Statistical Evaluation of NDE Reliability in the Aerospace Industry

The goal of this paper is to review the statistical methods used in the aerospace industries to evaluate NDE reliability. The techniques presented are consistent with the damage tolerant design and structural maintenance philosophies of the aerospace industry. The first part of this paper establishes the evaluation criteria and discusses the history of NDE reliability evaluations. The second part describes the state-of-the-art analysis methods through examples from the retirement for cause (RFC) inspection system evaluation. The last part of the paper discusses some techniques used to rate operator performance and deal with false calls

POD Assessment Using Real Aircraft Engine Components

The economic drive towards using military aircraft beyond their initial design life has created a great interest in damage-tolerance (DT) based maintenance philosophy. The DT approach relies on routine nondestructive inspections (NDI) and requires the NDI performance to be quantified in terms of probability of detection (POD). From the POD-flaw size relationship, the detection limit of inspection techniques, in terms of flaw size, is established and then used to calculate safe inspection interval [1].</p

Measuring Differences Among Probability of Detection Curves

Probability of Detection (POD) curves are compared by two statistical methods to quantify system-to-system differences. The first method assesses performance among a group of inspection systems through an adaptation of statistical analysis of variance (ANOVA). The second method uses a chi-squared statistic to test for a difference between two systems. Examples using eddy current data are given for each technique.</p

Submicroscopic Gametocytes and the Transmission of Antifolate-Resistant Plasmodium falciparum in Western Kenya

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites. In the present study, we determine the association between parasite mutations, submicroscopic P. falciparum gametocytemia and malaria transmission to mosquitoes. METHODOLOGY/PRINCIPAL FINDINGS: Samples from children treated with SP alone or in combination with artesunate (AS) or amodiaquine were genotyped for SNPs in the dhfr and dhps genes. Gametocytemia was determined by microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification (Pfs25 QT-NASBA). Transmission was determined by membrane-feeding assays. We observed no wild type infections, 66.5% (127/191) of the infections expressed mutations at all three dhfr codons prior to treatment. The presence of all three mutations was not related to higher Pfs25 QT-NASBA gametocyte prevalence or density during follow-up, compared to double mutant infections. The proportion of infected mosquitoes or oocyst burden was also not related to the number of mutations. Addition of AS to SP reduced gametocytemia and malaria transmission during follow-up. CONCLUSIONS/SIGNIFICANCE: In our study population where all infections had at least a double mutation in the dhfr gene, additional mutations were not related to increased submicroscopic gametocytemia or enhanced malaria transmission. The absence of wild-type infections is likely to have reduced our power to detect differences. Our data further support the use of ACT to reduce the transmission of drug-resistant malaria parasites

A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria

<p>Abstract</p> <p>Background</p> <p>An assessment of the correlation between anti-malarial treatment outcome and molecular markers would improve the early detection and monitoring of drug resistance by <it>Plasmodium falciparum</it>. The purpose of this systematic review was to determine the risk of treatment failure associated with specific polymorphisms in the parasite genome or gene copy number.</p> <p>Methods</p> <p>Clinical studies of non-severe malaria reporting on target genetic markers (SNPs for <it>pfmdr1</it>, <it>pfcrt</it>, <it>dhfr</it>, <it>dhps</it>, gene copy number for <it>pfmdr1</it>) providing complete information on inclusion criteria, outcome, follow up and genotyping, were included. Three investigators independently extracted data from articles. Results were stratified by gene, codon, drug and duration of follow-up. For each study and aggregate data the random effect odds ratio (OR) with 95%CIs was estimated and presented as Forest plots. An OR with a lower 95^thconfidence interval > 1 was considered consistent with a failure being associated to a given gene mutation.</p> <p>Results</p> <p>92 studies were eligible among the selection from computerized search, with information on <it>pfcrt </it>(25/159 studies), <it>pfmdr1 </it>(29/236 studies), <it>dhfr </it>(18/373 studies), <it>dhps </it>(20/195 studies). The risk of therapeutic failure after chloroquine was increased by the presence of <it>pfcrt </it>K76T (Day 28, OR = 7.2 [95%CI: 4.5–11.5]), <it>pfmdr1 </it>N86Y was associated with both chloroquine (Day 28, OR = 1.8 [95%CI: 1.3–2.4]) and amodiaquine failures (OR = 5.4 [95%CI: 2.6–11.3, p < 0.001]). For sulphadoxine-pyrimethamine the <it>dhfr </it>single (S108N) (Day 28, OR = 3.5 [95%CI: 1.9–6.3]) and triple mutants (S108N, N51I, C59R) (Day 28, OR = 3.1 [95%CI: 2.0–4.9]) and <it>dhfr</it>-<it>dhps </it>quintuple mutants (Day 28, OR = 5.2 [95%CI: 3.2–8.8]) also increased the risk of treatment failure. Increased <it>pfmdr1 </it>copy number was correlated with treatment failure following mefloquine (OR = 8.6 [95%CI: 3.3–22.9]).</p> <p>Conclusion</p> <p>When applying the selection procedure for comparative analysis, few studies fulfilled all inclusion criteria compared to the large number of papers identified, but heterogeneity was limited. Genetic molecular markers were related to an increased risk of therapeutic failure. Guidelines are discussed and a checklist for further studies is proposed.</p

Dynamic metabolic control: towards precision engineering of metabolism

Advances in metabolic engineering have led to the synthesis of a wide variety of valuable chemicals in microorganisms. The key to commercializing these processes is the improvement of titer, productivity, yield, and robustness. Traditional approaches to enhancing production use the “push–pull-block” strategy that modulates enzyme expression under static control. However, strains are often optimized for specific laboratory set-up and are sensitive to environmental fluctuations. Exposure to sub-optimal growth conditions during large-scale fermentation often reduces their production capacity. Moreover, static control of engineered pathways may imbalance cofactors or cause the accumulation of toxic intermediates, which imposes burden on the host and results in decreased production. To overcome these problems, the last decade has witnessed the emergence of a new technology that uses synthetic regulation to control heterologous pathways dynamically, in ways akin to regulatory networks found in nature. Here, we review natural metabolic control strategies and recent developments in how they inspire the engineering of dynamically regulated pathways. We further discuss the challenges of designing and engineering dynamic control and highlight how model-based design can provide a powerful formalism to engineer dynamic control circuits, which together with the tools of synthetic biology, can work to enhance microbial production

Probabilistic Consequences of Imperfect NDE

This paper presents results of Monte Carlo simulation of the Retirement-for-Cause (RFC) engine maintenance system as developed by Pratt and Whitney Aircraft and the U. S. Air Force. The Retirement-for-Cause concept is addressed, conventional Monte Carlo modeling techniques are explained, and an alternative approach developed at Pratt and Whitney is presented. Next, a simplified non-ideal Non-Destructive-Evaluation (NDE) model with fixed probabilities of Type I and Type II errors is described and simulation results obtained using this model are presented and discussed. An appendix presents a survey of various methods used to model NDE.</p

A study of the survival of retinal ganglion cells following a damage of the retinocolicular projection at the brachium of superior colliculus in adult hamsters

The need to quantify and validate nondestructive inspection (NDI) performance capabilities has become increasingly necessary with the application of fatigue and fracture mechanics as the basis of design for modern engineering systems. The demand for quantitative characterization of NDI performance capabilities has led to the development of several analytical tools for this purpose

Modelling the steady state deformation stress under various deformation conditions using a single irreversible thermodynamics based formulation

A new unified description for the steady state deformation stress in single and polycrystalline metals and for various deformation conditions is presented. The new formulation for dislocation controlled deformation stems from the field of irreversible thermodynamics. The model applies to conditions of dynamic recovery as well as dynamic recrystallization and has been validated for constant strain rate and creep loading conditions. Unlike existing approaches, the new model captures transitions between deformation mechanisms within a single formulation. For conditions of dynamic recrystallization, the average dislocation density is found to be a function of the shear strain rate and a term combining the dislocation climb velocity and the grain boundary velocity. © 2009 Acta Materialia Inc.link_to_subscribed_fulltex