have direct interactions with the FAD ligand. Using molecular dynamics (MD) simulations and normal mode analysis (NMA), we found that the p.Ala84Thr and p.Phe128Ser mutations are most likely to alter the protein structure near the FAD binding site as well as disrupt the stability of the FAD binding required for the activation of ETF:QO. Intriguingly, NMA revealed that several reported disease-causing mutations in the ETF:QO protein show highly correlated motions with the FAD-binding site. Based on the present findings, we conclude that the changes made to the amino acids in ETF:QO are likely to influence the FAD-binding stability.

Computational analysis of a novel mutation in ETFDH gene highlights its long-range effects on the FAD-binding motif

PubMed Central

2011-01-01

Background Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is an autosomal recessive disease caused by the defects in the mitochondrial electron transfer system and the metabolism of fatty acids. Recently, mutations in electron transfer flavoprotein dehydrogenase (ETFDH) gene, encoding electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) have been reported to be the major causes of riboflavin-responsive MADD. To date, no studies have been performed to explore the functional impact of these mutations or their mechanism of disrupting enzyme activity. Results High resolution melting (HRM) analysis and sequencing of the entire ETFDH gene revealed a novel mutation (p.Phe128Ser) and the hotspot mutation (p.Ala84Thr) from a patient with MADD. According to the predicted 3D structure of ETF:QO, the two mutations are located within the flavin adenine dinucleotide (FAD) binding domain; however, the two residues do not have direct interactions with the FAD ligand. Using molecular dynamics (MD) simulations and normal mode analysis (NMA), we found that the p.Ala84Thr and p.Phe128Ser mutations are most likely to alter the protein structure near the FAD binding site as well as disrupt the stability of the FAD binding required for the activation of ETF:QO. Intriguingly, NMA revealed that several reported disease-causing mutations in the ETF:QO protein show highly correlated motions with the FAD-binding site. Conclusions Based on the present findings, we conclude that the changes made to the amino acids in ETF:QO are likely to influence the FAD-binding stability. PMID:22013910

75 FR 39610 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-09

... Effectiveness of Proposed Rule Change Amending Financial Industry Regulatory Authority, Inc. Online Form NMA... Substance of the Proposed Rule Change FINRA is proposing to amend online Form NMA, the standardized... Proposed Rule Change 1. Purpose Form NMA is the standardized online membership application form applicants...

Density-cluster NMA: A new protein decomposition technique for coarse-grained normal mode analysis.

PubMed

Demerdash, Omar N A; Mitchell, Julie C

2012-07-01

Normal mode analysis has emerged as a useful technique for investigating protein motions on long time scales. This is largely due to the advent of coarse-graining techniques, particularly Hooke's Law-based potentials and the rotational-translational blocking (RTB) method for reducing the size of the force-constant matrix, the Hessian. Here we present a new method for domain decomposition for use in RTB that is based on hierarchical clustering of atomic density gradients, which we call Density-Cluster RTB (DCRTB). The method reduces the number of degrees of freedom by 85-90% compared with the standard blocking approaches. We compared the normal modes from DCRTB against standard RTB using 1-4 residues in sequence in a single block, with good agreement between the two methods. We also show that Density-Cluster RTB and standard RTB perform well in capturing the experimentally determined direction of conformational change. Significantly, we report superior correlation of DCRTB with B-factors compared with 1-4 residue per block RTB. Finally, we show significant reduction in computational cost for Density-Cluster RTB that is nearly 100-fold for many examples. Copyright © 2012 Wiley Periodicals, Inc.

Antithrombotic therapy in patients receiving saphenous vein coronary artery bypass grafts: a protocol for a systematic review and network meta-analysis.

PubMed

Solo, Karla; Martin, Janet; Lavi, Shahar; Kabali, Conrad; John-Baptiste, Ava; Nevis, Immaculate F; Choudhury, Tawfiq; Mamas, Mamas A; Bagur, Rodrigo

2018-04-07

The current evidence for the prevention of saphenous vein graft failure (SVGF) after coronary artery bypass graft (CABG) surgery consists of direct head-to-head comparison of treatments (including placebo) in randomised-controlled trials (RCTs) and observational studies. However, summarising the evidence using traditional pairwise meta-analyses does not allow the inclusion of data from treatments that have not been compared head to head. Exclusion of such comparisons could impact the precision of pooled estimates in a meta-analysis. Hence, to address the challenge of whether aspirin alone or in addition to another antithrombotic agent is a more effective regimen to improve SVG patency, a network meta-analysis (NMA) is necessary. The objectives of this study are to synthesise the available evidence on antithrombotic agents (or their combination) and estimate the treatment effects among direct and indirect treatment comparisons on SVGF and major adverse cardiovascular events, and to generate a treatment ranking according to their efficacy and safety outcomes. We will perform a systematic review of RCTs evaluating antithrombotic agents in patients undergoing CABG. A comprehensive English literature search will be conducted using electronic databases and grey literature resources to identify published and unpublished articles. Two individuals will independently and in duplicate screen potential studies, assess the eligibility of potential studies and extract data. Risk of bias and quality of evidence will also be evaluated independently and in duplicate. We will investigate the data to ensure its suitability for NMA, including adequacy of the outcome data and transitivity of treatment effects. We plan to estimate the pooled direct, indirect and the mixed effects for all antithrombotic agents using a NMA. Due to the nature of the study, there are no ethical concerns nor informed consent required. We anticipate that this NMA will be the first to simultaneously assess the relative effects of multiple antithrombotic agents in patients undergoing CABG. The results of this NMA will inform clinicians, patients and guideline developers the best available evidence on comparative effects benefits of antithrombotic agents after CABG while considering the side effect profile to support future clinical decision-making. We will disseminate the results of our systematic review and NMA through a peer-reviewed journal. CRD42017065678. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

One more river to cross--looking back, moving forward: advancing the NMA "equality agenda" in the era of 21st-century medicine.

PubMed

Gadson, Sandra L

2005-10-01

The following is an excerpt of the inaugural address given July 27, 2005 by Sandra L. Gadson, MD, who was installed as the 106th president of the National Medical Association (NMA) during NMA's 2005 Annual Convention and Scientific Assembly in New York, NY.

Synthesis, Characterization, and Cross-Linking Strategy of a Quercetin-Based Epoxidized Monomer as a Naturally-Derived Replacement for BPA in Epoxy Resins.

PubMed

Kristufek, Samantha L; Yang, Guozhen; Link, Lauren A; Rohde, Brian J; Robertson, Megan L; Wooley, Karen L

2016-08-23

The natural polyphenolic compound quercetin was functionalized and cross-linked to afford a robust epoxy network. Quercetin was selectively methylated and functionalized with glycidyl ether moieties using a microwave-assisted reaction on a gram scale to afford the desired monomer (Q). This quercetin-derived monomer was treated with nadic methyl anhydride (NMA) to obtain a cross-linked network (Q-NMA). The thermal and mechanical properties of this naturally derived network were compared to those of a conventional diglycidyl ether bisphenol A-derived counterpart (DGEBA-NMA). Q-NMA had similar thermal properties [i.e., glass transition (Tg ) and decomposition (Td ) temperatures] and comparable mechanical properties (i.e., Young's Modulus, storage modulus) to that of DGEBA-NMA. However, it had a lower tensile strength and higher flexural modulus at elevated temperatures. The application of naturally derived, sustainable compounds for the replacement of commercially available petrochemical-based epoxies is of great interest to reduce the environmental impact of these materials. Q-NMA is an attractive candidate for the replacement of bisphenol A-based epoxies in various specialty engineering applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improved ex vivo blood compatibility of central venous catheter with noble metal alloy coating.

PubMed

Vafa Homann, Manijeh; Johansson, Dorota; Wallen, Håkan; Sanchez, Javier

2016-10-01

Central line associated bloodstream infections (CLABSIs) are a serious cause of morbidity and mortality induced by the use of central venous catheters (CVCs). Nobel metal alloy (NMA) coating is an advanced surface modification that prevents microbial adhesion and growth on catheters and thereby reduces the risk of infection. In vitro microbiological analyses have shown up to 90% reduction in microbial adhesion on coated CVC compared to uncoated ones. This study aimed to assess the blood compatibility of NMA-coated CVC according to ISO 10993-4. Hemolysis, thrombin-antithrombin (TAT) complex, platelet counts, fibrin deposition, and C3a and SC5b-9 complement activation were analyzed in human blood exposed to the NMA-coated and control CVCs using a Chandler-loop model. NMA-coated CVC did not induce hemolysis and fell in the "nonhemolytic" category according to ASTM F756-00. Significantly lower amounts of TAT were generated and less fibrin was deposited on NMA-coated CVC than on uncoated ones. Slightly higher platelet counts and lower complement markers were observed for NMA-coated CVC compared to uncoated ones. These data suggest that the NMA-coated CVC has better ex vivo blood compatibility compared to uncoated CVC. © 2015 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1359-1365, 2016. © 2015 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc.

The impact of targeted Rheumatoid Arthritis pharmacological treatment on mental health: A systematic review and network meta-analysis.

PubMed

Matcham, Faith; Galloway, James; Hotopf, Matthew; Roberts, Emmert; Scott, Ian C; Steer, Sophia; Norton, Sam

2018-06-06

Rheumatoid Arthritis (RA) pharmacotherapy may impact mental health (MH) outcomes by improving pain and stiffness; and potentially via targeting inflammatory processes common to RA and depression. The objectives of this review were to i) ascertain the frequency of MH assessment in RA pharmacotherapy trials; ii) quantify the efficacy of RA pharmacotherapy efficacy on MH outcomes; iii) explore the clinical and demographic factors related to MH outcomes. CENTRAL, PsychINFO, Web of Science, Medline, Embase and CINAHL were systematically searched from inception to March 2017 for randomised trials of disease-modifying anti-rheumatic drugs (DMARDs) in adult RA patients. The primary outcome was MH; self-reported physical health was extracted as a secondary outcome. Pairwise meta-analysis (PMA) created pooled effect sizes and 95%CIs for comparisons of all treatments versus comparators (active or placebo). Network meta-analysis (NMA) provided effect size estimates of targeted biologic DMARDs (bDMARDs) versus conventional synthetic DMARDs (csDMARDs) using indirect comparisons of different treatment modalities. 71 eligible studies were identified. 57 studies were included in the PMA, representing 23,535 patients. bDMARDs showed small effects on MH (standardised mean difference (SMD) versus csDMARDs = 0.19 to 0.30), and moderate effects on self-reported physical health (SMD versus csDMARDs = 0.46 to 0.50), with NMA determining no significant differences in effectiveness between bDMARD mode of action on either outcome. Effective pharmacotherapy alone is unlikely to substantially improve MH outcomes for most RA patients. Integrated MH care provided within routine clinical practice is essential to optimise mental and physical health outcomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A study of N-methylacetamide in water clusters: based on atom-bond electronegativity equalization method fused into molecular mechanics.

PubMed

Yang, Zhong-Zhi; Qian, Ping

2006-08-14

N-methylacetamide (NMA) is a very interesting compound and often serves as a model of the peptide bond. The interaction between NMA and water provides a convenient prototype for the solvation of the peptides in aqueous solutions. Here we present NMA-water potential model based on atom-bond electronegativity equalization method fused into molecular mechanics (ABEEM/MM) that is to take ABEEM charges of all atoms, bonds, and lone-pair electrons of NMA and water molecules into the electrostatic interaction term in molecular mechanics. The model has the following characters: (1)it allows the charges in system to fluctuate responding to the ambient environment; (2) for two major types of intermolecular hydrogen bonds, which are the hydrogen bond forming between the lone-pair electron on amide oxygen and the water hydrogen, and the one forming between the lone-pair electron on water oxygen and the amide hydrogen, we take special treatments in describing the electrostatic interaction by the use of the parameters k(lpO=, H) and k(lpO(-), HN(-)), respectively. The newly constructed potential model based on ABEEM/MM is first applied to amide-water clusters and reproduces gas-phase state properties of NMA(H(2)O)(n) (n=1-3) including optimal structures, dipole moments, ABEEM charge distributions, energy difference of the isolated trans- and cis-NMA, interaction energies, hydrogen bonding cooperative effects, and so on, whose results show the good agreement with those measured by available experiments and calculated by ab initio methods. In order to further test the reasonableness of this model and the correctness and transferability of the parameters, many static properties of the larger NMA-water complexes NMA(H(2)O)(n) (n=4-6) are also studied including optimal structures and interaction energies. The results also show fair consistency with those of our quantum chemistry calculations.

Growth, structural, optical, thermal and dielectric properties of lanthanum chloride—thiourea—L tartaric acid coordinated complex

NASA Astrophysics Data System (ADS)

Slathia, Goldy; Bamzai, K. K.

2017-11-01

Lanthanum chloride—thiourea—l tartaric acid coordinated complex was grown in the form of single crystal by slow evaporation of supersaturated solutions at room temperature. This coordinated complex crystallizes in orthorhombic crystal system having space group P nma. The crystallinity and purity was tested by powder x-ray diffraction. Fourier transform infra red and Raman spectroscopy analysis provide the evidences on structure and mode of coordination. The scanning electron microscopy (SEM) analysis shows the morphology evolution as brought by the increase in composition of lanthanum chloride. The band transitions due to C=O and C=S chromophores remain active in grown complexes and are recorded in the UV-vis optical spectrum. The thermal effects such as dehydration, melting and decomposition were observed by the thermogravimetric and differential thermo analytical (TGA/DTA) analysis. Electrical properties were studied by dielectric analysis in frequency range 100-30 MHz at various temperatures. Increase in values of dielectric constant was observed with change in lanthanum concentration in the coordinated complex.

Psychological interventions for positive symptoms in schizophrenia: protocol for a network meta-analysis of randomised controlled trials

PubMed Central

Salanti, Georgia; Reitmeir, Cornelia; Wallis, Sofia; Barbui, Corrado; Leucht, Stefan

2018-01-01

Introduction There is rising awareness that we need multidisciplinary approaches integrating psychological treatments for schizophrenia, but a comprehensive evidence based on their relative efficacy is lacking. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs) to rank psychological treatments for schizophrenia according to their efficacy, acceptability and tolerability. Methods and analysis We will include all RCTs comparing a psychological treatment aimed at positive symptoms of schizophrenia with another psychological intervention or with a no treatment condition (waiting-list and treatment as usual). We will include studies on adult patients with schizophrenia, excluding specific subpopulations (eg, first-episode patients or patients with psychiatric comorbidities). Primary outcome will be the change in positive symptoms on a published rating scale. Secondary outcomes will be acceptability (dropout), change in overall and negative symptoms of schizophrenia, response, relapse, adherence, depression, quality of life, functioning and adverse events. Published and unpublished studies will be sought through database searches, trial registries and websites. Study selection and data extraction will be conducted by at least two independent reviewers. We will conduct random-effects NMA to synthesise all evidences for each outcome and obtain a comprehensive ranking of all treatments. NMA will be conducted in Stata and R within a frequentist framework. The risk of bias in studies will be evaluated using the Cochrane Risk of Bias tool and the credibility of the evidence will be evaluated using an adaptation of the Grading of Recommendations Assessment, Development and Evaluation framework to NMA, recommended by the Cochrane guidance. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. Ethics and dissemination No ethical issues are foreseen. Results from this study will be published in peer-reviewed journals and presented at relevant conferences. PROSPERO registration number CRD42017067795. PMID:29540411

Software and package applicating for network meta-analysis: A usage-based comparative study.

PubMed

Xu, Chang; Niu, Yuming; Wu, Junyi; Gu, Huiyun; Zhang, Chao

2017-12-21

To compare and analyze the characteristics and functions of software applications for network meta-analysis (NMA). PubMed, EMbase, The Cochrane Library, the official websites of Bayesian inference Using Gibbs Sampling (BUGS), Stata and R, and Google were searched to collect the software and packages for performing NMA; software and packages published up to March 2016 were included. After collecting the software, packages, and their user guides, we used the software and packages to calculate a typical example. All characteristics, functions, and computed results were compared and analyzed. Ten types of software were included, including programming and non-programming software. They were developed mainly based on Bayesian or frequentist theory. Most types of software have the characteristics of easy operation, easy mastery, exact calculation, or excellent graphing. However, there was no single software that performed accurate calculations with superior graphing; this could only be achieved through the combination of two or more types of software. This study suggests that the user should choose the appropriate software according to personal programming basis, operational habits, and financial ability. Then, the choice of the combination of BUGS and R (or Stata) software to perform the NMA is considered. © 2017 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

PDB-NMA of a protein homodimer reproduces distinct experimental motility asymmetry.

PubMed

Tirion, Monique M; Ben-Avraham, Daniel

2018-01-16

We have extended our analytically derived PDB-NMA formulation, Atomic Torsional Modal Analysis or ATMAN (Tirion and ben-Avraham 2015 Phys. Rev. E 91 032712), to include protein dimers using mixed internal and Cartesian coordinates. A test case on a 1.3 [Formula: see text] resolution model of a small homodimer, ActVA-ORF6, consisting of two 112-residue subunits identically folded in a compact 50 [Formula: see text] sphere, reproduces the distinct experimental Debye-Waller motility asymmetry for the two chains, demonstrating that structure sensitively selects vibrational signatures. The vibrational analysis of this PDB entry, together with biochemical and crystallographic data, demonstrates the cooperative nature of the dimeric interaction of the two subunits and suggests a mechanical model for subunit interconversion during the catalytic cycle.

PDB-NMA of a protein homodimer reproduces distinct experimental motility asymmetry

NASA Astrophysics Data System (ADS)

Tirion, Monique M.; ben-Avraham, Daniel

2018-03-01

We have extended our analytically derived PDB-NMA formulation, Atomic Torsional Modal Analysis or ATMAN (Tirion and ben-Avraham 2015 Phys. Rev. E 91 032712), to include protein dimers using mixed internal and Cartesian coordinates. A test case on a 1.3 {\\mathringA} resolution model of a small homodimer, ActVA-ORF6, consisting of two 112-residue subunits identically folded in a compact 50 {\\mathringA} sphere, reproduces the distinct experimental Debye-Waller motility asymmetry for the two chains, demonstrating that structure sensitively selects vibrational signatures. The vibrational analysis of this PDB entry, together with biochemical and crystallographic data, demonstrates the cooperative nature of the dimeric interaction of the two subunits and suggests a mechanical model for subunit interconversion during the catalytic cycle.

A Network Meta-Analysis of the Relative Efficacy of Treatments for Actinic Keratosis of the Face or Scalp in Europe

PubMed Central

Vegter, Stefan; Tolley, Keith

2014-01-01

Background Several treatments are available for actinic keratosis (AK) on the face and scalp. Most treatment modalities were compared to placebo and therefore little is known on their relative efficacy. Objectives To compare the different treatments for mild to moderate AK on the face and scalp available in clinical practice in Europe. Methods A network meta-analysis (NMA) was performed on the outcome “complete patient clearance”. Ten treatment modalities were included: two 5-aminolaevulinic acid photodynamic therapies (ALA-PDT), applied as gel (BF-200 ALA) or patch; methyl-aminolevulinate photodynamic therapy (MAL-PDT); three modalities with imiquimod (IMI), applied as a 4-week or 16-week course with 5% imiquimod, or a 2–3 week course with 3.75% imiquimod; cryotherapy; diclofenac 3% in 2.5% hyaluronic acid; 0.5% 5-fluorouracil (5-FU); and ingenol mebutate (IMB). The only data available for 5% 5-FU was from one small study and was determined to be too limited to be reliably included in the analysis. For BF-200 ALA and MAL-PDT, data from illumination with narrow-band lights were selected as these are typically used in clinical practice. The NMA was performed with a random-effects Bayesian model. Results 25 trials on 5,562 patients were included in the NMA. All active treatments were significantly better than placebo. BF-200 ALA showed the highest efficacy compared to placebo to achieve total patient clearance. BF-200 ALA had the highest probability to be the best treatment and the highest SUCRA score (64.8% and 92.1%), followed by IMI 5% 4 weeks (10.1% and 74.2%) and 5-FU 0.5% (7.2% and 66.8%). Conclusions This NMA showed that BF-200 ALA, using narrow-band lights, was the most efficacious treatment for mild to moderate AK on the face and scalp. This analysis is relevant for clinical decision making and health technology assessment, assisting the improved management of AK. PMID:24892649

A polarizable QM/MM approach to the molecular dynamics of amide groups solvated in water

NASA Astrophysics Data System (ADS)

Schwörer, Magnus; Wichmann, Christoph; Tavan, Paul

2016-03-01

The infrared (IR) spectra of polypeptides are dominated by the so-called amide bands. Because they originate from the strongly polar and polarizable amide groups (AGs) making up the backbone, their spectral positions sensitively depend on the local electric fields. Aiming at accurate computations of these IR spectra by molecular dynamics (MD) simulations, which derive atomic forces from a hybrid quantum and molecular mechanics (QM/MM) Hamiltonian, here we consider the effects of solvation in bulk liquid water on the amide bands of the AG model compound N-methyl-acetamide (NMA). As QM approach to NMA we choose grid-based density functional theory (DFT). For the surrounding MM water, we develop, largely based on computations, a polarizable molecular mechanics (PMM) model potential called GP6P, which features six Gaussian electrostatic sources (one induced dipole, five static partial charge distributions) and, therefore, avoids spurious distortions of the DFT electron density in hybrid DFT/PMM simulations. Bulk liquid GP6P is shown to have favorable properties at the thermodynamic conditions of the parameterization and beyond. Lennard-Jones (LJ) parameters of the DFT fragment NMA are optimized by comparing radial distribution functions in the surrounding GP6P liquid with reference data obtained from a "first-principles" DFT-MD simulation. Finally, IR spectra of NMA in GP6P water are calculated from extended DFT/PMM-MD trajectories, in which the NMA is treated by three different DFT functionals (BP, BLYP, B3LYP). Method-specific frequency scaling factors are derived from DFT-MD simulations of isolated NMA. The DFT/PMM-MD simulations with GP6P and with the optimized LJ parameters then excellently predict the effects of aqueous solvation and deuteration observed in the IR spectra of NMA. As a result, the methods required to accurately compute such spectra by DFT/PMM-MD also for larger peptides in aqueous solution are now at hand.

A polarizable QM/MM approach to the molecular dynamics of amide groups solvated in water

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

Schwörer, Magnus; Wichmann, Christoph; Tavan, Paul, E-mail: tavan@physik.uni-muenchen.de

2016-03-21

The infrared (IR) spectra of polypeptides are dominated by the so-called amide bands. Because they originate from the strongly polar and polarizable amide groups (AGs) making up the backbone, their spectral positions sensitively depend on the local electric fields. Aiming at accurate computations of these IR spectra by molecular dynamics (MD) simulations, which derive atomic forces from a hybrid quantum and molecular mechanics (QM/MM) Hamiltonian, here we consider the effects of solvation in bulk liquid water on the amide bands of the AG model compound N-methyl-acetamide (NMA). As QM approach to NMA we choose grid-based density functional theory (DFT). Formore » the surrounding MM water, we develop, largely based on computations, a polarizable molecular mechanics (PMM) model potential called GP6P, which features six Gaussian electrostatic sources (one induced dipole, five static partial charge distributions) and, therefore, avoids spurious distortions of the DFT electron density in hybrid DFT/PMM simulations. Bulk liquid GP6P is shown to have favorable properties at the thermodynamic conditions of the parameterization and beyond. Lennard-Jones (LJ) parameters of the DFT fragment NMA are optimized by comparing radial distribution functions in the surrounding GP6P liquid with reference data obtained from a “first-principles” DFT-MD simulation. Finally, IR spectra of NMA in GP6P water are calculated from extended DFT/PMM-MD trajectories, in which the NMA is treated by three different DFT functionals (BP, BLYP, B3LYP). Method-specific frequency scaling factors are derived from DFT-MD simulations of isolated NMA. The DFT/PMM-MD simulations with GP6P and with the optimized LJ parameters then excellently predict the effects of aqueous solvation and deuteration observed in the IR spectra of NMA. As a result, the methods required to accurately compute such spectra by DFT/PMM-MD also for larger peptides in aqueous solution are now at hand.« less

A network meta-analysis of atomoxetine and osmotic release oral system methylphenidate in the treatment of attention-deficit/hyperactivity disorder in adult patients.

PubMed

Bushe, Chris; Day, Kathleen; Reed, Victoria; Karlsdotter, Kristina; Berggren, Lovisa; Pitcher, Ashley; Televantou, Foula; Haynes, Virginia

2016-05-01

The lack of head-to-head clinical studies powered to compare atomoxetine and osmotic release oral system (OROS) methylphenidate necessitates treatment comparison by methods that include indirect evidence such as network meta-analysis (NMA). A NMA assessing the relative treatment effects of atomoxetine and OROS methylphenidate in adults with attention-deficit/hyperactivity disorder (ADHD) was conducted. Studies were identified by systematic literature review. Analyses summarised improvements in efficacy, measured by ADHD-specific scales, using Cohen'sdto calculate the standardised mean difference (SMD), and all cause discontinuations. Results showed effect sizes (SMD, 95% credible interval (CrI)) relative to placebo that did not differ significantly between atomoxetine (0.46, 0.36-0.56) and OROS methylphenidate (0.51, 0.40-0.63) in clinical studies of up to 12 weeks' duration (SMD, 95% CrI for atomoxetine versus OROS methylphenidate: -0.05, -0.18-0.08). Patients treated with these medications responded better than those given placebo across all analyses. There was also no significant difference in discontinuation rates between atomoxetine and OROS methylphenidate (odds ratio, 95% CrI: 0.85, 0.53-1.35). Between-study heterogeneity was low overall. Results of this NMA suggest that the efficacy of atomoxetine and OROS methylphenidate in adults does not differ significantly. Clinical guidelines may require amendment to reflect these recent data. © The Author(s) 2016.

Comparison of sedation strategies for critically ill patients: a protocol for a systematic review incorporating network meta-analyses.

PubMed

Hutton, Brian; Burry, Lisa D; Kanji, Salmaan; Mehta, Sangeeta; Guenette, Melanie; Martin, Claudio M; Fergusson, Dean A; Adhikari, Neill K; Egerod, Ingrid; Williamson, David; Straus, Sharon; Moher, David; Ely, E Wesley; Rose, Louise

2016-09-20

Sedatives and analgesics are administered to provide sedation and manage agitation and pain in most critically ill mechanically ventilated patients. Various sedation administration strategies including protocolized sedation and daily sedation interruption are used to mitigate drug pharmacokinetic limitations and minimize oversedation, thereby shortening the duration of mechanical ventilation. At present, it is unclear which strategy is most effective, as few have been directly compared. Our review will use network meta-analysis (NMA) to compare and rank sedation strategies to determine their efficacy and safety for mechanically ventilated patients. We will search the following from 1980 to March 2016: Ovid MEDLINE, CINAHL, Embase, PsycINFO, and Web of Science. We will also search the Cochrane Library, gray literature, and the International Clinical Trials Registry Platform. We will use a validated randomized control trial search filter to identify studies evaluating any strategy to optimize sedation in mechanically ventilated adult patients. Authors will independently extract data from eligible studies in duplicate and complete the Cochrane Risk of Bias tool. Our outcomes of interest include duration of mechanical ventilation, time to first extubation, ICU and hospital length of stay, re-intubation, tracheostomy, mortality, total sedative and opioid exposure, health-related quality of life, and adverse events. To inform our NMA, we will first conduct conventional pair-wise meta-analyses using random-effects models. Where appropriate, we will perform Bayesian NMA using WinBUGS software. There are multiple strategies to optimize sedation for mechanically ventilated patients. Current ICU guidelines recommend protocolized sedation or daily sedation interruption. Our systematic review incorporating NMA will provide a unified analysis of all sedation strategies to determine the relative efficacy and safety of interventions that may not have been compared directly. We will provide knowledge users, decision makers, and professional societies with ranking of multiple sedation strategies to inform future sedation guidelines. PROSPERO CRD42016037480.

Safety and efficacy of minimalist approach in transfemoral transcatheter aortic valve replacement: insights from the Optimized transCathEter vAlvular interventioN-Transcatheter Aortic Valve Implantation (OCEAN-TAVI) registry.

PubMed

Hosoba, Soh; Yamamoto, Masanori; Shioda, Kayoko; Sago, Mitsuru; Koyama, Yutaka; Shimura, Tetsuro; Kagase, Ai; Tada, Norio; Naganuma, Toru; Araki, Motoharu; Yamanaka, Futoshi; Shirai, Shinichi; Watanabe, Yusuke; Hayashida, Kentaro

2018-03-01

Favourable results have been reported for monitored anaesthesia care that includes local anaesthesia and conscious sedation [minimalist approach (MA)] for transfemoral transcatheter aortic valve replacement (TAVR). However, the efficacy of MA is still controversial in Japan. We describe our experience from a Japanese multicentre registry. Between October 2013 and April 2016, 1215 consecutive Japanese patients with symptomatic, severe aortic stenosis undergoing TAVR with self-expandable or balloon-expandable valves were prospectively included in the Optimized transCathEter vAlvular intervention-Transcatheter Aortic Valve Implantation (OCEAN-TAVI) registry. Of these patients, we retrospectively reviewed 921 consecutive patients who underwent elective transfemoral-TAVR. We evaluated the perioperative results of MA-TAVR and non-minimalist approach (NMA) TAVR using propensity score matching analysis. A total of 118 patients underwent MA-TAVR, and 802 patients underwent NMA-TAVR [median age 84 vs 85 years, P = 0.25; Society of Thoracic Surgeons (STS) score 7.6 vs 6.4, P = 0.01]. One hundred eighteen matched pairs were compared after propensity score matching. In-hospital mortality and stroke/transient ischaemic attack were not significantly different between the MA-TAVR and the NMA-TAVR groups (2.5% vs 0.8%, P = 0.3; 1.7% vs 0.8%, P = 0.6, respectively). Major or life-threatening bleeding and the transfusion rate were significantly lower in the MA-TAVR group (3.4% vs 17%, P = 0.003; 6.8% vs 29%, P = 0.0002, respectively). The total intensive care unit days and length of hospital stay were significantly lower in the MA-TAVR group (P ≤ 0.0002). MA-TAVR has similar results to NMA-TAVR in terms of mortality and stroke in this Japanese multicentre registry. Shorter procedure time and hospital stays were seen in the MA-TAVR group. MA-TAVR is as safe and effective as NMA-TAVR. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Molecular dynamics: deciphering the data.

PubMed

Dauber-Osguthorpe, P; Maunder, C M; Osguthorpe, D J

1996-06-01

The dynamic behaviour of molecules is important in determining their activity. Molecular dynamics (MD) simulations give a detailed description of motion, from small fluctuations to conformational transitions, and can include solvent effects. However, extracting useful information about conformational motion from a trajectory is not trivial. We have used digital signal-processing techniques to characterise the motion in MD simulations, including: calculating the frequency distribution, applying filtering functions, and extraction of vectors defining the characteristic motion for each frequency in an MD simulation. We describe here some typical results obtained for peptides and proteins. The nature of the low-frequency modes of motion, as obtained from MD and normal mode (NM) analysis, of Ace-(Ala)31-Nma and of a proline mutant is discussed. Low-frequency modes extracted from the MD trajectories of Rop protein and phospholipase A2 reveal characteristic motions of secondary structure elements, as well as concerned motions that are of significance to the protein's biological activity. MD simulations are also used frequently as a tool for conformational searches and for investigating protein folding/unfolding. We have developed a novel method that uses time-domain filtering to channel energy into conformational motion and thus enhance conformational transitions. The selectively enhanced molecular dynamics method is tested on the small molecule hexane.

Molecular dynamics: Deciphering the data

NASA Astrophysics Data System (ADS)

Dauber-Osguthorpe, Pnina; Maunder, Colette M.; Osguthorpe, David J.

1996-06-01

The dynamic behaviour of molecules is important in determining their activity. Molecular dynamics (MD) simulations give a detailed description of motion, from small fluctuations to conformational transitions, and can include solvent effects. However, extracting useful information about conformational motion from a trajectory is not trivial. We have used digital signal-processing techniques to characterise the motion in MD simulations, including: calculating the frequency distribution, applying filtering functions, and extraction of vectors defining the characteristic motion for each frequency in an MD simulation. We describe here some typical results obtained for peptides and proteins. The nature of the low-frequency modes of motion, as obtained from MD and normal mode (NM) analysis, of Ace-(Ala)31-Nma and of a proline mutant is discussed. Low-frequency modes extracted from the MD trajectories of Rop protein and phospholipase A2 reveal characteristic motions of secondary structure elements, as well as concerted motions that are of significance to the protein's biological activity. MD simulations are also used frequently as a tool for conformational searches and for investigating protein folding/unfolding. We have developed a novel method that uses time-domain filtering to channel energy into conformational motion and thus enhance conformational transitions. The selectively enhanced molecular dynamics method is tested on the small molecule hexane.

Risk of Myocardial Infarction in Patients with Long-Term Non-Vitamin K Antagonist Oral Anticoagulant Treatment.

PubMed

Tornyos, Adrienn; Kehl, Dániel; D'Ascenzo, Fabrizio; Komócsi, András

2016-01-01

The relative cardiovascular (CV) safety of oral anticoagulants continues to be debated, and in particular concerns for risk of myocardial infarction (MI) have been raised. We analyzed the risk of MI in patients treated long term with oral anticoagulants (vitamin K antagonists [VKA], direct thrombin inhibitors or activated X factor antagonist) for atrial fibrillation, deep vein thrombosis or pulmonary embolism using a network meta-analysis (NMA). Randomized, phase 3 trials comparing novel anticoagulants to VKA were searched. Information on study design and clinical outcomes was extracted. The primary end-point of the analysis was the occurrence of MI or acute coronary syndrome. A Bayesian multiple treatment analysis was performed using fixed-effect and random-effects modeling. Twelve trials including 100,524 randomized patients were analyzed. The odds for MI in NMA were worse with dabigatran when compared to VKA, rivaroxaban, apixaban, and edoxaban (OR: 0.66 CI: 0.49-0.87; OR: 0.56 CI: 0.38-0.82, OR: 0.59 CI 0.40-0.88, and OR: 0.71 CI: 0.50-1.0, respectively).The posterior probability of being the first best choice of treatment was 53.5% for rivaroxaban, 33.8% for apixaban, 9.5% for ximelagatran, 2.0% for edoxaban, 1.2% for VKA, and 0.007% for dabigatran. There is a considerable heterogeneity regarding CV safety among oral anticoagulants. Differences in risk of MI may influence the choice of treatment. Multiple treatment NMA found 29%-44% higher odds of MI with dabigatran supporting the concerns regarding its CV safety. Copyright © 2015 Elsevier Inc. All rights reserved.

Safety profile of biologic drugs in the therapy of Crohn disease: A systematic review and network meta-analysis.

PubMed

Moćko, Paweł; Kawalec, Paweł; Pilc, Andrzej

2016-12-01

Crohn disease (CD) is an inflammatory bowel disease which occurs especially in developed countries of Western Europe and North America. The aim of the study was to compare the safety profile of biologic drugs in patients with CD. A systematic literature search was performed using PubMed, Embase, and CENTRAL databases, until April 27, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, vedolizumab, certolizumab pegol, and ustekinumab) with one another or with placebo in patients with CD. The network meta-analysis (NMA) was conducted for an induction phase (6-10 weeks) and maintenance phase (52-56 weeks) with a Bayesian hierarchical random effects model in the ADDIS ® software. The PROSPERO registration number was CRD42016032606. Ten RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, vedolizumab, certolizumab pegol, and ustekinumab, and in the case of the maintenance phase-of infliximab, adalimumab, and vedolizumab. There were no significant differences in the rate of adverse events in patients treated with biologics. Statistical analysis revealed that vedolizumab had the greatest probability of being the safest treatment in most endpoints in the induction phase and adalimumab-in the maintenance phase. No significant differences between the biologics in the relative safety profile analysis were observed. Further studies are needed to confirm our findings, including head-to-head comparisons between the analyzed biologics. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

77 FR 15445 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-15

... Effectiveness of Proposed Rule Change To Amend Online Form NMA, the Standardized Membership Application Form... online Form NMA, the standardized membership application form applicants must file pursuant to NASD Rule...), each applicant for FINRA membership must complete and electronically file the standardized online Form...

Network meta-analysis of multiple outcome measures accounting for borrowing of information across outcomes.

PubMed

Achana, Felix A; Cooper, Nicola J; Bujkiewicz, Sylwia; Hubbard, Stephanie J; Kendrick, Denise; Jones, David R; Sutton, Alex J

2014-07-21

Network meta-analysis (NMA) enables simultaneous comparison of multiple treatments while preserving randomisation. When summarising evidence to inform an economic evaluation, it is important that the analysis accurately reflects the dependency structure within the data, as correlations between outcomes may have implication for estimating the net benefit associated with treatment. A multivariate NMA offers a framework for evaluating multiple treatments across multiple outcome measures while accounting for the correlation structure between outcomes. The standard NMA model is extended to multiple outcome settings in two stages. In the first stage, information is borrowed across outcomes as well across studies through modelling the within-study and between-study correlation structure. In the second stage, we make use of the additional assumption that intervention effects are exchangeable between outcomes to predict effect estimates for all outcomes, including effect estimates on outcomes where evidence is either sparse or the treatment had not been considered by any one of the studies included in the analysis. We apply the methods to binary outcome data from a systematic review evaluating the effectiveness of nine home safety interventions on uptake of three poisoning prevention practices (safe storage of medicines, safe storage of other household products, and possession of poison centre control telephone number) in households with children. Analyses are conducted in WinBUGS using Markov Chain Monte Carlo (MCMC) simulations. Univariate and the first stage multivariate models produced broadly similar point estimates of intervention effects but the uncertainty around the multivariate estimates varied depending on the prior distribution specified for the between-study covariance structure. The second stage multivariate analyses produced more precise effect estimates while enabling intervention effects to be predicted for all outcomes, including intervention effects on outcomes not directly considered by the studies included in the analysis. Accounting for the dependency between outcomes in a multivariate meta-analysis may or may not improve the precision of effect estimates from a network meta-analysis compared to analysing each outcome separately.

Double-layer interlaced nested multi-ring array metallic mesh for high-performance transparent electromagnetic interference shielding.

PubMed

Wang, Heyan; Lu, Zhengang; Liu, Yeshu; Tan, Jiubin; Ma, Limin; Lin, Shen

2017-04-15

We report a nested multi-ring array metallic mesh (NMA-MM) that shows a highly uniform diffraction pattern theoretically and experimentally. Then a high-performance transparent electromagnetic interference (EMI) shielding structure is constituted by the double-layer interlaced NMA-MMs separated by transparent quartz-glass substrate. Experimental results show that double-layer interlaced NMA-MM structure exhibits a shielding effectiveness (SE) of over 27 dB in the Ku-band, with a maximal SE of 37 dB at 12 GHz, normalized optical transmittance of 90%, and minimal image quality degradation due to the interlaced arrangement. It thus shows great potential for practical applications in transparent EMI shielding devices.

Early CMV Viremia Is Associated with Impaired Viral Control following Nonmyeloablative Hematopoietic Cell Transplantation with a Total Lymphoid Irradiation and Antithymocyte Globulin Preparative Regimen

PubMed Central

Schaenman, Joanna M.; Shashidhar, Sumana; Rhee, Chanu; Wong, Jonathan; Navato, Shelly; Wong, Ruby M.; Ho, Dora Y.; Arai, Sally; Johnston, Laura; Brown, Janice M.

2017-01-01

The reconstitution of immune function after hematopoietic cell transplant (HCT) plays an important role in the control of viral infections. Both donor and recipient cytomegalovirus (CMV) serostatus has been shown to contribute to effective immune function; however, the influence of a nonmyeloablative preparative (NMA) regimen using total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) on antiviral immune reconstitution has not yet been described. In 117 recipients of NMA HCT patients following ATG and TLI, not unexpectedly, CMV viremia was seen in approximately 60% of the seropositive patients regardless of donor serostatus, and recipient seropositivity significantly increased the odds of CMV viremia after transplant in a multivariate analysis. The administration of ATG and TLI resulted in a strikingly earlier viremia in the posttransplant period when compared to the previously reported timing of viremia following myeloablative preparative regimens, especially for transplant recipients who were seropositive for CMV with seronegative donors. Furthermore, early viremia in the setting of a CMV naïve donor was associated with a delay in functional antiviral control. These observations demonstrate the dynamic nature of immunity in relation to CMV antigen exposure in the complex environment resulting from NMA conditions where both donor and residual recipient immune response affect viral control. PMID:20736077

Network meta-analysis combining individual patient and aggregate data from a mixture of study designs with an application to pulmonary arterial hypertension.

PubMed

Thom, Howard H Z; Capkun, Gorana; Cerulli, Annamaria; Nixon, Richard M; Howard, Luke S

2015-04-12

Network meta-analysis (NMA) is a methodology for indirectly comparing, and strengthening direct comparisons of two or more treatments for the management of disease by combining evidence from multiple studies. It is sometimes not possible to perform treatment comparisons as evidence networks restricted to randomized controlled trials (RCTs) may be disconnected. We propose a Bayesian NMA model that allows to include single-arm, before-and-after, observational studies to complete these disconnected networks. We illustrate the method with an indirect comparison of treatments for pulmonary arterial hypertension (PAH). Our method uses a random effects model for placebo improvements to include single-arm observational studies into a general NMA. Building on recent research for binary outcomes, we develop a covariate-adjusted continuous-outcome NMA model that combines individual patient data (IPD) and aggregate data from two-arm RCTs with the single-arm observational studies. We apply this model to a complex comparison of therapies for PAH combining IPD from a phase-III RCT of imatinib as add-on therapy for PAH and aggregate data from RCTs and single-arm observational studies, both identified by a systematic review. Through the inclusion of observational studies, our method allowed the comparison of imatinib as add-on therapy for PAH with other treatments. This comparison had not been previously possible due to the limited RCT evidence available. However, the credible intervals of our posterior estimates were wide so the overall results were inconclusive. The comparison should be treated as exploratory and should not be used to guide clinical practice. Our method for the inclusion of single-arm observational studies allows the performance of indirect comparisons that had previously not been possible due to incomplete networks composed solely of available RCTs. We also built on many recent innovations to enable researchers to use both aggregate data and IPD. This method could be used in similar situations where treatment comparisons have not been possible due to restrictions to RCT evidence and where a mixture of aggregate data and IPD are available.

Regulatory tasks of national medical associations - international comparison and the Israeli case

PubMed Central

2013-01-01

Background In many countries, NMAs, along with other stakeholders, play a part in the regulation of physicians. The purpose of this paper is to compare and explain the level of involvement of NMAs in physician regulation in several developed countries, with a specific emphasis on Israel. Methods The authors conducted a review of the literature on physician regulation, focusing on licensing and registration, postgraduate training and physician disciplinary measures. Detailed country specific information was also obtained via the websites of relevant NMAs and regulatory bodies and correspondence with select NMAs. Five test cases were examined in detail: Germany, Israel, the Netherlands, the United Kingdom and the United States. The Israeli case will be discussed at greater length. Results Medical licensing usually lies in the hands of the government (on the national or state level). Specialist training, on the other hand, is often self-regulated and entrusted in the hands of the profession, frequently under the direct responsibility of the NMA, as in Israel, the Netherlands and Germany. In all the countries presented, other than Germany, the NMA is not involved in instituting disciplinary procedures in cases of alleged physician misconduct. Discussion The extent to which NMAs fulfill regulatory functions varies greatly from country to country. The relationship between government and the profession in the area of regulation often parallels the dominant mode of governance in the health care system as a whole. Specifically, the level of involvement of the Israeli Medical Association in medical regulation is a result of political, historical and ideological arrangements shaped vis-à-vis the government over the years. Conclusions In Continental Europe, co-operation between the NMA and the government is more common than in the USA and the UK. The Israeli regulatory model emerged in a European-like fashion, closer to the Netherlands than to Germany. The Israeli case, as well as the others, demonstrates the importance of history and ideology in shaping contemporary regulatory models. PMID:23425333

A network meta-analysis to compare simeprevir with boceprevir and telaprevir in combination with peginterferon-α and ribavirin in patients infected with genotype 1 Hepatitis C virus.

PubMed

Taieb, Vanessa; Pacou, Maud; Ho, Sophia; Pettré, Ségolène; Van Sanden, Suzy; Pisini, Marta; Ustianowski, Andrew; Mehnert, Angelika

2015-01-01

To conduct a network meta-analysis (NMA) to assess the relative efficacy and safety of simeprevir, a second generation oral protease inhibitor (PI), compared to telaprevir and boceprevir in combination with pegylated interferon-α and ribavirin (PR) in patients with chronic hepatitis C. A systematic literature review and NMA of randomized controlled trials involving anti-virals added to PR were conducted. Electronic database searches and hand searches were conducted to identify relevant publications. Outcomes of interest included sustained virologic response (SVR), incidence of adverse events (AEs), and discontinuation due to AEs. Networks were based on treatment-, dose-, and duration-specific nodes. Sub-group analyses were conducted to investigate heterogeneity, based on Metavir scores, sub-genotypes 1a/1b, and prior response. A total of 15 publications were considered for the base case of the meta-analysis. Simeprevir was associated with higher SVR rates than PR alone. Compared to telaprevir and boceprevir, SVR rates tended to be higher for simeprevir, with odds ratios ranging from 1.27 [0.81-2.00] to 2.61 [1.44-4.74] in treatment-naïve and from 1.04 [0.78-1.38] to 1.74 [0.84-3.61] in treatment-experienced patients, respectively. In terms of safety, the risks of anemia and discontinuations due to AEs were lower for simeprevir compared to PR alone, telaprevir, and boceprevir. The risk of rash was lower for simeprevir compared to telaprevir, and similar compared to PR alone and boceprevir. This NMA in genotype 1 HCV patients suggests a similar or better efficacy and tolerability profile for simeprevir compared to telaprevir and boceprevir.

The Chemical Shift Baseline for High-Pressure NMR Spectra of Proteins.

PubMed

Frach, Roland; Kibies, Patrick; Böttcher, Saraphina; Pongratz, Tim; Strohfeldt, Steven; Kurrmann, Simon; Koehler, Joerg; Hofmann, Martin; Kremer, Werner; Kalbitzer, Hans Robert; Reiser, Oliver; Horinek, Dominik; Kast, Stefan M

2016-07-18

High-pressure (HP) NMR spectroscopy is an important method for detecting rare functional states of proteins by analyzing the pressure response of chemical shifts. However, for the analysis of the shifts it is mandatory to understand the origin of the observed pressure dependence. Here we present experimental HP NMR data on the (15) N-enriched peptide bond model, N-methylacetamide (NMA), in water, combined with quantum-chemical computations of the magnetic parameters using a pressure-sensitive solvation model. Theoretical analysis of NMA and the experimentally used internal reference standard 4,4-dimethyl-4-silapentane-1-sulfonic (DSS) reveal that a substantial part of observed shifts can be attributed to purely solvent-induced electronic polarization of the backbone. DSS is only marginally responsive to pressure changes and is therefore a reliable sensor for variations in the local magnetic field caused by pressure-induced changes of the magnetic susceptibility of the solvent. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative efficacy of golimumab, infliximab, and adalimumab for moderately to severely active ulcerative colitis: a network meta-analysis accounting for differences in trial designs.

PubMed

Thorlund, Kristian; Druyts, Eric; Toor, Kabirraaj; Mills, Edward J

2015-05-01

To conduct a network meta-analysis (NMA) to establish the comparative efficacy of infliximab, adalimumab and golimumab for the treatment of moderately to severely active ulcerative colitis (UC). A systematic literature search identified five randomized controlled trials for inclusion in the NMA. One trial assessed golimumab, two assessed infliximab and two assessed adalimumab. Outcomes included clinical response, clinical remission, mucosal healing, sustained clinical response and sustained clinical remission. Innovative methods were used to allow inclusion of the golimumab trial data given the alternative design of this trial (i.e., two-stage re-randomization). After induction, no statistically significant differences were found between golimumab and adalimumab or between golimumab and infliximab. Infliximab was statistically superior to adalimumab after induction for all outcomes and treatment ranking suggested infliximab as the superior treatment for induction. Golimumab and infliximab were associated with similar efficacy for achieving maintained clinical remission and sustained clinical remission, whereas adalimumab was not significantly better than placebo for sustained clinical remission. Golimumab and infliximab were also associated with similar efficacy for achieving maintained clinical response, sustained clinical response and mucosal healing. Finally, golimumab 50 and 100 mg was statistically superior to adalimumab for clinical response and sustained clinical response, and golimumab 100 mg was also statistically superior to adalimumab for mucosal healing. The results of our NMA suggest that infliximab was statistically superior to adalimumab after induction, and that golimumab was statistically superior to adalimumab for sustained outcomes. Golimumab and infliximab appeared comparable in efficacy.

Highly sensitive current sensor utilizing CrNi-wire supported microfiber coils

NASA Astrophysics Data System (ADS)

Xie, Xiaodong; Li, Jie; Sun, Li-Peng; Jin, Long; Guan, Bai-ou

2013-09-01

High current sensitivity is obtained based on a microfiber that is wrapping around a chrome-nickel (CrNi) wire. Due to the strong heating effect of the CrNi wire with the flowing electric current, the mode index and the loop length of microfiber are changed, resulting in the shift of resonant wavelength. The measured current responsivity is as high as 220.65nm/A2, which is in two or three magnitude orders than the previously-obtained ones. We study the influence of component size to the structure performance, which is useful for future applications of current sensing or tuning devices.

Acupuncture and related therapies used as add-on or alternative to prokinetics for functional dyspepsia: overview of systematic reviews and network meta-analysis.

PubMed

Ho, Robin S T; Chung, Vincent C H; Wong, Charlene H L; Wu, Justin C Y; Wong, Samuel Y S; Wu, Irene X Y

2017-09-04

Prokinetics for functional dyspepsia (FD) have relatively higher number needed to treat values. Acupuncture and related therapies could be used as add-on or alternative. An overview of systematic reviews (SRs) and network meta-analyses (NMA) were performed to evaluate the comparative effectiveness of different acupuncture and related therapies. We conducted a comprehensive literature search for SRs of randomized controlled trials (RCTs) in eight international and Chinese databases. Data from eligible RCTs were extracted for random effect pairwise meta-analyses. NMA was used to explore the most effective treatment among acupuncture and related therapies used alone or as add-on to prokinetics, compared to prokinetics alone. From five SRs, 22 RCTs assessing various acupuncture and related therapies were included. No serious adverse events were reported. Two pairwise meta-analyses showed manual acupuncture has marginally stronger effect in alleviating global FD symptoms, compared to domperidone or itopride. Results from NMA showed combination of manual acupuncture and clebopride has the highest probability in alleviating patient reported global FD symptom. Combination of manual acupuncture and clebopride has the highest probability of being the most effective treatment for FD symptoms. Patients who are contraindicated for prokinetics may use manual acupuncture or moxibustion as alternative. Future confirmatory comparative effectiveness trials should compare clebopride add-on manual acupuncture with domperidone add-on manual acupuncture and moxibustion.

Network meta-analysis of multiple outcome measures accounting for borrowing of information across outcomes

PubMed Central

2014-01-01

Background Network meta-analysis (NMA) enables simultaneous comparison of multiple treatments while preserving randomisation. When summarising evidence to inform an economic evaluation, it is important that the analysis accurately reflects the dependency structure within the data, as correlations between outcomes may have implication for estimating the net benefit associated with treatment. A multivariate NMA offers a framework for evaluating multiple treatments across multiple outcome measures while accounting for the correlation structure between outcomes. Methods The standard NMA model is extended to multiple outcome settings in two stages. In the first stage, information is borrowed across outcomes as well across studies through modelling the within-study and between-study correlation structure. In the second stage, we make use of the additional assumption that intervention effects are exchangeable between outcomes to predict effect estimates for all outcomes, including effect estimates on outcomes where evidence is either sparse or the treatment had not been considered by any one of the studies included in the analysis. We apply the methods to binary outcome data from a systematic review evaluating the effectiveness of nine home safety interventions on uptake of three poisoning prevention practices (safe storage of medicines, safe storage of other household products, and possession of poison centre control telephone number) in households with children. Analyses are conducted in WinBUGS using Markov Chain Monte Carlo (MCMC) simulations. Results Univariate and the first stage multivariate models produced broadly similar point estimates of intervention effects but the uncertainty around the multivariate estimates varied depending on the prior distribution specified for the between-study covariance structure. The second stage multivariate analyses produced more precise effect estimates while enabling intervention effects to be predicted for all outcomes, including intervention effects on outcomes not directly considered by the studies included in the analysis. Conclusions Accounting for the dependency between outcomes in a multivariate meta-analysis may or may not improve the precision of effect estimates from a network meta-analysis compared to analysing each outcome separately. PMID:25047164

Safety Profile of Biologic Drugs in the Therapy of Ulcerative Colitis: A Systematic Review and Network Meta-Analysis.

PubMed

Moćko, Paweł; Kawalec, Paweł; Pilc, Andrzej

2016-08-01

We compared the safety profile of biologic drugs in patients with moderately to severely active ulcerative colitis (UC). A systematic literature search was performed using Medline (PubMed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases through February 9, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, golimumab, and vedolizumab) with one another or with placebo in patients with UC. Two reviewers independently conducted the search and selection of studies and rated the risk of bias in each trial. The network meta-analysis (NMA) was conducted for an induction phase (6-8 weeks) and maintenance phase (52-54 weeks) with a Bayesian hierarchical random effects model in Aggregate Data Drug Information System (ADDIS) software. The PROSPERO registration number was CRD42016032607. Seven RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, golimumab, and vedolizumab, and in the case of the maintenance phase of infliximab, adalimumab, golimumab, and vedolizumab. The methodological quality of the included RCTs was evaluated as low risk of bias, but high risk of bias in the case of attrition bias (incomplete outcome data) according to the Cochrane criteria. No significant differences were found in the rate of adverse events in patients treated with the reviewed biologics. Vedolizumab was most likely to have the most favorable safety profile in the induction phase as was infliximab for the maintenance phase. The assessment of the relative safety profile revealed no significant differences between the biologic drugs. Further studies are needed to confirm our findings including head-to-head comparisons between the analyzed biologics. © 2016 Pharmacotherapy Publications, Inc.

Evidences for Cooperative Resonance-Assisted Hydrogen Bonds in Protein Secondary Structure Analogs

NASA Astrophysics Data System (ADS)

Zhou, Yu; Deng, Geng; Zheng, Yan-Zhen; Xu, Jing; Ashraf, Hamad; Yu, Zhi-Wu

2016-11-01

Cooperative behaviors of the hydrogen bonding networks in proteins have been discovered for a long time. The structural origin of this cooperativity, however, is still under debate. Here we report a new investigation combining excess infrared spectroscopy and density functional theory calculation on peptide analogs, represented by N-methylformamide (NMF) and N-methylacetamide (NMA). Interestingly, addition of the strong hydrogen bond acceptor, dimethyl sulfoxide, to the pure analogs caused opposite effects, namely red- and blue-shift of the N-H stretching infrared absorption in NMF and NMA, respectively. The contradiction can be reconciled by the marked lowering of the energy levels of the self-associates between NMA molecules due to a cooperative effect of the hydrogen bonds. On the contrary, NMF molecules cannot form long-chain cooperative hydrogen bonds because they tend to form dimers. Even more interestingly, we found excellent linear relationships between changes on bond orders of N-H/N-C/C = O and the hydrogen bond energy gains upon the formation of hydrogen bonding multimers in NMA, suggesting strongly that the cooperativity originates from resonance-assisted hydrogen bonds. Our findings provide insights on the structures of proteins and may also shed lights on the rational design of novel molecular recognition systems.

Static Postural Stability in Chronic Ankle Instability, An Ankle Sprain and Healthy Ankles.

PubMed

Kwon, Yong Ung

2018-05-18

To identify the single leg balance (SLB) test that discriminates among healthy, coper, and chronic ankle instability (CAI) groups and to determine effects of ankle muscles on the balance error scoring system (BESS) among the three populations. 60 subjects (20 per group) performed the SLB test with eyes open (EO) and eyes closed (EC). Normalized mean amplitude (NMA) of the tibia anterior (TA), fibularis longus (FL), and medial gastrocnemius (MG) muscles and BESS were measured while performing the SLB test. The coper group had a lower error score than the CAI group in the EC. NMA was greater in the CAI group compared to in the healthy and coper groups regardless of muscle type. NMA of the TA was less than the PL and MG regardless of the group in the EO. The CAI group demonstrated greater NMAs of the PL and MG than the healthy and coper groups in the EC. The CAI group demonstrated greater NMA of the PL and MG by compensating their ankle muscles in the EO and EC. BESS suggests that the coper group may have coping mechanisms to stabilize static postural control compared to the CAI group. The EC may be better to detect static postural instability in the CAI or coper group. © Georg Thieme Verlag KG Stuttgart · New York.

Systematic review and network meta-analysis of tedizolid for the treatment of acute bacterial skin and skin structure infections caused by MRSA.

PubMed

McCool, Rachael; Gould, Ian M; Eales, Jacqui; Barata, Teresa; Arber, Mick; Fleetwood, Kelly; Glanville, Julie; Kauf, Teresa L

2017-01-07

Tedizolid, the active moiety of tedizolid phosphate, is approved in the United States, the European Union, Canada and a number of other countries for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). This network meta-analysis (NMA) evaluates the comparative effectiveness of tedizolid and other antibacterials indicated for the treatment of ABSSSI caused by MRSA. Systematic review of 10 databases was undertaken to inform an NMA to estimate the relative effectiveness of tedizolid and established monotherapy comparators (ceftaroline, daptomycin, linezolid, teicoplanin, tigecycline, vancomycin) for treating MRSA-associated ABSSSI. Randomized controlled trials enrolling adults with ABSSSI or complicated skin and skin structure infections caused by suspected/documented MRSA were eligible for inclusion. Networks were developed based on similarity of study design, patient characteristics, outcome measures and available data. Outcomes of interest included clinical response at end of therapy (EOT), post-therapy evaluation (PTE) or test-of-cure assessment and treatment discontinuations resulting from adverse events (AEs). Bayesian NMA was conducted for each outcome using fixed-effects and random effects models. Literature searches identified 3,618 records; 15 trials met the inclusion criteria and were considered suitable for NMA comparison. In fixed-effects models, tedizolid had higher odds of clinical response at EOT (odds ratio [OR], 1.7; credible interval, 1.0, 3.0) and PTE than vancomycin (OR, 1.6; credible interval, 1.1, 2.5). No differences in odds of clinical response at EOT or PTE were observed between tedizolid and other comparators. There was no evidence of a difference among treatments for discontinuation due to AEs. Results from random effects and fixed-effects models were generally consistent. Tedizolid was superior to vancomycin for clinical response at EOT and PTE. There was no evidence of a difference between tedizolid and other comparators and no evidence of a difference between tedizolid and all comparators when evaluating discontinuation due to AEs. These findings suggest that tedizolid provides an alternative option for the management of serious skin infections caused by suspected or documented MRSA. This study is subject to the limitations inherent in all NMAs, and the results should be interpreted accordingly.

Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis.

PubMed

Veroniki, Areti Angeliki; Rios, Patricia; Cogo, Elise; Straus, Sharon E; Finkelstein, Yaron; Kealey, Ryan; Reynen, Emily; Soobiah, Charlene; Thavorn, Kednapa; Hutton, Brian; Hemmelgarn, Brenda R; Yazdi, Fatemeh; D'Souza, Jennifer; MacDonald, Heather; Tricco, Andrea C

2017-07-20

Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers. 29 cohort studies including 5100 infants/children. Monotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group. Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes. The NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8.75) and carbamazepine+phenobarbital+valproate (OR 19.12, CrI 1.49 to 337.50) were associated with significantly greater odds of psychomotor delay compared with control. Valproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen. PROSPERO database (CRD42014008925). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis

PubMed Central

Veroniki, Areti Angeliki; Rios, Patricia; Cogo, Elise; Straus, Sharon E; Finkelstein, Yaron; Kealey, Ryan; Reynen, Emily; Soobiah, Charlene; Thavorn, Kednapa; Hutton, Brian; Hemmelgarn, Brenda R; Yazdi, Fatemeh; D'Souza, Jennifer; MacDonald, Heather; Tricco, Andrea C

2017-01-01

Objectives Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. Design and setting Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers. Participants 29 cohort studies including 5100 infants/children. Interventions Monotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group. Primary and secondary outcome measures Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes. Results The NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8.75) and carbamazepine+phenobarbital+valproate (OR 19.12, CrI 1.49 to 337.50) were associated with significantly greater odds of psychomotor delay compared with control. Conclusions Valproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen. Trial registration number PROSPERO database (CRD42014008925). PMID:28729328

Network meta-analysis of migraine disorder treatment by NSAIDs and triptans.

PubMed

Xu, Haiyang; Han, Wei; Wang, Jinghua; Li, Mingxian

2016-12-01

Migraine is a neurological disorder resulting in large socioeconomic burden. This network meta-analysis (NMA) is designed to compare the relative efficacy and tolerability of non-steroidal anti-inflammatory agents (NSAIDs) and triptans. We conducted systematic searches in database PubMed and Embase. Treatment effectiveness was compared by synthesizing direct and indirect evidences using NMA. The surface under curve ranking area (SUCRA) was created to rank those interventions. Eletriptan and rizatriptan are superior to sumatriptan, zolmitriptan, almotriptan, ibuprofen and aspirin with respect to pain-relief. When analyzing 2 h-nausea-absence, rizatriptan has a better efficacy than sumatriptan, while other treatments indicate no distinctive difference compared with placebo. Furthermore, sumatriptan demonstrates a higher incidence of all-adverse-event compared with diclofenac-potassium, ibuprofen and almotriptan. This study suggests that eletriptan may be the most suitable therapy for migraine from a comprehensive point of view. In the meantime ibuprofen may also be a good choice for its excellent tolerability. Multi-component medication also attracts attention and may be a promising avenue for the next generation of migraine treatment.

Elastic Network Model of a Nuclear Transport Complex

NASA Astrophysics Data System (ADS)

Ryan, Patrick; Liu, Wing K.; Lee, Dockjin; Seo, Sangjae; Kim, Young-Jin; Kim, Moon K.

2010-05-01

The structure of Kap95p was obtained from the Protein Data Bank (www.pdb.org) and analyzed RanGTP plays an important role in both nuclear protein import and export cycles. In the nucleus, RanGTP releases macromolecular cargoes from importins and conversely facilitates cargo binding to exportins. Although the crystal structure of the nuclear import complex formed by importin Kap95p and RanGTP was recently identified, its molecular mechanism still remains unclear. To understand the relationship between structure and function of a nuclear transport complex, a structure-based mechanical model of Kap95p:RanGTP complex is introduced. In this model, a protein structure is simply modeled as an elastic network in which a set of coarse-grained point masses are connected by linear springs representing biochemical interactions at atomic level. Harmonic normal mode analysis (NMA) and anharmonic elastic network interpolation (ENI) are performed to predict the modes of vibrations and a feasible pathway between locked and unlocked conformations of Kap95p, respectively. Simulation results imply that the binding of RanGTP to Kap95p induces the release of the cargo in the nucleus as well as prevents any new cargo from attaching to the Kap95p:RanGTP complex.

Ny-Alesund Geodetic Observatory

NASA Technical Reports Server (NTRS)

Sieber, Moritz

2013-01-01

In 2012 the 20-m telescope at Ny-Alesund, Svalbard, operated by the Norwegian Mapping Authority (NMA), took part in 163 out of 168 scheduled sessions of the IVS program. Since spring, all data was transferred by network, and the receiver monitoring computer was replaced by a bus-coupler. In autumn, the NMA received building permission for a new observatory from the Governor of Svalbard. The bidding process and first construction work for the infrastructure will start in 2013.

Ab Initio and Improved Empirical Potentials for the Calculation of the Anharmonic Vibrational States and Intramolecular Mode Coupling of N-Methylacetamide

NASA Technical Reports Server (NTRS)

Gregurick, Susan K.; Chaban, Galina M.; Gerber, R. Benny; Kwak, Dochou (Technical Monitor)

2001-01-01

The second-order Moller-Plesset ab initio electronic structure method is used to compute points for the anharmonic mode-coupled potential energy surface of N-methylacetamide (NMA) in the trans(sub ct) configuration, including all degrees of freedom. The vibrational states and the spectroscopy are directly computed from this potential surface using the Correlation Corrected Vibrational Self-Consistent Field (CC-VSCF) method. The results are compared with CC-VSCF calculations using both the standard and improved empirical Amber-like force fields and available low temperature experimental matrix data. Analysis of our calculated spectroscopic results show that: (1) The excellent agreement between the ab initio CC-VSCF calculated frequencies and the experimental data suggest that the computed anharmonic potentials for N-methylacetamide are of a very high quality; (2) For most transitions, the vibrational frequencies obtained from the ab initio CC-VSCF method are superior to those obtained using the empirical CC-VSCF methods, when compared with experimental data. However, the improved empirical force field yields better agreement with the experimental frequencies as compared with a standard AMBER-type force field; (3) The empirical force field in particular overestimates anharmonic couplings for the amide-2 mode, the methyl asymmetric bending modes, the out-of-plane methyl bending modes, and the methyl distortions; (4) Disagreement between the ab initio and empirical anharmonic couplings is greater than the disagreement between the frequencies, and thus the anharmonic part of the empirical potential seems to be less accurate than the harmonic contribution;and (5) Both the empirical and ab initio CC-VSCF calculations predict a negligible anharmonic coupling between the amide-1 and other internal modes. The implication of this is that the intramolecular energy flow between the amide-1 and the other internal modes may be smaller than anticipated. These results may have important implications for the anharmonic force fields of peptides, for which N-methylacetamide is a model.

Development and implementation of an empirical frequency map for use in MD simulations of isotope-edited proteins, and, Development, implementation, and evaluation of an online student portal as a textbook replacement in an advanced general chemistry course

NASA Astrophysics Data System (ADS)

Shorb, Justin Matthew

The first portion of this thesis describes an extension of work done in the Skinner group to develop an empirical frequency map for N-methylacetamide (NMA) in water. NMA is a peptide bond capped on either side by a methyl group and is therefore a common prototypical molecule used when studying complicated polypeptides and proteins. This amide bond is present along the backbone of every protein as it connects individual component amino acids. This amide bond also has a strong observable frequency in the IR due to the Amide-I mode (predominantly carbon-oxygen stretching motion). This project describes the simplification of the prior model for mapping the frequency of the Amide-I mode from the electric field due to the environment and develops a parallel implementation of this algorithm for use in larger biological systems, such as the trans-membrane portion of the tetrameric polypeptide bundle protein CD3zeta. The second portion of this thesis describes the development, implementation and evaluation of an online textbook within the context of a cohesive theoretical framework. The project begins by describing what is meant when discussing a digital textbook, including a survey of various types of digital media being used to deliver textbook-like content. This leads into the development of a theoretical framework based on constructivist pedagogical theory, hypertext learning theory, and chemistry visualization and representation frameworks. The implementation and design of ChemPaths, the general chemistry online text developed within the Chemistry Education Digital Library (ChemEd DL) is then described. The effectiveness of ChemPaths being used as a textbook replacement in an advanced general chemistry course is evaluated within the developed theoretical framework both qualitatively and quantitatively.

Analgesic efficacy of tramadol in cats with naturally occurring osteoarthritis.

PubMed

Monteiro, Beatriz P; Klinck, Mary P; Moreau, Maxim; Guillot, Martin; Steagall, Paulo V M; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Gauvin, Dominique; Del Castillo, Jérôme R E; Troncy, Eric

2017-01-01

This study aimed to (1) compare outcome assessments in normal and osteoarthritic cats and (2) evaluate the analgesic efficacy of tramadol in feline osteoarthritis (OA), in a prospective, randomised, blinded, placebo-controlled, crossover design. Twenty cats were included after clinical examination, blood work and full body radiographs were performed. In Phase 1, outcome assessments aimed to differentiate normal (n = 5; i.e. exempt of any radiographic and clinical sign of OA) from OA (n = 15) cats. In Phase 2, OA cats were treated twice daily with a placebo (PG: cornstarch 15 mg) or tramadol (TG: 3 mg/kg) orally for 19 days, with a 3-month washout period between treatments. Evaluations were performed in normal and OA cats at baseline and consisted of: 1) peak vertical force (PVF) after staircase exercise; 2) telemetered night-time motor activity (NMA); and 3) response to mechanical temporal summation (RMTS). After treatment, PVF, NMA and RMTS evaluations were repeated in OA cats. Data were analysed with mixed model methods with an alpha-threshold of 5%. Phase 1: 1) PVF (% of body weight; mean ± SD) was higher in normal (59 ± 10.5) than in OA cats (50.6 ± 5.7) (p = 0.005); 2) NMA (no unit) was not different between groups; 3) RMTS (number of stimuli; median (range)) was higher in normal [29.5 (23.5-30)] than in OA cats [14 (8.5-28)] (p < 0.0001). Phase 2: PVF, NMA and RMTS presented a treatment effect (p = 0.024, p = 0.008 and p = 0.018, respectively). No clinically important adverse-effects were observed. Outcome assessments such as kinetics (PVF) and evaluation of central sensitisation (RMTS) are discriminant of OA status. Mobility measured by NMA was not discriminant of OA status, however it increased in OA cats with tramadol treatment. Nociceptive hypersensitivity quantified by RMTS was evident in OA cats and was responsive to tramadol treatment.

The Global Research Collaboration of Network Meta-Analysis: A Social Network Analysis

PubMed Central

Li, Lun; Catalá-López, Ferrán; Alonso-Arroyo, Adolfo; Tian, Jinhui; Aleixandre-Benavent, Rafael; Pieper, Dawid; Ge, Long; Yao, Liang; Wang, Quan; Yang, Kehu

2016-01-01

Background and Objective Research collaborations in biomedical research have evolved over time. No studies have addressed research collaboration in network meta-analysis (NMA). In this study, we used social network analysis methods to characterize global collaboration patterns of published NMAs over the past decades. Methods PubMed, EMBASE, Web of Science and the Cochrane Library were searched (at 9th July, 2015) to include systematic reviews incorporating NMA. Two reviewers independently selected studies and cross-checked the standardized data. Data was analyzed using Ucinet 6.0 and SPSS 17.0. NetDraw software was used to draw social networks. Results 771 NMAs published in 336 journals from 3459 authors and 1258 institutions in 49 countries through the period 1997–2015 were included. More than three-quarters (n = 625; 81.06%) of the NMAs were published in the last 5-years. The BMJ (4.93%), Current Medical Research and Opinion (4.67%) and PLOS One (4.02%) were the journals that published the greatest number of NMAs. The UK and the USA (followed by Canada, China, the Netherlands, Italy and Germany) headed the absolute global productivity ranking in number of NMAs. The top 20 authors and institutions with the highest publication rates were identified. Overall, 43 clusters of authors (four major groups: one with 37 members, one with 12 members, one with 11 members and one with 10 members) and 21 clusters of institutions (two major groups: one with 62 members and one with 20 members) were identified. The most prolific authors were affiliated with academic institutions and private consulting firms. 181 consulting firms and pharmaceutical industries (14.39% of institutions) were involved in 199 NMAs (25.81% of total publications). Although there were increases in international and inter-institution collaborations, the research collaboration by authors, institutions and countries were still weak and most collaboration groups were small sizes. Conclusion Scientific production on NMA is increasing worldwide with research leadership of Western countries (most notably, the UK, the USA and Canada). More authors, institutions and nations are becoming involved in research collaborations, but frequently with limited international collaborations. PMID:27685998

Induction regimens for transplant-eligible patients with newly diagnosed multiple myeloma: a network meta-analysis of randomized controlled trials

PubMed Central

Zeng, Zi-Hang; Chen, Jia-Feng; Li, Yi-Xuan; Zhang, Ran; Xiao, Ling-Fei; Meng, Xiang-Yu

2017-01-01

Objective The aim of this study was to compare the early efficacy and survivals of induction regimens for transplant-eligible patients with untreated multiple myeloma. Materials and methods A comprehensive literature search in electronic databases was conducted for relevant randomized controlled trials (RCTs). Eligible studies were selected according to the predefined selection criteria, before they were evaluated for methodological quality. Basic characteristics and data for network meta-analysis (NMA) were extracted from included trials and pooled in our meta-analysis. The end points were the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results A total of 14 RCTs that included 4,763 patients were analyzed. The post-induction ORR was higher with bortezomib plus thalidomide plus dexamethasone (VTD) regimens, and VTD was better than the majority of other regimens. For OS, VTD plus cyclophosphamide (VTDC) regimens showed potential superiority over other regimens, but the difference was not statistically significant. The PFS was longer with thalidomide plus doxorubicin plus dexamethasone (TAD) regimens for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Conclusion The NMA demonstrated that the VTD, VTDC, and TAD regimens are most beneficial in terms of ORR, OS, and PFS for transplant-eligible patients with NDMM, respectively. PMID:28744159

Re-evaluation of the reported experimental values of the heat of vaporization of N-methylacetamide

PubMed Central

MacKerell, Alexander D.; Shim, Ji Hyun; Anisimov, Victor M.

2010-01-01

The accuracy of empirical force fields is inherently related to the quality of the target data used for optimization of the model. With the heat of vaporization (ΔHvap) of N-methylacetamide (NMA), a range of values have been reported as target data for optimization of the nonbond parameters associated with the peptide bond in proteins. In the present work, the original experimental data and Antoine constants used for the determination of the ΔHvap of NMA are reanalyzed. Based on this analysis, the wide range of ΔHvap values reported in the literature are shown to be due to incorrect reporting of the temperatures at which the original values were extracted and limitations in the quality of experimental vapor pressure-temperature data over a wide range of temperatures. Taking these problems into account, a consistent ΔHvap value is extracted from three studies for which experimental data are available. This analysis suggests that the most reliable value for ΔHvap is 13.0±0.1 at 410 K for use in force field optimization studies. The present results also indicate that similar analyses, including analysis of Antoine constants alone, may be of utility when reported ΔHvap values are not consistent for a given neat liquid. PMID:20445813

Accounting for correlation in network meta-analysis with multi-arm trials.

PubMed

Franchini, A J; Dias, S; Ades, A E; Jansen, J P; Welton, N J

2012-06-01

Multi-arm trials (trials with more than two arms) are particularly valuable forms of evidence for network meta-analysis (NMA). Trial results are available either as arm-level summaries, where effect measures are reported for each arm, or as contrast-level summaries, where the differences in effect between arms compare with the control arm chosen for the trial. We show that likelihood-based inference in both contrast-level and arm-level formats is identical if there are only two-arm trials, but that if there are multi-arm trials, results from the contrast-level format will be incorrect unless correlations are accounted for in the likelihood. We review Bayesian and frequentist software for NMA with multi-arm trials that can account for this correlation and give an illustrative example of the difference in estimates that can be introduced if the correlations are not incorporated. We discuss methods of imputing correlations when they cannot be derived from the reported results and urge trialists to report the standard error for the control arm even if only contrast-level summaries are reported. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2012 John Wiley & Sons, Ltd.

Network meta-analysis in health psychology and behavioural medicine: a primer.

PubMed

Molloy, G J; Noone, C; Caldwell, D; Welton, N J; Newell, J

2018-04-05

Progress in the science and practice of health psychology depends on the systematic synthesis of quantitative psychological evidence. Meta-analyses of experimental studies have led to important advances in understanding health-related behaviour change interventions. Fundamental questions regarding such interventions have been systematically investigated through synthesising relevant experimental evidence using standard pairwise meta-analytic procedures that provide reliable estimates of the magnitude, homogeneity and potential biases in effects observed. However, these syntheses only provide information about whether particular types of interventions work better than a control condition or specific alternative approaches. To increase the impact of health psychology on health-related policy-making, evidence regarding the comparative efficacy of all relevant intervention approaches - which may include biomedical approaches - is necessary. With the development of network meta-analysis (NMA), such evidence can be synthesised, even when direct head-to-head trials do not exist. However, care must be taken in its application to ensure reliable estimates of the effect sizes between interventions are revealed. This review paper describes the potential importance of NMA to health psychology, how the technique works and important considerations for its appropriate application within health psychology.

"For the good of the patient," survey of the physicians of the National Medical Association regarding perceptions of DTC advertising, Part II, 2006.

PubMed Central

Morris, Albert W.; Gadson, Sandra L.; Burroughs, Valentine

2007-01-01

BACKGROUND: Since the advent of direct-to-consumer (DTC) advertising in the 1980s, there have been numerous studies and surveys on the topic, addressing issues as varied as its impact on patient understanding of health conditions to its repercussions for drug spending. However, until 2001, there was a dearth of research on DTC advertising's impact on minority populations, specifically the African-American community. The National Medical Association (NMA) remedied that in 2001 by undertaking a landmark study that gauged African-American physicians' perceptions of DTC advertising, its impact on the doctor-patient relationship and, perhaps most importantly, its role in educating underserved populations about critical health issues and potential treatments. In 2006, the NMA decided to once again poll its members on this critical issue to gauge not only current perceptions but how the community's understanding of DTC advertising has changed since 2001. RESULTS: The 2006 survey revealed several clear trends: NMA physicians are more positive toward DTC advertising now than they were in 2001; African-American physicians see DTC advertising as providing substantial educational benefits; physicians believe that DTC advertising helps rather than hurts the doctor-patient relationship; and African-American physicians see the benefits of DTC advertising outweighing its drawbacks. It must be noted that NMA physicians also had clear concerns about DTC advertising that point to potential areas of improvement for pharmaceutical companies. PMID:17393955

"For the good of the patient," survey of the physicians of the National Medical Association regarding perceptions of DTC advertising, Part II, 2006.

PubMed

Morris, Albert W; Gadson, Sandra L; Burroughs, Valentine

2007-03-01

Since the advent of direct-to-consumer (DTC) advertising in the 1980s, there have been numerous studies and surveys on the topic, addressing issues as varied as its impact on patient understanding of health conditions to its repercussions for drug spending. However, until 2001, there was a dearth of research on DTC advertising's impact on minority populations, specifically the African-American community. The National Medical Association (NMA) remedied that in 2001 by undertaking a landmark study that gauged African-American physicians' perceptions of DTC advertising, its impact on the doctor-patient relationship and, perhaps most importantly, its role in educating underserved populations about critical health issues and potential treatments. In 2006, the NMA decided to once again poll its members on this critical issue to gauge not only current perceptions but how the community's understanding of DTC advertising has changed since 2001. The 2006 survey revealed several clear trends: NMA physicians are more positive toward DTC advertising now than they were in 2001; African-American physicians see DTC advertising as providing substantial educational benefits; physicians believe that DTC advertising helps rather than hurts the doctor-patient relationship; and African-American physicians see the benefits of DTC advertising outweighing its drawbacks. It must be noted that NMA physicians also had clear concerns about DTC advertising that point to potential areas of improvement for pharmaceutical companies.

What induces pocket openings on protein surface patches involved in protein-protein interactions?

PubMed

Eyrisch, Susanne; Helms, Volkhard

2009-02-01

We previously showed for the proteins BCL-X(L), IL-2, and MDM2 that transient pockets at their protein-protein binding interfaces can be identified by applying the PASS algorithm to molecular dynamics (MD) snapshots. We now investigated which aspects of the natural conformational dynamics of proteins induce the formation of such pockets. The pocket detection protocol was applied to three different conformational ensembles for the same proteins that were extracted from MD simulations of the inhibitor bound crystal conformation in water and the free crystal/NMR structure in water and in methanol. Additional MD simulations studied the impact of backbone mobility. The more efficient CONCOORD or normal mode analysis (NMA) techniques gave significantly smaller pockets than MD simulations, whereas tCONCOORD generated pockets comparable to those observed in MD simulations for two of the three systems. Our findings emphasize the influence of solvent polarity and backbone rearrangements on the formation of pockets on protein surfaces and should be helpful in future generation of transient pockets as putative ligand binding sites at protein-protein interfaces.

What induces pocket openings on protein surface patches involved in protein-protein interactions?

NASA Astrophysics Data System (ADS)

Eyrisch, Susanne; Helms, Volkhard

2009-02-01

We previously showed for the proteins BCL-XL, IL-2, and MDM2 that transient pockets at their protein-protein binding interfaces can be identified by applying the PASS algorithm to molecular dynamics (MD) snapshots. We now investigated which aspects of the natural conformational dynamics of proteins induce the formation of such pockets. The pocket detection protocol was applied to three different conformational ensembles for the same proteins that were extracted from MD simulations of the inhibitor bound crystal conformation in water and the free crystal/NMR structure in water and in methanol. Additional MD simulations studied the impact of backbone mobility. The more efficient CONCOORD or normal mode analysis (NMA) techniques gave significantly smaller pockets than MD simulations, whereas tCONCOORD generated pockets comparable to those observed in MD simulations for two of the three systems. Our findings emphasize the influence of solvent polarity and backbone rearrangements on the formation of pockets on protein surfaces and should be helpful in future generation of transient pockets as putative ligand binding sites at protein-protein interfaces.

Multi-arm Cost-Effectiveness Analysis (CEA) comparing different durations of adjuvant trastuzumab in early breast cancer, from the English NHS payer perspective

PubMed Central

Hunter, Rachael M.; Shemilt, Ian; Serra-Sastre, Victoria

2017-01-01

Background Trastuzumab improves survival in HER2+ breast cancer patients, with some evidence of adverse cardiac side effects. Current recommendations are to give adjuvant trastuzumab for one year or until recurrence, although trastuzumab treatment for only 9 or 10 weeks has shown similar survival rates to 12-month treatment. We present here a multi-arm joint analysis examining the relative cost-effectiveness of different durations of adjuvant trastuzumab. Methods and findings Network meta-analysis (NMA) was used to examine which trials’ data to include in the cost-effectiveness analysis (CEA). A network using FinHer (9 weeks vs. zero) and BCIRG006 (12 months vs. zero) trials offered the only jointly randomisable network so these trials were used in the CEA. The 3-arm CEA compared costs and quality-adjusted life-years (QALYs) associated with zero, 9-week and 12-month adjuvant trastuzumab durations in early breast cancer, using a decision tree followed by a Markov model that extrapolated the results to a lifetime time horizon. Pairwise incremental cost-effectiveness ratios (ICERs) were also calculated for each pair of regimens and used in budget impact analysis, and the Bucher method was used to check face validity of the findings. Addition of the PHARE trial (6 months vs. 12 months) to the network, in order to create a 4-arm CEA including the 6-month regimen, was not possible as late randomisation in this trial resulted in recruitment of a different patient population as evidenced by the NMA findings. The CEA results suggest that 9 weeks’ trastuzumab is cost-saving and leads to more QALYs than 12 months’, i.e. the former dominates the latter. The cost-effectiveness acceptability frontier (CEAF) favours zero trastuzumab at willingness-to-pay levels below £2,500/QALY and treatment for 9 weeks above this threshold. The combination of the NMA and Bucher investigations suggests that the 9-week duration is as efficacious as the 12-month duration for distant-disease-free survival and overall survival, and safer in terms of fewer adverse cardiac events. Conclusions Our CEA results suggest that 9-week trastuzumab dominates 12-month trastuzumab in cost-effectiveness terms at conventional thresholds of willingness to pay for a QALY, and the 9-week regimen is also suggested to be as clinically effective as the 12-month regimen according to the NMA and Bucher analyses. This finding agrees with the results of the E2198 head-to-head study that compared 10 weeks’ with 14 months’ trastuzumab and found no significant difference. Appropriate trial design and reporting is critical if results are to be synthesisable with existing evidence, as selection bias can lead to recruitment of a different patient population from existing trials. Our analysis was not based on head-to-head trials’ data, so the results should be viewed with caution. Short-duration trials would benefit from recruiting larger numbers of participants to reduce uncertainty in the synthesised results. PMID:28248984

Multi-arm Cost-Effectiveness Analysis (CEA) comparing different durations of adjuvant trastuzumab in early breast cancer, from the English NHS payer perspective.

PubMed

Clarke, Caroline S; Hunter, Rachael M; Shemilt, Ian; Serra-Sastre, Victoria

2017-01-01

Trastuzumab improves survival in HER2+ breast cancer patients, with some evidence of adverse cardiac side effects. Current recommendations are to give adjuvant trastuzumab for one year or until recurrence, although trastuzumab treatment for only 9 or 10 weeks has shown similar survival rates to 12-month treatment. We present here a multi-arm joint analysis examining the relative cost-effectiveness of different durations of adjuvant trastuzumab. Network meta-analysis (NMA) was used to examine which trials' data to include in the cost-effectiveness analysis (CEA). A network using FinHer (9 weeks vs. zero) and BCIRG006 (12 months vs. zero) trials offered the only jointly randomisable network so these trials were used in the CEA. The 3-arm CEA compared costs and quality-adjusted life-years (QALYs) associated with zero, 9-week and 12-month adjuvant trastuzumab durations in early breast cancer, using a decision tree followed by a Markov model that extrapolated the results to a lifetime time horizon. Pairwise incremental cost-effectiveness ratios (ICERs) were also calculated for each pair of regimens and used in budget impact analysis, and the Bucher method was used to check face validity of the findings. Addition of the PHARE trial (6 months vs. 12 months) to the network, in order to create a 4-arm CEA including the 6-month regimen, was not possible as late randomisation in this trial resulted in recruitment of a different patient population as evidenced by the NMA findings. The CEA results suggest that 9 weeks' trastuzumab is cost-saving and leads to more QALYs than 12 months', i.e. the former dominates the latter. The cost-effectiveness acceptability frontier (CEAF) favours zero trastuzumab at willingness-to-pay levels below £2,500/QALY and treatment for 9 weeks above this threshold. The combination of the NMA and Bucher investigations suggests that the 9-week duration is as efficacious as the 12-month duration for distant-disease-free survival and overall survival, and safer in terms of fewer adverse cardiac events. Our CEA results suggest that 9-week trastuzumab dominates 12-month trastuzumab in cost-effectiveness terms at conventional thresholds of willingness to pay for a QALY, and the 9-week regimen is also suggested to be as clinically effective as the 12-month regimen according to the NMA and Bucher analyses. This finding agrees with the results of the E2198 head-to-head study that compared 10 weeks' with 14 months' trastuzumab and found no significant difference. Appropriate trial design and reporting is critical if results are to be synthesisable with existing evidence, as selection bias can lead to recruitment of a different patient population from existing trials. Our analysis was not based on head-to-head trials' data, so the results should be viewed with caution. Short-duration trials would benefit from recruiting larger numbers of participants to reduce uncertainty in the synthesised results.

Comparison of the efficacy and safety of thrombectomy devices in acute stroke : a network meta-analysis of randomized trials.

PubMed

Saber, Hamidreza; Rajah, Gary B; Kherallah, Riyad Y; Jadhav, Ashutosh P; Narayanan, Sandra

2017-12-15

Mechanical thrombectomy (MT) is increasingly used for large-vessel occlusions (LVO), but randomized clinical trial (RCT) level data with regard to differences in clinical outcomes of MT devices are limited. We conducted a network meta-analysis (NMA) that enables comparison of modern MT devices (Trevo, Solitaire, Aspiration) and strategies (stent retriever vs aspiration) across trials. Relevant RCTs were identified by a systematic review. The efficacy outcome was 90-day functional independence (modified Rankin Scale (mRS) score 0-2). Safety outcomes were 90-day catastrophic outcome (mRS 5-6) and symptomatic intracranial hemorrhage (sICH). Fixed-effect Bayesian NMA was performed to calculate risk estimates and the rank probabilities. In a NMA of six relevant RCTs (SWIFT, TREVO2, EXTEND-IA, SWIFT-PRIME, REVASCAT, THERAPY; total of 871 patients, 472 Solitaire vs medical-only, 108 Aspiration vs medical-only, 178 Trevo vs Merci, and 113 Solitaire vs Merci) with medical-only arm as the reference, Trevo had the greatest functional independence (OR 4.14, 95% credible interval (CrI) 1.41-11.80; top rank probability 92%) followed by Solitaire (OR 2.55, 95% CrI 1.75-3.74; top rank probability 72%). Solitaire and Aspiration devices had the greatest top rank probability with respect to low sICH and catastrophic outcomes (76% and 91%, respectively), but without significant differences between each other. In a separate network of seven RCTs (MR-CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME, REVASCAT, THERAPY, ASTER; 1737 patients), first-line stent retriever was associated with a higher top rank probability of functional independence than aspiration (95% vs 54%), with comparable safety outcomes. These findings suggest that Trevo and Solitaire devices are associated with a greater likelihood of functional independence whereas Solitaire and Aspiration devices appear to be safer. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of oral premedication on the anaesthetic efficacy of inferior alveolar nerve block in patients with irreversible pulpitis - A systematic review and network meta-analysis of randomized controlled trials.

PubMed

Pulikkotil, S J; Nagendrababu, V; Veettil, S K; Jinatongthai, P; Setzer, F C

2018-02-26

This systematic review (SR; PROSPERO database: CRD42017075160) and network meta-analysis (NMA) identified the most effective oral premedication for anaesthetic success of inferior alveolar nerve blocks (IANB) in cases of irreversible pulpitis. Medline and Ebscohost databases were searched up until 10/2017. Randomized controlled trials (RCT) studying the effect of oral premedication, alone or in combination, on the success of IANB for cases of irreversible pulpitis, compared to placebo or other oral premedications, were included. Quality of the included studies was appraised by the revised Cochrane risk of bias tool for randomized trials. Pairwise analysis, NMA and quality of evidence assessment using GRADE criteria were performed. Nineteen studies (n = 1654 participants) were included. NMA demonstrated that compared to placebo, dexamethasone was most effective in increasing anaesthetic success (RR, 2.92 [95% CI 1.74,4.91]; SUCRA = 0.96), followed by NSAIDs (RR, 1.92 [95% CI 1.63,2.27], SUCRA = 0.738) and Tramadol (RR, 2.03 [95% CI 1.18,3.49], SUCRA = 0.737). Premedication with acetaminophen added to NSAIDs demonstrated similar efficacy as NSAIDs alone (RR, 1.06 [95% CI 0.79,1.43]). Sensitivity analyses proved the superiority of dexamethasone or NSAIDs over any other premedications. Subgroup analyses of specific dosages in comparison with placebo demonstrated that dexamethasone 0.5 mg was most effective, followed by ketorolac 10 mg, piroxicam 20 mg, ibuprofen 400 mg + acetaminophen 500 mg and Tramadol 50 mg. Ibuprofen 400 mg, 600 mg and 800 mg had a significantly improved IANB success, while Ibuprofen 300 mg had no effect. Oral premedication with dexamethasone, NSAIDs or Tramadol significantly increased anaesthetic success. More trials are needed to evaluate the premedication effects of dexamethasone or Tramadol for improved anaesthetic success of IANB when treating irreversible pulpitis. © 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Comparative efficacy of fixed-dose combinations of long-acting muscarinic antagonists and long-acting β2-agonists: a systematic review and network meta-analysis

PubMed Central

Schlueter, Max; Gonzalez-Rojas, N; Baldwin, Michael; Groenke, Lars; Voss, Florian; Reason, Tim

2016-01-01

Background: A number of long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) fixed-dose combinations (FDCs) for treatment of moderate-to-very severe chronic obstructive pulmonary disease (COPD) have recently become available, but none have been directly compared in head-to-head randomized controlled trials (RCTs). The purpose of this study was to assess the relative clinical benefit of all currently available LAMA/LABA FDCs using a Bayesian network meta-analysis (NMA). Methods: A systematic literature review identified RCTs investigating the efficacy, safety and quality of life associated with licensed LAMA/LABA FDCs for the treatment of moderate-to-very severe COPD. RCTs were screened for inclusion in the NMA using prespecified eligibility criteria. Data were extracted for outcomes of interest, including change in trough forced expiratory volume in 1 second (tFEV1) from baseline, St. George Respiratory Questionnaire (SGRQ) percentage of responders, Transition Dyspnea Index (TDI) percentage of responders, change in SGRQ score from baseline, change in TDI focal score from baseline, moderate-to-severe exacerbations, all-cause discontinuation, and discontinuation due to adverse events. Results: Following screening, a total of 27 trials from 26 publications with 30,361 subjects were eligible for inclusion in the NMA. Nonsignificant results were seen in most analyses comparing efficacy, exacerbations and discontinuation rates of included LAMA/LABA FDCs (i.e. aclidinium/formoterol 400/12 µg, glycopyrronium/indacaterol 110/50 µg, tiotropium + olodaterol 5/5 µg, umeclidinium/vilanterol 62.5/25 µg). Meta-regression controlling for post-bronchodilator percentage of tFEV1 predicted at baseline as well as meta-regression adjusting for concomitant use of inhaled corticosteroids at baseline was performed to assess the magnitude of effect modification and produced similar results as observed in the base case analysis. Conclusion: All LAMA/LABA FDCs were found to have similar efficacy and safety. Definitive assessment of the relative efficacy of different treatments can only be performed through direct comparison in head-to-head RCTs. In the absence of such data, this indirect comparison may be of value in clinical and health economic decision-making. PMID:26746383

Integrated Process Monitoring based on Systems of Sensors for Enhanced Nuclear Safeguards Sensitivity and Robustness

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

Humberto E. Garcia

This paper illustrates safeguards benefits that process monitoring (PM) can have as a diversion deterrent and as a complementary safeguards measure to nuclear material accountancy (NMA). In order to infer the possible existence of proliferation-driven activities, the objective of NMA-based methods is often to statistically evaluate materials unaccounted for (MUF) computed by solving a given mass balance equation related to a material balance area (MBA) at every material balance period (MBP), a particular objective for a PM-based approach may be to statistically infer and evaluate anomalies unaccounted for (AUF) that may have occurred within a MBP. Although possibly being indicativemore » of proliferation-driven activities, the detection and tracking of anomaly patterns is not trivial because some executed events may be unobservable or unreliably observed as others. The proposed similarity between NMA- and PM-based approaches is important as performance metrics utilized for evaluating NMA-based methods, such as detection probability (DP) and false alarm probability (FAP), can also be applied for assessing PM-based safeguards solutions. To this end, AUF count estimates can be translated into significant quantity (SQ) equivalents that may have been diverted within a given MBP. A diversion alarm is reported if this mass estimate is greater than or equal to the selected value for alarm level (AL), appropriately chosen to optimize DP and FAP based on the particular characteristics of the monitored MBA, the sensors utilized, and the data processing method employed for integrating and analyzing collected measurements. To illustrate the application of the proposed PM approach, a protracted diversion of Pu in a waste stream was selected based on incomplete fuel dissolution in a dissolver unit operation, as this diversion scenario is considered to be problematic for detection using NMA-based methods alone. Results demonstrate benefits of conducting PM under a system-centric strategy that utilizes data collected from a system of sensors and that effectively exploits known characterizations of sensors and facility operations in order to significantly improve anomaly detection, reduce false alarm, and enhance assessment robustness under unreliable partial sensor information.« less

Bacterial meningitis epidemiology and return of Neisseria meningitidis serogroup A cases in Burkina Faso in the five years following MenAfriVac mass vaccination campaign.

PubMed

Diallo, Alpha Oumar; Soeters, Heidi M; Yameogo, Issaka; Sawadogo, Guetawendé; Aké, Flavien; Lingani, Clément; Wang, Xin; Bita, Andre; Fall, Amadou; Sangaré, Lassana; Ouédraogo-Traoré, Rasmata; Medah, Isaïe; Bicaba, Brice; Novak, Ryan T

2017-01-01

Historically, Neisseria meningitidis serogroup A (NmA) caused large meningitis epidemics in sub-Saharan Africa. In 2010, Burkina Faso became the first country to implement a national meningococcal serogroup A conjugate vaccine (MACV) campaign. We analyzed nationwide meningitis surveillance data from Burkina Faso for the 5 years following MACV introduction. We examined Burkina Faso's aggregate reporting and national laboratory-confirmed case-based meningitis surveillance data from 2011-2015. We calculated incidence (cases per 100,000 persons), and described reported NmA cases. In 2011-2015, Burkina Faso reported 20,389 cases of suspected meningitis. A quarter (4,503) of suspected meningitis cases with cerebrospinal fluid specimens were laboratory-confirmed as either S. pneumoniae (57%), N. meningitidis (40%), or H. influenzae (2%). Average adjusted annual national incidence of meningococcal meningitis was 3.8 (range: 2.0-10.2 annually) and was highest among infants aged <1 year (8.4). N. meningitidis serogroup W caused the majority (64%) of meningococcal meningitis among all age groups. Only six confirmed NmA cases were reported in 2011-2015. Five cases were in children who were too young (n = 2) or otherwise not vaccinated (n = 3) during the 2010 MACV mass vaccination campaign; one case had documented MACV receipt, representing the first documented MACV failure. Meningococcal meningitis incidence in Burkina Faso remains relatively low following MACV introduction. However, a substantial burden remains and NmA transmission has persisted. MACV integration into routine childhood immunization programs is essential to ensure continued protection.

Spectral response of crystalline acetanilide and N -methylacetamide: Vibrational self-trapping in hydrogen-bonded crystals

NASA Astrophysics Data System (ADS)

Edler, Julian; Hamm, Peter

2004-06-01

Femtosecond pump-probe and Fourier transform infrared spectroscopy is applied to compare the spectral response of the amide I band and the NH-stretching band of acetanilide (ACN) and N -methylacetamide (NMA), as well as their deuterated derivatives. Both molecules form hydrogen-bonded molecular crystals that are regarded to be model systems for polypeptides and proteins. The amide I bands of both ACN and NMA show a temperature-dependent sideband, while the NH bands are accompanied by a sequence of equidistantly spaced satellite peaks. These spectral anomalies are interpreted as a signature of vibrational self-trapping. Two different types of states can be identified in both crystals in the pump-probe signal: a delocalized free-exciton state and a set of localized self-trapped states. The phonons that mediate self-trapping in ACN and deuterated ACN are identified by their temperature dependence, confirming our previous results. The study shows that the substructure of the NH band in NMA (amide A and amide B bands) originates, at least partly, from vibrational self-trapping and not, as often assumed, from a Fermi resonance.

Systematic Review and Network Meta-analysis of Idiopathic Pulmonary Fibrosis Treatments.

PubMed

Fleetwood, Kelly; McCool, Rachael; Glanville, Julie; Edwards, Susan C; Gsteiger, Sandro; Daigl, Monica; Fisher, Mark

2017-03-01

The antifibrotics pirfenidone and nintedanib are both approved for the treatment of idiopathic pulmonary fibrosis (IPF) by regulatory agencies and are recommended by health technology assessment bodies. Other treatments such as N-acetylcysteine are used in clinical practice but have not received regulatory approval. No head-to-head trials have been conducted to directly compare the efficacy of these therapies in IPF. To compare the efficacy of treatments for IPF. A systematic review was conducted up to April 2015. Phase II/III randomized controlled trials in adults with IPF were eligible. A Bayesian network meta-analysis (NMA) was used to compare pirfenidone, nintedanib, and N-acetylcysteine with respect to forced vital capacity (FVC) and mortality. Nine studies were included in the NMA. For change from baseline in FVC, the NMA indicated that pirfenidone and nintedanib were more effective than placebo after 1 year (pirfenidone vs. placebo: difference = 0.12 liter (L), 95% credible interval [CrI] = 0.03-0.21 L; nintedanib vs. placebo: difference = 0.11 L, 95% CrI = 0.00-0.22 L). There was no evidence that N-acetylcysteine had an effect on FVC compared with placebo (N-acetylcysteine vs. placebo: difference = 0.01 L, 95% CrI = -0.15-0.17 L). Patients treated with pirfenidone also had a lower risk of experiencing a decline in percent predicted FVC of ≥ 10% over 1 year (odds ratio [OR]: 0.58, 95% CrI = 0.40-0.88), whereas there was no conclusive evidence of a difference between nintedanib and placebo (OR: 0.65, 95% CrI = 0.42-1.02). The NMA indicated that pirfenidone reduced all-cause mortality relative to placebo over 1 year (hazard ratio [HR]: 0.52, 95% CrI = 0.28-0.92). There was no evidence of a difference in all-cause mortality between nintedanib and placebo (HR: 0.70, 95% CrI = 0.32-1.55), or N-acetylcysteine and placebo (HR: 2.00, 95% CrI=0.46-8.62). Our primary analysis of the available evidence indicates that over 1 year, pirfenidone and nintedanib are effective at reducing lung-function decline, and pirfenidone may reduce the odds of experiencing a decline in percent predicted FVC of ≥10% compared with placebo in the first year of treatment. The results of our analysis also suggest that pirfenidone improves survival. Fleetwood is an employee of Quantics Consulting. McCool and Glanville are employees of York Health Economics Consortium (YHEC). Quantics and YHEC received funding from F. Hoffmann-La Roche for conducting the systematic review and network meta-analysis reported in this paper. Edwards, Gsteiger, and Daigl are employees of F. Hoffmann-La Roche. Fisher was employed by InterMune UK, a wholly owned Roche subsidiary, until July 2015. He is currently employed by FIECON, which has received funding from F. Hoffmann-La Roche for consulting services. The systematic review and network meta-analysis reported in this paper were conducted by Fleetwood (Quantics Consulting) and McCool and Glanville (YHEC), funded by F. Hoffmann-La Roche. The original network analysis was funded by InterMune. Study concept and design were contributed by Edwards, Gsteiger, and Daigl, along with Fleetwood, McCool, and Glanville. Fleetwood, McCool, and Glanville collected the data, with assistance from Edwards, Gsteiger, and Daigl. Data interpretation was performed by Fleetwood and Fisher, with assistance from the other authors. The manuscript was written by Fleetwood, McCool, and Glanville, with assistance from Edwards, Daigl, and Fisher, and revised by all the authors.

Vibrational spectroscopic determination of local solvent electric field, solute-solvent electrostatic interaction energy, and their fluctuation amplitudes.

PubMed

Lee, Hochan; Lee, Gayeon; Jeon, Jonggu; Cho, Minhaeng

2012-01-12

IR probes have been extensively used to monitor local electrostatic and solvation dynamics. Particularly, their vibrational frequencies are highly sensitive to local solvent electric field around an IR probe. Here, we show that the experimentally measured vibrational frequency shifts can be inversely used to determine local electric potential distribution and solute-solvent electrostatic interaction energy. In addition, the upper limits of their fluctuation amplitudes are estimated by using the vibrational bandwidths. Applying this method to fully deuterated N-methylacetamide (NMA) in D(2)O and examining the solvatochromic effects on the amide I' and II' mode frequencies, we found that the solvent electric potential difference between O(═C) and D(-N) atoms of the peptide bond is about 5.4 V, and thus, the approximate solvent electric field produced by surrounding water molecules on the NMA is 172 MV/cm on average if the molecular geometry is taken into account. The solute-solvent electrostatic interaction energy is estimated to be -137 kJ/mol, by considering electric dipole-electric field interaction. Furthermore, their root-mean-square fluctuation amplitudes are as large as 1.6 V, 52 MV/cm, and 41 kJ/mol, respectively. We found that the water electric potential on a peptide bond is spatially nonhomogeneous and that the fluctuation in the electrostatic peptide-water interaction energy is about 10 times larger than the thermal energy at room temperature. This indicates that the peptide-solvent interactions are indeed important for the activation of chemical reactions in aqueous solution.

Cell and module formation research area

NASA Technical Reports Server (NTRS)

Bickler, D. B.

1982-01-01

Metallization is discussed. The influence of hydrogen on the firing of base-metal pastes in reducing atmospheres is reported. A method for optimization of metallization patterns is presented. A process sequence involving an AR coating and thick-film metallization system capable of penetrating the AR coating during firing is reported. Design and construction of the NMA implantation machine is reported. Implanted back-surface fields and NMA primary (front) junctions are discussed. The use of glass beads, a wave-soldering device, and ion milling is reported. Processing through the module fabrication and environmental testing of its design are reported. Metallization patterns by mathematical optimization are assessed.

Adaptive Attitude Control of the Crew Launch Vehicle

NASA Technical Reports Server (NTRS)

Muse, Jonathan

2010-01-01

An H(sub infinity)-NMA architecture for the Crew Launch Vehicle was developed in a state feedback setting. The minimal complexity adaptive law was shown to improve base line performance relative to a performance metric based on Crew Launch Vehicle design requirements for all most all of the Worst-on-Worst dispersion cases. The adaptive law was able to maintain stability for some dispersions that are unstable with the nominal control law. Due to the nature of the H(sub infinity)-NMA architecture, the augmented adaptive control signal has low bandwidth which is a great benefit for a manned launch vehicle.

Antidepressants in paediatric depression: do not look back in anger but around in awareness.

PubMed

Brent, David A; Gibbons, Robert D; Wilkinson, Paul; Dubicka, Bernadka

2018-02-01

In this paper, we summarise and critique a network meta-analysis (NMA) of antidepressant efficacy and tolerability for paediatric depression and an accompanying editorial. Although we agree that many of the extant studies are flawed, this meta-analysis showed clear efficacy of fluoxetine in the NMA, and for sertraline and escitalopram in pairwise analyses. Consequently, these papers underestimate the benefits of antidepressants for paediatric depression, and provide support for current practice guideline, which recommends the use of an antidepressant if the patient does not respond to psychotherapy. In these circumstances, fluoxetine should be the first choice, with escitalopram and sertraline as alternatives. Declaration of interest D.A.B. receives royalties from Guilford Press, has or will receive royalties from the electronic self-rated version of the C-SSRS from eResearch Technology, Inc., is on the editorial board of UpToDate, and is a reviewer for Healthwise. R.D.G. serves as an expert witness for the US Department of Justice, Pfizer, Wyeth and GSK; and is the founder of Adaptive Testing Technologies. P.W. receives personal fees from Lundbeck and Takeda. B.D. reports a licensing agreement with Lundbeck for a psychosocial treatment manual for depression. No other disclosures were reported.

Preventing the progression to type 2 diabetes mellitus in adults at high risk: a systematic review and network meta-analysis of lifestyle, pharmacological and surgical interventions.

PubMed

Stevens, John W; Khunti, Kamlesh; Harvey, Rebecca; Johnson, Maxine; Preston, Louise; Woods, Helen Buckley; Davies, Melanie; Goyder, Elizabeth

2015-03-01

Individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) have an increased risk of progression to Type 2 diabetes mellitus. The objective of this review was to quantify the effectiveness of lifestyle, pharmacological and surgical interventions in reducing the progression to Type 2 diabetes mellitus in people with IFG or IGT. A systematic review was carried out. A network meta-analysis (NMA) of log-hazard ratios was performed. Results are presented as hazard ratios and the probabilities of treatment rankings. 30 studies were included in the NMA. There was a reduced hazard of progression to Type 2 diabetes mellitus associated with all interventions versus standard lifestyle advice; glipizide, diet plus pioglitazone, diet plus exercise plus metformin plus rosiglitazone, diet plus exercise plus orlistat, diet plus exercise plus pedometer, rosiglitazone, orlistat and diet plus exercise plus voglibose produced the greatest effects. Lifestyle and some pharmacological interventions are beneficial in reducing the risk of progression to Type 2 diabetes mellitus. Lifestyle interventions require significant behaviour changes that may be achieved through incentives such as the use of pedometers. Adverse events and cost of pharmacological interventions should be taken into account when considering potential risks and benefits. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluation of Prediction of Polymorphisms of DNA Repair Genes on the Efficacy of Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer: A Network Meta-Analysis.

PubMed

Yu, Shao-Nan; Liu, Gui-Feng; Li, Xue-Feng; Fu, Bao-Hong; Dong, Li-Xin; Zhang, Shu-Hua

2017-12-01

This network meta-analysis (NMA) was conducted to compare the predictive value of 14 SNPs in eight DNA repair genes on the efficacy of platinum-based chemotherapy in patients with non-small cell lung cancer (NSCLC). These included ERCC1 (rs11615, rs3212986, rs3212948), XRCC1 (rs25487, rs25489, rs1799782), XPD (rs13181, rs1799793), XPG (rs1047768, rs17655), XPA (rs1800975), XRCC3 (rs861539), APE1 (rs3136820), and RRM1 (rs1042858). The PubMed and Cochrane library databases were reviewed from their inception to February 2017 and studies which met our inclusion criteria were included in our investigation. This network meta-analysis combines direct and indirect evidence to assess the predictive value of 14 SNPs in eight DNA repair genes on the efficacy of platinum-based chemotherapy in NSCLC. We evaluated the predictive value through the use of the odd ratios (OR) and drawing surface under the cumulative ranking curves (SUCRA). A total of 26 eligible cohort studies were enrolled in this NMA. The pairwise meta-analysis indicated that in terms of overall response ratio (ORR), ERCC1 (rs11615), XRCC1 (rs25487, rs1799782), and XPD (rs13181) polymorphisms are associated with the efficacy of platinum-based chemotherapy in NSCLC. The result of this NMA suggests that there is no significant difference in predictive value of 8 DNA repair genes on the efficacy of platinum-based chemotherapy in NSCLC patients. The rank of SUCRA values of the 14 SNPs in the eight DNA repair genes were: XPD (rs1799793)→ERCC1 (rs3212986)→XPA(rs1800975)→ERCC1(rs3212948)→XRCC1(rs25487)→XRCC3(rs861539)→APE1(rs3136820)→ERCC1(rs11615)→XRCC1(rs1799782)→RRM1(rs1042858)→XPD(rs13181)→XPG (rs1047768)→XPG(rs17655)→XRCC1(rs25489). ERCC1(rs11615), XRCC1(rs25487, rs1799782) and XPD(rs13181) polymorphisms were better predictors in evaluating the efficacy of platinum-based chemotherapy in NSCLC patients. J. Cell. Biochem. 118: 4782-4791, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Performance evaluation of PRIDE UNDA system with pyroprocessing feed material.

PubMed

An, Su Jung; Seo, Hee; Lee, Chaehun; Ahn, Seong-Kyu; Park, Se-Hwan; Ku, Jeong-Hoe

2017-04-01

The PRIDE (PyRoprocessing Integrated inactive DEmonstration) is an engineering-scale pyroprocessing test-bed facility that utilizes depleted uranium (DU) instead of spent fuel as a process material. As part of the ongoing effort to enhance pyroprocessing safeguardability, UNDA (Unified Non-Destructive Assay), a system integrating three different non-destructive assay techniques, namely, neutron, gamma-ray, and mass measurement, for nuclear material accountancy (NMA) was developed. In the present study, UNDA's NMA capability was evaluated by measurement of the weight, 238 U mass, and U enrichment of oxide-reduction-process feed material (i.e., porous pellets). In the 238 U mass determination, the total neutron counts for porous pellets of six different weights were measured. The U enrichment of the porous pellets, meanwhile, was determined according to the gamma spectrums acquired using UNDA's NaI-based enrichment measurement system. The results demonstrated that the UNDA system, after appropriate corrections, could be used in PRIDE NMA applications with reasonable uncertainty. It is expected that in the near future, the UNDA system will be tested with next-step materials such as the products of the oxide-reduction and electro-refining processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of multiple interventions for older adults with Alzheimer disease or mild cognitive impairment: A PRISMA-compliant network meta-analysis.

PubMed

Liang, Jing-Hong; Xu, Yong; Lin, Lu; Jia, Rui-Xia; Zhang, Hong-Bo; Hang, Lei

2018-05-01

The increasing prevalence of Alzheimer disease (AD) emphasizes the need for effective treatments. Both pharmacological therapies such as nutrition therapy (NT) and nonpharmacologic therapies including traditional treatment or personalized treatment (e.g., physical exercise, music therapy, computerized cognitive training) have been approved for the treatment of AD or mild cognitive impairment (MCI) in numerous areas. The aim of this study was to compare 4 types of interventions, physical exercise (PE), music therapy (MT), computerized cognitive training (CCT), and NT, in older adults with mild to moderate AD or MCI and identify the most effective intervention for their cognitive function. We used a system of search strategies to identify relevant studies and include randomized controlled trials (RCTs), placebo-controlled trials evaluating the efficacy and safety of 4 interventions in patients with AD or MCI. We updated the relevant studies which were published before March 2017 as a full-text article. Using Bayesian network meta-analysis (NMA), we ranked cognitive ability based objectively on Mini-Mental State Examination (MMSE), and assessed neuropsychiatric symptoms based on Neuropsychiatric Inventory (NPI). Pairwise and network meta-analyses were sequentially performed for efficacy and safety of intervention compared to control group through RCTs included. We included 17 RCTs. Fifteen trials (n = 1747) were pooled for cognition and no obvious heterogeneity was found (I = 21.7%, P = .212) in NMA, the mean difference (MD) of PE (MD = 2.1, confidence interval [CI]: 0.44-3.8) revealed that PE was significantly efficacious in the treatment group in terms of MMSE. Five trials (n = 660) assessed neuropsychiatric symptoms with an obvious heterogeneity (I = 61.6%, P = .034), the MD of CCT (MD = -7.7, CI: -14 to -2.4), revealing that CCT was significantly efficacious in NPI. As the first NMA comparing different interventions for AD and MCI, our study suggests that PE and CCT might have a significant improvement in cognition and neuropsychiatric symptoms respectively. Moreover, nonpharmacological therapies might be better than pharmacological therapies.

An evaluation of the comparative effectiveness of geriatrician-led comprehensive geriatric assessment for improving patient and healthcare system outcomes for older adults: a protocol for a systematic review and network meta-analysis.

PubMed

Soobiah, Charlene; Daly, Caitlin; Blondal, Erik; Ewusie, Joycelyne; Ho, Joanne; Elliott, Meghan J; Yue, Rossini; Holroyd-Leduc, Jayna; Liu, Barbara; Marr, Sharon; Basran, Jenny; Tricco, Andrea C; Hamid, Jemila; Straus, Sharon E

2017-03-24

Comprehensive geriatric assessment (CGA) is an integrated model of care involving a geriatrician and an interdisciplinary team and can prioritize and manage complex health needs of older adults with multimorbidity. CGAs differ across healthcare settings, ranging from shared care conducted in primary care settings to specialized inpatient units in acute care. Models of care involving geriatricians vary across healthcare settings, and it is unclear which CGA model is most effective. Our objective is to conduct a systematic review and network meta-analysis (NMA) to examine the comparative effectiveness of various geriatrician-led CGAs and to identify which models improve patient and healthcare system level outcomes. An integrated knowledge translation approach will be used and knowledge users (KUs) including patients, caregivers, geriatricians, and healthcare policymakers will be involved throughout the review. Electronic databases including MEDLINE, EMBASE, Cochrane library, and Ageline will be searched from inception to November 2016 to identify relevant studies. Randomized controlled trials of older adults (≥65 years of age) that examine geriatrician-led CGAs compared to any intervention will be included. Primary and secondary outcomes will be selected by KUs to ensure the results are relevant to their decision-making. Two reviewers will independently screen the search results, extract data, and assess risk of bias. Data will be synthesized using an NMA to allow for multiple comparisons using direct (head-to-head) as well as indirect evidence. Interventions will be ranked according to their effectiveness using surface under the cumulative ranking curve (SUCRA). As the proportion of older adults grows worldwide, the demand for specialized geriatric services that help manage complex health needs of older adults with multimorbidity will increase in many countries. Results from this systematic review and NMA will enhance decision-making and the efficient allocation of scarce geriatric resources. Moreover, active involvement of KUs throughout the review process will ensure the results are relevant to different levels of decision-making. PROSPERO CRD42014014008.

Comparative safety and effectiveness of perinatal antiretroviral therapies for HIV-infected women and their children: Systematic review and network meta-analysis including different study designs.

PubMed

Veroniki, Areti Angeliki; Antony, Jesmin; Straus, Sharon E; Ashoor, Huda M; Finkelstein, Yaron; Khan, Paul A; Ghassemi, Marco; Blondal, Erik; Ivory, John D; Hutton, Brian; Gough, Kevin; Hemmelgarn, Brenda R; Lillie, Erin; Vafaei, Afshin; Tricco, Andrea C

2018-01-01

Nearly all newly infected children acquire Human Immunodeficiency virus (HIV) via mother-to-child transmission (MTCT) during pregnancy, labour or breastfeeding from untreated HIV-positive mothers. Antiretroviral therapy (ART) is the standard care for pregnant women with HIV. However, evidence of ART effectiveness and harms in infants and children of HIV-positive pregnant women exposed to ART has been largely inconclusive. The aim of our systematic review and network meta-analysis (NMA) was to evaluate the comparative safety and effectiveness of ART drugs in children exposed to maternal HIV and ART (or no ART/placebo) across different study designs. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (inception until December 7, 2015). Primary outcomes were any congenital malformations (CMs; safety), including overall major and minor CMs, and mother-to-child transmission (MTCT; effectiveness). Random-effects Bayesian pairwise meta-analyses and NMAs were conducted. After screening 6,468 citations and 1,373 full-text articles, 90 studies of various study designs and 90,563 patients were included. The NMA on CMs (20 studies, 7,503 children, 16 drugs) found that none of the ART drugs examined here were associated with a significant increase in CMs. However, zidovudine administered with lamivudine and indinavir was associated with increased risk of preterm births, zidovudine administered with nevirapine was associated with increased risk of stillbirths, and lamivudine administered with stavudine and efavirenz was associated with increased risk of low birth weight. A NMA on MTCT (11 studies, 10,786 patients, 6 drugs) found that zidovudine administered once (odds ratio [OR] = 0.39, 95% credible interval [CrI]: 0.19-0.83) or twice (OR = 0.43, 95% CrI: 0.21-0.68) was associated with significantly reduced risk of MTCT. Our findings suggest that ART drugs are not associated with an increased risk of CMs, yet some may increase adverse birth events. Some ART drugs (e.g., zidovudine) effectively reduce MTCT.

How do smoking cessation medicines compare with respect to their neuropsychiatric safety? A protocol for a systematic review, network meta-analysis and cost-effectiveness analysis.

PubMed

Thomas, Kyla H; Caldwell, Deborah; Dalili, Michael N; Gunnell, David; Munafò, Marcus R; Stevenson, Matt; Welton, Nicky J

2017-06-17

Cigarette smoking is one of the leading causes of early death in the UK and worldwide. Public health guidance recommends the use of varenicline, bupropion and nicotine replacement therapy (NRT) as smoking cessation aids in the UK. Additionally, the first electronic cigarette has been licensed for use as a smoking cessation medicine. However, there are ongoing concerns about the safety of these medicines. We present a protocol for a systematic review and network meta-analysis (NMA) to determine how these smoking cessation medicines compare to each other with respect to their neuropsychiatric safety in adult smokers. Secondary aims include updating the evidence regarding the effectiveness and cardiovascular safety of these medicines for use in a cost-effectiveness analysis. We will include randomised controlled trials and observational studies with control groups comparing monotherapy with varenicline, bupropion, NRT or electronic cigarette and combination therapies to each other, placebo or usual care. The primary composite safety outcome will be serious adverse events, defined as events that resulted in death, were life threatening, required hospitalisation or resulted in significant disability or congenital/birth defect. The preferred effectiveness outcome will be sustained smoking cessation defined as abstinence for a minimum of 6 months as determined by biochemical validation. We will include trials identified by previous reviews and search relevant databases for newly published trials as well as contacting study authors to identify unpublished information. We will conduct fixed-effect and random-effect meta-analyses for each pairwise comparison of treatments and outcome; where these estimates differ, we will consider reasons for heterogeneity, quantified using the between-study variance (τ 2 ). For each outcome, we will construct a NMA in a Bayesian framework which will be compared with the pair-wise results, allowing us to rank treatments. The effectiveness estimates from the NMA will be entered into a probabilistic economic model. Ethics approval is not required for this evidence synthesis study as it involves analysis of secondary data from randomised controlled trials and observational studies. The review will make an important contribution to the knowledge base around the effectiveness, safety and cost-effectiveness of smoking cessation medicines. Results will be disseminated to the general public, healthcare practitioners and clinicians, academics, industry and policy makers. CRD42016041302. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparative efficacy and acceptability of antidepressants, psychological interventions, and their combination for depressive disorder in children and adolescents: protocol for a network meta-analysis

PubMed Central

Zhou, Xinyu; Cipriani, Andrea; Zhang, Yuqing; Cuijpers, Pim; Hetrick, Sarah E; Weisz, John R; Pu, Juncai; Giovane, Cinzia Del; Furukawa, Toshiaki A; Barth, Jürgen; Coghill, David; Leucht, Stefan; Yang, Lining; Ravindran, Arun V; Xie, Peng

2017-01-01

Introduction Depressive disorder is common in children and adolescents, with important consequences and serious impairments in terms of personal and social functioning. While both pharmacological and psychological interventions have been shown to be effective, there is still uncertainty about the balance between these and what treatment strategy should be preferred in clinical practice. Therefore, we aim to compare and rank in a network meta-analysis (NMA) the commonly used psychological, pharmacological and combined interventions for depressive disorder in children and adolescents. Methods and analysis We will update the literature search of two previous NMAs for the identification of trials of antidepressant and psychotherapy alone for depressive disorder in children and adolescents. For identification of trials of combination interventions, seven databases (PubMed, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, CINAHL, LiLACS) will be searched from date of inception. We will also search ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and check relevant reports on the US Food and Drug Administration website for unpublished data. Building on our previous findings in the field, we will include any commonly prescribed oral antidepressants and any manualised or structured psychotherapies, as well as their combinations. Randomised controlled trials assessing any active intervention against active comparator or pill placebo/psychological controls in acute treatment for depressive disorder in children and adolescents will be included. The primary outcomes will be efficacy (mean change in depressive symptoms), and acceptability of treatment (dropout rate due to any cause). The secondary outcomes will be remission rate, tolerability of treatment (dropouts for adverse events), as well as suicide-related outcomes (suicidal behaviour or ideation). We will perform Bayesian NMAs for all relative outcome measures. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings. Dissemination This NMA will provide the most up to date and clinically useful information about the comparative efficacy and acceptability of antidepressants, psychological intervention and their combination in the acute treatment of children and adolescents with depressive disorder. This is the newest NMA and therefore these results are very important in terms of evidence-based medicine. The results will be disseminated through peer-reviewed publication. Protocol registration PROSPERO CRD42015020841. PMID:28801423

Efficacy of Lactobacillus reuteri DSM 17938 for infantile colic

PubMed Central

Gutiérrez-Castrellón, Pedro; Indrio, Flavia; Bolio-Galvis, Alexis; Jiménez-Gutiérrez, Carlos; Jimenez-Escobar, Irma; López-Velázquez, Gabriel

2017-01-01

Abstract Background: 5% to 40% of infants cry excessively, usually accompanied by fussiness and excessive of gas. There are no uniform criteria for treatment of infantile colic. Lactobacillus reuteri DSM 17938 has been used with promising results. The objective of this network-meta-analysis (NMA) is to compare the efficacy of L reuteri DSM 17938 with other interventions for infantile colic. Methods: RCTs, published between 1960 and 2015 for the treatment of infantile colic were included. Primary outcome was duration of crying after 21 to 28 days of treatment. Different databases were searched. Information was analyzed using control group as central axis. A random effect model was used. Hedges standard mean difference (SMD) and odds ratio (OR) were calculated. A SUCRA analysis was performed to evaluate superiority for each intervention. Results: 32 RCTs were analyzed, including 2242 patients. Studies with L reuteri DSM 17938 versus Ctrl., Diet versus Ctrl. and Acupuncture versus Ctrl. were the most influential studies in the NMA. L reuteri DSM 17938 [WMD −51.3 h (CI95% −72.2 to −30.5 h), P .0001] and dietetic approaches [WMD −37.4 h (CI95% −56.1 to −18.7 h), P .0001] were superior compared to the other treatments. Conclusions: L reuteri DSM 17938 and some dietetic approaches are better to other interventions for treatment of infantile colic. PMID:29390535

Misrepresentations of the Tuskegee Study of Untreated Syphilis.

PubMed

White, Robert M

2005-04-01

The Tuskegee Study of Untreated Syphilis (TSUS) is the subject of medical research, healthcare, ethics, race relations and fictitious media portrayals (e.g., movie, play). Unraveling misrepresentations about the TSUS is important because prevailing views continue to contribute to alleged mistrust of the medical system by the black community and compromised doctor-patient and researcher-participant relationships. A comparative analysis of standard TSUS information was conducted and included evidenced-based alternative information in an effort to: (a) contextualize the TSUS with accurate medical, public health and historical information and (b) balance claims of racism, nontreatment and denial of treatment. An article in the Winter 2003 Radcliffe Quarterly misrepresented the images of two historical African-American health institutions, the John A. Andrew Memorial Hospital and the Tuskegee Veterans Administration Hospital. A critical analysis challenges these pictorial misrepresentations and documents, in part, a continuing and prevailing pattern of biased misrepresentations in discussions about the TSUS. The National Medical Association (NMA) and the Journal of the National Medical Association have a history of advocacy for African-American health, a record of combating racial discrimination and a quest for truth about the status of the black community. As past NMA historical notables have performed through their advancement, service and leadership, health professionals now have the opportunity, obligation and information to educate the American community about the TSUS with evidenced-based information.

Report on Concepts & Approaches for SSBD for eCHEM

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

Murphy, Chantell Lynne-Marie

The verification of special nuclear material (SNM) in spent fuel pyroprocessing is an important safeguards challenge. The detection of spontaneous fission (SF) neutrons from curium is an accepted, non-destructive technique that has been applied to verify special nuclear material (SNM) content in used fuel and other materials in the fuel cycle. The nuclear material accounting (NMA) technique at the Korea Atomic Energy Research Institute’s Reference Engineering-scale Pyroprocessing Facility (REPF) is based on the Cm balance technique. Several publications have demonstrated the safeguards benefit from using process monitoring (PM) on nuclear facilities as a complementary measure to NMA. More recently, thismore » concept was expanded and preliminarily demonstrated for pyroprocessing. The concept of Signature Based Safeguards (SBS) is part of this expansion, and is built around the interpretation of input from various sensors in a declared facility coupled with complementary NMA methods to increase confidence and lower standard error inventory differences (SEID). The SBS methodology was conceptually developed and relies on near real time analysis of process monitoring data to detect material diversion complemented by robust containment and surveillance (C/S) measures. This work demonstrates one example of how the SBS framework can be used in the electrorefiner. In this SBS application, a combination of cyclic voltammetry (CV) and neutron counting is applied to track and monitor Pu mass balance. The main purpose of this experiment is to determine if meaningful information can be gained from CV measurements with regard to the Mg/Gd ratio. This data will be coupled with ICP-MS to verify Gd concentrations and analyzed for statistical significance. It is expected the CV data will register a significant change under the off-normal operating conditions. Knowing how to identify and interpret those changes may help inform how to target more traditional neutron counting methods, which could support a more efficient safeguards system. The experimental results will be compared with theoretical calculations and the ERAD simulations.« less

Evaluating the costs of glycemic response with canagliflozin versus dapagliflozin and empagliflozin as add-on to metformin in patients with type 2 diabetes mellitus in the United Arab Emirates.

PubMed

Schubert, Agata; Buchholt, Anders T; El Khoury, Antoine C; Kamal, Ahmed; Taieb, Vanessa

2017-06-01

This study evaluates the cost of achieving glycemic control with three sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin, dapagliflozin, and empagliflozin, in patients with type 2 diabetes mellitus (T2DM) from the payer perspective in the United Arab Emirates (UAE). A systematic literature review identified randomized controlled trials of antihyperglycemic agents as add-on to metformin in patients with T2DM of 26 ± 4 weeks in duration, published by 10 September 2014. A Bayesian network-meta analysis (NMA) compared HbA1c changes with canagliflozin 100 and 300 mg versus dapagliflozin 10 mg and empagliflozin 10 and 25 mg. The cost associated with a 1% placebo-adjusted HbA1c reduction with each SGLT2 inhibitor as add-on to metformin was calculated based on NMA results and UAE drug costs. In the NMA, canagliflozin 100 and 300 mg were associated with HbA1c reductions (-0.67% and -0.79%) compared with dapagliflozin 10 mg (-0.41%) and empagliflozin 10 and 25 mg (-0.57% and -0.64%). Probabilities of canagliflozin 100 mg performing better were 79%, 60%, and 53% versus dapagliflozin 10 mg and empagliflozin 10 and 25 mg, respectively; probabilities for canagliflozin 300 mg performing better were 88%, 72%, and 65%, respectively. The cost per 1%-point reduction in HbA1c was projected to be lower with canagliflozin 100 and 300 mg ($448 and $422) compared with dapagliflozin 10 mg ($785) and empagliflozin 10 and 25 mg ($527 and $563). Canagliflozin may provide a greater glycemic response at a lower effective cost than dapagliflozin or empagliflozin for patients with T2DM inadequately controlled with metformin from the payer perspective in the UAE.

Node-making process in network meta-analysis of nonpharmacological treatment are poorly reported.

PubMed

James, Arthur; Yavchitz, Amélie; Ravaud, Philippe; Boutron, Isabelle

2018-05-01

To identify methods to support the node-making process in network meta-analyses (NMAs) of nonpharmacological treatments. We proceeded in two stages. First, we conducted a literature review of guidelines and methodological articles about NMAs to identify methods proposed to lump interventions into nodes. Second, we conducted a systematic review of NMAs of nonpharmacological treatments to extract methods used by authors to support their node-making process. MEDLINE and Google Scholar were searched to identify articles assessing NMA guidelines or methodology intended for NMA authors. MEDLINE, CENTRAL, and EMBASE were searched to identify reports of NMAs including at least one nonpharmacological treatment. Both searches involved articles available from database inception to March 2016. From the methodological review, we identified and extracted methods proposed to lump interventions into nodes. From the systematic review, the reporting of the network was assessed as long as the method described supported the node-making process. Among the 116 articles retrieved in the literature review, 12 (10%) discussed the concept of lumping or splitting interventions in NMAs. No consensual method was identified during the methodological review, and expert consensus was the only method proposed to support the node-making process. Among 5187 references for the systematic review, we included 110 reports of NMAs published between 2007 and 2016. The nodes were described in the introduction section of 88 reports (80%), which suggested that the node content might have been a priori decided before the systematic review. Nine reports (8.1%) described a specific process or justification to build nodes for the network. Two methods were identified: (1) fit a previously published classification and (2) expert consensus. Despite the importance of NMA in the delivery of evidence when several interventions are available for a single indication, recommendations on the reporting of the node-making process in NMAs are lacking, and reporting of the node-making process in NMAs seems insufficient. Copyright © 2017 Elsevier Inc. All rights reserved.

Amide-induced phase separation of hexafluoroisopropanol-water mixtures depending on the hydrophobicity of amides.

PubMed

Takamuku, Toshiyuki; Wada, Hiroshi; Kawatoko, Chiemi; Shimomura, Takuya; Kanzaki, Ryo; Takeuchi, Munetaka

2012-06-21

Amide-induced phase separation of hexafluoro-2-propanol (HFIP)-water mixtures has been investigated to elucidate solvation properties of the mixtures by means of small-angle neutron scattering (SANS), (1)H and (13)C NMR, and molecular dynamics (MD) simulation. The amides included N-methylformamide (NMF), N-methylacetamide (NMA), and N-methylpropionamide (NMP). The phase diagrams of amide-HFIP-water ternary systems at 298 K showed that phase separation occurs in a closed-loop area of compositions as well as an N,N-dimethylformamide (DMF) system previously reported. The phase separation area becomes wider as the hydrophobicity of amides increases in the order of NMF < NMA < DMF < NMP. Thus, the evolution of HFIP clusters around amides due to the hydrophobic interaction gives rise to phase separation of the mixtures. In contrast, the disruption of HFIP clusters causes the recovery of the homogeneity of the ternary systems. The present results showed that HFIP clusters are evolved with increasing amide content to the lower phase separation concentration in the same mechanism among the four amide systems. However, the disruption of HFIP clusters in the NMP and DMF systems with further increasing amide content to the upper phase separation concentration occurs in a different way from those in the NMF and NMA systems.

Revisiting Statistical Aspects of Nuclear Material Accounting

DOE PAGES

Burr, T.; Hamada, M. S.

2013-01-01

Nuclear material accounting (NMA) is the only safeguards system whose benefits are routinely quantified. Process monitoring (PM) is another safeguards system that is increasingly used, and one challenge is how to quantify its benefit. This paper considers PM in the role of enabling frequent NMA, which is referred to as near-real-time accounting (NRTA). We quantify NRTA benefits using period-driven and data-driven testing. Period-driven testing makes a decision to alarm or not at fixed periods. Data-driven testing decides as the data arrives whether to alarm or continue testing. The difference between period-driven and datad-riven viewpoints is illustrated by using one-year andmore » two-year periods. For both one-year and two-year periods, period-driven NMA using once-per-year cumulative material unaccounted for (CUMUF) testing is compared to more frequent Shewhart and joint sequential cusum testing using either MUF or standardized, independently transformed MUF (SITMUF) data. We show that the data-driven viewpoint is appropriate for NRTA and that it can be used to compare safeguards effectiveness. In addition to providing period-driven and data-driven viewpoints, new features include assessing the impact of uncertainty in the estimated covariance matrix of the MUF sequence and the impact of both random and systematic measurement errors.« less

Photopic ERG negative response from amacrine cell signaling in RCS rat retinal degeneration.

PubMed

Machida, Shigeki; Raz-Prag, Dorit; Fariss, Robert N; Sieving, Paul A; Bush, Ronald A

2008-01-01

The authors investigated photopic electroretinographic changes during degeneration in the Royal College of Surgeons (RCS) and transgenic P23H rhodopsin rat models, including the cellular origins of a large corneal-negative component that persists in the RCS rat. Photopic and scotopic electroretinograms (ERGs) were recorded from dystrophic RCS (RCS-p(+)/Lav) rats (4-18 weeks old) and transgenic rhodopsin Pro23His line 1 (P23H) rats (4-30 weeks old). Age-matched congenic (RCS-rdy(+)p(+)/Lav) and Sprague-Dawley rats were used as controls. N-methyl-DL-aspartic acid (NMA), dopamine, and gamma-aminobutyric acid (GABA) were injected intravitreally, and optic nerve sectioning (ONS) was performed to suppress or remove inner retinal neuron activity. Retinal morphology for cone cell counts and immunohistochemistry for quantification of Kir4.1 channels were performed at various stages of degeneration. As degeneration progressed, the photopic ERG of RCS dystrophic rats was distinctly different from that of P23H rats, primarily because of the growth of a corneal-negative response (RCS-NPR) after the b-wave in RCS rats. This response had a peak time similar to the photopic negative response (PhNR) in controls but with a more gradual recovery phase, and it was not affected by ONS. The PhNR in P23H rats declined linearly with the b-wave. NMA and GABA eliminated the RCS-NPR and uncovered a larger b-wave in RCS rats at late stages of degeneration, but NMA had little effect on the ERG in P23H rats. The NMA-sensitive negative response in RCS rats declined with age more slowly than did the NMA-isolated b-wave. The density of Kir4.1 channels at the endfeet of Müller cells and in the proximal retina increased significantly between 6 to 10 weeks and 14 weeks of age in the RCS rat retina but not in the P23H rat retina. The photopic ERG of the dystrophic RCS rat retina becomes increasingly electronegative because of an aberrant negative response, originating from amacrine cell activity, which declines more slowly than the b-wave with degeneration. The absence of this response in the P23H rat indicates that the inner retinal cone pathway pathology is different in the two models. A relative increase in Kir4.1 channels on Müller cells of RCS retina may contribute to the enhanced negative ERG response in the RCS rat.

Treatments for bulimia nervosa: a network meta-analysis.

PubMed

Slade, Eric; Keeney, Edna; Mavranezouli, Ifigeneia; Dias, Sofia; Fou, Linyun; Stockton, Sarah; Saxon, Leanne; Waller, Glenn; Turner, Hannah; Serpell, Lucy; Fairburn, Christopher G; Kendall, Tim

2018-05-06

Bulimia nervosa (BN) is a severe eating disorder that can be managed using a variety of treatments including pharmacological, psychological, and combination treatments. We aimed to compare their effectiveness and to identify the most effective for the treatment of BN in adults. A search was conducted in Embase, Medline, PsycINFO, and Central from their inception to July 2016. Studies were included if they reported on treatments for adults who fulfilled diagnostic criteria for BN. Only randomised controlled trials (RCTs) that examined available psychological, pharmacological, or combination therapies licensed in the UK were included. We conducted a network meta-analysis (NMA) of RCTs. The outcome analysed was full remission at the end of treatment. We identified 21 eligible trials with 1828 participants involving 12 treatments, including wait list. The results of the NMA suggested that individual cognitive behavioural therapy (CBT) (specific to eating disorders) was most effective in achieving remission at the end of treatment compared with wait list (OR 3.89, 95% CrI 1.19-14.02), followed by guided cognitive behavioural self-help (OR 3.81, 95% CrI 1.51-10.90). Inconsistency checks did not identify any significant inconsistency between the direct and indirect evidence. The analysis suggested that the treatments that are most likely to achieve full remission are individual CBT (specific to eating disorders) and guided cognitive behavioural self-help, although no firm conclusions could be drawn due to the limited evidence base. There is a need for further research on the maintenance of treatment effects and the mediators of treatment outcome.

Data extraction for complex meta-analysis (DECiMAL) guide.

PubMed

Pedder, Hugo; Sarri, Grammati; Keeney, Edna; Nunes, Vanessa; Dias, Sofia

2016-12-13

As more complex meta-analytical techniques such as network and multivariate meta-analyses become increasingly common, further pressures are placed on reviewers to extract data in a systematic and consistent manner. Failing to do this appropriately wastes time, resources and jeopardises accuracy. This guide (data extraction for complex meta-analysis (DECiMAL)) suggests a number of points to consider when collecting data, primarily aimed at systematic reviewers preparing data for meta-analysis. Network meta-analysis (NMA), multiple outcomes analysis and analysis combining different types of data are considered in a manner that can be useful across a range of data collection programmes. The guide has been shown to be both easy to learn and useful in a small pilot study.

Long-Term Efficacy of Maintenance Therapy for Multiple Myeloma: A Quantitative Synthesis of 22 Randomized Controlled Trials.

PubMed

Li, Jie-Li; Fan, Guang-Yu; Liu, Yu-Jie; Zeng, Zi-Hang; Huang, Jing-Juan; Yang, Zong-Ming; Meng, Xiang-Yu

2018-01-01

We aimed to quantitatively synthesize data from randomized controlled trials (RCTs) concerning maintenance for multiple myeloma (MM). We searched electronic literature databases and conference proceedings to identify relevant RCTs. We selected eligible RCTs using predefined selection criteria. We conducted meta-analysis comparing maintenance containing new agents and conventional maintenance, and subgroup analysis by transplantation status and mainstay agent as well. We performed trial sequential analysis (TSA) to determine adequacy of sample size for overall and subgroup meta-analyses. We performed network meta-analysis (NMA) to compare and rank included regimens. A total of 22 RCTs involving 9,968 MM patients and 15 regimens were included, the overall quality of which was adequate. Significant heterogeneity was detected for progression-free survival (PFS) but not overall survival (OS). Meta-analyses showed that maintenance containing new agents significantly improved PFS but not OS [PFS: Hazard Ratio (HR) = 0.59, 95% Confidence Interval (CI) = 0.54 to 0.64; OS: HR = 0.93, 95% CI = 0.87 to 1.00], compared with controls. Subgroup analyses revealed lenalidomide (Len)-based therapies better than thalidomide-based ones (HR = 0.50 and 0.66, respectively; P = 0.001). NMA revealed that most of the maintenance regimens containing new agents were significantly better than simple observation in terms of PFS but not OS. Len single agent was the most effective, considering PFS and OS both. We concluded that conventional maintenance has very limited effect. Maintenance containing new agents is highly effective in improving PFS, but has very limited effect on OS. Maintenance with Len may have the largest survival benefits. Emerging strategies may further change the landscape of maintenance of MM.

Efficacy of antidepressive medication for depression in Parkinson disease: a network meta-analysis

PubMed Central

Zhuo, Chuanjun; Xue, Rong; Luo, Lanlan; Ji, Feng; Tian, Hongjun; Qu, Hongru; Lin, Xiaodong; Jiang, Ronghuan; Tao, Ran

2017-01-01

Abstract Background: Parkinson disease (PD) was considered as the 2nd most prevalent neurodegenerative disorder after Alzheimer disease, while depression is a prevailing nonmotor symptom of PD. Typically used antidepression medication includes tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), monoamine-oxidase inhibitors (MAOI), and dopamine agonists (DA). Our study aimed at evaluating the efficacy of antidepressive medications for depression of PD. Methods: Web of Science, PubMed, Embase, and the Cochrane library were searched for related articles. Traditional meta-analysis and network meta-analysis (NMA) were performed with outcomes including depression score, UPDRS-II, UPDRS-III, and adverse effects. Surface under the cumulative ranking curve (SUCRA) was also performed to illustrate the rank probabilities of different medications on various outcomes. The consistency of direct and indirect evidence was also assessed by node-splitting method. Results: Results of traditional pairwise meta-analysis were performed. Concerning depression score, significant improvement was observed in AD, MAOI, SSRI, and SNRI compared with placebo. NMA was performed and more information could be obtained. DA was illustrated to be effective over placebo concerning UPDRS-III, MAOI, and SNRI. DA demonstrated a better prognosis in UPDRS-II scores compared with placebo and MAOI. However, DA and SSRI demonstrated a significant increase in adverse effects compared with placebo. The SUCRA value was calculated to evaluate the ranking probabilities of all medications on investigated outcomes, and the consistency between direct and indirect evidences was assessed by node-splitting method. Conclusion: SSRI had a satisfying efficacy for the depression of PD patients and could improve activities of daily living and motor function of patient but the adverse effects are unneglectable. SNRI are the safest medication with high efficacy for depression as well while other outcomes are relatively poor. PMID:28562526

Misrepresentations of the Tuskegee Study of Untreated Syphilis.

PubMed Central

White, Robert M.

2005-01-01

The Tuskegee Study of Untreated Syphilis (TSUS) is the subject of medical research, healthcare, ethics, race relations and fictitious media portrayals (e.g., movie, play). Unraveling misrepresentations about the TSUS is important because prevailing views continue to contribute to alleged mistrust of the medical system by the black community and compromised doctor-patient and researcher-participant relationships. A comparative analysis of standard TSUS information was conducted and included evidenced-based alternative information in an effort to: (a) contextualize the TSUS with accurate medical, public health and historical information and (b) balance claims of racism, nontreatment and denial of treatment. An article in the Winter 2003 Radcliffe Quarterly misrepresented the images of two historical African-American health institutions, the John A. Andrew Memorial Hospital and the Tuskegee Veterans Administration Hospital. A critical analysis challenges these pictorial misrepresentations and documents, in part, a continuing and prevailing pattern of biased misrepresentations in discussions about the TSUS. The National Medical Association (NMA) and the Journal of the National Medical Association have a history of advocacy for African-American health, a record of combating racial discrimination and a quest for truth about the status of the black community. As past NMA historical notables have performed through their advancement, service and leadership, health professionals now have the opportunity, obligation and information to educate the American community about the TSUS with evidenced-based information. Images Figure 2 Figure 3 Figure 4 Figure 5 p581-a PMID:15868777

Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis.

PubMed

Freemantle, Nick; Chou, Engels; Frois, Christian; Zhuo, Daisy; Lehmacher, Walter; Vlajnic, Aleksandra; Wang, Hongwei; Chung, Hsing-Wen; Zhang, Quanwu; Wu, Eric; Gerrits, Charles

2016-02-15

To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM). This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO. Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed. 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: -0.08; 95% credible interval (CrI): -0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; -0.28 to 0.32), degludec (-0.12; -0.42 to 0.20) and premixed insulin (0.26; -0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; -0.31 to 1.71), NPH (-0.76; -1.75 to 0.21) and degludec (-0.63; -1.63 to 0.35), but significantly lower compared with premixed insulin (-1.83; -2.85 to -0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19 to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings. NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Comparative Effectiveness of Phosphate Binders in Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis.

PubMed

Sekercioglu, Nigar; Thabane, Lehana; Díaz Martínez, Juan Pablo; Nesrallah, Gihad; Longo, Christopher J; Busse, Jason W; Akhtar-Danesh, Noori; Agarwal, Arnav; Al-Khalifah, Reem; Iorio, Alfonso; Guyatt, Gordon H

2016-01-01

Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been linked to poor health outcomes, including diminished quality and length of life. This condition is characterized by high phosphate levels and requires phosphate-lowering agents-phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on patient-important outcomes in patients with CKD-MBD. Data sources included MEDLINE and EMBASE Trials from 1996 to February 2016. We also searched the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD, randomized them to receive calcium (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet, placebo or no treatment, and reported effects on all-cause mortality, cardiovascular mortality or hospitalization at ≥4 weeks follow-up. We performed network meta-analyses (NMA) for all cause-mortality for individual agents (seven-node analysis) and conventional meta-analysis of calcium vs. NCBPBs for all-cause mortality, cardiovascular mortality and hospitalization. In the NMAs, we calculated the effect estimates for direct, indirect and network meta-analysis estimates; for both NMA and conventional meta-analysis, we pooled treatment effects as risk ratios (RR) and calculated 95% confidence intervals (CIs) using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each paired comparison. Our search yielded 1190 citations, of which 71 RCTs were retrieved for full review and 15 proved eligible. With 13 eligible studies from a prior review, we included 28 studies with 8335 participants; 25 trials provided data for our quantitative synthesis. Results suggest higher mortality with calcium than either sevelamer (NMA RR, 1.89 [95% CI, 1.02 to 3.50], moderate quality evidence) or NCBPBs (conventional meta-analysis RR, 1.76 [95% CI, 1.21 to 2.56, moderate quality evidence). Conventional meta-analysis suggested no difference in cardiovascular mortality between calcium and NCBPBs (RR, 2.54 [95% CI, 0.67 to 9.62 low quality evidence). Our results suggest higher hospitalization, although non-significant, with calcium than NCBPBs (RR, 1.293 [95% CI, 0.94 to 1.74, moderate quality evidence). Use of calcium results in higher mortality than either sevelamer in particular and NCBPBs in general (moderate quality evidence). Our results raise questions about whether administration of calcium as an intervention for CKD- MBD remains ethical. Further research is needed to explore the effects of different types of phosphate binders, including novel agents such as iron, on quality and quantity of life. PROSPERO CRD-42016032945.

Development and fabrication of a solar cell junction processing system

NASA Technical Reports Server (NTRS)

1984-01-01

A processing system capable of producing solar cell junctions by ion implantation followed by pulsed electron beam annealing was developed and constructed. The machine was to be capable of processing 4-inch diameter single-crystal wafers at a rate of 10(7) wafers per year. A microcomputer-controlled pulsed electron beam annealer with a vacuum interlocked wafer transport system was designed, built and demonstrated to produce solar cell junctions on 4-inch wafers with an AMI efficiency of 12%. Experiments showed that a non-mass-analyzed (NMA) ion beam could implant 10 keV phosphorous dopant to form solar cell junctions which were equivalent to mass-analyzed implants. A NMA ion implanter, compatible with the pulsed electron beam annealer and wafer transport system was designed in detail but was not built because of program termination.

Isolation of high-quality total RNA from leaves of Myrciaria dubia "CAMU CAMU".

PubMed

Gómez, Juan Carlos Castro; Reátegui, Alina Del Carmen Egoavil; Flores, Julián Torres; Saavedra, Roberson Ramírez; Ruiz, Marianela Cobos; Correa, Sixto Alfredo Imán

2013-01-01

Myrciaria dubia is a main source of vitamin C for people in the Amazon region. Molecular studies of M. dubia require high-quality total RNA from different tissues. So far, no protocols have been reported for total RNA isolation from leaves of this species. The objective of this research was to develop protocols for extracting high-quality total RNA from leaves of M. dubia. Total RNA was purified following two modified protocols developed for leaves of other species (by Zeng and Yang, and by Reid et al.) and one modified protocol developed for fruits of the studied species (by Silva). Quantity and quality of purified total RNA were assessed by spectrophotometric and electrophoretic analysis. Additionally, quality of total RNA was evaluated with reverse-transcription polymerase chain reaction (RT-PCR). With these three modified protocols we were able to isolate high-quality RNA (A260nm/A280nm >1.9 and A260nm/A230nm >2.0). Highest yield was produced with the Zeng and Yang modified protocol (384±46µg ARN/g fresh weight). Furthermore, electrophoretic analysis showed the integrity of isolated RNA and the absence of DNA. Another proof of the high quality of our purified RNA was the successful cDNA synthesis and amplification of a segment of the M. dubia actin 1 gene. We report three modified protocols for isolation total RNA from leaves of M. dubia. The modified protocols are easy, rapid, low in cost, and effective for high-quality and quantity total RNA isolation suitable for cDNA synthesis and polymerase chain reaction.

Systematic review with network meta-analysis: the efficacy of anti-tumour necrosis factor-alpha agents for the treatment of ulcerative colitis.

PubMed

Stidham, R W; Lee, T C H; Higgins, P D R; Deshpande, A R; Sussman, D A; Singal, A G; Elmunzer, B J; Saini, S D; Vijan, S; Waljee, A K

2014-04-01

Antibodies against tumour necrosis factor-alpha (anti-TNF) are effective therapies in the treatment of ulcerative colitis (UC), but their comparative efficacy is unknown. To perform a network meta-analysis comparing the efficacy of anti-TNF agents in UC. After screening 506 studies, reviewers extracted information on seven studies. Traditional meta-analysis (TMA) was used to compare each anti-TNF agent to placebo. Bayesian network meta-analysis (NMA) was performed to compare the effects of anti-TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated. Compared to placebo, TMA revealed that anti-TNF agents result in a higher likelihood of induction of remission and response (RR: 2.45, 95% CI: 1.72-3.47 and RR: 1.65, 95% CI: 1.37-1.99 respectively) as well as maintenance of remission and response (RR: 2.00, 95% CI: 1.52-2.62 and RR: 1.76, 95% CI: 1.46-2.14 respectively). Individually, infliximab, adalimumab and goliumumab resulted in a higher likelihood of induction and maintenance for both remission and response. NMA found nonsignificant trends in comparisons of the individual agents. The required sample sizes for direct head-to-head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively. This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis. However, network meta-analysis demonstrates that no single agent is clinically superior to the others and therefore, other factors such as cost, safety, route of administration and patient preference should dictate our choice of anti-TNF agents. A randomised comparative efficacy trial between infliximab and adalimumab in UC is of practical size and should be performed. © 2014 John Wiley & Sons Ltd.

Review of Malaria Epidemics in Ethiopia using Enhanced Climate Services (ENACTS)

NASA Astrophysics Data System (ADS)

Muhammad, A.

2015-12-01

Malaria is a disease directly linked to temperature and rainfall. In Ethiopia, the influence of climate variables on malaria transmission and the subsequent role of ENSO in the rise of malaria incidence are becoming more recognized. Numerous publications attest to the extreme sensitivity of malaria to climate in Ethiopia. The majority of large-scale epidemics in the past were associated with climatic factors such as temperature and rainfall. However, there is limited information on climate variability and ENSO at the district level to aid in public health decision-making. Since 2008, the National Meteorogy Agency (NMA) and the International Research Institute for Climate and Society (IRI) have been collaborating on improving climate services in Ethiopia. This collaboration spurred the implementation of the Enhancing National Climate Services (ENACTS) initiative and the creation of the IRI Data Library (DL) NMA Ethiopia Maproom. ENACTS provides reliable and readily accessible climate data at high resolutions and the Maproom uses ENACTS to build a collection of maps and other figures that monitor climate and societal conditions at present and in the recent past (1981-2010). A recent analysis exploring the relationship of rainfall and temperature ENACTS products to malaria epidemics in proceeding rainy seasons within 12 woredas found above normal temperature anomalies to be more readily associated with epidemics when compared to above normal rainfall anomalies, regardless of the ENSO phase (Figure 1-2).

National Medical Association

MedlinePlus

... Updates Health Care Reform Policy Letters & Statements Health Information Technology Mazique Symposium Resources Policy Beat Links Contact Us Education About NMA CME Continuing Medical Education CME Mission Statement About William ... Information Appointments Meeting and Delegate Criteria HOD Private Page ...

Comparative efficacy and acceptability of antidepressants, psychological interventions, and their combination for depressive disorder in children and adolescents: protocol for a network meta-analysis.

PubMed

Zhou, Xinyu; Cipriani, Andrea; Zhang, Yuqing; Cuijpers, Pim; Hetrick, Sarah E; Weisz, John R; Pu, Juncai; Giovane, Cinzia Del; Furukawa, Toshiaki A; Barth, Jürgen; Coghill, David; Leucht, Stefan; Yang, Lining; Ravindran, Arun V; Xie, Peng

2017-08-11

Depressive disorder is common in children and adolescents, with important consequences and serious impairments in terms of personal and social functioning. While both pharmacological and psychological interventions have been shown to be effective, there is still uncertainty about the balance between these and what treatment strategy should be preferred in clinical practice. Therefore, we aim to compare and rank in a network meta-analysis (NMA) the commonly used psychological, pharmacological and combined interventions for depressive disorder in children and adolescents. We will update the literature search of two previous NMAs for the identification of trials of antidepressant and psychotherapy alone for depressive disorder in children and adolescents. For identification of trials of combination interventions, seven databases (PubMed, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, CINAHL, LiLACS) will be searched from date of inception. We will also search ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and check relevant reports on the US Food and Drug Administration website for unpublished data. Building on our previous findings in the field, we will include any commonly prescribed oral antidepressants and any manualised or structured psychotherapies, as well as their combinations. Randomised controlled trials assessing any active intervention against active comparator or pill placebo/psychological controls in acute treatment for depressive disorder in children and adolescents will be included. The primary outcomes will be efficacy (mean change in depressive symptoms), and acceptability of treatment (dropout rate due to any cause). The secondary outcomes will be remission rate, tolerability of treatment (dropouts for adverse events), as well as suicide-related outcomes (suicidal behaviour or ideation). We will perform Bayesian NMAs for all relative outcome measures. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings. This NMA will provide the most up to date and clinically useful information about the comparative efficacy and acceptability of antidepressants, psychological intervention and their combination in the acute treatment of children and adolescents with depressive disorder. This is the newest NMA and therefore these results are very important in terms of evidence-based medicine. The results will be disseminated through peer-reviewed publication. PROSPERO CRD42015020841. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Structural relaxation in the hydrogen-bonding liquids N-methylacetamide and water studied by optical Kerr effect spectroscopy.

PubMed

Turton, David A; Wynne, Klaas

2008-04-21

Structural relaxation in the peptide model N-methylacetamide (NMA) is studied experimentally by ultrafast optical Kerr effect spectroscopy over the normal-liquid temperature range and compared to the relaxation measured in water at room temperature. It is seen that in both hydrogen-bonding liquids, beta relaxation is present, and in each case, it is found that this can be described by the Cole-Cole function. For NMA in this temperature range, the alpha and beta relaxations are each found to have an Arrhenius temperature dependence with indistinguishable activation energies. It is known that the variations on the Debye function, including the Cole-Cole function, are unphysical, and we introduce two general modifications: One allows for the initial rise of the function, determined by the librational frequencies, and the second allows the function to be terminated in the alpha relaxation.

What is the optimal systemic treatment of men with metastatic, hormone-naive prostate cancer? A STOPCAP systematic review and network meta-analysis.

PubMed

Vale, C L; Fisher, D J; White, I R; Carpenter, J R; Burdett, S; Clarke, N W; Fizazi, K; Gravis, G; James, N D; Mason, M D; Parmar, M K B; Rydzewska, L H; Sweeney, C J; Spears, M R; Sydes, M R; Tierney, J F

2018-05-01

Our prior Systemic Treatment Options for Cancer of the Prostate systematic reviews showed improved survival for men with metastatic hormone-naive prostate cancer when abiraterone acetate plus prednisolone/prednisone (AAP) or docetaxel (Doc), but not zoledronic acid (ZA), were added to androgen-deprivation therapy (ADT). Trial evidence also suggests a benefit of combining celecoxib (Cel) with ZA and ADT. To establish the optimal treatments, a network meta-analysis (NMA) was carried out based on aggregate data (AD) from all available studies. Overall survival (OS) and failure-free survival data from completed Systemic Treatment Options for Cancer of the Prostate reviews of Doc, ZA and AAP and from recent trials of ZA and Cel contributed to this comprehensive AD-NMA. The primary outcome was OS. Correlations between treatment comparisons within one multi-arm, multi-stage trial were estimated from control-arm event counts. Network consistency and a common heterogeneity variance were assumed. We identified 10 completed trials which had closed to recruitment, and one trial in which recruitment was ongoing, as eligible for inclusion. Results are based on six trials including 6204 men (97% of men randomised in all completed trials). Network estimates of effects on OS were consistent with reported comparisons with ADT alone for AAP [hazard ration (HR) = 0.61, 95% confidence interval (CI) 0.53-0.71], Doc (HR = 0.77, 95% CI 0.68-0.87), ZA + Cel (HR = 0.78, 95% CI 0.62-0.97), ZA + Doc (HR = 0.79, 95% CI 0.66-0.94), Cel (HR = 0.94 95% CI 0.75-1.17) and ZA (HR = 0.90 95% CI 0.79-1.03). The effect of ZA + Cel is consistent with the additive effects of the individual treatments. Results suggest that AAP has the highest probability of being the most effective treatment both for OS (94% probability) and failure-free survival (100% probability). Doc was the second-best treatment of OS (35% probability). Uniquely, we have included all available results and appropriately accounted for inclusion of multi-arm, multi-stage trials in this AD-NMA. Our results support the use of AAP or Doc with ADT in men with metastatic hormone-naive prostate cancer. AAP appears to be the most effective treatment, but it is not clear to what extent and whether this is due to a true increased benefit with AAP or the variable features of the individual trials. To fully account for patient variability across trials, changes in prognosis or treatment effects over time and the potential impact of treatment on progression, a network meta-analysis based on individual participant data is in development.

Molecular inspired models for prediction and control of directional FSO/RF wireless networks

NASA Astrophysics Data System (ADS)

Llorca, Jaime; Milner, Stuart D.; Davis, Christopher C.

2010-08-01

Directional wireless networks using FSO and RF transmissions provide wireless backbone support for mobile communications in dynamic environments. The heterogeneous and dynamic nature of such networks challenges their robustness and requires self-organization mechanisms to assure end-to-end broadband connectivity. We developed a framework based on the definition of a potential energy function to characterize robustness in communication networks and the study of first and second order variations of the potential energy to provide prediction and control strategies for network performance optimization. In this paper, we present non-convex molecular potentials such as the Morse Potential, used to describe the potential energy of bonds within molecules, for the characterization of communication links in the presence of physical constraints such as the power available at the network nodes. The inclusion of the Morse Potential translates into adaptive control strategies where forces on network nodes drive the release, retention or reconfiguration of communication links for network performance optimization. Simulation results show the effectiveness of our self-organized control mechanism, where the physical topology reorganizes to maximize the number of source to destination communicating pairs. Molecular Normal Mode Analysis (NMA) techniques for assessing network performance degradation in dynamic networks are also presented. Preliminary results show correlation between peaks in the eigenvalues of the Hessian of the network potential and network degradation.

Comparative safety and effectiveness of cognitive enhancers for Alzheimer's dementia: protocol for a systematic review and individual patient data network meta-analysis

PubMed Central

Veroniki, Areti Angeliki; Straus, Sharon E; Ashoor, Huda M; Hamid, Jemila S; Hemmelgarn, Brenda R; Holroyd-Leduc, Jayna; Majumdar, Sumit R; McAuley, Glenn; Tricco, Andrea C

2016-01-01

Introduction Alzheimer's dementia (AD) is the most common cause of dementia, and several organisations, such as the National Institute for Health and Care Excellence, suggest that management of patients with AD should be tailored to their needs. To date, little research has been conducted on the treatment effect in different subgroups of patients with AD. The aim of this study is to examine the comparative effectiveness and safety of cognitive enhancers for different patient characteristics. Methods and analysis We will update our previous literature search from January 2015 forward, using the same terms and electronic databases (eg, MEDLINE) from our previous review. We will additionally search grey literature and scan the reference lists of the included studies. Randomised clinical trials of any duration conducted at any time comparing cognitive enhancers alone or in any combination against other cognitive enhancers, or placebo in adults with AD will be eligible. The outcomes of interest are cognition according to the Mini-Mental State Examination, and overall serious adverse events. For each outcome and treatment comparison, we will perform a Bayesian hierarchical random-effects meta-analysis combining the individual patient data (IPD) from each eligible study. If the identified treatment comparisons form a connected network diagram, we will perform an IPD network meta-analysis (NMA) to estimate subgroup effects for patients with different characteristics, such as AD severity and sex. We will combine aggregated data from studies that we will not be able to obtain IPD, with the IPD provided by the original authors, in a single model. We will use the PRISMA-IPD and PRISMA-NMA statements to report our findings. Ethics and dissemination The findings of this study will be of interest to stakeholders, including decision makers, guideline developers, clinicians, methodologists and patients, and they will help to improve guidelines for the management of patients with AD. Trial registration number CRD42015023507. PMID:26769792

Efficacy of non-surgical treatments for androgenetic alopecia: a systematic review and network meta-analysis.

PubMed

Gupta, Aditya K; Mays, Rachel R; Dotzert, Michelle S; Versteeg, Sarah G; Shear, Neil H; Piguet, Vincent

2018-05-24

Androgenetic alopecia, or male/female pattern baldness, is the most common type of progressive hair loss disorder. The aim of this paper is to review recent advances in non-surgical treatments for androgenetic alopecia and identify the most effective treatments. A network meta-analysis (NMA) was conducted of the available literature of the six most common non-surgical treatment options for treating androgenetic alopecia in both men and women; dutasteride 0.5mg, finasteride 1mg, low level laser therapy (LLLT), minoxidil 2%, minoxidil 5% and platelet rich plasma (PRP). Seventy-eight studies met the inclusion criteria and twenty-two studies had the data necessary for a network meta-analysis. Relative effects show LLLT as the superior treatment. Relative effects show PRP, finasteride 1 mg (male), finasteride 1 mg (female), minoxidil 5%, minoxidil 2% and dutasteride (male) are approximately equivalent in mean change hair count following treatment. Minoxidil 5% and minoxidil 2% reported the most drug-related adverse events (n=45 and n=23, respectively). The quality of evidence of minoxidil 2% vs. minoxidil 5% was high; minoxidil 5% vs. placebo was moderate; dutasteride (male) vs. placebo, finasteride (female) vs placebo, minoxidil 2% vs. placebo, minoxidil 5% vs. LLLT was low and finasteride (male) vs. placebo, LLLT vs. sham, PRP vs. placebo, finasteride vs. minoxidil 2% was very low. Results of this NMA indicate the emergence of novel, non-hormonal therapies as effective treatments for hair loss; however, the quality of evidence is generally low. High quality randomized controlled trials and head to head trials are required to support these findings and aid in the development of more standardized protocols, particularly for PRP. Regardless, this analysis may aid physicians in clinical decision making and highlight the variety of non-surgical hair restoration options for patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Nitric oxide is a potential down-regulating molecule in autoimmune disease: inhibition of nitric oxide production renders PVG rats highly susceptible to EAE.

PubMed

Cowden, W B; Cullen, F A; Staykova, M A; Willenborg, D O

1998-08-01

Rat strains vary in their susceptibility to experimental autoimmune encephalomyelitis (EAE) and in many cases, factors other than MHC antigens are thought to play a role in this. We found that PVG rats, which have a very low susceptibility to EAE, were rendered highly susceptible to clinical disease when treated with N-methylarginine (NMA) an inhibitor of nitric oxide synthase (NOS). The clinical course of the ensuing disease in NMA-treated PVG rats was in most cases fulminating in nature and accompanied by some mortality. Following immunisation with myelin basic protein (MBP)-complete Freund's adjuvant (CFA), PVG rats developed higher serum levels of the surrogate markers of nitric oxide production, reactive nitrogen intermediates (RNI; nitrite and nitrate), than did their Lewis counterparts. This in vivo finding was reflected in vitro, where the levels of RNI produced in 24, 48 and 72 h IFN-gamma-stimulated spleen cell cultures for PVG rats were significantly higher than those for Lewis rats. A mechanism by which increased NO production might protect PVG rats against clinical EAE was suggested by the finding that lymph node cells, isolated from NMA-treated MBP-immunised PVG rats, proliferated in response to MBP at a rate approximately 3 x greater than those from MBP-immunised, saline treated rats. Thus, the greater number of MBP-specific T cells generated in the NOS inhibitor-treated vs. untreated rats could account for their increased susceptibility to developing clinical EAE. The findings in this study suggest that NO plays a role in protecting PVG rats against developing EAE.

Transcranial direct current stimulation (tDCS) for improving capacity in activities and arm function after stroke: a network meta-analysis of randomised controlled trials.

PubMed

Elsner, Bernhard; Kwakkel, Gert; Kugler, Joachim; Mehrholz, Jan

2017-09-13

Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving capacity in activities of daily living (ADL) and upper limb function after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types. We performed a systematic review of randomised trials using network meta-analysis (NMA), searching the following databases until 5 July 2016: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of ADL capacity, versus control, after stroke. CRD42016042055. We included 26 studies with 754 participants. Our NMA showed evidence of an effect of cathodal tDCS in improving our primary outcome, that of ADL capacity (standardized mean difference, SMD = 0.42; 95% CI 0.14 to 0.70). tDCS did not improve our secondary outcome, that of arm function, measured by the Fugl-Meyer upper extremity assessment (FM-UE). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events. Comparing different forms of tDCS shows that cathodal tDCS is the most promising treatment option to improve ADL capacity in people with stroke.

Preventing necrotizing enterocolitis by food additives in neonates: A network meta-analysis revealing the efficacy and safety.

PubMed

Yu, Wentao; Sui, Wu; Mu, Linsong; Yi, Wenying; Li, Haijuan; Wei, Liqin; Yin, Weihong

2017-05-01

Necrotizing enterocolitis (NEC) is a serious multifactorial gastrointestinal disease which is often discovered in premature infants. Various additives have been used to prevent NEC; yet, their relative efficacy and safety remain disputed. This study aims to compare the efficacy and safety of 5 food additives, namely, probiotics, probiotics + fructo-oligosaccharides, pentoxifylline, arginine, and lactoferrin in preventing NEC in neonates. Embase, PubMed, and Cochrane Library had been searched for all eligible randomized control trials. Odds ratios (ORs) were estimated for dichotomous data and mean differences with 95% credible intervals (CrIs) were estimated for continuous data. Surface under the cumulative ranking curve was used to rank efficacy and safety of the prevention methods on each endpoint. A total of 27 eligible studies with 4649 preterm infants were included in this network meta-analysis (NMA), and the efficacy and safety of 5 food additives were evaluated. Probiotic and arginine exhibited better preventive efficacy compared with placebo (OR = 0.50, 95% CrIs: 0.32-0.73; OR = 0.30, 95% CrIs: 0.12-0.73, respectively). Only probiotic achieved a considerable decrease in the risk of mortality compared to placebo (OR = 0.68, 95% CrIs: 0.46-0.98). NEC patients with lactoferrin appeared to have lower incidence of sepsis than those of placebo (OR = 0.13, 95% CrIs: 0.03-0.61) or probiotic (OR = 0.18, 95% CrIs: 0.03-0.83). Based on this NMA, probiotics had the potential to be the most preferable additive, since it exhibited a significant superiority for NEC and mortality as well as a relatively balanced performance in safety.

A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures.

PubMed

Davis, Sarah; Martyn-St James, Marrissa; Sanderson, Jean; Stevens, John; Goka, Edward; Rawdin, Andrew; Sadler, Susi; Wong, Ruth; Campbell, Fiona; Stevenson, Matt; Strong, Mark; Selby, Peter; Gittoes, Neil

2016-10-01

Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax ® and Fosamax ® Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel ® and Actonel Once a Week ® , Warner Chilcott UK Ltd), ibandronic acid (Bonviva ® , Roche Products Ltd) and zoledronic acid (Aclasta ® , Novartis Pharmaceuticals UK Ltd)] for the prevention of fragility fracture and to assess their cost-effectiveness at varying levels of fracture risk. For the clinical effectiveness review, six electronic databases and two trial registries were searched: MEDLINE, EMBASE, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science and BIOSIS Previews, Clinicaltrials.gov and World Health Organization International Clinical Trials Registry Platform. Searches were limited by date from 2008 until September 2014. A systematic review and network meta-analysis (NMA) of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years (QALYs) for each bisphosphonate treatment strategy and a strategy of no treatment for a simulated cohort of patients with heterogeneous characteristics. The model was populated with effectiveness evidence from the systematic review and NMA. All other parameters were estimated from published sources. A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture ® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX ® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net benefit (INB) was estimated using non-parametric regression. Probabilistic sensitivity analysis (PSA) and scenario analyses were used to assess uncertainty. Forty-six randomised controlled trials (RCTs) were included in the clinical effectiveness systematic review, with 27 RCTs providing data for the fracture NMA and 35 RCTs providing data for the femoral neck bone mineral density (BMD) NMA. All treatments had beneficial effects on fractures versus placebo, with hazard ratios varying from 0.41 to 0.92 depending on treatment and fracture type. The effects on vertebral fractures and percentage change in BMD were statistically significant for all treatments. There was no evidence of a difference in effect on fractures between bisphosphonates. A statistically significant difference in the incidence of influenza-like symptoms was identified from the RCTs for zoledronic acid compared with placebo. Reviews of observational studies suggest that upper gastrointestinal symptoms are frequently reported in the first month of oral bisphosphonate treatment, but pooled analyses of placebo-controlled trials found no statistically significant difference. A strategy of no treatment was estimated to have the maximum INB for patients with a 10-year QFracture risk under 1.5%, whereas oral bisphosphonates provided maximum INB at higher levels of risk. However, the PSA suggested that there is considerable uncertainty regarding whether or not no treatment is the optimal strategy until the QFracture score is around 5.5%. In the model using FRAX, the mean INBs were positive for all oral bisphosphonate treatments across all risk categories. Intravenous bisphosphonates were estimated to have lower INBs than oral bisphosphonates across all levels of fracture risk when estimated using either QFracture or FRAX. We assumed that all treatment strategies are viable alternatives across the whole population. Bisphosphonates are effective in preventing fragility fractures. However, the benefit-to-risk ratio in the lowest-risk patients may be debatable given the low absolute QALY gains and the potential for adverse events. We plan to extend the analysis to include non-bisphosphonate therapies. This study is registered as PROSPERO CRD42013006883. The National Institute for Health Research Health Technology Assessment programme.

Chinese Herbal Medicine for Improving Quality of Life Among Nonsmall Cell Lung Cancer Patients: Overview of Systematic Reviews and Network Meta-Analysis.

PubMed

Wu, Xinyin; Chung, Vincent C H; Lu, Ping; Poon, Simon K; Hui, Edwin P; Lau, Alexander Y L; Balneaves, Lynda G; Wong, Samuel Y S; Wu, Justin C Y

2016-01-01

For patients with nonsmall cell lung cancer (NSCLC) receiving chemotherapy, current clinical evidence has indicated add-on benefit of Chinese herbal medicine (CHM) in improving quality of life (QoL). However, the relative performance among different CHM is unknown. The aim of this overview of systematic reviews (SRs) and network meta-analyses (NMA) is to evaluate the comparative effectiveness of different CHM. Seven electronic databases including both international databases and Chinese databases were searched. SRs focus on randomized controlled trials (RCTs) with comparison of CHM plus chemotherapy against chemotherapy alone on QoL among NSCLC patients were considered eligible. Data from RCTs were extracted for random effect pairwise meta-analyses. Pooled relative risk (RR) with 95% confidence interval (CI) was used to quantify the impact of CHM on QoL. NMA was used to explore the most effective CHM for improving QoL when used with chemotherapy. From 14 SRs, 61 RCTs (n = 4247) assessing 11 different CHM were included. Result from pairwise meta-analyses showed 6 CHM (Kang-lai-te injection, Shei-qi-fu-zheng injection, Compound ku-shen injection, Kang-ai injection, Zi-jin-long tablet, and Shen-fu injection) has significant beneficial effect on QoL among NSCLC patients when used with chemotherapy, even after adjustment for publication bias. Pooled RR varied from 1.38 (95% CI: 1.11-1.72, I2 = 0.0%, Kang-lai-te injection) to 3.36 (95% CI: 1.30-8.66, I2 = 0.0%, Zi-jin-long tablet). One trial comparing Hai-shen-su (a protein extract from Tegillarca granosa L.) plus chemotherapy with chemotherapy also demonstrated beneficial effect of combined treatment (RR = 3.13, 95% CI: 1.41-6.98). Results from NMA showed no differences on the comparative effectiveness among CHM, but Hai-shen-su plus chemotherapy has the highest probability (62.3%) of being the best option for improving QoL. Use of CHM on top of chemotherapy can significantly improve QoL in NSCLC patients. Although Hai-shen-su showed the highest probability of being the best add-on to chemotherapy, the effectiveness of all 11 CHM reviewed appeared to be similar. In the future, rigorous placebo controlled trials with proper blinding are needed to confirm the effectiveness of CHM.

Cognitive-Behavioural Analysis System of Psychotherapy (CBASP), a drug, or their combination: differential therapeutics for persistent depressive disorder: a study protocol of an individual participant data network meta-analysis

PubMed Central

Schramm, Elisabeth; Weitz, Erica S; Salanti, Georgia; Efthimiou, Orestis; Michalak, Johannes; Watanabe, Norio; Keller, Martin B; Kocsis, James H; Klein, Daniel N; Cuijpers, Pim

2016-01-01

Introduction Despite important advances in psychological and pharmacological treatments of persistent depressive disorders in the past decades, their responses remain typically slow and poor, and differential responses among different modalities of treatments or their combinations are not well understood. Cognitive-Behavioural Analysis System of Psychotherapy (CBASP) is the only psychotherapy that has been specifically designed for chronic depression and has been examined in an increasing number of trials against medications, alone or in combination. When several treatment alternatives are available for a certain condition, network meta-analysis (NMA) provides a powerful tool to examine their relative efficacy by combining all direct and indirect comparisons. Individual participant data (IPD) meta-analysis enables exploration of impacts of individual characteristics that lead to a differentiated approach matching treatments to specific subgroups of patients. Methods and analysis We will search for all randomised controlled trials that compared CBASP, pharmacotherapy or their combination, in the treatment of patients with persistent depressive disorder, in Cochrane CENTRAL, PUBMED, SCOPUS and PsycINFO, supplemented by personal contacts. Individual participant data will be sought from the principal investigators of all the identified trials. Our primary outcomes are depression severity as measured on a continuous observer-rated scale for depression, and dropouts for any reason as a proxy measure of overall treatment acceptability. We will conduct a one-step IPD-NMA to compare CBASP, medications and their combinations, and also carry out a meta-regression to identify their prognostic factors and effect moderators. The model will be fitted in OpenBUGS, using vague priors for all location parameters. For the heterogeneity we will use a half-normal prior on the SD. Ethics and dissemination This study requires no ethical approval. We will publish the findings in a peer-reviewed journal. The study results will contribute to more finely differentiated therapeutics for patients suffering from this chronically disabling disorder. Trial registration number CRD42016035886. PMID:27147393

Two-Dimensional Lead(II) Halide-Based Hybrid Perovskites Templated by Acene Alkylamines: Crystal Structures, Optical Properties, and Piezoelectricity.

PubMed

Du, Ke-Zhao; Tu, Qing; Zhang, Xu; Han, Qiwei; Liu, Jie; Zauscher, Stefan; Mitzi, David B

2017-08-07

A series of two-dimensional (2D) hybrid organic-inorganic perovskite (HOIP) crystals, based on acene alkylamine cations (i.e., phenylmethylammonium (PMA), 2-phenylethylammonium (PEA), 1-(2-naphthyl)methanammonium (NMA), and 2-(2-naphthyl)ethanammonium (NEA)) and lead(II) halide (i.e., PbX 4 2- , X = Cl, Br, and I) frameworks, and their corresponding thin films were fabricated and examined for structure-property relationship. Several new or redetermined crystal structures are reported, including those for (NEA) 2 PbI 4 , (NEA) 2 PbBr 4 , (NMA) 2 PbBr 4 , (PMA) 2 PbBr 4 , and (PEA) 2 PbI 4 . Non-centrosymmetric structures from among these 2D HOIPs were confirmed by piezoresponse force microscopy-especially noteworthy is the structure of (PMA) 2 PbBr 4 , which was previously reported as centrosymmetric. Examination of the impact of organic cation and inorganic layer choice on the exciton absorption/emission properties, among the set of compounds considered, reveals that perovskite layer distortion (i.e., Pb-I-Pb bond angle between adjacent PbI 6 octahedra) has a more global effect on the exciton properties than octahedral distortion (i.e., variation of I-Pb-I bond angles and discrepancy among Pb-I bond lengths within each PbI 6 octahedron). In addition to the characteristic sharp exciton emission for each perovskite, (PMA) 2 PbCl 4 , (PEA) 2 PbCl 4 , (NMA) 2 PbCl 4 , and (PMA) 2 PbBr 4 exhibit separate, broad "white" emission in the long wavelength range. Piezoelectric compounds identified from these 2D HOIPs may be considered for future piezoresponse-type energy or electronic applications.

The respective contribution of lumbar segments to the generation of locomotion in the isolated spinal cord of newborn rat.

PubMed

Bertrand, S; Cazalets, Jean-René

2002-11-01

Various studies on isolated neonatal rat spinal cord have pointed to the predominant role played by the rostral lumbar area in the generation of locomotor activity. In the present study, the role of the various regions of the lumbar spinal cord in locomotor genesis was further examined using compartmentalization and transections of the cord. We report that the synaptic drive received by caudal motoneurons following N-methyl-d-l-aspartate (NMA)/5-HT superfusion on the entire lumbar cord is different from that triggered by the same compounds specifically applied on the rostral segments. These differences appear to be due to the direct action of NMA/5-HT on motoneuron membrane potential, rather than on premotoneuronal input activation. In order to assess the possible participation of the caudal lumbar segments in locomotor rhythm generation, the segments were over-stimulated with high concentrations of NMA or K+. We find that significant variations in motor cycle period occurred during the over-activation of the rostral segments. Over-activation of caudal segments only si+gnificantly increased the caudal ventral roots burst amplitude. We find that low 5-HT concentrations were unable to induce fictive locomotion under our experimental conditions. When a hemi-transection of the cord was performed between the L2-L3 segments, rhythmic bursting in the ipsilateral L5 disappeared while rhythmicity persisted on the contralateral side. Sectioning of the remaining L2-L3 side totally suppressed rhythmic activity in both L5 ventral roots. These results show that the thoracolumbar part of the cord constitutes the key area for locomotor pattern generation.

Downregulation of Axl in non-MYCN amplified neuroblastoma cell lines reduces migration.

PubMed

Duijkers, Floor A M; Meijerink, Jules P P; Pieters, Rob; van Noesel, Max M

2013-05-25

Neuroblastomas (NBL) are common pediatric solid tumors with a variable clinical course. At diagnosis half of all neuroblastoma patients presents with metastatic disease. The mechanisms of metastasis are largely unknown. Gene expression profiles (HU133plus2.0 arrays, Affymetrix) of 17 NBL and 5 peripheral neuro-ectodermal cell lines were used to identify a subgroup of non-MYCN amplified (non-NMA) NBL cell lines with a distinct gene expression profile and characterized by high expression of AXL. Axl is a tyrosine kinase receptor which plays a role in the metastatic process of several types of cancer. We hypothesized that Axl contributes to the metastasizing potential of non-NMA NBL and tested if AXL silencing diminishes malignant properties of high Axl expressing cell lines. AXL was silenced in two non-NMA NBL cell lines by using a lentiviral shRNA construct that was able to transduce these cell lines with more than 90% infection efficiency. Axl mRNA and protein level were efficiently knocked-down resulting in a decrease of migration of Axl positive cell lines GI-M-EN and SH-EP-2, and decreased invasion of GI-M-EN. Morphologically, Axl knockdown induced more rounded cells with a loss of contact. Intracellularly, we observed induction of stress fibers (immunofluorescence F-actin). These changes in cytoskeleton were associated with decreased migration, but were not accompanied by changes in genes involved in epithelial to mesenchymal transition such as CDH2, VIM or MMP9. No effects were observed for cell proliferation, apoptosis or downstream pathways. In conclusion, AXL is identified as a possible mediator of NBL metastasis. Copyright © 2013 Elsevier B.V. All rights reserved.

A High-Sensitivity Current Sensor Utilizing CrNi Wire and Microfiber Coils

PubMed Central

Xie, Xiaodong; Li, Jie; Sun, Li-Peng; Shen, Xiang; Jin, Long; Guan, Bai-ou

2014-01-01

We obtain an extremely high current sensitivity by wrapping a section of microfiber on a thin-diameter chromium-nickel wire. Our detected current sensitivity is as high as 220.65 nm/A2 for a structure length of only 35 μm. Such sensitivity is two orders of magnitude higher than the counterparts reported in the literature. Analysis shows that a higher resistivity or/and a thinner diameter of the metal wire may produce higher sensitivity. The effects of varying the structure parameters on sensitivity are discussed. The presented structure has potential for low-current sensing or highly electrically-tunable filtering applications. PMID:24824372

A high-sensitivity current sensor utilizing CrNi wire and microfiber coils.

PubMed

Xie, Xiaodong; Li, Jie; Sun, Li-Peng; Shen, Xiang; Jin, Long; Guan, Bai-ou

2014-05-12

We obtain an extremely high current sensitivity by wrapping a section of microfiber on a thin-diameter chromium-nickel wire. Our detected current sensitivity is as high as 220.65 nm/A2 for a structure length of only 35 μm. Such sensitivity is two orders of magnitude higher than the counterparts reported in the literature. Analysis shows that a higher resistivity or/and a thinner diameter of the metal wire may produce higher sensitivity. The effects of varying the structure parameters on sensitivity are discussed. The presented structure has potential for low-current sensing or highly electrically-tunable filtering applications.

Comparative effectiveness of glycemic control in patients with type 2 diabetes treated with GLP-1 receptor agonists: a network meta-analysis of placebo-controlled and active-comparator trials

PubMed Central

Orme, Michelle E; Nguyen, Hiep; Lu, Jackie Y; Thomas, Susan A

2017-01-01

Background Clinical studies of patients with type 2 diabetes show that GLP-1 receptor agonists (GLP-1 RAs) improve glycemic control and promote weight loss. We conducted a Bayesian network meta-analysis (NMA) of placebo- and active-controlled randomized trials to assess the comparative effectiveness of liraglutide, albiglutide, dulaglutide, and exenatide twice daily and once weekly, with a focus on glycemic control. Materials and methods We searched Medline, Embase, and the Cochrane Library (up to December 2014) for core registration programs for US-approved GLP-1 RAs. Patients reaching an A1C target of <7% were analyzed with a binomial model and change in A1C from baseline with a normal model. A covariate analysis assessed the impact of baseline A1C and treatment background on outcomes. Results The base-case NMA used 23 trials reporting A1C outcomes at ~6 month follow-up. The results, unadjusted and adjusted for baseline A1C, indicated that all GLP-1 RAs resulted in statistically significantly lower A1C at follow-up compared with placebo. The odds of reaching the <7% target were also significantly better compared with placebo. With dulaglutide, exenatide once weekly, and liraglutide, the absolute reduction in A1C at 6 months was 0.9%–1.4%, and was significantly better than exenatide twice daily. Albiglutide was not significantly different from exenatide twice daily. We estimate that ~50% of patients will meet the <7% A1C target within 6 months of commencing GLP-1 RAs. Conclusion This was a comprehensive assessment of the comparative effectiveness of GLP-1 RAs and A1C outcome. GLP-1 RAs are a viable addition to oral antidiabetes therapy, and dulaglutide, exenatide once weekly, and liraglutide are the most effective. PMID:28435304

Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis

PubMed Central

Zhao, Ying Jiao; Tan, Gloria; Teng, Monica; Tee, Caroline; Tan, Ban Hock; Ong, Benjamin; Lim, Boon Peng; Chai, Louis Yi Ann

2015-01-01

Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care setting. PMID:26525782

Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis.

PubMed

Zhao, Ying Jiao; Khoo, Ai Leng; Tan, Gloria; Teng, Monica; Tee, Caroline; Tan, Ban Hock; Ong, Benjamin; Lim, Boon Peng; Chai, Louis Yi Ann

2016-01-01

Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care setting. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Shorter Course Tacro After NMA, Related Donor PBSCT With High-dose Posttransplant Cy for Hard-to-Engraft Malignancies

ClinicalTrials.gov

2018-03-13

Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Myeloproliferative Disorders; Multiple Myeloma; Plasma Cell Neoplasm; Plasma Cell Dyscrasia; Myelofibrosis; Polycythemia Vera; Essential Thrombocythemia; Plasma Cell Leukemia

Neonatal metabolic acidosis at birth: In search of a reliable marker.

PubMed

Racinet, C; Ouellet, P; Charles, F; Daboval, T

2016-06-01

A newborn may present acidemia on the umbilical artery blood which can result from respiratory acidosis or metabolic acidosis or be of mixed origin. Currently, in the absence of a satisfactory definition, the challenge is to determine the most accurate marker for metabolic acidosis, which can be deleterious for the neonate. We reviewed the methodological and physiological aspects of the perinatal literature to search for the best marker of NMA. Base deficit and pH have been criticized as the standard criteria to predict outcome. The proposed threshold of pathogenicity is not based on convincing studies. The algorithms of various blood gas analyzers differ and do not take into account the specific neonatal acid-base profile. Birth-related neonatal eucapnic pH is described as the most pertinent marker of NMA at birth. The various means of calculating this value and the level below which it seems to play a possible pathogenic role are presented. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Measurement of carbon distribution in nuclear fuel pin cladding specimens by means of a secondary ion mass spectrometer

NASA Astrophysics Data System (ADS)

Bart, Gerhard; Aerne, Ernst Tino; Burri, Martin; Zwicky, Hans-Urs

1986-11-01

Cladding carburization during irradiation of advanced mixed uranium plutonium carbide fast breeder reactor fuel is possibly a life limiting fuel pin factor. The quantitative assessment of such clad carbon embrittlement is difficult to perform by electron microprobe analysis because of sample surface contamination, and due to the very low energy of the carbon K α X-ray transition. The work presented here describes a method developed at the Swiss Federal Institute for Reactor Research (EIR) to use shielded secondary ion mass spectrometry (SIMS) as an accurate tool to determine radial distribution profiles of carbon in radioactive stainless steel fuel pin cladding. Compared with nuclear microprobe analysis (NMA) [1], which is also an accurate method for carbon analysis, the SIMS method distinguishes itself by its versatility for simultaneous determination of additional impurities.

Cognitive-Behavioural Analysis System of Psychotherapy (CBASP), a drug, or their combination: differential therapeutics for persistent depressive disorder: a study protocol of an individual participant data network meta-analysis.

PubMed

Furukawa, Toshi A; Schramm, Elisabeth; Weitz, Erica S; Salanti, Georgia; Efthimiou, Orestis; Michalak, Johannes; Watanabe, Norio; Cipriani, Andrea; Keller, Martin B; Kocsis, James H; Klein, Daniel N; Cuijpers, Pim

2016-05-04

Despite important advances in psychological and pharmacological treatments of persistent depressive disorders in the past decades, their responses remain typically slow and poor, and differential responses among different modalities of treatments or their combinations are not well understood. Cognitive-Behavioural Analysis System of Psychotherapy (CBASP) is the only psychotherapy that has been specifically designed for chronic depression and has been examined in an increasing number of trials against medications, alone or in combination. When several treatment alternatives are available for a certain condition, network meta-analysis (NMA) provides a powerful tool to examine their relative efficacy by combining all direct and indirect comparisons. Individual participant data (IPD) meta-analysis enables exploration of impacts of individual characteristics that lead to a differentiated approach matching treatments to specific subgroups of patients. We will search for all randomised controlled trials that compared CBASP, pharmacotherapy or their combination, in the treatment of patients with persistent depressive disorder, in Cochrane CENTRAL, PUBMED, SCOPUS and PsycINFO, supplemented by personal contacts. Individual participant data will be sought from the principal investigators of all the identified trials. Our primary outcomes are depression severity as measured on a continuous observer-rated scale for depression, and dropouts for any reason as a proxy measure of overall treatment acceptability. We will conduct a one-step IPD-NMA to compare CBASP, medications and their combinations, and also carry out a meta-regression to identify their prognostic factors and effect moderators. The model will be fitted in OpenBUGS, using vague priors for all location parameters. For the heterogeneity we will use a half-normal prior on the SD. This study requires no ethical approval. We will publish the findings in a peer-reviewed journal. The study results will contribute to more finely differentiated therapeutics for patients suffering from this chronically disabling disorder. CRD42016035886. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Graduated compression stockings for the prevention of deep-vein thrombosis in postoperative surgical patients: a systematic review and economic model with a value of information analysis.

PubMed

Wade, Ros; Sideris, Eleftherios; Paton, Fiona; Rice, Stephen; Palmer, Stephen; Fox, Dave; Woolacott, Nerys; Spackman, Eldon

2015-11-01

Deep-vein thrombosis (DVT) can occur in surgical patients. Routine prophylaxis can be pharmacological and/or mechanical [e.g. graduated compression stockings (GCSs)]. GCSs are available in knee length or thigh length. To establish the expected value of undertaking additional research addressing the relative effectiveness of thigh-length GCSs versus knee-length GCSs, in addition to pharmacoprophylaxis, for prevention of DVT in surgical patients. Systematic review and economic model, including value of information (VOI) analysis. Randomised controlled trials (RCTs) assessing thigh- or knee-length GCSs in surgical patients were eligible for inclusion. The primary outcome was incidence of DVT. DVT complications and GCSs adverse events were assessed. Random-effects meta-analysis was performed. To draw on a wider evidence base, a random-effects network meta-analysis (NMA) was undertaken for the outcome DVT. A review of trials and observational studies of patient adherence was also conducted. A decision-analytic model was developed to assess the cost-effectiveness of thigh- and knee-length GCSs and the VOI. Twenty-three RCTs were included in the review of effectiveness. There was substantial variation between trials in terms of the patient characteristics, interventions and methods of outcome assessment. Five trials comparing knee-length with thigh-length GCSs with or without pharmacoprophylaxis were pooled; the summary estimate of effect indicated a non-significant trend favouring thigh-length GCSs [odds ratio (OR) 1.48, 95% confidence interval (CI) 0.80 to 2.73]. Thirteen trials were included in the NMA. In the base-case analysis, thigh-length GCSs with pharmacoprophylaxis were more effective than knee-length GCSs with pharmacoprophylaxis (knee vs. thigh OR 1.76, 95% credible interval 0.82 to 3.53). Overall, thigh-length stockings with pharmacoprophylaxis was the most effective treatment, with a 0.73 probability of being the most effective treatment in a new trial of all the treatments. Patient adherence was generally higher with knee-length GCSs, and patients preferred knee-length GCSs. Thigh-length GCSs were found to be cost-effective in all but the subgroup with the lowest baseline risk, although the absolute differences in costs and effects were relatively small. The expected value of perfect information ranged from £0.2M to £178.0M depending on the scenario and subgroup. The relative effect parameters had the highest expected value of partial perfect information and ranged from £2.0M to £39.4M. The value of further research was most evident in the high-risk subgroups. There was substantial variation across the included trials in terms of patient and intervention characteristics. Many of the included trials were old and poorly reported, which reduces the reliability of the results of the review. Given that the results from both the standard meta-analysis and the NMA lacked precision (CIs were wide) owing to the heterogeneous evidence base, a new definitive trial in high-risk patients may be warranted. However, the efficiency of any further research (i.e. whether this represents value for money) is dependent on several factors, including the acquisition price of GCSs, expected compliance with thigh-length GCSs wear, and whether or not uncertainty can be resolved around possible effect modifiers, as well as the feasibility and actual cost of undertaking the proposed research. This study is registered as PROSPERO CRD42014007202. The National Institute for Health Research Health Technology Assessment programme.

Efficacy of Pharmacist Based Diabetes Educational Interventions on Clinical Outcomes of Adults With Type 2 Diabetes Mellitus: A Network Meta-Analysis.

PubMed

Bukhsh, Allah; Khan, Tahir M; Lee, Shaun W H; Lee, Learn-Han; Chan, Kok-Gan; Goh, Bey-Hing

2018-01-01

Background: Comparative efficacy of different pharmacist based interventions on glycemic control of type 2 diabetes patients is unclear. This review aimed to evaluate and compare the efficacy of different pharmacist based interventions on clinical outcomes of type 2 diabetes patients. Methods: A systematic search was conducted across five databases from date of database inception to September 2017. All randomized clinical trials evaluating the efficacy of pharmacist based interventions on type 2 diabetes patients were included for network meta-analysis (NMA). The protocol is available with PROSPERO (CRD42017078854). Results: A total of 43 studies, involving 6259 type 2 diabetes patients, were included. NMA demonstrated that all interventions significantly lowered glycosylated hemoglobin (HbA1c) levels compared to usual care, but there was no statistical evidence from this study that one intervention was significantly better than the other for reducing HbA1c levels. Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy for reducing HbA1c levels [-0.86, 95% CI -0.983, -0.727; p < 0.001]. Pharmacist based diabetes education plus pharmaceutical care was observed to be statistically significant in lowering levels of systolic blood pressure [-4.94; 95%CI -8.65, -1.23] and triglycerides levels [-0.26, 95%CI -0.51, -0.01], as compared to the interventions which involved diabetes education by pharmacist, and for body mass index (BMI) [-0.57; 95%CI -1.25, -0.12] in comparison to diabetes education by health care team involving pharmacist as member. Conclusion: The findings of this review demonstrate that all interventions had a significantly positive effect on HbA1c, but there was no statistical evidence from this study that one intervention was significantly better than the other for achieving glycemic control.Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy on HbA1c and rest of the clinical outcomes.

Association of Distance from Transplantation Center and Place of Residence on Outcomes after Allogeneic Hematopoietic Cell Transplantation.

PubMed

Khera, Nandita; Gooley, Ted; Flowers, Mary E D; Sandmaier, Brenda M; Loberiza, Fausto; Lee, Stephanie J; Appelbaum, Frederick

2016-07-01

Regionalization of specialized health services can deliver high-quality care but may have an adverse impact on access and outcomes because of distance from the regional centers. In the case of hematopoietic cell transplantation (HCT), the effect of increased distance between the transplantation center and the rural/urban residence is unclear because of conflicting results from the existing studies. We examined the association between distance from primary residence to the transplantation center and rural versus urban residence with clinical outcomes after allogeneic HCT in a large cohort of patients. Overall mortality (OM), nonrelapse mortality (NRM), and relapse in all patients and those who survived for 200 days after HCT were assessed in 2849 patients who received their first allogeneic HCT between 2000 and 2010 at Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance. Median distance from FHCRC was 263 miles (range, 0 to 2740 miles) and 83% of patients were urban residents. The association between distance and the hazard of OM varied according to conditioning intensity: myeloablative (MA) versus nonmyeloablative (NMA). Among MA patients, there was no evidence of an increased risk of mortality with increased distance, but for NMA patients, the results did show a suggestion of increased risk of mortality for some distances, although globally the difference was not statistically significant. In the subgroup of patients who survived 200 days, there was no evidence that the risks of OM, relapse, or NRM were increased with increasing distance. We did not find any association between longer distance from transplantation center and urban/rural residence and outcomes after MA HCT. In patients undergoing NMA transplantations, this relationship and how it is influenced by factors such as age, payers, and comorbidities needs to be further investigated. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Effects of endothelin, calcium channel blockade and EDRF inhibition on the contractility of human uteroplacental arteries.

PubMed

Fried, G; Liu, Y A

1994-08-01

In order to examine the possibility that endothelin might be important in the regulation of placental blood flow, human uteroplacental vessels were superfused in vitro to study the contractile effect of endothelin as compared with a known strong contractor of placental blood vessels, serotonin (5-HT). The contractile responses were compared in the presence and absence of calcium channel blocking agents, as well as in the presence of L-NMA, an inhibitor of EDRF/nitric oxide. Endothelin (ET, 10(-10)-10(-6) M) and 5-HT (10(-8)-10(-4) M) induced contractions in the vessels. Maximal contractions in the presence of endothelin were elicited at 10(-7) M, whereas 5-HT elicited maximal contractions at 10(-5) M. At 10(-7) M, ET was more potent than 5-HT. The calcium-channel blocking agents nifedipine, diltiazem and NiCl2 relaxed the vessels by 5-15% from baseline. The contractile response to ET in the presence of nifedipine or diltiazem was reduced by 55 and 67%, respectively. The response of 5-HT in the presence of nifedipine was reduced by 58%. The contractile response to 5-HT as well as ET in the presence of both nifedipine and NiCl2 was not significantly lower than in the presence of nifedipine only. The EDRF-inhibiting agent L-NMA caused a small contractile response at concentrations of 10(-6)-10(-5) M. ET as well as 5-HT added after pretreatment with L-NMA produced a larger contractile response than ET or 5-HT alone. The results show that ET has a strong contractile effect on placental blood vessels at concentrations likely to occur during labor and delivery. The mechanism whereby ET as well as 5-HT contracts placental vessel smooth muscle appears to partly involve nifedipine- and diltiazem-sensitive calcium channels, but almost half of the response depends on mobilization of calcium through other means.

Comparative efficacy and tolerability of pharmacological interventions for attention-deficit/hyperactivity disorder in children, adolescents and adults: protocol for a systematic review and network meta-analysis

PubMed Central

Cortese, Samuele; Adamo, Nicoletta; Mohr-Jensen, Christina; Hayes, Adrian J; Bhatti, Sahar; Carucci, Sara; Del Giovane, Cinzia; Atkinson, Lauren Z; Banaschewski, Tobias; Simonoff, Emily; Zuddas, Alessandro; Barbui, Corrado; Purgato, Marianna; Steinhausen, Hans-Christoph; Shokraneh, Farhad; Xia, Jun; Coghill, David

2017-01-01

Introduction Attention-deficit/hyperactivity disorder (ADHD) is a major public health issue. Pharmacological treatments play an important role in the multimodal treatment of ADHD. Currently, there is a lack of up-to-date and comprehensive evidence on how available ADHD drugs compare and rank in terms of efficacy and tolerability, in children or adolescents as well as in adults. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs), to rank pharmacological treatments for ADHD according to their efficacy and tolerability profiles. Methods and analysis We will search a broad range of electronic databases, including PubMed, MEDLINE, EMBASE, PsycINFO, ERIC and Web of Science, with no date or language restrictions. We will also search for unpublished studies using international clinical trial registries and contacting relevant drug companies. We will identify and include available parallel-group, cross-over and cluster randomised trials that compare methylphenidate, dexmethylphenidate, amphetamine derivatives (including lisdexamfetamine), atomoxetine, clonidine, guanfacine, bupropion or modafinil (as oral therapy) either with each other or to placebo, in children, adolescents or adults with ADHD. Primary outcomes will be efficacy (indicated by reduction in severity of ADHD core symptoms measured on a standardised scale) and tolerability (the proportion of patients who left a study early due to side effects). Secondary outcomes will be global functioning, acceptability (proportion of patients who left the study early by any cause) and changes in blood pressure and body weight. NMA will be conducted in STATA within a frequentist framework. The quality of RCTs will be evaluated using the Cochrane risk of bias tool, and the quality of the evidence will be assessed using the GRADE approach. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. Ethics and dissemination No ethical issues are foreseen. Results from this study will be published in a peer-reviewed journal and possibly presented at relevant national and international conferences. Trial registration number CRD42014008976. PMID:28073796

Continuous Hypergolic Monitor Network for Shipboard Applications

DTIC Science & Technology

2005-08-30

PEI Oxidizers MON-25 Polyamines and Polycarbonyls Ethanol SXFA Acetone PEO Octane Poly(ethylene-co-vinyl acetate) ( PEVA ), Polyisobutylene...polyvinylacetate ( PEVA ). These tests were performed under variable humidity and temperature (Figure 13) and under low humidity at ambient temperature...Test of Chemoselective Polymers Against Interferents with Variable Temperature and Humidity. Key: PEVA black; PEI red; SXFA blue; NmA yellow

Enhanced magnetostrictive properties of nanocrystalline Dy3+ substituted Fe-rich Co0.8Fe2.2O4 for sensor applications

NASA Astrophysics Data System (ADS)

Kharat, Shahaji P.; Swadipta, Roy; Kambale, R. C.; Kolekar, Y. D.; Ramana, C. V.

2017-10-01

We report on the enhanced magnetostrictive properties of nanocrystalline Dysprosium (Dy3+) substituted iron-rich cobalt ferrites (Co0.8Fe(2.2-x)DyxO4, referred to as CFDO). The CFDO samples with a variable Dy concentration (x = 0.000-0.075) were synthesized by the sol-gel auto-combustion method. The phase purity and crystal structure were confirmed from X-ray diffraction analyses coupled with Rietveld refinement. Surface morphology analysis using scanning electron microscopy imaging indicates the agglomerated magnetic particles with a non-uniform particle size distribution, which is desirable to transfer the strain. The magnetostriction coefficient (λ11) measurements indicate that the CFDO with Dy concentration x = 0.025 exhibits the highest strain sensitivity, (dλ/dH) ˜1.432 nm/A (for H ≤ 1000 Oe). On the other hand, the magnetostriction coefficient (λ12) measurements indicate that the Dy concentration x = 0.075 exhibits the larger (dλ/dH) ˜ 0.615 nm/A (for H ≤ 1000 Oe). The maximum λ11value of 166 ppm (at H = 3300 Oe) was observed for a compound with Dy concentration x = 0.050. Magnetization measurements indicate that the saturation magnetization and coercivity of CFDO samples are dependent on the Dy3+content; the highest value of squareness ratio of 0.424 was observed for x = 0.050. The interplay between strain sensitivity (dλ/dH) and instantaneous susceptibility (dM/dH), as derived from magnetostriction and magnetization results, demonstrates that these CFDO materials may be useful for developing torque/stress sensors, as a constituent magnetostrictive phase for making the magnetoelectric composite materials and thus suitable for magnetoelectric sensor applications.

Generating the evidence for risk reduction: a contribution to the future of food-based dietary guidelines.

PubMed

Schwingshackl, Lukas; Schlesinger, Sabrina; Devleesschauwer, Brecht; Hoffmann, Georg; Bechthold, Angela; Schwedhelm, Carolina; Iqbal, Khalid; Knüppel, Sven; Boeing, Heiner

2018-04-30

A major advantage of analyses on the food group level is that the results are better interpretable compared with nutrients or complex dietary patterns. Such results are also easier to transfer into recommendations on primary prevention of non-communicable diseases. As a consequence, food-based dietary guidelines (FBDG) are now the preferred approach to guide the population regarding their dietary habits. However, such guidelines should be based on a high grade of evidence as requested in many other areas of public health practice. The most straightforward approach to generate evidence is meta-analysing published data based on a careful definition of the research question. Explicit definitions of study questions should include participants, interventions/exposure, comparisons, outcomes and study design. Such type of meta-analyses should not only focus on categorical comparisons, but also on linear and non-linear dose-response associations. Risk of bias of the individual studies of the meta-analysis should be assessed, rated and the overall credibility of the results scored (e.g. using NutriGrade). Tools such as a measurement tool to assess systematic reviews or ROBIS are available to evaluate the methodological quality/risk of bias of meta-analyses. To further evaluate the complete picture of evidence, we propose conducting network meta-analyses (NMA) of intervention trials, mostly on intermediate disease markers. To rank food groups according to their impact, disability-adjusted life years can be used for the various clinical outcomes and the overall results can be compared across the food groups. For future FBDG, we recommend to implement evidence from pairwise and NMA and to quantify the health impact of diet-disease relationships.

Short- and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome: a systematic review of randomised controlled trials and network meta-analysis.

PubMed

Armoiry, X; Kan, A; Melendez-Torres, G J; Court, R; Sutcliffe, P; Auguste, P; Madan, J; Counsell, C; Clarke, A

2018-05-01

Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short- and long-term clinical effectiveness of these drugs in CIS. We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies. We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR = 0.64, 95% CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression. Meta-analyses confirmed that IFN-β and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs.

Specific Non-Local Interactions Are Not Necessary for Recovering Native Protein Dynamics

PubMed Central

Dasgupta, Bhaskar; Kasahara, Kota; Kamiya, Narutoshi; Nakamura, Haruki; Kinjo, Akira R.

2014-01-01

The elastic network model (ENM) is a widely used method to study native protein dynamics by normal mode analysis (NMA). In ENM we need information about all pairwise distances, and the distance between contacting atoms is restrained to the native value. Therefore ENM requires O(N2) information to realize its dynamics for a protein consisting of N amino acid residues. To see if (or to what extent) such a large amount of specific structural information is required to realize native protein dynamics, here we introduce a novel model based on only O(N) restraints. This model, named the ‘contact number diffusion’ model (CND), includes specific distance restraints for only local (along the amino acid sequence) atom pairs, and semi-specific non-local restraints imposed on each atom, rather than atom pairs. The semi-specific non-local restraints are defined in terms of the non-local contact numbers of atoms. The CND model exhibits the dynamic characteristics comparable to ENM and more correlated with the explicit-solvent molecular dynamics simulation than ENM. Moreover, unrealistic surface fluctuations often observed in ENM were suppressed in CND. On the other hand, in some ligand-bound structures CND showed larger fluctuations of buried protein atoms interacting with the ligand compared to ENM. In addition, fluctuations from CND and ENM show comparable correlations with the experimental B-factor. Although there are some indications of the importance of some specific non-local interactions, the semi-specific non-local interactions are mostly sufficient for reproducing the native protein dynamics. PMID:24625758

Efficacy and Safety of Different Bisphosphonates for Bone Loss Prevention in Kidney Transplant Recipients: A Network Meta-Analysis of Randomized Controlled Trials

PubMed Central

Yang, Yan; Qiu, Shi; Tang, Xi; Li, Xin-Rui; Deng, Ling-Hui; Wei, Qiang; Fu, Ping

2018-01-01

Background: Mineral and bone disorder is one of the severe complications in kidney transplant recipients (KTRs). Previous studies showed that bisphosphonates had favorable effects on bone mineral density (BMD). We sought to compare different bisphosphonate regimens and rank their strategies. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to April 01, 2017, for randomized controlled trials (RCTs) comparing bisphosphonate treatments in adult KTRs. The primary outcome was BMD change. We executed the tool recommended by the Cochrane Collaboration to evaluate the risk of bias. We performed pairwise meta-analyses using random effects models and network meta-analysis (NMA) using Bayesian models and assessed the quality of evidence. Results: A total of 21 RCTs (1332 participants) comparing 6 bisphosphonate regimens were included. All bisphosphonates showed a significantly increased percentage change in BMD at the lumbar spine compared to calcium except clodronate. Pamidronate with calcium and Vitamin D analogs showed improved BMD in comparison to clodronate with calcium (mean difference [MD], 9.84; 95% credibility interval [CrI], 1.06–19.70). The combination of calcium and Vitamin D analogs had a significantly lower influence than adding either pamidronate or alendronate (MD, 6.34; 95% CrI, 2.59–11.01 and MD, 6.16; 95% CrI, 0.54–13.24, respectively). In terms of percentage BMD change at the femoral neck, both pamidronate and ibandronate combined with calcium demonstrated a remarkable gain compared with calcium (MD, 7.02; 95% CrI, 0.30–13.29 and MD, 7.30; 95% CrI, 0.32–14.22, respectively). The combination of ibandronate with calcium displayed a significant increase in absolute BMD compared to any other treatments and was ranked best. Conclusions: Our NMA suggested that new-generation bisphosphonates such as ibandronate were more favorable in KTRs to improve BMD. However, the conclusion should be treated with caution due to indirect comparisons. PMID:29578126

Efficacy of Pharmacist Based Diabetes Educational Interventions on Clinical Outcomes of Adults With Type 2 Diabetes Mellitus: A Network Meta-Analysis

PubMed Central

Bukhsh, Allah; Khan, Tahir M.; Lee, Shaun W. H.; Lee, Learn-Han; Chan, Kok-Gan; Goh, Bey-Hing

2018-01-01

Background: Comparative efficacy of different pharmacist based interventions on glycemic control of type 2 diabetes patients is unclear. This review aimed to evaluate and compare the efficacy of different pharmacist based interventions on clinical outcomes of type 2 diabetes patients. Methods: A systematic search was conducted across five databases from date of database inception to September 2017. All randomized clinical trials evaluating the efficacy of pharmacist based interventions on type 2 diabetes patients were included for network meta-analysis (NMA). The protocol is available with PROSPERO (CRD42017078854). Results: A total of 43 studies, involving 6259 type 2 diabetes patients, were included. NMA demonstrated that all interventions significantly lowered glycosylated hemoglobin (HbA1c) levels compared to usual care, but there was no statistical evidence from this study that one intervention was significantly better than the other for reducing HbA1c levels. Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy for reducing HbA1c levels [−0.86, 95% CI −0.983, −0.727; p < 0.001]. Pharmacist based diabetes education plus pharmaceutical care was observed to be statistically significant in lowering levels of systolic blood pressure [−4.94; 95%CI −8.65, −1.23] and triglycerides levels [−0.26, 95%CI −0.51, −0.01], as compared to the interventions which involved diabetes education by pharmacist, and for body mass index (BMI) [−0.57; 95%CI −1.25, −0.12] in comparison to diabetes education by health care team involving pharmacist as member. Conclusion: The findings of this review demonstrate that all interventions had a significantly positive effect on HbA1c, but there was no statistical evidence from this study that one intervention was significantly better than the other for achieving glycemic control.Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy on HbA1c and rest of the clinical outcomes. PMID:29692730

Systematic review and network meta-analysis of the efficacy and safety of tumour necrosis factor inhibitor-methotrexate combination therapy versus triple therapy in rheumatoid arthritis.

PubMed

Fleischmann, Roy; Tongbram, Vanita; van Vollenhoven, Ronald; Tang, Derek H; Chung, James; Collier, David; Urs, Shilpa; Ndirangu, Kerigo; Wells, George; Pope, Janet

2017-01-01

Clinical trials have not consistently demonstrated differences between tumour necrosis factor inhibitor (TNFi) plus methotrexate and triple therapy (methotrexate plus hydroxychloroquine plus sulfasalazine) in rheumatoid arthritis (RA). The study objective was to estimate the efficacy, radiographic benefits, safety and patient-reported outcomes of TNFi-methotrexate versus triple therapy in patients with RA. A systematic review and network meta-analysis (NMA) of randomised controlled trials of TNFi-methotrexate or triple therapy as one of the treatment arms in patients with an inadequate response to or who were naive to methotrexate was conducted. American College of Rheumatology 70% response criteria (ACR70) at 6 months was the prespecified primary endpoint to evaluate depth of response. Data from direct and indirect comparisons between TNFi-methotrexate and triple therapy were pooled and quantitatively analysed using fixed-effects and random-effects Bayesian models. We analysed 33 studies in patients with inadequate response to methotrexate and 19 in patients naive to methotrexate. In inadequate responders, triple therapy was associated with lower odds of achieving ACR70 at 6 months compared with TNFi-methotrexate (OR 0.35, 95% credible interval (CrI) 0.19 to 0.64). Most secondary endpoints tended to favour TNFi-methotrexate in terms of OR direction; however, no clear increased likelihood of achieving these endpoints was observed for either therapy. The odds of infection were lower with triple therapy than with TNFi-methotrexate (OR 0.08, 95% CrI 0.00 to 0.57). There were no differences observed between the two regimens in patients naive to methotrexate. In this NMA, triple therapy was associated with 65% lower odds of achieving ACR70 at 6 months compared with TNFi-methotrexate in patients with inadequate response to methotrexate. Although secondary endpoints numerically favoured TNFi-methotrexate, no clear differences were observed. The odds of infection were greater with TNFi-methotrexate. No differences were observed for patients naive to methotrexate. These results may help inform care of patients who fail methotrexate first-line therapy.

Comparative efficacy and tolerability of pharmacological interventions for attention-deficit/hyperactivity disorder in children, adolescents and adults: protocol for a systematic review and network meta-analysis.

PubMed

Cortese, Samuele; Adamo, Nicoletta; Mohr-Jensen, Christina; Hayes, Adrian J; Bhatti, Sahar; Carucci, Sara; Del Giovane, Cinzia; Atkinson, Lauren Z; Banaschewski, Tobias; Simonoff, Emily; Zuddas, Alessandro; Barbui, Corrado; Purgato, Marianna; Steinhausen, Hans-Christoph; Shokraneh, Farhad; Xia, Jun; Cipriani, Andrea; Coghill, David

2017-01-10

Attention-deficit/hyperactivity disorder (ADHD) is a major public health issue. Pharmacological treatments play an important role in the multimodal treatment of ADHD. Currently, there is a lack of up-to-date and comprehensive evidence on how available ADHD drugs compare and rank in terms of efficacy and tolerability, in children or adolescents as well as in adults. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs), to rank pharmacological treatments for ADHD according to their efficacy and tolerability profiles. We will search a broad range of electronic databases, including PubMed, MEDLINE, EMBASE, PsycINFO, ERIC and Web of Science, with no date or language restrictions. We will also search for unpublished studies using international clinical trial registries and contacting relevant drug companies. We will identify and include available parallel-group, cross-over and cluster randomised trials that compare methylphenidate, dexmethylphenidate, amphetamine derivatives (including lisdexamfetamine), atomoxetine, clonidine, guanfacine, bupropion or modafinil (as oral therapy) either with each other or to placebo, in children, adolescents or adults with ADHD. Primary outcomes will be efficacy (indicated by reduction in severity of ADHD core symptoms measured on a standardised scale) and tolerability (the proportion of patients who left a study early due to side effects). Secondary outcomes will be global functioning, acceptability (proportion of patients who left the study early by any cause) and changes in blood pressure and body weight. NMA will be conducted in STATA within a frequentist framework. The quality of RCTs will be evaluated using the Cochrane risk of bias tool, and the quality of the evidence will be assessed using the GRADE approach. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. No ethical issues are foreseen. Results from this study will be published in a peer-reviewed journal and possibly presented at relevant national and international conferences. CRD42014008976. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Comparative effectiveness and acceptability of the FDA-licensed proton pump inhibitors for erosive esophagitis: A PRISMA-compliant network meta-analysis.

PubMed

Li, Mei-Juan; Li, Qing; Sun, Min; Liu, Li-Qin

2017-09-01

This study compared the effectiveness and acceptability of all Food and Drug Administration (FDA)-recommended dose proton pump inhibitors (PPIs) in erosive esophagitis (EE): Dexlansoprazole 60 mg, Esomeprazole 40 mg, Esomeprazole 20 mg, Pantoprazole 40 mg, Lansoprazole 30 mg, Rabeprazole 20 mg, Omeprazole 20 mg. A systematic literature search was performed using PubMed, Embase, and Cochrane Library. Totally, 25 randomized controlled trials (RCTs) met study selection criteria and were incorporated in this network meta-analysis (NMA) study. For the NMA, eligible RCTs of adults with EE verified by endoscopic examination were randomly assigned to the licensed PPIs at least 4 weeks of continuous therapy. The primary efficacy outcome was the endoscopic healing rates at 4 and 8 weeks. Heartburn relief rates were a secondary efficacy outcome. The rates of withdrawal were analyzed as a safety outcome. In comparison to the common comparator omeprazole 20 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [odds ratio (OR), 1.46 (95% confidence interval, 95% CI, 1.24-1.71)] and 8 weeks [1.58 (1.29-1.92)], and improved the heartburn relief rates [1.29 (1.07-1.56)]. In comparison to lansoprazole 30 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [1.30 (1.10-1.53)] and 8 weeks [1.37 (1.13-1.67)], and improved the heartburn relief rates [1.29 (1.03-1.62)]. In terms of acceptability, only dexlansoprazole 60 mg had significantly more all-cause discontinuation than omeprazole 20 mg [1.54 (1.03-2.29)], pantoprazole 40 mg [1.68 (1.08-2.63)], and lansoprazole 30 mg [1.38 (1.02-1.88)]. The standard-dose esomeprazole 40 mg had more superiority in mucosal erosion healing and heartburn relief. Esomeprazole 40 mg, pantoprazole 40 mg, esomeprazole 20 mg, and lansoprazole 30 mg showed more benefits in effectiveness and acceptability than other interventions.

Systematic review and network meta-analysis of the efficacy and safety of tumour necrosis factor inhibitor–methotrexate combination therapy versus triple therapy in rheumatoid arthritis

PubMed Central

Fleischmann, Roy; Tongbram, Vanita; van Vollenhoven, Ronald; Tang, Derek H; Chung, James; Collier, David; Urs, Shilpa; Ndirangu, Kerigo; Wells, George; Pope, Janet

2017-01-01

Objective Clinical trials have not consistently demonstrated differences between tumour necrosis factor inhibitor (TNFi) plus methotrexate and triple therapy (methotrexate plus hydroxychloroquine plus sulfasalazine) in rheumatoid arthritis (RA). The study objective was to estimate the efficacy, radiographic benefits, safety and patient-reported outcomes of TNFi–methotrexate versus triple therapy in patients with RA. Methods A systematic review and network meta-analysis (NMA) of randomised controlled trials of TNFi–methotrexate or triple therapy as one of the treatment arms in patients with an inadequate response to or who were naive to methotrexate was conducted. American College of Rheumatology 70% response criteria (ACR70) at 6 months was the prespecified primary endpoint to evaluate depth of response. Data from direct and indirect comparisons between TNFi–methotrexate and triple therapy were pooled and quantitatively analysed using fixed-effects and random-effects Bayesian models. Results We analysed 33 studies in patients with inadequate response to methotrexate and 19 in patients naive to methotrexate. In inadequate responders, triple therapy was associated with lower odds of achieving ACR70 at 6 months compared with TNFi–methotrexate (OR 0.35, 95% credible interval (CrI) 0.19 to 0.64). Most secondary endpoints tended to favour TNFi–methotrexate in terms of OR direction; however, no clear increased likelihood of achieving these endpoints was observed for either therapy. The odds of infection were lower with triple therapy than with TNFi−methotrexate (OR 0.08, 95% CrI 0.00 to 0.57). There were no differences observed between the two regimens in patients naive to methotrexate. Conclusions In this NMA, triple therapy was associated with 65% lower odds of achieving ACR70 at 6 months compared with TNFi–methotrexate in patients with inadequate response to methotrexate. Although secondary endpoints numerically favoured TNFi–methotrexate, no clear differences were observed. The odds of infection were greater with TNFi–methotrexate. No differences were observed for patients naive to methotrexate. These results may help inform care of patients who fail methotrexate first-line therapy. PMID:28123782

Structural and biochemical studies on Vibrio cholerae Hsp31 reveals a novel dimeric form and Glutathione-independent Glyoxalase activity

PubMed Central

Dey, Sanjay

2017-01-01

Vibrio cholerae experiences a highly hostile environment at human intestine which triggers the induction of various heat shock genes. The hchA gene product of V. cholerae O395, referred to a hypothetical intracellular protease/amidase VcHsp31, is one such stress-inducible homodimeric protein. Our current study demonstrates that VcHsp31 is endowed with molecular chaperone, amidopeptidase and robust methylglyoxalase activities. Through site directed mutagenesis coupled with biochemical assays on VcHsp31, we have confirmed the role of residues in the vicinity of the active site towards amidopeptidase and methylglyoxalase activities. VcHsp31 suppresses the aggregation of insulin in vitro in a dose dependent manner. Through crystal structures of VcHsp31 and its mutants, grown at various temperatures, we demonstrate that VcHsp31 acquires two (Type-I and Type-II) dimeric forms. Type-I dimer is similar to EcHsp31 where two VcHsp31 monomers associate in eclipsed manner through several intersubunit hydrogen bonds involving their P-domains. Type-II dimer is a novel dimeric organization, where some of the intersubunit hydrogen bonds are abrogated and each monomer swings out in the opposite directions centering at their P-domains, like twisting of wet cloth. Normal mode analysis (NMA) of Type-I dimer shows similar movement of the individual monomers. Upon swinging, a dimeric surface of ~400Å2, mostly hydrophobic in nature, is uncovered which might bind partially unfolded protein substrates. We propose that, in solution, VcHsp31 remains as an equilibrium mixture of both the dimers. With increase in temperature, transformation to Type-II form having more exposed hydrophobic surface, occurs progressively accounting for the temperature dependent increase of chaperone activity of VcHsp31. PMID:28235098

The Effectiveness of Counterterrorist Policies in Uzbekistan

DTIC Science & Technology

2012-12-01

ABBREVIATIONS AI – Amnesty International APK – Adalet ve Kalkınma Partisi (Justice and Development Party of Turkey) CIA – Central Intelligence Agency...Using StockMarket Data,” The Journal of Economic Perspectives 20, No. 2 (2006): 193–206; Ceasefires, unemployment rates, and price indexes in...Uzbekistan as well. The worsening economic conditions, high rates of unemployment , large and growing numbers of young males, repressive and corrupt

Effects of Acetylcholinesterase Inhibition on Cholinergic Transmission in the Hippocampal Slice.

DTIC Science & Technology

1985-02-08

compare desensitizing and non- desensitizing amino acids with the changes produced by comparable treatment with carbachol , a cholinergic agonist. We...strong evidence that the effect is due to a classical desensitization of an extra synaptic receptor (Fig. 4). Carbachol (1 min. perfusion) produced a...15 minutes) of the following: glutamate (G),n-methyl-aspartate (NMA), homocysteate (H), or carbachol (C). Each ofthese compounds depolarizes the

Is the Good-Imitator-Poor-Talker Profile Syndrome-Specific in Down Syndrome?: Evidence from Standardised Imitation and Language Measures

ERIC Educational Resources Information Center

Vanvuchelen, M.; Feys, H.; De Weerdt, W.

2011-01-01

The emergence of the Down syndrome (DS) behavioural phenotype during early development may be of great importance for early intervention. The main goal of this study was to investigate the good-imitator-poor-talker developmental profile in DS at preschool age. Twenty children with Down syndrome (DS; mean nonverbal mental age NMA 1 y10 m) and 15…

Mechanism of alcohol-enhanced lucigenin chemiluminescence in alkaline solution.

PubMed

Chi, Quan; Chen, Wanying; He, Zhike

2015-11-01

The chemiluminescence (CL) of lucigenin (Luc(2+)) can be enhanced by different alcohols in alkaline solution. The effect of different fatty alcohols on the CL of lucigenin was related to the carbon chain length and the number of hydroxyl groups. Glycerol provides the greatest enhancement. UV/Vis absorption spectra and fluorescence spectra showed that N-methylacridone (NMA) was produced in the CL reaction in the presence of different alcohols. The peak of the CL spectrum was located at 470 nm in all cases, indicating that the luminophore was always the excited-state NMA. The quenching of lucigenin CL by superoxide dismutase (SOD) and the electron spin resonance (ESR) results with the spin trap of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) demonstrated that superoxide anions (O2 (•-)) were generated from dissolved oxygen in the CL reaction and that glycerol and dihydroxyacetone (DHA) can promote O2 (•-) production by the reduction of dissolved oxygen in alkaline solution. It was assumed that the enhancement provided by different alcohols was related to the solvent effect and reducing capacity. Glycerol and DHA can also reduce Luc(2+) into lucigenin cation radicals (Luc(•+) ), which react with O2 (•-) to produce CL, and glycerol can slowly transform into DHA, which is oxidized quickly in alkaline solution. Copyright © 2015 John Wiley & Sons, Ltd.

Relative benefit-risk comparing diclofenac to other traditional non-steroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors in patients with osteoarthritis or rheumatoid arthritis: a network meta-analysis.

PubMed

van Walsem, Anneloes; Pandhi, Shaloo; Nixon, Richard M; Guyot, Patricia; Karabis, Andreas; Moore, R Andrew

2015-03-19

There is argument over the benefits and risks of drugs for treating chronic musculoskeletal pain. This study compared the efficacy, safety, and tolerability of diclofenac, ibuprofen, naproxen, celecoxib, and etoricoxib for patients with pain caused by osteoarthritis (OA) or rheumatoid arthritis (RA). A systematic literature review used Medline and EMBASE to identify randomised controlled trials. Efficacy outcomes assessed included: pain relief measured by visual analogue scale (VAS); Western Ontario McMaster Universities Arthritis Index (WOMAC) VAS or WOMAC Likert scale; physical functioning measured by WOMAC VAS or Likert scale; and patient global assessment (PGA) of disease severity measured on VAS or 5-point Likert scale. Safety outcomes included: Antiplatelet Trialists' Collaboration (APTC), major cardiovascular (CV) and major upper gastrointestinal (GI) events, and withdrawals. Data for each outcome were synthesized by a Bayesian network meta-analysis (NMA). For efficacy assessments, labelled doses for OA treatment were used for the base case while labelled doses for RA treatment were also included in the sensitivity analysis. Pooled data across dose ranges were used for safety. Efficacy, safety, and tolerability data were found for 146,524 patients in 176 studies included in the NMA. Diclofenac (150 mg/day) was likely to be more effective in alleviating pain than celecoxib (200 mg/day), naproxen (1000 mg/day), and ibuprofen (2400 mg/day), and similar to etoricoxib (60 mg/day); a lower dose of diclofenac (100 mg/day) was comparable to all other treatments in alleviating pain. Improved physical function with diclofenac (100 and 150 mg/day) was mostly comparable to all other treatments. PGA with diclofenac (100 and 150 mg/day) was likely to be more effective or comparable to all other treatments. All active treatments were similar for APTC and major CV events. Major upper GI events with diclofenac were lower compared to naproxen and ibuprofen, comparable to celecoxib, and higher than etoricoxib. Risk of withdrawal with diclofenac was lower compared to ibuprofen, similar to celecoxib and naproxen, and higher than etoricoxib. The benefit-risk profile of diclofenac was comparable to other treatments used for pain relief in OA and RA; benefits and risks vary in individuals and need consideration when making treatment decisions.

Upfront allogeneic stem cell transplantation after reduced-intensity/nonmyeloablative conditioning for patients with myelodysplastic syndrome: a study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

PubMed

Damaj, Gandhi; Mohty, Mohammad; Robin, Marie; Michallet, Mauricette; Chevallier, Patrice; Beguin, Yves; Nguyen, Stephanie; Bories, Pierre; Blaise, Didier; Maillard, Natacha; Rubio, Marie Therese; Fegueux, Nathalie; Cornillon, Jerome; Clavert, Aline; Huynh, Anne; Adès, Lionel; Thiébaut-Bertrand, Anne; Hermine, Olivier; Vigouroux, Stephane; Fenaux, Pierre; Duhamel, Alain; Yakoub-Agha, Ibrahim

2014-09-01

Cytoreduction before allogeneic stem cell transplantation (allo-SCT) for patients with myelodysplastic syndromes remains a debatable issue. After excluding patients who had received preconditioning induction chemotherapy, we analyzed 128 consecutive patients with myelodysplastic syndrome who received reduced-intensity or nonmyeloablative conditioning (RIC/NMA) allo-SCT. Among them, 40 received azacitidine (AZA) before transplant (AZA group) and 88 were transplanted up front (best supportive care [BSC] group). At diagnosis, 55 patients had intermediate 2 or high-risk scores per the International Prognostic Scoring System and 33 had a high cytogenetic risk score. Progression to a more advanced disease before allo-SCT was recorded in 22 patients. Source of stem cells were blood (n = 112) or marrow (n = 16) from sibling (n = 78) or HLA-matched unrelated (n = 50) donors. With a median follow-up of 60 months, 3-year overall survival, relapse-free survival, cumulative incidence of relapse, and nonrelapse mortality were, respectively, 53% versus 53% (P = .69), 37% versus 42% (P = .78), 35% versus 36% (P = .99), and 20% versus 23% (P = .74), for the AZA group and BSC group, respectively. Multivariate analysis confirmed the absence of statistical differences in outcome between the AZA and BSC groups, after adjusting for potential confounders using the propensity score approach. The absence of cytoreduction before RIC/NMA allo-SCT did not seem to alter the outcome. However, our results emphasize the need to perform prospective protocols to delineate the role of debulking strategy and to identify subsets of patients who may benefit from this approach. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The Development of the Dental Liquid Ration

DTIC Science & Technology

1993-10-01

taste like norma components of a meal. Thirty products supporting a three-day menu cycle consist of products such as chicken barbecue, lyonnaise ... potatoes , buttered corn, and chocolate mocha cake. There are also six flavors of at I nma deiryahake. The ULR cmme packaged in either individual serving...wide variety of entrees, vegetables, Itards,, and desserts. Prodxts inlude O~d~m hBazecu, tLczmise Potatoes , Broccoli au Grat~in, aMd dcxoolate Mocha

Scrambled Sobol Sequences via Permutation

DTIC Science & Technology

2009-01-01

LCG LCG64 LFG MLFG PMLCG Sobol Scrambler PermutationScrambler LinearScrambler <<uses>> PermuationFactory StaticFactory DynamicFactory <<uses>> Figure 3...Phy., 19:252–256, 1979. [2] Emanouil I. Atanassov. A new efficient algorithm for generating the scrambled sobol ’ sequence. In NMA ’02: Revised Papers...Deidre W.Evan, and Micheal Mascagni. On the scrambled sobol sequence. In ICCS2005, pages 775–782, 2005. [7] Richard Durstenfeld. Algorithm 235: Random

Spectral Estimation: An Overdetermined Rational Model Equation Approach.

DTIC Science & Technology

1982-09-15

A-A123 122 SPECTRAL ESTIMATION: AN OVERDETERMINEO RATIONAL MODEL 1/2 EQUATION APPROACH..(U) ARIZONA STATE UNIV TEMPE DEPT OF ELECTRICAL AND COMPUTER...2 0 447,_______ 4. TITLE (mAd Sabile) S. TYPE or REPORT a PEP40D COVERED Spectral Estimation; An Overdeteruined Rational Final Report 9/3 D/8 to...andmmd&t, by uwek 7a5 4 Rational Spectral Estimation, ARMA mo~Ie1, AR model, NMA Mdle, Spectrum, Singular Value Decomposition. Adaptivb Implementatlan

Dopaminergic modulation of locomotor network activity in the neonatal mouse spinal cord

PubMed Central

Sharples, Simon A.; Humphreys, Jennifer M.; Jensen, A. Marley; Dhoopar, Sunny; Delaloye, Nicole; Clemens, Stefan

2015-01-01

Dopamine is now well established as a modulator of locomotor rhythms in a variety of developing and adult vertebrates. However, in mice, while all five dopamine receptor subtypes are present in the spinal cord, it is unclear which receptor subtypes modulate the rhythm. Dopamine receptors can be grouped into two families—the D1/5 receptor group and the D2/3/4 group, which have excitatory and inhibitory effects, respectively. Our data suggest that dopamine exerts contrasting dose-dependent modulatory effects via the two receptor families. Our data show that administration of dopamine at concentrations >35 μM slowed and increased the regularity of a locomotor rhythm evoked by bath application of 5-hydroxytryptamine (5-HT) and N-methyl-d(l)-aspartic acid (NMA). This effect was independent of the baseline frequency of the rhythm that was manipulated by altering the NMA concentration. We next examined the contribution of the D1- and D2-like receptor families on the rhythm. Our data suggest that the D1-like receptor contributes to enhancement of the stability of the rhythm. Overall, the D2-like family had a pronounced slowing effect on the rhythm; however, quinpirole, the D2-like agonist, also enhanced rhythm stability. These data indicate a receptor-dependent delegation of the modulatory effects of dopamine on the spinal locomotor pattern generator. PMID:25652925

Beyond Point Charges: Dynamic Polarization from Neural Net Predicted Multipole Moments.

PubMed

Darley, Michael G; Handley, Chris M; Popelier, Paul L A

2008-09-09

Intramolecular polarization is the change to the electron density of a given atom upon variation in the positions of the neighboring atoms. We express the electron density in terms of multipole moments. Using glycine and N-methylacetamide (NMA) as pilot systems, we show that neural networks can capture the change in electron density due to polarization. After training, modestly sized neural networks successfully predict the atomic multipole moments from the nuclear positions of all atoms in the molecule. Accurate electrostatic energies between two atoms can be then obtained via a multipole expansion, inclusive of polarization effects. As a result polarization is successfully modeled at short-range and without an explicit polarizability tensor. This approach puts charge transfer and multipolar polarization on a common footing. The polarization procedure is formulated within the context of quantum chemical topology (QCT). Nonbonded atom-atom interactions in glycine cover an energy range of 948 kJ mol(-1), with an average energy difference between true and predicted energy of 0.2 kJ mol(-1), the largest difference being just under 1 kJ mol(-1). Very similar energy differences are found for NMA, which spans a range of 281 kJ mol(-1). The current proof-of-concept enables the construction of a new protein force field that incorporates electron density fragments that dynamically respond to their fluctuating environment.

Preventing Emergence Agitation Using Ancillary Drugs with Sevoflurane for Pediatric Anesthesia: A Network Meta-Analysis.

PubMed

Wang, Xin; Deng, Qi; Liu, Bin; Yu, Xiangdi

2017-11-01

Using sevoflurane for pediatric anesthesia plays a pivotal role in surgeries. Emergence agitation (EA) is a major adverse event accompanied with pediatric anesthesia. Other anesthetic adjuvants can be combined with sevoflurane in clinical practices for different purposes. However, it is uncertain that such a practice may have substantial influence on the risk of EA. We conducted a literature search in online databases, including PubMed, Embase, Cochrane Library, and Clinical Trials. Key data were extracted from eligible randomized control trials (RCTs). Both pairwise and network meta-analysis (NMA) were conducted for synthesizing data from eligible studies. The relative risk of EA was assessed using the odds ratios (ORs) and their corresponding 95 % confidence intervals (CI) or credible intervals (CrI). Ranking scheme based on the surface under the cumulative ranking curve (SUCRA) values was produced. Several key assumptions of NMA such as heterogeneity, degree of consistence, and publication bias were validated by different statistical or graphical approaches. Evidence from 67 randomized control trials was synthesized. The relative risk of EA associated with eight anesthetic adjuvants was analyzed, including ketamine, propofol, dexmedetomidine, clonidine, midazolam, fentanyl, remifentanil, and sufentanil. Patients with the following anesthetic adjuvants appeared to have significantly reduced risk of EA in relation to those with placebo: dexmedetomidine (OR = 0.18, 95 % CrI 0.12-0.25), fentanyl (OR = 0.19, 95 % CrI 0.12-0.30), sufentanil (OR = 0.20, 95 % CrI 0.08-0.50), ketamine (OR = 0.21, 95 % CrI 0.13-0.34), clonidine (OR = 0.25, 95 % CrI 0.14-0.46), propofol (OR = 0.32, 95 % CrI 0.18-0.56), midazolam (OR = 0.46, 95 % CrI 0.27-0.77), and remifentanil (OR = 0.29, 95 % CrI 0.13-0.68). The SUCRA values for each anesthetic adjuvant were: dexmedetomidine (73.65 %), fentanyl (68.04 %), sufentanil (60.81 %), ketamine (59.99 %), clonidine (47.74 %), remifentanil (40.15 %), propofol (33.23 %), midazolam (16.33 %), and placebo (0.06 %). Incorporating anesthetic adjuvants particularly dexmedetomidine into sevoflurane appeared to be significantly associated with a decreased risk of EA in pediatric anesthesia.

Superconducting Oxide Films for Multispectral Infrared Sensors

DTIC Science & Technology

1989-02-07

films of both low - and high-temperature supercon- resistances below our measurement sensitivity of 4x 10-10 ductors, including BaPb,-Bi2 O.,’ NbN /BN, 2...Simon, " NbN /BN Granular Films - A states, such as normal metal barriers, will improve the noise Sensitive, High-Speed Detector For Pulsed Far- Infrared ...A. W. Kleinsasser, and R. L Sandstrom, "Electron Trap States and Low Frequency Noise in Tunnel Summary and Conclusions Junctions", IREE Trans. nMa n

Lithospheric Models of the Middle East to Improve Seismic Source Parameter Determination/Event Location Accuracy

DTIC Science & Technology

2012-09-01

State Award Nos. DE-AC52-07NA27344/24.2.3.2 and DOS_SIAA-11-AVC/NMA-1 ABSTRACT The Middle East is a tectonically complex and seismically...active region. The ability to accurately locate earthquakes and other seismic events in this region is complicated by tectonics , the uneven...and seismic source parameters show that this activity comes from tectonic events. This work is informed by continuous or event-based regional

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

Calderon-Garciduenas, L.; Roy-Ocotla, G.

Southwest metropolitan Mexico City (SWMMC) inhabitants have been exposed several hours per day for the last 6 years to photochemical smog, ozone being the most important oxidant pollutant. Subjects exposed to the SWMMC atmosphere develop several histopathological changes in their nasal mucosa: dysplasia is the most significant, affecting 78.72% of adult individuals within 60 or more days of residence in SWMMC. This study was originally designed to explore whether chemical intervention could modify nasal dysplasia, as determined by nasal cytology, in a defined adult population. In a placebo-controlled, randomized, double-blind trial, 177 healthy male subjects were divided into 5 groupsmore » to whom 5000 IU of vitamin A, 100 IU of vitamin E, a combination of vitamins A and E (5000 IU + 100 IU), 16 mg of beta-carotene, or placebo were administered daily for 4 months. Sixteen clinical and cytological variables were monitored. No effect on dysplasia was seen at the end of the 4-month trial; however, an apparent reversibility as well as progression of the dysplastic nasal lesions and high correlation coefficients between dysplasia and nasal cytology of polymorphonuclear leukocytes (PMNs; 0.85), squamous metaplasia (SM; 0.50), and nasal mucosa atrophy (NMA; 0.41) were found. A mathematical theoretical nasal dysplasia (tD) predictor equation for SWMMC adult male inhabitants is proposed (tD = 0.85 delta PMNs + 0.50 delta SM + 0.41 delta NMA + 0.98), in which PMNs are the best single dysplasia predictor, and all variables are independent.« less

Comparative effectiveness and acceptability of the FDA-licensed proton pump inhibitors for erosive esophagitis

PubMed Central

Li, Mei-Juan; Li, Qing; Sun, Min; Liu, Li-Qin

2017-01-01

Abstract Background: This study compared the effectiveness and acceptability of all Food and Drug Administration (FDA)-recommended dose proton pump inhibitors (PPIs) in erosive esophagitis (EE): Dexlansoprazole 60 mg, Esomeprazole 40 mg, Esomeprazole 20 mg, Pantoprazole 40 mg, Lansoprazole 30 mg, Rabeprazole 20 mg, Omeprazole 20 mg. Methods: A systematic literature search was performed using PubMed, Embase, and Cochrane Library. Totally, 25 randomized controlled trials (RCTs) met study selection criteria and were incorporated in this network meta-analysis (NMA) study. Results: For the NMA, eligible RCTs of adults with EE verified by endoscopic examination were randomly assigned to the licensed PPIs at least 4 weeks of continuous therapy. The primary efficacy outcome was the endoscopic healing rates at 4 and 8 weeks. Heartburn relief rates were a secondary efficacy outcome. The rates of withdrawal were analyzed as a safety outcome. In comparison to the common comparator omeprazole 20 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [odds ratio (OR), 1.46 (95% confidence interval, 95% CI, 1.24–1.71)] and 8 weeks [1.58 (1.29–1.92)], and improved the heartburn relief rates [1.29 (1.07–1.56)]. In comparison to lansoprazole 30 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [1.30 (1.10–1.53)] and 8 weeks [1.37 (1.13–1.67)], and improved the heartburn relief rates [1.29 (1.03–1.62)]. In terms of acceptability, only dexlansoprazole 60 mg had significantly more all-cause discontinuation than omeprazole 20 mg [1.54 (1.03–2.29)], pantoprazole 40 mg [1.68 (1.08–2.63)], and lansoprazole 30 mg [1.38 (1.02–1.88)]. Conclusion: The standard-dose esomeprazole 40 mg had more superiority in mucosal erosion healing and heartburn relief. Esomeprazole 40 mg, pantoprazole 40 mg, esomeprazole 20 mg, and lansoprazole 30 mg showed more benefits in effectiveness and acceptability than other interventions. PMID:28953640

Viral Penetration of High Efficiency Particulate Air (HEPA) Filters

DTIC Science & Technology

2007-02-01

ml. For aerosol studies the MS2 coli phage was either diluted in sterile distilled water or 0.5% tryptone to a concentration ~108 PFU/mL. Collison...increased to 38%; an increase of 30.5% over MS2 suspended in water . The mass curve is not complete, and thus the fraction of particles in the 100–300 nm...a decrease of 14% over what is observed for MS2 suspended in water . The overall number of particles generated by MS2 + 0.5% tryptone and MS2 in

Nasal cytology in southwest metropolitan Mexico City inhabitants: a pilot intervention study.

PubMed Central

Calderon-Garcidueñas, L; Roy-Ocotla, G

1993-01-01

Southwest metropolitan Mexico City (SWMMC) inhabitants have been exposed several hours per day for the last 6 years to photochemical smog, ozone being the most important oxidant pollutant. Subjects exposed to the SWMMC atmosphere develop several histopathological changes in their nasal mucosa: dysplasia is the most significant, affecting 78.72% of adult individuals within 60 or more days of residence in SWMMC. This study was originally designed to explore whether chemical intervention could modify nasal dysplasia, as determined by nasal cytology, in a defined adult population. In a placebo-controlled, randomized, double-blind trial, 177 healthy male subjects were divided into 5 groups to whom 5000 IU of vitamin A, 100 IU of vitamin E, a combination of vitamins A and E (5000 IU + 100 IU), 16 mg of beta-carotene, or placebo were administered daily for 4 months. Sixteen clinical and cytological variables were monitored. No effect on dysplasia was seen at the end of the 4-month trial; however, an apparent reversibility as well as progression of the dysplastic nasal lesions and high correlation coefficients between dysplasia and nasal cytology of polymorphonuclear leukocytes (PMNs; 0.85), squamous metaplasia (SM; 0.50), and nasal mucosa atrophy (NMA; 0.41) were found. A mathematical theoretical nasal dysplasia (tD) predictor equation for SWMMC adult male inhabitants is proposed (tD = 0.85 delta PMNs + 0.50 delta SM + 0.41 delta NMA + 0.98), in which PMNs are the best single dysplasia predictor, and all variables are independent.(ABSTRACT TRUNCATED AT 250 WORDS) Images p138-a Figure 1. Figure 2. Figure 3. Figure 4. PMID:8354200

Cost of Glycemic Target Achievement with Sodium Glucose Co-transporter 2 Inhibitors in Patients with Type 2 Diabetes in the UK.

PubMed

Evans, Marc; Achha, Sayeed; Neslusan, Cheryl

2017-10-01

Diabetes-related costs make up a large portion of healthcare expenditures in the UK. Many of these costs are related to treatment of diabetes-related complications. Reducing HbA1c to <7.0% (53 mmol/mol) reduces the incidence of complications and comorbidities. Metformin plus sulfonylurea is the most common dual oral combination therapy in the UK. The costs of achieving HbA1c <7.0% in patients inadequately controlled on metformin plus sulfonylurea were analyzed for the sodium glucose co-transporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin from the perspective of the UK National Health System. A Bayesian network meta-analysis (NMA) was used to compare the proportion of patients with type 2 diabetes mellitus inadequately controlled on metformin plus sulfonylurea that achieved HbA1c <7.0% after 26 weeks with canagliflozin 100 and 300 mg, dapagliflozin 10 mg, and empagliflozin 10 and 25 mg; odds ratios (ORs) and pairwise probabilities (P) for canagliflozin versus dapagliflozin and empagliflozin were calculated. The costs associated with achieving HbA1c <7.0% were estimated on the basis of medication costs and the proportion of patients achieving the HbA1c goal. NMA results showed that a higher proportion of patients treated with canagliflozin 300 mg achieved HbA1c <7.0% (41%) compared with those treated with dapagliflozin 10 mg (25%), empagliflozin 10 mg (23%), empagliflozin 25 mg (28%), or canagliflozin 100 mg (27%). The odds of achieving HbA1c <7.0% were greater with canagliflozin 300 mg than with dapagliflozin 10 mg (OR 2.03 [P = 94%]), empagliflozin 10 mg (OR 2.29 [P = 99%]), or empagliflozin 25 mg (OR 1.71 [P = 93%]). The per patient costs of achieving HbA1c <7.0% at 26 weeks were £881, £580, £951, £1034, and £849 with canagliflozin 100 and 300 mg, dapagliflozin 10 mg, and empagliflozin 10 and 25 mg. This analysis suggests that, in the UK, canagliflozin 300 mg provides the best value for money among all SGLT2 inhibitors in terms of achieving HbA1c <7.0% when used as part of triple therapy with metformin plus sulfonylurea. Janssen Global Services, LLC, Raritan, NJ, USA.

Tobacco control: consensus report of the National Medical Association.

PubMed

Marable, Sharon; Crim, Courtney; Dennis, Gary C; Epps, Roselyn Payne; Freeman, Harold; Mills, Sherry; Coolchan, Eric T; Robinson, Lawrence; Robinson, Robert; Cole, Lorraine; Payne, Pamela H

2002-02-01

Tobacco Control remains one of the greatest determinants for reducing the morbidity and mortality of African Americans. To examine the scope and consequences of tobacco use among African Americans and characterize its implications for the National Medical Association physician membership and their patients, and identify policy, education, advocacy and research issues in Tobacco Control for the organization. Literature review using the MEDLINE database from January 1966 to August 1999 Week 1, searching Medical Subject Heading (MeSH) reading combined with text words "Black" or "African American" and "Tobacco" as a search term, identified 130 articles/110 abstracts published between 1988 and February 1999. The panel selected 61 appropriate articles and a paper summarizing the literature review was developed. The summary paper was used as background material for a formal consensus panel discussion on July 16-17, 1999. Consensus among committee members was reached via mail, fax and e-mail using the summary review paper, annotated bibliographies key informant surveys, and previous NMA resolutions on tobacco control. A formal working session was held on July 16-17, 1999 in which four areas of concentration of issues were determined: Policy, Advocacy, Education and Research. All committee members approved the final report. Because tobacco control issues in African Americans are both complex and poorly understood, the panel views the NMA's role as pivotal in the coordination of resources and capacity-building to address all four areas identified. Stronger partner-ships with traditional federal and nonprofit agencies associated with tobacco control/advocacy in African Americans as well as nontraditional organizations (i.e., churches, academia, marketing and media organizations) also must occur to strengthen the infra-structure needed to assess needs, design appropriate interventions and evaluate the appropriateness, effectiveness and efficacy of tobacco control efforts in African American communities.

[Experimental study on therapeutic effect of Dabuyin Wan on true precocious puberty in female rats].

PubMed

Cheng, Min; Ye, Xiao-Di; Miao, Yun-Ping; Chen, Ai-Ying; Zheng, Gao-Li

2013-02-01

To study the therapeutic effect of Dabuyin Wan on true precocious puberty of female rats and its possible mechanism. Twenty-two-day-old female SD rats were subcutaneously injected with 40 mg x kg(-1) N-methyl-DL-aspartic acid (NMA) at 14:00 and 16:00 every day; meanwhile, the rats were given Dabuyin Wan for intervention. Visual inspection was conducted for the time of vaginal opening. The first estrus was observed by yaginal smear test. Their ovaries and uterus were weighed to calculate organ coefficients. Conventional pathological slices were made to observe morphological changes in ovaries and uterus and calculate the thickness of uterine walls and the number of corpus luteums. The level of E2 in serum was detected to assess the therapeutic effect of Dabuyin Wan on NMA precocious puberty in rats. expressions of GnRH, GPR54 and Kiss-1 mRNA in hypothalamus were measured by semi-quantitative RT-PCR to investigate the possible mechanism of Dabuyin Wan. Dabuyin Wan at 3.24 g x kg(-1) and 1.62 g x kg(-1) significantly decreased the organ coefficients in rats with precocious puberty (P < 0.05), decrease the number of vaginal openings in rats (P < 0.01) and the thickness of uterine walls and the number of corpus luteums (P < 0.05), and notably down-regulated expressions of GnRH, GPR54 and Kiss-1 mRNA in hypothalamus (P < 0.05), without significant impact on E2 in serum. Dabuyin Wan may inhibit GnRH synthesis and release as well as startup of hypothalamic-pituitary-gonadal axis by down-regulating Kiss-1/GPR54 mRNA expression in hypothalamus, in order to realize the therapeutic effect on true precocious puberty.

Aberrant expressions of c-KIT and DOG-1 in mucinous and nonmucinous colorectal carcinomas and relation to clinicopathologic features and prognosis.

PubMed

Foda, Abd Al-Rahman Mohammad; Mohamed, Mie Ali

2015-10-01

c-KIT and DOG-1 are 2 highly expressed proteins in gastrointestinal stromal tumors. Few studies had investigated c-KIT, but not DOG-1, expression in colorectal carcinoma (CRC). This study aims to investigate expressions of c-KIT and DOG-1 in colorectal mucinous carcinoma and nonmucinous carcinoma using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal mucinous (MA) and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique, and immunohistochemistry for c-KIT and DOG-1 was done. We found that aberrant c-KIT expression was detected in 12 cases (8%); 6 cases (4%) showed strong expression. Aberrant DOG-1 expression was detected in 15 cases (10%); among them, only 4 cases (2.7%) showed strong expression. Nonmucinous adenocarcinoma showed a significantly high expression of c-KIT, but not DOG-1, than MA. Aberrant c-KIT and DOG-1 expressions were significantly unrelated but were associated with excessive microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. In conclusion, aberrant c-KIT and DOG-1 expressions in CRC are rare events, either in NMA or MA. Nonmucinous adenocarcinoma showed a significantly higher expression of c-KIT, but not DOG-1, than MA. The expressions of both in CRC are significantly unrelated but are associated with microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. So, c-KIT and DOG-1 immunostaining is not a cost-effective method of identifying patients with CRC who may benefit from treatment with tyrosine kinase inhibitors. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis.

PubMed

Tricco, Andrea C; Blondal, Erik; Veroniki, Areti Angeliki; Soobiah, Charlene; Vafaei, Afshin; Ivory, John; Strifler, Lisa; Cardoso, Roberta; Reynen, Emily; Nincic, Vera; Ashoor, Huda; Ho, Joanne; Ng, Carmen; Johnson, Christy; Lillie, Erin; Antony, Jesmin; Roberts, Derek J; Hemmelgarn, Brenda R; Straus, Sharon E

2016-12-23

Although serotonin (5-HT 3 ) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT 3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT 3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13-4.17). For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall. Most 5-HT 3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting. This study was registered at PROSPERO: ( CRD42013003564 ).

Positive correlation between blood pressure or heart rate and chymase-dependent angiotensin II-forming activity in circulating mononuclear leukocytes measured by new ELISA.

PubMed

Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Urata, Hidenori

2018-01-01

The aim of the present study was to establish a convenient clinically applicable assay method for chymase-dependent angiotensin II forming activity of circulating mononuclear leukocytes (CML), which was potentially a marker of tissue chymase activity. Using this method, association between CML chymase activity and clinical parameters was determined. Cardiovascular outpatients (n = 170) without taking antihypertensive medication were recruited. An ELISA for chymase-dependent angiotensin II-forming activity in CML was established using Nma /Dnp-modified angiotensin I. Logistic regression analysis revealed that age and male gender were significant independent determinants of the increased CML chymase activity. After adjustment by age and gender, the CML chymase activity was positively correlated with systolic blood pressure, pulse rate, and the brain natriuretic peptide level. The relation between blood pressure and CML chymase activity suggests that it might reflect that increased tissue chymase activity contributes to systemic high blood pressure and heart rate because plasma chymase is inactive due to inhibitory plasma inhibitors.

Novel ionic liquid matrices for qualitative and quantitative detection of carbohydrates by matrix assisted laser desorption/ionization mass spectrometry.

PubMed

Zhao, Xiaoyong; Shen, Shanshan; Wu, Datong; Cai, Pengfei; Pan, Yuanjiang

2017-09-08

Analysis of carbohydrates based on matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is still challenging and researchers have been devoting themselves to efficient matrices discovery. In the present study, the design, synthesis, qualitative and quantitative performance of non-derivative ionic liquid matrices (ILMs) were reported. DHB/N-methylaniline (N-MA) and DHB/N-ethylaniline (N-EA), performing best for carbohydrate detection, have been screened out. The limit of detection for oligosaccharide provided by DHB/N-MA and DHB/N-EA were as low as 10 fmol. DHB/N-MA and DHB/N-EA showed significantly higher ion generation efficiency than DHB. The comparison of capacity to probe polysaccharide between these two ILMs and DHB also revealed their powerful potential. Their outstanding performance were probably due to lower proton affinities and stronger UV absorption at λ = 355 nm. What is more, taking DHB/N-MA as an example, quantitative analysis of fructo-oligosaccharide mixtures extracted and identified from rice noodles has been accomplished sensitively using an internal standard method. Overall, DHB/N-MA and DHB/N-EA exhibited excellent performance and might be significant sources as the carbohydrate matrices. Copyright © 2017 Elsevier B.V. All rights reserved.

Neutral dipole-dipole dimers: A new field in science

NASA Astrophysics Data System (ADS)

Kosower, Edward M.; Borz, Galina

2018-03-01

Dimer formation with dipole neutralization produces species such as low polarity water (LPW) compatible with hydrophobic surfaces (Phys. Chem. Chem. Phys. 2015, 17, 24895-24900) Dimerization and dipole neutralization occurs for N-methylacetamide on polyethylene, a behavior drastically different from its contortions in acetonitrile on AgBr:AgCl planar crystals (AgX) (ChemPhysChem 2014, 15, 3598-3607). The weak infrared absorption of the amide dimer on polyethylene is shown experimentally. Dimerization of palmitic acid is shown along with some of the many ramifications for intracellular systems. Polyoligomers of water are present on polyethylene surfaces. Some high resolution spectra of three of the polyoligomers of water are shown along with a mechanistic scheme for polyoligomer formation and dissolution. The structures of some of the oligomers are known from spectroscopic studies of water on AgX. The scope of the article begins with PE, generally accepted as hydrophobic. The IR of PE revealed not only that water was present but that it appeared in two forms, oligomers (O) and polyoligomers (PO). How did we recognize what they were? These species had been observed as especially strong "marker" peaks in the spectra1 of water placed on planar AgX, a platform developed by Katzir and his coworkers [6]. But there was a problem: the proximity to PE of oligomers with substantial (calculated) dipole moments and thus polarity, including cyclic hexamers of water (chair and boat forms), the cyclic pentamer, the books I and II, and the cyclic trimer [7a]. Another link was needed, a role perfectly fit by the already cited low polarity water (LPW). The choice was experimentally supported by the detection of low intensity absorption in the bending region.Some important generalities flow from these results. What other dimers might be present in the biological or chemical world? Palmitic acid dimer (PAD) would be a candidate for decreasing the polarity of the acid (PA). Another possibility might be N-methylacylamides of which we have noted N-methylacetamide (NMA). We had found that NMA in a polar solvent on AgX was very acrobatic, forming first a 310-helix, an α-helix, a π-helix and a planar form in succession. In sharp contrast, we discovered that NMA forms a dimer (NMAD) and becomes immiscible with the water present on the PE surface. One may vary the acyl group and even include functional groups. Another aspect of the surface behavior of water is the formation of oligomers and polyoligomers. We will show a diagram that explains the formation of polyoligomers from oligomers and their ultimate formation of oligomers with apposed dipoles. This Scope summary should make it easier to follow the description of the varied phenomena found for the PE-water system.

Network meta-analysis of diagnostic test accuracy studies identifies and ranks the optimal diagnostic tests and thresholds for health care policy and decision-making.

PubMed

Owen, Rhiannon K; Cooper, Nicola J; Quinn, Terence J; Lees, Rosalind; Sutton, Alex J

2018-07-01

Network meta-analyses (NMA) have extensively been used to compare the effectiveness of multiple interventions for health care policy and decision-making. However, methods for evaluating the performance of multiple diagnostic tests are less established. In a decision-making context, we are often interested in comparing and ranking the performance of multiple diagnostic tests, at varying levels of test thresholds, in one simultaneous analysis. Motivated by an example of cognitive impairment diagnosis following stroke, we synthesized data from 13 studies assessing the efficiency of two diagnostic tests: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), at two test thresholds: MMSE <25/30 and <27/30, and MoCA <22/30 and <26/30. Using Markov chain Monte Carlo (MCMC) methods, we fitted a bivariate network meta-analysis model incorporating constraints on increasing test threshold, and accounting for the correlations between multiple test accuracy measures from the same study. We developed and successfully fitted a model comparing multiple tests/threshold combinations while imposing threshold constraints. Using this model, we found that MoCA at threshold <26/30 appeared to have the best true positive rate, whereas MMSE at threshold <25/30 appeared to have the best true negative rate. The combined analysis of multiple tests at multiple thresholds allowed for more rigorous comparisons between competing diagnostics tests for decision making. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Topotecan, pegylated liposomal doxorubicin hydrochloride, paclitaxel, trabectedin and gemcitabine for advanced recurrent or refractory ovarian cancer: a systematic review and economic evaluation.

PubMed

Edwards, Steven J; Barton, Samantha; Thurgar, Elizabeth; Trevor, Nicola

2015-01-01

Ovarian cancer is the fifth most common cancer in the UK, and the fourth most common cause of cancer death. Of those people successfully treated with first-line chemotherapy, 55-75% will relapse within 2 years. At this time, it is uncertain which chemotherapy regimen is more clinically effective and cost-effective for the treatment of recurrent, advanced ovarian cancer. To determine the comparative clinical effectiveness and cost-effectiveness of topotecan (Hycamtin(®), GlaxoSmithKline), pegylated liposomal doxorubicin hydrochloride (PLDH; Caelyx(®), Schering-Plough), paclitaxel (Taxol(®), Bristol-Myers Squibb), trabectedin (Yondelis(®), PharmaMar) and gemcitabine (Gemzar(®), Eli Lilly and Company) for the treatment of advanced, recurrent ovarian cancer. Electronic databases (MEDLINE(®), EMBASE, Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluations Database) and trial registries were searched, and company submissions were reviewed. Databases were searched from inception to May 2013. A systematic review of the clinical and economic literature was carried out following standard methodological principles. Double-blind, randomised, placebo-controlled trials, evaluating topotecan, PLDH, paclitaxel, trabectedin and gemcitabine, and economic evaluations were included. A network meta-analysis (NMA) was carried out. A de novo economic model was developed. For most outcomes measuring clinical response, two networks were constructed: one evaluating platinum-based regimens and one evaluating non-platinum-based regimens. In people with platinum-sensitive disease, NMA found statistically significant benefits for PLDH plus platinum, and paclitaxel plus platinum for overall survival (OS) compared with platinum monotherapy. PLDH plus platinum significantly prolonged progression-free survival (PFS) compared with paclitaxel plus platinum. Of the non-platinum-based treatments, PLDH monotherapy and trabectedin plus PLDH were found to significantly increase OS, but not PFS, compared with topotecan monotherapy. In people with platinum-resistant/-refractory (PRR) disease, NMA found no statistically significant differences for any treatment compared with alternative regimens in OS and PFS. Economic modelling indicated that, for people with platinum-sensitive disease and receiving platinum-based therapy, the estimated probabilistic incremental cost-effectiveness ratio [ICER; incremental cost per additional quality-adjusted life-year (QALY)] for paclitaxel plus platinum compared with platinum was £24,539. Gemcitabine plus carboplatin was extendedly dominated, and PLDH plus platinum was strictly dominated. For people with platinum-sensitive disease and receiving non-platinum-based therapy, the probabilistic ICERs associated with PLDH compared with paclitaxel, and trabectedin plus PLDH compared with PLDH, were estimated to be £25,931 and £81,353, respectively. Topotecan was strictly dominated. For people with PRR disease, the probabilistic ICER associated with topotecan compared with PLDH was estimated to be £324,188. Paclitaxel was strictly dominated. As platinum- and non-platinum-based treatments were evaluated separately, the comparative clinical effectiveness and cost-effectiveness of these regimens is uncertain in patients with platinum-sensitive disease. For platinum-sensitive disease, it was not possible to compare the clinical effectiveness and cost-effectiveness of platinum-based therapies with non-platinum-based therapies. For people with platinum-sensitive disease and treated with platinum-based therapies, paclitaxel plus platinum could be considered cost-effective compared with platinum at a threshold of £30,000 per additional QALY. For people with platinum-sensitive disease and treated with non-platinum-based therapies, it is unclear whether PLDH would be considered cost-effective compared with paclitaxel at a threshold of £30,000 per additional QALY; trabectedin plus PLDH is unlikely to be considered cost-effective compared with PLDH. For patients with PRR disease, it is unlikely that topotecan would be considered cost-effective compared with PLDH. Randomised controlled trials comparing platinum with non-platinum-based treatments might help to verify the comparative effectiveness of these regimens. This study is registered as PROSPERO CRD42013003555. The National Institute for Health Research Health Technology Assessment programme.

Seasonal differences in the secretion of luteinising hormone and prolactin in response to N-methyl-DL-aspartate in starlings (Sturnus vulgaris).

PubMed

Dawson, A

2005-02-01

In birds, unlike mammals, seasonal changes in reproductive function are associated with marked changes in the amount of gonadotrophin-releasing hormone (GnRH) stored in the hypothalamus. Prolonged exposure to long photoperiods leads to photorefractoriness after the breeding season. Photorefractory birds have low hypothalamic concentrations of chicken GnRH-I (cGnRH-I). Exposure to short photoperiods results in renewed cGnRH-I synthesis and increased hypothalamic stores. Birds are then photosensitive and subsequent exposure to an increase in photoperiod results in increased cGnRH-I secretion and gonadal maturation. However, it is unclear whether the reverse is true at the time of gonadal regression during long photoperiods (i.e. that a decrease in GnRH-I synthesis precedes regression). Hypothalamic stores of cGnRH-I, and possibly therefore of releasable GnRH-I, decrease after regression. Single injections of the glutamate agonist N-methyl-DL-aspartate (NMA) were used as a probe to assess releasable stores of cGnRH-I in male starlings at four physiologically different reproductive stages. Treatment induced the greatest increase in luteinising hormone (LH) in photosensitive birds in January, and a slight increase in sexually mature birds in April. There was a slight but significant increase in June, immediately after testicular regression, but no increase in fully photorefractory birds in September. These data confirm that photorefractoriness is associated with a lack of releasable cGnRH-I, but that decreased synthesis of cGnRH-I is not the proximate cause of regression. There was an increase in prolactin in response to NMA at all times. The magnitude of the response was proportional to pre-treatment concentrations, with the greatest response in June. It is suggested that high circulating prolactin may fine-tune the timing of gonadal regression in advance of the inhibition of cGnRH-I synthesis.

Colorimetric recognition of 6-benzylaminopurine in environmental samples by using thioglycolic acid functionalized silver nanoparticles

NASA Astrophysics Data System (ADS)

Zheng, Mingda; He, Jiang; Wang, Yingying; Wang, Chenge; Ma, Shuang; Sun, Xiaohan

2018-03-01

A simple and selective colorimetric sensor thioglycolic acid capped silver nanoparticles (TGA-AgNPs) was developed for the detection of 6-benzylaminopurine (6-BAP). The synthesized TGA-AgNPs were characterized by UV-vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopic (TEM) techniques. The TGA-AgNPs as a sensor for binding 6-BAP through hydrogen-bonding and π-π bonding that causes large conjugate clusters, resulting in a color change from yellow to reddish orange. The surface plasmon resonance (SPR) band of TGA-AgNPs at 397 nm is red-shifted to 510 nm, which confirms that 6-BAP induces the aggregation of TGA-AgNPs. Under the optimized conditions, a linear relationship between the absorption ratio (A510 nm/A397 nm) and 6-BAP concentration was found in the range of 4-26 μM. The detection limit of 6-BAP was 0.2 μM, which is lower than the other analytical techniques. Moreover, the proposed sensor was successfully applied for the detection of 6-BAP in environmental samples with good recoveries. The proposed assay provides a simple and cost-effective method for the analysis of 6-BAP in vegetable and water samples.

A Cost-effectiveness Analysis of Surgery, Endothermal Ablation, Ultrasound-guided Foam Sclerotherapy and Compression Stockings for Symptomatic Varicose Veins.

PubMed

Marsden, G; Perry, M; Bradbury, A; Hickey, N; Kelley, K; Trender, H; Wonderling, D; Davies, A H

2015-12-01

The aim was to investigate the cost-effectiveness of interventional treatment for varicose veins (VV) in the UK NHS, and to inform the national clinical guideline on VV, published by the National Institute of Health and Care Excellence. An economic analysis was constructed to compare the cost-effectiveness of surgery, endothermal ablation (ETA), ultrasound-guided foam sclerotherapy (UGFS), and compression stockings (CS). The analysis was based on a Markov decision model, which was developed in consultation with members of the NICE guideline development group (GDG). The model had a 5-year time horizon, and took the perspective of the UK National Health Service. Clinical inputs were based on a network meta-analysis (NMA), informed by a systematic review of the clinical literature. Outcomes were expressed as costs and quality-adjusted life years (QALYs). All interventional treatments were found to be cost-effective compared with CS at a cost-effectiveness threshold of £20,000 per QALY gained. ETA was found to be the most cost-effective strategy overall, with an incremental cost-effectiveness ratio of £3,161 per QALY gained compared with UGFS. Surgery and CS were dominated by ETA. Interventional treatment for VV is cost-effective in the UK NHS. Specifically, based on current data, ETA is the most cost-effective treatment in people for whom it is suitable. The results of this research were used to inform recommendations within the NICE guideline on VV. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Acute myeloid leukemia developing in a granulocyte colony-stimulating factor-mobilized stem cell donor: A case report and review of the literature.

PubMed

Haddad, Housam; Wungjiranirun, Manida; Gergis, Usama

2016-09-01

We describe the first case of a FLT-3 mutated AML in a healthy donor, 3years after recombinant human granulocyte colony stimulating factor (rhG-CSF)-mobilized peripheral blood stem cell (PBSC) harvest. The patient had a myeloablative (MA) matched unrelated donor (MUD) stem cell transplant (SCT) for refractory AML. However, he experienced a secondary graft failure. He had a second non myeloablative (NMA) on day +75 from a second MUD. He achieved a complete neutrophil and platelet engraftment. After 4years of follow up, he is alive in complete remission with full second donor chimerism. Copyright © 2015 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

Synthesis and optical properties of Pr and Ti doped BiFeO{sub 3} ceramics

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

Singh, Vikash, E-mail: vikash.singh@abes.ac.in; Applied Science and Humanities, ABES EC, Ghaziabad; Sharma, Subhash

2016-05-23

Bi{sub 1-x}Pr{sub x}Fe{sub 1-x}Ti{sub x}O{sub 3} ceramics with x = 0.00, 0.10 and 0.20 were synthesized by solid state reaction method. Rietveld fitting of diffraction data reveals structural transition from rhombohedral phase (R{sub 3C}) for x ≤ 0.10 to orthorhombic phase (P{sub nma}) for x = 0.20. FTIR spectra exhibit broad absorption bands, which may be due to the overlapping of Fe-O and Bi-O vibrations in these ceramics. UV-visible spectroscopy results show strong absorption of light in the spectral range of 400-600 nm, indicating optical band gap in the visible region for these samples.

Systematic review, network meta-analysis and economic evaluation of biological therapy for the management of active psoriatic arthritis.

PubMed

Cawson, Matthew Richard; Mitchell, Stephen Andrew; Knight, Chris; Wildey, Henry; Spurden, Dean; Bird, Alex; Orme, Michelle Elaine

2014-01-20

An updated economic evaluation was conducted to compare the cost-effectiveness of the four tumour necrosis factor (TNF)-α inhibitors adalimumab, etanercept, golimumab and infliximab in active, progressive psoriatic arthritis (PsA) where response to standard treatment has been inadequate. A systematic review was conducted to identify relevant, recently published studies and the new trial data were synthesised, via a Bayesian network meta-analysis (NMA), to estimate the relative efficacy of the TNF-α inhibitors in terms of Psoriatic Arthritis Response Criteria (PsARC) response, Health Assessment Questionnaire (HAQ) scores and Psoriasis Area and Severity Index (PASI). A previously developed economic model was updated with the new meta-analysis results and current cost data. The model was adapted to delineate patients by PASI 50%, 75% and 90% response rates to differentiate between psoriasis outcomes. All four licensed TNF-α inhibitors were significantly more effective than placebo in achieving PsARC response in patients with active PsA. Adalimumab, etanercept and infliximab were significantly more effective than placebo in improving HAQ scores in patients who had achieved a PsARC response and in improving HAQ scores in PsARC non-responders. In an analysis using 1,000 model simulations, on average etanercept was the most cost-effective treatment and, at the National Institute for Health and Care Excellence willingness-to-pay threshold of between £20,000 to £30,000, etanercept is the preferred option. The economic analysis agrees with the conclusions from the previous models, in that biologics are shown to be cost-effective for treating patients with active PsA compared with the conventional management strategy. In particular, etanercept is cost-effective compared with the other biologic treatments.

Which method is best for the induction of labour? A systematic review, network meta-analysis and cost-effectiveness analysis.

PubMed

Alfirevic, Zarko; Keeney, Edna; Dowswell, Therese; Welton, Nicky J; Medley, Nancy; Dias, Sofia; Jones, Leanne V; Gyte, Gillian; Caldwell, Deborah M

2016-08-01

More than 150,000 pregnant women in England and Wales have their labour induced each year. Multiple pharmacological, mechanical and complementary methods are available to induce labour. To assess the relative effectiveness, safety and cost-effectiveness of labour induction methods and, data permitting, effects in different clinical subgroups. We carried out a systematic review using Cochrane methods. The Cochrane Pregnancy and Childbirth Group's Trials Register was searched (March 2014). This contains over 22,000 reports of controlled trials (published from 1923 onwards) retrieved from weekly searches of OVID MEDLINE (1966 to current); Cochrane Central Register of Controlled Trials (The Cochrane Library); EMBASE (1982 to current); Cumulative Index to Nursing and Allied Health Literature (1984 to current); ClinicalTrials.gov; the World Health Organization International Clinical Trials Registry Portal; and hand-searching of relevant conference proceedings and journals. We included randomised controlled trials examining interventions to induce labour compared with placebo, no treatment or other interventions in women eligible for third-trimester induction. We included outcomes relating to efficacy, safety and acceptability to women. In addition, for the economic analysis we searched the Database of Abstracts of Reviews of Effects, and Economic Evaluations Databases, NHS Economic Evaluation Database and the Health Technology Assessment database. We carried out a network meta-analysis (NMA) using all of the available evidence, both direct and indirect, to produce estimates of the relative effects of each treatment compared with others in a network. We developed a de novo decision tree model to estimate the cost-effectiveness of various methods. The costs included were the intervention and other hospital costs incurred (price year 2012-13). We reviewed the literature to identify preference-based utilities for the health-related outcomes in the model. We calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit. We represent uncertainty in the optimal intervention using cost-effectiveness acceptability curves. We identified 1190 studies; 611 were eligible for inclusion. The interventions most likely to achieve vaginal delivery (VD) within 24 hours were intravenous oxytocin with amniotomy [posterior rank 2; 95% credible intervals (CrIs) 1 to 9] and higher-dose (≥ 50 µg) vaginal misoprostol (rank 3; 95% CrI 1 to 6). Compared with placebo, several treatments reduced the odds of caesarean section, but we observed considerable uncertainty in treatment rankings. For uterine hyperstimulation, double-balloon catheter had the highest probability of being among the best three treatments, whereas vaginal misoprostol (≥ 50 µg) was most likely to increase the odds of excessive uterine activity. For other safety outcomes there were insufficient data or there was too much uncertainty to identify which treatments performed 'best'. Few studies collected information on women's views. Owing to incomplete reporting of the VD within 24 hours outcome, the cost-effectiveness analysis could compare only 20 interventions. The analysis suggested that most interventions have similar utility and differ mainly in cost. With a caveat of considerable uncertainty, titrated (low-dose) misoprostol solution and buccal/sublingual misoprostol had the highest likelihood of being cost-effective. There was considerable uncertainty in findings and there were insufficient data for some planned subgroup analyses. Overall, misoprostol and oxytocin with amniotomy (for women with favourable cervix) is more successful than other agents in achieving VD within 24 hours. The ranking according to safety of different methods was less clear. The cost-effectiveness analysis suggested that titrated (low-dose) oral misoprostol solution resulted in the highest utility, whereas buccal/sublingual misoprostol had the lowest cost. There was a high degree of uncertainty as to the most cost-effective intervention. Future trials should be powered to detect a method that is more cost-effective than misoprostol solution and report outcomes included in this NMA. This study is registered as PROSPERO CRD42013005116. The National Institute for Health Research Health Technology Assessment programme.

Dressings and topical agents for treating pressure ulcers.

PubMed

Westby, Maggie J; Dumville, Jo C; Soares, Marta O; Stubbs, Nikki; Norman, Gill

2017-06-22

Pressure ulcers, also known as bedsores, decubitus ulcers and pressure injuries, are localised areas of injury to the skin or the underlying tissue, or both. Dressings are widely used to treat pressure ulcers and promote healing, and there are many options to choose from including alginate, hydrocolloid and protease-modulating dressings. Topical agents have also been used as alternatives to dressings in order to promote healing.A clear and current overview of all the evidence is required to facilitate decision-making regarding the use of dressings or topical agents for the treatment of pressure ulcers. Such a review would ideally help people with pressure ulcers and health professionals assess the best treatment options. This review is a network meta-analysis (NMA) which assesses the probability of complete ulcer healing associated with alternative dressings and topical agents. To assess the effects of dressings and topical agents for healing pressure ulcers in any care setting. We aimed to examine this evidence base as a whole, determining probabilities that each treatment is the best, with full assessment of uncertainty and evidence quality. In July 2016 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses, guidelines and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. Published or unpublished randomised controlled trials (RCTs) comparing the effects of at least one of the following interventions with any other intervention in the treatment of pressure ulcers (Stage 2 or above): any dressing, or any topical agent applied directly to an open pressure ulcer and left in situ. We excluded from this review dressings attached to external devices such as negative pressure wound therapies, skin grafts, growth factor treatments, platelet gels and larval therapy. Two review authors independently performed study selection, risk of bias assessment and data extraction. We conducted network meta-analysis using frequentist mega-regression methods for the efficacy outcome, probability of complete healing. We modelled the relative effectiveness of any two treatments as a function of each treatment relative to the reference treatment (saline gauze). We assumed that treatment effects were similar within dressings classes (e.g. hydrocolloid, foam). We present estimates of effect with their 95% confidence intervals for individual treatments compared with every other, and we report ranking probabilities for each intervention (probability of being the best, second best, etc treatment). We assessed the certainty (quality) of the body of evidence using GRADE for each network comparison and for the network as whole. We included 51 studies (2947 participants) in this review and carried out NMA in a network of linked interventions for the sole outcome of probability of complete healing. The network included 21 different interventions (13 dressings, 6 topical agents and 2 supplementary linking interventions) and was informed by 39 studies in 2127 participants, of whom 783 had completely healed wounds.We judged the network to be sparse: overall, there were relatively few participants, with few events, both for the number of interventions and the number of mixed treatment contrasts; most studies were small or very small. The consequence of this sparseness is high imprecision in the evidence, and this, coupled with the (mainly) high risk of bias in the studies informing the network, means that we judged the vast majority of the evidence to be of low or very low certainty. We have no confidence in the findings regarding the rank order of interventions in this review (very low-certainty evidence), but we report here a summary of results for some comparisons of interventions compared with saline gauze. We present here only the findings from evidence which we did not consider to be very low certainty, but these reported results should still be interpreted in the context of the very low certainty of the network as a whole.It is not clear whether regimens involving protease-modulating dressings increase the probability of pressure ulcer healing compared with saline gauze (risk ratio (RR) 1.65, 95% confidence interval (CI) 0.92 to 2.94) (moderate-certainty evidence: low risk of bias, downgraded for imprecision). This risk ratio of 1.65 corresponds to an absolute difference of 102 more people healed with protease modulating dressings per 1000 people treated than with saline gauze alone (95% CI 13 fewer to 302 more). It is unclear whether the following interventions increase the probability of healing compared with saline gauze (low-certainty evidence): collagenase ointment (RR 2.12, 95% CI 1.06 to 4.22); foam dressings (RR 1.52, 95% CI 1.03 to 2.26); basic wound contact dressings (RR 1.30, 95% CI 0.65 to 2.58) and polyvinylpyrrolidone plus zinc oxide (RR 1.31, 95% CI 0.37 to 4.62); the latter two interventions both had confidence intervals consistent with both a clinically important benefit and a clinically important harm, and the former two interventions each had high risk of bias as well as imprecision. A network meta-analysis (NMA) of data from 39 studies (evaluating 21 dressings and topical agents for pressure ulcers) is sparse and the evidence is of low or very low certainty (due mainly to risk of bias and imprecision). Consequently we are unable to determine which dressings or topical agents are the most likely to heal pressure ulcers, and it is generally unclear whether the treatments examined are more effective than saline gauze.More research is needed to determine whether particular dressings or topical agents improve the probability of healing of pressure ulcers. The NMA is uninformative regarding which interventions might best be included in a large trial, and it may be that research is directed towards prevention, leaving clinicians to decide which treatment to use on the basis of wound symptoms, clinical experience, patient preference and cost.

A white dean and black physicians at the epicenter of the civil rights movement.

PubMed

deShazo, Richard D; Smith, Robert; Skipworth, Leigh Baldwin

2014-06-01

Robert Q. Marston, MD, a gregarious Rhodes and Markel Scholar, native Virginian, and well-connected National Institutes of Health-trained medical scientist found himself the new dean and hospital director of a promising academic medical center at age 38. It was 1961 and the University of Mississippi Medical Center (UMMC) in Jackson was, unknown to him, about to be at the geographic center of the struggle for African American civil rights. That struggle would entangle UMMC in a national search for social justice and change the course of American history and American medicine. Shortly after his arrival, the new dean received and refused a written request from the Secretary of the Mississippi Chapter of the National Medical Association (NMA) to make educational venues at the segregated medical center available to black physicians. The same year, UMMC became the primary medical provider for sick and injured Freedom Riders, sit-in and demonstration participants, and others who breached the racial divide defined by the state's feared Sovereignty Commission. That divide was violently enforced by collaboration among law enforcement, Citizens' Councils, and the Ku Klux Klan. The crescendo of the civil rights struggle that attended Marston's arrival included a deadly riot following James Meredith's integration of the Ole Miss campus in Oxford in 1962, the death of National Association for the Advancement of Colored People (NAACP) Field Secretary Medgar Evers at UMMC in 1963, a national controversy over UMMC's role in the autopsies of 3 civil rights workers murdered in Neshoba County, an attempt at limited compliance to Title VI of the Civil Rights Act of 1964, and a federal civil rights complaint against UMMC by the NAACP Legal and Educational Fund in 1965. That complaint noted that UMMC was out of compliance with the Civil Rights Act of 1964 and seriously threatened its federal funding and academic operations. Marston developed a compliance strategy that included the hiring of the first black faculty member, a request for an immediate federal civil rights inspection, and secretive overnight integration of the hospitals and clinics. A key to his strategy was engagement of support from the black community, with whom he had previously developed no relationship. Marston asked NAACP Field Director Charles Evers for support, and met with 5 black Mississippi physicians. Among the 5 was Robert Smith, MD, a founding member of the Medical Committee for Human Rights, the NMA officer whose request for NMA membership-access to the medical center was ignored. He was unaware of their local and national civil rights roles and active dialogue with the federal government on implementation of Title VI. The desire of the black physicians to see UMMC become an equal opportunity health resource resulted in their quiet assistance that aided UMMC compliance initiatives and played a major role in the successful outcome of the 1965 investigation of the charges of Title VI violations. This success established Marston as a national figure in academic medicine and contributed to his selection for positions as Director of The National Institutes of Health and President of the University of Florida. As commemorations of the 50(th) anniversary of Freedom Summer of 1964 proceed, UMMC has become arguably the most racially integrated academic health center in the United States. Copyright © 2014 Elsevier Inc. All rights reserved.

Principal Component Relaxation Mode Analysis of an All-Atom Molecular Dynamics Simulation of Human Lysozyme

NASA Astrophysics Data System (ADS)

Nagai, Toshiki; Mitsutake, Ayori; Takano, Hiroshi

2013-02-01

A new relaxation mode analysis method, which is referred to as the principal component relaxation mode analysis method, has been proposed to handle a large number of degrees of freedom of protein systems. In this method, principal component analysis is carried out first and then relaxation mode analysis is applied to a small number of principal components with large fluctuations. To reduce the contribution of fast relaxation modes in these principal components efficiently, we have also proposed a relaxation mode analysis method using multiple evolution times. The principal component relaxation mode analysis method using two evolution times has been applied to an all-atom molecular dynamics simulation of human lysozyme in aqueous solution. Slow relaxation modes and corresponding relaxation times have been appropriately estimated, demonstrating that the method is applicable to protein systems.

Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation.

PubMed

Melendez-Torres, G J; Auguste, Peter; Armoiry, Xavier; Maheswaran, Hendramoorthy; Court, Rachel; Madan, Jason; Kan, Alan; Lin, Stephanie; Counsell, Carl; Patterson, Jacoby; Rodrigues, Jeremy; Ciccarelli, Olga; Fraser, Hannah; Clarke, Aileen

2017-09-01

At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-β) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-β and GA in relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other. Searches were undertaken in January and February 2016 in databases including The Cochrane Library, MEDLINE and the Science Citation Index. We limited some database searches to specific start dates based on previous, relevant systematic reviews. Two reviewers screened titles and abstracts with recourse to a third when needed. The Cochrane tool and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and Philips checklists were used for appraisal. Narrative synthesis and, when possible, random-effects meta-analysis and network meta-analysis (NMA) were performed. Cost-effectiveness analysis used published literature, findings from the Department of Health's risk-sharing scheme (RSS) and expert opinion. A de novo economic model was built for CIS. The base case used updated RSS data, a NHS and Personal Social Services perspective, a 50-year time horizon, 2014/15 prices and a discount rate of 3.5%. Outcomes are reported as incremental cost-effectiveness ratios (ICERs). We undertook probabilistic sensitivity analysis. In total, 6420 publications were identified, of which 63 relating to 35 randomised controlled trials (RCTs) were included. In total, 86% had a high risk of bias. There was very little difference between drugs in reducing moderate or severe relapse rates in RRMS. All were beneficial compared with BSC, giving a pooled rate ratio of 0.65 [95% confidence interval (CI) 0.56 to 0.76] for ARR and a hazard ratio of 0.70 (95% CI, 0.55 to 0.87) for time to disability progression confirmed at 3 months. NMA suggested that 20 mg of GA given subcutaneously had the highest probability of being the best at reducing ARR. Three separate cost-effectiveness searches identified > 2500 publications, with 26 included studies informing the narrative synthesis and model inputs. In the base case using a modified RSS the mean incremental cost was £31,900 for pooled DMTs compared with BSC and the mean incremental quality-adjusted life-years (QALYs) were 0.943, giving an ICER of £33,800 per QALY gained for people with RRMS. In probabilistic sensitivity analysis the ICER was £34,000 per QALY gained. In sensitivity analysis, using the assessment group inputs gave an ICER of £12,800 per QALY gained for pooled DMTs compared with BSC. Pegylated IFN-β-1 (125 µg) was the most cost-effective option of the individual DMTs compared with BSC (ICER £7000 per QALY gained); GA (20 mg) was the most cost-effective treatment for CIS (ICER £16,500 per QALY gained). Although we built a de novo model for CIS that incorporated evidence from our systematic review of clinical effectiveness, our findings relied on a population diagnosed with CIS before implementation of the revised 2010 McDonald criteria. DMTs were clinically effective for RRMS and CIS but cost-effective only for CIS. Both RCT evidence and RSS data are at high risk of bias. Research priorities include comparative studies with longer follow-up and systematic review and meta-synthesis of qualitative studies. This study is registered as PROSPERO CRD42016043278. The National Institute for Health Research Health Technology Assessment programme.

Population-Level Persistence of Immunity 2 Years After the PsA-TT Mass-Vaccination Campaign in Mali.

PubMed

Basta, Nicole E; Borrow, Ray; Berthe, Abdoulaye; Dembélé, Awa Traoré Eps; Onwuchekwa, Uma; Townsend, Kelly; Boukary, Rahamatou M; Mabey, Lesley; Findlow, Helen; Bai, Xilian; Sow, Samba O

2015-11-15

In 2010, Africa's first preventive meningococcal mass vaccination campaign was launched using a newly developed Neisseria meningitidis group A (NmA) polysaccharide-tetanus toxoid conjugate vaccine, PsA-TT (MenAfriVac), designed specifically for the meningitis belt. Given PsA-TT's recent introduction, the duration of protection against meningococcal group A is unknown. We conducted a household-based, age-stratified seroprevalence survey in Bamako, Mali, in 2012, 2 years after the vaccination campaign targeted all 1- to 29-year-olds. Randomly selected participants who had been eligible for PsA-TT provided a blood sample and responded to a questionnaire. Sera were analyzed to assess NmA-specific serum bactericidal antibody titers using rabbit complement (rSBA) and NmA-specific immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. The proportion of participants putatively protected and the age group- and sex-specific rSBA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) were determined. Two years postvaccination, nearly all of the 800 participants (99.0%; 95% confidence interval [CI], 98.3%-99.7%) maintained NmA-specific rSBA titers ≥8, the accepted threshold for protection; 98.6% (95% CI, 97.8%-99.4%) had titers ≥128, and 89.5% (95% CI, 87.4%-91.6%) had titers ≥1024. The rSBA GMTs were significantly higher in females than in males aged <18 years at vaccination (P < .0001). NmA-specific IgG levels ≥2 µg/mL were found in 88.5% (95% CI, 86.3%-90.7%) of participants. Two years after PsA-TT introduction, a very high proportion of the population targeted for vaccination maintains high antibody titers against NmA. Assessing the duration of protection provided by PsA-TT is a priority for implementing evidence-based vaccination strategies. Representative, population-based seroprevalence studies complement clinical trials and provide this key evidence. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Cabazitaxel for Hormone-Relapsed Metastatic Prostate Cancer Previously Treated With a Docetaxel-Containing Regimen: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

PubMed

Kearns, Benjamin; Pandor, Abdullah; Stevenson, Matt; Hamilton, Jean; Chambers, Duncan; Clowes, Mark; Graham, John; Kumar, M Satish

2017-04-01

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures cabazitaxel (Jevtana ® , Sanofi, UK) to submit evidence for the clinical and cost effectiveness of cabazitaxel for treatment of patients with metastatic hormone-relapsed prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the company's submission to NICE. Clinical evidence for cabazitaxel was derived from a multinational randomised open-label phase III trial (TROPIC) of cabazitaxel plus prednisone or prednisolone compared with mitoxantrone plus prednisone or prednisolone, which was assumed to represent best supportive care. The NICE final scope identified a further three comparators: abiraterone in combination with prednisone or prednisolone; enzalutamide; and radium-223 dichloride for the subgroup of people with bone metastasis only (no visceral metastasis). The company did not consider radium-223 dichloride to be a relevant comparator. Neither abiraterone nor enzalutamide has been directly compared in a trial with cabazitaxel. Instead, clinical evidence was synthesised within a network meta-analysis (NMA). Results from TROPIC showed that cabazitaxel was associated with a statistically significant improvement in both overall survival and progression-free survival compared with mitoxantrone. Results from a random-effects NMA, as conducted by the company and updated by the ERG, indicated that there was no statistically significant difference between the three active treatments for both overall survival and progression-free survival. Utility data were not collected as part of the TROPIC trial, and were instead taken from the company's UK early access programme. Evidence on resource use came from the TROPIC trial, supplemented by both expert clinical opinion and a UK clinical audit. List prices were used for mitoxantrone, abiraterone and enzalutamide as directed by NICE, although commercial in-confidence patient-access schemes (PASs) are in place for abiraterone and enzalutamide. The confidential PAS was used for cabazitaxel. Sequential use of the advanced hormonal therapies (abiraterone and enzalutamide) does not usually occur in clinical practice in the UK. Hence, cabazitaxel could be used within two pathways of care: either when an advanced hormonal therapy was used pre-docetaxel, or when one was used post-docetaxel. The company believed that the former pathway was more likely to represent standard National Health Service (NHS) practice, and so their main comparison was between cabazitaxel and mitoxantrone, with effectiveness data from the TROPIC trial. Results of the company's updated cost-effectiveness analysis estimated a probabilistic incremental cost-effectiveness ratio (ICER) of £45,982 per quality-adjusted life-year (QALY) gained, which the committee considered to be the most plausible value for this comparison. Cabazitaxel was estimated to be both cheaper and more effective than abiraterone. Cabazitaxel was estimated to be cheaper but less effective than enzalutamide, resulting in an ICER of £212,038 per QALY gained for enzalutamide compared with cabazitaxel. The ERG noted that radium-223 is a valid comparator (for the indicated sub-group), and that it may be used in either of the two care pathways. Hence, its exclusion leads to uncertainty in the cost-effectiveness results. In addition, the company assumed that there would be no drug wastage when cabazitaxel was used, with cost-effectiveness results being sensitive to this assumption: modelling drug wastage increased the ICER comparing cabazitaxel with mitoxantrone to over £55,000 per QALY gained. The ERG updated the company's NMA and used a random effects model to perform a fully incremental analysis between cabazitaxel, abiraterone, enzalutamide and best supportive care using PASs for abiraterone and enzalutamide. Results showed that both cabazitaxel and abiraterone were extendedly dominated by the combination of best supportive care and enzalutamide. Preliminary guidance from the committee, which included wastage of cabazitaxel, did not recommend its use. In response, the company provided both a further discount to the confidential PAS for cabazitaxel and confirmation from NHS England that it is appropriate to supply and purchase cabazitaxel in pre-prepared intravenous-infusion bags, which would remove the cost of drug wastage. As a result, the committee recommended use of cabazitaxel as a treatment option in people with an Eastern Cooperative Oncology Group performance status of 0 or 1 whose disease had progressed during or after treatment with at least 225 mg/m 2 of docetaxel, as long as it was provided at the discount agreed in the PAS and purchased in either pre-prepared intravenous-infusion bags or in vials at a reduced price to reflect the average per-patient drug wastage.

Relaxation mode analysis and Markov state relaxation mode analysis for chignolin in aqueous solution near a transition temperature

NASA Astrophysics Data System (ADS)

Mitsutake, Ayori; Takano, Hiroshi

2015-09-01

It is important to extract reaction coordinates or order parameters from protein simulations in order to investigate the local minimum-energy states and the transitions between them. The most popular method to obtain such data is principal component analysis, which extracts modes of large conformational fluctuations around an average structure. We recently applied relaxation mode analysis for protein systems, which approximately estimates the slow relaxation modes and times from a simulation and enables investigations of the dynamic properties underlying the structural fluctuations of proteins. In this study, we apply this relaxation mode analysis to extract reaction coordinates for a system in which there are large conformational changes such as those commonly observed in protein folding/unfolding. We performed a 750-ns simulation of chignolin protein near its folding transition temperature and observed many transitions between the most stable, misfolded, intermediate, and unfolded states. We then applied principal component analysis and relaxation mode analysis to the system. In the relaxation mode analysis, we could automatically extract good reaction coordinates. The free-energy surfaces provide a clearer understanding of the transitions not only between local minimum-energy states but also between the folded and unfolded states, even though the simulation involved large conformational changes. Moreover, we propose a new analysis method called Markov state relaxation mode analysis. We applied the new method to states with slow relaxation, which are defined by the free-energy surface obtained in the relaxation mode analysis. Finally, the relaxation times of the states obtained with a simple Markov state model and the proposed Markov state relaxation mode analysis are compared and discussed.

Experimental Analysis of Dampened Breathing Mode Oscillation on Hall Thruster Performance

DTIC Science & Technology

2013-03-01

38 4.5 Analysis of Discharge RMS Effect on Breathing Mode Amplitude...20 xii EXPERIMENTAL ANALYSIS OF DAMPENED BREATHING MODE OSCILLATION ON HALL EFFECT THRUSTER...the large error in the data presented above prevents many conclusions from being drawn. 4.5 Analysis of Discharge RMS Effect on Breathing Mode

Update in Cardiovascular Safety of Glucagon Like Peptide-1 Receptor Agonists In Patients With Type 2 Diabetes. A Mixed Treatment Comparison Meta-Analysis of Randomised Controlled Trials.

PubMed

Al Yami, Majed S; Alfayez, Osamah M; Alsheikh, Razan

2018-03-29

The aim of this mixed treatment comparison (MTC) meta-analysis was to determine glucagon like peptide-1 (GLP-1) receptor agonists' effects on cardiovascular (CV) outcomes in patients with type 2 diabetes (T2DM). A comprehensive, systematic review was conducted using EMBASE and Medline databases. All included trials were large CV outcome trials of GLP-1 agonists versus placebo in T2DM. The primary outcomes of this MTC meta-analysis were death from CV causes, non-fatal MI, and non-fatal stroke. Hospitalisation for heart failure (HF) was evaluated as a secondary endpoint. A total of four trials, including 33,457 patients, met eligibility criteria and were retained for the meta-analysis. Our pairwise meta-analysis results showed a 13% reduction in death from cardiovascular causes in patients who received GLP-1 agonists versus placebo (RR 0.87, 95% CI: 0.78-0.96). However, no statistically significant reduction was observed with GLP-1 agonists in terms of reducing non-fatal MI (RR 0.95, 95% CI: 0.86-1.04), non-fatal stroke events (RR 0.89, 95% CI: 0.76-1.03), and rates of HF hospitalisation (RR 0.94, 95% CI: 0.84-1.04). The network meta-analysis (NMA) showed no significant differences among all the interventions. Glucagon like peptide-1 therapy was associated with a significant reduction in cardiovascular (CV) death. However, GLP-1 agonists seem to have a safety profile comparable to placebo in terms of reducing non-fatal myocardial infarction (MI), non-fatal stroke events, and rates of HF hospitalisation. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Systematic review with network meta-analysis: comparative efficacy and tolerability of different intravenous iron formulations for the treatment of iron deficiency anaemia in patients with inflammatory bowel disease.

PubMed

Aksan, A; Işık, H; Radeke, H H; Dignass, A; Stein, J

2017-05-01

Iron deficiency anaemia (IDA) is a common complication of inflammatory bowel disease (IBD) associated with reduced quality of life and increased hospitalisation rates. While the best way of treating IDA in IBD patients is not clearly established, current European guidelines recommend intravenous iron therapy in IBD patients with severe anaemia or intolerance to oral iron compounds. To compare the efficacy and tolerability of different intravenous iron formulations used to treat IDA in IBD patients in a systematic review and Bayesian network meta-analysis (NMA), PROSPERO registration number: 42016046565. In June 2016, we systematically searched for studies analysing efficacy and safety of intravenous iron for IDA therapy in IBD. Primary outcome was therapy response, defined as Hb normalisation or increase ≥2 g/dL. Five randomised, controlled trials (n = 1143 patients) were included in a network meta-analysis. Only ferric carboxymaltose was significantly more effective than oral iron [OR=1.9, 95% CrI: (1.1;3.2)]. Rank probabilities showed ferric carboxymaltose to be most effective, followed by iron sucrose, iron isomaltose and oral iron. Pooled data from the systematic review (n = 1746 patients) revealed adverse event rates of 12.0%, 15.3%, 12.0%, 17.0% for ferric carboxymaltose, iron sucrose, iron dextran and iron isomaltose respectively. One drug-related serious adverse event (SAE) each was reported for ferric carboxymaltose and iron isomaltoside, and one possibly drug-related SAE for iron sucrose. Ferric carboxymaltose was the most effective intravenous iron formulation, followed by iron sucrose. In addition, ferric carboxymaltose tended to be better tolerated. Thus, nanocolloidal IV iron products exhibit differing therapeutic and safety characteristics and are not interchangeable. © 2017 John Wiley & Sons Ltd.

Time-frequency analysis : mathematical analysis of the empirical mode decomposition.

DOT National Transportation Integrated Search

2009-01-01

Invented over 10 years ago, empirical mode : decomposition (EMD) provides a nonlinear : time-frequency analysis with the ability to successfully : analyze nonstationary signals. Mathematical : Analysis of the Empirical Mode Decomposition : is a...

Relaxation mode analysis of a peptide system: comparison with principal component analysis.

PubMed

Mitsutake, Ayori; Iijima, Hiromitsu; Takano, Hiroshi

2011-10-28

This article reports the first attempt to apply the relaxation mode analysis method to a simulation of a biomolecular system. In biomolecular systems, the principal component analysis is a well-known method for analyzing the static properties of fluctuations of structures obtained by a simulation and classifying the structures into some groups. On the other hand, the relaxation mode analysis has been used to analyze the dynamic properties of homopolymer systems. In this article, a long Monte Carlo simulation of Met-enkephalin in gas phase has been performed. The results are analyzed by the principal component analysis and relaxation mode analysis methods. We compare the results of both methods and show the effectiveness of the relaxation mode analysis.

Failure Mode, Effects, and Criticality Analysis (FMECA)

DTIC Science & Technology

1993-04-01

Preliminary Failure Modes, Effects and Criticality Analysis (FMECA) of the Brayton Isotope Power System Ground Demonstration System, Report No. TID 27301...No. TID/SNA - 3015, Aeroject Nuclear Systems Co., Sacramento, California: 1970. 95. Taylor , J.R. A Formalization of Failure Mode Analysis of Control...Roskilde, Denmark: 1973. 96. Taylor , J.R. A Semi-Automatic Method for Oualitative Failure Mode Analysis. Report No. RISO-M-1707. Available from a

Failure mode analysis to predict product reliability.

NASA Technical Reports Server (NTRS)

Zemanick, P. P.

1972-01-01

The failure mode analysis (FMA) is described as a design tool to predict and improve product reliability. The objectives of the failure mode analysis are presented as they influence component design, configuration selection, the product test program, the quality assurance plan, and engineering analysis priorities. The detailed mechanics of performing a failure mode analysis are discussed, including one suggested format. Some practical difficulties of implementation are indicated, drawn from experience with preparing FMAs on the nuclear rocket engine program.

Functional Characterization of Lpt3 and Lpt6, the Inner-Core Lipooligosaccharide Phosphoethanolamine Transferases from Neisseria meningitidis▿

PubMed Central

Wenzel, Cory Q.; St. Michael, Frank; Stupak, Jacek; Li, Jianjun; Cox, Andrew D.; Richards, James C.

2010-01-01

The lipooligosaccharide (LOS) of Neisseria meningitidis contains heptose (Hep) residues that are modified with phosphoethanolamine (PEtn) at the 3 (3-PEtn) and/or 6 (6-PEtn) position. The lpt3 (NMB2010) and lpt6 (NMA0408) genes of N. meningitidis, which are proposed to encode the required HepII 3- and 6-PEtn transferases, respectively, were cloned and overexpressed as C-terminally polyhistidine-tagged fusion proteins in Escherichia coli and found to localize to the inner membrane, based on sucrose density gradient centrifugation. Lpt3-His6 and Lpt6-His6 were purified from Triton X-100-solubilized membranes by nickel chelation chromatography, and dot blot analysis of enzymatic reactions with 3-PEtn- and 6-PEtn-specific monoclonal antibodies demonstrated conclusively that Lpt3 and Lpt6 are phosphatidylethanolamine-dependent LOS HepII 3- and 6-PEtn transferases, respectively, and that both enzymes are capable of transferring PEtn to both fully acylated LOS and de-O-acylated (de-O-Ac) LOS. Further enzymatic studies using capillary electrophoresis-mass spectrometry (MS) demonstrated that both Lpt3 and Lpt6 are capable of transferring PEtn to de-O-Ac LOS molecules already containing PEtn at the 6 and 3 positions of HepII, respectively, demonstrating that there is no obligate order of PEtn addition in the generation of 3,6-di-PEtn LOS moieties in vitro. PMID:19854897

Removal of polycyclic aromatic hydrocarbons in soil spiked with model mixtures of petroleum hydrocarbons and heterocycles using biosurfactants from Rhodococcus ruber IEGM 231.

PubMed

Ivshina, Irina; Kostina, Ludmila; Krivoruchko, Anastasiya; Kuyukina, Maria; Peshkur, Tatyana; Anderson, Peter; Cunningham, Colin

2016-07-15

Removal of polycyclic aromatic hydrocarbons (PAHs) in soil using biosurfactants (BS) produced by Rhodococcus ruber IEGM 231 was studied in soil columns spiked with model mixtures of major petroleum constituents. A crystalline mixture of single PAHs (0.63g/kg), a crystalline mixture of PAHs (0.63g/kg) and polycyclic aromatic sulfur heterocycles (PASHs), and an artificially synthesized non-aqueous phase liquid (NAPL) containing PAHs (3.00g/kg) dissolved in alkanes C10-C19 were used for spiking. Percentage of PAH removal with BS varied from 16 to 69%. Washing activities of BS were 2.5 times greater than those of synthetic surfactant Tween 60 in NAPL-spiked soil and similar to Tween 60 in crystalline-spiked soil. At the same time, amounts of removed PAHs were equal and consisted of 0.3-0.5g/kg dry soil regardless the chemical pattern of a model mixture of petroleum hydrocarbons and heterocycles used for spiking. UV spectra for soil before and after BS treatment were obtained and their applicability for differentiated analysis of PAH and PASH concentration changes in remediated soil was shown. The ratios A254nm/A288nm revealed that BS increased biotreatability of PAH-contaminated soils. Copyright © 2016 Elsevier B.V. All rights reserved.

Remote and chronic access to the third cerebral ventricle of the unrestrained prepubertal rhesus monkey.

PubMed

Gay, V L; Mikuma, N; Plant, T M

1993-03-01

One channel of a commercially available standard-size three-channel fluid swivel was modified to permit continuous access to the brain of unrestrained prepubertal rhesus monkeys via a continuous length of small-bore Teflon tube originating from a swivel device on top of the animal's cage and terminating in the third cerebral ventricle. This system was employed to achieve continuous access to the third cerebroventricle in four monkeys for periods of up to 12 mo. The value of the system for studies of the neurochemical control of hypothalamic-releasing factor secretion was established by monitoring adenohypophysial responses to neurotransmitter receptor agonists infused into the third ventricle. Specifically, repetitive infusions of morphine (30 micrograms/infusion) elicited a robust train of prolactin discharges, and third ventricular administration of N-methyl-DL-aspartic acid (NMA; 20 micrograms) resulted in striking discharges of LH.

Structures and interactions in N-methylacetamide-water mixtures studied by IR spectra and density functional theory

NASA Astrophysics Data System (ADS)

Zhang, Rong; Li, Haoran; Lei, Yi; Han, Shijun

2004-05-01

IR spectra have been performed to study the structures and interactions in N-methylacetamide and water mixtures. Because of the competitions of acceptor and donor of the strong hydrogen bonds, some interesting phenomena of red shifts and blue shifts are observed in νCO and νN-H. It is due to the blue-shifting C-H⋯O hydrogen bond, the νC-H blue shifts more obviously. Then some representative cluster structures are suggested and further investigated by density functional theory method. The changes in bond length and frequency shift of the structures give good reasons for the red shift and blue shift, which represents excellent agreement with the IR experiment. The investigations of IR spectra and DFT calculations reveal that the weak C-H⋯O interactions play different roles compared with the classical strong hydrogen bonds in the NMA-water mixtures.

Ultrasonic and spectral studies on charge transfer complexes of anisole and certain aromatic amines

NASA Astrophysics Data System (ADS)

Rajesh, R.; Raj Muhamed, R.; Justin Adaikala Baskar, A.; Kannappan, V.

2016-10-01

Stability constants of two complexes of anisole with aniline and N-methylaniline (NMA) are determined from the measured ultrasonic velocity in n-hexane medium at four different temperatures. Acoustic and excess thermo acoustic parameters [excess ultrasonic velocity (uE), excess molar volume (VE), excess internal pressure (πiE)] are reported for these systems at four different temperatures. The trend in acoustic and excess parameters with concentration in the two systems establishes the formation of hydrogen bonded complexes between anisole and the two amines. Thermodynamic properties are computed for the two complexes from the variation in K with temperature. The formation of these complexes is also established by UV spectral method and their spectral characteristics and stability constants are determined. K values of these complexes obtained by ultrasonic and UV spectroscopic techniques agree well. Aniline forms more stable complex than N-methylaniline with anisole in n-hexane medium.

Failure-Modes-And-Effects Analysis Of Software Logic

NASA Technical Reports Server (NTRS)

Garcia, Danny; Hartline, Thomas; Minor, Terry; Statum, David; Vice, David

1996-01-01

Rigorous analysis applied early in design effort. Method of identifying potential inadequacies and modes and effects of failures caused by inadequacies (failure-modes-and-effects analysis or "FMEA" for short) devised for application to software logic.

Failure Mode and Effects Analysis (FMEA) Introductory Overview

DTIC Science & Technology

2012-06-14

Failure Mode and Effects Analysis ( FMEA ) Introductory Overview TARDEC Systems Engineering Risk Management Team POC: Kadry Rizk or Gregor Ratajczak...2. REPORT TYPE Briefing Charts 3. DATES COVERED 01-05-2012 to 23-05-2012 4. TITLE AND SUBTITLE Failure Mode and Effects Analysis ( FMEA ) 5a...18 WELCOME Welcome to “An introductory overview of Failure Mode and Effects Analysis ( FMEA )”, A brief concerning the use and benefits of FMEA

Restricted Modal Analysis Applied to Internal Annular Combustor Autospectra and Cross-Spectra Measurements

NASA Technical Reports Server (NTRS)

Miles, Jeffrey Hilton

2007-01-01

A treatment of the modal decomposition of the pressure field in a combustor as determined by two pressure time history measurements is developed herein. It is applied to a Pratt and Whitney PW4098 engine combustor over a range of operating conditions. For modes other than the plane wave the assumption is made that there are distinct frequency bands in which the individual modes, including the plane wave mode, overlap such that if circumferential mode m and circumferential mode m-1 are present then circumferential mode m-2 is not. In the analysis used herein at frequencies above the first cutoff mode frequency, only pairs of circumferential modes are individually present at each frequency. Consequently, this is a restricted modal analysis. As part of the analysis one specifies mode cut-on frequencies. This creates a set of frequencies that each mode spans. One finding was the successful use of the same modal span frequencies over a range of operating conditions for this particular engine. This suggests that for this case the cut-on frequencies are in proximity at each operating condition. Consequently, the combustion noise spectrum related to the circumferential modes might not change much with operating condition.

Electrostatic waves driven by electron beam in lunar wake plasma

NASA Astrophysics Data System (ADS)

Sreeraj, T.; Singh, S. V.; Lakhina, G. S.

2018-05-01

A linear analysis of electrostatic waves propagating parallel to the ambient field in a four component homogeneous, collisionless, magnetised plasma comprising fluid protons, fluid He++, electron beam, and suprathermal electrons following kappa distribution is presented. In the absence of electron beam streaming, numerical analysis of the dispersion relation shows six modes: two electron acoustic modes (modes 1 and 6), two fast ion acoustic modes (modes 2 and 5), and two slow ion acoustic modes (modes 3 and 4). The modes 1, 2 and 3 and modes 4, 5, and 6 have positive and negative phase speeds, respectively. With an increase in electron beam speed, the mode 6 gets affected the most and the phase speed turns positive from negative. The mode 6 thus starts to merge with modes 2 and 3 and generates the electron beam driven fast and slow ion acoustic waves unstable with a finite growth. The electron beam driven slow ion-acoustic waves occur at lower wavenumbers, whereas fast ion-acoustic waves occur at a large value of wavenumbers. The effect of various other parameters has also been studied. We have applied this analysis to the electrostatic waves observed in lunar wake during the first flyby of the ARTEMIS mission. The analysis shows that the low (high) frequency waves observed in the lunar wake could be the electron beam driven slow (fast) ion-acoustic modes.

Transient analysis mode participation for modal survey target mode selection using MSC/NASTRAN DMAP

NASA Technical Reports Server (NTRS)

Barnett, Alan R.; Ibrahim, Omar M.; Sullivan, Timothy L.; Goodnight, Thomas W.

1994-01-01

Many methods have been developed to aid analysts in identifying component modes which contribute significantly to component responses. These modes, typically targeted for dynamic model correlation via a modal survey, are known as target modes. Most methods used to identify target modes are based on component global dynamic behavior. It is sometimes unclear if these methods identify all modes contributing to responses important to the analyst. These responses are usually those in areas of hardware design concerns. One method used to check the completeness of target mode sets and identify modes contributing significantly to important component responses is mode participation. With this method, the participation of component modes in dynamic responses is quantified. Those modes which have high participation are likely modal survey target modes. Mode participation is most beneficial when it is used with responses from analyses simulating actual flight events. For spacecraft, these responses are generated via a structural dynamic coupled loads analysis. Using MSC/NASTRAN DMAP, a method has been developed for calculating mode participation based on transient coupled loads analysis results. The algorithm has been implemented to be compatible with an existing coupled loads methodology and has been used successfully to develop a set of modal survey target modes.

A scoping review of indirect comparison methods and applications using individual patient data.

PubMed

Veroniki, Areti Angeliki; Straus, Sharon E; Soobiah, Charlene; Elliott, Meghan J; Tricco, Andrea C

2016-04-27

Several indirect comparison methods, including network meta-analyses (NMAs), using individual patient data (IPD) have been developed to synthesize evidence from a network of trials. Although IPD indirect comparisons are published with increasing frequency in health care literature, there is no guidance on selecting the appropriate methodology and on reporting the methods and results. In this paper we examine the methods and reporting of indirect comparison methods using IPD. We searched MEDLINE, Embase, the Cochrane Library, and CINAHL from inception until October 2014. We included published and unpublished studies reporting a method, application, or review of indirect comparisons using IPD and at least three interventions. We identified 37 papers, including a total of 33 empirical networks. Of these, only 9 (27 %) IPD-NMAs reported the existence of a study protocol, whereas 3 (9 %) studies mentioned that protocols existed without providing a reference. The 33 empirical networks included 24 (73 %) IPD-NMAs and 9 (27 %) matching adjusted indirect comparisons (MAICs). Of the 21 (64 %) networks with at least one closed loop, 19 (90 %) were IPD-NMAs, 13 (68 %) of which evaluated the prerequisite consistency assumption, and only 5 (38 %) of the 13 IPD-NMAs used statistical approaches. The median number of trials included per network was 10 (IQR 4-19) (IPD-NMA: 15 [IQR 8-20]; MAIC: 2 [IQR 3-5]), and the median number of IPD trials included in a network was 3 (IQR 1-9) (IPD-NMA: 6 [IQR 2-11]; MAIC: 2 [IQR 1-2]). Half of the networks (17; 52 %) applied Bayesian hierarchical models (14 one-stage, 1 two-stage, 1 used IPD as an informative prior, 1 unclear-stage), including either IPD alone or with aggregated data (AD). Models for dichotomous and continuous outcomes were available (IPD alone or combined with AD), as were models for time-to-event data (IPD combined with AD). One in three indirect comparison methods modeling IPD adjusted results from different trials to estimate effects as if they had come from the same, randomized, population. Key methodological and reporting elements (e.g., evaluation of consistency, existence of study protocol) were often missing from an indirect comparison paper.

Characterization of Mannheimia haemolytica isolated from feedlot cattle that were healthy or treated for bovine respiratory disease

PubMed Central

Klima, Cassidy L.; Alexander, Trevor W.; Hendrick, Steve; McAllister, Tim A.

2014-01-01

Mannheimia haemolytica is the principal bacterial pathogen associated with bovine respiratory disease (BRD). As an opportunistic pathogen, M. haemolytica is also frequently isolated from the respiratory tract of healthy cattle. This study examined the characteristics of M. haemolytica collected using deep nasal swabs from healthy cattle (n = 49) and cattle diagnosed with BRD (n = 41). Isolates were analyzed by pulsed-field gel electrophoresis (PFGE), serotyped, and tested for antimicrobial susceptibility. Polymerase chain reaction (PCR) was used to screen isolates for virulence [leukotoxin C (lktC), putative adhesin (ahs), outer-membrane lipoprotein (gs60), O-sialoglycoprotease (gcp), transferring-binding protein B (tbpB) and UDP-N-acetyl-D-glucosamine-2-epimerase (nmaA)] and antimicrobial resistance [tet(H), blaROB-1, erm(X), erm(42), msr(E)-mph(E) and aphA-1] genes. Isolates were genetically diverse but in three instances, M. haemolytica with the same pulsotype, resistance phenotype, and genotype were collected from cattle with BRD. This occurred once between cattle located in two different feedlots, once between cattle in the same feedlot, but in different pens, and once among cattle from the same feedlot in the same pen. Isolates from healthy cattle were primarily serotype 2 (75.5%) while those from individuals with BRD were serotype 1 (70.7%) or 6 (19.5%). Resistance to at least one antibiotic occurred more frequently (P < 0.001) in M. haemolytica collected from cattle with BRD (37%) compared with those that were healthy (2%). Overall, tetracycline resistance (18%) was the most prevalent resistant phenotype. All tetracycline-resistant M. haemolytica encoded tet(H). Ampicillin resistance (6%) and neomycin resistance (15%) were detected and corresponded to the presence of the blaROB-1 and aphA-1 genes, respectively. Tilmicosin resistance (6%) was also detected, but the resistance genes responsible were not identified. The virulence genes lktC, ahs, gs60, and gcp were present in all isolates examined, while tbpB and nmaA were only detected in serotype 1 and serotype 6 isolates indicating they may be potential targets for serotype-specific identification or vaccine development. These results provide the first reported evidence of transmission and spread of antimicrobial-resistant M. haemolytica that have contributed to bovine respiratory disease in western Canadian feedlots. PMID:24396179

Effect of graft source on unrelated donor hemopoietic stem cell transplantation in adults with acute myeloid leukemia after reduced-intensity or nonmyeloablative conditioning: a study from the Société Francaise de Greffe de Moelle et de Thérapie Cellulaire.

PubMed

Malard, Florent; Milpied, Noel; Blaise, Didier; Chevallier, Patrice; Michallet, Mauricette; Lioure, Bruno; Clément, Laurence; Hicheri, Yosr; Cordonnier, Catherine; Huynh, Anne; Yakoub-Agha, Ibrahim; Peffault de Latour, Regis; Mohty, Mohamad

2015-06-01

This retrospective report compared the 4-year outcomes of allogeneic stem cell transplantation (allo-SCT) in 651 adult patients with acute myeloid leukemia receiving a reduced-intensity (RIC) or nonmyeloablative conditioning (NMA) regimen according to the type of unrelated donors. These were either umbilical cord blood (UCB, n = 205), a 9/10 mismatched unrelated donor (MisMUD, n = 99), or a 10/10 matched unrelated donor (MUD, n = 347) graft. Neutrophil recovery was slower in UCB (74.5% by day 42) compared with MisMUD (94.8%) and MUD (95.6%) (P < .001). There was no significant difference in nonrelapse mortality between UCB and both MUD (hazard ratio [HR], 1.05; 95% confidence interval [CI], .62 to 1.78; P = .85) and MisMUD (HR, 1.58; 95% CI, .88 to 2.83; P = .13) The relapse/progression was similar between UCB and MisMUD (HR, .62; 95% CI, .37 to 1.03; P = .07), but was significantly lower in MUD compared with UCB (HR, .60; 95% CI, .39 to .92; P = .02). The rate of extensive chronic graft-versus-host disease (GVHD) was similar between UCB and both MUD (HR, 2.15; 95% CI, .93 to 4.97; P = .08) and MisMUD (HR, 1.84; 95% CI, .68 to 4.95; P = .23). The rate of severe grade III and IV acute GVHD was significantly increased in MisMUD compared with UCB (HR, 2.61; 95% CI, 1.30 to 5.23; P = .007). There was no significant difference in overall survival between UCB and both MisMUD (HR, .98; 95% CI, .66 to 1.45; P = .92) and MUD (HR, .74; 95% CI, .52 to 1.03; P = .08). These data suggest that in the setting of RIC/NMA, allo-SCT UCB is a valid alternative graft source, with significantly less chronic GVHD, compared with MisMUD, when there is no MUD available or when urgent transplantation is needed. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Further Development of Rotating Rake Mode Measurement Data Analysis

NASA Technical Reports Server (NTRS)

Dahl, Milo D.; Hixon, Ray; Sutliff, Daniel L.

2013-01-01

The Rotating Rake mode measurement system was designed to measure acoustic duct modes generated by a fan stage. After analysis of the measured data, the mode amplitudes and phases were quantified. For low-speed fans within axisymmetric ducts, mode power levels computed from rotating rake measured data would agree with the far-field power levels on a tone by tone basis. However, this agreement required that the sound from the noise sources within the duct propagated outward from the duct exit without reflection at the exit and previous studies suggested conditions could exist where significant reflections could occur. To directly measure the modes propagating in both directions within a duct, a second rake was mounted to the rotating system with an offset in both the axial and the azimuthal directions. The rotating rake data analysis technique was extended to include the data measured by the second rake. The analysis resulted in a set of circumferential mode levels at each of the two rake microphone locations. Radial basis functions were then least-squares fit to this data to obtain the radial mode amplitudes for the modes propagating in both directions within the duct. The fit equations were also modified to allow evanescent mode amplitudes to be computed. This extension of the rotating rake data analysis technique was tested using simulated data, numerical code produced data, and preliminary in-duct measured data.

Analysis of Dual Mode Systems in an Urban Area : Volume 3. Description of the Analysis Techniques and Data Sources.

DOT National Transportation Integrated Search

1973-12-01

Various forms of Dual Mode transportation were analyzed in order to assess the economic viability of the dual mode concept. Specially designed new small Dual Mode vehicles, modifications of existing automobiles, and pallet systems, all operating in c...

Analysis of Dual Mode Systems in an Urban Area : Volume 3. Description of the Analysis Techniques and Data Sources

DOT National Transportation Integrated Search

1973-12-01

Various forms of Dual Mode transportation were analyzed in order to assess the economic viability of the dual mode concept. Specially designed new small Dual Mode vehicles, modifications of existing automobiles, and pallet systems, all operating in c...

Analysis and Prediction of Sea Ice Evolution using Koopman Mode Decomposition Techniques

DTIC Science & Technology

Koopman Mode Analysis was newly applied to southern hemisphere sea ice concentration data. The resulting Koopman modes from analysis of both the...southern and northern hemisphere sea ice concentration data shows geographical regions where sea ice coverage has decreased over multiyear time scales.

Geometrically nonlinear analysis of adhesively bonded joints

NASA Technical Reports Server (NTRS)

Dattaguru, B.; Everett, R. A., Jr.; Whitcomb, J. D.; Johnson, W. S.

1982-01-01

A geometrically nonlinear finite element analysis of cohesive failure in typical joints is presented. Cracked-lap-shear joints were chosen for analysis. Results obtained from linear and nonlinear analysis show that nonlinear effects, due to large rotations, significantly affect the calculated mode 1, crack opening, and mode 2, inplane shear, strain-energy-release rates. The ratio of the mode 1 to mode 2 strain-energy-relase rates (G1/G2) was found to be strongly affected by he adhesive modulus and the adherend thickness. The ratios between 0.2 and 0.8 can be obtained by varying adherend thickness and using either a single or double cracked-lap-shear specimen configuration. Debond growth rate data, together with the analysis, indicate that mode 1 strain-energy-release rate governs debond growth. Results from the present analysis agree well with experimentally measured joint opening displacements.

Independent Orbiter Assessment (IOA): Analysis of the crew equipment subsystem

NASA Technical Reports Server (NTRS)

Sinclair, Susan; Graham, L.; Richard, Bill; Saxon, H.

1987-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical (PCIs) items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The independent analysis results coresponding to the Orbiter crew equipment hardware are documented. The IOA analysis process utilized available crew equipment hardware drawings and schematics for defining hardware assemblies, components, and hardware items. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode. Of the 352 failure modes analyzed, 78 were determined to be PCIs.

Analytical and experimental investigation of a 1/8-scale dynamic model of the shuttle orbiter. Volume 3B: Supporting data

NASA Technical Reports Server (NTRS)

Mason, P. W.; Harris, H. G.; Zalesak, J.; Bernstein, M.

1974-01-01

The NASA Structural Analysis System (NASTRAN) Model 1 finite element idealization, input data, and detailed analytical results are presented. The data presented include: substructuring analysis for normal modes, plots of member data, plots of symmetric free-free modes, plots of antisymmetric free-free modes, analysis of the wing, analysis of the cargo doors, analysis of the payload, and analysis of the orbiter.

A Framework for Creating a Function-based Design Tool for Failure Mode Identification

NASA Technical Reports Server (NTRS)

Arunajadai, Srikesh G.; Stone, Robert B.; Tumer, Irem Y.; Clancy, Daniel (Technical Monitor)

2002-01-01

Knowledge of potential failure modes during design is critical for prevention of failures. Currently industries use procedures such as Failure Modes and Effects Analysis (FMEA), Fault Tree analysis, or Failure Modes, Effects and Criticality analysis (FMECA), as well as knowledge and experience, to determine potential failure modes. When new products are being developed there is often a lack of sufficient knowledge of potential failure mode and/or a lack of sufficient experience to identify all failure modes. This gives rise to a situation in which engineers are unable to extract maximum benefits from the above procedures. This work describes a function-based failure identification methodology, which would act as a storehouse of information and experience, providing useful information about the potential failure modes for the design under consideration, as well as enhancing the usefulness of procedures like FMEA. As an example, the method is applied to fifteen products and the benefits are illustrated.

Asymmetric transmission and reflection spectra of FBG in single-multi-single mode fiber structure.

PubMed

Chai, Quan; Liu, Yanlei; Zhang, Jianzhong; Yang, Jun; Chen, Yujin; Yuan, Libo; Peng, Gang-Ding

2015-05-04

We give a comprehensive theoretical analysis and simulation of a FBG in single-multi-single mode fiber structure (FBG-in-SMS), based on the coupled mode analysis and the mode interference analysis. This enables us to explain the experimental observations, its asymmetric transmission and reflection spectra with the similar temperature responses near the spectral range of Bragg wavelengths. The transmission spectrum shift during FBG written-in process is observed and discussed. The analysis results are useful in the design of the SMS structure based sensors and filters.

Stingray Failure Mode, Effects and Criticality Analysis: WEC Risk Registers

DOE Data Explorer

Ken Rhinefrank

2016-07-25

Analysis method to systematically identify all potential failure modes and their effects on the Stingray WEC system. This analysis is incorporated early in the development cycle such that the mitigation of the identified failure modes can be achieved cost effectively and efficiently. The FMECA can begin once there is enough detail to functions and failure modes of a given system, and its interfaces with other systems. The FMECA occurs coincidently with the design process and is an iterative process which allows for design changes to overcome deficiencies in the analysis.Risk Registers for major subsystems completed according to the methodology described in "Failure Mode Effects and Criticality Analysis Risk Reduction Program Plan.pdf" document below, in compliance with the DOE Risk Management Framework developed by NREL.

An Analysis Technique/Automated Tool for Comparing and Tracking Analysis Modes of Different Finite Element Models

NASA Technical Reports Server (NTRS)

Towner, Robert L.; Band, Jonathan L.

2012-01-01

An analysis technique was developed to compare and track mode shapes for different Finite Element Models. The technique may be applied to a variety of structural dynamics analyses, including model reduction validation (comparing unreduced and reduced models), mode tracking for various parametric analyses (e.g., launch vehicle model dispersion analysis to identify sensitivities to modal gain for Guidance, Navigation, and Control), comparing models of different mesh fidelity (e.g., a coarse model for a preliminary analysis compared to a higher-fidelity model for a detailed analysis) and mode tracking for a structure with properties that change over time (e.g., a launch vehicle from liftoff through end-of-burn, with propellant being expended during the flight). Mode shapes for different models are compared and tracked using several numerical indicators, including traditional Cross-Orthogonality and Modal Assurance Criteria approaches, as well as numerical indicators obtained by comparing modal strain energy and kinetic energy distributions. This analysis technique has been used to reliably identify correlated mode shapes for complex Finite Element Models that would otherwise be difficult to compare using traditional techniques. This improved approach also utilizes an adaptive mode tracking algorithm that allows for automated tracking when working with complex models and/or comparing a large group of models.

OVERVIEW: USING MODE OF ACTION AND LIFE STAGE INFORMATION TO EVALUATE THE HUMAN RELEVANCE OF ANIMAL TOXICITY DATA.

EPA Science Inventory

A manuscript summarizes a workshop aimed at developing a framework to determine the relevancy of animal modes-of-action for extrapolation to humans. A complete mode of action human relevance analysis - as distinct from mode of action (MOA) analysis alone - depends on robust info...

Analysis of Dual Mode Systems in an Urban Area : Volume 4A. Program Documentation of the Transportation Economic Analysis Model.

DOT National Transportation Integrated Search

1973-12-01

Various forms of Dual Mode Transportation were analyzed in order to assess the economic viability of the Dual Mode concept. A Dual Mode vehicle is one which operates under manual control on a streee network for some portionof its trip, and operates u...

Acceleration effects in solid propellant rocket motors

NASA Technical Reports Server (NTRS)

Langhenry, M. T.

1986-01-01

The performance variations due to acceleration loads imposed on spinning solid propellant rocket motors are investigated. The four potentially most significant modes of acceleration-induced phenomena are identified from a study of the literature and modeled. The four modes are a mechanical mode which deals with deformations of the propellant and case: a thermodynamic mode which covers acceleration-induced combustion phenomena; a stress mode which covers the stressed propellant's effect on burn rate; and a gas dynamic mode which deals with changes in gas flow in the chamber and through the nozzle. Simplified models of each mode are developed or taken from the literature and are added to an internal ballistics evaluation computer program. The resulting analysis is the first to include all of the modes. In order to do this an original analysis of the mechanical and stress modes was necessary. However, the analysis shows that the stress mode is not important for the circular perforated grains studied. The other effects are shown to have a significant influence on solid rocket motor performance. The magnitude of the different mode effects are such that one may not be ignored over the others as has been done in the past. The results of the analysis are compared to published rocket motor data. The comparisons indicate an erosive burning effect that is a function of spin rate. A qualitative explanation of the erosive effect is presented.

Multi-mode phase speed measurements with array-based analysis: Application to the North American continent

NASA Astrophysics Data System (ADS)

Matsuzawa, H.; Yoshizawa, K.

2017-12-01

Recent high-density broad-band seismic networks allow us to construct improved 3-D upper mantle models with unprecedented horizontal resolution using surface waves. Such dispersion measurements have been primarily based on the analysis of fundamental mode. Higher-mode information can be of help in enhancing vertical resolution of 3-D models, but their dispersion analysis is intrinsically difficult, since wave-packets of several modes are overlapped each other in an observed seismogram. In this study, we measure phase dispersion of multi-mode surface waves with an array-based analysis. Our method is modeled on a one-dimensional frequency-wavenumber method originally developed by Nolet (1975, GRL), which can be applied to a set of broadband seismic records observed in a linear array along a great circle path. Through this analysis, we can obtain a spectrogram in c-T (phase speed - period) domain, which is characterized by mode-branch dispersion curves and relative spectral powers for each mode. Synthetic experiments indicate that we can separate the modal contribution using a long linear array with typical array length of about 2000 to 4000 km. The method is applied to a large data set from USArray using nearly 400 seismic events in 2007 - 2014 with Mw 6.5 or greater. Our phase-speed maps for the fundamental-mode Love and Rayleigh waves and the first higher-mode Rayleigh waves match well with the earlier models. The phase speed maps reflect typical large-scale features of regional seismic structure in North America, but smaller-scale variations are less constrained in our model, since our measured phase speeds represent path-average features over a long path (about a few thousands kilometers). Our multi-mode dispersion measurements can also be used for the extraction of mode-branch waveforms for the first a few modes. This can be done by applying a narrow filter around the dispersion curves of a target mode in c-T spectrogram. The mode-branch waveforms can then be reconstructed based on a linear Radon transform (e.g., Luo et al., 2015, GJI). Synthetic experiments suggest that we can successfully retrieve the mode-branch waveforms for several mode branches, which can be used in the secondary analysis for constraining local-scale heterogeneity with enhanced depth resolution.

Comparative study of various normal mode analysis techniques based on partial Hessians.

PubMed

Ghysels, An; Van Speybroeck, Veronique; Pauwels, Ewald; Catak, Saron; Brooks, Bernard R; Van Neck, Dimitri; Waroquier, Michel

2010-04-15

Standard normal mode analysis becomes problematic for complex molecular systems, as a result of both the high computational cost and the excessive amount of information when the full Hessian matrix is used. Several partial Hessian methods have been proposed in the literature, yielding approximate normal modes. These methods aim at reducing the computational load and/or calculating only the relevant normal modes of interest in a specific application. Each method has its own (dis)advantages and application field but guidelines for the most suitable choice are lacking. We have investigated several partial Hessian methods, including the Partial Hessian Vibrational Analysis (PHVA), the Mobile Block Hessian (MBH), and the Vibrational Subsystem Analysis (VSA). In this article, we focus on the benefits and drawbacks of these methods, in terms of the reproduction of localized modes, collective modes, and the performance in partially optimized structures. We find that the PHVA is suitable for describing localized modes, that the MBH not only reproduces localized and global modes but also serves as an analysis tool of the spectrum, and that the VSA is mostly useful for the reproduction of the low frequency spectrum. These guidelines are illustrated with the reproduction of the localized amine-stretch, the spectrum of quinine and a bis-cinchona derivative, and the low frequency modes of the LAO binding protein. 2009 Wiley Periodicals, Inc.

Comparative Study of Various Normal Mode Analysis Techniques Based on Partial Hessians

PubMed Central

GHYSELS, AN; VAN SPEYBROECK, VERONIQUE; PAUWELS, EWALD; CATAK, SARON; BROOKS, BERNARD R.; VAN NECK, DIMITRI; WAROQUIER, MICHEL

2014-01-01

Standard normal mode analysis becomes problematic for complex molecular systems, as a result of both the high computational cost and the excessive amount of information when the full Hessian matrix is used. Several partial Hessian methods have been proposed in the literature, yielding approximate normal modes. These methods aim at reducing the computational load and/or calculating only the relevant normal modes of interest in a specific application. Each method has its own (dis)advantages and application field but guidelines for the most suitable choice are lacking. We have investigated several partial Hessian methods, including the Partial Hessian Vibrational Analysis (PHVA), the Mobile Block Hessian (MBH), and the Vibrational Subsystem Analysis (VSA). In this article, we focus on the benefits and drawbacks of these methods, in terms of the reproduction of localized modes, collective modes, and the performance in partially optimized structures. We find that the PHVA is suitable for describing localized modes, that the MBH not only reproduces localized and global modes but also serves as an analysis tool of the spectrum, and that the VSA is mostly useful for the reproduction of the low frequency spectrum. These guidelines are illustrated with the reproduction of the localized amine-stretch, the spectrum of quinine and a bis-cinchona derivative, and the low frequency modes of the LAO binding protein. PMID:19813181

State-plane analysis of parallel resonant converter

NASA Technical Reports Server (NTRS)

Oruganti, R.; Lee, F. C.

1985-01-01

A method for analyzing the complex operation of a parallel resonant converter is developed, utilizing graphical state-plane techniques. The comprehensive mode analysis uncovers, for the first time, the presence of other complex modes besides the continuous conduction mode and the discontinuous conduction mode and determines their theoretical boundaries. Based on the insight gained from the analysis, a novel, high-frequency resonant buck converter is proposed. The voltage conversion ratio of the new converter is almost independent of load.

Multivariate frequency domain analysis of protein dynamics

NASA Astrophysics Data System (ADS)

Matsunaga, Yasuhiro; Fuchigami, Sotaro; Kidera, Akinori

2009-03-01

Multivariate frequency domain analysis (MFDA) is proposed to characterize collective vibrational dynamics of protein obtained by a molecular dynamics (MD) simulation. MFDA performs principal component analysis (PCA) for a bandpass filtered multivariate time series using the multitaper method of spectral estimation. By applying MFDA to MD trajectories of bovine pancreatic trypsin inhibitor, we determined the collective vibrational modes in the frequency domain, which were identified by their vibrational frequencies and eigenvectors. At near zero temperature, the vibrational modes determined by MFDA agreed well with those calculated by normal mode analysis. At 300 K, the vibrational modes exhibited characteristic features that were considerably different from the principal modes of the static distribution given by the standard PCA. The influences of aqueous environments were discussed based on two different sets of vibrational modes, one derived from a MD simulation in water and the other from a simulation in vacuum. Using the varimax rotation, an algorithm of the multivariate statistical analysis, the representative orthogonal set of eigenmodes was determined at each vibrational frequency.

Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis.

PubMed

Kengkla, Kirati; Kongpakwattana, Khachen; Saokaew, Surasak; Apisarnthanarak, Anucha; Chaiyakunapruk, Nathorn

2018-01-01

To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection. We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events. A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections. Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dual throat thruster cold flow analysis

NASA Technical Reports Server (NTRS)

Lundgreen, R. B.; Nickerson, G. R.; Obrien, C. J.

1978-01-01

The concept was evaluated with cold flow (nitrogen gas) testing and through analysis for application as a tripropellant engine for single-stage-to-orbit type missions. Three modes of operation were tested and analyzed: (1) Mode 1 Series Burn, (2) Mode 1 Parallel Burn, and (3) Mode 2. Primary emphasis was placed on the Mode 2 plume attachment aerodynamics and performance. The conclusions from the test data analysis are as follows: (1) the concept is aerodynamically feasible, (2) the performance loss is as low as 0.5 percent, (3) the loss is minimized by an optimum nozzle spacing corresponding to an AF-ATS ratio of about 1.5 or an Le/Rtp ratio of 3.0 for the dual throat hardware tested, requiring only 4% bleed flow, (4) the Mode 1 and Mode 2 geometry requirements are compatible and pose no significant design problems.

Zero-mode waveguides

DOEpatents

Levene, Michael J.; Korlach, Jonas; Turner, Stephen W.; Craighead, Harold G.; Webb, Watt W.

2007-02-20

The present invention is directed to a method and an apparatus for analysis of an analyte. The method involves providing a zero-mode waveguide which includes a cladding surrounding a core where the cladding is configured to preclude propagation of electromagnetic energy of a frequency less than a cutoff frequency longitudinally through the core of the zero-mode waveguide. The analyte is positioned in the core of the zero-mode waveguide and is then subjected, in the core of the zero-mode waveguide, to activating electromagnetic radiation of a frequency less than the cut-off frequency under conditions effective to permit analysis of the analyte in an effective observation volume which is more compact than if the analysis were carried out in the absence of the zero-mode waveguide.

Few-mode fiber, splice and SDM component characterization by spatially-diverse optical vector network analysis.

PubMed

Rommel, Simon; Mendinueta, José Manuel Delgado; Klaus, Werner; Sakaguchi, Jun; Olmos, Juan José Vegas; Awaji, Yoshinari; Monroy, Idelfonso Tafur; Wada, Naoya

2017-09-18

This paper discusses spatially diverse optical vector network analysis for space division multiplexing (SDM) component and system characterization, which is becoming essential as SDM is widely considered to increase the capacity of optical communication systems. Characterization of a 108-channel photonic lantern spatial multiplexer, coupled to a 36-core 3-mode fiber, is experimentally demonstrated, extracting the full impulse response and complex transfer function matrices as well as insertion loss (IL) and mode-dependent loss (MDL) data. Moreover, the mode-mixing behavior of fiber splices in the few-mode multi-core fiber and their impact on system IL and MDL are analyzed, finding splices to cause significant mode-mixing and to be non-negligible in system capacity analysis.

Mod 1 wind turbine generator failure modes and effects analysis

NASA Technical Reports Server (NTRS)

1979-01-01

A failure modes and effects analysis (FMEA) was directed primarily at identifying those critical failure modes that would be hazardous to life or would result in major damage to the system. Each subsystem was approached from the top down, and broken down to successive lower levels where it appeared that the criticality of the failure mode warranted more detail analysis. The results were reviewed by specialists from outside the Mod 1 program, and corrective action taken wherever recommended.

Pad-mode-induced instantaneous mode instability for simple models of brake systems

NASA Astrophysics Data System (ADS)

Oberst, S.; Lai, J. C. S.

2015-10-01

Automotive disc brake squeal is fugitive, transient and remains difficult to predict. In particular, instantaneous mode squeal observed experimentally does not seem to be associated with mode coupling and its mechanism is not clear. The effects of contact pressures, friction coefficients as well as material properties (pressure and temperature dependency and anisotropy) for brake squeal propensity have not been systematically explored. By analysing a finite element model of an isotropic pad sliding on a plate similar to that of a previously reported experimental study, pad modes have been identified and found to be stable using conventional complex eigenvalue analysis. However, by subjecting the model to contact pressure harmonic excitation for a range of pressures and friction coefficients, a forced response analysis reveals that the dissipated energy for pad modes is negative and becomes more negative with increasing contact pressures and friction coefficients, indicating the potential for instabilities. The frequency of the pad mode in the sliding direction is within the range of squeal frequencies observed experimentally. Nonlinear time series analysis of the vibration velocity also confirms the evolution of instabilities induced by pad modes as the friction coefficient increases. By extending this analysis to a more realistic but simple brake model in the form of a pad-on-disc system, in-plane pad-modes, which a complex eigenvalue analysis predicts to be stable, have also been identified by negative dissipated energy for both isotropic and anisotropic pad material properties. The influence of contact pressures on potential instabilities has been found to be more dominant than changes in material properties owing to changes in pressure or temperature. Results here suggest that instantaneous mode squeal is likely caused by in-plane pad-mode instabilities.

Independent Orbiter Assessment (IOA): Analysis of the pyrotechnics subsystem

NASA Technical Reports Server (NTRS)

Robinson, W. W.

1988-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results corresponding to the Orbiter Pyrotechnics hardware. The IOA analysis process utilized available pyrotechnics hardware drawings and schematics for defining hardware assemblies, components, and hardware items. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode.

Mode structure of a quantum cascade laser

NASA Astrophysics Data System (ADS)

Bogdanov, A. A.; Suris, R. A.

2011-03-01

We analyze the mode structure of a quantum cascade laser (QCL) cavity considering the surface plasmon-polariton modes and familiar modes of hollow resonator jointly, within a single model. We present a comprehensive mode structure analysis of the laser cavity, varying its geometric parameters and free electron concentration inside cavity layers within a wide range. Our analysis covers, in particular, the cases of metal-insulator-metal and insulator-metal-insulator waveguides. We discuss the phenomenon of negative dispersion for eigenmodes in detail and explain the nature of this phenomenon. We specify a waveguide parameters domain in which negative dispersion exists. The mode structure of QCL cavity is considered in the case of the anisotropic electrical properties of the waveguide materials. We show that anisotropy of the waveguide core results in propagation of Langmuir modes that are degenerated in the case of the isotropic core. Comparative analysis of optical losses due to free carrier absorption is presented for different modes within the frequency range from terahertz to ultraviolet frequencies.

Risk Based Reliability Centered Maintenance of DOD Fire Protection Systems

DTIC Science & Technology

1999-01-01

2.2.3 Failure Mode and Effect Analysis ( FMEA )............................ 2.2.4 Failure Mode Risk Characterization...Step 2 - System functions and functional failures definition Step 3 - Failure mode and effect analysis ( FMEA ) Step 4 - Failure mode risk...system). The Interface Location column identifies the location where the FMEA of the fire protection system began or stopped. For example, for the fire

Zero-mode clad waveguides for performing spectroscopy with confined effective observation volumes

DOEpatents

Levene, Michael J.; Korlach, Jonas; Turner, Stephen W.; Craighead, Harold G.; Webb, Watt W.

2005-07-12

The present invention is directed to a method and an apparatus for analysis of an analyte. The method involves providing a zero-mode waveguide which includes a cladding surrounding a core where the cladding is configured to preclude propagation of electromagnetic energy of a frequency less than a cutoff frequency longitudinally through the core of the zero-mode waveguide. The analyte is positioned in the core of the zero-mode waveguide and is then subjected, in the core of the zero-mode waveguide, to activating electromagnetic radiation of a frequency less than the cut-off frequency under conditions effective to permit analysis of the analyte in an effective observation volume which is more compact than if the analysis were carried out in the absence of the zero-mode waveguide.

Colorimetric detection of melamine based on p-chlorobenzenesulfonic acid-modified AuNPs

NASA Astrophysics Data System (ADS)

Li, Jianfang; Huang, Pengcheng; Wu, Fangying

2016-06-01

A highly selective and sensitive method is developed for colorimetric detection of melamine using gold nanoparticles (AuNPs) functionalized with p-chlorobenzenesulfonic acid. The addition of melamine induced the aggregation of AuNPs, as evidenced from the morphological characterizations and the color changed from red wine to blue, which could also be monitored by the UV-visible spectrometer and even naked eyes. This process caused a significant increase in the absorbance ratio (A650nm/A520nm) of p-chlorobenzenesulfonic acid-AuNPs. Under optimized conditions, the system exhibited a linear response to melamine in the range of 6.0 × 10-7-1.5 × 10-6 mol L-1 with a correlation coefficient of 0.997, and the limit of detection can even be 2.3 nM, which was much lower than some other methods and the safe limits (20 μM in both the USA and EU, 8.0 μM for infant formula in China, 1.2 μM in the CAC (Codex Alimentarius Commission) review for melamine in liquid infant formula). More importantly, the developed method presented excellent tolerance to coexisting common metal ions such as Ca2+, Zn2+, whose concentration is 1000 times of melamine, so that it had been applied to the analysis of melamine in liquid milk and milk powder with the recovery of 97.0-101 % and 100-103 %, respectively, indicating that the proposed method is quite a highly effective means to determine melamine in milk products.

An evaluation of intraoperative and postoperative outcomes of torsional mode versus longitudinal ultrasound mode phacoemulsification: a Meta-analysis.

PubMed

Leon, Pia; Umari, Ingrid; Mangogna, Alessandro; Zanei, Andrea; Tognetto, Daniele

2016-01-01

To evaluate and compare the intraoperative parameters and postoperative outcomes of torsional mode and longitudinal mode of phacoemulsification. Pertinent studies were identified by a computerized MEDLINE search from January 2002 to September 2013. The Meta-analysis is composed of two parts. In the first part the intraoperative parameters were considered: ultrasound time (UST) and cumulative dissipated energy (CDE). The intraoperative values were also distinctly considered for two categories (moderate and hard cataract group) depending on the nuclear opacity grade. In the second part of the study the postoperative outcomes as the best corrected visual acuity (BCVA) and the endothelial cell loss (ECL) were taken in consideration. The UST and CDE values proved statistically significant in support of torsional mode for both moderate and hard cataract group. The analysis of BCVA did not present statistically significant difference between the two surgical modalities. The ECL count was statistically significant in support of torsional mode (P<0.001). The Meta-analysis shows the superiority of the torsional mode for intraoperative parameters (UST, CDE) and postoperative ECL outcomes.

An evaluation of intraoperative and postoperative outcomes of torsional mode versus longitudinal ultrasound mode phacoemulsification: a Meta-analysis

PubMed Central

Leon, Pia; Umari, Ingrid; Mangogna, Alessandro; Zanei, Andrea; Tognetto, Daniele

2016-01-01

AIM To evaluate and compare the intraoperative parameters and postoperative outcomes of torsional mode and longitudinal mode of phacoemulsification. METHODS Pertinent studies were identified by a computerized MEDLINE search from January 2002 to September 2013. The Meta-analysis is composed of two parts. In the first part the intraoperative parameters were considered: ultrasound time (UST) and cumulative dissipated energy (CDE). The intraoperative values were also distinctly considered for two categories (moderate and hard cataract group) depending on the nuclear opacity grade. In the second part of the study the postoperative outcomes as the best corrected visual acuity (BCVA) and the endothelial cell loss (ECL) were taken in consideration. RESULTS The UST and CDE values proved statistically significant in support of torsional mode for both moderate and hard cataract group. The analysis of BCVA did not present statistically significant difference between the two surgical modalities. The ECL count was statistically significant in support of torsional mode (P<0.001). CONCLUSION The Meta-analysis shows the superiority of the torsional mode for intraoperative parameters (UST, CDE) and postoperative ECL outcomes. PMID:27366694

Performance of Different Analytical Software Packages in Quantification of DNA Methylation by Pyrosequencing.

PubMed

Grasso, Chiara; Trevisan, Morena; Fiano, Valentina; Tarallo, Valentina; De Marco, Laura; Sacerdote, Carlotta; Richiardi, Lorenzo; Merletti, Franco; Gillio-Tos, Anna

2016-01-01

Pyrosequencing has emerged as an alternative method of nucleic acid sequencing, well suited for many applications which aim to characterize single nucleotide polymorphisms, mutations, microbial types and CpG methylation in the target DNA. The commercially available pyrosequencing systems can harbor two different types of software which allow analysis in AQ or CpG mode, respectively, both widely employed for DNA methylation analysis. Aim of the study was to assess the performance for DNA methylation analysis at CpG sites of the two pyrosequencing software which allow analysis in AQ or CpG mode, respectively. Despite CpG mode having been specifically generated for CpG methylation quantification, many investigations on this topic have been carried out with AQ mode. As proof of equivalent performance of the two software for this type of analysis is not available, the focus of this paper was to evaluate if the two modes currently used for CpG methylation assessment by pyrosequencing may give overlapping results. We compared the performance of the two software in quantifying DNA methylation in the promoter of selected genes (GSTP1, MGMT, LINE-1) by testing two case series which include DNA from paraffin embedded prostate cancer tissues (PC study, N = 36) and DNA from blood fractions of healthy people (DD study, N = 28), respectively. We found discrepancy in the two pyrosequencing software-based quality assignment of DNA methylation assays. Compared to the software for analysis in the AQ mode, less permissive criteria are supported by the Pyro Q-CpG software, which enables analysis in CpG mode. CpG mode warns the operators about potential unsatisfactory performance of the assay and ensures a more accurate quantitative evaluation of DNA methylation at CpG sites. The implementation of CpG mode is strongly advisable in order to improve the reliability of the methylation analysis results achievable by pyrosequencing.

Analysis of self-homodyne detection for 6-mode fiber with low-modal crosstalk

NASA Astrophysics Data System (ADS)

Guo, Meng; Hu, Guijun

2017-12-01

In this paper, we present an appropriate analysis on self-homodyne coherent system with 56 × 5 × 3 Gb / s WDM-PDM-MDM quadrature phase-shift keying (QPSK) signals using 6-mode weakly coupled few mode fiber. The mode division technology can effectively improve the spectral efficiency (SE) of self-homodyne detection. Of all the LP modes, LP01 mode is used to transmit the pilot tone (PT), while the others for signal channels. The influence of inter-mode crosstalk is analyzed. The proposed frequency domain MMA shows a better BER performance for intra-mode crosstalk elimination. The path-length misalignment's influence caused by mode differential group delay (MDGD) is also investigated. The system tolerance for different laser's line-width is compared as well as the influence of PT filter's bandwidth.

Product Support Manager Guidebook

DTIC Science & Technology

2011-04-01

package is being developed using supportability analysis concepts such as Failure Mode, Effects and Criticality Analysis (FMECA), Fault Tree Analysis ( FTA ...Analysis (LORA) Condition Based Maintenance + (CBM+) Fault Tree Analysis ( FTA ) Failure Mode, Effects, and Criticality Analysis (FMECA) Maintenance Task...Reporting and Corrective Action System (FRACAS), Fault Tree Analysis ( FTA ), Level of Repair Analysis (LORA), Maintenance Task Analysis (MTA

Independent Orbiter Assessment (IOA): Analysis of the communication and tracking subsystem

NASA Technical Reports Server (NTRS)

Gardner, J. R.; Robinson, W. M.; Trahan, W. H.; Daley, E. S.; Long, W. C.

1987-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results corresponding to the Orbiter Communication and Tracking hardware. The IOA analysis process utilized available Communication and Tracking hardware drawings and schematics for defining hardware assemblies, components, and hardware items. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode.

Failure Mode Identification Through Clustering Analysis

NASA Technical Reports Server (NTRS)

Arunajadai, Srikesh G.; Stone, Robert B.; Tumer, Irem Y.; Clancy, Daniel (Technical Monitor)

2002-01-01

Research has shown that nearly 80% of the costs and problems are created in product development and that cost and quality are essentially designed into products in the conceptual stage. Currently, failure identification procedures (such as FMEA (Failure Modes and Effects Analysis), FMECA (Failure Modes, Effects and Criticality Analysis) and FTA (Fault Tree Analysis)) and design of experiments are being used for quality control and for the detection of potential failure modes during the detail design stage or post-product launch. Though all of these methods have their own advantages, they do not give information as to what are the predominant failures that a designer should focus on while designing a product. This work uses a functional approach to identify failure modes, which hypothesizes that similarities exist between different failure modes based on the functionality of the product/component. In this paper, a statistical clustering procedure is proposed to retrieve information on the set of predominant failures that a function experiences. The various stages of the methodology are illustrated using a hypothetical design example.

Therapies for bruxism: a systematic review and network meta-analysis (protocol).

PubMed

Mesko, Mauro Elias; Hutton, Brian; Skupien, Jovito Adiel; Sarkis-Onofre, Rafael; Moher, David; Pereira-Cenci, Tatiana

2017-01-13

Bruxism is a sleep disorder characterized by grinding and clenching of the teeth that may be related to irreversible tooth injuries. It is a prevalent condition occurring in up to 31% of adults. However, there is no definitive answer as to which of the many currently available treatments (including drug therapy, intramuscular injections, physiotherapy, biofeedback, kinesiotherapy, use of intraoral devices, or psychological therapy) is the best for the clinical management of the different manifestations of bruxism. The aim of this systematic review and network meta-analysis is to answer the following question: what is the best treatment for adult bruxists? Comprehensive searches of the Cochrane Library, MEDLINE (via PubMed), Scopus, and LILACS will be completed using the following keywords: bruxism and therapies and related entry terms. Studies will be included, according to the eligibility criteria (Controlled Clinical Trials and Randomized Clinical Trials, considering specific outcome measures for bruxism). The reference lists of included studies will be hand searched. Relevant data will be extracted from included studies using a specially designed data extraction sheet. Risk of bias of the included studies will be assessed, and the overall strength of the evidence will be summarized (i.e., GRADE). A random effects model will be used for all pairwise meta-analyses (with a 95% confidence interval). A Bayesian network meta-analysis will explore the relative benefits between the various treatments. The review will be reported using the Preferred Reporting Items for Systematic Reviews incorporating Network Meta-Analyses (PRISMA-NMA) statement. This systematic review aims at identifying and evaluating therapies to treat bruxism. This systematic review may lead to several recommendations, for both patients and researchers, as which is the best therapy for a specific patient case and how future studies need to be designed, considering what is available now and what is the reality of the patient. PROSPERO CRD42015023308.

Comparison of Pathogen Eradication Rate and Safety of Anti-Bacterial Agents for Bronchitis: A Network Meta-Analysis.

PubMed

Wang, Jinghua; Xu, Haiyang; Wang, Dunwei; Li, Mingxian

2017-10-01

A large number of population in both developing and developed countries are affected by bronchitis, among all the factors, bacterial infection was considered as a critical cause of acute exacerbations of chronic bronchitis. Although several anti-bacterial agents were proved to have the effect of alleviating bronchitis, their relative efficacies and potential side effects remained not clear. We are keen to compare the pathogen eradication rate and safety of anti-bacterial agents for bronchitis. Relevant studies were searched in multiple sources and data were extracted from eligible studies. Then conventional meta-analysis and network meta-analysis (NMA) were conducted to determine the relative efficacy and safety of bronchitis medications. The efficacy of bronchitis medications was determined by using the outcome of pathogen eradication, including total pathogen eradication, pathogen eradication of Haemophilus influenzae, pathogen eradication of Moraxella catarrhalis, and pathogen eradication of Streptococcus pneumoniae. In addition, safety was assessed by using the outcome of adverse effects and diarrhoea. A 27 RCTs with 9,414 participants were included in the study. Among the medications, gatifloxacin and moxifloxacin exhibited better performance than clarithromycin with respect to pathogen eradication of H. influenzae (OR = 21.37, CI: 1.22-541.28; OR = 7.43, CI: 1.79-30.50). Clarithromycin, gemifloxacin, levofloxacin, moxifloxacin, and telithromycin appeared to be more preferable than amoxicillin + clavulanate and azithromycin with respect to diarrhoea (all OR <1). The surface under the cumulative ranking curve (SUCRA) results suggested that gemifloxacin and levofloxacin had a relatively high ranking in total pathogen eradication, whereas amoxicillin + clavulanate and azithromycin exhibited relatively lower ranking with respect to adverse effects and diarrhoea. Gemifloxacin and levofloxacin are more preferable than others for lowering respiratory tract inflammation and infections considering their balanced performance between pathogen eradication and adverse effects. J. Cell. Biochem. 118: 3171-3183, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The influence of implant-abutment connection to peri-implant bone loss: A systematic review and meta-analysis.

PubMed

Caricasulo, Riccardo; Malchiodi, Luciano; Ghensi, Paolo; Fantozzi, Giuliano; Cucchi, Alessandro

2018-05-15

Different implant-abutment connections are available and it has been claimed they could have an effect on marginal bone loss. The aim of this review is to establish if implant connection configuration influences peri-implant bone loss (PBL) after functional loading. A specific question was formulated according to the Population, Intervention, Control, and Outcome (PICO): Does the type of implant-abutment connection (external, internal, or conical) have an influence on peri-implant bone loss? A PubMed/MEDLINE electronic search was conducted to identify English language publications published in international journals during the last decade (from 2006 to 2016). The search was conducted by using the Medical Subject Headings (MeSH) keywords "dental implants OR dental abutment AND external connection OR internal connection OR conical connection OR Morse Taper." Selected studies were randomized clinical trials and prospective studies; in vitro studies, case reports and retrospective studies were excluded. Titles and abstracts and, in the second phase, full texts, were evaluated autonomously and in duplicate by two reviewers. A total of 1649 articles were found, but only 14 studies met the pre-established inclusion criteria and were considered suitable for meta-analytic analysis. The network meta-analysis (NMA) suggested a significant difference between the external and the conical connections; this was less evident for the internal and conical ones. Platform-switching (PS) seemed to positively affect bone levels, non-regarding the implant-connection it was applied to. Within the limitations of this systematic review, it can be concluded that crestal bone levels are better maintained in the short-medium term when internal kinds of interface are adopted. In particular, conical connections seem to be more advantageous, showing lower peri-implant bone loss, but further studies are necessary to investigate the efficacy of implant-abutment connection on stability of crestal bone levels. © 2018 Wiley Periodicals, Inc.

Use of failure mode and effects analysis for proactive identification of communication and handoff failures from organ procurement to transplantation.

PubMed

Steinberger, Dina M; Douglas, Stephen V; Kirschbaum, Mark S

2009-09-01

A multidisciplinary team from the University of Wisconsin Hospital and Clinics transplant program used failure mode and effects analysis to proactively examine opportunities for communication and handoff failures across the continuum of care from organ procurement to transplantation. The team performed a modified failure mode and effects analysis that isolated the multiple linked, serial, and complex information exchanges occurring during the transplantation of one solid organ. Failure mode and effects analysis proved effective for engaging a diverse group of persons who had an investment in the outcome in analysis and discussion of opportunities to improve the system's resilience for avoiding errors during a time-pressured and complex process.

Silver nanoparticles-based colorimetric array for the detection of Thiophanate-methyl

NASA Astrophysics Data System (ADS)

Zheng, Mingda; Wang, Yingying; Wang, Chenge; Wei, Wei; Ma, Shuang; Sun, Xiaohan; He, Jiang

2018-06-01

A simple and selective colorimetric sensor based on citrate capped silver nanoparticles (Cit-AgNPs) is proposed for the detection of Thiophanate-methyl (TM) with high sensitivity and selectivity. The method based on the color change of Cit-AgNPs from yellow to cherry red with the addition of TM to Cit-AgNPs that caused a red-shift on the surface plasmon resonance (SPR) band from 394 nm to 525 nm due to the hydrogen-bonding and substitution. The density functional theory (DFT) method was also calculated the interactions between the TM and citrate ions. Under the optimized conditions, a linear relationship between the absorption ratio (A525nm/A394nm) and TM concentration was found in the range of 2-100 μM with correlation coefficient (R2) of 0.988. The detection limit of TM was 0.12 μM by UV-vis spectrometer. Moreover, the applicability of colorimetric sensor is successfully verified by the detection of TM in environmental samples with good recoveries.

Weighted Fuzzy Risk Priority Number Evaluation of Turbine and Compressor Blades Considering Failure Mode Correlations

NASA Astrophysics Data System (ADS)

Gan, Luping; Li, Yan-Feng; Zhu, Shun-Peng; Yang, Yuan-Jian; Huang, Hong-Zhong

2014-06-01

Failure mode, effects and criticality analysis (FMECA) and Fault tree analysis (FTA) are powerful tools to evaluate reliability of systems. Although single failure mode issue can be efficiently addressed by traditional FMECA, multiple failure modes and component correlations in complex systems cannot be effectively evaluated. In addition, correlated variables and parameters are often assumed to be precisely known in quantitative analysis. In fact, due to the lack of information, epistemic uncertainty commonly exists in engineering design. To solve these problems, the advantages of FMECA, FTA, fuzzy theory, and Copula theory are integrated into a unified hybrid method called fuzzy probability weighted geometric mean (FPWGM) risk priority number (RPN) method. The epistemic uncertainty of risk variables and parameters are characterized by fuzzy number to obtain fuzzy weighted geometric mean (FWGM) RPN for single failure mode. Multiple failure modes are connected using minimum cut sets (MCS), and Boolean logic is used to combine fuzzy risk priority number (FRPN) of each MCS. Moreover, Copula theory is applied to analyze the correlation of multiple failure modes in order to derive the failure probabilities of each MCS. Compared to the case where dependency among multiple failure modes is not considered, the Copula modeling approach eliminates the error of reliability analysis. Furthermore, for purpose of quantitative analysis, probabilities importance weight from failure probabilities are assigned to FWGM RPN to reassess the risk priority, which generalize the definition of probability weight and FRPN, resulting in a more accurate estimation than that of the traditional models. Finally, a basic fatigue analysis case drawn from turbine and compressor blades in aeroengine is used to demonstrate the effectiveness and robustness of the presented method. The result provides some important insights on fatigue reliability analysis and risk priority assessment of structural system under failure correlations.

Time-Frequency Analysis of the Dispersion of Lamb Modes

NASA Technical Reports Server (NTRS)

Prosser, W. H.; Seale, Michael D.; Smith, Barry T.

1999-01-01

Accurate knowledge of the velocity dispersion of Lamb modes is important for ultrasonic nondestructive evaluation methods used in detecting and locating flaws in thin plates and in determining their elastic stiffness coefficients. Lamb mode dispersion is also important in the acoustic emission technique for accurately triangulating the location of emissions in thin plates. In this research, the ability to characterize Lamb mode dispersion through a time-frequency analysis (the pseudo-Wigner-Ville distribution) was demonstrated. A major advantage of time-frequency methods is the ability to analyze acoustic signals containing multiple propagation modes, which overlap and superimpose in the time domain signal. By combining time-frequency analysis with a broadband acoustic excitation source, the dispersion of multiple Lamb modes over a wide frequency range can be determined from as little as a single measurement. In addition, the technique provides a direct measurement of the group velocity dispersion. The technique was first demonstrated in the analysis of a simulated waveform in an aluminum plate in which the Lamb mode dispersion was well known. Portions of the dispersion curves of the AO, A I , So, and S2 Lamb modes were obtained from this one waveform. The technique was also applied for the analysis of experimental waveforms from a unidirectional graphite/epoxy composite plate. Measurements were made both along and perpendicular to the fiber direction. In this case, the signals contained only the lowest order symmetric and antisymmetric modes. A least squares fit of the results from several source to detector distances was used. Theoretical dispersion curves were calculated and are shown to be in good agreement with experimental results.

Differential Lipid Profiles of Normal Human Brain Matter and Gliomas by Positive and Negative Mode Desorption Electrospray Ionization – Mass Spectrometry Imaging

PubMed Central

Pirro, Valentina; Hattab, Eyas M.; Cohen-Gadol, Aaron A.; Cooks, R. Graham

2016-01-01

Desorption electrospray ionization—mass spectrometry (DESI-MS) imaging was used to analyze unmodified human brain tissue sections from 39 subjects sequentially in the positive and negative ionization modes. Acquisition of both MS polarities allowed more complete analysis of the human brain tumor lipidome as some phospholipids ionize preferentially in the positive and others in the negative ion mode. Normal brain parenchyma, comprised of grey matter and white matter, was differentiated from glioma using positive and negative ion mode DESI-MS lipid profiles with the aid of principal component analysis along with linear discriminant analysis. Principal component–linear discriminant analyses of the positive mode lipid profiles was able to distinguish grey matter, white matter, and glioma with an average sensitivity of 93.2% and specificity of 96.6%, while the negative mode lipid profiles had an average sensitivity of 94.1% and specificity of 97.4%. The positive and negative mode lipid profiles provided complementary information. Principal component–linear discriminant analysis of the combined positive and negative mode lipid profiles, via data fusion, resulted in approximately the same average sensitivity (94.7%) and specificity (97.6%) of the positive and negative modes when used individually. However, they complemented each other by improving the sensitivity and specificity of all classes (grey matter, white matter, and glioma) beyond 90% when used in combination. Further principal component analysis using the fused data resulted in the subgrouping of glioma into two groups associated with grey and white matter, respectively, a separation not apparent in the principal component analysis scores plots of the separate positive and negative mode data. The interrelationship of tumor cell percentage and the lipid profiles is discussed, and how such a measure could be used to measure residual tumor at surgical margins. PMID:27658243

Statins in adult patients with HIV: Protocol for a systematic review and network meta-analysis.

PubMed

Roever, Leonardo; Resende, Elmiro Santos; Diniz, Angélica Lemos Debs; Penha-Silva, Nilson; O'Connell, João Lucas; Gomes, Paulo Fernando Silva; Zanetti, Hugo Ribeiro; Roerver-Borges, Anaisa Silva; Veloso, Fernando César; Fidale, Thiago Montes; Casella-Filho, Antonio; Dourado, Paulo Magno Martins; Chagas, Antonio Carlos Palandri; Ali-Hasan-Al-Saegh, Sadeq; Reis, Paulo Eduardo Ocke; Pinto, Rogério de Melo; Oliveira, Gustavo B F; Avezum, Álvaro; Neto, Mansueto; Durães, André; Silva, Rose Mary Ferreira Lisboa da; Grande, Antonio José; Denardi, Celise; Lopes, Renato Delascio; Nerlekar, Nitesh; Alizadeh, Shahab; Hernandez, Adrian V; Biondi-Zoccai, Giuseppe

2018-04-01

Patients with HIV have been found to suffer from lipid abnormalities, including elevated levels of total and LDL-cholesterol as well as triglyceride levels. Abnormal lipid levels are associated with an increased risk of developing cardiovascular diseases, which are significant causes of mortality among the general population. Therefore, the objective of the current study is to conduct a systematic review with network meta-analysis to compare the effects of statins classes on HIV patients. Randomized clinical trials (RCTs) and observational studies published in English up to 31 December 2017, and which include direct and/or indirect evidence, will be included. Studies will be retrieved by searching four electronic databases and cross-referencing. Dual selection and abstraction of data will occur. The primary outcome will all-cause mortality, new event of acute myocardial infarction, stroke (hemorrhagic and ischemic), hospitalization for acute coronary syndrome and urgent revascularization procedures and cardiovascular mortality. Secondary outcomes will be assessment of the differences in change of total cholesterol (TC), low-density lipoprotein (LDL-C), apolipoprotein B (ApoB), high density lipoprotein (HDL-C). Risk of bias will be assessed using the Cochrane Risk of Bias assessment instrument for RCTs and the Strengthening the Reporting of Observational Studies in Epidemiology instrument for observational studies. Network meta-analysis will be performed using multivariate random-effects meta-regression models. The surface under the cumulative ranking curve will be used to provide a hierarchy of statins that reduce cardiovascular mortality in HIV patients. A revised version of the Cochrane Risk of Bias tool (RoB 2.0) will be used to assess the risk of bias in eligible RCTs. Results will be synthesized and analyzed using network meta-analysis (NMA). Overall strength of the evidence and publication bias will be evaluated. Subgroup and sensitivity analysis will also be performed. Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. The evidence will determine which combination of interventions are most promising for current practice and further investigation. PROSPERO (CRD42017072996).

Participation of National Medical Associations in quality improvement activities - International comparison and the Israeli case

PubMed Central

2014-01-01

Background Many countries have devoted considerable efforts in an attempt to improve the performance of their health care systems. National Medical Associations (NMAs), along with other stakeholders, play a part in the promotion of such activities. The purpose of this paper is to explore the nature and level of participation of NMAs in activities of quality improvement in medicine, with a specific emphasis on Israel. Methods The authors conducted a survey among NMAs around the world inquiring as to their involvement in three central aspects of quality improvement: clinical guidelines, quality measurement and continuing medical education (CME). In addition, they conducted a review of the literature in order to gather more information and complete the data collected in the survey. The findings were processed and analyzed comparatively. Results Most of the NMAs surveyed participate in quality improvement activities at least to some extent. NMAs' main involvement is in the regulation of CME and they are involved to a much lesser extent in the preparation of clinical guidelines and in quality measurement. In Israel, the Israeli Medical Association (IMA) has a dominant role in both the preparation of clinical guidelines and the regulation of CME credits. Discussion It is possible that the expertise maintained by the profession, coupled with the organizational power of the NMA as a union, is viewed as beneficial for regulating educational activities in medicine such as CME. Conversely, the issuing of clinical guidelines is usually regarded as a typical scientific activity, and therefore often rests in the hands of professional medical societies. Quality measurement is regarded as a distinctive administrative tool and is usually found in the province of governments. Based on the typology that we introduced in our previous paper, we discovered that the extent of NMAs’ involvement in quality improvement coincides with the mode of governance of the health care system. Conclusions The nature and level of participation of NMAs in activities of quality improvement varies widely. Collaboration of NMAs in this field with other stakeholders is not uncommon, and may contribute to the further development of quality improvement in medicine. PMID:24808940

Restricted Acoustic Modal Analysis Applied to Internal Combustor Spectra and Cross-Spectra Measurements

NASA Technical Reports Server (NTRS)

Miles, Jeffrey Hilton

2006-01-01

A treatment of the modal decomposition of the pressure field in a combustor as determined by two Kulite pressure measurements is developed herein. It is applied to a Pratt & Whitney PW4098 engine combustor over a range of operating conditions. For modes other than the plane wave the new part of the treatment is the assumption that there are distinct frequency bands in which the individual modes, including the plane wave mode, overlap such that if circumferential mode m and circumferential mode m-1 are present than circumferential mode m 2 is not. Consequently, in the analysis used herein at frequencies above the first cut-off mode frequency, only pairs of circumferential modes are individually present at each frequency. Consequently, this is a restricted modal analysis. A new result is that the successful use of the same modal span frequencies over a range of operating conditions for this particular engine suggests that the temperature, T, and the velocity, v, of the flow at each operating condition are related by c(sup 2)-v(sup 2) = a constant where c is the speed of sound.

Seismic Analysis of Pulsating Subdwarf B Star EPIC 212508753 Using the K2 Mission

NASA Astrophysics Data System (ADS)

Crooke, John; Reed, Michael D.; Baran, Andrzej; Telting, John H.; Østensen, Roy H.

2018-01-01

EPIC 212508753 is a subdwarf B (hot horizontal branch, sdB) star which has been observed by the Kepler Space Telescope during its extended mission, K2, in short cadence mode where a new image is obtained roughly every minute for about 75 days. Using time series analysis of the data we have found the star to be a rare hybrid pulsator with both g- and p-mode pulsations where most of the pulsations are p modes. These pulsators are extremely important as p modes sample near the surface and g modes can sample deeper, near to the core. This means that hybrid pulsators allow us to characterize the entire star. The hotter, predominantly p-mode pulsators are rarer so that makes EPIC 212508753 particularly interesting for seismic study. In this poster we will present preliminary results of our analysis of K2 data. We have discovered frequency multiplets in both the p- and g-mode regions which we use to identify pulsation modes and determine that EPIC 212508753 rotates like a solid body, in contrast to some other sdB stars.

Risk analysis of analytical validations by probabilistic modification of FMEA.

PubMed

Barends, D M; Oldenhof, M T; Vredenbregt, M J; Nauta, M J

2012-05-01

Risk analysis is a valuable addition to validation of an analytical chemistry process, enabling not only detecting technical risks, but also risks related to human failures. Failure Mode and Effect Analysis (FMEA) can be applied, using a categorical risk scoring of the occurrence, detection and severity of failure modes, and calculating the Risk Priority Number (RPN) to select failure modes for correction. We propose a probabilistic modification of FMEA, replacing the categorical scoring of occurrence and detection by their estimated relative frequency and maintaining the categorical scoring of severity. In an example, the results of traditional FMEA of a Near Infrared (NIR) analytical procedure used for the screening of suspected counterfeited tablets are re-interpretated by this probabilistic modification of FMEA. Using this probabilistic modification of FMEA, the frequency of occurrence of undetected failure mode(s) can be estimated quantitatively, for each individual failure mode, for a set of failure modes, and the full analytical procedure. Copyright © 2012 Elsevier B.V. All rights reserved.

[Failure mode and effects analysis (FMEA) of insulin in a mother-child university-affiliated health center].

PubMed

Berruyer, M; Atkinson, S; Lebel, D; Bussières, J-F

2016-01-01

Insulin is a high-alert drug. The main objective of this descriptive cross-sectional study was to evaluate the risks associated with insulin use in healthcare centers. The secondary objective was to propose corrective measures to reduce the main risks associated with the most critical failure modes in the analysis. We conducted a failure mode and effects analysis (FMEA) in obstetrics-gynecology, neonatology and pediatrics. Five multidisciplinary meetings occurred in August 2013. A total of 44 out of 49 failure modes were analyzed. Nine out of 44 (20%) failure modes were deemed critical, with a criticality score ranging from 540 to 720. Following the multidisciplinary meetings, everybody agreed that an FMEA was a useful tool to identify failure modes and their relative importance. This approach identified many corrective measures. This shared experience increased awareness of safety issues with insulin in our mother-child center. This study identified the main failure modes and associated corrective measures. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Causality analysis of leading singular value decomposition modes identifies rotor as the dominant driving normal mode in fibrillation

NASA Astrophysics Data System (ADS)

Biton, Yaacov; Rabinovitch, Avinoam; Braunstein, Doron; Aviram, Ira; Campbell, Katherine; Mironov, Sergey; Herron, Todd; Jalife, José; Berenfeld, Omer

2018-01-01

Cardiac fibrillation is a major clinical and societal burden. Rotors may drive fibrillation in many cases, but their role and patterns are often masked by complex propagation. We used Singular Value Decomposition (SVD), which ranks patterns of activation hierarchically, together with Wiener-Granger causality analysis (WGCA), which analyses direction of information among observations, to investigate the role of rotors in cardiac fibrillation. We hypothesized that combining SVD analysis with WGCA should reveal whether rotor activity is the dominant driving force of fibrillation even in cases of high complexity. Optical mapping experiments were conducted in neonatal rat cardiomyocyte monolayers (diameter, 35 mm), which were genetically modified to overexpress the delayed rectifier K+ channel IKr only in one half of the monolayer. Such monolayers have been shown previously to sustain fast rotors confined to the IKr overexpressing half and driving fibrillatory-like activity in the other half. SVD analysis of the optical mapping movies revealed a hierarchical pattern in which the primary modes corresponded to rotor activity in the IKr overexpressing region and the secondary modes corresponded to fibrillatory activity elsewhere. We then applied WGCA to evaluate the directionality of influence between modes in the entire monolayer using clear and noisy movies of activity. We demonstrated that the rotor modes influence the secondary fibrillatory modes, but influence was detected also in the opposite direction. To more specifically delineate the role of the rotor in fibrillation, we decomposed separately the respective SVD modes of the rotor and fibrillatory domains. In this case, WGCA yielded more information from the rotor to the fibrillatory domains than in the opposite direction. In conclusion, SVD analysis reveals that rotors can be the dominant modes of an experimental model of fibrillation. Wiener-Granger causality on modes of the rotor domains confirms their preferential driving influence on fibrillatory modes.

Waveguides for performing enzymatic reactions

DOEpatents

Levene; Michael J. , Korlach; Jonas , Turner; Stephen W. , Craighead; Harold G. , Webb; Watt W.

2007-11-06

The present invention is directed to a method and an apparatus for analysis of an analyte. The method involves providing a zero-mode waveguide which includes a cladding surrounding a core where the cladding is configured to preclude propagation of electromagnetic energy of a frequency less than a cutoff frequency longitudinally through the core of the zero-mode waveguide. The analyte is positioned in the core of the zero-mode waveguide and is then subjected, in the core of the zero-mode wave guide, to activating electromagnetic radiation of a frequency less than the cut-off frequency under conditions effective to permit analysis of the analyte in an effective observation volume which is more compact than if the analysis were carried out in the absence of the zero-mode waveguide.

Numerical design and analysis of parasitic mode oscillations for 95 GHz gyrotron beam tunnel

NASA Astrophysics Data System (ADS)

Kumar, Nitin; Singh, Udaybir; Yadav, Vivek; Kumar, Anil; Sinha, A. K.

2013-05-01

The beam tunnel, equipped with the high lossy ceramics, is designed for 95 GHz gyrotron. The geometry of the beam tunnel is optimized considering the maximum RF absorption (ideally 100%) and the suppression of parasitic oscillations. The excitation of parasitic modes is a concerning problem for high frequency, high power gyrotrons. Considering the problem of parasitic mode excitation in beam tunnel, a detail analysis is performed for the suppression of these kinds of modes. Trajectory code EGUN and CST Microwave Studio are used for the simulations of electron beam trajectory and electromagnetic analysis, respectively.

Fracture modes in notched angleplied composite laminates

NASA Technical Reports Server (NTRS)

Irvine, T. B.; Ginty, C. A.

1984-01-01

The Composite Durability Structural Analysis (CODSTRAN) computer code is used to determine composite fracture. Fracture modes in solid and notched, unidirectional and angleplied graphite/epoxy composites were determined by using CODSTRAN. Experimental verification included both nondestructive (ultrasonic C-Scanning) and destructive (scanning electron microscopy) techniques. The fracture modes were found to be a function of ply orientations and whether the composite is notched or unnotched. Delaminations caused by stress concentrations around notch tips were also determined. Results indicate that the composite mechanics, structural analysis, laminate analysis, and fracture criteria modules embedded in CODSTRAN are valid for determining composite fracture modes.

Comparative Investigation of Normal Modes and Molecular Dynamics of Hepatitis C NS5B Protein

NASA Astrophysics Data System (ADS)

Asafi, M. S.; Yildirim, A.; Tekpinar, M.

2016-04-01

Understanding dynamics of proteins has many practical implications in terms of finding a cure for many protein related diseases. Normal mode analysis and molecular dynamics methods are widely used physics-based computational methods for investigating dynamics of proteins. In this work, we studied dynamics of Hepatitis C NS5B protein with molecular dynamics and normal mode analysis. Principal components obtained from a 100 nanoseconds molecular dynamics simulation show good overlaps with normal modes calculated with a coarse-grained elastic network model. Coarse-grained normal mode analysis takes at least an order of magnitude shorter time. Encouraged by this good overlaps and short computation times, we analyzed further low frequency normal modes of Hepatitis C NS5B. Motion directions and average spatial fluctuations have been analyzed in detail. Finally, biological implications of these motions in drug design efforts against Hepatitis C infections have been elaborated.

On the Use of Material-Dependent Damping in ANSYS for Mode Superposition Transient Analysis

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

Nie, J.; Wei, X.

The mode superposition method is often used for dynamic analysis of complex structures, such as the seismic Category I structures in nuclear power plants, in place of the less efficient full method, which uses the full system matrices for calculation of the transient responses. In such applications, specification of material-dependent damping is usually desirable because complex structures can consist of multiple types of materials that may have different energy dissipation capabilities. A recent review of the ANSYS manual for several releases found that the use of material-dependent damping is not clearly explained for performing a mode superposition transient dynamic analysis.more » This paper includes several mode superposition transient dynamic analyses using different ways to specify damping in ANSYS, in order to determine how material-dependent damping can be specified conveniently in a mode superposition transient dynamic analysis.« less

Orbiter subsystem hardware/software interaction analysis. Volume 8: Forward reaction control system

NASA Technical Reports Server (NTRS)

Becker, D. D.

1980-01-01

The results of the orbiter hardware/software interaction analysis for the AFT reaction control system are presented. The interaction between hardware failure modes and software are examined in order to identify associated issues and risks. All orbiter subsystems and interfacing program elements which interact with the orbiter computer flight software are analyzed. The failure modes identified in the subsystem/element failure mode and effects analysis are discussed.

An efficient scan diagnosis methodology according to scan failure mode for yield enhancement

NASA Astrophysics Data System (ADS)

Kim, Jung-Tae; Seo, Nam-Sik; Oh, Ghil-Geun; Kim, Dae-Gue; Lee, Kyu-Taek; Choi, Chi-Young; Kim, InSoo; Min, Hyoung Bok

2008-12-01

Yield has always been a driving consideration during fabrication of modern semiconductor industry. Statistically, the largest portion of wafer yield loss is defective scan failure. This paper presents efficient failure analysis methods for initial yield ramp up and ongoing product with scan diagnosis. Result of our analysis shows that more than 60% of the scan failure dies fall into the category of shift mode in the very deep submicron (VDSM) devices. However, localization of scan shift mode failure is very difficult in comparison to capture mode failure because it is caused by the malfunction of scan chain. Addressing the biggest challenge, we propose the most suitable analysis method according to scan failure mode (capture / shift) for yield enhancement. In the event of capture failure mode, this paper describes the method that integrates scan diagnosis flow and backside probing technology to obtain more accurate candidates. We also describe several unique techniques, such as bulk back-grinding solution, efficient backside probing and signal analysis method. Lastly, we introduce blocked chain analysis algorithm for efficient analysis of shift failure mode. In this paper, we contribute to enhancement of the yield as a result of the combination of two methods. We confirm the failure candidates with physical failure analysis (PFA) method. The direct feedback of the defective visualization is useful to mass-produce devices in a shorter time. The experimental data on mass products show that our method produces average reduction by 13.7% in defective SCAN & SRAM-BIST failure rates and by 18.2% in wafer yield rates.

How to apply clinical cases and medical literature in the framework of a modified "failure mode and effects analysis" as a clinical reasoning tool--an illustration using the human biliary system.

PubMed

Wong, Kam Cheong

2016-04-06

Clinicians use various clinical reasoning tools such as Ishikawa diagram to enhance their clinical experience and reasoning skills. Failure mode and effects analysis, which is an engineering methodology in origin, can be modified and applied to provide inputs into an Ishikawa diagram. The human biliary system is used to illustrate a modified failure mode and effects analysis. The anatomical and physiological processes of the biliary system are reviewed. Failure is defined as an abnormality caused by infective, inflammatory, obstructive, malignancy, autoimmune and other pathological processes. The potential failures, their effect(s), main clinical features, and investigation that can help a clinician to diagnose at each anatomical part and physiological process are reviewed and documented in a modified failure mode and effects analysis table. Relevant medical and surgical cases are retrieved from the medical literature and weaved into the table. A total of 80 clinical cases which are relevant to the modified failure mode and effects analysis for the human biliary system have been reviewed and weaved into a designated table. The table is the backbone and framework for further expansion. Reviewing and updating the table is an iterative and continual process. The relevant clinical features in the modified failure mode and effects analysis are then extracted and included in the relevant Ishikawa diagram. This article illustrates an application of engineering methodology in medicine, and it sows the seeds of potential cross-pollination between engineering and medicine. Establishing a modified failure mode and effects analysis can be a teamwork project or self-directed learning process, or a mix of both. Modified failure mode and effects analysis can be deployed to obtain inputs for an Ishikawa diagram which in turn can be used to enhance clinical experiences and clinical reasoning skills for clinicians, medical educators, and students.

The Topographic Data Deluge - Collecting and Maintaining Data in a 21ST Century Mapping Agency

NASA Astrophysics Data System (ADS)

Holland, D. A.; Pook, C.; Capstick, D.; Hemmings, A.

2016-06-01

In the last few years, the number of sensors and data collection systems available to a mapping agency has grown considerably. In the field, in addition to total stations measuring position, angles and distances, the surveyor can choose from hand-held GPS devices, multi-lens imaging systems or laser scanners, which may be integrated with a laptop or tablet to capture topographic data directly in the field. These systems are joined by mobile mapping solutions, mounted on large or small vehicles, or sometimes even on a backpack carried by a surveyor walking around a site. Such systems allow the raw data to be collected rapidly in the field, while the interpretation of the data can be performed back in the office at a later date. In the air, large format digital cameras and airborne lidar sensors are being augmented with oblique camera systems, taking multiple views at each camera position and being used to create more realistic 3D city models. Lower down in the atmosphere, Unmanned Aerial Vehicles (or Remotely Piloted Aircraft Systems) have suddenly become ubiquitous. Hundreds of small companies have sprung up, providing images from UAVs using ever more capable consumer cameras. It is now easy to buy a 42 megapixel camera off the shelf at the local camera shop, and Canon recently announced that they are developing a 250 megapixel sensor for the consumer market. While these sensors may not yet rival the metric cameras used by today's photogrammetrists, the rapid developments in sensor technology could eventually lead to the commoditization of high-resolution camera systems. With data streaming in from so many sources, the main issue for a mapping agency is how to interpret, store and update the data in such a way as to enable the creation and maintenance of the end product. This might be a topographic map, ortho-image or a digital surface model today, but soon it is just as likely to be a 3D point cloud, textured 3D mesh, 3D city model, or Building Information Model (BIM) with all the data interpretation and modelling that entails. In this paper, we describe research/investigations into the developing technologies and outline the findings for a National Mapping Agency (NMA). We also look at the challenges that these new data collection systems will bring to an NMA, and suggest ways that we may work to meet these challenges and deliver the products desired by our users.

Time-Frequency Analysis of the Dispersion of Lamb Modes

NASA Technical Reports Server (NTRS)

Prosser, W. H.; Seale, Michael D.; Smith, Barry T.

1999-01-01

Accurate knowledge of the velocity dispersion of Lamb modes is important for ultrasonic nondestructive evaluation methods used in detecting and locating flaws in thin plates and in determining their elastic stiffness coefficients. Lamb mode dispersion is also important in the acoustic emission technique for accurately triangulating the location of emissions in thin plates. In this research, the ability to characterize Lamb mode dispersion through a time-frequency analysis (the pseudo Wigner-Ville distribution) was demonstrated. A major advantage of time-frequency methods is the ability to analyze acoustic signals containing multiple propagation modes, which overlap and superimpose in the time domain signal. By combining time-frequency analysis with a broadband acoustic excitation source, the dispersion of multiple Lamb modes over a wide frequency range can be determined from as little as a single measurement. In addition, the technique provides a direct measurement of the group velocity dispersion. The technique was first demonstrated in the analysis of a simulated waveform in an aluminum plate in which the Lamb mode dispersion was well known. Portions of the dispersion curves of the A(sub 0), A(sub 1), S(sub 0), and S(sub 2)Lamb modes were obtained from this one waveform. The technique was also applied for the analysis of experimental waveforms from a unidirectional graphite/epoxy composite plate. Measurements were made both along, and perpendicular to the fiber direction. In this case, the signals contained only the lowest order symmetric and antisymmetric modes. A least squares fit of the results from several source to detector distances was used. Theoretical dispersion curves were calculated and are shown to be in good agreement with experimental results.

Real English Project Report.

ERIC Educational Resources Information Center

Cautin, Harvey; Regan, Edward

Requirements are discussed for an information retrieval language that enables users to employ natural language sentences in interaction with computer-stored files. Anticipated modes of operation of the system are outlined. These are: the search mode, the dictionary mode, the tables mode, and the statistical mode. Analysis of sample sentences…

Design and analysis of large-core single-mode windmill single crystal sapphire optical fiber

DOE PAGES

Cheng, Yujie; Hill, Cary; Liu, Bo; ...

2016-06-01

We present a large-core single-mode “windmill” single crystal sapphire optical fiber (SCSF) design, which exhibits single-mode operation by stripping off the higher-order modes (HOMs) while maintaining the fundamental mode. The “windmill” SCSF design was analyzed using the finite element analysis method, in which all the HOMs are leaky. The numerical simulation results show single-mode operation in the spectral range from 0.4 to 2 μm in the windmill SCSF, with an effective core diameter as large as 14 μm. Such fiber is expected to improve the performance of many of the current sapphire fiber optic sensor structures.

Cross-mode bioelectrical impedance analysis in a standing position for estimating fat-free mass validated against dual-energy x-ray absorptiometry.

PubMed

Huang, Ai-Chun; Chen, Yu-Yawn; Chuang, Chih-Lin; Chiang, Li-Ming; Lu, Hsueh-Kuan; Lin, Hung-Chi; Chen, Kuen-Tsann; Hsiao, An-Chi; Hsieh, Kuen-Chang

2015-11-01

Bioelectrical impedance analysis (BIA) is commonly used to assess body composition. Cross-mode (left hand to right foot, Z(CR)) BIA presumably uses the longest current path in the human body, which may generate better results when estimating fat-free mass (FFM). We compared the cross-mode with the hand-to-foot mode (right hand to right foot, Z(HF)) using dual-energy x-ray absorptiometry (DXA) as the reference. We hypothesized that when comparing anthropometric parameters using stepwise regression analysis, the impedance value from the cross-mode analysis would have better prediction accuracy than that from the hand-to-foot mode analysis. We studied 264 men and 232 women (mean ages, 32.19 ± 14.95 and 34.51 ± 14.96 years, respectively; mean body mass indexes, 24.54 ± 3.74 and 23.44 ± 4.61 kg/m2, respectively). The DXA-measured FFMs in men and women were 58.85 ± 8.15 and 40.48 ± 5.64 kg, respectively. Multiple stepwise linear regression analyses were performed to construct sex-specific FFM equations. The correlations of FFM measured by DXA vs. FFM from hand-to-foot mode and estimated FFM by cross-mode were 0.85 and 0.86 in women, with standard errors of estimate of 2.96 and 2.92 kg, respectively. In men, they were 0.91 and 0.91, with standard errors of the estimates of 3.34 and 3.48 kg, respectively. Bland-Altman plots showed limits of agreement of -6.78 to 6.78 kg for FFM from hand-to-foot mode and -7.06 to 7.06 kg for estimated FFM by cross-mode for men, and -5.91 to 5.91 and -5.84 to 5.84 kg, respectively, for women. Paired t tests showed no significant differences between the 2 modes (P > .05). Hence, cross-mode BIA appears to represent a reasonable and practical application for assessing FFM in Chinese populations. Copyright © 2015 Elsevier Inc. All rights reserved.

Bicoherence Analysis of Electrostatic Interchange Mode Coupling in a Turbulent Laboratory Magnetosphere

NASA Astrophysics Data System (ADS)

Abler, M. C.; Saperstein, A.; Yan, J. R.; Mauel, M. E.

2017-10-01

Plasmas confined by a strong dipole field exhibit interchange and entropy mode turbulence, which previous experiments have shown respond locally to active feedback. On the Collisionless Terrella Experiment (CTX), this turbulence is characterized by low frequency, low order, quasi-coherent modes with complex spectral dynamics. We apply bicoherence analysis to study nonlinear phase coupling in a variety of scenarios. First, we study the self-interaction of the naturally occurring interchange turbulence; this analysis is then expanded to include the effects of driven modes in the frequency range of the background turbulent oscillations. Initial measurements of coupling coefficients are presented in both cases. Driven low frequency interchange modes are observed to generate multiple harmonics which persist throughout the plasma, becoming weaker as they propagate away from the actuator in the direction of the electron magnetic drift. Future work is also discussed, including application of wavelet bicoherence analysis, excitation of interchange modes at multiple frequencies, and applications to planetary magnetospheres. Supported by NSF-DOE Partnership for Plasma Science Grants DOE-DE-FG02-00ER54585.

Finite-element analysis of vibrational modes in piezoelectric ceramic disks.

PubMed

Kunkel, H A; Locke, S; Pikeroen, B

1990-01-01

The natural vibrational modes of axially symmetric piezoelectric ceramic disks have been calculated by the finite-element method. The disks are of the type used as active elements in compressional wave ultrasonic transducers, and are electrically polarized in thickness with full electrodes on the disk's major faces. To optimize disk geometry for ultrasonic transducer application, the dependence of the vibrational modes on the disk diameter-to-thickness ratio for ratios from 0.2 (a tall cylinder) to 10.0 (a thin disk) has been studied. Series and parallel resonance frequencies for each of the modes are determined through an eigenfrequency analysis, and effective electromechanical coupling coefficients are calculated. The modal displacement fields in the disk are calculated to determine the physical nature of each mode. An analysis of the complete spectrum of piezoelectrically active modes as a function of diameter-thickness ratio is presented for the ceramic PZT-5H, including and identification of radial, edge, length expander, thickness shear, and thickness extensional vibrations. From this analysis, optimal diameter-to-thickness ratios for good transducer performance are discussed.

Analysis on the mechanism of pulse-shortening in an X-band triaxial klystron amplifier due to the asymmetric mode competition

NASA Astrophysics Data System (ADS)

Qi, Zumin; Zhang, Jun; Xie, Yongjie; Zhang, Yi; Wang, Zehua; Zhou, Xiaofeng; Zhu, Jianhui; Zi, Yanyong; Zhong, Huihuang

2016-12-01

Asymmetric mode competitions are observed in the design of an X-band triaxial klystron amplifier with an asymmetric input cavity, and the generation mechanism of the asymmetric mode competition is analyzed in the paper. The results indicate that the asymmetric modes are excited in the buncher cavity. The asymmetric mode (coaxial TM612 mode) in the buncher cavity with the highest shunt impedance can start up first among the asymmetric modes with negative beam loading conductance. The coupling of the corresponding coaxial TE mode between the buncher and input cavity exacerbates the start oscillation of the asymmetric mode competition. The rationality of the analysis is demonstrated by cutting off the propagation of the corresponding coaxial TE modes between the buncher cavity and the input cavity, and the asymmetric mode competitions are thoroughly suppressed by specially designed reflectors and lossy material. In simulation, a microwave with a power of 1.28 GW and a frequency of 9.375 GHz is generated, and the extraction efficiency and the gain are 34.5% and 41.5 dB, respectively.

Analysis and Prediction of Sea Ice Evolution using Koopman Mode Decomposition Techniques

DTIC Science & Technology

2018-04-30

Title: Analysis and Prediction of Sea Ice Evolution using Koopman Mode Decomposition Techniques Subject: Monthly Progress Report Period of...Resources: N/A TOTAL: $18,687 2 TECHNICAL STATUS REPORT Abstract The program goal is analysis of sea ice dynamical behavior using Koopman Mode Decompo...sition (KMD) techniques. The work in the program’s first month consisted of improvements to data processing code, inclusion of additional arctic sea ice

Waveguides for performing spectroscopy with confined effective observation volumes

DOEpatents

Levene, Michael J.; Korlach, Jonas; Turner, Stephen W.; Craighead, Harold G.; Webb, Watt W.

2006-03-14

The present invention is directed to a method and an apparatus for analysis of an analyte. The method involves providing a zero-mode waveguide which includes a cladding surrounding a core where the cladding is configured to preclude propagation of electromagnetic energy of a frequency less than a cutoff frequency longitudinally through the core of the zero-mode waveguide. The analyte is positioned in the core of the zero-mode waveguide and is then subjected, in the core of the zero-mode waveguide, to activating electromagnetic radiation of a frequency less than the cut-off frequency under conditions effective to permit analysis of the analyte in an effective observation volume which is more compact than if the analysis were carried out in the absence of the zero-mode waveguide.

An Innovative Structural Mode Selection Methodology: Application for the X-33 Launch Vehicle Finite Element Model

NASA Technical Reports Server (NTRS)

Hidalgo, Homero, Jr.

2000-01-01

An innovative methodology for determining structural target mode selection and mode selection based on a specific criterion is presented. An effective approach to single out modes which interact with specific locations on a structure has been developed for the X-33 Launch Vehicle Finite Element Model (FEM). We presented Root-Sum-Square (RSS) displacement method computes resultant modal displacement for each mode at selected degrees of freedom (DOF) and sorts to locate modes with highest values. This method was used to determine modes, which most influenced specific locations/points on the X-33 flight vehicle such as avionics control components, aero-surface control actuators, propellant valve and engine points for use in flight control stability analysis and for flight POGO stability analysis. Additionally, the modal RSS method allows for primary or global target vehicle modes to also be identified in an accurate and efficient manner.

List mode multichannel analyzer

DOEpatents

Archer, Daniel E [Livermore, CA; Luke, S John [Pleasanton, CA; Mauger, G Joseph [Livermore, CA; Riot, Vincent J [Berkeley, CA; Knapp, David A [Livermore, CA

2007-08-07

A digital list mode multichannel analyzer (MCA) built around a programmable FPGA device for onboard data analysis and on-the-fly modification of system detection/operating parameters, and capable of collecting and processing data in very small time bins (<1 millisecond) when used in histogramming mode, or in list mode as a list mode MCA.

Analysis of the vortices in the inner flow of reversible pump turbine with the new omega vortex identification method

NASA Astrophysics Data System (ADS)

Zhang, Yu-ning; Liu, Kai-hua; Li, Jin-wei; Xian, Hai-zhen; Du, Xiao-ze

2018-05-01

Reversible pump turbines are widely employed in the pumped hydro energy storage power plants. The frequent shifts among various operational modes for the reversible pump turbines pose various instability problems, e.g., the strong pressure fluctuation, the shaft swing, and the impeller damage. The instability is related to the vortices generated in the channels of the reversible pump turbines in the generating mode. In the present paper, a new omega vortex identification method is applied to the vortex analysis of the reversible pump turbines. The main advantage of the adopted algorithm is that it is physically independent of the selected values for the vortex identification in different working modes. Both weak and strong vortices can be identified by setting the same omega value in the whole passage of the reversible pump turbine. Five typical modes (turbine mode, runaway mode, turbine brake mode, zero-flow-rate mode and reverse pump mode) at several typical guide vane openings are selected for the analysis and comparisons. The differences between various modes and different guide vane openings are compared both qualitatively in terms of the vortex distributions and quantitatively in terms of the areas of the vortices in the reversible pump turbines. Our findings indicate that the new omega method could be successfully applied to the vortex identification in the reversible pump turbines.

Analysis of Dual Rotating Rake Data from the NASA Glenn Advanced Noise Control Fan Duct with Artificial Sources

NASA Technical Reports Server (NTRS)

Dahl, Milo D.; Sutliff, Daniel L.

2014-01-01

The Rotating Rake mode measurement system was designed to measure acoustic duct modes generated by a fan stage. Initially, the mode amplitudes and phases were quantified from a single rake measurement at one axial location. To directly measure the modes propagating in both directions within a duct, a second rake was mounted to the rotating system with an offset in both the axial and the azimuthal directions. The rotating rake data analysis technique was then extended to include the data measured by the second rake. The analysis resulted in a set of circumferential mode levels at each of the two rake microphone locations. Radial basis functions were then least-squares fit to this data to obtain the radial mode amplitudes for the modes propagating in both directions within the duct. Validation experiments have been conducted using artificial acoustic sources. Results are shown for the measurement of the standing waves in the duct from sound generated by one and two acoustic sources that are separated into the component modes propagating in both directions within the duct. Measured reflection coefficients from the open end of the duct are compared to analytical predictions.

Nonlinear analysis of generalized cross-field current instability

NASA Technical Reports Server (NTRS)

Yoon, Peter H.; Lui, Anthony T. Y.

1993-01-01

Analysis of the generalized cross-field current instability is carried out in which cross-field drift of both the ions and electrons and their temperatures are permitted to vary in time. The unstable mode under consideration is the electromagnetic generalization of the classical modified-two-stream instability. The generalized instability is made of the modified-two-stream and ion-Weibel modes. The relative importance of the features associated with the ion-Weibel mode and those of the modified-two-stream mode is assessed. Specific applications are made to the Earth's neutral sheet prior to substorm onset and to the Earth's bow shock. The numerical solution indicates that the ion-Weibel mode dominates in the Earth's neutral sheet environment. In contrast, the situation for the bow shock is dominated by the modified-two-stream mode. Notable differences are found between the present calculation and previous results on ion-Weibel mode which restrict the analysis to only parallel propagating waves. However, in the case of Earth's bow shock for which the ion-Weibel mode plays no important role, the inclusion of the electromagnetic ion response is found to differ little from the previous results which treats ions responding only to the electrostatic component of the excited waves.

Dual Rotating Rake Measurements of Higher-Order Duct Modes: Validation Using Experimental and Numerical Data

NASA Technical Reports Server (NTRS)

Dahl, Milo D.; Hixon, Duane R.; Sutliff, Daniel L.

2018-01-01

A rotating rake mode measurement system was designed to measure acoustic duct modes generated by a fan stage. After analysis of the measured data, the mode coefficient amplitudes and phases were quantified. Early studies using this system found that mode power levels computed from rotating rake measured data would agree with the far-field power levels. However, this agreement required that the sound from the noise sources within the duct propagated outward from the duct exit without reflection and previous studies suggested conditions could exist where significant reflections could occur. This paper shows that mounting a second rake to the rotating system, with an offset in both the axial and the azimuthal directions, measures the data necessary to determine the modes propagating in both directions within a duct. The rotating rake data analysis technique was extended to include the data measured by the second rake. The analysis resulted in a set of circumferential mode coefficients at each of the two rake microphone locations. Radial basis functions were then least-squares fit to this data to obtain the radial mode coefficients for the modes propagating in both directions within the duct while accounting for the presence of evanescent modes. The validation of the dual-rotating-rake measurements was conducted using data from a combination of experiments and numerical calculations to compute reflection coefficients and other mode coefficient ratios. Compared to results from analytical and numerical computations, the results from dual-rotating-rake measured data followed the expected trends when frequency, mode number, and duct termination geometry were changed.

A NASTRAN primer for the analysis of rotating flexible blades

NASA Technical Reports Server (NTRS)

Lawrence, Charles; Aiello, Robert A.; Ernst, Michael A.; Mcgee, Oliver G.

1987-01-01

This primer provides documentation for using MSC NASTRAN in analyzing rotating flexible blades. The analysis of these blades includes geometrically nonlinear (large displacement) analysis under centrifugal loading, and frequency and mode shape (normal modes) determination. The geometrically nonlinear analysis using NASTRAN Solution sequence 64 is discussed along with the determination of frequencies and mode shapes using Solution Sequence 63. A sample problem with the complete NASTRAN input data is included. Items unique to rotating blade analyses, such as setting angle and centrifugal softening effects are emphasized.

Cycles till failure of silver-zinc cells with competing failure modes - Preliminary data analysis

NASA Technical Reports Server (NTRS)

Sidik, S. M.; Leibecki, H. F.; Bozek, J. M.

1980-01-01

The data analysis of cycles to failure of silver-zinc electrochemical cells with competing failure modes is presented. The test ran 129 cells through charge-discharge cycles until failure; preliminary data analysis consisted of response surface estimate of life. Batteries fail through low voltage condition and an internal shorting condition; a competing failure modes analysis was made using maximum likelihood estimation for the extreme value life distribution. Extensive residual plotting and probability plotting were used to verify data quality and selection of model.

Shuttle structural dynamics characteristics: The analysis and verification

NASA Technical Reports Server (NTRS)

Modlin, C. T., Jr.; Zupp, G. A., Jr.

1985-01-01

The space shuttle introduced a new dimension in the complexity of the structural dynamics of a space vehicle. The four-body configuration exhibited structural frequencies as low as 2 hertz with a model density on the order of 10 modes per hertz. In the verification process, certain mode shapes and frequencies were identified by the users as more important than others and, as such, the test objectives were oriented toward experimentally extracting those modes and frequencies for analysis and test correlation purposes. To provide the necessary experimental data, a series of ground vibration tests (GVT's) was conducted using test articles ranging from the 1/4-scale structural replica of the space shuttle to the full-scale vehicle. The vibration test and analysis program revealed that the mode shapes and frequency correlations below 10 hertz were good. The quality of correlation of modes between 10 and 20 hertz ranged from good to fair and that of modes above 20 hertz ranged from poor to good. Since the most important modes, based on user preference, were below 10 hertz, it was judged that the shuttle structural dynamic models were adequate for flight certifications.

Dynamics Evolution Investigation of Mack Mode Instability in a Hypersonic Boundary Layer by Bicoherence Spectrum Analysis

NASA Astrophysics Data System (ADS)

Han, Jian; Jiang, Nan

2012-07-01

The instability of a hypersonic boundary layer on a cone is investigated by bicoherence spectrum analysis. The experiment is conducted at Mach number 6 in a hypersonic wind tunnel. The time series signals of instantaneous fluctuating surface-thermal-flux are measured by Pt-thin-film thermocouple temperature sensors mounted at 28 stations on the cone surface along streamwise direction to investigate the development of the unstable disturbances. The bicoherence spectrum analysis based on wavelet transform is employed to investigate the nonlinear interactions of the instability of Mack modes in hypersonic laminar boundary layer transition. The results show that wavelet bicoherence is a powerful tool in studying the unstable mode nonlinear interaction of hypersonic laminar-turbulent transition. The first mode instability gives rise to frequency shifts to higher unstable modes at the early stage of hypersonic laminar-turbulent transition. The modulations subsequently lead to the second mode instability occurrence. The second mode instability governs the last stage of instability and final breakdown to turbulence with multi-scale disturbances growth.

Therapeutic mode preferences and associated factors among Norwegian undergraduate occupational therapy students: A cross-sectional exploratory study.

PubMed

Yazdani, Farzaneh; Carstensen, Tove; Bonsaksen, Tore

2017-03-01

The Intentional Relationship Model is specifically focused on the relational aspect of therapy. The model describes six therapeutic modes; these represent different types of interaction for the therapist. However, preferences for therapeutic mode use are under researched. This study aims to describe preferences for therapeutic modes in undergraduate occupational therapy students, as well as to explore factors associated to each of the therapeutic modes. A sample of 96 occupational therapy students, based at two different Norwegian universities, participated in the study. They completed the Norwegian Self-Assessment of Modes Questionnaire along with sociodemographic information. Descriptive analysis, bivariate correlation and linear regression analysis were employed. The problem-solving mode was most frequently endorsed. There were generally weak associations between the variables, but female sex and being a student in the education program in Trondheim were associated with higher preference for collaboration. There is diversity in students' preferences for the modes, but the problem-solving mode was the most preferred. Students need to be aware of the mode they feel more comfortable with and make sure they use modes that fit with the specific client. The occupational therapy education programs need to incorporate raising awareness about therapeutic modes.

Dynamic fracture mechanics analysis for an edge delamination crack

NASA Technical Reports Server (NTRS)

Rizzi, Stephen A.; Doyle, James F.

1994-01-01

A global/local analysis is applied to the problem of a panel with an edge delamination crack subject to an impulse loading to ascertain the dynamic J integral. The approach uses the spectral element method to obtain the global dynamic response and local resultants to obtain the J integral. The variation of J integral along the crack front is shown. The crack behavior is mixed mode (Mode 2 and Mode 3), but is dominated by the Mode 2 behavior.

Investigation of Association Between Hip Osteoarthritis Susceptibility Loci and Radiographic Proximal Femur Shape

PubMed Central

Thiagarajah, Shankar; Wilkinson, J. Mark; Panoutsopoulou, Kalliope; Day‐Williams, Aaron G.; Cootes, Timothy F.; Wallis, Gillian A.; Loughlin, John; Arden, Nigel; Birrell, Fraser; Carr, Andrew; Chapman, Kay; Deloukas, Panos; Doherty, Michael; McCaskie, Andrew; Ollier, William E. R.; Rai, Ashok; Ralston, Stuart H.; Spector, Timothy D.; Valdes, Ana M.; Wallis, Gillian A.; Mark Wilkinson, J.; Zeggini, Eleftheria

2015-01-01

Objective To test whether previously reported hip morphology or osteoarthritis (OA) susceptibility loci are associated with proximal femur shape as represented by statistical shape model (SSM) modes and as univariate or multivariate quantitative traits. Methods We used pelvic radiographs and genotype data from 929 subjects with unilateral hip OA who had been recruited previously for the Arthritis Research UK Osteoarthritis Genetics Consortium genome‐wide association study. We built 3 SSMs capturing the shape variation of the OA‐unaffected proximal femur in the entire mixed‐sex cohort and for male/female‐stratified cohorts. We selected 41 candidate single‐nucleotide polymorphisms (SNPs) previously reported as being associated with hip morphology (for replication analysis) or OA (for discovery analysis) and for which genotype data were available. We performed 2 types of analysis for genotype–phenotype associations between these SNPs and the modes of the SSMs: 1) a univariate analysis using individual SSM modes and 2) a multivariate analysis using combinations of SSM modes. Results The univariate analysis identified association between rs4836732 (within the ASTN2 gene) and mode 5 of the female SSM (P = 0.0016) and between rs6976 (within the GLT8D1 gene) and mode 7 of the mixed‐sex SSM (P = 0.0003). The multivariate analysis identified association between rs5009270 (near the IFRD1 gene) and a combination of modes 3, 4, and 9 of the mixed‐sex SSM (P = 0.0004). Evidence of associations remained significant following adjustment for multiple testing. All 3 SNPs had previously been associated with hip OA. Conclusion These de novo findings suggest that rs4836732, rs6976, and rs5009270 may contribute to hip OA susceptibility by altering proximal femur shape. PMID:25939412

Asymptotic modal analysis and statistical energy analysis

NASA Technical Reports Server (NTRS)

Dowell, Earl H.

1992-01-01

Asymptotic Modal Analysis (AMA) is a method which is used to model linear dynamical systems with many participating modes. The AMA method was originally developed to show the relationship between statistical energy analysis (SEA) and classical modal analysis (CMA). In the limit of a large number of modes of a vibrating system, the classical modal analysis result can be shown to be equivalent to the statistical energy analysis result. As the CMA result evolves into the SEA result, a number of systematic assumptions are made. Most of these assumptions are based upon the supposition that the number of modes approaches infinity. It is for this reason that the term 'asymptotic' is used. AMA is the asymptotic result of taking the limit of CMA as the number of modes approaches infinity. AMA refers to any of the intermediate results between CMA and SEA, as well as the SEA result which is derived from CMA. The main advantage of the AMA method is that individual modal characteristics are not required in the model or computations. By contrast, CMA requires that each modal parameter be evaluated at each frequency. In the latter, contributions from each mode are computed and the final answer is obtained by summing over all the modes in the particular band of interest. AMA evaluates modal parameters only at their center frequency and does not sum the individual contributions from each mode in order to obtain a final result. The method is similar to SEA in this respect. However, SEA is only capable of obtaining spatial averages or means, as it is a statistical method. Since AMA is systematically derived from CMA, it can obtain local spatial information as well.

Theoretical analysis of a ceramic plate thickness-shear mode piezoelectric transformer.

PubMed

Xu, Limei; Zhang, Ying; Fan, Hui; Hu, Junhui; Yang, Jiashi

2009-03-01

We perform a theoretical analysis on a ceramic plate piezoelectric transformer operating with thickness-shear modes. Mindlin's first-order theory of piezoelectric plates is employed, and a forced vibration solution is obtained. Transforming ratio, resonant frequencies, and vibration mode shapes are calculated, and the effects of plate thickness and electrode dimension are examined.

Design of a dual-mode electrochemical measurement and analysis system.

PubMed

Yang, Jr-Fu; Wei, Chia-Ling; Wu, Jian-Fu; Liu, Bin-Da

2013-01-01

A dual-mode electrochemical measurement and analysis system is proposed. This system includes a dual-mode chip, which was designed and fabricated by using TSMC 0.35 µm 3.3 V/5 V 2P4M mixed-signal CMOS process. Two electrochemical measurement and analysis methods, chronopotentiometry and voltammetry, can be performed by using the proposed chip and system. The proposed chip and system are verified successfully by performing voltammetry and chronopotentiometry on solutions.

Aeroelastic Stability of Idling Wind Turbines

NASA Astrophysics Data System (ADS)

Wang, Kai; Riziotis, Vasilis A.; Voutsinas, Spyros G.

2016-09-01

Wind turbine rotors in idling operation mode can experience high angles of attack, within the post stall region that are capable of triggering stall-induced vibrations. In the present paper rotor stability in slow idling operation is assessed on the basis of non-linear time domain and linear eigenvalue analysis. Analysis is performed for a 10 MW conceptual wind turbine designed by DTU. First the flow conditions that are likely to favour stall induced instabilities are identified through non-linear time domain aeroelastic analysis. Next, for the above specified conditions, eigenvalue stability simulations are performed aiming at identifying the low damped modes of the turbine. Finally the results of the eigenvalue analysis are evaluated through computations of the work of the aerodynamic forces by imposing harmonic vibrations following the shape and frequency of the various modes. Eigenvalue analysis indicates that the asymmetric and symmetric out-of-plane modes have the lowest damping. The results of the eigenvalue analysis agree well with those of the time domain analysis.

Meta-analysis of the role of delivery mode in postpartum depression (Iran 1997-2011)

PubMed Central

Bahadoran, Parvin; Oreizi, Hamid Reza; Safari, Saeideh

2014-01-01

Background: Postpartum period is the riskiest time for mood disorders and psychosis. Postpartum depression is the most important mood disorder after delivery, which can be accompanied by mother-child and family relationship disorders. Meta-analysis with the integration of research results demonstrates to investigate the association between the mode of delivery and postpartum depression. Materials and Methods: This meta-analysis uses the Rosenthal and Robin approach. For this purpose, 18 studies which were acceptable in terms of methodology were selected and meta-analysis was conducted on them. Research instrument was a checklist of meta-analysis. After summarizing the results of the studies, effect sizes were calculated manually and combined based on meta-analysis method. Results: The findings showed that the amount of effect size (in term of Cohen d) of delivery mode on postpartum depression was 0/30 (P < 0.001). Conclusion: Delivery mode on maternal mental health is assessed medium. Meta analysis also indicates moderator variables role, and researcher must focus in these variables. PMID:25540791

Comparison of Collisional and Electron-Based Dissociation Modes for Middle-Down Analysis of Multiply Glycosylated Peptides

NASA Astrophysics Data System (ADS)

Khatri, Kshitij; Pu, Yi; Klein, Joshua A.; Wei, Juan; Costello, Catherine E.; Lin, Cheng; Zaia, Joseph

2018-04-01

Analysis of singly glycosylated peptides has evolved to a point where large-scale LC-MS analyses can be performed at almost the same scale as proteomics experiments. While collisionally activated dissociation (CAD) remains the mainstay of bottom-up analyses, it performs poorly for the middle-down analysis of multiply glycosylated peptides. With improvements in instrumentation, electron-activated dissociation (ExD) modes are becoming increasingly prevalent for proteomics experiments and for the analysis of fragile modifications such as glycosylation. While these methods have been applied for glycopeptide analysis in isolated studies, an organized effort to compare their efficiencies, particularly for analysis of multiply glycosylated peptides (termed here middle-down glycoproteomics), has not been made. We therefore compared the performance of different ExD modes for middle-down glycopeptide analyses. We identified key features among the different dissociation modes and show that increased electron energy and supplemental activation provide the most useful data for middle-down glycopeptide analysis. [Figure not available: see fulltext.

Effect of heterogeneity and assumed mode of inheritance on lod scores.

PubMed

Durner, M; Greenberg, D A

1992-02-01

Heterogeneity is a major factor in many common, complex diseases and can confound linkage analysis. Using computer-simulated heterogeneous data we tested what effect unlinked families have on a linkage analysis when heterogeneity is not taken into account. We created 60 data sets of 40 nuclear families each with different proportions of linked and unlinked families and with different modes of inheritance. The ascertainment probability was 0.05, the disease had a penetrance of 0.6, and the recombination fraction for the linked families was zero. For the analysis we used a variety of assumed modes of inheritance and penetrances. Under these conditions we looked at the effect of the unlinked families on the lod score, the evaluation of the mode of inheritance, and the estimate of penetrance and of the recombination fraction in the linked families. 1. When the analysis was done under the correct mode of inheritance for the linked families, we found that the mode of inheritance of the unlinked families had minimal influence on the highest maximum lod score (MMLS) (i.e., we maximized the maximum lod score with respect to penetrance). Adding sporadic families decreased the MMLS less than adding recessive or dominant unlinked families. 2. The mixtures of dominant linked families with unlinked families always led to a higher MMLS when analyzed under the correct (dominant) mode of inheritance than when analyzed under the incorrect mode of inheritance. In the mixtures with recessive linked families, assuming the correct mode of inheritance generally led to a higher MMLS, but we observed broad variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Hybrid PD and effective multi-mode positive position feedback control for slewing and vibration suppression of a smart flexible manipulator

NASA Astrophysics Data System (ADS)

Lou, Jun-qiang; Wei, Yan-ding; Yang, Yi-ling; Xie, Feng-ran

2015-03-01

A hybrid control strategy for slewing and vibration suppression of a smart flexible manipulator is presented in this paper. It consists of a proportional derivative controller to realize motion control, and an effective multi-mode positive position feedback (EMPPF) controller to suppress the multi-mode vibration. Rather than treat each mode equally as the standard multi-mode PPF, the essence of the EMPPF is that control forces of different modes are applied according to the mode parameters of the respective modes, so the vibration modes with less vibration energy receive fewer control forces. Stability conditions for the close loop system are established through stability analysis. Optimal parameters of the EMPPF controller are obtained using the method of root locus analysis. The performance of the proposed strategy is demonstrated by simulation and experiments. Experimental results show that the first two vibration modes of the manipulator are effectively suppressed. The setting time of the setup descends approximately 55%, reaching 3.12 s from 5.67 s.

Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model.

PubMed

Archer, Rachel; Tappenden, Paul; Ren, Shijie; Martyn-St James, Marrissa; Harvey, Rebecca; Basarir, Hasan; Stevens, John; Carroll, Christopher; Cantrell, Anna; Lobo, Alan; Hoque, Sami

2016-05-01

Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. UC can have a considerable impact on patients' quality of life. The burden for the NHS is substantial. To evaluate the clinical effectiveness and safety of interventions, to evaluate the incremental cost-effectiveness of all interventions and comparators (including medical and surgical options), to estimate the expected net budget impact of each intervention, and to identify key research priorities. Peer-reviewed publications, European Public Assessment Reports and manufacturers' submissions. The following databases were searched from inception to December 2013 for clinical effectiveness searches and from inception to January 2014 for cost-effectiveness searches for published and unpublished research evidence: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and NHS Economic Evaluation Database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science and Bioscience Information Service Previews. The US Food and Drug Administration website and the European Medicines Agency website were also searched, as were research registers, conference proceedings and key journals. A systematic review [including network meta-analysis (NMA)] was conducted to evaluate the clinical effectiveness and safety of named interventions. The health economic analysis included a review of published economic evaluations and the development of a de novo model. Ten randomised controlled trials were included in the systematic review. The trials suggest that adult patients receiving infliximab (IFX) [Remicade(®), Merck Sharp & Dohme Ltd (MSD)], adalimumab (ADA) (Humira(®), AbbVie) or golimumab (GOL) (Simponi(®), MSD) were more likely to achieve clinical response and remission than those receiving placebo (PBO). Hospitalisation data were limited, but suggested more favourable outcomes for ADA- and IFX-treated patients. Data on the use of surgical intervention were sparse, with a potential benefit for intervention-treated patients. Data were available from one trial to support the use of IFX in paediatric patients. Safety issues identified included serious infections, malignancies and administration site reactions. Based on the NMA, in the induction phase, all biological treatments were associated with statistically significant beneficial effects relative to PBO, with the greatest effect associated with IFX. For patients in response following induction, all treatments except ADA and GOL 100 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although these were not significant. The greatest effects at 8-32 and 32-52 weeks were associated with 100 mg of GOL and 5 mg/kg of IFX, respectively. For patients in remission following induction, all treatments except ADA at 8-32 weeks and GOL 50 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although only the effect of ADA at 32-52 weeks was significant. The greatest effects were associated with GOL (at 8-32 weeks) and ADA (at 32-52 weeks). The economic analysis suggests that colectomy is expected to dominate drug therapies, but for some patients, colectomy may not be considered acceptable. In circumstances in which only drug options are considered, IFX and GOL are expected to be ruled out because of dominance, while the incremental cost-effectiveness ratio for ADA versus conventional treatment is approximately £50,300 per QALY gained. The health economic model is subject to several limitations: uncertainty associated with extrapolating trial data over a lifetime horizon, the model does not consider explicit sequential pathways of non-biological treatments, and evidence relating to complications of colectomy was identified through consideration of approaches used within previous models rather than a full systematic review. Adult patients receiving IFX, ADA or GOL were more likely to achieve clinical response and remission than those receiving PBO. Further data are required to conclusively demonstrate the effect of interventions on hospitalisation and surgical outcomes. The economic analysis indicates that colectomy is expected to dominate medical treatments for moderate to severe UC. This study is registered as PROSPERO CRD42013006883. The National Institute for Health Research Health Technology Assessment programme.

Independent Orbiter Assessment (IOA): Analysis of the active thermal control subsystem

NASA Technical Reports Server (NTRS)

Sinclair, S. K.; Parkman, W. E.

1987-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical (PCIs) items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The independent analysis results corresponding to the Orbiter Active Thermal Control Subsystem (ATCS) are documented. The major purpose of the ATCS is to remove the heat, generated during normal Shuttle operations from the Orbiter systems and subsystems. The four major components of the ATCS contributing to the heat removal are: Freon Coolant Loops; Radiator and Flow Control Assembly; Flash Evaporator System; and Ammonia Boiler System. In order to perform the analysis, the IOA process utilized available ATCS hardware drawings and schematics for defining hardware assemblies, components, and hardware items. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode. Of the 310 failure modes analyzed, 101 were determined to be PCIs.

Independent Orbiter Assessment (IOA): Analysis of the hydraulics/water spray boiler subsystem

NASA Technical Reports Server (NTRS)

Duval, J. D.; Davidson, W. R.; Parkman, William E.

1986-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items (PCIs). To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results for the Orbiter Hydraulics/Water Spray Boiler Subsystem. The hydraulic system provides hydraulic power to gimbal the main engines, actuate the main engine propellant control valves, move the aerodynamic flight control surfaces, lower the landing gear, apply wheel brakes, steer the nosewheel, and dampen the external tank (ET) separation. Each hydraulic system has an associated water spray boiler which is used to cool the hydraulic fluid and APU lubricating oil. The IOA analysis process utilized available HYD/WSB hardware drawings, schematics and documents for defining hardware assemblies, components, and hardware items. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode. Of the 430 failure modes analyzed, 166 were determined to be PCIs.

Independent Orbiter Assessment (IOA): Analysis of the remote manipulator system

NASA Technical Reports Server (NTRS)

Tangorra, F.; Grasmeder, R. F.; Montgomery, A. D.

1987-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items (PCIs). To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The independent analysis results for the Orbiter Remote Manipulator System (RMS) are documented. The RMS hardware and software are primarily required for deploying and/or retrieving up to five payloads during a single mission, capture and retrieve free-flying payloads, and for performing Manipulator Foot Restraint operations. Specifically, the RMS hardware consists of the following components: end effector; displays and controls; manipulator controller interface unit; arm based electronics; and the arm. The IOA analysis process utilized available RMS hardware drawings, schematics and documents for defining hardware assemblies, components and hardware items. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode. Of the 574 failure modes analyzed, 413 were determined to be PCIs.

Acoustic mode measurements in the inlet of a model turbofan using a continuously rotating rake: Data collection/analysis techniques

NASA Technical Reports Server (NTRS)

Hall, David G.; Heidelberg, Laurence; Konno, Kevin

1993-01-01

The rotating microphone measurement technique and data analysis procedures are documented which are used to determine circumferential and radial acoustic mode content in the inlet of the Advanced Ducted Propeller (ADP) model. Circumferential acoustic mode levels were measured at a series of radial locations using the Doppler frequency shift produced by a rotating inlet microphone probe. Radial mode content was then computed using a least squares curve fit with the measured radial distribution for each circumferential mode. The rotating microphone technique is superior to fixed-probe techniques because it results in minimal interference with the acoustic modes generated by rotor-stator interaction. This effort represents the first experimental implementation of a measuring technique developed by T. G. Sofrin. Testing was performed in the NASA Lewis Low Speed Anechoic Wind Tunnel at a simulated takeoff condition of Mach 0.2. The design is included of the data analysis software and the performance of the rotating rake apparatus. The effect of experiment errors is also discussed.

Acoustic mode measurements in the inlet of a model turbofan using a continuously rotating rake - Data collection/analysis techniques

NASA Technical Reports Server (NTRS)

Hall, David G.; Heidelberg, Laurence; Konno, Kevin

1993-01-01

The rotating microphone measurement technique and data analysis procedures are documented which are used to determine circumferential and radial acoustic mode content in the inlet of the Advanced Ducted Propeller (ADP) model. Circumferential acoustic mode levels were measured at a series of radial locations using the Doppler frequency shift produced by a rotating inlet microphone probe. Radial mode content was then computed using a least squares curve fit with the measured radial distribution for each circumferential mode. The rotating microphone technique is superior to fixed-probe techniques because it results in minimal interference with the acoustic modes generated by rotor-stator interaction. This effort represents the first experimental implementation of a measuring technique developed by T. G. Sofrin. Testing was performed in the NASA Lewis Low Speed Anechoic Wind Tunnel at a simulated takeoff condition of Mach 0.2. The design is included of the data analysis software and the performance of the rotating rake apparatus. The effect of experiment errors is also discussed.

Clinical risk analysis with failure mode and effect analysis (FMEA) model in a dialysis unit.

PubMed

Bonfant, Giovanna; Belfanti, Pietro; Paternoster, Giuseppe; Gabrielli, Danila; Gaiter, Alberto M; Manes, Massimo; Molino, Andrea; Pellu, Valentina; Ponzetti, Clemente; Farina, Massimo; Nebiolo, Pier E

2010-01-01

The aim of clinical risk management is to improve the quality of care provided by health care organizations and to assure patients' safety. Failure mode and effect analysis (FMEA) is a tool employed for clinical risk reduction. We applied FMEA to chronic hemodialysis outpatients. FMEA steps: (i) process study: we recorded phases and activities. (ii) Hazard analysis: we listed activity-related failure modes and their effects; described control measures; assigned severity, occurrence and detection scores for each failure mode and calculated the risk priority numbers (RPNs) by multiplying the 3 scores. Total RPN is calculated by adding single failure mode RPN. (iii) Planning: we performed a RPNs prioritization on a priority matrix taking into account the 3 scores, and we analyzed failure modes causes, made recommendations and planned new control measures. (iv) Monitoring: after failure mode elimination or reduction, we compared the resulting RPN with the previous one. Our failure modes with the highest RPN came from communication and organization problems. Two tools have been created to ameliorate information flow: "dialysis agenda" software and nursing datasheets. We scheduled nephrological examinations, and we changed both medical and nursing organization. Total RPN value decreased from 892 to 815 (8.6%) after reorganization. Employing FMEA, we worked on a few critical activities, and we reduced patients' clinical risk. A priority matrix also takes into account the weight of the control measures: we believe this evaluation is quick, because of simple priority selection, and that it decreases action times.

Automatic Implementation of Prony Analysis for Electromechanical Mode Identification from Phasor Measurements

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

Zhou, Ning; Huang, Zhenyu; Tuffner, Francis K.

2010-07-31

Small signal stability problems are one of the major threats to grid stability and reliability. Prony analysis has been successfully applied on ringdown data to monitor electromechanical modes of a power system using phasor measurement unit (PMU) data. To facilitate an on-line application of mode estimation, this paper developed a recursive algorithm for implementing Prony analysis and proposed an oscillation detection method to detect ringdown data in real time. By automatically detect ringdown data, the proposed method helps guarantee that Prony analysis is applied properly and timely on the ringdown data. Thus, the mode estimation results can be performed reliablymore » and timely. The proposed method is tested using Monte Carlo simulations based on a 17-machine model and is shown to be able to properly identify the oscillation data for on-line application of Prony analysis.« less

Independent Orbiter Assessment (IOA): Analysis of the life support and airlock support subsystems

NASA Technical Reports Server (NTRS)

Arbet, Jim; Duffy, R.; Barickman, K.; Saiidi, Mo J.

1987-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results corresponding to the Orbiter Life Support System (LSS) and Airlock Support System (ALSS). Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode. The LSS provides for the management of the supply water, collection of metabolic waste, management of waste water, smoke detection, and fire suppression. The ALSS provides water, oxygen, and electricity to support an extravehicular activity in the airlock.

Interactive multi-mode blade impact analysis

NASA Technical Reports Server (NTRS)

Alexander, A.; Cornell, R. W.

1978-01-01

The theoretical methodology used in developing an analysis for the response of turbine engine fan blades subjected to soft-body (bird) impacts is reported, and the computer program developed using this methodology as its basis is described. This computer program is an outgrowth of two programs that were previously developed for the purpose of studying problems of a similar nature (a 3-mode beam impact analysis and a multi-mode beam impact analysis). The present program utilizes an improved missile model that is interactively coupled with blade motion which is more consistent with actual observations. It takes into account local deformation at the impact area, blade camber effects, and the spreading of the impacted missile mass on the blade surface. In addition, it accommodates plate-type mode shapes. The analysis capability in this computer program represents a significant improvement in the development of the methodology for evaluating potential fan blade materials and designs with regard to foreign object impact resistance.

Transportation of U. S. Grains: A Modal Share Analysis, 1978-95

DOT National Transportation Integrated Search

1998-03-01

This analysis of grain movements by transport mode updates a 1992 study. It : provides information about changes in the competitiveness and relative : efficiencies between the modes. The goal of this analysis was to estimate the : tonnages of grain r...

Procedure for Failure Mode, Effects, and Criticality Analysis (FMECA)

NASA Technical Reports Server (NTRS)

1966-01-01

This document provides guidelines for the accomplishment of Failure Mode, Effects, and Criticality Analysis (FMECA) on the Apollo program. It is a procedure for analysis of hardware items to determine those items contributing most to system unreliability and crew safety problems.

Independent Orbiter Assessment (IOA): Analysis of the guidance, navigation, and control subsystem

NASA Technical Reports Server (NTRS)

Trahan, W. H.; Odonnell, R. A.; Pietz, K. C.; Hiott, J. M.

1986-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) is presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The independent analysis results corresponding to the Orbiter Guidance, Navigation, and Control (GNC) Subsystem hardware are documented. The function of the GNC hardware is to respond to guidance, navigation, and control software commands to effect vehicle control and to provide sensor and controller data to GNC software. Some of the GNC hardware for which failure modes analysis was performed includes: hand controllers; Rudder Pedal Transducer Assembly (RPTA); Speed Brake Thrust Controller (SBTC); Inertial Measurement Unit (IMU); Star Tracker (ST); Crew Optical Alignment Site (COAS); Air Data Transducer Assembly (ADTA); Rate Gyro Assemblies; Accelerometer Assembly (AA); Aerosurface Servo Amplifier (ASA); and Ascent Thrust Vector Control (ATVC). The IOA analysis process utilized available GNC hardware drawings, workbooks, specifications, schematics, and systems briefs for defining hardware assemblies, components, and circuits. Each hardware item was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode.

Analysis of Dual Mode Systems in an Urban Area : Volume 2. Study Results.

DOT National Transportation Integrated Search

1973-12-01

Various forms of Dual Mode transportation were analyzed in order to assess the economic viability of the dual mode concept. Specially designed new small Dual Mode vehicles, modifications of existing automobiles, and pallet systems, all operating in c...

Analysis of Dual Mode Systems in an Urban Area : Volume 1. Summary.

DOT National Transportation Integrated Search

1973-12-01

Various forms of Dual Mode transportation were analyzed in order to assess the economic viability of the dual mode concept. Specially designed new small Dual Mode vehicles, modifications of existing automobiles, and pallet systems, all operating in c...

Experimental strain modal analysis for beam-like structure by using distributed fiber optics and its damage detection

NASA Astrophysics Data System (ADS)

Cheng, Liangliang; Busca, Giorgio; Cigada, Alfredo

2017-07-01

Modal analysis is commonly considered as an effective tool to obtain the intrinsic characteristics of structures including natural frequencies, modal damping ratios, and mode shapes, which are significant indicators for monitoring the health status of engineering structures. The complex mode indicator function (CMIF) can be regarded as an effective numerical tool to perform modal analysis. In this paper, experimental strain modal analysis based on the CMIF has been introduced. Moreover, a distributed fiber-optic sensor, as a dense measuring device, has been applied to acquire strain data along a beam surface. Thanks to the dense spatial resolution of the distributed fiber optics, more detailed mode shapes could be obtained. In order to test the effectiveness of the method, a mass lump—considered as a linear damage component—has been attached to the surface of the beam, and damage detection based on strain mode shape has been carried out. The results manifest that strain modal parameters can be estimated effectively by utilizing the CMIF based on the corresponding simulations and experiments. Furthermore, damage detection based on strain mode shapes benefits from the accuracy of strain mode shape recognition and the excellent performance of the distributed fiber optics.

Development of STS/Centaur failure probabilities liftoff to Centaur separation

NASA Technical Reports Server (NTRS)

Hudson, J. M.

1982-01-01

The results of an analysis to determine STS/Centaur catastrophic vehicle response probabilities for the phases of vehicle flight from STS liftoff to Centaur separation from the Orbiter are presented. The analysis considers only category one component failure modes as contributors to the vehicle response mode probabilities. The relevant component failure modes are grouped into one of fourteen categories of potential vehicle behavior. By assigning failure rates to each component, for each of its failure modes, the STS/Centaur vehicle response probabilities in each phase of flight can be calculated. The results of this study will be used in a DOE analysis to ascertain the hazard from carrying a nuclear payload on the STS.

Application of failure mode and effects analysis to intracranial stereotactic radiation surgery by linear accelerator.

PubMed

Masini, Laura; Donis, Laura; Loi, Gianfranco; Mones, Eleonora; Molina, Elisa; Bolchini, Cesare; Krengli, Marco

2014-01-01

The aim of this study was to analyze the application of the failure modes and effects analysis (FMEA) to intracranial stereotactic radiation surgery (SRS) by linear accelerator in order to identify the potential failure modes in the process tree and adopt appropriate safety measures to prevent adverse events (AEs) and near-misses, thus improving the process quality. A working group was set up to perform FMEA for intracranial SRS in the framework of a quality assurance program. FMEA was performed in 4 consecutive tasks: (1) creation of a visual map of the process; (2) identification of possible failure modes; (3) assignment of a risk probability number (RPN) to each failure mode based on tabulated scores of severity, frequency of occurrence and detectability; and (4) identification of preventive measures to minimize the risk of occurrence. The whole SRS procedure was subdivided into 73 single steps; 116 total possible failure modes were identified and a score of severity, occurrence, and detectability was assigned to each. Based on these scores, RPN was calculated for each failure mode thus obtaining values from 1 to 180. In our analysis, 112/116 (96.6%) RPN values were <60, 2 (1.7%) between 60 and 125 (63, 70), and 2 (1.7%) >125 (135, 180). The 2 highest RPN scores were assigned to the risk of using the wrong collimator's size and incorrect coordinates on the laser target localizer frame. Failure modes and effects analysis is a simple and practical proactive tool for systematic analysis of risks in radiation therapy. In our experience of SRS, FMEA led to the adoption of major changes in various steps of the SRS procedure.

Active Control of Fan Noise: Feasibility Study. Volume 6; Theoretical Analysis for Coupling of Active Noise Control Actuator Ring Sources to an Annular Duct with Flow

NASA Technical Reports Server (NTRS)

Kraft, R. E.

1996-01-01

The objective of this effort is to develop an analytical model for the coupling of active noise control (ANC) piston-type actuators that are mounted flush to the inner and outer walls of an annular duct to the modes in the duct generated by the actuator motion. The analysis will be used to couple the ANC actuators to the modal analysis propagation computer program for the annular duct, to predict the effects of active suppression of fan-generated engine noise sources. This combined program will then be available to assist in the design or evaluation of ANC systems in fan engine annular exhaust ducts. An analysis has been developed to predict the modes generated in an annular duct due to the coupling of flush-mounted ring actuators on the inner and outer walls of the duct. The analysis has been combined with a previous analysis for the coupling of modes to a cylindrical duct in a FORTRAN computer program to perform the computations. The method includes the effects of uniform mean flow in the duct. The program can be used for design or evaluation purposes for active noise control hardware for turbofan engines. Predictions for some sample cases modeled after the geometry of the NASA Lewis ANC Fan indicate very efficient coupling in both the inlet and exhaust ducts for the m = 6 spinning mode at frequencies where only a single radial mode is cut-on. Radial mode content in higher order cut-off modes at the source plane and the required actuator displacement amplitude to achieve 110 dB SPL levels in the desired mode were predicted. Equivalent cases with and without flow were examined for the cylindrical and annular geometry, and little difference was found for a duct flow Mach number of 0.1. The actuator ring coupling program will be adapted as a subroutine to the cylindrical duct modal analysis and the exhaust duct modal analysis. This will allow the fan source to be defined in terms of characteristic modes at the fan source plane and predict the propagation to the arbitrarily-located ANC source plane. The actuator velocities can then be determined to generate the anti-phase mode. The resulting combined fan source/ANC pressure can then be calculated at any desired wall sensor position. The actuator velocities can be determined manually or using a simulation of a control system feedback loop. This will provide a very useful ANC system design and evaluation tool.

Analysis of parasitic oscillations in 42 GHz gyrotron beam tunnel

NASA Astrophysics Data System (ADS)

Kumar, N.; Singh, U.; Singh, T. P.; Sinha, A. K.

2011-02-01

Parasitic oscillation excitation analysis has been carried out for the 42 GHz gyrotron beam tunnel. This article presents a systematic approach for the analysis of parasitic oscillation excitation. The electron trajectory code EGUN has been used for the estimation of the electron beam parameters in the beam tunnel. The electromagnetic simulation code CST-MS has been used for the eigenmode and Q value analysis. The analysis of the parasitic oscillations has been performed for the symmetric TE modes and the first three cavity side copper rings. Four different approaches- the Q value study, the mode maxima-electron beam radius mismatching, the electron cyclotron frequency-mode excitation frequency mismatching and the backward wave interaction analysis- have been used for the parasitic oscillation analysis.

[Failure mode effect analysis applied to preparation of intravenous cytostatics].

PubMed

Santos-Rubio, M D; Marín-Gil, R; Muñoz-de la Corte, R; Velázquez-López, M D; Gil-Navarro, M V; Bautista-Paloma, F J

2016-01-01

To proactively identify risks in the preparation of intravenous cytostatic drugs, and to prioritise and establish measures to improve safety procedures. Failure Mode Effect Analysis methodology was used. A multidisciplinary team identified potential failure modes of the procedure through a brainstorming session. The impact associated with each failure mode was assessed with the Risk Priority Number (RPN), which involves three variables: occurrence, severity, and detectability. Improvement measures were established for all identified failure modes, with those with RPN>100 considered critical. The final RPN (theoretical) that would result from the proposed measures was also calculated and the process was redesigned. A total of 34 failure modes were identified. The initial accumulated RPN was 3022 (range: 3-252), and after recommended actions the final RPN was 1292 (range: 3-189). RPN scores >100 were obtained in 13 failure modes; only the dispensing sub-process was free of critical points (RPN>100). A final reduction of RPN>50% was achieved in 9 failure modes. This prospective risk analysis methodology allows the weaknesses of the procedure to be prioritised, optimize use of resources, and a substantial improvement in the safety of the preparation of cytostatic drugs through the introduction of double checking and intermediate product labelling. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

Visual and Plasmon Resonance Absorption Sensor for Adenosine Triphosphate Based on the High Affinity between Phosphate and Zr(IV)

PubMed Central

Qi, Wenjing; Liu, Zhongyuan; Zhang, Wei; Halawa, Mohamed Ibrahim; Xu, Guobao

2016-01-01

Zr(IV) can form phosphate and Zr(IV) (–PO32−–Zr4+–) complex owing to the high affinity between Zr(IV) with phosphate. Zr(IV) can induce the aggregation of gold nanoparticles (AuNPs), while adenosine triphosphate(ATP) can prevent Zr(IV)-induced aggregation of AuNPs. Herein, a visual and plasmon resonance absorption (PRA)sensor for ATP have been developed using AuNPs based on the high affinity between Zr(IV)with ATP. AuNPs get aggregated in the presence of certain concentrations of Zr(IV). After the addition of ATP, ATP reacts with Zr(IV) and prevents AuNPs from aggregation, enabling the detection of ATP. Because of the fast interaction of ATP with Zr(IV), ATP can be detected with a detection limit of 0.5 μM within 2 min by the naked eye. Moreover, ATP can be detected by the PRA technique with higher sensitivity. The A520nm/A650nm values in PRA spectra increase linearly with the concentrations of ATP from 0.1 μM to 15 μM (r = 0.9945) with a detection limit of 28 nM. The proposed visual and PRA sensor exhibit good selectivity against adenosine, adenosine monophosphate, guanosine triphosphate, cytidine triphosphate and uridine triphosphate. The recoveries for the analysis of ATP in synthetic samples range from 95.3% to 102.0%. Therefore, the proposed novel sensor for ATP is promising for real-time or on-site detection of ATP. PMID:27754349

Linkage analysis in nuclear families. 2: Relationship between affected sib-pair tests and lod score analysis.

PubMed

Knapp, M; Seuchter, S A; Baur, M P

1994-01-01

It is believed that the main advantage of affected sib-pair tests is that their application requires no information about the underlying genetic mechanism of the disease. However, here it is proved that the mean test, which can be considered the most prominent of the affected sib-pair tests, is equivalent to lod score analysis for an assumed recessive mode of inheritance, irrespective of the true mode of the disease. Further relationships of certain sib-pair tests and lod score analysis under specific assumed genetic modes are investigated.

FIBER AND INTEGRATED OPTICS, LASER APPLICATIONS, AND OTHER PROBLEMS IN QUANTUM ELECTRONICS: Optical components for the analysis and formation of the transverse mode composition

NASA Astrophysics Data System (ADS)

Golub, M. A.; Sisakyan, I. N.; Soĭfer, V. A.; Uvarov, G. V.

1989-04-01

Theoretical and experimental investigations are reported of new mode optical components (elements) which are analogs of sinusoidal phase diffraction gratings with a variable modulation depth. Expressions are derived for nonlinear predistortion and depth of modulation, which are essential for effective operation of amplitude and phase mode optical components in devices used for analysis and formation of the transverse mode composition of coherent radiation. An estimate is obtained of the energy efficiency of phase and amplitude mode optical components, and a comparison is made with the results of an experimental investigation of a set of phase optical components matched to Gauss-Laguerre modes. It is shown that the improvement in the energy efficiency of phase mode components, compared with amplitude components, is the same as the improvement achieved using a phase diifraction grating, compared with amplitude grating with the same depth of modulation.

Multibody model reduction by component mode synthesis and component cost analysis

NASA Technical Reports Server (NTRS)

Spanos, J. T.; Mingori, D. L.

1990-01-01

The classical assumed-modes method is widely used in modeling the dynamics of flexible multibody systems. According to the method, the elastic deformation of each component in the system is expanded in a series of spatial and temporal functions known as modes and modal coordinates, respectively. This paper focuses on the selection of component modes used in the assumed-modes expansion. A two-stage component modal reduction method is proposed combining Component Mode Synthesis (CMS) with Component Cost Analysis (CCA). First, each component model is truncated such that the contribution of the high frequency subsystem to the static response is preserved. Second, a new CMS procedure is employed to assemble the system model and CCA is used to further truncate component modes in accordance with their contribution to a quadratic cost function of the system output. The proposed method is demonstrated with a simple example of a flexible two-body system.

Modes and emergent time scales of embayed beach dynamics

NASA Astrophysics Data System (ADS)

Ratliff, Katherine M.; Murray, A. Brad

2014-10-01

In this study, we use a simple numerical model (the Coastline Evolution Model) to explore alongshore transport-driven shoreline dynamics within generalized embayed beaches (neglecting cross-shore effects). Using principal component analysis (PCA), we identify two primary orthogonal modes of shoreline behavior that describe shoreline variation about its unchanging mean position: the rotation mode, which has been previously identified and describes changes in the mean shoreline orientation, and a newly identified breathing mode, which represents changes in shoreline curvature. Wavelet analysis of the PCA mode time series reveals characteristic time scales of these modes (typically years to decades) that emerge within even a statistically constant white-noise wave climate (without changes in external forcing), suggesting that these time scales can arise from internal system dynamics. The time scales of both modes increase linearly with shoreface depth, suggesting that the embayed beach sediment transport dynamics exhibit a diffusive scaling.

Normal mode analysis and applications in biological physics.

PubMed

Dykeman, Eric C; Sankey, Otto F

2010-10-27

Normal mode analysis has become a popular and often used theoretical tool in the study of functional motions in enzymes, viruses, and large protein assemblies. The use of normal modes in the study of these motions is often extremely fruitful since many of the functional motions of large proteins can be described using just a few normal modes which are intimately related to the overall structure of the protein. In this review, we present a broad overview of several popular methods used in the study of normal modes in biological physics including continuum elastic theory, the elastic network model, and a new all-atom method, recently developed, which is capable of computing a subset of the low frequency vibrational modes exactly. After a review of the various methods, we present several examples of applications of normal modes in the study of functional motions, with an emphasis on viral capsids.

Independent Orbiter Assessment (IOA): Analysis of the atmospheric revitalization pressure control subsystem

NASA Technical Reports Server (NTRS)

Saiidi, M. J.; Duffy, R. E.; Mclaughlin, T. D.

1986-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis/Critical Items List (FMEA/CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The independent analysis results corresponding to the Orbiter Atmospheric Revitalization and Pressure Control Subsystem (ARPCS) are documented. The ARPCS hardware was categorized into the following subdivisions: (1) Atmospheric Make-up and Control (including the Auxiliary Oxygen Assembly, Oxygen Assembly, and Nitrogen Assembly); and (2) Atmospheric Vent and Control (including the Positive Relief Vent Assembly, Negative Relief Vent Assembly, and Cabin Vent Assembly). The IOA analysis process utilized available ARPCS hardware drawings and schematics for defining hardware assemblies, components, and hardware items. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode.

Independent Orbiter Assessment (IOA): Analysis of the mechanical actuation subsystem

NASA Technical Reports Server (NTRS)

Bacher, J. L.; Montgomery, A. D.; Bradway, M. W.; Slaughter, W. T.

1987-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results corresponding to the Orbiter Mechanical Actuation System (MAS) hardware. Specifically, the MAS hardware consists of the following components: Air Data Probe (ADP); Elevon Seal Panel (ESP); External Tank Umbilical (ETU); Ku-Band Deploy (KBD); Payload Bay Doors (PBD); Payload Bay Radiators (PBR); Personnel Hatches (PH); Vent Door Mechanism (VDM); and Startracker Door Mechanism (SDM). The IOA analysis process utilized available MAS hardware drawings and schematics for defining hardware assemblies, components, and hardware items. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode.

Three-dimensional vibration analysis of a uniform beam with offset inertial masses at the ends

NASA Technical Reports Server (NTRS)

Robertson, D. K.

1985-01-01

Analysis of a flexible beam with displaced end-located inertial masses is presented. The resulting three-dimensional mode shape is shown to consist of two one-plane bending modes and one torsional mode. These three components of the mode shapes are shown to be linear combinations of trigonometric and hyperbolic sine and cosine functions. Boundary conditions are derived to obtain nonlinear algebraic equations through kinematic coupling of the general solutions of the three governing partial differential equations. A method of solution which takes these boundary conditions into account is also presented. A computer program has been written to obtain unique solutions to the resulting nonlinear algebraic equations. This program, which calculates natural frequencies and three-dimensional mode shapes for any number of modes, is presented and discussed.

Ultrasonic guided wave propagation across waveguide transitions: energy transfer and mode conversion.

PubMed

Puthillath, Padmakumar; Galan, Jose M; Ren, Baiyang; Lissenden, Cliff J; Rose, Joseph L

2013-05-01

Ultrasonic guided wave inspection of structures containing adhesively bonded joints requires an understanding of the interaction of guided waves with geometric and material discontinuities or transitions in the waveguide. Such interactions result in mode conversion with energy being partitioned among the reflected and transmitted modes. The step transition between an aluminum layer and an aluminum-adhesive-aluminum multi-layer waveguide is analyzed as a model structure. Dispersion analysis enables assessment of (i) synchronism through dispersion curve overlap and (ii) wavestructure correlation. Mode-pairs in the multi-layer waveguide are defined relative to a prescribed mode in a single layer as being synchronized and having nearly perfect wavestructure matching. Only a limited number of mode-pairs exist, and each has a unique frequency range. A hybrid model based on semi-analytical finite elements and the normal mode expansion is implemented to assess mode conversion at a step transition in a waveguide. The model results indicate that synchronism and wavestructure matching is associated with energy transfer through the step transition, and that the energy of an incident wave mode in a single layer is transmitted almost entirely to the associated mode-pair, where one exists. This analysis guides the selection of incident modes that convert into transmitted modes and improve adhesive joint inspection with ultrasonic guided waves.

Phonon Transport at Crystalline Si/Ge Interfaces: The Role of Interfacial Modes of Vibration

PubMed Central

Gordiz, Kiarash; Henry, Asegun

2016-01-01

We studied the modal contributions to heat conduction at crystalline Si and crystalline Ge interfaces and found that more than 15% of the interface conductance arises from less than 0.1% of the modes in the structure. Using the recently developed interface conductance modal analysis (ICMA) method along with a new complimentary methodology, we mapped the correlations between modes, which revealed that a small group of interfacial modes, which exist between 12–13 THz, exhibit extremely strong correlation with other modes in the system. It is found that these interfacial modes (e.g., modes with large eigen vectors for interfacial atoms) are enabled by the degree of anharmonicity near the interface, which is higher than in the bulk, and therefore allows this small group of modes to couple to all others. The analysis sheds light on the nature of localized vibrations at interfaces and can be enlightening for other investigations of localization. PMID:26979787

Q-mode versus R-mode principal component analysis for linear discriminant analysis (LDA)

NASA Astrophysics Data System (ADS)

Lee, Loong Chuen; Liong, Choong-Yeun; Jemain, Abdul Aziz

2017-05-01

Many literature apply Principal Component Analysis (PCA) as either preliminary visualization or variable con-struction methods or both. Focus of PCA can be on the samples (R-mode PCA) or variables (Q-mode PCA). Traditionally, R-mode PCA has been the usual approach to reduce high-dimensionality data before the application of Linear Discriminant Analysis (LDA), to solve classification problems. Output from PCA composed of two new matrices known as loadings and scores matrices. Each matrix can then be used to produce a plot, i.e. loadings plot aids identification of important variables whereas scores plot presents spatial distribution of samples on new axes that are also known as Principal Components (PCs). Fundamentally, the scores matrix always be the input variables for building classification model. A recent paper uses Q-mode PCA but the focus of analysis was not on the variables but instead on the samples. As a result, the authors have exchanged the use of both loadings and scores plots in which clustering of samples was studied using loadings plot whereas scores plot has been used to identify important manifest variables. Therefore, the aim of this study is to statistically validate the proposed practice. Evaluation is based on performance of external error obtained from LDA models according to number of PCs. On top of that, bootstrapping was also conducted to evaluate the external error of each of the LDA models. Results show that LDA models produced by PCs from R-mode PCA give logical performance and the matched external error are also unbiased whereas the ones produced with Q-mode PCA show the opposites. With that, we concluded that PCs produced from Q-mode is not statistically stable and thus should not be applied to problems of classifying samples, but variables. We hope this paper will provide some insights on the disputable issues.

Ongoing Analysis of Rocket Based Combined Cycle Engines by the Applied Fluid Dynamics Analysis Group at Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Ruf, Joseph; Holt, James B.; Canabal, Francisco

1999-01-01

This paper presents the status of analyses on three Rocket Based Combined Cycle configurations underway in the Applied Fluid Dynamics Analysis Group (TD64). TD64 is performing computational fluid dynamics analysis on a Penn State RBCC test rig, the proposed Draco axisymmetric RBCC engine and the Trailblazer engine. The intent of the analysis on the Penn State test rig is to benchmark the Finite Difference Navier Stokes code for ejector mode fluid dynamics. The Draco engine analysis is a trade study to determine the ejector mode performance as a function of three engine design variables. The Trailblazer analysis is to evaluate the nozzle performance in scramjet mode. Results to date of each analysis are presented.

Extended Testability Analysis Tool

NASA Technical Reports Server (NTRS)

Melcher, Kevin; Maul, William A.; Fulton, Christopher

2012-01-01

The Extended Testability Analysis (ETA) Tool is a software application that supports fault management (FM) by performing testability analyses on the fault propagation model of a given system. Fault management includes the prevention of faults through robust design margins and quality assurance methods, or the mitigation of system failures. Fault management requires an understanding of the system design and operation, potential failure mechanisms within the system, and the propagation of those potential failures through the system. The purpose of the ETA Tool software is to process the testability analysis results from a commercial software program called TEAMS Designer in order to provide a detailed set of diagnostic assessment reports. The ETA Tool is a command-line process with several user-selectable report output options. The ETA Tool also extends the COTS testability analysis and enables variation studies with sensor sensitivity impacts on system diagnostics and component isolation using a single testability output. The ETA Tool can also provide extended analyses from a single set of testability output files. The following analysis reports are available to the user: (1) the Detectability Report provides a breakdown of how each tested failure mode was detected, (2) the Test Utilization Report identifies all the failure modes that each test detects, (3) the Failure Mode Isolation Report demonstrates the system s ability to discriminate between failure modes, (4) the Component Isolation Report demonstrates the system s ability to discriminate between failure modes relative to the components containing the failure modes, (5) the Sensor Sensor Sensitivity Analysis Report shows the diagnostic impact due to loss of sensor information, and (6) the Effect Mapping Report identifies failure modes that result in specified system-level effects.

A combined cICA-EEMD analysis of EEG recordings from depressed or schizophrenic patients during olfactory stimulation

NASA Astrophysics Data System (ADS)

Götz, Th; Stadler, L.; Fraunhofer, G.; Tomé, A. M.; Hausner, H.; Lang, E. W.

2017-02-01

Objective. We propose a combination of a constrained independent component analysis (cICA) with an ensemble empirical mode decomposition (EEMD) to analyze electroencephalographic recordings from depressed or schizophrenic subjects during olfactory stimulation. Approach. EEMD serves to extract intrinsic modes (IMFs) underlying the recorded EEG time. The latter then serve as reference signals to extract the most similar underlying independent component within a constrained ICA. The extracted modes are further analyzed considering their power spectra. Main results. The analysis of the extracted modes reveals clear differences in the related power spectra between the disease characteristics of depressed and schizophrenic patients. Such differences appear in the high frequency γ-band in the intrinsic modes, but also in much more detail in the low frequency range in the α-, θ- and δ-bands. Significance. The proposed method provides various means to discriminate both disease pictures in a clinical environment.

Bending strength of delaminated aerospace composites.

PubMed

Kinawy, Moustafa; Butler, Richard; Hunt, Giles W

2012-04-28

Buckling-driven delamination is considered among the most critical failure modes in composite laminates. This paper examines the propagation of delaminations in a beam under pure bending. A pre-developed analytical model to predict the critical buckling moment of a thin sub-laminate is extended to account for propagation prediction, using mixed-mode fracture analysis. Fractography analysis is performed to distinguish between mode I and mode II contributions to the final failure of specimens. Comparison between experimental results and analysis shows agreement to within 5 per cent in static propagation moment for two different materials. It is concluded that static fracture is almost entirely driven by mode II effects. This result was unexpected because it arises from a buckling mode that opens the delamination. For this reason, and because of the excellent repeatability of the experiments, the method of testing may be a promising means of establishing the critical value of mode II fracture toughness, G(IIC), of the material. Fatigue testing on similar samples showed that buckled delamination resulted in a fatigue threshold that was over 80 per cent lower than the static propagation moment. Such an outcome highlights the significance of predicting snap-buckling moment and subsequent propagation for design purposes.

Reduced rank models for travel time estimation of low order mode pulses.

PubMed

Chandrayadula, Tarun K; Wage, Kathleen E; Worcester, Peter F; Dzieciuch, Matthew A; Mercer, James A; Andrew, Rex K; Howe, Bruce M

2013-10-01

Mode travel time estimation in the presence of internal waves (IWs) is a challenging problem. IWs perturb the sound speed, which results in travel time wander and mode scattering. A standard approach to travel time estimation is to pulse compress the broadband signal, pick the peak of the compressed time series, and average the peak time over multiple receptions to reduce variance. The peak-picking approach implicitly assumes there is a single strong arrival and does not perform well when there are multiple arrivals due to scattering. This article presents a statistical model for the scattered mode arrivals and uses the model to design improved travel time estimators. The model is based on an Empirical Orthogonal Function (EOF) analysis of the mode time series. Range-dependent simulations and data from the Long-range Ocean Acoustic Propagation Experiment (LOAPEX) indicate that the modes are represented by a small number of EOFs. The reduced-rank EOF model is used to construct a travel time estimator based on the Matched Subspace Detector (MSD). Analysis of simulation and experimental data show that the MSDs are more robust to IW scattering than peak picking. The simulation analysis also highlights how IWs affect the mode excitation by the source.

Inversion of high frequency surface waves with fundamental and higher modes

USGS Publications Warehouse

Xia, J.; Miller, R.D.; Park, C.B.; Tian, G.

2003-01-01

The phase velocity of Rayleigh-waves of a layered earth model is a function of frequency and four groups of earth parameters: compressional (P)-wave velocity, shear (S)-wave velocity, density, and thickness of layers. For the fundamental mode of Rayleigh waves, analysis of the Jacobian matrix for high frequencies (2-40 Hz) provides a measure of dispersion curve sensitivity to earth model parameters. S-wave velocities are the dominant influence of the four earth model parameters. This thesis is true for higher modes of high frequency Rayleigh waves as well. Our numerical modeling by analysis of the Jacobian matrix supports at least two quite exciting higher mode properties. First, for fundamental and higher mode Rayleigh wave data with the same wavelength, higher modes can "see" deeper than the fundamental mode. Second, higher mode data can increase the resolution of the inverted S-wave velocities. Real world examples show that the inversion process can be stabilized and resolution of the S-wave velocity model can be improved when simultaneously inverting the fundamental and higher mode data. ?? 2002 Elsevier Science B.V. All rights reserved.

The magnetic particle in a box: Analytic and micromagnetic analysis of probe-localized spin wave modes

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

Adur, Rohan, E-mail: adur@physics.osu.edu; Du, Chunhui; Manuilov, Sergei A.

2015-05-07

The dipole field from a probe magnet can be used to localize a discrete spectrum of standing spin wave modes in a continuous ferromagnetic thin film without lithographic modification to the film. Obtaining the resonance field for a localized mode is not trivial due to the effect of the confined and inhomogeneous magnetization precession. We compare the results of micromagnetic and analytic methods to find the resonance field of localized modes in a ferromagnetic thin film, and investigate the accuracy of these methods by comparing with a numerical minimization technique that assumes Bessel function modes with pinned boundary conditions. Wemore » find that the micromagnetic technique, while computationally more intensive, reveals that the true magnetization profiles of localized modes are similar to Bessel functions with gradually decaying dynamic magnetization at the mode edges. We also find that an analytic solution, which is simple to implement and computationally much faster than other methods, accurately describes the resonance field of localized modes when exchange fields are negligible, and demonstrating the accessibility of localized mode analysis.« less

Mode instability in one-dimensional anharmonic lattices: Variational equation approach

NASA Astrophysics Data System (ADS)

Yoshimura, K.

1999-03-01

The stability of normal mode oscillations has been studied in detail under the single-mode excitation condition for the Fermi-Pasta-Ulam-β lattice. Numerical experiments indicate that the mode stability depends strongly on k/N, where k is the wave number of the initially excited mode and N is the number of degrees of freedom in the system. It has been found that this feature does not change when N increases. We propose an average variational equation - approximate version of the variational equation - as a theoretical tool to facilitate a linear stability analysis. It is shown that this strong k/N dependence of the mode stability can be explained from the view point of the linear stability of the relevant orbits. We introduce a low-dimensional approximation of the average variational equation, which approximately describes the time evolution of variations in four normal mode amplitudes. The linear stability analysis based on this four-mode approximation demonstrates that the parametric instability mechanism plays a crucial role in the strong k/N dependence of the mode stability.

The effect of pressure anisotropy on ballooning modes in tokamak plasmas

NASA Astrophysics Data System (ADS)

Johnston, A.; Hole, M. J.; Qu, Z. S.; Hezaveh, H.

2018-06-01

Edge Localised Modes are thought to be caused by a spectrum of magnetohydrodynamic instabilities, including the ballooning mode. While ballooning modes have been studied extensively both theoretically and experimentally, the focus of the vast majority of this research has been on isotropic plasmas. The prevalence of pressure anisotropy in modern tokamaks thus motivates further study of these modes. This paper presents a numerical analysis of ballooning modes in anisotropic equilibria. The investigation was conducted using the newly-developed codes HELENA+ATF and MISHKA-A, which adds anisotropic physics to equilibria and stability analysis. We have examined the impact of anisotropy on the stability of an n = 30 ballooning mode, confirming results conform to previous calculations in the isotropic limit. Growth rates of ballooning modes in equilibria with different levels of anisotropy were then calculated using the stability code MISHKA-A. The key finding was that the level of anisotropy had a significant impact on ballooning mode growth rates. For {T}\\perp > {T}| | , typical of ICRH heating, the growth rate increases, while for {T}\\perp < {T}| | , typical of neutral beam heating, the growth rate decreases.

Effects of Crimped Fiber Paths on Mixed Mode Delamination Behaviors in Woven Fabric Composites

DTIC Science & Technology

2016-09-01

continuum finite - element models. Three variations of a plain-woven fabric architecture—each of which had different crimped fiber paths—were considered... Finite - Element Analysis Fracture Mechanics Fracture Toughness Mixed Modes Strain Energy Release Rate 16. SECURITY...polymer FB Fully balanced laminate FEA Finite - element analysis FTCM Fracture toughness conversion mechanism G Shear modulus GI, GII, GIII Mode

Efficient analysis of mode profiles in elliptical microcavity using dynamic-thermal electron-quantum medium FDTD method.

PubMed

Khoo, E H; Ahmed, I; Goh, R S M; Lee, K H; Hung, T G G; Li, E P

2013-03-11

The dynamic-thermal electron-quantum medium finite-difference time-domain (DTEQM-FDTD) method is used for efficient analysis of mode profile in elliptical microcavity. The resonance peak of the elliptical microcavity is studied by varying the length ratio. It is observed that at some length ratios, cavity mode is excited instead of whispering gallery mode. This depicts that mode profiles are length ratio dependent. Through the implementation of the DTEQM-FDTD on graphic processing unit (GPU), the simulation time is reduced by 300 times as compared to the CPU. This leads to an efficient optimization approach to design microcavity lasers for wide range of applications in photonic integrated circuits.

Failure mode and effects analysis and fault tree analysis of surface image guided cranial radiosurgery.

PubMed

Manger, Ryan P; Paxton, Adam B; Pawlicki, Todd; Kim, Gwe-Ya

2015-05-01

Surface image guided, Linac-based radiosurgery (SIG-RS) is a modern approach for delivering radiosurgery that utilizes optical stereoscopic imaging to monitor the surface of the patient during treatment in lieu of using a head frame for patient immobilization. Considering the novelty of the SIG-RS approach and the severity of errors associated with delivery of large doses per fraction, a risk assessment should be conducted to identify potential hazards, determine their causes, and formulate mitigation strategies. The purpose of this work is to investigate SIG-RS using the combined application of failure modes and effects analysis (FMEA) and fault tree analysis (FTA), report on the effort required to complete the analysis, and evaluate the use of FTA in conjunction with FMEA. A multidisciplinary team was assembled to conduct the FMEA on the SIG-RS process. A process map detailing the steps of the SIG-RS was created to guide the FMEA. Failure modes were determined for each step in the SIG-RS process, and risk priority numbers (RPNs) were estimated for each failure mode to facilitate risk stratification. The failure modes were ranked by RPN, and FTA was used to determine the root factors contributing to the riskiest failure modes. Using the FTA, mitigation strategies were formulated to address the root factors and reduce the risk of the process. The RPNs were re-estimated based on the mitigation strategies to determine the margin of risk reduction. The FMEA and FTAs for the top two failure modes required an effort of 36 person-hours (30 person-hours for the FMEA and 6 person-hours for two FTAs). The SIG-RS process consisted of 13 major subprocesses and 91 steps, which amounted to 167 failure modes. Of the 91 steps, 16 were directly related to surface imaging. Twenty-five failure modes resulted in a RPN of 100 or greater. Only one of these top 25 failure modes was specific to surface imaging. The riskiest surface imaging failure mode had an overall RPN-rank of eighth. Mitigation strategies for the top failure mode decreased the RPN from 288 to 72. Based on the FMEA performed in this work, the use of surface imaging for monitoring intrafraction position in Linac-based stereotactic radiosurgery (SRS) did not greatly increase the risk of the Linac-based SRS process. In some cases, SIG helped to reduce the risk of Linac-based RS. The FMEA was augmented by the use of FTA since it divided the failure modes into their fundamental components, which simplified the task of developing mitigation strategies.

Independent Orbiter Assessment (IOA): Analysis of the nose wheel steering subsystem

NASA Technical Reports Server (NTRS)

Mediavilla, Anthony Scott

1986-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The independent analysis results for the Orbiter Nose Wheel Steering (NWS) hardware are documented. The NWS hardware provides primary directional control for the Orbiter vehicle during landing rollout. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode. The original NWS design was envisioned as a backup system to differential braking for directional control of the Orbiter during landing rollout. No real effort was made to design the NWS system as fail operational. The brakes have much redundancy built into their design but the poor brake/tire performance has forced the NSTS to upgrade NWS to the primary mode of directional control during rollout. As a result, a large percentage of the NWS system components have become Potential Critical Items (PCI).

Dynamic Stability Analysis of Linear Time-varying Systems via an Extended Modal Identification Approach

NASA Astrophysics Data System (ADS)

Ma, Zhisai; Liu, Li; Zhou, Sida; Naets, Frank; Heylen, Ward; Desmet, Wim

2017-03-01

The problem of linear time-varying(LTV) system modal analysis is considered based on time-dependent state space representations, as classical modal analysis of linear time-invariant systems and current LTV system modal analysis under the "frozen-time" assumption are not able to determine the dynamic stability of LTV systems. Time-dependent state space representations of LTV systems are first introduced, and the corresponding modal analysis theories are subsequently presented via a stability-preserving state transformation. The time-varying modes of LTV systems are extended in terms of uniqueness, and are further interpreted to determine the system's stability. An extended modal identification is proposed to estimate the time-varying modes, consisting of the estimation of the state transition matrix via a subspace-based method and the extraction of the time-varying modes by the QR decomposition. The proposed approach is numerically validated by three numerical cases, and is experimentally validated by a coupled moving-mass simply supported beam experimental case. The proposed approach is capable of accurately estimating the time-varying modes, and provides a new way to determine the dynamic stability of LTV systems by using the estimated time-varying modes.

Independent Orbiter Assessment (IOA): Analysis of the displays and controls subsystem

NASA Technical Reports Server (NTRS)

Trahan, W. H.; Prust, E. E.

1987-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results corresponding to the Orbiter Displays and Controls (D and C) subsystem hardware. The function of the D and C hardware is to provide the crew with the monitor, command, and control capabilities required for management of all normal and contingency mission and flight operations. The D and C hardware for which failure modes analysis was performed consists of the following: Acceleration Indicator (G-METER); Head Up Display (HUD); Display Driver Unit (DDU); Alpha/Mach Indicator (AMI); Horizontal Situation Indicator (HSI); Attitude Director Indicator (ADI); Propellant Quantity Indicator (PQI); Surface Position Indicator (SPI); Altitude/Vertical Velocity Indicator (AVVI); Caution and Warning Assembly (CWA); Annunciator Control Assembly (ACA); Event Timer (ET); Mission Timer (MT); Interior Lighting; and Exterior Lighting. Each hardware item was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode.

Electric dipole radiation at VLF in a uniform warm magneto-plasma.

NASA Technical Reports Server (NTRS)

Wang, T. N. C.; Bell, T. F.

1972-01-01

Use of a linear full electromagnetic wave theory to calculate the input impedance of an electric antenna embedded in a uniform, lossless, unbounded warm magnetoplasma, which is assumed to consist of warm electrons and cold ions. In calculating the dipole radiation resistance for the thermal modes and the thermally modified whistler mode the analysis includes the finite temperature only for the electrons. In deriving the formal solution of the warm plasma dipole input impedance a full-wave analysis is used and two antenna orientations are considered, parallel and perpendicular to the static magnetic field. A general dispersion equation governing the modes of propagation is derived and a detailed analysis is made of the propagation characteristics of these modes.

Combinatorial complexity of pathway analysis in metabolic networks.

PubMed

Klamt, Steffen; Stelling, Jörg

2002-01-01

Elementary flux mode analysis is a promising approach for a pathway-oriented perspective of metabolic networks. However, in larger networks it is hampered by the combinatorial explosion of possible routes. In this work we give some estimations on the combinatorial complexity including theoretical upper bounds for the number of elementary flux modes in a network of a given size. In a case study, we computed the elementary modes in the central metabolism of Escherichia coli while utilizing four different substrates. Interestingly, although the number of modes occurring in this complex network can exceed half a million, it is still far below the upper bound. Hence, to a certain extent, pathway analysis of central catabolism is feasible to assess network properties such as flexibility and functionality.

Analysis of the STS-126 Flow Control Valve Structural-Acoustic Coupling Failure

NASA Technical Reports Server (NTRS)

Jones, Trevor M.; Larko, Jeffrey M.; McNelis, Mark E.

2010-01-01

During the Space Transportation System mission STS-126, one of the main engine's flow control valves incurred an unexpected failure. A section of the valve broke off during liftoff. It is theorized that an acoustic mode of the flowing fuel, coupled with a structural mode of the valve, causing a high cycle fatigue failure. This report documents the analysis efforts conducted in an attempt to verify this theory. Hand calculations, computational fluid dynamics, and finite element methods are all implemented and analyses are performed using steady-state methods in addition to transient analysis methods. The conclusion of the analyses is that there is a critical acoustic mode that aligns with a structural mode of the valve

Certolizumab Pegol for Treating Rheumatoid Arthritis Following Inadequate Response to a TNF-α Inhibitor: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

PubMed

Bermejo, Iñigo; Stevenson, Matt; Archer, Rachel; Stevens, John W; Goka, Edward; Clowes, Mark; Scott, David L; Young, Adam

2017-11-01

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (UCB Pharma) of certolizumab pegol (CZP; Cimzia ® ) to submit evidence of its clinical and cost effectiveness for the treatment of rheumatoid arthritis (RA) following inadequate response to a tumour necrosis factor-α inhibitor (TNFi). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based upon the company's submission to NICE. The clinical effectiveness evidence in the company's submission for CZP was based predominantly on six randomised controlled trials (RCTs) comparing the efficacy of CZP against placebo. The clinical effectiveness review identified no head-to-head evidence on the efficacy of CZP against the comparators within the scope; therefore, the company performed a network meta-analysis (NMA). The company's NMA concluded that CZP had a similar efficacy to that of its comparators. The company submitted a Markov model that assessed the incremental cost effectiveness of CZP versus comparator biologic disease-modifying antirheumatic drugs (bDMARDs) for the treatment of RA from the perspective of the National Health Service for three decision problems, each of which followed an inadequate response to a TNFi. These were (1) a comparison against rituximab (RTX) in combination with methotrexate (MTX); (2) a comparison against bDMARDs when RTX was contraindicated or withdrawn due to an adverse event; and (3) a comparison against bDMARDs when MTX was contraindicated or withdrawn due to an adverse event. Results from the company's economic evaluation showed that CZP resulted in a similar number of quality-adjusted life years (QALYs) produced at similar or lower costs compared with comparator bDMARDs. The commercial-in-confidence patient access schemes for abatacept and tocilizumab could not be incorporated by the company, but were incorporated by the ERG in a confidential appendix for the NICE Appraisal Committee (AC). The company estimated that the addition of CZP before RTX in a sequence for patients who could receive MTX produced more QALYs at an increased cost, with a cost per QALY of £33,222. Following a critique of the model, the ERG undertook exploratory analyses that did not change the conclusions reached based on the company's economic evaluation in relation to the comparison with bDMARDs. The ERG estimated that where CZP replaced RTX, CZP was dominated, as it produced fewer QALYs at an increased cost. The AC concluded that there was little difference in effectiveness between CZP and comparator bDMARDs and that equivalence among bDMARDs could be accepted. The AC consequently recommended CZP plus MTX for people for whom RTX is contraindicated or not tolerated and CZP monotherapy for people for whom MTX is contraindicated or not tolerated. The AC concluded that CZP plus MTX could not be considered a cost-effective use of National Health Service resources when RTX plus MTX is a treatment option.

Discriminant analysis to predict the occurrence of ELMS in H-mode discharges

NASA Astrophysics Data System (ADS)

Kardaun, O. J. W. F.; Itoh, S.-I.; Itoh, K.; Kardaun, J. W. P. F.

1993-08-01

After an exposition of its theoretical background, discriminant analysis is applied to the H-mode confinement database to find the region in plasma parameter space in which H-mode with small ELM's (Edge Localized Modes) is likely to occur. The boundary of this region is determined by the condition that the probability of appearance of such a type of H-mode, as a function of the plasma parameters, should be larger than some threshold value and larger than the corresponding probability for other types of H-mode (i.e., H-mode without ELM's or with giant ELM's). In practice, the discrimination has been performed for the ASDEX, JET and JFT-2M tokamaks using four instantaneous plasma parameters (injected power Pinj, magnetic field Bt, plasma current Ip and line averaged electron density ne) and taking also memory effects of the plasma and the distance between the plasma and the wall into account, while using variables that are normalized with respect to machine size. Generally speaking, it is found that there is a substantial overlap between the region of H-mode with small ELM's and the region of the two other types of H-mode. However, the ELM-free and the giant ELM H-modes relatively rarely appear in the region, that, according to the analysis, is allocated to small ELM's. A reliable production of H-mode with only small ELM's seems well possible by choosing this regime in parameter space. In the present study, it was not attempted to arrive at a unified discrimination across the machines. So, projection from one machine to another remains difficult, and a reliable determination of the region where small ELM's occur still requires a training sample from the device under consideration.

Separation of crack extension modes in orthotropic delamination models

NASA Technical Reports Server (NTRS)

Beuth, Jack L.

1995-01-01

In the analysis of an interface crack between dissimilar elastic materials, the mode of crack extension is typically not unique, due to oscillatory behavior of near-tip stresses and displacements. This behavior currently limits the applicability of interfacial fracture mechanics as a means to predict composite delamination. The Virtual Crack Closure Technique (VCCT) is a method used to extract mode 1 and mode 2 energy release rates from numerical fracture solutions. The mode of crack extension extracted from an oscillatory solution using the VCCT is not unique due to the dependence of mode on the virtual crack extension length, Delta. In this work, a method is presented for using the VCCT to extract Delta-independent crack extension modes for the case of an interface crack between two in-plane orthotropic materials. The method does not involve altering the analysis to eliminate its oscillatory behavior. Instead, it is argued that physically reasonable, Delta-independent modes of crack extension can be extracted from oscillatory solutions. Knowledge of near-tip fields is used to determine the explicit Delta dependence of energy release rate parameters. Energy release rates are then defined that are separated from the oscillatory dependence on Delta. A modified VCCT using these energy release rate definitions is applied to results from finite element analyses, showing that Delta-independent modes of crack extension result. The modified technique has potential as a consistent method for extracting crack extension modes from numerical solutions. The Delta-independent modes extracted using this technique can also serve as guides for testing the convergence of finite element models. Direct applications of this work include the analysis of planar composite delamination problems, where plies or debonded laminates are modeled as in-plane orthotropic materials.

Ongoing Analyses of Rocket Based Combined Cycle Engines by the Applied Fluid Dynamics Analysis Group at Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Ruf, Joseph H.; Holt, James B.; Canabal, Francisco

2001-01-01

This paper presents the status of analyses on three Rocket Based Combined Cycle (RBCC) configurations underway in the Applied Fluid Dynamics Analysis Group (TD64). TD64 is performing computational fluid dynamics (CFD) analysis on a Penn State RBCC test rig, the proposed Draco axisymmetric RBCC engine and the Trailblazer engine. The intent of the analysis on the Penn State test rig is to benchmark the Finite Difference Navier Stokes (FDNS) code for ejector mode fluid dynamics. The Draco analysis was a trade study to determine the ejector mode performance as a function of three engine design variables. The Trailblazer analysis is to evaluate the nozzle performance in scramjet mode. Results to date of each analysis are presented.

Elementary Mode Analysis: A Useful Metabolic Pathway Analysis Tool for Characterizing Cellular Metabolism

PubMed Central

Trinh, Cong T.; Wlaschin, Aaron; Srienc, Friedrich

2010-01-01

Elementary Mode Analysis is a useful Metabolic Pathway Analysis tool to identify the structure of a metabolic network that links the cellular phenotype to the corresponding genotype. The analysis can decompose the intricate metabolic network comprised of highly interconnected reactions into uniquely organized pathways. These pathways consisting of a minimal set of enzymes that can support steady state operation of cellular metabolism represent independent cellular physiological states. Such pathway definition provides a rigorous basis to systematically characterize cellular phenotypes, metabolic network regulation, robustness, and fragility that facilitate understanding of cell physiology and implementation of metabolic engineering strategies. This mini-review aims to overview the development and application of elementary mode analysis as a metabolic pathway analysis tool in studying cell physiology and as a basis of metabolic engineering. PMID:19015845

SU-E-T-635: Process Mapping of Eye Plaque Brachytherapy

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

Huynh, J; Kim, Y

Purpose: To apply a risk-based assessment and analysis technique (AAPM TG 100) to eye plaque brachytherapy treatment of ocular melanoma. Methods: The role and responsibility of personnel involved in the eye plaque brachytherapy is defined for retinal specialist, radiation oncologist, nurse and medical physicist. The entire procedure was examined carefully. First, major processes were identified and then details for each major process were followed. Results: Seventy-one total potential modes were identified. Eight major processes (corresponding detailed number of modes) are patient consultation (2 modes), pretreatment tumor localization (11), treatment planning (13), seed ordering and calibration (10), eye plaque assembly (10),more » implantation (11), removal (11), and deconstruction (3), respectively. Half of the total modes (36 modes) are related to physicist while physicist is not involved in processes such as during the actual procedure of suturing and removing the plaque. Conclusion: Not only can failure modes arise from physicist-related procedures such as treatment planning and source activity calibration, but it can also exist in more clinical procedures by other medical staff. The improvement of the accurate communication for non-physicist-related clinical procedures could potentially be an approach to prevent human errors. More rigorous physics double check would reduce the error for physicist-related procedures. Eventually, based on this detailed process map, failure mode and effect analysis (FMEA) will identify top tiers of modes by ranking all possible modes with risk priority number (RPN). For those high risk modes, fault tree analysis (FTA) will provide possible preventive action plans.« less

Default-Mode Network Functional Connectivity in Aphasia: Therapy-Induced Neuroplasticity

ERIC Educational Resources Information Center

Marcotte, Karine; Perlbarg, Vincent; Marrelec, Guillaume; Benali, Habib; Ansaldo, Ana Ines

2013-01-01

Previous research on participants with aphasia has mainly been based on standard functional neuroimaging analysis. Recent studies have shown that functional connectivity analysis can detect compensatory activity, not revealed by standard analysis. Little is known, however, about the default-mode network in aphasia. In the current study, we studied…

Cycles till failure of silver-zinc cells with completing failures modes: Preliminary data analysis

NASA Technical Reports Server (NTRS)

Sidik, S. M.; Leibecki, H. F.; Bozek, J. M.

1980-01-01

One hundred and twenty nine cells were run through charge-discharge cycles until failure. The experiment design was a variant of a central composite factorial in five factors. Preliminary data analysis consisted of response surface estimation of life. Batteries fail under two basic modes; a low voltage condition and an internal shorting condition. A competing failure modes analysis using maximum likelihood estimation for the extreme value life distribution was performed. Extensive diagnostics such as residual plotting and probability plotting were employed to verify data quality and choice of model.

Failure Modes and Effects Analysis (FMEA): A Bibliography

NASA Technical Reports Server (NTRS)

2000-01-01

Failure modes and effects analysis (FMEA) is a bottom-up analytical process that identifies process hazards, which helps managers understand vulnerabilities of systems, as well as assess and mitigate risk. It is one of several engineering tools and techniques available to program and project managers aimed at increasing the likelihood of safe and successful NASA programs and missions. This bibliography references 465 documents in the NASA STI Database that contain the major concepts, failure modes or failure analysis, in either the basic index of the major subject terms.

Dynamic elementary mode modelling of non-steady state flux data.

PubMed

Folch-Fortuny, Abel; Teusink, Bas; Hoefsloot, Huub C J; Smilde, Age K; Ferrer, Alberto

2018-06-18

A novel framework is proposed to analyse metabolic fluxes in non-steady state conditions, based on the new concept of dynamic elementary mode (dynEM): an elementary mode activated partially depending on the time point of the experiment. Two methods are introduced here: dynamic elementary mode analysis (dynEMA) and dynamic elementary mode regression discriminant analysis (dynEMR-DA). The former is an extension of the recently proposed principal elementary mode analysis (PEMA) method from steady state to non-steady state scenarios. The latter is a discriminant model that permits to identify which dynEMs behave strongly different depending on the experimental conditions. Two case studies of Saccharomyces cerevisiae, with fluxes derived from simulated and real concentration data sets, are presented to highlight the benefits of this dynamic modelling. This methodology permits to analyse metabolic fluxes at early stages with the aim of i) creating reduced dynamic models of flux data, ii) combining many experiments in a single biologically meaningful model, and iii) identifying the metabolic pathways that drive the organism from one state to another when changing the environmental conditions.

Laser dissection sampling modes for direct mass spectral analysis [using a hybrid optical microscopy/laser ablation liquid vortex capture/electrospray ionization system

DOE PAGES

Cahill, John F.; Kertesz, Vilmos; Van Berkel, Gary J.

2016-02-01

Here, laser microdissection coupled directly with mass spectrometry provides the capability of on-line analysis of substrates with high spatial resolution, high collection efficiency, and freedom on shape and size of the sampling area. Establishing the merits and capabilities of the different sampling modes that the system provides is necessary in order to select the best sampling mode for characterizing analytically challenging samples. The capabilities of laser ablation spot sampling, laser ablation raster sampling, and laser 'cut and drop' sampling modes of a hybrid optical microscopy/laser ablation liquid vortex capture electrospray ionization mass spectrometry system were compared for the analysis ofmore » single cells and tissue. Single Chlamydomonas reinhardtii cells were monitored for their monogalactosyldiacylglycerol (MGDG) and diacylglyceryltrimethylhomo-Ser (DGTS) lipid content using the laser spot sampling mode, which was capable of ablating individual cells (4-15 m) even when agglomerated together. Turbid Allium Cepa cells (150 m) having unique shapes difficult to precisely measure using the other sampling modes could be ablated in their entirety using laser raster sampling. Intact microdissections of specific regions of a cocaine-dosed mouse brain tissue were compared using laser 'cut and drop' sampling. Since in laser 'cut and drop' sampling whole and otherwise unmodified sections are captured into the probe, 100% collection efficiencies were achieved. Laser ablation spot sampling has the highest spatial resolution of any sampling mode, while laser ablation raster sampling has the highest sampling area adaptability of the sampling modes. In conclusion, laser ablation spot sampling has the highest spatial resolution of any sampling mode, useful in this case for the analysis of single cells. Laser ablation raster sampling was best for sampling regions with unique shapes that are difficult to measure using other sampling modes. Laser 'cut and drop' sampling can be used for cases where the highest sensitivity is needed, for example, monitoring drugs present in trace amounts in tissue.« less

Laser dissection sampling modes for direct mass spectral analysis [using a hybrid optical microscopy/laser ablation liquid vortex capture/electrospray ionization system

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

Cahill, John F.; Kertesz, Vilmos; Van Berkel, Gary J.

Here, laser microdissection coupled directly with mass spectrometry provides the capability of on-line analysis of substrates with high spatial resolution, high collection efficiency, and freedom on shape and size of the sampling area. Establishing the merits and capabilities of the different sampling modes that the system provides is necessary in order to select the best sampling mode for characterizing analytically challenging samples. The capabilities of laser ablation spot sampling, laser ablation raster sampling, and laser 'cut and drop' sampling modes of a hybrid optical microscopy/laser ablation liquid vortex capture electrospray ionization mass spectrometry system were compared for the analysis ofmore » single cells and tissue. Single Chlamydomonas reinhardtii cells were monitored for their monogalactosyldiacylglycerol (MGDG) and diacylglyceryltrimethylhomo-Ser (DGTS) lipid content using the laser spot sampling mode, which was capable of ablating individual cells (4-15 m) even when agglomerated together. Turbid Allium Cepa cells (150 m) having unique shapes difficult to precisely measure using the other sampling modes could be ablated in their entirety using laser raster sampling. Intact microdissections of specific regions of a cocaine-dosed mouse brain tissue were compared using laser 'cut and drop' sampling. Since in laser 'cut and drop' sampling whole and otherwise unmodified sections are captured into the probe, 100% collection efficiencies were achieved. Laser ablation spot sampling has the highest spatial resolution of any sampling mode, while laser ablation raster sampling has the highest sampling area adaptability of the sampling modes. In conclusion, laser ablation spot sampling has the highest spatial resolution of any sampling mode, useful in this case for the analysis of single cells. Laser ablation raster sampling was best for sampling regions with unique shapes that are difficult to measure using other sampling modes. Laser 'cut and drop' sampling can be used for cases where the highest sensitivity is needed, for example, monitoring drugs present in trace amounts in tissue.« less

Spatio-temporal analysis of irregular vocal fold oscillations: Biphonation due to desynchronization of spatial modes

NASA Astrophysics Data System (ADS)

Neubauer, Jürgen; Mergell, Patrick; Eysholdt, Ulrich; Herzel, Hanspeter

2001-12-01

This report is on direct observation and modal analysis of irregular spatio-temporal vibration patterns of vocal fold pathologies in vivo. The observed oscillation patterns are described quantitatively with multiline kymograms, spectral analysis, and spatio-temporal plots. The complex spatio-temporal vibration patterns are decomposed by empirical orthogonal functions into independent vibratory modes. It is shown quantitatively that biphonation can be induced either by left-right asymmetry or by desynchronized anterior-posterior vibratory modes, and the term ``AP (anterior-posterior) biphonation'' is introduced. The presented phonation examples show that for normal phonation the first two modes sufficiently explain the glottal dynamics. The spatio-temporal oscillation pattern associated with biphonation due to left-right asymmetry can be explained by the first three modes. Higher-order modes are required to describe the pattern for biphonation induced by anterior-posterior vibrations. Spatial irregularity is quantified by an entropy measure, which is significantly higher for irregular phonation than for normal phonation. Two asymmetry measures are introduced: the left-right asymmetry and the anterior-posterior asymmetry, as the ratios of the fundamental frequencies of left and right vocal fold and of anterior-posterior modes, respectively. These quantities clearly differentiate between left-right biphonation and anterior-posterior biphonation. This paper proposes methods to analyze quantitatively irregular vocal fold contour patterns in vivo and complements previous findings of desynchronization of vibration modes in computer modes and in in vitro experiments.

Scaling of mode shapes from operational modal analysis using harmonic forces

NASA Astrophysics Data System (ADS)

Brandt, A.; Berardengo, M.; Manzoni, S.; Cigada, A.

2017-10-01

This paper presents a new method for scaling mode shapes obtained by means of operational modal analysis. The method is capable of scaling mode shapes on any structure, also structures with closely coupled modes, and the method can be used in the presence of ambient vibration from traffic or wind loads, etc. Harmonic excitation can be relatively easily accomplished by using general-purpose actuators, also for force levels necessary for driving large structures such as bridges and highrise buildings. The signal processing necessary for mode shape scaling by the proposed method is simple and the method can easily be implemented in most measurement systems capable of generating a sine wave output. The tests necessary to scale the modes are short compared to typical operational modal analysis test time. The proposed method is thus easy to apply and inexpensive relative to some other methods for scaling mode shapes that are available in literature. Although it is not necessary per se, we propose to excite the structure at, or close to, the eigenfrequencies of the modes to be scaled, since this provides better signal-to-noise ratio in the response sensors, thus permitting the use of smaller actuators. An extensive experimental activity on a real structure was carried out and the results reported demonstrate the feasibility and accuracy of the proposed method. Since the method utilizes harmonic excitation for the mode shape scaling, we propose to call the method OMAH.

Multi-mode reliability-based design of horizontal curves.

PubMed

Essa, Mohamed; Sayed, Tarek; Hussein, Mohamed

2016-08-01

Recently, reliability analysis has been advocated as an effective approach to account for uncertainty in the geometric design process and to evaluate the risk associated with a particular design. In this approach, a risk measure (e.g. probability of noncompliance) is calculated to represent the probability that a specific design would not meet standard requirements. The majority of previous applications of reliability analysis in geometric design focused on evaluating the probability of noncompliance for only one mode of noncompliance such as insufficient sight distance. However, in many design situations, more than one mode of noncompliance may be present (e.g. insufficient sight distance and vehicle skidding at horizontal curves). In these situations, utilizing a multi-mode reliability approach that considers more than one failure (noncompliance) mode is required. The main objective of this paper is to demonstrate the application of multi-mode (system) reliability analysis to the design of horizontal curves. The process is demonstrated by a case study of Sea-to-Sky Highway located between Vancouver and Whistler, in southern British Columbia, Canada. Two noncompliance modes were considered: insufficient sight distance and vehicle skidding. The results show the importance of accounting for several noncompliance modes in the reliability model. The system reliability concept could be used in future studies to calibrate the design of various design elements in order to achieve consistent safety levels based on all possible modes of noncompliance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis of spurious oscillation modes for the shallow water and Navier-Stokes equations

USGS Publications Warehouse

Walters, R.A.; Carey, G.F.

1983-01-01

The origin and nature of spurious oscillation modes that appear in mixed finite element methods are examined. In particular, the shallow water equations are considered and a modal analysis for the one-dimensional problem is developed. From the resulting dispersion relations we find that the spurious modes in elevation are associated with zero frequency and large wave number (wavelengths of the order of the nodal spacing) and consequently are zero-velocity modes. The spurious modal behavior is the result of the finite spatial discretization. By means of an artificial compressibility and limiting argument we are able to resolve the similar problem for the Navier-Stokes equations. The relationship of this simpler analysis to alternative consistency arguments is explained. This modal approach provides an explanation of the phenomenon in question and permits us to deduce the cause of the very complex behavior of spurious modes observed in numerical experiments with the shallow water equations and Navier-Stokes equations. Furthermore, this analysis is not limited to finite element formulations, but is also applicable to finite difference formulations. ?? 1983.

Modeling and analysis of circular flexural-vibration-mode piezoelectric transformer.

PubMed

Huang, Yihua; Huang, Wei

2010-12-01

We propose a circular flexural-vibration-mode piezoelectric transformer and perform a theoretical analysis of the transformer. An equivalent circuit is derived from the equations of piezoelectricity and the Hamilton's principle. With this equivalent circuit, the voltage gain ratio, input impedance, and the efficiency of the circular flexural-vibration-mode piezoelectric transformer can be determined. The basic behavior of the transformer is shown by numerical results.

Analysis of Fin-Line at Millimeter Wavelengths.

DTIC Science & Technology

1982-07-01

8217.gation Constants, Field Calculation. 20, AaSTRAC ’Continue on reverse side If necessary and identify by bt~ck number; --- An analysis of fin-line is...presented along with numerical and experimental results. Dispersion characteristics and field distributions are given for a number of single-mode and...characteristics and field distri- butions are given for a number of single-mode and multi-mode configurations. Agreement between theory and experiment is shown

Detecting coupled collective motions in protein by independent subspace analysis

NASA Astrophysics Data System (ADS)

Sakuraba, Shun; Joti, Yasumasa; Kitao, Akio

2010-11-01

Protein dynamics evolves in a high-dimensional space, comprising aharmonic, strongly correlated motional modes. Such correlation often plays an important role in analyzing protein function. In order to identify significantly correlated collective motions, here we employ independent subspace analysis based on the subspace joint approximate diagonalization of eigenmatrices algorithm for the analysis of molecular dynamics (MD) simulation trajectories. From the 100 ns MD simulation of T4 lysozyme, we extract several independent subspaces in each of which collective modes are significantly correlated, and identify the other modes as independent. This method successfully detects the modes along which long-tailed non-Gaussian probability distributions are obtained. Based on the time cross-correlation analysis, we identified a series of events among domain motions and more localized motions in the protein, indicating the connection between the functionally relevant phenomena which have been independently revealed by experiments.

New method for designing serial resonant power converters

NASA Astrophysics Data System (ADS)

Hinov, Nikolay

2017-12-01

In current work is presented one comprehensive method for design of serial resonant energy converters. The method is based on new simplified approach in analysis of such kind power electronic devices. It is grounded on supposing resonant mode of operation when finding relation between input and output voltage regardless of other operational modes (when controlling frequency is below or above resonant frequency). This approach is named `quasiresonant method of analysis', because it is based on assuming that all operational modes are `sort of' resonant modes. An estimation of error was made because of the a.m. hypothesis and is compared to the classic analysis. The `quasiresonant method' of analysis gains two main advantages: speed and easiness in designing of presented power circuits. Hence it is very useful in practice and in teaching Power Electronics. Its applicability is proven with mathematic modelling and computer simulation.

B-1 Systems Approach to Training. Task Analysis Listings

DTIC Science & Technology

1975-07-01

OFF FUEL VALVES AND PUMPS PHR-OFF FUEL VALVES AND PUMPS = AUTO ^FT TFR MODE LAND SELECTOR SWITCHES TQ *QFF...TFR MODE SWITCH-RIGHT «JFT L TFR MODE SELECT SWITCH TQ * TF1 CHECKLIST TFR MODE SWITCH-LEFT TFR MODE SWITCH-LEFT...DOOR HANDLE ENTRY LADDER CONTROL SWITCH ENTRY LADDER CONTROL SWITCH = DN* 16.1.1.001.OC* SET TANK FILL VALVE SWS ON

Constant-frequency, clamped-mode resonant converters

NASA Technical Reports Server (NTRS)

Tsai, Fu-Sheng; Materu, Peter; Lee, Fred C.

1987-01-01

Two novel clamped-mode resonant converters are proposed which operate at a constant frequency while retaining many desired features of conventional series- and parallel-resonant converters. State-plane analysis techniques are used to identify all possible operating modes and define their mode boundaries. Control-to-output characteristics are derived that specify the regions for natural and forced commutation. The predicted operating modes are verified using a prototype circuit.

Algorithm Summary and Evaluation: Automatic Implementation of Ringdown Analysis for Electromechanical Mode Identification from Phasor Measurements

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

Zhou, Ning; Huang, Zhenyu; Tuffner, Francis K.

2010-02-28

Small signal stability problems are one of the major threats to grid stability and reliability. Prony analysis has been successfully applied on ringdown data to monitor electromechanical modes of a power system using phasor measurement unit (PMU) data. To facilitate an on-line application of mode estimation, this paper develops a recursive algorithm for implementing Prony analysis and proposed an oscillation detection method to detect ringdown data in real time. By automatically detecting ringdown data, the proposed method helps guarantee that Prony analysis is applied properly and timely on the ringdown data. Thus, the mode estimation results can be performed reliablymore » and timely. The proposed method is tested using Monte Carlo simulations based on a 17-machine model and is shown to be able to properly identify the oscillation data for on-line application of Prony analysis. In addition, the proposed method is applied to field measurement data from WECC to show the performance of the proposed algorithm.« less

Dynamic Analysis With Stress Mode Animation by the Integrated Force Method

NASA Technical Reports Server (NTRS)

Patnaik, Surya N.; Coroneos, Rula M.; Hopkins, Dale A.

1997-01-01

Dynamic animation of stresses and displacements, which complement each other, can be a useful tool in the analysis and design of structural components. At the present time only displacement-mode animation is available through the popular stiffness formulation. This paper attempts to complete this valuable visualization tool by augmenting the existing art with stress mode animation. The reformulated method of forces, which in the literature is known as the integrated force method (IFM), became the analyzer of choice for the development of stress mode animation because stresses are the primary unknowns of its dynamic analysis. Animation of stresses and displacements, which have been developed successfully through the IFM analyzers, is illustrated in several examples along with a brief introduction to IFM dynamic analysis. The usefulness of animation in design optimization is illustrated considering the spacer structure component of the International Space Station as an example. An overview of the integrated force method analysis code (IFM/ANALYZERS) is provided in the appendix.

On behavior peculiarity of electron plasma

NASA Astrophysics Data System (ADS)

Gordeeva, N. M.; Yushkanov, A. A.

2018-03-01

The analysis of the analytical solution of the problem of the behavior of electron plasma in the AC electric field is fulfilled. Debye mode describes shielding of the external electric field in the plasma. The analysis of the region of existence of Debye mode, depending on the plasma parameters has been realized. A non-trivial dependence of the region of existence of Debye mode on the degree of degeneracy of the electron gas are revealed. For the case of nearly degenerate electron gas Debye mode has several areas of existence, depending on the frequency of the electric field.

Fiber-guided modes conversion using superposed helical gratings

NASA Astrophysics Data System (ADS)

Ma, Yancheng; Fang, Liang; Wu, Guoan

2017-03-01

Optical fibers can support various modal forms, including vector modes, linear polarization (LP) modes, and orbital angular momentum (OAM) modes, etc. The modal correlation among these modes is investigated via Jones matrix, associated with polarization and helical phase corresponding to spin angular momentum (SAM) and OAM of light, respectively. We can generate different modal forms by adopting superposed helical gratings (SHGs) with opposite helix orientations. Detailed analysis and discussion on mode conversion is given as for mode coupling in optical fibers with both low and high contrast index, respectively. Our study may deepen the understanding for various fiber-guided modes and mode conversion among them via fiber gratings.

Asymmetric Arginine dimethylation of Epstein-Barr virus nuclear antigen 2 promotes DNA targeting

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

Gross, Henrik; Barth, Stephanie; Palermo, Richard D.

The Epstein-Barr virus (EBV) growth-transforms B-lymphocytes. The virus-encoded nuclear antigen 2 (EBNA2) is essential for transformation and activates gene expression by association with DNA-bound transcription factors such as RBPJkappa (CSL/CBF1). We have previously shown that EBNA2 contains symmetrically dimethylated Arginine (sDMA) residues. Deletion of the RG-repeat results in a reduced ability of the virus to immortalise B-cells. We now show that the RG repeat also contains asymmetrically dimethylated Arginines (aDMA) but neither non-methylated (NMA) Arginines nor citrulline residues. We demonstrate that only aDMA-containing EBNA2 is found in a complex with DNA-bound RBPJkappa in vitro and preferentially associates with the EBNA2-responsivemore » EBV C, LMP1 and LMP2A promoters in vivo. Inhibition of methylation in EBV-infected cells results in reduced expression of the EBNA2-regulated viral gene LMP1, providing additional evidence that methylation is a prerequisite for DNA-binding by EBNA2 via association with the transcription factor RBPJkappa.« less

Proteases and caspase-like activity in the yeast Saccharomyces cerevisiae.

PubMed

Wilkinson, Derek; Ramsdale, Mark

2011-10-01

A variety of proteases have been implicated in yeast PCD (programmed cell death) including the metacaspase Mca1 and the separase Esp1, the HtrA-like serine protease Nma111, the cathepsin-like serine carboxypeptideases and a range of vacuolar proteases. Proteasomal activity is also shown to have an important role in determining cell fate, with both pro- and anti-apoptotic roles. Caspase 3-, 6- and 8-like activities are detected upon stimulation of yeast PCD, but not all of this activity is associated with Mca1, implicating other proteases with caspase-like activity in the yeast cell death response. Global proteolytic events that accompany PCD are discussed alongside a consideration of the conservation of the death-related degradome (both at the level of substrate choice and cleavage site). The importance of both gain-of-function changes in the degradome as well as loss-of-function changes are highlighted. Better understanding of both death-related proteases and their substrates may facilitate the design of future antifungal drugs or the manipulation of industrial yeasts for commercial exploitation.

On the use of attachment modes in substructure coupling for dynamic analysis

NASA Technical Reports Server (NTRS)

Craig, R. R., Jr.; Chang, C.-J.

1977-01-01

Substructure coupling or component-mode synthesis may be employed in the solution of dynamics problems for complex structures. Although numerous substructure-coupling methods have been devised, little attention has been devoted to methods employing attachment modes. In the present paper the various mode sets (normal modes, constraint modes, attachment modes) are defined. A generalized substructure-coupling procedure is described. Those substructure-coupling methods which employ attachment modes are described in detail. One of these methods is shown to lead to results (e.g., system natural frequencies) comparable to or better than those obtained by the Hurty (1965) method.

Two-mode elliptical-core weighted fiber sensors for vibration analysis

NASA Technical Reports Server (NTRS)

Vengsarkar, Ashish M.; Murphy, Kent A.; Fogg, Brian R.; Miller, William V.; Greene, Jonathan A.; Claus, Richard O.

1992-01-01

Two-mode, elliptical-core optical fibers are demonstrated in weighted, distributed and selective vibration-mode-filtering applications. We show how appropriate placement of optical fibers on a vibrating structure can lead to vibration mode filtering. Selective vibration-mode suppression on the order of 10 dB has been obtained using tapered two-mode, circular-core fibers with tapering functions that match the second derivatives of the modes of vibration to be enhanced. We also demonstrate the use of chirped, two-mode gratings in fibers as spatial modal sensors that are equivalents of shaped piezoelectric sensors.

Analysis Of Provided Service Quality In Flowers And Living Plants Transport

NASA Astrophysics Data System (ADS)

Poliaková, Adela

2015-06-01

This paper analyses quality of the living flowers and plants transportation. A part of this paper compares the demands for a particular transport mode and a practical demonstration of these transport modes within a specific transport mode. The paper presents a survey of quality of services provided by individual transport modes.

Bayesian Hierarchical Classes Analysis

ERIC Educational Resources Information Center

Leenen, Iwin; Van Mechelen, Iven; Gelman, Andrew; De Knop, Stijn

2008-01-01

Hierarchical classes models are models for "N"-way "N"-mode data that represent the association among the "N" modes and simultaneously yield, for each mode, a hierarchical classification of its elements. In this paper we present a stochastic extension of the hierarchical classes model for two-way two-mode binary data. In line with the original…

Atomistic modeling of the low-frequency mechanical modes and Raman spectra of icosahedral virus capsids

NASA Astrophysics Data System (ADS)

Dykeman, Eric C.; Sankey, Otto F.

2010-02-01

We describe a technique for calculating the low-frequency mechanical modes and frequencies of a large symmetric biological molecule where the eigenvectors of the Hessian matrix are determined with full atomic detail. The method, which follows order N methods used in electronic structure theory, determines the subset of lowest-frequency modes while using group theory to reduce the complexity of the problem. We apply the method to three icosahedral viruses of various T numbers and sizes; the human viruses polio and hepatitis B, and the cowpea chlorotic mottle virus, a plant virus. From the normal-mode eigenvectors, we use a bond polarizability model to predict a low-frequency Raman scattering profile for the viruses. The full atomic detail in the displacement patterns combined with an empirical potential-energy model allows a comparison of the fully atomic normal modes with elastic network models and normal-mode analysis with only dihedral degrees of freedom. We find that coarse-graining normal-mode analysis (particularly the elastic network model) can predict the displacement patterns for the first few (˜10) low-frequency modes that are global and cooperative.

Efficient vibration mode analysis of aircraft with multiple external store configurations

NASA Technical Reports Server (NTRS)

Karpel, M.

1988-01-01

A coupling method for efficient vibration mode analysis of aircraft with multiple external store configurations is presented. A set of low-frequency vibration modes, including rigid-body modes, represent the aircraft. Each external store is represented by its vibration modes with clamped boundary conditions, and by its rigid-body inertial properties. The aircraft modes are obtained from a finite-element model loaded by dummy rigid external stores with fictitious masses. The coupling procedure unloads the dummy stores and loads the actual stores instead. The analytical development is presented, the effects of the fictitious mass magnitudes are discussed, and a numerical example is given for a combat aircraft with external wing stores. Comparison with vibration modes obtained by a direct (full-size) eigensolution shows very accurate coupling results. Once the aircraft and stores data bases are constructed, the computer time for analyzing any external store configuration is two to three orders of magnitude less than that of a direct solution.

Vibration mode analysis of the proton exchange membrane fuel cell stack

NASA Astrophysics Data System (ADS)

Liu, B.; Liu, L. F.; Wei, M. Y.; Wu, C. W.

2016-11-01

Proton exchange membrane fuel cell (PEMFC) stacks usually undergo vibration during packing, transportation, and serving time, in particular for those used in the automobiles or portable equipment. To study the stack vibration response, based on finite element method (FEM), a mode analysis is carried out in the present paper. Using this method, we can distinguish the local vibration from the stack global modes, predict the vibration responses, such as deformed shape and direction, and discuss the effects of the clamping configuration and the clamping force magnitude on vibration modes. It is found that when the total clamping force remains the same, increasing the bolt number can strengthen the stack resistance to vibration in the clamping direction, but cannot obviously strengthen stack resistance to vibration in the translations perpendicular to clamping direction and the three axis rotations. Increasing the total clamping force can increase both of the stack global mode and the bolt local mode frequencies, but will decrease the gasket local mode frequency.

Basal Insulin Regimens for Adults with Type 1 Diabetes Mellitus: A Systematic Review and Network Meta-Analysis.

PubMed

Dawoud, Dalia; O'Mahony, Rachel; Wonderling, David; Cobb, Jill; Higgins, Bernard; Amiel, Stephanie A

2018-02-01

To assess the relative efficacy and safety of basal insulin regimens in adults with type 1 diabetes mellitus (T1DM). A systematic review and Bayesian network meta-analysis (NMA) of randomized controlled trials comparing two or more basal insulin regimens were conducted. The following basal insulin regimens were included: Neutral Protamine Hagedorn (iNPH) (once [od], twice [bid], and four times daily [qid]), insulin detemir (iDet) (od and bid), insulin glargine 100 IU (iGlarg) (od), and insulin degludec (iDegl) (od). We searched the following databases: MEDLINE via OVID, Embase via OVID, and the Cochrane Library (Wiley). Study quality was appraised using Cochrane risk-of-bias checklist for randomized controlled trials. Two outcomes (change in hemoglobin A 1c [HbA 1c ] and rate of severe/major hypoglycemia [SH]) were analyzed. Network inconsistency was assessed using Bucher and chi-square tests. Thirty studies met the eligibility criteria. Twenty-five were included in the HbA 1c network and 16 in the SH network. All studies were of moderate quality. No network inconsistency was evident in the HbA 1c network. Of the seven regimens of interest, iDet (bid) had the highest probability of being best (mean change in HbA 1c -0.48; 95% credible interval -0.69 to -0.29). In contrast, the SH network demonstrated both considerable uncertainty and significant network inconsistency (χ 2 test, P = 0.003). Of the specified frequency regimens, iDet (bid) had the highest probability of being the best basal insulin regimen in terms of reduction in HbA 1c . Ranking of the regimens in terms of the SH rate was highly uncertain and no clear conclusion could be made. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

An Analysis of Mode Effects in the 2010 Course Experience Questionnaire

ERIC Educational Resources Information Center

Carroll, David

2011-01-01

Historically, responses to the Course Experience Questionnaire (CEQ) were required to be collected by self-administered paper or online questionnaire to be eligible for official analysis. CEQ responses collected by telephone were excluded from the final analysis file to minimise the potential for bias due to mode effects: systematic variation in…

Availability Analysis of Dual Mode Systems

DOT National Transportation Integrated Search

1974-04-01

The analytical procedures presented define a method of evaluating the effects of failures in a complex dual-mode system based on a worst case steady-state analysis. The computed result is an availability figure of merit and not an absolute prediction...

Refurbishment of Railroad Crossties : A Technical and Economic Analysis

DOT National Transportation Integrated Search

1977-12-01

An analysis of the principal modes of failure for wooden railroad crossties was conducted and an evaluation of the technical and economic feasibility of refurbishing these ties was conducted. Among the principal modes of structural deterioration, onl...

Independent Orbiter Assessment (IOA): Analysis of the auxiliary power unit

NASA Technical Reports Server (NTRS)

Barnes, J. E.

1986-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results corresponding to the Orbiter Auxiliary Power Unit (APU). The APUs are required to provide power to the Orbiter hydraulics systems during ascent and entry flight phases for aerosurface actuation, main engine gimballing, landing gear extension, and other vital functions. For analysis purposes, the APU system was broken down into ten functional subsystems. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode. A preponderance of 1/1 criticality items were related to failures that allowed the hydrazine fuel to escape into the Orbiter aft compartment, creating a severe fire hazard, and failures that caused loss of the gas generator injector cooling system.

Independent Orbiter Assessment (IOA): Analysis of the electrical power generation/fuel cell powerplant subsystem

NASA Technical Reports Server (NTRS)

Brown, K. L.; Bertsch, P. J.

1986-01-01

Results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results corresponding to the Orbiter Electrical Power Generation (EPG)/Fuel Cell Powerplant (FCP) hardware. The EPG/FCP hardware is required for performing functions of electrical power generation and product water distribution in the Orbiter. Specifically, the EPG/FCP hardware consists of the following divisions: (1) Power Section Assembly (PSA); (2) Reactant Control Subsystem (RCS); (3) Thermal Control Subsystem (TCS); and (4) Water Removal Subsystem (WRS). The IOA analysis process utilized available EPG/FCP hardware drawings and schematics for defining hardware assemblies, components, and hardware items. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode.

Independent Orbiter Assessment (IOA): Analysis of the orbital maneuvering system

NASA Technical Reports Server (NTRS)

Prust, C. D.; Paul, D. J.; Burkemper, V. J.

1987-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The independent analysis results for the Orbital Maneuvering System (OMS) hardware are documented. The OMS provides the thrust to perform orbit insertion, orbit circularization, orbit transfer, rendezvous, and deorbit. The OMS is housed in two independent pods located one on each side of the tail and consists of the following subsystems: Helium Pressurization; Propellant Storage and Distribution; Orbital Maneuvering Engine; and Electrical Power Distribution and Control. The IOA analysis process utilized available OMS hardware drawings and schematics for defining hardware assemblies, components, and hardware items. Each level of hardware was evaluted and analyzed for possible failure modes and effects. Criticality was asigned based upon the severity of the effect for each failure mode.

Variable optical attenuator and dynamic mode group equalizer for few mode fibers.

PubMed

Blau, Miri; Weiss, Israel; Gerufi, Jonathan; Sinefeld, David; Bin-Nun, Moran; Lingle, Robert; Grüner-Nielsen, Lars; Marom, Dan M

2014-12-15

Variable optical attenuation (VOA) for three-mode fiber is experimentally presented, utilizing an amplitude spatial light modulator (SLM), achieving up to -28dB uniform attenuation for all modes. Using the ability to spatially vary the attenuation distribution with the SLM, we also achieve up to 10dB differential attenuation between the fiber's two supported mode group (LP₀₁ and LP₁₁). The spatially selective attenuation serves as the basis of a dynamic mode-group equalizer (DME), potentially gain-balancing mode dependent optical amplification. We extend the experimental three mode DME functionality with a performance analysis of a fiber supporting 6 spatial modes in four mode groups. The spatial modes' distribution and overlap limit the available dynamic range and performance of the DME in the higher mode count case.

Nonlinear Reduced Order Random Response Analysis of Structures with Shallow Curvature

NASA Technical Reports Server (NTRS)

Przekop, Adam; Rizzi, Stephen A.

2006-01-01

The goal of this investigation is to further develop nonlinear modal numerical simulation methods for application to geometrically nonlinear response of structures with shallow curvature under random loadings. For reduced order analysis, the modal basis selection must be capable of reflecting the coupling in both the linear and nonlinear stiffness. For the symmetric shallow arch under consideration, four categories of modal basis functions are defined. Those having symmetric transverse displacements (ST modes) can be designated as transverse dominated (ST-T) modes and in-plane dominated (ST-I) modes. Those having anti-symmetric transverse displacements (AT modes) can similarly be designated as transverse dominated (AT-T) modes and in-plane dominated (AT-I) modes. The response of an aluminum arch under a uniformly distributed transverse random loading is investigated. Results from nonlinear modal simulations made using various modal bases are compared with those obtained from a numerical simulation in physical degrees-of-freedom. While inclusion of ST-T modes is important for all response regimes, it is found that the ST-I modes become increasingly important in the nonlinear response regime, and that AT-T and AT-I modes are critical in the autoparametric regime.

Nonlinear Reduced Order Random Response Analysis of Structures With Shallow Curvature

NASA Technical Reports Server (NTRS)

Przekop, Adam; Rizzi, Stephen A.

2005-01-01

The goal of this investigation is to further develop nonlinear modal numerical simulation methods for application to geometrically nonlinear response of structures with shallow curvature under random loadings. For reduced order analysis, the modal basis selection must be capable of reflecting the coupling in both the linear and nonlinear stiffness. For the symmetric shallow arch under consideration, four categories of modal basis functions are defined. Those having symmetric transverse displacements (ST modes) can be designated as transverse dominated (ST-T) modes and in-plane dominated (ST-I) modes. Those having anti-symmetric transverse displacements (AT modes) can similarly be designated as transverse dominated (AT-T) modes and in-plane dominated (AT-I) modes. The response of an aluminum arch under a uniformly distributed transverse random loading is investigated. Results from nonlinear modal simulations made using various modal bases are compared with those obtained from a numerical simulation in physical degrees-of-freedom. While inclusion of ST-T modes is important for all response regimes, it is found that the ST-I modes become increasingly important in the nonlinear response regime, and that AT-T and AT-I modes are critical in the autoparametric regime.

Analysis of complex elastic structures by a Rayleigh-Ritz component modes method using Lagrange multipliers. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Klein, L. R.

1974-01-01

The free vibrations of elastic structures of arbitrary complexity were analyzed in terms of their component modes. The method was based upon the use of the normal unconstrained modes of the components in a Rayleigh-Ritz analysis. The continuity conditions were enforced by means of Lagrange Multipliers. Examples of the structures considered are: (1) beams with nonuniform properties; (2) airplane structures with high or low aspect ratio lifting surface components; (3) the oblique wing airplane; and (4) plate structures. The method was also applied to the analysis of modal damping of linear elastic structures. Convergence of the method versus the number of modes per component and/or the number of components is discussed and compared to more conventional approaches, ad-hoc methods, and experimental results.

FIBER AND INTEGRATED OPTICS: Use of the offset method in an analysis of a non-Gaussian field distribution in single-mode fiber waveguides

NASA Astrophysics Data System (ADS)

Belov, A. V.; Kurkov, Andrei S.; Chikolini, A. V.

1990-08-01

An offset method is modified to allow an analysis of the distribution of fields in a single-mode fiber waveguide without recourse to the Gaussian approximation. A new approximation for the field is obtained for fiber waveguides with a step refractive index profile and a special analysis employing the Hankel transformation is applied to waveguides with a distributed refractive index. The field distributions determined by this method are compared with the corresponding distributions calculated from the refractive index of a preform from which the fibers are drawn. It is shown that these new approaches can be used to determine the dimensions of a mode spot defined in different ways and to forecast the dispersion characteristics of single-mode fiber waveguides.

Surface instability of a thin electrolyte film undergoing coupled electroosmotic and electrophoretic flows in a microfluidic channel.

PubMed

Ray, Bahni; Reddy, Puchalapalli Dinesh Sankar; Bandyopadhyay, Dipankar; Joo, Sang W; Sharma, Ashutosh; Qian, Shizhi; Biswas, Gautam

2011-11-01

We consider the stability of a thin liquid film with a free charged surface resting on a solid charged substrate by performing a general Orr-Sommerfeld (O-S) analysis complemented by a long-wave (LW) analysis. An externally applied field generates an electroosmotic flow (EOF) near the solid substrate and an electrophoretic flow (EPF) at the free surface. The EPF retards the EOF when both the surfaces have the same sign of the potential and can even lead to the flow reversal in a part of the film. In conjunction with the hydrodynamic stress, the Maxwell stress is also considered in the problem formulation. The electrokinetic potential at the liquid-air and solid-liquid interfaces is modelled by the Poisson-Boltzmann equation with the Debye-Hückel approximation. The O-S analysis shows a finite-wavenumber shear mode of instability when the inertial forces are strong and an LW interfacial mode of instability in the regime where the viscous force dominates. Interestingly, both the modes are found to form beyond a critical flow rate. The shear (interfacial) mode is found to be dominant when the film is thick (thin), the electric field applied is strong (weak), and the zeta-potentials on the liquid-air and solid-liquid interfaces are high (small). The LW analysis predicts the presence of the interfacial mode, but fails to capture the shear mode. The change in the propagation direction of the interfacial mode with the zeta-potential is predicted by both O-S and LW analyses. The parametric range in which the LW analysis is valid is thus demonstrated. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Independent Orbiter Assessment (IOA): Assessment of the EPD and C/remote manipulator system FMEA/CIL

NASA Technical Reports Server (NTRS)

Robinson, W. W.

1988-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA effort first completed an analysis of the Electrical Power Distribution and Control (EPD and C)/Remote Manipulator System (RMS) hardware, generating draft failure modes and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA analysis of the EPD and C/RMS hardware initially generated 345 failure mode worksheets and identified 117 Potential Critical Items (PCIs) before starting the assessment process. These analysis results were compared to the proposed NASA Post 51-L baseline of 132 FMEAs and 66 CIL items.

Comparative analysis of guide mode of government - oriented industry guidance funds under china’s new normal of economic growth

NASA Astrophysics Data System (ADS)

Sun, Chunling; Cheng, Xuemei

2017-11-01

The government-oriented industry guidance Funds solve the problem of financing difficulty and high innovation under the background of China’s new normal. Through the provinces and cities of the policies and regulations of the collation and comparative analysis, it will be divided into three modes. And then compare among three modes and analyze applicability to guide the construction of provinces and cities.

Finite element analysis of a percussion device for pulmonary diagnostics

NASA Astrophysics Data System (ADS)

Dhar, Aneesh

A pneumothorax is a medical condition where one or both lungs are unable to remain expanded due to air in the pleural space. Finite Element Analysis simulations were conducted on a Percussion Device, which is able to diagnose a pneumothorax using an automated percussion technique. The simulations helped determine the natural modes of vibration of the Percussion Device. These modes were then compared to the motion experimentally measured by an accelerometer on the Percussion Device. It was observed that the modes of the percussion head occurred in the range of 0 to 100 Hz, while the sensor membrane modes occurred in the range of 600 to 900 Hz. Most of these modes were found to match with peaks in the experimental spectra. The simulations performed are reliable and provide an understanding of the contribution of the normal modes to the complex signals measured using the Percussion Device.

Analysis of the hot-cavity mode composition of an X-band overmoded relativistic backward wave oscillators

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

Yuan, Yuzhang; Zhang, Jun; Zhong, Huihuang

Overmoded RBWO (Relativistic Backward Wave Oscillators) is utilized more and more often for its high power capacity. However, both sides of SWS (Slow Wave Structure) of overmoded RBWO consist multi TM{sub 0n} modes; in order to achieve the design of reflector, it is essential to make clear of the mode composition of TM{sub 0n}. NUDT (National University of Defence Technology) had done research of the output mode composition in overmoded O-type Cerenkov HPM (High Power Microwave) Oscillators in detail, but in the area where the electron beam exists, the influence of electron beam must be taken into account. Hot-cavity dispersionmore » equation is figured out in this article first, and then analyzes the hot-cavity mode composition of an X-band overmoded RBWO tentatively. The results show that in collimating hole, the hot-cavity mode analysis is more accurate.« less

Dependence of Actuation Strain of Dielectric Elastomer on Equi-biaxial, Pure Shear and Uniaxial Modes of Pre-stretching

NASA Astrophysics Data System (ADS)

Kumar, Ajeet; Ahmad, Dilshad; Patra, Karali

2018-02-01

A dielectric elastomer is capable of large deformation under three basic modes of deformation: equi-biaxial, pure shear and uniaxial. Pre-stretching of dielectric elastomer improves the actuation strain appreciably. Experimental results shows that pre-stretching using equal biaxial mode can result to higher actuation strain compared to other two modes of stretching, i.e., uniaxial and pure shear. However, analysis of the experimental results shows that the actuation strain is independent of the modes of pre-stretching rather it is dependent upon the thickness stretch. For same thickness stretch at a particular voltage, the actuation strain is almost similar for all pre-stretching modes. Power trend lines are obtained to predict the actuation strain at any thickness stretch for a particular voltage. The present analysis opens the door to easily design the actuators, sensors and energy harvesting devices.

SU-F-T-246: Evaluation of Healthcare Failure Mode And Effect Analysis For Risk Assessment

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

Harry, T; University of California, San Diego, La Jolla, CA; Manger, R

Purpose: To evaluate the differences between the Veteran Affairs Healthcare Failure Modes and Effect Analysis (HFMEA) and the AAPM Task Group 100 Failure and Effect Analysis (FMEA) risk assessment techniques in the setting of a stereotactic radiosurgery (SRS) procedure were compared respectively. Understanding the differences in the techniques methodologies and outcomes will provide further insight into the applicability and utility of risk assessments exercises in radiation therapy. Methods: HFMEA risk assessment analysis was performed on a stereotactic radiosurgery procedure. A previous study from our institution completed a FMEA of our SRS procedure and the process map generated from this workmore » was used for the HFMEA. The process of performing the HFMEA scoring was analyzed, and the results from both analyses were compared. Results: The key differences between the two risk assessments are the scoring criteria for failure modes and identifying critical failure modes for potential hazards. The general consensus among the team performing the analyses was that scoring for the HFMEA was simpler and more intuitive then the FMEA. The FMEA identified 25 critical failure modes while the HFMEA identified 39. Seven of the FMEA critical failure modes were not identified by the HFMEA and 21 of the HFMEA critical failure modes were not identified by the FMEA. HFMEA as described by the Veteran Affairs provides guidelines on which failure modes to address first. Conclusion: HFMEA is a more efficient model for identifying gross risks in a process than FMEA. Clinics with minimal staff, time and resources can benefit from this type of risk assessment to eliminate or mitigate high risk hazards with nominal effort. FMEA can provide more in depth details but at the cost of elevated effort.« less

Post-buckling of a pressured biopolymer spherical shell with the mode interaction

NASA Astrophysics Data System (ADS)

Zhang, Lei; Ru, C. Q.

2018-03-01

Imperfection sensitivity is essential for mechanical behaviour of biopolymer shells characterized by high geometric heterogeneity. The present work studies initial post-buckling and imperfection sensitivity of a pressured biopolymer spherical shell based on non-axisymmetric buckling modes and associated mode interaction. Our results indicate that for biopolymer spherical shells with moderate radius-to-thickness ratio (say, less than 30) and smaller effective bending thickness (say, less than 0.2 times average shell thickness), the imperfection sensitivity predicted based on the axisymmetric mode without the mode interaction is close to the present results based on non-axisymmetric modes with the mode interaction with a small (typically, less than 10%) relative errors. However, for biopolymer spherical shells with larger effective bending thickness, the maximum load an imperfect shell can sustain predicted by the present non-axisymmetric analysis can be significantly (typically, around 30%) lower than those predicted based on the axisymmetric mode without the mode interaction. In such cases, a more accurate non-axisymmetric analysis with the mode interaction, as given in the present work, is required for imperfection sensitivity of pressured buckling of biopolymer spherical shells. Finally, the implications of the present study to two specific types of biopolymer spherical shells (viral capsids and ultrasound contrast agents) are discussed.

Ultra-high spatial resolution multi-energy CT using photon counting detector technology

NASA Astrophysics Data System (ADS)

Leng, S.; Gutjahr, R.; Ferrero, A.; Kappler, S.; Henning, A.; Halaweish, A.; Zhou, W.; Montoya, J.; McCollough, C.

2017-03-01

Two ultra-high-resolution (UHR) imaging modes, each with two energy thresholds, were implemented on a research, whole-body photon-counting-detector (PCD) CT scanner, referred to as sharp and UHR, respectively. The UHR mode has a pixel size of 0.25 mm at iso-center for both energy thresholds, with a collimation of 32 × 0.25 mm. The sharp mode has a 0.25 mm pixel for the low-energy threshold and 0.5 mm for the high-energy threshold, with a collimation of 48 × 0.25 mm. Kidney stones with mixed mineral composition and lung nodules with different shapes were scanned using both modes, and with the standard imaging mode, referred to as macro mode (0.5 mm pixel and 32 × 0.5 mm collimation). Evaluation and comparison of the three modes focused on the ability to accurately delineate anatomic structures using the high-spatial resolution capability and the ability to quantify stone composition using the multi-energy capability. The low-energy threshold images of the sharp and UHR modes showed better shape and texture information due to the achieved higher spatial resolution, although noise was also higher. No noticeable benefit was shown in multi-energy analysis using UHR compared to standard resolution (macro mode) when standard doses were used. This was due to excessive noise in the higher resolution images. However, UHR scans at higher dose showed improvement in multi-energy analysis over macro mode with regular dose. To fully take advantage of the higher spatial resolution in multi-energy analysis, either increased radiation dose, or application of noise reduction techniques, is needed.

Modal-pushover-based ground-motion scaling procedure

USGS Publications Warehouse

Kalkan, Erol; Chopra, Anil K.

2011-01-01

Earthquake engineering is increasingly using nonlinear response history analysis (RHA) to demonstrate the performance of structures. This rigorous method of analysis requires selection and scaling of ground motions appropriate to design hazard levels. This paper presents a modal-pushover-based scaling (MPS) procedure to scale ground motions for use in a nonlinear RHA of buildings. In the MPS method, the ground motions are scaled to match to a specified tolerance, a target value of the inelastic deformation of the first-mode inelastic single-degree-of-freedom (SDF) system whose properties are determined by the first-mode pushover analysis. Appropriate for first-mode dominated structures, this approach is extended for structures with significant contributions of higher modes by considering elastic deformation of second-mode SDF systems in selecting a subset of the scaled ground motions. Based on results presented for three actual buildings-4, 6, and 13-story-the accuracy and efficiency of the MPS procedure are established and its superiority over the ASCE/SEI 7-05 scaling procedure is demonstrated.

Risk analysis by FMEA as an element of analytical validation.

PubMed

van Leeuwen, J F; Nauta, M J; de Kaste, D; Odekerken-Rombouts, Y M C F; Oldenhof, M T; Vredenbregt, M J; Barends, D M

2009-12-05

We subjected a Near-Infrared (NIR) analytical procedure used for screening drugs on authenticity to a Failure Mode and Effects Analysis (FMEA), including technical risks as well as risks related to human failure. An FMEA team broke down the NIR analytical method into process steps and identified possible failure modes for each step. Each failure mode was ranked on estimated frequency of occurrence (O), probability that the failure would remain undetected later in the process (D) and severity (S), each on a scale of 1-10. Human errors turned out to be the most common cause of failure modes. Failure risks were calculated by Risk Priority Numbers (RPNs)=O x D x S. Failure modes with the highest RPN scores were subjected to corrective actions and the FMEA was repeated, showing reductions in RPN scores and resulting in improvement indices up to 5.0. We recommend risk analysis as an addition to the usual analytical validation, as the FMEA enabled us to detect previously unidentified risks.

Modes of embayed beach dynamics: analysis reveals emergent timescales

NASA Astrophysics Data System (ADS)

Murray, K. T.; Murray, A.; Limber, P. W.; Ells, K. D.

2013-12-01

Embayed beaches, or beaches positioned between rocky headlands, exhibit morphologic changes over many length and time scales. Beach sediment is transported as a result of the day-to-day wave forcing, causing patterns of erosion and accretion. We use the Rocky Coastline Evolution Model (RCEM) to investigate how patterns of shoreline change depend on wave climate (the distribution of wave-approach angles) and beach characteristics. Measuring changes in beach width through time allows us to track the evolution of the shape of the beach and the movement of sand within it. By using Principle Component Analysis (PCA), these changes can be categorized into modes, where the first few modes explain the majority of the variation in the time series. We analyze these modes and how they vary as a function of wave climate and headland/bay aspect ratio. In the purposefully simple RCEM, sediment transport is wave-driven and affected by wave shadowing behind the headlands. The rock elements in our model experiments (including the headlands) are fixed and unerodable so that this analysis can focus purely on sand dynamics between the headlands, without a sand contribution from the headlands or cliffs behind the beach. The wave climate is characterized by dictating the percentage of offshore waves arriving from the left and the percentage of waves arriving from high angles (very oblique to the coastline orientation). A high-angle dominated wave climate tends to amplify coastline perturbations, whereas a lower-angle wave climate is diffusive. By changing the headland/bay aspect ratio and wave climate, we can perform PCA analysis of generalized embayed beaches with differing anatomy and wave climate forcings. Previous work using PCA analysis of embayed beaches focused on specific locations and shorter timescales (<30 years; Short and Trembanis, 2004). By using the RCEM, we can more broadly characterize beach dynamics over longer timescales. The first two PCA modes, which explain a majority of the beach width time series variation (typically >70%), are a 'breathing' mode and a 'rotational' mode. The newly identified breathing mode captures the sand movement from the middle of the beach towards the edges (thickening the beach along the headlands), and the rotational mode describes the movement of sand towards one headland or another, both in response to stochastic fluctuations about the mean wave climate. The two main modes operate independently and on different timescales. In a weakly low-angle dominated wave climate, the breathing mode tends to be the first mode (capturing the most variance), but with greater low-angle dominance (greater morphological diffusivity), the rotational mode tends to be first. The aspect ratio of the bay also affects the order of the modes, because wave shadowing affects sediment transport behind the headlands. Previous work has attributed beach rotation to changes in various climate indices such as the North Atlantic Oscillation (Thomas et al., 2011); however, PCA analysis of the RCEM results suggests that embayed beaches can have characteristic timescales of sand movement that result from internal system dynamics, emerging even within a statistically constant wave climate. These results suggest that morphologic changes in embayed beaches can occur independently of readily identifiable shifts in forcing.

Independent Orbiter Assessment (IOA): Analysis of the body flap subsystem

NASA Technical Reports Server (NTRS)

Wilson, R. E.; Riccio, J. R.

1986-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items (PCIs). To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The independent analysis results for the Orbiter Body Flap (BF) subsystem hardware are documented. The BF is a large aerosurface located at the trailing edge of the lower aft fuselage of the Orbiter. The proper function of the BF is essential during the dynamic flight phases of ascent and entry. During the ascent phase of flight, the BF trails in a fixed position. For entry, the BF provides elevon load relief, trim control, and acts as a heat shield for the main engines. Specifically, the BF hardware comprises the following components: Power Drive Unit (PDU), rotary actuators, and torque tubes. The IOA analysis process utilized available BF hardware drawings and schematics for defining hardware assemblies, components, and hardware items. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode. Of the 35 failure modes analyzed, 19 were determined to be PCIs.

Frankfurt, Germany: 1030/1090 MegaHertz Signal Analysis

DOT National Transportation Integrated Search

1996-07-01

The Data Link Test Analysis System (DATAS) was used in the Frankfort, Germany : to collect data in the frequency band used by Air Traffic Control Radar : Beacon (ATCRBS), Mode Select (Mode S), and Traffic Alert and Collision : Avoidance (TCAS). Data ...

Linear stability analysis of detonations via numerical computation and dynamic mode decomposition

NASA Astrophysics Data System (ADS)

Kabanov, Dmitry I.; Kasimov, Aslan R.

2018-03-01

We introduce a new method to investigate linear stability of gaseous detonations that is based on an accurate shock-fitting numerical integration of the linearized reactive Euler equations with a subsequent analysis of the computed solution via the dynamic mode decomposition. The method is applied to the detonation models based on both the standard one-step Arrhenius kinetics and two-step exothermic-endothermic reaction kinetics. Stability spectra for all cases are computed and analyzed. The new approach is shown to be a viable alternative to the traditional normal-mode analysis used in detonation theory.

Independent Orbiter Assessment (IOA): Analysis of the elevon subsystem

NASA Technical Reports Server (NTRS)

Wilson, R. E.; Riccio, J. R.

1986-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results for the Orbiter Elevon system hardware. The elevon actuators are located at the trailing edge of the wing surface. The proper function of the elevons is essential during the dynamic flight phases of ascent and entry. In the ascent phase of flight, the elevons are used for relieving high wing loads. For entry, the elevons are used to pitch and roll the vehicle. Specifically, the elevon system hardware comprises the following components: flow cutoff valve; switching valve; electro-hydraulic (EH) servoactuator; secondary delta pressure transducer; bypass valve; power valve; power valve check valve; primary actuator; primary delta pressure transducer; and primary actuator position transducer. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode. Of the 25 failure modes analyzed, 18 were determined to be PCIs.

Independent Orbiter Assessment (IOA): Assessment of the life support and airlock support systems, volume 1

NASA Technical Reports Server (NTRS)

Arbet, J. D.; Duffy, R. E.; Barickman, K.; Saiidi, M. J.

1988-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA effort first completed an analysis of the Life Support and Airlock Support Systems (LSS and ALSS) hardware, generating draft failure modes and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA results were then compared to the NASA FMEA/CIL baseline with proposed Post 51-L updates included. The discrepancies were flagged for potential future resolution. This report documents the results of that comparison for the Orbiter LSS and ALSS hardware. The IOA product for the LSS and ALSS analysis consisted of 511 failure mode worksheets that resulted in 140 potential critical items. Comparison was made to the NASA baseline which consisted of 456 FMEAs and 101 CIL items. The IOA analysis identified 39 failure modes, 6 of which were classified as CIL items, for components not covered by the NASA FMEAs. It was recommended that these failure modes be added to the NASA FMEA baseline. The overall assessment produced agreement on all but 301 FMEAs which caused differences in 111 CIL items.

Evaluation of cell count and classification capabilities in body fluids using a fully automated Sysmex XN equipped with high-sensitive Analysis (hsA) mode and DI-60 hematology analyzer system.

PubMed

Takemura, Hiroyuki; Ai, Tomohiko; Kimura, Konobu; Nagasaka, Kaori; Takahashi, Toshihiro; Tsuchiya, Koji; Yang, Haeun; Konishi, Aya; Uchihashi, Kinya; Horii, Takashi; Tabe, Yoko; Ohsaka, Akimichi

2018-01-01

The XN series automated hematology analyzer has been equipped with a body fluid (BF) mode to count and differentiate leukocytes in BF samples including cerebrospinal fluid (CSF). However, its diagnostic accuracy is not reliable for CSF samples with low cell concentration at the border between normal and pathologic level. To overcome this limitation, a new flow cytometry-based technology, termed "high sensitive analysis (hsA) mode," has been developed. In addition, the XN series analyzer has been equipped with the automated digital cell imaging analyzer DI-60 to classify cell morphology including normal leukocytes differential and abnormal malignant cells detection. Using various BF samples, we evaluated the performance of the XN-hsA mode and DI-60 compared to manual microscopic examination. The reproducibility of the XN-hsA mode showed good results in samples with low cell densities (coefficient of variation; % CV: 7.8% for 6 cells/μL). The linearity of the XN-hsA mode was established up to 938 cells/μL. The cell number obtained using the XN-hsA mode correlated highly with the corresponding microscopic examination. Good correlation was also observed between the DI-60 analyses and manual microscopic classification for all leukocyte types, except monocytes. In conclusion, the combined use of cell counting with the XN-hsA mode and automated morphological analyses using the DI-60 mode is potentially useful for the automated analysis of BF cells.

Computation of elementary modes: a unifying framework and the new binary approach

PubMed Central

Gagneur, Julien; Klamt, Steffen

2004-01-01

Background Metabolic pathway analysis has been recognized as a central approach to the structural analysis of metabolic networks. The concept of elementary (flux) modes provides a rigorous formalism to describe and assess pathways and has proven to be valuable for many applications. However, computing elementary modes is a hard computational task. In recent years we assisted in a multiplication of algorithms dedicated to it. We require a summarizing point of view and a continued improvement of the current methods. Results We show that computing the set of elementary modes is equivalent to computing the set of extreme rays of a convex cone. This standard mathematical representation provides a unified framework that encompasses the most prominent algorithmic methods that compute elementary modes and allows a clear comparison between them. Taking lessons from this benchmark, we here introduce a new method, the binary approach, which computes the elementary modes as binary patterns of participating reactions from which the respective stoichiometric coefficients can be computed in a post-processing step. We implemented the binary approach in FluxAnalyzer 5.1, a software that is free for academics. The binary approach decreases the memory demand up to 96% without loss of speed giving the most efficient method available for computing elementary modes to date. Conclusions The equivalence between elementary modes and extreme ray computations offers opportunities for employing tools from polyhedral computation for metabolic pathway analysis. The new binary approach introduced herein was derived from this general theoretical framework and facilitates the computation of elementary modes in considerably larger networks. PMID:15527509

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

Cheong, S-K; Kim, J

Purpose: The aim of the study is the application of a Failure Modes and Effects Analysis (FMEA) to access the risks for patients undergoing a Low Dose Rate (LDR) Prostate Brachytherapy Treatment. Methods: FMEA was applied to identify all the sub processes involved in the stages of identifying patient, source handling, treatment preparation, treatment delivery, and post treatment. These processes characterize the radiation treatment associated with LDR Prostate Brachytherapy. The potential failure modes together with their causes and effects were identified and ranked in order of their importance. Three indexes were assigned for each failure mode: the occurrence rating (O),more » the severity rating (S), and the detection rating (D). A ten-point scale was used to score each category, ten being the number indicating most severe, most frequent, and least detectable failure mode, respectively. The risk probability number (RPN) was calculated as a product of the three attributes: RPN = O X S x D. The analysis was carried out by a working group (WG) at UPMC. Results: The total of 56 failure modes were identified including 32 modes before the treatment, 13 modes during the treatment, and 11 modes after the treatment. In addition to the protocols already adopted in the clinical practice, the prioritized risk management will be implanted to the high risk procedures on the basis of RPN score. Conclusion: The effectiveness of the FMEA method was established. The FMEA methodology provides a structured and detailed assessment method for the risk analysis of the LDR Prostate Brachytherapy Procedure and can be applied to other radiation treatment modes.« less

Enhanced direct ambient analysis by differential mobility-filtered desorption electrospray ionization-mass spectrometry.

PubMed

Galhena, Asiri S; Harris, Glenn A; Kwasnik, Mark; Fernández, Facundo M

2010-11-15

Desorption electrospray ionization (DESI) is rapidly becoming established as one of the most powerful ionization techniques allowing direct surface analysis by mass spectrometry (MS) in the ambient environment. DESI provides a significant number of unique analytical capabilities for a broad range of applications, both quantitative and qualitative in nature including biological tissue imaging, pharmaceutical quality control, in vivo analysis, proteomics, metabolomics, forensics, and explosives detection. Despite its growing adoption as a powerful high throughput analysis tool, DESI-MS analysis at trace levels often suffers from background chemical interferences generated during the electrospray ionization processes. In order to improve sensitivity and selectivity, a differential mobility (DM) ion separation cell was successfully interfaced to a custom-built DESI ion source. This new hybrid platform can be operated in two modes: the "DM-off" mode for standard DESI analysis and "DM-on mode" where DESI-generated ions are detected after discrimination by the differential mobility cell. The performance of the DESI-DM-MS platform was tested with several samples typically amenable to DESI analysis, including counterfeit pharmaceuticals and binary mixtures of isobaric chemicals of importance in the pharmaceutical and food industries. In the DM-on mode, DESI-MS signal-to-noise ratios were improved by 70-190% when compared to the DM-off mode. Also, the addition of the DM cell enabled selective in-source ion activation of specific DESI-generated precursor ions, providing tandem MS-like spectra in a single stage mass spectrometer.

SU-E-T-421: Failure Mode and Effects Analysis (FMEA) of Xoft Electronic Brachytherapy for the Treatment of Superficial Skin Cancers

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

Hoisak, J; Manger, R; Dragojevic, I

Purpose: To perform a failure mode and effects analysis (FMEA) of the process for treating superficial skin cancers with the Xoft Axxent electronic brachytherapy (eBx) system, given the recent introduction of expanded quality control (QC) initiatives at our institution. Methods: A process map was developed listing all steps in superficial treatments with Xoft eBx, from the initial patient consult to the completion of the treatment course. The process map guided the FMEA to identify the failure modes for each step in the treatment workflow and assign Risk Priority Numbers (RPN), calculated as the product of the failure mode’s probability ofmore » occurrence (O), severity (S) and lack of detectability (D). FMEA was done with and without the inclusion of recent QC initiatives such as increased staffing, physics oversight, standardized source calibration, treatment planning and documentation. The failure modes with the highest RPNs were identified and contrasted before and after introduction of the QC initiatives. Results: Based on the FMEA, the failure modes with the highest RPN were related to source calibration, treatment planning, and patient setup/treatment delivery (Fig. 1). The introduction of additional physics oversight, standardized planning and safety initiatives such as checklists and time-outs reduced the RPNs of these failure modes. High-risk failure modes that could be mitigated with improved hardware and software interlocks were identified. Conclusion: The FMEA analysis identified the steps in the treatment process presenting the highest risk. The introduction of enhanced QC initiatives mitigated the risk of some of these failure modes by decreasing their probability of occurrence and increasing their detectability. This analysis demonstrates the importance of well-designed QC policies, procedures and oversight in a Xoft eBx programme for treatment of superficial skin cancers. Unresolved high risk failure modes highlight the need for non-procedural quality initiatives such as improved planning software and more robust hardware interlock systems.« less

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

Mossahebi, S; Feigenberg, S; Nichols, E

Purpose: GammaPod™, the first stereotactic radiotherapy device for early stage breast cancer treatment, has been recently installed and commissioned at our institution. A multidisciplinary working group applied the failure mode and effects analysis (FMEA) approach to perform a risk analysis. Methods: FMEA was applied to the GammaPod™ treatment process by: 1) generating process maps for each stage of treatment; 2) identifying potential failure modes and outlining their causes and effects; 3) scoring the potential failure modes using the risk priority number (RPN) system based on the product of severity, frequency of occurrence, and detectability (ranging 1–10). An RPN of highermore » than 150 was set as the threshold for minimal concern of risk. For these high-risk failure modes, potential quality assurance procedures and risk control techniques have been proposed. A new set of severity, occurrence, and detectability values were re-assessed in presence of the suggested mitigation strategies. Results: In the single-day image-and-treat workflow, 19, 22, and 27 sub-processes were identified for the stages of simulation, treatment planning, and delivery processes, respectively. During the simulation stage, 38 potential failure modes were found and scored, in terms of RPN, in the range of 9-392. 34 potential failure modes were analyzed in treatment planning with a score range of 16-200. For the treatment delivery stage, 47 potential failure modes were found with an RPN score range of 16-392. The most critical failure modes consisted of breast-cup pressure loss and incorrect target localization due to patient upper-body alignment inaccuracies. The final RPN score of these failure modes based on recommended actions were assessed to be below 150. Conclusion: FMEA risk analysis technique was applied to the treatment process of GammaPod™, a new stereotactic radiotherapy technology. Application of systematic risk analysis methods is projected to lead to improved quality of GammaPod™ treatments. Ying Niu and Cedric Yu are affiliated with Xcision Medical Systems.« less

Effective representation of amide III, II, I, and A modes on local vibrational modes: Analysis of ab initio quantum calculation results.

PubMed

Hahn, Seungsoo

2016-10-28

The Hamiltonian matrix for the first excited vibrational states of a protein can be effectively represented by local vibrational modes constituting amide III, II, I, and A modes to simulate various vibrational spectra. Methods for obtaining the Hamiltonian matrix from ab initio quantum calculation results are discussed, where the methods consist of three steps: selection of local vibrational mode coordinates, calculation of a reduced Hessian matrix, and extraction of the Hamiltonian matrix from the Hessian matrix. We introduce several methods for each step. The methods were assessed based on the density functional theory calculation results of 24 oligopeptides with four different peptide lengths and six different secondary structures. The completeness of a Hamiltonian matrix represented in the reduced local mode space is improved by adopting a specific atom group for each amide mode and reducing the effect of ignored local modes. The calculation results are also compared to previous models using C=O stretching vibration and transition dipole couplings. We found that local electric transition dipole moments of the amide modes are mainly bound on the local peptide planes. Their direction and magnitude are well conserved except amide A modes, which show large variation. Contrary to amide I modes, the vibrational coupling constants of amide III, II, and A modes obtained by analysis of a dipeptide are not transferable to oligopeptides with the same secondary conformation because coupling constants are affected by the surrounding atomic environment.

Analysis of the partially filled viscous ring damper. [application as nutation damper for spinning satellite

NASA Technical Reports Server (NTRS)

Alfriend, K. T.

1973-01-01

A ring partially filled with a viscous fluid has been analyzed as a nutation damper for a spinning satellite. The fluid has been modelled as a rigid slug of finite length moving in a tube and resisted by a linear viscous force. It is shown that there are two distinct modes of motion, called the spin synchronous mode and the nutation synchronous mode. Time constants for each mode are obtained for both the symmetric and asymmetric satellite. The effects of a stop in the tube and an offset of the ring from the spin axis are also investigated. An analysis of test results is also given including a determination of the effect of gravity on the time constants in the two modes.

System for determining the angle of impact of an object on a structure

NASA Technical Reports Server (NTRS)

Prosser, William H. (Inventor); Gorman, Michael R. (Inventor)

1993-01-01

A method for determining the angle of impact of an object on a thin-walled structure which determines the angle of impact through analysis of the acoustic waves which result when an object impacts a structure is presented. Transducers are placed on and in the surface of the structure which sense the wave caused in the structure by impact. The waves are recorded and saved for analysis. For source motion normal to the surface, the antisymmetric mode has a large amplitude while that of the symmetric mode is very small. As the source angle increases with respect to the surface normal, the symmetric mode amplitude increases while the antisymmetric mode amplitude decreases. Thus, the angle of impact is determined by measuring the relative amplitudes of these two lowest order modes.

Buckling analysis of non-prismatic columns based on modified vibration modes

NASA Astrophysics Data System (ADS)

Rahai, A. R.; Kazemi, S.

2008-10-01

In this paper, a new procedure is formulated for the buckling analysis of tapered column members. The calculation of the buckling loads was carried out by using modified vibrational mode shape (MVM) and energy method. The change of stiffness within a column is characterized by introducing a tapering index. It is shown that, the changes in the vibrational mode shapes of a tapered column can be represented by considering a linear combination of various modes of uniform-section columns. As a result, by making use of these modified mode shapes (MVM) and applying the principle of stationary total potential energy, the buckling load of tapered columns can be obtained. Several numerical examples on tapered columns demonstrate the accuracy and efficiency of the proposed analytical method.

Filtration of human EEG recordings from physiological artifacts with empirical mode method

NASA Astrophysics Data System (ADS)

Grubov, Vadim V.; Runnova, Anastasiya E.; Khramova, Marina V.

2017-03-01

In the paper we propose the new method for dealing with noise and physiological artifacts in experimental human EEG recordings. The method is based on analysis of EEG signals with empirical mode decomposition (Hilbert-Huang transform). We consider noises and physiological artifacts on EEG as specific oscillatory patterns that cause problems during EEG analysis and can be detected with additional signals recorded simultaneously with EEG (ECG, EMG, EOG, etc.) We introduce the algorithm of the method with following steps: empirical mode decomposition of EEG signal, choosing of empirical modes with artifacts, removing empirical modes with artifacts, reconstruction of the initial EEG signal. We test the method on filtration of experimental human EEG signals from eye-moving artifacts and show high efficiency of the method.

Failure Modes and Effects Analysis (FMEA) Assistant Tool Feasibility Study

NASA Technical Reports Server (NTRS)

Flores, Melissa; Malin, Jane T.

2013-01-01

An effort to determine the feasibility of a software tool to assist in Failure Modes and Effects Analysis (FMEA) has been completed. This new and unique approach to FMEA uses model based systems engineering concepts to recommend failure modes, causes, and effects to the user after they have made several selections from pick lists about a component s functions and inputs/outputs. Recommendations are made based on a library using common failure modes identified over the course of several major human spaceflight programs. However, the tool could be adapted for use in a wide range of applications from NASA to the energy industry.

Failure Modes and Effects Analysis (FMEA) Assistant Tool Feasibility Study

NASA Astrophysics Data System (ADS)

Flores, Melissa D.; Malin, Jane T.; Fleming, Land D.

2013-09-01

An effort to determine the feasibility of a software tool to assist in Failure Modes and Effects Analysis (FMEA) has been completed. This new and unique approach to FMEA uses model based systems engineering concepts to recommend failure modes, causes, and effects to the user after they have made several selections from pick lists about a component's functions and inputs/outputs. Recommendations are made based on a library using common failure modes identified over the course of several major human spaceflight programs. However, the tool could be adapted for use in a wide range of applications from NASA to the energy industry.

[Failure modes and effects analysis in the prescription, validation and dispensing process].

PubMed

Delgado Silveira, E; Alvarez Díaz, A; Pérez Menéndez-Conde, C; Serna Pérez, J; Rodríguez Sagrado, M A; Bermejo Vicedo, T

2012-01-01

To apply a failure modes and effects analysis to the prescription, validation and dispensing process for hospitalised patients. A work group analysed all of the stages included in the process from prescription to dispensing, identifying the most critical errors and establishing potential failure modes which could produce a mistake. The possible causes, their potential effects, and the existing control systems were analysed to try and stop them from developing. The Hazard Score was calculated, choosing those that were ≥ 8, and a Severity Index = 4 was selected independently of the hazard Score value. Corrective measures and an implementation plan were proposed. A flow diagram that describes the whole process was obtained. A risk analysis was conducted of the chosen critical points, indicating: failure mode, cause, effect, severity, probability, Hazard Score, suggested preventative measure and strategy to achieve so. Failure modes chosen: Prescription on the nurse's form; progress or treatment order (paper); Prescription to incorrect patient; Transcription error by nursing staff and pharmacist; Error preparing the trolley. By applying a failure modes and effects analysis to the prescription, validation and dispensing process, we have been able to identify critical aspects, the stages in which errors may occur and the causes. It has allowed us to analyse the effects on the safety of the process, and establish measures to prevent or reduce them. Copyright © 2010 SEFH. Published by Elsevier Espana. All rights reserved.

Spatiotemporal Filtering Using Principal Component Analysis and Karhunen-Loeve Expansion Approaches for Regional GPS Network Analysis

NASA Technical Reports Server (NTRS)

Dong, D.; Fang, P.; Bock, F.; Webb, F.; Prawirondirdjo, L.; Kedar, S.; Jamason, P.

2006-01-01

Spatial filtering is an effective way to improve the precision of coordinate time series for regional GPS networks by reducing so-called common mode errors, thereby providing better resolution for detecting weak or transient deformation signals. The commonly used approach to regional filtering assumes that the common mode error is spatially uniform, which is a good approximation for networks of hundreds of kilometers extent, but breaks down as the spatial extent increases. A more rigorous approach should remove the assumption of spatially uniform distribution and let the data themselves reveal the spatial distribution of the common mode error. The principal component analysis (PCA) and the Karhunen-Loeve expansion (KLE) both decompose network time series into a set of temporally varying modes and their spatial responses. Therefore they provide a mathematical framework to perform spatiotemporal filtering.We apply the combination of PCA and KLE to daily station coordinate time series of the Southern California Integrated GPS Network (SCIGN) for the period 2000 to 2004. We demonstrate that spatially and temporally correlated common mode errors are the dominant error source in daily GPS solutions. The spatial characteristics of the common mode errors are close to uniform for all east, north, and vertical components, which implies a very long wavelength source for the common mode errors, compared to the spatial extent of the GPS network in southern California. Furthermore, the common mode errors exhibit temporally nonrandom patterns.

A streamlined failure mode and effects analysis.

PubMed

Ford, Eric C; Smith, Koren; Terezakis, Stephanie; Croog, Victoria; Gollamudi, Smitha; Gage, Irene; Keck, Jordie; DeWeese, Theodore; Sibley, Greg

2014-06-01

Explore the feasibility and impact of a streamlined failure mode and effects analysis (FMEA) using a structured process that is designed to minimize staff effort. FMEA for the external beam process was conducted at an affiliate radiation oncology center that treats approximately 60 patients per day. A structured FMEA process was developed which included clearly defined roles and goals for each phase. A core group of seven people was identified and a facilitator was chosen to lead the effort. Failure modes were identified and scored according to the FMEA formalism. A risk priority number,RPN, was calculated and used to rank failure modes. Failure modes with RPN > 150 received safety improvement interventions. Staff effort was carefully tracked throughout the project. Fifty-two failure modes were identified, 22 collected during meetings, and 30 from take-home worksheets. The four top-ranked failure modes were: delay in film check, missing pacemaker protocol/consent, critical structures not contoured, and pregnant patient simulated without the team's knowledge of the pregnancy. These four failure modes had RPN > 150 and received safety interventions. The FMEA was completed in one month in four 1-h meetings. A total of 55 staff hours were required and, additionally, 20 h by the facilitator. Streamlined FMEA provides a means of accomplishing a relatively large-scale analysis with modest effort. One potential value of FMEA is that it potentially provides a means of measuring the impact of quality improvement efforts through a reduction in risk scores. Future study of this possibility is needed.

Bicoherence Analysis of Electrostatic Interchange Mode Coupling in a Turbulent Laboratory Magnetosphere

NASA Astrophysics Data System (ADS)

Abler, M. C.; Mauel, M. E.; Saperstein, A.

2017-12-01

Plasmas confined by a strong dipole field exhibit interchange and entropy mode turbulence, which previous experiments have shown respond locally to active feedback [1]. On the Collisionless Terrella Experiment (CTX), this turbulence is characterized by low frequency, low order, quasi-coherent modes with complex spectral dynamics. We apply bicoherence analysis [2] to study nonlinear phase coupling in a variety of scenarios. First, we study the self-interaction of the naturally occurring interchange turbulence; this analysis is then expanded to include the effects of single or multiple driven modes in the frequency range of the background turbulent oscillations. Initial measurements of coupling coefficients are presented in both cases. Driven low frequency interchange modes are observed to generate multiple harmonics which persist throughout the plasma, becoming weaker as they propagate away from the actuator in the direction of the electron magnetic drift. Future work is also discussed, including application of wavelet bicoherence analysis and applications to planetary magnetospheres. [1] Roberts, Mauel, and Worstell, Phys Plasmas (2015). [2] Grierson, Worstell, and Mauel, Phys Plasmas (2009). Supported by NSF-DOE Partnership for Plasma Science Grants DOE-DE-FG02-00ER54585 and NSF-PHY-1201896.

Practical guidelines to select and scale earthquake records for nonlinear response history analysis of structures

USGS Publications Warehouse

Kalkan, Erol; Chopra, Anil K.

2010-01-01

Earthquake engineering practice is increasingly using nonlinear response history analysis (RHA) to demonstrate performance of structures. This rigorous method of analysis requires selection and scaling of ground motions appropriate to design hazard levels. Presented herein is a modal-pushover-based scaling (MPS) method to scale ground motions for use in nonlinear RHA of buildings and bridges. In the MPS method, the ground motions are scaled to match (to a specified tolerance) a target value of the inelastic deformation of the first-'mode' inelastic single-degree-of-freedom (SDF) system whose properties are determined by first-'mode' pushover analysis. Appropriate for first-?mode? dominated structures, this approach is extended for structures with significant contributions of higher modes by considering elastic deformation of second-'mode' SDF system in selecting a subset of the scaled ground motions. Based on results presented for two bridges, covering single- and multi-span 'ordinary standard' bridge types, and six buildings, covering low-, mid-, and tall building types in California, the accuracy and efficiency of the MPS procedure are established and its superiority over the ASCE/SEI 7-05 scaling procedure is demonstrated.

Influence of the Strain History on TWIP Steel Deformation Mechanisms in the Deep-Drawing Process

NASA Astrophysics Data System (ADS)

Lapovok, R.; Timokhina, I.; Mester, A.-K.; Weiss, M.; Shekhter, A.

2018-03-01

A study of preferable deformation modes on strain path and strain level in a TWIP steel sheet was performed. Different strain paths were obtained by stretch forming of specimens with various shapes and tensile tests. TEM analysis was performed on samples cut from various locations in the deformed specimens, which had different strain paths and strain levels and the preferable deformation modes were identified. Stresses caused by various strain paths were considered and an analytical analysis performed to identify the preferable deformation modes for the case of single crystal. For a single crystal, in assumption of the absence of lattice rotation, the strain path and the level of accumulated equivalent strain define the preferable deformation mode. For a polycrystalline material, such analytical analysis is not possible due to the large number of grains and, therefore, numerical simulation was employed. For the polycrystalline material, the role of strain path diminishes due to the presence of a large number of grains with random orientations and the effect of accumulated strain becomes dominant. However, at small strains the strain path still defines the level of twinning activity. TEM analysis experimentally confirmed that various deformation modes lead to different deformation strengthening mechanisms.

Influence of the Strain History on TWIP Steel Deformation Mechanisms in the Deep-Drawing Process

NASA Astrophysics Data System (ADS)

Lapovok, R.; Timokhina, I.; Mester, A.-K.; Weiss, M.; Shekhter, A.

2018-06-01

A study of preferable deformation modes on strain path and strain level in a TWIP steel sheet was performed. Different strain paths were obtained by stretch forming of specimens with various shapes and tensile tests. TEM analysis was performed on samples cut from various locations in the deformed specimens, which had different strain paths and strain levels and the preferable deformation modes were identified. Stresses caused by various strain paths were considered and an analytical analysis performed to identify the preferable deformation modes for the case of single crystal. For a single crystal, in assumption of the absence of lattice rotation, the strain path and the level of accumulated equivalent strain define the preferable deformation mode. For a polycrystalline material, such analytical analysis is not possible due to the large number of grains and, therefore, numerical simulation was employed. For the polycrystalline material, the role of strain path diminishes due to the presence of a large number of grains with random orientations and the effect of accumulated strain becomes dominant. However, at small strains the strain path still defines the level of twinning activity. TEM analysis experimentally confirmed that various deformation modes lead to different deformation strengthening mechanisms.

Evaluation of MARC for the analysis of rotating composite blades

NASA Technical Reports Server (NTRS)

Bartos, Karen F.; Ernst, Michael A.

1993-01-01

The suitability of the MARC code for the analysis of rotating composite blades was evaluated using a four-task process. A nonlinear displacement analysis and subsequent eigenvalue analysis were performed on a rotating spring mass system to ensure that displacement-dependent centrifugal forces were accounted for in the eigenvalue analysis. Normal modes analyses were conducted on isotropic plates with various degrees of twist to evaluate MARC's ability to handle blade twist. Normal modes analyses were conducted on flat composite plates to validate the newly developed coupled COBSTRAN-MARC methodology. Finally, normal modes analyses were conducted on four composite propfan blades that were designed, analyzed, and fabricated at NASA Lewis Research Center. Results were compared with experimental data. The research documented herein presents MARC as a viable tool for the analysis of rotating composite blades.

Evaluation of MARC for the analysis of rotating composite blades

NASA Astrophysics Data System (ADS)

Bartos, Karen F.; Ernst, Michael A.

1993-03-01

The suitability of the MARC code for the analysis of rotating composite blades was evaluated using a four-task process. A nonlinear displacement analysis and subsequent eigenvalue analysis were performed on a rotating spring mass system to ensure that displacement-dependent centrifugal forces were accounted for in the eigenvalue analysis. Normal modes analyses were conducted on isotropic plates with various degrees of twist to evaluate MARC's ability to handle blade twist. Normal modes analyses were conducted on flat composite plates to validate the newly developed coupled COBSTRAN-MARC methodology. Finally, normal modes analyses were conducted on four composite propfan blades that were designed, analyzed, and fabricated at NASA Lewis Research Center. Results were compared with experimental data. The research documented herein presents MARC as a viable tool for the analysis of rotating composite blades.

The effects of solvent on the conformation and the collective motions of protein: Normal mode analysis and molecular dynamics simulations of melittin in water and in vacuum

NASA Astrophysics Data System (ADS)

Kitao, Akio; Hirata, Fumio; Gō, Nobuhiro

1991-12-01

The effects of solvent on the conformation and dynamics of protein is studied by computer simulation. The dynamics is studied by focusing mainly on collective motions of the protein molecule. Three types of simulation, normal mode analysis, molecular dynamics in vacuum, and molecular dynamics in water are applied to melittin, the major component of bee venom. To define collective motions principal, component analysis as well as normal mode analysis has been carried out. The principal components with large fluctuation amplitudes have a very good correspondence with the low-frequency normal modes. Trajectories of the molecular dynamics simulation are projected onto the principal axes. From the projected motions time correlation functions are calculated. The results indicate that the very-low-frequency modes, whose frequencies are less than ≈ 50 cm -1, are overdamping in water with relaxation times roushly twice as long as the period of the oscillatory motion. Effective Langevin mode analysis is carried out by using the friction coefficient matrix determined from the velocity correlation function calculated from the molecular dynamics trajectory in water. This analysis reproduces the results of the simulation in water reasonably well. The presence of the solvent water is found also to affect the shape of the potential energy surface in such a way that it produces many local minima with low-energy barriers in between, the envelope of which is given by the surface in vacuum. Inter-minimum transitions endow the conformational dynamics of proteins in water another diffusive character, which already exists in the intra-minimum collective motions.

AADL Fault Modeling and Analysis Within an ARP4761 Safety Assessment

DTIC Science & Technology

2014-10-01

Analysis Generator 27 3.2.3 Mapping to OpenFTA Format File 27 3.2.4 Mapping to Generic XML Format 28 3.2.5 AADL and FTA Mapping Rules 28 3.2.6 Issues...PSSA), System Safety Assessment (SSA), Common Cause Analysis (CCA), Fault Tree Analysis ( FTA ), Failure Modes and Effects Analysis (FMEA), Failure...Modes and Effects Summary, Mar - kov Analysis (MA), and Dependence Diagrams (DDs), also referred to as Reliability Block Dia- grams (RBDs). The

Independent Orbiter Assessment (IOA): Assessment of the Orbiter Experiment (OEX) subsystem

NASA Technical Reports Server (NTRS)

Compton, J. M.

1988-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA effort first completed an analysis of the Orbiter Experiments (OEX) hardware, generating draft failure modes and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA results were then compared to the NASA FMEA/CIL baseline with proposed Post 51-L updates included. A resolution of each discrepancy from the comparison is provided through additional analysis as required. The results of that comparison for the Orbiter OEX hardware are documented. The IOA product for the OEX analysis consisted of 82 failure mode worksheets that resulted in two potential critical items being identified.

Analysis of structural dynamic data from Skylab. Volume 2: Skylab analytical and test model data

NASA Technical Reports Server (NTRS)

Demchak, L.; Harcrow, H.

1976-01-01

The orbital configuration test modal data, analytical test correlation modal data, and analytical flight configuration modal data are presented. Tables showing the generalized mass contributions (GMCs) for each of the thirty tests modes are given along with the two dimensional mode shape plots and tables of GMCs for the test correlated analytical modes. The two dimensional mode shape plots for the analytical modes and uncoupled and coupled modes of the orbital flight configuration at three development phases of the model are included.

Adaptive Filtration of Physiological Artifacts in EEG Signals in Humans Using Empirical Mode Decomposition

NASA Astrophysics Data System (ADS)

Grubov, V. V.; Runnova, A. E.; Hramov, A. E.

2018-05-01

A new method for adaptive filtration of experimental EEG signals in humans and for removal of different physiological artifacts has been proposed. The algorithm of the method includes empirical mode decomposition of EEG, determination of the number of empirical modes that are considered, analysis of the empirical modes and search for modes that contains artifacts, removal of these modes, and reconstruction of the EEG signal. The method was tested on experimental human EEG signals and demonstrated high efficiency in the removal of different types of physiological EEG artifacts.

Detecting intrinsic dynamics of traffic flow with recurrence analysis and empirical mode decomposition

NASA Astrophysics Data System (ADS)

Xiong, Hui; Shang, Pengjian; Bian, Songhan

2017-05-01

In this paper, we apply the empirical mode decomposition (EMD) method to the recurrence plot (RP) and recurrence quantification analysis (RQA), to evaluate the frequency- and time-evolving dynamics of the traffic flow. Based on the cumulative intrinsic mode functions extracted by the EMD, the frequency-evolving RP regarding different oscillation of modes suggests that apparent dynamics of the data considered are mainly dominated by its components of medium- and low-frequencies while severely affected by fast oscillated noises contained in the signal. Noises are then eliminated to analyze the intrinsic dynamics and consequently, the denoised time-evolving RQA diversely characterizes the properties of the signal and marks crucial points more accurately where white bands in the RP occur, whereas a strongly qualitative agreement exists between all the non-denoised RQA measures. Generally, the EMD combining with the recurrence analysis sheds more reliable, abundant and inherent lights into the traffic flow, which is meaningful to the empirical analysis of complex systems.

Ray propagation path analysis of acousto-ultrasonic signals in composites

NASA Technical Reports Server (NTRS)

Kautz, Harold E.

1987-01-01

The most important result was the demonstration that acousto-ultrasonic (AU) energy introduced into a laminated graphite/resin propagates by two modes through the structure. The first mode, along the graphite fibers, is the faster. The second mode, through the resin matrix, besides being slower is also more strongly attenuated at the higher frequencies. This demonstration was accomplished by analyzing the time and frequency domain of the composite AU signal and comparing them to the same for a neat resin specimen of the same chemistry and geometry as the composite matrix. Analysis of the fine structure of AU spectra was accomplished by various geometrical strategies. It was shown that the multitude of narrow peaks associated with AU spectra are the effect of the many pulse arrivals in the signal. The shape and distribution of the peaks is mainly determined by the condition of nonnormal reflections of ray paths. A cepstrum analysis was employed which can be useful in detecting characteristic times. Analysis of propagation modes can be accomplished while ignoring the fine structure.

Statistical analysis of mirror mode waves in sheath regions driven by interplanetary coronal mass ejection

NASA Astrophysics Data System (ADS)

Ala-Lahti, Matti M.; Kilpua, Emilia K. J.; Dimmock, Andrew P.; Osmane, Adnane; Pulkkinen, Tuija; Souček, Jan

2018-05-01

We present a comprehensive statistical analysis of mirror mode waves and the properties of their plasma surroundings in sheath regions driven by interplanetary coronal mass ejection (ICME). We have constructed a semi-automated method to identify mirror modes from the magnetic field data. We analyze 91 ICME sheath regions from January 1997 to April 2015 using data from the Wind spacecraft. The results imply that similarly to planetary magnetosheaths, mirror modes are also common structures in ICME sheaths. However, they occur almost exclusively as dip-like structures and in mirror stable plasma. We observe mirror modes throughout the sheath, from the bow shock to the ICME leading edge, but their amplitudes are largest closest to the shock. We also find that the shock strength (measured by Alfvén Mach number) is the most important parameter in controlling the occurrence of mirror modes. Our findings suggest that in ICME sheaths the dominant source of free energy for mirror mode generation is the shock compression. We also suggest that mirror modes that are found deeper in the sheath are remnants from earlier times of the sheath evolution, generated also in the vicinity of the shock.

Extension of the ADjoint Approach to a Laminar Navier-Stokes Solver

NASA Astrophysics Data System (ADS)

Paige, Cody

The use of adjoint methods is common in computational fluid dynamics to reduce the cost of the sensitivity analysis in an optimization cycle. The forward mode ADjoint is a combination of an adjoint sensitivity analysis method with a forward mode automatic differentiation (AD) and is a modification of the reverse mode ADjoint method proposed by Mader et al.[1]. A colouring acceleration technique is presented to reduce the computational cost increase associated with forward mode AD. The forward mode AD facilitates the implementation of the laminar Navier-Stokes (NS) equations. The forward mode ADjoint method is applied to a three-dimensional computational fluid dynamics solver. The resulting Euler and viscous ADjoint sensitivities are compared to the reverse mode Euler ADjoint derivatives and a complex-step method to demonstrate the reduced computational cost and accuracy. Both comparisons demonstrate the benefits of the colouring method and the practicality of using a forward mode AD. [1] Mader, C.A., Martins, J.R.R.A., Alonso, J.J., and van der Weide, E. (2008) ADjoint: An approach for the rapid development of discrete adjoint solvers. AIAA Journal, 46(4):863-873. doi:10.2514/1.29123.

Mode evolution in polarization maintain few mode fibers and applications in mode-division-multiplexing systems

NASA Astrophysics Data System (ADS)

Li, Yan; Zeng, Xinglin; Mo, Qi; Li, Wei; Liu, Zhijian; Wu, Jian

2016-10-01

In few-mode polarization-maintaining-fiber (FM-PMF), the effective-index splitting exists not only between orthogonally polarization state but also between degenerated modes within a high-order mode group. Hence besides the polarization state evolution, the mode patterns in each LP set are need to be analyzed. In this letter, the completed firstorder mode (LP11 mode) evolution in PM-FMF is analyzed and represented by analogous Jones vector and Poincarésphere respectively. Furthermore, with Jones matrix analysis, the modal dynamics in FM-PMFs is conveniently analyzed. The conclusions are used to propose a PM-FMF based LP11 mode rotator and an PM-FMF based OAM generator. Both simulation and experiments are conducted to investigate performance of the two devices.

Two-step relaxation mode analysis with multiple evolution times applied to all-atom molecular dynamics protein simulation.

PubMed

Karasawa, N; Mitsutake, A; Takano, H

2017-12-01

Proteins implement their functionalities when folded into specific three-dimensional structures, and their functions are related to the protein structures and dynamics. Previously, we applied a relaxation mode analysis (RMA) method to protein systems; this method approximately estimates the slow relaxation modes and times via simulation and enables investigation of the dynamic properties underlying the protein structural fluctuations. Recently, two-step RMA with multiple evolution times has been proposed and applied to a slightly complex homopolymer system, i.e., a single [n]polycatenane. This method can be applied to more complex heteropolymer systems, i.e., protein systems, to estimate the relaxation modes and times more accurately. In two-step RMA, we first perform RMA and obtain rough estimates of the relaxation modes and times. Then, we apply RMA with multiple evolution times to a small number of the slowest relaxation modes obtained in the previous calculation. Herein, we apply this method to the results of principal component analysis (PCA). First, PCA is applied to a 2-μs molecular dynamics simulation of hen egg-white lysozyme in aqueous solution. Then, the two-step RMA method with multiple evolution times is applied to the obtained principal components. The slow relaxation modes and corresponding relaxation times for the principal components are much improved by the second RMA.

Quantitative transmission Raman spectroscopy of pharmaceutical tablets and capsules.

PubMed

Johansson, Jonas; Sparén, Anders; Svensson, Olof; Folestad, Staffan; Claybourn, Mike

2007-11-01

Quantitative analysis of pharmaceutical formulations using the new approach of transmission Raman spectroscopy has been investigated. For comparison, measurements were also made in conventional backscatter mode. The experimental setup consisted of a Raman probe-based spectrometer with 785 nm excitation for measurements in backscatter mode. In transmission mode the same system was used to detect the Raman scattered light, while an external diode laser of the same type was used as excitation source. Quantitative partial least squares models were developed for both measurement modes. The results for tablets show that the prediction error for an independent test set was lower for the transmission measurements with a relative root mean square error of about 2.2% as compared with 2.9% for the backscatter mode. Furthermore, the models were simpler in the transmission case, for which only a single partial least squares (PLS) component was required to explain the variation. The main reason for the improvement using the transmission mode is a more representative sampling of the tablets compared with the backscatter mode. Capsules containing mixtures of pharmaceutical powders were also assessed by transmission only. The quantitative results for the capsules' contents were good, with a prediction error of 3.6% w/w for an independent test set. The advantage of transmission Raman over backscatter Raman spectroscopy has been demonstrated for quantitative analysis of pharmaceutical formulations, and the prospects for reliable, lean calibrations for pharmaceutical analysis is discussed.

Interface conductance modal analysis of lattice matched InGaAs/InP

NASA Astrophysics Data System (ADS)

Gordiz, Kiarash; Henry, Asegun

2016-05-01

We studied the heat conduction at InGaAs/InP interfaces and found that the total value of interface conductance was quite high ˜830 MW m-2 K-1. The modal contributions to the thermal interface conductance (TIC) were then investigated to determine the mode responsible. Using the recently developed interface conductance modal analysis method, we showed that more than 70% of the TIC arises from extended modes in the system. The lattice dynamics calculations across the interface revealed that, unlike any other interfaces previously studied, the different classes of vibration around the interface of InGaAs/InP naturally segregate into distinct regions with respect to frequency. In addition, interestingly, the entire region of frequency overlap between the sides of the interface is occupied by extended modes, whereby the two materials vibrate together with a single frequency. We also mapped the correlations between modes, which showed that the contribution by extended modes to the TIC primarily arises from coupling to the modes that have the same frequencies of vibration (i.e., autocorrelations). Moreover, interfacial modes despite their low population still contribute more than 6% to interfacial thermal transport. The analysis sheds light on the nature of heat conduction by different classes of vibration that exist in interfacial systems, which has technological relevance to applications such as thermophotovoltaics and optoelectronics.

Two-step relaxation mode analysis with multiple evolution times applied to all-atom molecular dynamics protein simulation

NASA Astrophysics Data System (ADS)

Karasawa, N.; Mitsutake, A.; Takano, H.

2017-12-01

Proteins implement their functionalities when folded into specific three-dimensional structures, and their functions are related to the protein structures and dynamics. Previously, we applied a relaxation mode analysis (RMA) method to protein systems; this method approximately estimates the slow relaxation modes and times via simulation and enables investigation of the dynamic properties underlying the protein structural fluctuations. Recently, two-step RMA with multiple evolution times has been proposed and applied to a slightly complex homopolymer system, i.e., a single [n ] polycatenane. This method can be applied to more complex heteropolymer systems, i.e., protein systems, to estimate the relaxation modes and times more accurately. In two-step RMA, we first perform RMA and obtain rough estimates of the relaxation modes and times. Then, we apply RMA with multiple evolution times to a small number of the slowest relaxation modes obtained in the previous calculation. Herein, we apply this method to the results of principal component analysis (PCA). First, PCA is applied to a 2-μ s molecular dynamics simulation of hen egg-white lysozyme in aqueous solution. Then, the two-step RMA method with multiple evolution times is applied to the obtained principal components. The slow relaxation modes and corresponding relaxation times for the principal components are much improved by the second RMA.

Density perturbation mode structure of high frequency compressional and global Alfvén eigenmodes in the National Spherical Torus Experiment using a novel reflectometer analysis technique

NASA Astrophysics Data System (ADS)

Crocker, N. A.; Kubota, S.; Peebles, W. A.; Rhodes, T. L.; Fredrickson, E. D.; Belova, E.; Diallo, A.; LeBlanc, B. P.; Sabbagh, S. A.

2018-01-01

Reflectometry measurements of compressional (CAE) and global (GAE) Alfvén eigenmodes are analyzed to obtain the amplitude and spatial structure of the density perturbations associated with the modes. A novel analysis technique developed for this purpose is presented. The analysis also naturally yields the amplitude and spatial structure of the density contour radial displacement, which is found to be 2-4 times larger than the value estimated directly from the reflectometer measurements using the much simpler ‘mirror approximation’. The modes were driven by beam ions in a high power (6 MW) neutral beam heated H-mode discharge (#141398) in the National Spherical Torus Experiment. The results of the analysis are used to assess the contribution of the modes to core energy transport and ion heating. The total displacement amplitude of the modes, which is shown to be larger than previously estimated (Crocker et al 2013 Nucl. Fusion 53 43017), is compared to the predicted threshold (Gorelenkov et al 2010 Nucl. Fusion 50 84012) for the anomalously high heat diffusion inferred from transport modeling in similar NSTX discharges. The results of the analysis also have strong implications for the energy transport via coupling of CAEs to kinetic Alfvén waves seen in simulations with the Hybrid MHD code (Belova et al 2015 Phys. Rev. Lett. 115 15001). Finally, the amplitudes of the observed CAEs fall well below the threshold for causing significant ion heating by stochastic velocity space diffusion (Gates et al 2001 Phys. Rev. Lett. 87 205003).

Does the Addition of M-Mode to B-Mode Ultrasound Increase the Accuracy of Identification of Lung Sliding in Traumatic Pneumothoraces?

PubMed

Avila, Jacob; Smith, Ben; Mead, Therese; Jurma, Duane; Dawson, Matthew; Mallin, Michael; Dugan, Adam

2018-04-24

It is unknown whether the addition of M-mode to B-mode ultrasound (US) has any effect on the overall accuracy of interpretation of lung sliding in the evaluation of a pneumothorax by emergency physicians. This study aimed to determine what effect, if any, this addition has on US interpretation by emergency physicians of varying training levels. One hundred forty emergency physicians were randomized via online software to receive a quiz with B-mode clips alone or B-mode with corresponding M-mode images and asked to identify the presence or absence of lung sliding. The sensitivity, specificity, and accuracy of the diagnosis of lung sliding with and without M-mode US were compared. Overall, the sensitivities, specificities, and accuracies of B-mode + M-mode US versus B-mode US alone were 93.1% and 93.2% (P = .8), 96.0% and 89.8% (P < .0001), and 91.5% and 94.5% (P = .0091), respectively. A subgroup analysis showed that in those providers with fewer than 250 total US scans done previously, M-mode US increased accuracy from 88.2% (95% confidence interval, 86.2%-90.2%) to 94.4% (92.8%-96.0%; P = .001) and increased the specificity from 87.0% (84.5%-89.5%) to 97.2% (95.4%-99.0%; P < .0001) compared with B-mode US alone. There was no statistically significant difference observed in the sensitivity, specificity, and accuracy of B-mode + M-mode US compared with B-mode US alone in those with more than 250 scans. The addition of M-mode images to B-mode clips aids in the accurate diagnosis of lung sliding by emergency physicians. The subgroup analysis showed that the benefit of M-mode US disappears after emergency physicians have performed more than 250 US examinations. © 2018 by the American Institute of Ultrasound in Medicine.

draco: Analysis and simulation of drift scan radio data

NASA Astrophysics Data System (ADS)

Shaw, J. Richard

2017-12-01

draco analyzes transit radio data with the m-mode formalism. It is telescope agnostic, and is used as part of the analysis and simulation pipeline for the CHIME (Canadian Hydrogen Intensity Mapping Experiment) telescope. It can simulate time stream data from maps of the sky (using the m-mode formalism) and add gain fluctuations and correctly correlated instrumental noise (i.e. Wishart distributed). Further, it can perform various cuts on the data and make maps of the sky from data using the m-mode formalism.

Pedestal turbulence simulations using GENE

NASA Astrophysics Data System (ADS)

Liu, Xing; Kotschenreuther, M.; Hatch, D. R.; Zheng, L. J.; Mahajan, S.; Diallo, A.; Groebner, R. J.; Hubbard, A. E.; Hughes, J. W.; Maggi, C. F.; Saarelma, S.; JET Contributors

2017-10-01

We match frequencies, power balance, and other transport characteristics of several pedestals-two DIIID ELMy H-modes and a C-Mod I-mode, and attempt this for a C-Mod ELMy H-mode. Observed quasi-coherent fluctuations (QCFs) on the DIIID shots are identified as MTMs. The MTMs match frequency and power balance (with slight adjustment of temperature profile), and cause low transport in the density, ion heat and impurity channels- consistent with observed inter-ELM evolution of ion and electron temperature, electron and impurity density, or transport analysis of those channels. KBM can be ruled out as the dominant agent for heat transport. We find the Weakly Coherent Mode on C-Mod I-mode may be an electrostatic heavy particle/ITG mode. Analysis is ongoing for the C-Mod ELMy H-mode QCF. Pedestal density profiles in JET-ILW are consistent with ITG induced particle pinch. Work supported by US DOE under DE-FC02-04ER54698, DE-FG02-04ER54742 and DE-FC02-99ER54512 and by Eurofusion under Grant No. 633053.