Orbit Transfer Vehicle Engine Study. Phase A, extension 1: Advanced expander cycle engine optimization

NASA Technical Reports Server (NTRS)

Mellish, J. A.

1979-01-01

The performance optimization of expander cycle engines at vacuum thrust levels of 10K, 15K, and 20K lb is discussed. The optimization is conducted for a maximum engine length with an extendible nozzle in the retracted position of 60 inches and an engine mixture ratio of 6.0:1. The thrust chamber geometry and cycle analyses are documented. In addition, the sensitivity of a recommended baseline expander cycle to component performance variations is determined and chilldown/start propellant consumptions are estimated.

Cost effectiveness of imatinib compared with interferon-alpha or hydroxycarbamide for first-line treatment of chronic myeloid leukaemia.

PubMed

Dalziel, Kim; Round, Ali; Garside, Ruth; Stein, Ken

2005-01-01

To evaluate the cost utility of imatinib compared with interferon (IFN)-alpha or hydroxycarbamide (hydroxyurea) for first-line treatment of chronic myeloid leukaemia. A cost-utility (Markov) model within the setting of the UK NHS and viewed from a health system perspective was adopted. Transition probabilities and relative risks were estimated from published literature. Costs of drug treatment, outpatient care, bone marrow biopsies, radiography, blood transfusions and inpatient care were obtained from the British National Formulary and local hospital databases. Costs (pound, year 2001-03 values) were discounted at 6%. Quality-of-life (QOL) data were obtained from the published literature and discounted at 1.5%. The main outcome measure was cost per QALY gained. Extensive one-way sensitivity analyses were performed along with probabilistic (stochastic) analysis. The incremental cost-effectiveness ratio (ICER) of imatinib, compared with IFNalpha, was pound26,180 per QALY gained (one-way sensitivity analyses ranged from pound19,449 to pound51,870) and compared with hydroxycarbamide was pound86,934 per QALY (one-way sensitivity analyses ranged from pound69,701 to pound147,095) [ pound1=$US1.691=euro1.535 as at 31 December 2002].Based on the probabilistic sensitivity analysis, 50% of the ICERs for imatinib, compared with IFNalpha, fell below a threshold of approximately pound31,000 per QALY gained. Fifty percent of ICERs for imatinib, compared with hydroxycarbamide, fell below approximately pound95,000 per QALY gained. This model suggests, given its underlying data and assumptions, that imatinib may be moderately cost effective when compared with IFNalpha but considerably less cost effective when compared with hydroxycarbamide. There are, however, many uncertainties due to the lack of long-term data.

Domain decomposition for aerodynamic and aeroacoustic analyses, and optimization

NASA Technical Reports Server (NTRS)

Baysal, Oktay

1995-01-01

The overarching theme was the domain decomposition, which intended to improve the numerical solution technique for the partial differential equations at hand; in the present study, those that governed either the fluid flow, or the aeroacoustic wave propagation, or the sensitivity analysis for a gradient-based optimization. The role of the domain decomposition extended beyond the original impetus of discretizing geometrical complex regions or writing modular software for distributed-hardware computers. It induced function-space decompositions and operator decompositions that offered the valuable property of near independence of operator evaluation tasks. The objectives have gravitated about the extensions and implementations of either the previously developed or concurrently being developed methodologies: (1) aerodynamic sensitivity analysis with domain decomposition (SADD); (2) computational aeroacoustics of cavities; and (3) dynamic, multibody computational fluid dynamics using unstructured meshes.

Orbital transfer vehicle concept definition and system analysis study, 1986. Volume 9: Study extension results

NASA Technical Reports Server (NTRS)

Kofal, Allen E.

1987-01-01

The purpose of this extension to the OTV Concept Definition and Systems Analysis Study was to improve the definition of the OTV Program that will be most beneficial to the nation in the 1995 to 2010 timeframe. The implications of the defined mission and defined launch vehicle are investigated. The key mission requirements identified for the Space Transportation Architecture Study (STAS) were established and reflect a need for early capability and more ambitious capability growth. The key technical objectives and related issues addressed are summarized. The analyses of selected areas including aerobrake design, proximity operations, and the balance of EVA and IVA operations used in the support of the OTV at the space-base were enhanced. Sensitivity studies were conducted to establish how the OTV program should be tailored to meet changing circumstances.

An optimal search filter for retrieving systematic reviews and meta-analyses

PubMed Central

2012-01-01

Background Health-evidence.ca is an online registry of systematic reviews evaluating the effectiveness of public health interventions. Extensive searching of bibliographic databases is required to keep the registry up to date. However, search filters have been developed to assist in searching the extensive amount of published literature indexed. Search filters can be designed to find literature related to a certain subject (i.e. content-specific filter) or particular study designs (i.e. methodological filter). The objective of this paper is to describe the development and validation of the health-evidence.ca Systematic Review search filter and to compare its performance to other available systematic review filters. Methods This analysis of search filters was conducted in MEDLINE, EMBASE, and CINAHL. The performance of thirty-one search filters in total was assessed. A validation data set of 219 articles indexed between January 2004 and December 2005 was used to evaluate performance on sensitivity, specificity, precision and the number needed to read for each filter. Results Nineteen of 31 search filters were effective in retrieving a high level of relevant articles (sensitivity scores greater than 85%). The majority achieved a high degree of sensitivity at the expense of precision and yielded large result sets. The main advantage of the health-evidence.ca Systematic Review search filter in comparison to the other filters was that it maintained the same level of sensitivity while reducing the number of articles that needed to be screened. Conclusions The health-evidence.ca Systematic Review search filter is a useful tool for identifying published systematic reviews, with further screening to identify those evaluating the effectiveness of public health interventions. The filter that narrows the focus saves considerable time and resources during updates of this online resource, without sacrificing sensitivity. PMID:22512835

Bile acids: analysis in biological fluids and tissues

PubMed Central

Griffiths, William J.; Sjövall, Jan

2010-01-01

The formation of bile acids/bile alcohols is of major importance for the maintenance of cholesterol homeostasis. Besides their functions in lipid absorption, bile acids/bile alcohols are regulatory molecules for a number of metabolic processes. Their effects are structure-dependent, and numerous metabolic conversions result in a complex mixture of biologically active and inactive forms. Advanced methods are required to characterize and quantify individual bile acids in these mixtures. A combination of such analyses with analyses of the proteome will be required for a better understanding of mechanisms of action and nature of endogenous ligands. Mass spectrometry is the basic detection technique for effluents from chromatographic columns. Capillary liquid chromatography-mass spectrometry with electrospray ionization provides the highest sensitivity in metabolome analysis. Classical gas chromatography-mass spectrometry is less sensitive but offers extensive structure-dependent fragmentation increasing the specificity in analyses of isobaric isomers of unconjugated bile acids. Depending on the nature of the bile acid/bile alcohol mixture and the range of concentration of individuals, different sample preparation sequences, from simple extractions to group separations and derivatizations, are applicable. We review the methods currently available for the analysis of bile acids in biological fluids and tissues, with emphasis on the combination of liquid and gas phase chromatography with mass spectrometry. PMID:20008121

Responding to Nonwords in the Lexical Decision Task: Insights from the English Lexicon Project

PubMed Central

Yap, Melvin J.; Sibley, Daragh E.; Balota, David A.; Ratcliff, Roger; Rueckl, Jay

2014-01-01

Researchers have extensively documented how various statistical properties of words (e.g., word-frequency) influence lexical processing. However, the impact of lexical variables on nonword decision-making performance is less clear. This gap is surprising, since a better specification of the mechanisms driving nonword responses may provide valuable insights into early lexical processes. In the present study, item-level and participant-level analyses were conducted on the trial-level lexical decision data for almost 37,000 nonwords in the English Lexicon Project in order to identify the influence of different psycholinguistic variables on nonword lexical decision performance, and to explore individual differences in how participants respond to nonwords. Item-level regression analyses reveal that nonword response time was positively correlated with number of letters, number of orthographic neighbors, number of affixes, and baseword number of syllables, and negatively correlated with Levenshtein orthographic distance and baseword frequency. Participant-level analyses also point to within- and between-session stability in nonword responses across distinct sets of items, and intriguingly reveal that higher vocabulary knowledge is associated with less sensitivity to some dimensions (e.g., number of letters) but more sensitivity to others (e.g., baseword frequency). The present findings provide well-specified and interesting new constraints for informing models of word recognition and lexical decision. PMID:25329078

The tarsal taste of honey bees: behavioral and electrophysiological analyses

PubMed Central

de Brito Sanchez, Maria Gabriela; Lorenzo, Esther; Su, Songkun; Liu, Fanglin; Zhan, Yi; Giurfa, Martin

2014-01-01

Taste plays a crucial role in the life of honey bees as their survival depends on the collection and intake of nectar and pollen, and other natural products. Here we studied the tarsal taste of honey bees through a series of behavioral and electrophysiological analyses. We characterized responsiveness to various sweet, salty and bitter tastants delivered to gustatory sensilla of the fore tarsi. Behavioral experiments showed that stimulation of opposite fore tarsi with sucrose and bitter substances or water yielded different outcomes depending on the stimulation sequence. When sucrose was applied first, thereby eliciting proboscis extension, no bitter substance could induce proboscis retraction, thus suggesting that the primacy of sucrose stimulation induced a central excitatory state. When bitter substances or water were applied first, sucrose stimulation could still elicit proboscis extension but to a lower level, thus suggesting central inhibition based on contradictory gustatory input on opposite tarsi. Electrophysiological experiments showed that receptor cells in the gustatory sensilla of the tarsomeres are highly sensitive to saline solutions at low concentrations. No evidence for receptors responding specifically to sucrose or to bitter substances was found in these sensilla. Receptor cells in the gustatory sensilla of the claws are highly sensitive to sucrose. Although bees do not possess dedicated bitter-taste receptors in the tarsi, indirect bitter detection is possible because bitter tastes inhibit sucrose receptor cells of the claws when mixed with sucrose solution. By combining behavioral and electrophysiological approaches, these results provide the first integrative study on tarsal taste detection in the honey bee. PMID:24550801

The tarsal taste of honey bees: behavioral and electrophysiological analyses.

PubMed

de Brito Sanchez, Maria Gabriela; Lorenzo, Esther; Su, Songkun; Liu, Fanglin; Zhan, Yi; Giurfa, Martin

2014-01-01

Taste plays a crucial role in the life of honey bees as their survival depends on the collection and intake of nectar and pollen, and other natural products. Here we studied the tarsal taste of honey bees through a series of behavioral and electrophysiological analyses. We characterized responsiveness to various sweet, salty and bitter tastants delivered to gustatory sensilla of the fore tarsi. Behavioral experiments showed that stimulation of opposite fore tarsi with sucrose and bitter substances or water yielded different outcomes depending on the stimulation sequence. When sucrose was applied first, thereby eliciting proboscis extension, no bitter substance could induce proboscis retraction, thus suggesting that the primacy of sucrose stimulation induced a central excitatory state. When bitter substances or water were applied first, sucrose stimulation could still elicit proboscis extension but to a lower level, thus suggesting central inhibition based on contradictory gustatory input on opposite tarsi. Electrophysiological experiments showed that receptor cells in the gustatory sensilla of the tarsomeres are highly sensitive to saline solutions at low concentrations. No evidence for receptors responding specifically to sucrose or to bitter substances was found in these sensilla. Receptor cells in the gustatory sensilla of the claws are highly sensitive to sucrose. Although bees do not possess dedicated bitter-taste receptors in the tarsi, indirect bitter detection is possible because bitter tastes inhibit sucrose receptor cells of the claws when mixed with sucrose solution. By combining behavioral and electrophysiological approaches, these results provide the first integrative study on tarsal taste detection in the honey bee.

When does mass screening for open neural tube defects in low-risk pregnancies result in cost savings?

PubMed Central

Tosi, L L; Detsky, A S; Roye, D P; Morden, M L

1987-01-01

Using a decision analysis model, we estimated the savings that might be derived from a mass prenatal screening program aimed at detecting open neural tube defects (NTDs) in low-risk pregnancies. Our baseline analysis showed that screening v. no screening could be expected to save approximately $8 per pregnancy given a cost of $7.50 for the maternal serum alpha-feto-protein (MSAFP) test and a cost of $42,507 for hospital and rehabilitation services for the first 10 years of life for a child with spina bifida. When a more liberal estimate of the costs of caring for such a child was used, the savings with the screening program were more substantial. We performed extensive sensitivity analyses, which showed that the savings were somewhat sensitive to the cost of the MSAFP test and highly sensitive to the specificity (but not the sensitivity) of the test. A screening program for NTDs in low-risk pregnancies may result in substantial savings in direct health care costs if the screening protocol is followed rigorously and efficiently. PMID:2433011

FEAST: sensitive local alignment with multiple rates of evolution.

PubMed

Hudek, Alexander K; Brown, Daniel G

2011-01-01

We present a pairwise local aligner, FEAST, which uses two new techniques: a sensitive extension algorithm for identifying homologous subsequences, and a descriptive probabilistic alignment model. We also present a new procedure for training alignment parameters and apply it to the human and mouse genomes, producing a better parameter set for these sequences. Our extension algorithm identifies homologous subsequences by considering all evolutionary histories. It has higher maximum sensitivity than Viterbi extensions, and better balances specificity. We model alignments with several submodels, each with unique statistical properties, describing strongly similar and weakly similar regions of homologous DNA. Training parameters using two submodels produces superior alignments, even when we align with only the parameters from the weaker submodel. Our extension algorithm combined with our new parameter set achieves sensitivity 0.59 on synthetic tests. In contrast, LASTZ with default settings achieves sensitivity 0.35 with the same false positive rate. Using the weak submodel as parameters for LASTZ increases its sensitivity to 0.59 with high error. FEAST is available at http://monod.uwaterloo.ca/feast/.

Reanalysis, compatibility and correlation in analysis of modified antenna structures

NASA Technical Reports Server (NTRS)

Levy, R.

1989-01-01

A simple computational procedure is synthesized to process changes in the microwave-antenna pathlength-error measure when there are changes in the antenna structure model. The procedure employs structural modification reanalysis methods combined with new extensions of correlation analysis to provide the revised rms pathlength error. Mainframe finite-element-method processing of the structure model is required only for the initial unmodified structure, and elementary postprocessor computations develop and deal with the effects of the changes. Several illustrative computational examples are included. The procedure adapts readily to processing spectra of changes for parameter studies or sensitivity analyses.

Exotic decays of the 125 GeV Higgs boson

DOE PAGES

Curtin, David; Essig, Rouven; Gori, Stefania; ...

2014-10-13

We perform an extensive survey of nonstandard Higgs decays that are consistent with the 125 GeV Higgs-like resonance. Our aim is to motivate a large set of new experimental analyses on the existing and forthcoming data from the Large Hadron Collider (LHC). The explicit search for exotic Higgs decays presents a largely untapped discovery opportunity for the LHC collaborations, as such decays may be easily missed by other searches. We emphasize that the Higgs is uniquely sensitive to the potential existence of new weakly coupled particles and provide a unified discussion of a large class of both simplified and completemore » models that give rise to characteristic patterns of exotic Higgs decays. We assess the status of exotic Higgs decays after LHC run I. In many cases we are able to set new nontrivial constraints by reinterpreting existing experimental analyses. We point out that improvements are possible with dedicated analyses and perform some preliminary collider studies. As a result, we prioritize the analyses according to their theoretical motivation and their experimental feasibility.« less

The sensitivity of the ESA DELTA model

NASA Astrophysics Data System (ADS)

Martin, C.; Walker, R.; Klinkrad, H.

Long-term debris environment models play a vital role in furthering our understanding of the future debris environment, and in aiding the determination of a strategy to preserve the Earth orbital environment for future use. By their very nature these models have to make certain assumptions to enable informative future projections to be made. Examples of these assumptions include the projection of future traffic, including launch and explosion rates, and the methodology used to simulate break-up events. To ensure a sound basis for future projections, and consequently for assessing the effectiveness of various mitigation measures, it is essential that the sensitivity of these models to variations in key assumptions is examined. The DELTA (Debris Environment Long Term Analysis) model, developed by QinetiQ for the European Space Agency, allows the future projection of the debris environment throughout Earth orbit. Extensive analyses with this model have been performed under the auspices of the ESA Space Debris Mitigation Handbook and following the recent upgrade of the model to DELTA 3.0. This paper draws on these analyses to present the sensitivity of the DELTA model to changes in key model parameters and assumptions. Specifically the paper will address the variation in future traffic rates, including the deployment of satellite constellations, and the variation in the break-up model and criteria used to simulate future explosion and collision events.

Responding to nonwords in the lexical decision task: Insights from the English Lexicon Project.

PubMed

Yap, Melvin J; Sibley, Daragh E; Balota, David A; Ratcliff, Roger; Rueckl, Jay

2015-05-01

Researchers have extensively documented how various statistical properties of words (e.g., word frequency) influence lexical processing. However, the impact of lexical variables on nonword decision-making performance is less clear. This gap is surprising, because a better specification of the mechanisms driving nonword responses may provide valuable insights into early lexical processes. In the present study, item-level and participant-level analyses were conducted on the trial-level lexical decision data for almost 37,000 nonwords in the English Lexicon Project in order to identify the influence of different psycholinguistic variables on nonword lexical decision performance and to explore individual differences in how participants respond to nonwords. Item-level regression analyses reveal that nonword response time was positively correlated with number of letters, number of orthographic neighbors, number of affixes, and base-word number of syllables, and negatively correlated with Levenshtein orthographic distance and base-word frequency. Participant-level analyses also point to within- and between-session stability in nonword responses across distinct sets of items, and intriguingly reveal that higher vocabulary knowledge is associated with less sensitivity to some dimensions (e.g., number of letters) but more sensitivity to others (e.g., base-word frequency). The present findings provide well-specified and interesting new constraints for informing models of word recognition and lexical decision. (c) 2015 APA, all rights reserved).

Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity.

PubMed

Dunn, Julia P; Kessler, Robert M; Feurer, Irene D; Volkow, Nora D; Patterson, Bruce W; Ansari, Mohammad S; Li, Rui; Marks-Shulman, Pamela; Abumrad, Naji N

2012-05-01

Midbrain dopamine (DA) neurons, which are involved with reward and motivation, are modulated by hormones that regulate food intake (insulin, leptin, and acyl ghrelin [AG]). We hypothesized that these hormones are associated with deficits in DA signaling in obesity. We assessed the relationships between fasting levels of insulin and leptin, and AG, BMI, and insulin sensitivity index (S(I)) with the availability of central DA type 2 receptor (D2R). We measured D2R availability using positron emission tomography and [(18)F]fallypride (radioligand that competes with endogenous DA) in lean (n = 8) and obese (n = 14) females. Fasting hormones were collected prior to scanning and S(I) was determined by modified oral glucose tolerance test. Parametric image analyses revealed associations between each metabolic measure and D2R. The most extensive findings were negative associations of AG with clusters involving the striatum and inferior temporal cortices. Regional regression analyses also found extensive negative relationships between AG and D2R in the caudate, putamen, ventral striatum (VS), amygdala, and temporal lobes. S(I) was negatively associated with D2R in the VS, while insulin was not. In the caudate, BMI and leptin were positively associated with D2R availability. The direction of associations of leptin and AG with D2R availability are consistent with their opposite effects on DA levels (decreasing and increasing, respectively). After adjusting for BMI, AG maintained a significant relationship in the VS. We hypothesize that the increased D2R availability in obese subjects reflects relatively reduced DA levels competing with the radioligand. Our findings provide evidence for an association between the neuroendocrine hormones and DA brain signaling in obese females.

Application of recombinant antigen 5 allergens from seven allergy-relevant Hymenoptera species in diagnostics.

PubMed

Schiener, M; Eberlein, B; Moreno-Aguilar, C; Pietsch, G; Serrano, P; McIntyre, M; Schwarze, L; Russkamp, D; Biedermann, T; Spillner, E; Darsow, U; Ollert, M; Schmidt-Weber, C B; Blank, S

2017-01-01

Hymenoptera stings can cause severe anaphylaxis in untreated venom-allergic patients. A correct diagnosis regarding the relevant species for immunotherapy is often hampered by clinically irrelevant cross-reactivity. In vespid venom allergy, cross-reactivity between venoms of different species can be a diagnostic challenge. To address immunological IgE cross-reactivity on molecular level, seven recombinant antigens 5 of the most important Vespoidea groups were assessed by different diagnostic setups. The antigens 5 of yellow jackets, hornets, European and American paper wasps, fire ants, white-faced hornets, and Polybia wasps were recombinantly produced in insect cells, immunologically and structurally characterized, and their sIgE reactivity assessed by ImmunoCAP, ELISA, cross-inhibition, and basophil activation test (BAT) in patients with yellow jacket or Polistes venom allergy of two European geographical areas. All recombinant allergens were correctly folded and structural models and patient reactivity profiles suggested the presence of conserved and unique B-cell epitopes. All antigens 5 showed extensive cross-reactivity in sIgE analyses, inhibition assays, and BAT. This cross-reactivity was more pronounced in ImmunoCAP measurements with venom extracts than in sIgE analyses with recombinant antigens 5. Dose-response curves with the allergens in BAT allowed a differentiated individual dissection of relevant sensitization. Due to extensive cross-reactivity in various diagnostic settings, antigens 5 are inappropriate markers for differential sIgE diagnostics in vespid venom allergy. However, the newly available antigens 5 from further vespid species and the combination of recombinant allergen-based sIgE measurements with BAT represents a practicable way to diagnose clinically relevant sensitization in vespid venom allergy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Coal gasification systems engineering and analysis, volume 2

NASA Technical Reports Server (NTRS)

1980-01-01

The major design related features of each generic plant system were characterized in a catalog. Based on the catalog and requirements data, approximately 17 designs and cost estimates were developed for MBG and alternate products. A series of generic trade studies was conducted to support all of the design studies. A set of cost and programmatic analyses were conducted to supplement the designs. The cost methodology employed for the design and sensitivity studies was documented and implemented in a computer program. Plant design and construction schedules were developed for the K-T, Texaco, and B&W MBG plant designs. A generic work breakdown structure was prepared, based on the K-T design, to coincide with TVA's planned management approach. An extensive set of cost sensitivity analyses was completed for K-T, Texaco, and B&W design. Product price competitiveness was evaluated for MBG and the alternate products. A draft management policy and procedures manual was evaluated. A supporting technology development plan was developed to address high technology risk issues. The issues were identified and ranked in terms of importance and tractability, and a plan developed for obtaining data or developing technology required to mitigate the risk.

Optical imaging of RNAi-mediated silencing of cancer

NASA Astrophysics Data System (ADS)

Ochiya, Takahiro; Honma, Kimi; Takeshita, Fumitaka; Nagahara, Shunji

2008-02-01

RNAi has rapidly become a powerful tool for drug target discovery and validation in an in vitro culture system and, consequently, interest is rapidly growing for extension of its application to in vivo systems, such as animal disease models and human therapeutics. Cancer is one obvious application for RNAi therapeutics, because abnormal gene expression is thought to contribute to the pathogenesis and maintenance of the malignant phenotype of cancer and thereby many oncogenes and cell-signaling molecules present enticing drug target possibilities. RNAi, potent and specific, could silence tumor-related genes and would appear to be a rational approach to inhibit tumor growth. In subsequent in vivo studies, the appropriate cancer model must be developed for an evaluation of siRNA effects on tumors. How to evaluate the effect of siRNA in an in vivo therapeutic model is also important. Accelerating the analyses of these models and improving their predictive value through whole animal imaging methods, which provide cancer inhibition in real time and are sensitive to subtle changes, are crucial for rapid advancement of these approaches. Bioluminescent imaging is one of these optically based imaging methods that enable rapid in vivo analyses of a variety of cellular and molecular events with extreme sensitivity.

Phylogenetic study of Class Armophorea (Alveolata, Ciliophora) based on 18S-rDNA data.

PubMed

da Silva Paiva, Thiago; do Nascimento Borges, Bárbara; da Silva-Neto, Inácio Domingos

2013-12-01

The 18S rDNA phylogeny of Class Armophorea, a group of anaerobic ciliates, is proposed based on an analysis of 44 sequences (out of 195) retrieved from the NCBI/GenBank database. Emphasis was placed on the use of two nucleotide alignment criteria that involved variation in the gap-opening and gap-extension parameters and the use of rRNA secondary structure to orientate multiple-alignment. A sensitivity analysis of 76 data sets was run to assess the effect of variations in indel parameters on tree topologies. Bayesian inference, maximum likelihood and maximum parsimony phylogenetic analyses were used to explore how different analytic frameworks influenced the resulting hypotheses. A sensitivity analysis revealed that the relationships among higher taxa of the Intramacronucleata were dependent upon how indels were determined during multiple-alignment of nucleotides. The phylogenetic analyses rejected the monophyly of the Armophorea most of the time and consistently indicated that the Metopidae and Nyctotheridae were related to the Litostomatea. There was no consensus on the placement of the Caenomorphidae, which could be a sister group of the Metopidae + Nyctorheridae, or could have diverged at the base of the Spirotrichea branch or the Intramacronucleata tree.

Phylogenetic study of Class Armophorea (Alveolata, Ciliophora) based on 18S-rDNA data

PubMed Central

da Silva Paiva, Thiago; do Nascimento Borges, Bárbara; da Silva-Neto, Inácio Domingos

2013-01-01

The 18S rDNA phylogeny of Class Armophorea, a group of anaerobic ciliates, is proposed based on an analysis of 44 sequences (out of 195) retrieved from the NCBI/GenBank database. Emphasis was placed on the use of two nucleotide alignment criteria that involved variation in the gap-opening and gap-extension parameters and the use of rRNA secondary structure to orientate multiple-alignment. A sensitivity analysis of 76 data sets was run to assess the effect of variations in indel parameters on tree topologies. Bayesian inference, maximum likelihood and maximum parsimony phylogenetic analyses were used to explore how different analytic frameworks influenced the resulting hypotheses. A sensitivity analysis revealed that the relationships among higher taxa of the Intramacronucleata were dependent upon how indels were determined during multiple-alignment of nucleotides. The phylogenetic analyses rejected the monophyly of the Armophorea most of the time and consistently indicated that the Metopidae and Nyctotheridae were related to the Litostomatea. There was no consensus on the placement of the Caenomorphidae, which could be a sister group of the Metopidae + Nyctorheridae, or could have diverged at the base of the Spirotrichea branch or the Intramacronucleata tree. PMID:24385862

Bacillus anthracis lethal toxin induces TNF-α–independent hypoxia-mediated toxicity in mice

PubMed Central

Moayeri, Mahtab; Haines, Diana; Young, Howard A.; Leppla, Stephen H.

2003-01-01

Bacillus anthracis lethal toxin (LT) is the major virulence factor of anthrax and reproduces most of the laboratory manifestations of the disease in animals. We studied LT toxicity in BALB/cJ and C57BL/6J mice. BALB/cJ mice became terminally ill earlier and with higher frequency than C57BL/6J mice. Timed histopathological analysis identified bone marrow, spleen, and liver as major affected organs in both mouse strains. LT induced extensive hypoxia. Crisis was due to extensive liver necrosis accompanied by pleural edema. There was no evidence of disseminated intravascular coagulation or renal dysfunction. Instead, analyses revealed hepatic dysfunction, hypoalbuminemia, and vascular/oxygenation insufficiency. Of 50 cytokines analyzed, BALB/cJ mice showed rapid but transitory increases in specific factors including KC, MCP-1/JE, IL-6, MIP-2, G-CSF, GM-CSF, eotaxin, FasL, and IL-1β. No changes in TNF-α occurred. The C57BL/6J mice did not mount a similar cytokine response. These factors were not induced in vitro by LT treatment of toxin-sensitive macrophages. The evidence presented shows that LT kills mice through a TNF-α–independent, FasL-independent, noninflammatory mechanism that involves hypoxic tissue injury but does not require macrophage sensitivity to toxin. PMID:12952916

Scoping and sensitivity analyses for the Demonstration Tokamak Hybrid Reactor (DTHR)

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

Sink, D.A.; Gibson, G.

1979-03-01

The results of an extensive set of parametric studies are presented which provide analytical data of the effects of various tokamak parameters on the performance and cost of the DTHR (Demonstration Tokamak Hybrid Reactor). The studies were centered on a point design which is described in detail. Variations in the device size, neutron wall loading, and plasma aspect ratio are presented, and the effects on direct hardware costs, fissile fuel production (breeding), fusion power production, electrical power consumption, and thermal power production are shown graphically. The studies considered both ignition and beam-driven operations of DTHR and yielded results based onmore » two empirical scaling laws presently used in reactor studies. Sensitivity studies were also made for variations in the following key parameters: the plasma elongation, the minor radius, the TF coil peak field, the neutral beam injection power, and the Z/sub eff/ of the plasma.« less

Additional EIPC Study Analysis: Interim Report on High Priority Topics

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

Hadley, Stanton W

Between 2010 and 2012 the Eastern Interconnection Planning Collaborative (EIPC) conducted a major long-term resource and transmission study of the Eastern Interconnection (EI). With guidance from a Stakeholder Steering Committee (SSC) that included representatives from the Eastern Interconnection States Planning Council (EISPC) among others, the project was conducted in two phases. Phase 1 involved a long-term capacity expansion analysis that involved creation of eight major futures plus 72 sensitivities. Three scenarios were selected for more extensive transmission- focused evaluation in Phase 2. Five power flow analyses, nine production cost model runs (including six sensitivities), and three capital cost estimations weremore » developed during this second phase. The results from Phase 1 and 2 provided a wealth of data that could be examined further to address energy-related questions. A list of 13 topics was developed for further analysis; this paper discusses the first five.« less

Pharmacoeconomic evaluations of pharmacogenetic and genomic screening programmes: a systematic review on content and adherence to guidelines.

PubMed

Vegter, Stefan; Boersma, Cornelis; Rozenbaum, Mark; Wilffert, Bob; Navis, Gerjan; Postma, Maarten J

2008-01-01

The fields of pharmacogenetics and pharmacogenomics have become important practical tools to progress goals in medical and pharmaceutical research and development. As more screening tests are being developed, with some already used in clinical practice, consideration of cost-effectiveness implications is important. A systematic review was performed on the content of and adherence to pharmacoeconomic guidelines of recent pharmacoeconomic analyses performed in the field of pharmacogenetics and pharmacogenomics. Economic analyses of screening strategies for genetic variations, which were evidence-based and assumed to be associated with drug efficacy or safety, were included in the review. The 20 papers included cover a variety of healthcare issues, including screening tests on several cytochrome P450 (CYP) enzyme genes, thiopurine S-methyltransferase (TMPT) and angiotensin-converting enzyme (ACE) insertion deletion (ACE I/D) polymorphisms. Most economic analyses reported that genetic screening was cost effective and often even clearly dominated existing non-screening strategies. However, we found a lack of standardization regarding aspects such as the perspective of the analysis, factors included in the sensitivity analysis and the applied discount rates. In particular, an important limitation of several studies related to the failure to provide a sufficient evidence-based rationale for an association between genotype and phenotype. Future economic analyses should be conducted utilizing correct methods, with adherence to guidelines and including extensive sensitivity analyses. Most importantly, genetic screening strategies should be based on good evidence-based rationales. For these goals, we provide a list of recommendations for good pharmacoeconomic practice deemed useful in the fields of pharmacogenetics and pharmacogenomics, regardless of country and origin of the economic analysis.

Escitalopram in the Treatment of Adolescent Depression: A Randomized, Double-Blind, Placebo-Controlled Extension Trial

PubMed Central

Robb, Adelaide; Bose, Anjana

2013-01-01

Abstract Objective The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). Methods Adolescents (12–17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10–20 mg versus placebo could enroll in a 16–24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). Results Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were mild/moderate and not related to the study drug. AEs suggestive of self-harm occurred in 5.7% and 7.1% of placebo and escitalopram patients. Occurrence of suicidal behavior and/or suicidal ideation assessed by C-SSRS was 10.9% (14/128) for placebo and 14.5% (19/131) for escitalopram. Conclusions Extended use of escitalopram was generally safe and resulted in modest improvement in efficacy in adolescents with MDD. PMID:24041408

Escitalopram in the treatment of adolescent depression: a randomized, double-blind, placebo-controlled extension trial.

PubMed

Findling, Robert L; Robb, Adelaide; Bose, Anjana

2013-09-01

The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). Adolescents (12-17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10-20 mg versus placebo could enroll in a 16-24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥ 40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤ 2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤ 28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥ 5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were mild/moderate and not related to the study drug. AEs suggestive of self-harm occurred in 5.7% and 7.1% of placebo and escitalopram patients. Occurrence of suicidal behavior and/or suicidal ideation assessed by C-SSRS was 10.9% (14/128) for placebo and 14.5% (19/131) for escitalopram. Extended use of escitalopram was generally safe and resulted in modest improvement in efficacy in adolescents with MDD.

Medialization thyroplasty versus injection laryngoplasty: a cost minimization analysis.

PubMed

Tam, Samantha; Sun, Hongmei; Sarma, Sisira; Siu, Jennifer; Fung, Kevin; Sowerby, Leigh

2017-02-20

Medialization thyroplasty and injection laryngoplasty are widely accepted treatment options for unilateral vocal fold paralysis. Although both procedures result in similar clinical outcomes, little is known about the corresponding medical care costs. Medialization thyroplasty requires expensive operating room resources while injection laryngoplasty utilizes outpatient resources but may require repeated procedures. The purpose of this study, therefore, is to quantify the cost differences in adult patients with unilateral vocal fold paralysis undergoing medialization thyroplasty versus injection laryngoplasty. Cost minimization analysis conducted using a decision tree model. A decision tree model was constructed to capture clinical scenarios for medialization thyroplasty and injection laryngoplasty. Probabilities for various events were obtained from a retrospective cohort from the London Health Sciences Centre, Canada. Costs were derived from the published literature and the London Health Science Centre. All costs were reported in 2014 Canadian dollars. Time horizon was 5 years. The study was conducted from an academic hospital perspective in Canada. Various sensitivity analyses were conducted to assess differences in procedure-specific costs and probabilities of key events. Sixty-three patients underwent medialization thyroplasty and 41 underwent injection laryngoplasty. Cost of medialization thyroplasty was C$2499.10 per patient whereas those treated with injection laryngoplasty cost C$943.19. Results showed that cost savings with IL were C$1555.91. Deterministic and probabilistic sensitivity analyses suggested cost savings ranged from C$596 to C$3626. Treatment with injection laryngoplasty results in cost savings of C$1555.91 per patient. Our extensive sensitivity analyses suggest that switching from medialization thyroplasty to injection laryngoplasty will lead to a minimum cost savings of C$596 per patient. Considering the significant cost savings and similar effectiveness, injection laryngoplasty should be strongly considered as a preferred treatment option for patients diagnosed with unilateral vocal fold paralysis.

Comparative costs and cost-effectiveness of behavioural interventions as part of HIV prevention strategies.

PubMed

Hsu, Justine; Zinsou, Cyprien; Parkhurst, Justin; N'Dour, Marguerite; Foyet, Léger; Mueller, Dirk H

2013-01-01

Behavioural interventions have been widely integrated in HIV/AIDS social marketing prevention strategies and are considered valuable in settings with high levels of risk behaviours and low levels of HIV/AIDS awareness. Despite their widespread application, there is a lack of economic evaluations comparing different behaviour change communication methods. This paper analyses the costs to increase awareness and the cost-effectiveness to influence behaviour change for five interventions in Benin. Cost and cost-effectiveness analyses used economic costs and primary effectiveness data drawn from surveys. Costs were collected for provider inputs required to implement the interventions in 2009 and analysed by 'person reached'. Cost-effectiveness was analysed by 'person reporting systematic condom use'. Sensitivity analyses were performed on all uncertain variables and major assumptions. Cost-per-person reached varies by method, with public outreach events the least costly (US$2.29) and billboards the most costly (US$25.07). Influence on reported behaviour was limited: only three of the five interventions were found to have a significant statistical correlation with reported condom use (i.e. magazines, radio broadcasts, public outreach events). Cost-effectiveness ratios per person reporting systematic condom use resulted in the following ranking: magazines, radio and public outreach events. Sensitivity analyses indicate rankings are insensitive to variation of key parameters although ratios must be interpreted with caution. This analysis suggests that while individual interventions are an attractive use of resources to raise awareness, this may not translate into a cost-effective impact on behaviour change. The study found that the extensive reach of public outreach events did not seem to influence behaviour change as cost-effectively when compared with magazines or radio broadcasts. Behavioural interventions are context-specific and their effectiveness influenced by a multitude of factors. Further analyses using a quasi-experimental design would be useful to programme implementers and policy makers as they face decisions regarding which HIV prevention activities to prioritize.

Lung Reference Set A Application: LaszloTakacs - Biosystems (2010) — EDRN Public Portal

Cancer.gov

We would like to access the NCI lung cancer Combined Pre-Validation Reference Set A in order to further validate a lung cancer diagnostic test candidate. Our test is based on a panel of antibodies which have been tested on 4 different cohorts (see below, paragraph “Preliminary Data and Methods”). This Reference Set A, whose clinical setting is “Diagnosis of lung cancer”, will be used to validate the panel of monoclonal antibodies which have been demonstrated by extensive data analysis to provide the best discrimination between controls and Lung Cancer patient plasma samples, sensitivity and specificity values from ROC analyses are superior than 85 %.

Manpower Mix for Health Services

PubMed Central

Shuman, Larry J.; Young, John P.; Naddor, Eliezer

1971-01-01

A model is formulated to determine the mix of manpower and technology needed to provide health services of acceptable quality at a minimum total cost to the community. Total costs include both the direct costs associated with providing the services and with developing additional manpower and the indirect costs (shortage costs) resulting from not providing needed services. The model is applied to a hypothetical neighborhood health center, and its sensitivity to alternative policies is investigated by cost-benefit analyses. Possible extensions of the model to include dynamic elements in health delivery systems are discussed, as is its adaptation for use in hospital planning, with a changed objective function. PMID:5095652

ASPeak: an abundance sensitive peak detection algorithm for RIP-Seq.

PubMed

Kucukural, Alper; Özadam, Hakan; Singh, Guramrit; Moore, Melissa J; Cenik, Can

2013-10-01

Unlike DNA, RNA abundances can vary over several orders of magnitude. Thus, identification of RNA-protein binding sites from high-throughput sequencing data presents unique challenges. Although peak identification in ChIP-Seq data has been extensively explored, there are few bioinformatics tools tailored for peak calling on analogous datasets for RNA-binding proteins. Here we describe ASPeak (abundance sensitive peak detection algorithm), an implementation of an algorithm that we previously applied to detect peaks in exon junction complex RNA immunoprecipitation in tandem experiments. Our peak detection algorithm yields stringent and robust target sets enabling sensitive motif finding and downstream functional analyses. ASPeak is implemented in Perl as a complete pipeline that takes bedGraph files as input. ASPeak implementation is freely available at https://sourceforge.net/projects/as-peak under the GNU General Public License. ASPeak can be run on a personal computer, yet is designed to be easily parallelizable. ASPeak can also run on high performance computing clusters providing efficient speedup. The documentation and user manual can be obtained from http://master.dl.sourceforge.net/project/as-peak/manual.pdf.

BEATBOX v1.0: Background Error Analysis Testbed with Box Models

NASA Astrophysics Data System (ADS)

Knote, Christoph; Barré, Jérôme; Eckl, Max

2018-02-01

The Background Error Analysis Testbed (BEATBOX) is a new data assimilation framework for box models. Based on the BOX Model eXtension (BOXMOX) to the Kinetic Pre-Processor (KPP), this framework allows users to conduct performance evaluations of data assimilation experiments, sensitivity analyses, and detailed chemical scheme diagnostics from an observation simulation system experiment (OSSE) point of view. The BEATBOX framework incorporates an observation simulator and a data assimilation system with the possibility of choosing ensemble, adjoint, or combined sensitivities. A user-friendly, Python-based interface allows for the tuning of many parameters for atmospheric chemistry and data assimilation research as well as for educational purposes, for example observation error, model covariances, ensemble size, perturbation distribution in the initial conditions, and so on. In this work, the testbed is described and two case studies are presented to illustrate the design of a typical OSSE experiment, data assimilation experiments, a sensitivity analysis, and a method for diagnosing model errors. BEATBOX is released as an open source tool for the atmospheric chemistry and data assimilation communities.

Extensive genetic and DNA methylation variation contribute to heterosis in triploid loquat hybrids.

PubMed

Liu, Chao; Wang, Mingbo; Wang, Lingli; Guo, Qigao; Liang, Guolu

2018-04-24

We aim to overcome the unclear origin of the loquat and elucidate the heterosis mechanism of the triploid loquat. Here we investigated the genetic and epigenetic variations between the triploid plant and its parental lines using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified fragment length polymorphism (MSAP) analyses. We show that in addition to genetic variations, extensive DNA methylation variation occurred during the formation process of triploid loquat, with the triploid hybrid having increased DNA methylation compared to the parents. Furthermore, a correlation existed between genetic variation and DNA methylation remodeling, suggesting that genome instability may lead to DNA methylation variation or vice versa. Sequence analysis of the MSAP bands revealed that over 53% of them overlap with protein-coding genes, which may indicate a functional role of the differential DNA methylation in gene regulation and hence heterosis phenotypes. Consistent with this, the genetic and epigenetic alterations were associated closely to the heterosis phenotypes of triploid loquat, and this association varied for different traits. Our results suggested that the formation of triploid is accompanied by extensive genetic and DNA methylation variation, and these changes contribute to the heterosis phenotypes of the triploid loquats from the two cross lines.

Wound infection secondary to snakebite.

PubMed

Wagener, M; Naidoo, M; Aldous, C

2017-03-29

Snakebites can produce severe local and systemic septic complications as well as being associated with significant overall morbidity and even mortality. A prospective audit was undertaken to determine the bacterial causation of wound infection secondary to snakebite, and attempt to quantify the burden of disease. The audit was undertaken at Ngwelezane Hospital, which provides both regional and tertiary services for north-eastern KwaZulu-Natal Province, South Africa, over a 4-month period. Records of patients who required surgical debridement for extensive skin and soft-tissue necrosis were analysed. At the time of debridement, tissue samples of necrotic or infected tissue were sent for bacteriological analysis as standard of care. Microbiology results were analysed. A total of 164 patients were admitted to hospital for management of snakebite, of whom 57 required surgical debridement and 42 were included in the final microbiological analysis. Children were found to be the most frequent victims of snakebite; 57.8% of patients in this study were aged ≤10 years and 73.7% ≤15 years. Culture showed a single organism in 32/42 cases, two organisms in 8 and no growth in 2. Eight different types of organisms were cultured, five of them more than once. Thirty-five specimens (83.3%) grew Gram-negative Enterobacteriaceae, the most frequent being Morganella morganii and Proteus species. Thirteen specimens (31.0%) grew Enterococcus faecalis. Gram-negative Enterobacteriaceae showed 31.4% sensitivity to ampicillin, 40.0% sensitivity to amoxicillin plus clavulanic acid, 34.3% sensitivity to cefuroxime, 97.1% sensitivity to ceftriaxone, and 100% sensitivity to ciprofloxacin, gentamicin and amikacin. E. faecalis was 92.3% sensitive to amoxicillin, 92.3% sensitive to amoxicillin plus clavulanic acid, 100% sensitive to ciprofloxacin, 92.3% resistant to erythromycin and 100% resistant to ceftriaxone. Children are particularly vulnerable to snakebite, and the consequences can be devastating. While the majority of patients in this study were shown to have secondary bacterial infection, debridement and subsequent wound management is considered the mainstay of treatment. Common organisms are Enterobacteriaceae and enterococci. There appears to be a role for antibiotics in the management of these patients. A good antibiotic policy is strongly advocated.

How often do sensitivity analyses for economic parameters change cost-utility analysis conclusions?

PubMed

Schackman, Bruce R; Gold, Heather Taffet; Stone, Patricia W; Neumann, Peter J

2004-01-01

There is limited evidence about the extent to which sensitivity analysis has been used in the cost-effectiveness literature. Sensitivity analyses for health-related QOL (HR-QOL), cost and discount rate economic parameters are of particular interest because they measure the effects of methodological and estimation uncertainties. To investigate the use of sensitivity analyses in the pharmaceutical cost-utility literature in order to test whether a change in economic parameters could result in a different conclusion regarding the cost effectiveness of the intervention analysed. Cost-utility analyses of pharmaceuticals identified in a prior comprehensive audit (70 articles) were reviewed and further audited. For each base case for which sensitivity analyses were reported (n = 122), up to two sensitivity analyses for HR-QOL (n = 133), cost (n = 99), and discount rate (n = 128) were examined. Article mentions of thresholds for acceptable cost-utility ratios were recorded (total 36). Cost-utility ratios were denominated in US dollars for the year reported in each of the original articles in order to determine whether a different conclusion would have been indicated at the time the article was published. Quality ratings from the original audit for articles where sensitivity analysis results crossed the cost-utility ratio threshold above the base-case result were compared with those that did not. The most frequently mentioned cost-utility thresholds were $US20,000/QALY, $US50,000/QALY, and $US100,000/QALY. The proportions of sensitivity analyses reporting quantitative results that crossed the threshold above the base-case results (or where the sensitivity analysis result was dominated) were 31% for HR-QOL sensitivity analyses, 20% for cost-sensitivity analyses, and 15% for discount-rate sensitivity analyses. Almost half of the discount-rate sensitivity analyses did not report quantitative results. Articles that reported sensitivity analyses where results crossed the cost-utility threshold above the base-case results (n = 25) were of somewhat higher quality, and were more likely to justify their sensitivity analysis parameters, than those that did not (n = 45), but the overall quality rating was only moderate. Sensitivity analyses for economic parameters are widely reported and often identify whether choosing different assumptions leads to a different conclusion regarding cost effectiveness. Changes in HR-QOL and cost parameters should be used to test alternative guideline recommendations when there is uncertainty regarding these parameters. Changes in discount rates less frequently produce results that would change the conclusion about cost effectiveness. Improving the overall quality of published studies and describing the justifications for parameter ranges would allow more meaningful conclusions to be drawn from sensitivity analyses.

Towards semantically sensitive text clustering: a feature space modeling technology based on dimension extension.

PubMed

Liu, Yuanchao; Liu, Ming; Wang, Xin

2015-01-01

The objective of text clustering is to divide document collections into clusters based on the similarity between documents. In this paper, an extension-based feature modeling approach towards semantically sensitive text clustering is proposed along with the corresponding feature space construction and similarity computation method. By combining the similarity in traditional feature space and that in extension space, the adverse effects of the complexity and diversity of natural language can be addressed and clustering semantic sensitivity can be improved correspondingly. The generated clusters can be organized using different granularities. The experimental evaluations on well-known clustering algorithms and datasets have verified the effectiveness of our approach.

Towards Semantically Sensitive Text Clustering: A Feature Space Modeling Technology Based on Dimension Extension

PubMed Central

Liu, Yuanchao; Liu, Ming; Wang, Xin

2015-01-01

The objective of text clustering is to divide document collections into clusters based on the similarity between documents. In this paper, an extension-based feature modeling approach towards semantically sensitive text clustering is proposed along with the corresponding feature space construction and similarity computation method. By combining the similarity in traditional feature space and that in extension space, the adverse effects of the complexity and diversity of natural language can be addressed and clustering semantic sensitivity can be improved correspondingly. The generated clusters can be organized using different granularities. The experimental evaluations on well-known clustering algorithms and datasets have verified the effectiveness of our approach. PMID:25794172

Assessing Instructional Sensitivity Using the Pre-Post Difference Index: A Nontechnical Tool for Extension Educators

ERIC Educational Resources Information Center

Adedokun, Omolola A.

2018-01-01

This article provides an illustrative description of the pre-post difference index (PPDI), a simple, nontechnical yet robust tool for examining the instructional sensitivity of assessment items. Extension educators often design pretest-posttest instruments to assess the impact of their curricula on participants' knowledge and understanding of the…

Thermodynamic modeling of transcription: sensitivity analysis differentiates biological mechanism from mathematical model-induced effects.

PubMed

Dresch, Jacqueline M; Liu, Xiaozhou; Arnosti, David N; Ay, Ahmet

2010-10-24

Quantitative models of gene expression generate parameter values that can shed light on biological features such as transcription factor activity, cooperativity, and local effects of repressors. An important element in such investigations is sensitivity analysis, which determines how strongly a model's output reacts to variations in parameter values. Parameters of low sensitivity may not be accurately estimated, leading to unwarranted conclusions. Low sensitivity may reflect the nature of the biological data, or it may be a result of the model structure. Here, we focus on the analysis of thermodynamic models, which have been used extensively to analyze gene transcription. Extracted parameter values have been interpreted biologically, but until now little attention has been given to parameter sensitivity in this context. We apply local and global sensitivity analyses to two recent transcriptional models to determine the sensitivity of individual parameters. We show that in one case, values for repressor efficiencies are very sensitive, while values for protein cooperativities are not, and provide insights on why these differential sensitivities stem from both biological effects and the structure of the applied models. In a second case, we demonstrate that parameters that were thought to prove the system's dependence on activator-activator cooperativity are relatively insensitive. We show that there are numerous parameter sets that do not satisfy the relationships proferred as the optimal solutions, indicating that structural differences between the two types of transcriptional enhancers analyzed may not be as simple as altered activator cooperativity. Our results emphasize the need for sensitivity analysis to examine model construction and forms of biological data used for modeling transcriptional processes, in order to determine the significance of estimated parameter values for thermodynamic models. Knowledge of parameter sensitivities can provide the necessary context to determine how modeling results should be interpreted in biological systems.

Sensitization to minor cat allergen components is associated with type-2 biomarkers in young asthmatics.

PubMed

Tsolakis, N; Malinovschi, A; Nordvall, L; Mattsson, L; Lidholm, J; Pedroletti, C; Janson, C; Borres, M P; Alving, K

2018-03-25

Cat allergy is a major trigger of asthma world-wide. Molecular patterns of cat sensitization vary between individuals, but their relationship to inflammation in asthmatics has not been extensively studied. To investigate the prevalence and levels of IgE antibodies against different cat allergen components and their relationship to type-2 inflammation and total IgE among young asthmatic subjects sensitized to furry animals. Patients with asthma (age 10-35 years; n = 266) and IgE sensitization to cat, dog or horse extract (ImmunoCAP), were analysed for IgE to the cat allergen components Fel d 1 (secretoglobin), Fel d 2 (serum albumin), Fel d 4 and Fel d 7 (lipocalins). Independent associations between IgE-antibody concentrations, and fraction of exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, and total IgE were analysed by multiple linear regression after adjustment for possible confounders. The level of IgE against Fel d 2 was independently related to FeNO (P = .012) and total IgE (P < .001), and IgE against Fel d 4 associated with Β-Eos count (P = .009) and total IgE (P < .001). IgE antibodies against Fel d 1 or cat extract did not independently relate to these inflammatory markers (P = .23-.51). Levels of IgE to lipocalin (Fel d 4) and serum albumin (Fel d 2), but not to secretoglobin (Fel d 1) or cat extract, were independently associated with type-2 biomarkers and total IgE in young asthmatics. We suggest that measurement of IgE to minor cat allergen components may be useful when investigating asthma morbidity in cat allergic subjects. © 2018 John Wiley & Sons Ltd.

The predictive value of magnetic resonance imaging of retinoblastoma for the likelihood of high-risk pathologic features.

PubMed

Hiasat, Jamila G; Saleh, Alaa; Al-Hussaini, Maysa; Al Nawaiseh, Ibrahim; Mehyar, Mustafa; Qandeel, Monther; Mohammad, Mona; Deebajah, Rasha; Sultan, Iyad; Jaradat, Imad; Mansour, Asem; Yousef, Yacoub A

2018-06-01

To evaluate the predictive value of magnetic resonance imaging in retinoblastoma for the likelihood of high-risk pathologic features. A retrospective study of 64 eyes enucleated from 60 retinoblastoma patients. Contrast-enhanced magnetic resonance imaging was performed before enucleation. Main outcome measures included demographics, laterality, accuracy, sensitivity, and specificity of magnetic resonance imaging in detecting high-risk pathologic features. Optic nerve invasion and choroidal invasion were seen microscopically in 34 (53%) and 28 (44%) eyes, respectively, while they were detected in magnetic resonance imaging in 22 (34%) and 15 (23%) eyes, respectively. The accuracy of magnetic resonance imaging in detecting prelaminar invasion was 77% (sensitivity 89%, specificity 98%), 56% for laminar invasion (sensitivity 27%, specificity 94%), 84% for postlaminar invasion (sensitivity 42%, specificity 98%), and 100% for optic cut edge invasion (sensitivity100%, specificity 100%). The accuracy of magnetic resonance imaging in detecting focal choroidal invasion was 48% (sensitivity 33%, specificity 97%), and 84% for massive choroidal invasion (sensitivity 53%, specificity 98%), and the accuracy in detecting extrascleral extension was 96% (sensitivity 67%, specificity 98%). Magnetic resonance imaging should not be the only method to stratify patients at high risk from those who are not, eventhough it can predict with high accuracy extensive postlaminar optic nerve invasion, massive choroidal invasion, and extrascleral tumor extension.

The child health exposure analysis resource as a vehicle to measure environment in the environmental influences on child health outcomes program.

PubMed

Wright, Robert O; Teitelbaum, Susan; Thompson, Claudia; Balshaw, David

2018-04-01

Demonstrate the role of environment as a predictor of child health. The children's health exposure analysis resource (CHEAR) assists the Environmental influences on child health outcomes (ECHO) program in understanding the time sensitive and dynamic nature of perinatal and childhood environment on developmental trajectories by providing a central infrastructure for the analysis of biological samples from the ECHO cohort awards. CHEAR will assist ECHO cohorts in defining the critical or sensitive period for effects associated with environmental exposures. Effective incorporation of these principles into multiple existing cohorts requires extensive multidisciplinary expertise, creativity, and flexibility. The pursuit of life course - informed research within the CHEAR/ECHO structure represents a shift in focus from single exposure inquiries to one that addresses multiple environmental risk factors linked through shared vulnerabilities. CHEAR provides ECHO both targeted analyses of inorganic and organic toxicants, nutrients, and social-stress markers and untargeted analyses to assess the exposome and discovery of exposure-outcome relationships. Utilization of CHEAR as a single site for characterization of environmental exposures within the ECHO cohorts will not only support the investigation of the influence of environment on children's health but also support the harmonization of data across the disparate cohorts that comprise ECHO.

Cost-effectiveness of methadone maintenance therapy as HIV prevention in an Indonesian high-prevalence setting: a mathematical modeling study.

PubMed

Wammes, Joost J G; Siregar, Adiatma Y; Hidayat, Teddy; Raya, Reynie P; van Crevel, Reinout; van der Ven, André J; Baltussen, Rob

2012-09-01

Indonesia faces an HIV epidemic that is in rapid transition. Injecting drug users (IDUs) are among the most heavily affected risk populations, with estimated prevalence of HIV reaching 50% or more in most parts of the country. Although Indonesia started opening methadone clinics in 2003, coverage remains low. We used the Asian Epidemic Model and Resource Needs Model to evaluate the long-term population-level preventive impact of expanding Methadone Maintenance Therapy (MMT) in West Java (43 million people). We compared intervention costs and the number of incident HIV cases in the intervention scenario with current practice to establish the cost per infection averted by expanding MMT. An extensive sensitivity analysis was performed on costs and epidemiological input, as well as on the cost-effectiveness calculation itself. Our analysis shows that expanding MMT from 5% coverage now to 40% coverage in 2019 would avert approximately 2400 HIV infections, at a cost of approximately US$7000 per HIV infection averted. Sensitivity analyses demonstrate that the use of alternative assumptions does not change the study conclusions. Our analyses suggest that expanding MMT is cost-effective, and support government policies to make MMT widely available as an integrated component of HIV/AIDS control in West Java. Copyright © 2012 Elsevier B.V. All rights reserved.

The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations.

PubMed

Hutton, Brian; Salanti, Georgia; Caldwell, Deborah M; Chaimani, Anna; Schmid, Christopher H; Cameron, Chris; Ioannidis, John P A; Straus, Sharon; Thorlund, Kristian; Jansen, Jeroen P; Mulrow, Cynthia; Catalá-López, Ferrán; Gøtzsche, Peter C; Dickersin, Kay; Boutron, Isabelle; Altman, Douglas G; Moher, David

2015-06-02

The PRISMA statement is a reporting guideline designed to improve the completeness of reporting of systematic reviews and meta-analyses. Authors have used this guideline worldwide to prepare their reviews for publication. In the past, these reports typically compared 2 treatment alternatives. With the evolution of systematic reviews that compare multiple treatments, some of them only indirectly, authors face novel challenges for conducting and reporting their reviews. This extension of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement was developed specifically to improve the reporting of systematic reviews incorporating network meta-analyses. A group of experts participated in a systematic review, Delphi survey, and face-to-face discussion and consensus meeting to establish new checklist items for this extension statement. Current PRISMA items were also clarified. A modified, 32-item PRISMA extension checklist was developed to address what the group considered to be immediately relevant to the reporting of network meta-analyses. This document presents the extension and provides examples of good reporting, as well as elaborations regarding the rationale for new checklist items and the modification of previously existing items from the PRISMA statement. It also highlights educational information related to key considerations in the practice of network meta-analysis. The target audience includes authors and readers of network meta-analyses, as well as journal editors and peer reviewers.

Dakota, a multilevel parallel object-oriented framework for design optimization, parameter estimation, uncertainty quantification, and sensitivity analysis version 6.0 theory manual

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

Adams, Brian M.; Ebeida, Mohamed Salah; Eldred, Michael S

The Dakota (Design Analysis Kit for Optimization and Terascale Applications) toolkit provides a exible and extensible interface between simulation codes and iterative analysis methods. Dakota contains algorithms for optimization with gradient and nongradient-based methods; uncertainty quanti cation with sampling, reliability, and stochastic expansion methods; parameter estimation with nonlinear least squares methods; and sensitivity/variance analysis with design of experiments and parameter study methods. These capabilities may be used on their own or as components within advanced strategies such as surrogate-based optimization, mixed integer nonlinear programming, or optimization under uncertainty. By employing object-oriented design to implement abstractions of the key components requiredmore » for iterative systems analyses, the Dakota toolkit provides a exible and extensible problem-solving environment for design and performance analysis of computational models on high performance computers. This report serves as a theoretical manual for selected algorithms implemented within the Dakota software. It is not intended as a comprehensive theoretical treatment, since a number of existing texts cover general optimization theory, statistical analysis, and other introductory topics. Rather, this manual is intended to summarize a set of Dakota-related research publications in the areas of surrogate-based optimization, uncertainty quanti cation, and optimization under uncertainty that provide the foundation for many of Dakota's iterative analysis capabilities.« less

STARLSE -- Starlink Extensions to the VAX Language Sensitive Editor

NASA Astrophysics Data System (ADS)

Warren-Smith, R. F.

STARLSE is a ``Starlink Sensitive'' editor based on the VAX Language Sensitive Editor (LSE). It exploits the extensibility of LSE to provide additional features which assist in the writing of portable Fortran 77 software with a standard Starlink style. STARLSE is intended mainly for use by those writing ADAM applications and subroutine libraries for distribution as part of the Starlink Software Collection, although it may also be suitable for other software projects. It is designed to integrate with the SST (Simple Software Tools) package.

Mercury orbiter transport study

NASA Technical Reports Server (NTRS)

Friedlander, A. L.; Feingold, H.

1977-01-01

A data base and comparative performance analyses of alternative flight mode options for delivering a range of payload masses to Mercury orbit are provided. Launch opportunities over the period 1980-2000 are considered. Extensive data trades are developed for the ballistic flight mode option utilizing one or more swingbys of Venus. Advanced transport options studied include solar electric propulsion and solar sailing. Results show the significant performance tradeoffs among such key parameters as trip time, payload mass, propulsion system mass, orbit size, launch year sensitivity and relative cost-effectiveness. Handbook-type presentation formats, particularly in the case of ballistic mode data, provide planetary program planners with an easily used source of reference information essential in the preliminary steps of mission selection and planning.

Highly Reusable Space Transportation (HRST) Baseline Concepts and Analysis: Rocket/RBCC Options. Part 2; A Comparative Study

NASA Technical Reports Server (NTRS)

Woodcock, Gordon

1997-01-01

This study is an extension of a previous effort by the Principal Investigator to develop baseline data to support comparative analysis of Highly Reusable Space Transportation (HRST) concepts. The analyses presented herin develop baseline data bases for two two-stage-to-orbit (TSTO) concepts: (1) Assisted horizontal take-off all rocket (assisted HTOHL); and (2) Assisted vertical take-off rocket based combined cycle (RBCC). The study objectives were to: (1) Provide configuration definitions and illustrations for assisted HTOHL and assisted RBCC; (2) Develop a rationalization approach and compare these concepts with the HRST reference; and (3) Analyze TSTO configurations which try to maintain SSTO benefits while reducing inert weight sensitivity.

Translation and cross-cultural adaptation of a family booklet on comfort care in dementia: sensitive topics revised before implementation.

PubMed

van der Steen, Jenny T; Hertogh, Cees M P M; de Graas, Tjomme; Nakanishi, Miharu; Toscani, Franco; Arcand, Marcel

2013-02-01

Families of patients with dementia may need support in difficult end-of-life decision making. Such guidance may be culturally sensitive. To support families in Canada, a booklet was developed to aid decision making on palliative care issues. For reasons of cost effectiveness and promising effects, we prepared for its implementation in Italy, the Netherlands and Japan. Local teams translated and adapted the booklet to local ethical, legal and medical standards where needed, retaining guidance on palliative care. Using qualitative content analyses, we grouped and compared adaptations to understand culturally sensitive aspects. Three themes emerged: (1) relationships among patient, physician and other professionals-the authority of the physician was more explicit in adapted versions; (2) patient rights and family position-adding detail about local regulations; and (3) typology of treatments and decisions. Considerations underlying palliative care decisions were detailed (Dutch and Italian versions), and the Japanese version frequently referred to professional and legal standards, and life-prolongation was a competing goal. Text on artificial feeding or fluids and euthanasia was revised extensively. Providing artificial feeding and fluids and discussing euthanasia may be particularly sensitive topics, and guidance on these subjects needs careful consideration of ethical aspects and possible adaptations to local standards and practice. The findings may promote cross-national debate on sensitive, core issues regarding end-of-life care in dementia.

Differences in executive functioning between violent and non-violent offenders.

PubMed

Meijers, J; Harte, J M; Meynen, G; Cuijpers, P

2017-07-01

A growing body of neuropsychological and neurobiological research shows a relationship between functioning of the prefrontal cortex and criminal and violent behaviour. The prefrontal cortex is crucial for executive functions such as inhibition, attention, working memory, set-shifting and planning. A deficit in these functions - a prefrontal deficit - may result in antisocial, impulsive or even aggressive behaviour. While several meta-analyses show large effect sizes for the relationship between a prefrontal deficit, executive dysfunction and criminality, there are few studies investigating differences in executive functions between violent and non-violent offenders. Considering the relevance of identifying risk factors for violent offending, the current study explores whether a distinction between violent and non-violent offenders can be made using an extensive neuropsychological test battery. Male remand prisoners (N = 130) in Penitentiary Institution Amsterdam Over-Amstel were administered an extensive neuropsychological test battery (Cambridge Automated Neuropsychological Test Battery; CANTAB) measuring response inhibition, planning, attention, set-shifting, working memory and impulsivity/reward sensitivity. Violent offenders performed significantly worse on the stop-signal task (partial correlation r = 0.205, p = 0.024), a task measuring response inhibition. No further differences were found between violent and non-violent offenders. Explorative analyses revealed a significant relationship between recidivism and planning (partial correlation r = -0.209, p = 0.016). Violent offenders show worse response inhibition compared to non-violent offenders, suggesting a more pronounced prefrontal deficit in violent offenders than in non-violent offenders.

Impact of production strategies and animal performance on economic values of dairy sheep traits.

PubMed

Krupová, Z; Wolfová, M; Krupa, E; Oravcová, M; Daňo, J; Huba, J; Polák, P

2012-03-01

The objective of this study was to carry out a sensitivity analysis on the impact of various production strategies and performance levels on the relative economic values (REVs) of traits in dairy sheep. A bio-economic model implemented in the program package ECOWEIGHT was used to simulate the profit function for a semi-extensive production system with the Slovak multi-purpose breed Improved Valachian and to calculate the REV of 14 production and functional traits. The following production strategies were analysed: differing proportions of milk processed to cheese, customary weaning and early weaning of lambs with immediate sale or sale after artificial rearing, seasonal lambing in winter and aseasonal lambing in autumn. Results of the sensitivity analysis are presented in detail for the four economically most important traits: 150 days milk yield, conception rate of ewes, litter size and ewe productive lifetime. Impacts of the differences in the mean value of each of these four traits on REVs of all other traits were also examined. Simulated changes in the production circumstances had a higher impact on the REV for milk yield than on REVs of the other traits investigated. The proportion of milk processed to cheese, weaning management strategy for lambs and level of milk yield were the main factors influencing the REV of milk yield. The REVs for conception rate of ewes were highly sensitive to the current mean level of the trait. The REV of ewe productive lifetime was most sensitive to variation in ewe conception rate, and the REV of litter size was most affected by weaning strategy for lambs. On the basis of the results of sensitivity analyses, it is recommended that economic values of traits for the overall breeding objective for dairy sheep be calculated as the weighted average of the economic values obtained for the most common production strategies of Slovak dairy sheep farms and that economic values be adjusted after substantial changes in performance levels of the traits.

Additional EIPC Study Analysis. Final Report

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

Hadley, Stanton W; Gotham, Douglas J.; Luciani, Ralph L.

Between 2010 and 2012 the Eastern Interconnection Planning Collaborative (EIPC) conducted a major long-term resource and transmission study of the Eastern Interconnection (EI). With guidance from a Stakeholder Steering Committee (SSC) that included representatives from the Eastern Interconnection States Planning Council (EISPC) among others, the project was conducted in two phases. Phase 1 involved a long-term capacity expansion analysis that involved creation of eight major futures plus 72 sensitivities. Three scenarios were selected for more extensive transmission- focused evaluation in Phase 2. Five power flow analyses, nine production cost model runs (including six sensitivities), and three capital cost estimations weremore » developed during this second phase. The results from Phase 1 and 2 provided a wealth of data that could be examined further to address energy-related questions. A list of 14 topics was developed for further analysis. This paper brings together the earlier interim reports of the first 13 topics plus one additional topic into a single final report.« less

On the sensitivity of annual streamflow to air temperature

USGS Publications Warehouse

Milly, Paul C.D.; Kam, Jonghun; Dunne, Krista A.

2018-01-01

Although interannual streamflow variability is primarily a result of precipitation variability, temperature also plays a role. The relative weakness of the temperature effect at the annual time scale hinders understanding, but may belie substantial importance on climatic time scales. Here we develop and evaluate a simple theory relating variations of streamflow and evapotranspiration (E) to those of precipitation (P) and temperature. The theory is based on extensions of the Budyko water‐balance hypothesis, the Priestley‐Taylor theory for potential evapotranspiration ( ), and a linear model of interannual basin storage. The theory implies that the temperature affects streamflow by modifying evapotranspiration through a Clausius‐Clapeyron‐like relation and through the sensitivity of net radiation to temperature. We apply and test (1) a previously introduced “strong” extension of the Budyko hypothesis, which requires that the function linking temporal variations of the evapotranspiration ratio (E/P) and the index of dryness ( /P) at an annual time scale is identical to that linking interbasin variations of the corresponding long‐term means, and (2) a “weak” extension, which requires only that the annual evapotranspiration ratio depends uniquely on the annual index of dryness, and that the form of that dependence need not be known a priori nor be identical across basins. In application of the weak extension, the readily observed sensitivity of streamflow to precipitation contains crucial information about the sensitivity to potential evapotranspiration and, thence, to temperature. Implementation of the strong extension is problematic, whereas the weak extension appears to capture essential controls of the temperature effect efficiently.

Direct potable reuse microbial risk assessment methodology: Sensitivity analysis and application to State log credit allocations.

PubMed

Soller, Jeffrey A; Eftim, Sorina E; Nappier, Sharon P

2018-01-01

Understanding pathogen risks is a critically important consideration in the design of water treatment, particularly for potable reuse projects. As an extension to our published microbial risk assessment methodology to estimate infection risks associated with Direct Potable Reuse (DPR) treatment train unit process combinations, herein, we (1) provide an updated compilation of pathogen density data in raw wastewater and dose-response models; (2) conduct a series of sensitivity analyses to consider potential risk implications using updated data; (3) evaluate the risks associated with log credit allocations in the United States; and (4) identify reference pathogen reductions needed to consistently meet currently applied benchmark risk levels. Sensitivity analyses illustrated changes in cumulative annual risks estimates, the significance of which depends on the pathogen group driving the risk for a given treatment train. For example, updates to norovirus (NoV) raw wastewater values and use of a NoV dose-response approach, capturing the full range of uncertainty, increased risks associated with one of the treatment trains evaluated, but not the other. Additionally, compared to traditional log-credit allocation approaches, our results indicate that the risk methodology provides more nuanced information about how consistently public health benchmarks are achieved. Our results indicate that viruses need to be reduced by 14 logs or more to consistently achieve currently applied benchmark levels of protection associated with DPR. The refined methodology, updated model inputs, and log credit allocation comparisons will be useful to regulators considering DPR projects and design engineers as they consider which unit treatment processes should be employed for particular projects. Published by Elsevier Ltd.

The impact of slice-reduced computed tomography on histogram-based densitometry assessment of lung fibrosis in patients with systemic sclerosis.

PubMed

Nguyen-Kim, Thi Dan Linh; Maurer, Britta; Suliman, Yossra A; Morsbach, Fabian; Distler, Oliver; Frauenfelder, Thomas

2018-04-01

To evaluate usability of slice-reduced sequential computed tomography (CT) compared to standard high-resolution CT (HRCT) in patients with systemic sclerosis (SSc) for qualitative and quantitative assessment of interstitial lung disease (ILD) with respect to (I) detection of lung parenchymal abnormalities, (II) qualitative and semiquantitative visual assessment, (III) quantification of ILD by histograms and (IV) accuracy for the 20%-cut off discrimination. From standard chest HRCT of 60 SSc patients sequential 9-slice-computed tomography (reduced HRCT) was retrospectively reconstructed. ILD was assessed by visual scoring and quantitative histogram parameters. Results from standard and reduced HRCT were compared using non-parametric tests and analysed by univariate linear regression analyses. With respect to the detection of parenchymal abnormalities, only the detection of intrapulmonary bronchiectasis was significantly lower in reduced HRCT compared to standard HRCT (P=0.039). No differences were found comparing visual scores for fibrosis severity and extension from standard and reduced HRCT (P=0.051-0.073). All scores correlated significantly (P<0.001) to histogram parameters derived from both, standard and reduced HRCT. Significant higher values of kurtosis and skewness for reduced HRCT were found (both P<0.001). In contrast to standard HRCT histogram parameters from reduced HRCT showed significant discrimination at cut-off 20% fibrosis (sensitivity 88% kurtosis and skewness; specificity 81% kurtosis and 86% skewness; cut-off kurtosis ≤26, cut-off skewness ≤4; both P<0.001). Reduced HRCT is a robust method to assess lung fibrosis in SSc with minimal radiation dose with no difference in scoring assessment of lung fibrosis severity and extension in comparison to standard HRCT. In contrast to standard HRCT histogram parameters derived from the approach of reduced HRCT could discriminate at a threshold of 20% lung fibrosis with high sensitivity and specificity. Hence it might be used to detect early disease progression of lung fibrosis in context of monitoring and treatment of SSc patients.

Cost effectiveness analysis of immunotherapy in patients with grass pollen allergic rhinoconjunctivitis in Germany.

PubMed

Westerhout, K Y; Verheggen, B G; Schreder, C H; Augustin, M

2012-01-01

An economic evaluation was conducted to assess the outcomes and costs as well as cost-effectiveness of the following grass-pollen immunotherapies: OA (Oralair; Stallergenes S.A., Antony, France) vs GRZ (Grazax; ALK-Abelló, Hørsholm, Denmark), and ALD (Alk Depot SQ; ALK-Abelló) (immunotherapy agents alongside symptomatic medication) and symptomatic treatment alone for grass pollen allergic rhinoconjunctivitis. The costs and outcomes of 3-year treatment were assessed for a period of 9 years using a Markov model. Treatment efficacy was estimated using an indirect comparison of available clinical trials with placebo as a common comparator. Estimates for immunotherapy discontinuation, occurrence of asthma, health state utilities, drug costs, resource use, and healthcare costs were derived from published sources. The analysis was conducted from the insurant's perspective including public and private health insurance payments and co-payments by insurants. Outcomes were reported as quality-adjusted life years (QALYs) and symptom-free days. The uncertainty around incremental model results was tested by means of extensive deterministic univariate and probabilistic multivariate sensitivity analyses. In the base case analysis the model predicted a cost-utility ratio of OA vs symptomatic treatment of €14,728 per QALY; incremental costs were €1356 (95%CI: €1230; €1484) and incremental QALYs 0.092 (95%CI: 0.052; 0.140). OA was the dominant strategy compared to GRZ and ALD, with estimated incremental costs of -€1142 (95%CI: -€1255; -€1038) and -€54 (95%CI: -€188; €85) and incremental QALYs of 0.015 (95%CI: -0.025; 0.056) and 0.027 (95%CI: -0.022; 0.075), respectively. At a willingness-to-pay threshold of €20,000, the probability of OA being the most cost-effective treatment was predicted to be 79%. Univariate sensitivity analyses show that incremental outcomes were moderately sensitive to changes in efficacy estimates. The main study limitation was the requirement of an indirect comparison involving several steps to assess relative treatment effects. The analysis suggests OA to be cost-effective compared to GRZ and ALD, and a symptomatic treatment. Sensitivity analyses showed that uncertainty surrounding treatment efficacy estimates affected the model outcomes.

Defining the Value of Future Research to Identify the Preferred Treatment of Meniscal Tear in the Presence of Knee Osteoarthritis

PubMed Central

Losina, Elena; Dervan, Elizabeth E.; Paltiel, A. David; Dong, Yan; Wright, R. John; Spindler, Kurt P.; Mandl, Lisa A.; Jones, Morgan H.; Marx, Robert G.; Safran-Norton, Clare E.; Katz, Jeffrey N.

2015-01-01

Background Arthroscopic partial meniscectomy (APM) is extensively used to relieve pain in patients with symptomatic meniscal tear (MT) and knee osteoarthritis (OA). Recent studies have failed to show the superiority of APM compared to other treatments. We aim to examine whether existing evidence is sufficient to reject use of APM as a cost-effective treatment for MT+OA. Methods We built a patient-level microsimulation using Monte Carlo methods and evaluated three strategies: Physical therapy (‘PT’) alone; PT followed by APM if subjects continued to experience pain (‘Delayed APM’); and ‘Immediate APM’. Our subject population was US adults with symptomatic MT and knee OA over a 10 year time horizon. We assessed treatment outcomes using societal costs, quality-adjusted life years (QALYs), and calculated incremental cost-effectiveness ratios (ICERs), incorporating productivity costs as a sensitivity analysis. We also conducted a value-of-information analysis using probabilistic sensitivity analyses. Results Calculated ICERs were estimated to be $12,900/QALY for Delayed APM as compared to PT and $103,200/QALY for Immediate APM as compared to Delayed APM. In sensitivity analyses, inclusion of time costs made Delayed APM cost-saving as compared to PT. Improving efficacy of Delayed APM led to higher incremental costs and lower incremental effectiveness of Immediate APM in comparison to Delayed APM. Probabilistic sensitivity analyses indicated that PT had 3.0% probability of being cost-effective at a willingness-to-pay (WTP) threshold of $50,000/QALY. Delayed APM was cost effective 57.7% of the time at WTP = $50,000/QALY and 50.2% at WTP = $100,000/QALY. The probability of Immediate APM being cost-effective did not exceed 50% unless WTP exceeded $103,000/QALY. Conclusions We conclude that current cost-effectiveness evidence does not support unqualified rejection of either Immediate or Delayed APM for the treatment of MT+OA. The amount to which society would be willing to pay for additional information on treatment outcomes greatly exceeds the cost of conducting another randomized controlled trial on APM. PMID:26086246

Correlation between the enhancement of flunitrazepam binding by GABA and seizure susceptibility in mice

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

Marley, R.J.; Wehner, J.M.

Various populations of mice exhibit differential sensitivity to seizure-inducing agents. The relationship of seizure susceptibility to alterations in the GABA receptor complex was investigated in six different populations of mice consisting of four inbred strains (C57BL, DBA, C3H, and BALB) and two selected lines (long sleep and short sleep). Seizure activity was induced by intraperitoneal administration of the GAD inhibitor, 3-mercaptopropionic acid, and latencies to seizure onset and tonus were measured. In naive mice of the same populations, GABA enhancement of TH-flunitrazepam binding was measured in extensively washed whole brain membranes at several GABA concentrations. Both differential seizure sensitivity tomore » 3-mercaptopropionic acid and differential enhancement of TH-flunitrazepam binding by GABA were observed in these six populations of mice. Correlational analyses indicated a positive correlation between the degree of GABA enhancement of TH-flunitrazepam binding and resistance to the seizure-inducing properties of 3-mercaptopropionic acid. These data suggest that genetic differences in sensitivity to seizure-inducing agents that disrupt the GABAergic system may be related to differences in coupling between the various receptors associated with the GABA receptor complex.« less

How Extension Can Help Communities Conduct Impact Analyses.

ERIC Educational Resources Information Center

Wisconsin Univ., Madison. Dept. of Agricultural Journalism.

Intended to provide guidance to Extension specialists and agents faced with requests for impact analyses from communities experiencing economic development, this report also summarizes issues that need to be considered. The first section, on private sector impacts, addresses questions on predicting changes in production, employment, and housing…

Robust artificial neural network for reliability and sensitivity analyses of complex non-linear systems.

PubMed

Oparaji, Uchenna; Sheu, Rong-Jiun; Bankhead, Mark; Austin, Jonathan; Patelli, Edoardo

2017-12-01

Artificial Neural Networks (ANNs) are commonly used in place of expensive models to reduce the computational burden required for uncertainty quantification, reliability and sensitivity analyses. ANN with selected architecture is trained with the back-propagation algorithm from few data representatives of the input/output relationship of the underlying model of interest. However, different performing ANNs might be obtained with the same training data as a result of the random initialization of the weight parameters in each of the network, leading to an uncertainty in selecting the best performing ANN. On the other hand, using cross-validation to select the best performing ANN based on the ANN with the highest R 2 value can lead to biassing in the prediction. This is as a result of the fact that the use of R 2 cannot determine if the prediction made by ANN is biased. Additionally, R 2 does not indicate if a model is adequate, as it is possible to have a low R 2 for a good model and a high R 2 for a bad model. Hence, in this paper, we propose an approach to improve the robustness of a prediction made by ANN. The approach is based on a systematic combination of identical trained ANNs, by coupling the Bayesian framework and model averaging. Additionally, the uncertainties of the robust prediction derived from the approach are quantified in terms of confidence intervals. To demonstrate the applicability of the proposed approach, two synthetic numerical examples are presented. Finally, the proposed approach is used to perform a reliability and sensitivity analyses on a process simulation model of a UK nuclear effluent treatment plant developed by National Nuclear Laboratory (NNL) and treated in this study as a black-box employing a set of training data as a test case. This model has been extensively validated against plant and experimental data and used to support the UK effluent discharge strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quality of clinical and economic evidence in dossier formulary submissions.

PubMed

Colmenero, Fernando; Sullivan, Sean D; Palmer, Jennifer A; Brauer, Carmen A; Bungay, Kathleen; Watkins, John; Neumann, Peter J

2007-07-01

To investigate the quality and completeness of clinical and economic data in dossiers submitted by drug companies to a health plan using Academy of Managed Care Pharmacy guidelines (the Format) for formulary submissions. We reviewed the quality of economic analyses in dossiers submitted to Premera Blue Cross Health Plan (Mountlake Terrace, Washington; enrollment 1.6 million) between January 2002 and September 2005. For dossiers submitted in 2003, we examined the clinical studies included. Dossiers were audited with a data collection form to judge the types of clinical studies used to support labeled and off-label indications, and the quality and transparency of economic analyses. We compared economic analyses for high-cost (30-day treatment cost > $1000) versus low-cost products, and for "innovative" versus "me-too" drugs. Evidence to support off-label indications often was included in 2003 dossiers, but the information was less extensive and of poorer quality than data for labeled indications. Of 115 dossiers submitted between 2002 and 2005, 53 (46%) included economic analyses. The economic analyses had low levels of compliance with standards: only 43% performed sensitivity analysis; 38% stated the study perspective; 37% discussed relevant treatment alternatives; 20% stated assumptions clearly; and 18% mentioned caveats to conclusions. Economic analyses of high-cost products and innovative products had higher compliance with recommended practices. Drug companies are submitting dossiers of evidence to formulary committees. Dossiers often included clinical data to support off-label indications, but concerns persist about their quality. About half of dossiers included economic analyses, but these analyses had relatively low levels of compliance with recommended practices.

Is prevention of atopic eczema with hydrolyzed formulas cost-effective? A health economic evaluation from Germany.

PubMed

Mertens, Janina; Stock, Stephanie; Lüngen, Markus; von Berg, Andrea; Krämer, Ursula; Filipiak-Pittroff, Birgit; Heinrich, Joachim; Koletzko, Sibylle; Grübl, Armin; Wichmann, H-Erich; Bauer, Carl-P; Reinhardt, Dietrich; Berdel, Dietrich; Gerber, Andreas

2012-09-01

The German Infant Nutritional Intervention (GINI) trial, a prospective, randomized, double-blind intervention, enrolled children with a hereditary risk for atopy. When fed with certain hydrolyzed formulas for the first 4 months of life, the risk was reduced by 26-45% in PP and 8-29% in intention-to-treat (ITT) analyses compared with children fed with regular cow's milk at age 6. The objective was to assess the cost-effectiveness of feeding hydrolyzed formulas. Cost-effectiveness was assessed with a decision tree model programmed in TreeAge. Costs and effects over a 6-yr period were analyzed from the perspective of the German statutory health insurance (SHI) and a societal perspective at a 3% effective discount rate followed by sensitivity analyses. The extensively hydrolyzed casein formula would be the most cost-saving strategy with savings of 478 € per child treated in the ITT analysis (CI95%: 12 €; 852 €) and 979 € in the PP analysis (95%CI: 355 €; 1455 €) from a societal perspective. If prevented cases are considered, the partially whey hydrolyzed formula is cost-saving (ITT -5404 €, PP -6358 €). From an SHI perspective, the partially whey hydrolyzed formula is cost-effective, but may also be cost-saving depending on the scenario. An extensively hydrolyzed whey formula also included into the analysis was dominated in all analyses. For the prevention of AE, two formulas can be cost-effective or even cost-saving. We recommend that SHI should reimburse formula feeding or at least the difference between costs for cow's milk formula and the most cost-effective formula. © 2012 John Wiley & Sons A/S.

Cost effectiveness of the addition of a comprehensive CT scan to the abdomen and pelvis for the detection of cancer after unprovoked venous thromboembolism.

PubMed

Coyle, Kathryn; Carrier, Marc; Lazo-Langner, Alejandro; Shivakumar, Sudeep; Zarychanski, Ryan; Tagalakis, Vicky; Solymoss, Susan; Routhier, Nathalie; Douketis, James; Coyle, Douglas

2017-03-01

Unprovoked venous thromboembolism (VTE) can be the first manifestation of cancer. It is unclear if extensive screening for occult cancer including a comprehensive computed tomography (CT) scan of the abdomen/pelvis is cost-effective in this patient population. To assess the health care related costs, number of missed cancer cases and health related utility values of a limited screening strategy with and without the addition of a comprehensive CT scan of the abdomen/pelvis and to identify to what extent testing should be done in these circumstances to allow early detection of occult cancers. Cost effectiveness analysis using data that was collected alongside the SOME randomized controlled trial which compared an extensive occult cancer screening including a CT of the abdomen/pelvis to a more limited screening strategy in patients with a first unprovoked VTE, was used for the current analyses. Analyses were conducted with a one-year time horizon from a Canadian health care perspective. Primary analysis was based on complete cases, with sensitivity analysis using appropriate multiple imputation methods to account for missing data. Data from a total of 854 patients with a first unprovoked VTE were included in these analyses. The addition of a comprehensive CT scan was associated with higher costs ($551 CDN) with no improvement in utility values or number of missed cancers. Results were consistent when adopting multiple imputation methods. The addition of a comprehensive CT scan of the abdomen/pelvis for the screening of occult cancer in patients with unprovoked VTE is not cost effective, as it is both more costly and not more effective in detecting occult cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Research applications for an Object and Action Naming Battery to assess naming skills in adult Spanish-English bilingual speakers.

PubMed

Edmonds, Lisa A; Donovan, Neila J

2014-06-01

Virtually no valid materials are available to evaluate confrontation naming in Spanish-English bilingual adults in the U.S. In a recent study, a large group of young Spanish-English bilingual adults were evaluated on An Object and Action Naming Battery (Edmonds & Donovan in Journal of Speech, Language, and Hearing Research 55:359-381, 2012). Rasch analyses of the responses resulted in evidence for the content and construct validity of the retained items. However, the scope of that study did not allow for extensive examination of individual item characteristics, group analyses of participants, or the provision of testing and scoring materials or raw data, thereby limiting the ability of researchers to administer the test to Spanish-English bilinguals and to score the items with confidence. In this study, we present the in-depth information described above on the basis of further analyses, including (1) online searchable spreadsheets with extensive empirical (e.g., accuracy and name agreeability) and psycholinguistic item statistics; (2) answer sheets and instructions for scoring and interpreting the responses to the Rasch items; (3) tables of alternative correct responses for English and Spanish; (4) ability strata determined for all naming conditions (English and Spanish nouns and verbs); and (5) comparisons of accuracy across proficiency groups (i.e., Spanish dominant, English dominant, and balanced). These data indicate that the Rasch items from An Object and Action Naming Battery are valid and sensitive for the evaluation of naming in young Spanish-English bilingual adults. Additional information based on participant responses for all of the items on the battery can provide researchers with valuable information to aid in stimulus development and response interpretation for experimental studies in this population.

A novel high light-inducible carotenoid-binding protein complex in the thylakoid membranes of Synechocystis PCC 6803

PubMed Central

Daddy, Soumana; Zhan, Jiao; Jantaro, Saowarath; He, Chenliu; He, Qingfang; Wang, Qiang

2015-01-01

Synechocystis sp. PCC 6803 is a model cyanobacterium extensively used to study photosynthesis. Here we reveal a novel high light-inducible carotenoid-binding protein complex (HLCC) in the thylakoid membranes of Synechocystis PCC 6803 cells exposed to high intensity light. Zeaxanthin and myxoxanthophyll accounted for 29.8% and 54.8%, respectively, of the carotenoids bound to the complex. Using Blue-Native PAGE followed by 2D SDS-PAGE and mass spectrometry, we showed that the HLCC consisted of Slr1128, IsiA, PsaD, and HliA/B. We confirmed these findings by SEAD fluorescence cross-linking and anti-PsaD immuno-coprecipitation analyses. The expression of genes encoding the protein components of the HLCC was enhanced by high light illumination and artificial oxidative stress. Deletion of these proteins resulted in impaired state transition and increased sensitivity to oxidative and/or high light stress, as indicated by increased membrane peroxidation. Therefore, the HLCC protects thylakoid membranes from extensive photooxidative damage, likely via a mechanism involving state transition. PMID:25820628

Chikungunya virus nsP4 RNA-dependent RNA polymerase core domain displays detergent-sensitive primer extension and terminal adenylyltransferase activities.

PubMed

Chen, Ming Wei; Tan, Yaw Bia; Zheng, Jie; Zhao, Yongqian; Lim, Bee Ting; Cornvik, Tobias; Lescar, Julien; Ng, Lisa Fong Poh; Luo, Dahai

2017-07-01

Chikungunya virus (CHIKV) is an important arboviral infectious agent in tropical and subtropical regions, often causing persistent and debilitating disease. The viral enzyme non-structural protein 4 (nsP4), as RNA-dependent RNA polymerase (RdRP), catalyzes the formation of negative-sense, genomic and subgenomic viral RNAs. Here we report a truncated nsP4 construct that is soluble, stable and purified recombinantly from Escherichia coli. Sequence analyses and homology modelling indicate that all necessary RdRP elements are included. Hydrogen/deuterium exchange with mass spectrometry was used to analyze solvent accessibility and flexibility of subdomains. Fluorophore-conjugated RNA ligands were designed and screened by using fluorescence anisotropy to select a suitable substrate for RdRP assays. Assay trials revealed that nsP4 core domain is conditionally active upon choice of detergent species, and carries out both primed extension and terminal adenylyltransferase activities. The polymerization assay can be further developed to screen for antiviral compounds in vitro. Copyright © 2017 Elsevier B.V. All rights reserved.

Lorentz-symmetry test at Planck-scale suppression with nucleons in a spin-polarized 133Cs cold atom clock

NASA Astrophysics Data System (ADS)

Pihan-Le Bars, H.; Guerlin, C.; Lasseri, R.-D.; Ebran, J.-P.; Bailey, Q. G.; Bize, S.; Khan, E.; Wolf, P.

2017-04-01

We introduce an improved model that links the frequency shift of the 133Cs hyperfine Zeeman transitions |F =3 ,mF ⟩↔|F =4 ,mF ⟩ to the Lorentz-violating Standard Model extension (SME) coefficients of the proton and neutron. The new model uses Lorentz transformations developed to second order in boost and additionally takes the nuclear structure into account, beyond the simple Schmidt model used previously in Standard Model extension analyses, thereby providing access to both proton and neutron SME coefficients including the isotropic coefficient c˜T T. Using this new model in a second analysis of the data delivered by the FO2 dual Cs/Rb fountain at Paris Observatory and previously analyzed in [1], we improve by up to 13 orders of magnitude the present maximum sensitivities for laboratory tests [2] on the c˜Q, c˜T J, and c˜T T coefficients for the neutron and on the c˜Q coefficient for the proton, reaching respectively 10-20, 10-17, 10-13, and 10-15 GeV .

A novel high light-inducible carotenoid-binding protein complex in the thylakoid membranes of Synechocystis PCC 6803.

PubMed

Daddy, Soumana; Zhan, Jiao; Jantaro, Saowarath; He, Chenliu; He, Qingfang; Wang, Qiang

2015-03-30

Synechocystis sp. PCC 6803 is a model cyanobacterium extensively used to study photosynthesis. Here we reveal a novel high light-inducible carotenoid-binding protein complex (HLCC) in the thylakoid membranes of Synechocystis PCC 6803 cells exposed to high intensity light. Zeaxanthin and myxoxanthophyll accounted for 29.8% and 54.8%, respectively, of the carotenoids bound to the complex. Using Blue-Native PAGE followed by 2D SDS-PAGE and mass spectrometry, we showed that the HLCC consisted of Slr1128, IsiA, PsaD, and HliA/B. We confirmed these findings by SEAD fluorescence cross-linking and anti-PsaD immuno-coprecipitation analyses. The expression of genes encoding the protein components of the HLCC was enhanced by high light illumination and artificial oxidative stress. Deletion of these proteins resulted in impaired state transition and increased sensitivity to oxidative and/or high light stress, as indicated by increased membrane peroxidation. Therefore, the HLCC protects thylakoid membranes from extensive photooxidative damage, likely via a mechanism involving state transition.

Manned geosynchronous mission requirements and systems analysis study extension. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1981-01-01

A study was performed to determine the types of manned missions that will likely be performed in the late 1980's or early 1990's timeframe, to define MOTV configurations which satisfy these missions requirements, and to develop a program plan for its development. Twenty generic missions were originally defined for MOTV but, to simplify the selection process, five of these missions were selected as typical and used as Design Reference Missions. Systems and subsystems requirements were re-examined and sensitivity analyses performed to determine optimum point designs. Turnaround modes were considered to determine the most effective combination of ground based and spaced based activities. A preferred concept for the crew capsule and for the mission mode was developed.

Emergence of hysteresis loop in social contagions on complex networks.

PubMed

Su, Zhen; Wang, Wei; Li, Lixiang; Xiao, Jinghua; Stanley, H Eugene

2017-07-21

Understanding the spreading mechanisms of social contagions in complex network systems has attracted much attention in the physics community. Here we propose a generalized threshold model to describe social contagions. Using extensive numerical simulations and theoretical analyses, we find that a hysteresis loop emerges in the system. Specifically, the steady state of the system is sensitive to the initial conditions of the dynamics of the system. In the steady state, the adoption size increases discontinuously with the transmission probability of information about social contagions, and trial size exhibits a non-monotonic pattern, i.e., it first increases discontinuously then decreases continuously. Finally we study social contagions on heterogeneous networks and find that network topology does not qualitatively affect our results.

The financial attractiveness assessment of large waste management projects registered as clean development mechanism

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

Bufoni, André Luiz, E-mail: bufoni@facc.ufrj.br; Oliveira, Luciano Basto; Rosa, Luiz Pinguelli

Highlights: • Projects are not financially attractive without registration as CDMs. • WM benchmarks and indicators are converging and reducing in variance. • A sensitivity analysis reveal that revenue has more of an effect on the financial results. • Results indicate that an extensive database would reduce WM project risk and capital costs. • Disclosure standards would make information more comparable worldwide. - Abstract: This study illustrates the financial analyses for demonstration and assessment of additionality presented in the project design (PDD) and enclosed documents of the 431 large Clean Development Mechanisms (CDM) classified as the ‘waste handling and disposalmore » sector’ (13) over the past ten years (2004–2014). The expected certified emissions reductions (CER) of these projects total 63.54 million metric tons of CO{sub 2}eq, where eight countries account for 311 projects and 43.36 million metric tons. All of the projects declare themselves ‘not financially attractive’ without CER with an estimated sum of negative results of approximately a half billion US$. The results indicate that WM benchmarks and indicators are converging and reducing in variance, and the sensitivity analysis reveals that revenues have a greater effect on the financial results. This work concludes that an extensive financial database with simple standards for disclosure would greatly diminish statement problems and make information more comparable, reducing the risk and capital costs of WM projects.« less

Cost-effectiveness of bedaquiline in MDR and XDR tuberculosis in Italy

PubMed Central

Codecasa, Luigi R.; Toumi, Mondher; D’Ausilio, Anna; Aiello, Andrea; Damele, Francesco; Termini, Roberta; Uglietti, Alessia; Hettle, Robert; Graziano, Giorgio; De Lorenzo, Saverio

2017-01-01

ABSTRACT Objective: To evaluate the cost-effectiveness of bedaquiline plus background drug regimens (BR) for multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in Italy. Methods: A Markov model was adapted to the Italian setting to estimate the incremental cost-effectiveness ratio (ICER) of bedaquiline plus BR (BBR) versus BR in the treatment of MDR-TB and XDR-TB over 10 years, from both the National Health Service (NHS) and societal perspective. Cost-effectiveness was evaluated in terms of life-years gained (LYG). Clinical data were sourced from trials; resource consumption for compared treatments was modelled according to advice from an expert clinicians panel. NHS tariffs for inpatient and outpatient resource consumption were retrieved from published Italian sources. Drug costs were provided by reference centres for disease treatment in Italy. A 3% annual discount was applied to both cost and effectiveness. Deterministic and probabilistic sensitivity analyses were conducted. Results: Over 10 years, BBR vs. BR alone is cost-effective, with ICERs of €16,639/LYG and €4081/LYG for the NHS and society, respectively. The sensitivity analyses confirmed the robustness of the results from both considered perspectives. Conclusion: In Italy, BBR vs. BR alone has proven to be cost-effective in the treatment of MDR-TB and XDR-TB under a range of scenarios. PMID:28265350

Law enforcement tools available at the Savannah River Site

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

Hofstetter, K.J.

A number of nuclear technologies developed and applied at the Savannah River Site in support of nuclear weapons material production and environmental remediation can be applied to problems in law enforcement. Techniques and equipment for high-sensitivity analyses of samples are available to identify and quantify trace elements and establish origins and histories of forensic evidence removed from crime scenes. While some of theses capabilities are available at local crime laboratories, state-of-the-art equipment and breakthroughs in analytical techniques are continually being developed at DOE laboratories. Extensive experience with the handling of radioactive samples at the DOE labs minimizes the chances ofmore » cross-contamination of evidence received from law enforcement. In addition to high-sensitivity analyses, many of the field techniques developed for use in a nuclear facility can assist law enforcement personnel in detecting illicit materials and operations, in retrieving of pertinent evidence and in surveying crime scenes. Some of these tools include chemical sniffers, hand-held detectors, thermal imaging, etc. In addition, mobile laboratories can be deployed to a crime scene to provide field screening of potential evidence. A variety of portable sensors can be deployed on vehicle, aerial, surface or submersible platforms to assist in the location of pertinent evidence or illicit operations. Several specific nuclear technologies available to law enforcement and their potential uses are discussed.« less

Subcortical volumetric changes across the adult lifespan: subregional thalamic atrophy accounts for age-related sensorimotor performance declines.

PubMed

Serbruyns, Leen; Leunissen, Inge; Huysmans, Toon; Cuypers, Koen; Meesen, Raf L; van Ruitenbeek, Peter; Sijbers, Jan; Swinnen, Stephan P

2015-04-01

Even though declines in sensorimotor performance during healthy aging have been documented extensively, its underlying neural mechanisms remain unclear. Here, we explored whether age-related subcortical atrophy plays a role in sensorimotor performance declines, and particularly during bimanual manipulative performance (Purdue Pegboard Test). The thalamus, putamen, caudate and pallidum of 91 participants across the adult lifespan (ages 20-79 years) were automatically segmented. In addition to studying age-related changes in the global volume of each subcortical structure, local deformations within these structures, indicative of subregional volume changes, were assessed by means of recently developed shape analyses. Results showed widespread age-related global and subregional atrophy, as well as some notable subregional expansion. Even though global atrophy failed to explain the observed performance declines with aging, shape analyses indicated that atrophy in left and right thalamic subregions, specifically subserving connectivity with the premotor, primary motor and somatosensory cortical areas, mediated the relation between aging and performance decline. It is concluded that subregional volume assessment by means of shape analyses offers a sensitive tool with high anatomical resolution in the search for specific age-related associations between brain structure and behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

SVDS plume impingement modeling development. Sensitivity analysis supporting level B requirements

NASA Technical Reports Server (NTRS)

Chiu, P. B.; Pearson, D. J.; Muhm, P. M.; Schoonmaker, P. B.; Radar, R. J.

1977-01-01

A series of sensitivity analyses (trade studies) performed to select features and capabilities to be implemented in the plume impingement model is described. Sensitivity analyses were performed in study areas pertaining to geometry, flowfield, impingement, and dynamical effects. Recommendations based on these analyses are summarized.

Using R-Project for Free Statistical Analysis in Extension Research

ERIC Educational Resources Information Center

Mangiafico, Salvatore S.

2013-01-01

One option for Extension professionals wishing to use free statistical software is to use online calculators, which are useful for common, simple analyses. A second option is to use a free computing environment capable of performing statistical analyses, like R-project. R-project is free, cross-platform, powerful, and respected, but may be…

Mixture models in diagnostic meta-analyses--clustering summary receiver operating characteristic curves accounted for heterogeneity and correlation.

PubMed

Schlattmann, Peter; Verba, Maryna; Dewey, Marc; Walther, Mario

2015-01-01

Bivariate linear and generalized linear random effects are frequently used to perform a diagnostic meta-analysis. The objective of this article was to apply a finite mixture model of bivariate normal distributions that can be used for the construction of componentwise summary receiver operating characteristic (sROC) curves. Bivariate linear random effects and a bivariate finite mixture model are used. The latter model is developed as an extension of a univariate finite mixture model. Two examples, computed tomography (CT) angiography for ruling out coronary artery disease and procalcitonin as a diagnostic marker for sepsis, are used to estimate mean sensitivity and mean specificity and to construct sROC curves. The suggested approach of a bivariate finite mixture model identifies two latent classes of diagnostic accuracy for the CT angiography example. Both classes show high sensitivity but mainly two different levels of specificity. For the procalcitonin example, this approach identifies three latent classes of diagnostic accuracy. Here, sensitivities and specificities are quite different as such that sensitivity increases with decreasing specificity. Additionally, the model is used to construct componentwise sROC curves and to classify individual studies. The proposed method offers an alternative approach to model between-study heterogeneity in a diagnostic meta-analysis. Furthermore, it is possible to construct sROC curves even if a positive correlation between sensitivity and specificity is present. Copyright © 2015 Elsevier Inc. All rights reserved.

PRISMA-Children (C) and PRISMA-Protocol for Children (P-C) Extensions: a study protocol for the development of guidelines for the conduct and reporting of systematic reviews and meta-analyses of newborn and child health research.

PubMed

Kapadia, Mufiza Z; Askie, Lisa; Hartling, Lisa; Contopoulos-Ioannidis, Despina; Bhutta, Zulfiqar A; Soll, Roger; Moher, David; Offringa, Martin

2016-04-18

Paediatric systematic reviews differ from adult systematic reviews in several key aspects such as considerations of child tailored interventions, justifiable comparators, valid outcomes and child sensitive search strategies. Available guidelines, including PRISMA-P (2015) and PRISMA (2009), do not cover all the complexities associated with reporting systematic reviews in the paediatric population. Using a collaborative, multidisciplinary structure, we aim to develop evidence-based and consensus-based PRISMA-P-C (Protocol for Children) and PRISMA-C (Children) Extensions to guide paediatric systematic review protocol and completed review reporting. This project's methodology follows published recommendations for developing reporting guidelines and involves the following six phases; (1) establishment of a steering committee representing key stakeholder groups; (2) a scoping review to identify potential Extension items; (3) three types of consensus activities including meetings of the steering committee to achieve high-level decisions on the content and methodology of the Extensions, a survey of key stakeholders to generate a list of possible items to include in the Extensions and a formal consensus meeting to select the reporting items to add to, or modify for, the Extension; (4) the preliminary checklist items generated in phase III will be evaluated against the existing evidence and reporting practices in paediatric systematic reviews; (5) extension statements and explanation and elaboration documents will provide detailed advice for each item and examples of good reporting; (6) development and implementation of effective knowledge translation of the extension checklist, and an evaluation of the Extensions by key stakeholders. This protocol was considered a quality improvement project by the Hospital for Sick Children's Ethics Committee and did not require ethical review. The resultant checklists, jointly developed with all relevant stakeholders, will be disseminated through peer-reviewed journals as well as national and international conference presentations. Endorsement of the checklist will be sought simultaneously in multiple journals. 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/

PRISMA-Children (C) and PRISMA-Protocol for Children (P-C) Extensions: a study protocol for the development of guidelines for the conduct and reporting of systematic reviews and meta-analyses of newborn and child health research

PubMed Central

Kapadia, Mufiza Z; Askie, Lisa; Hartling, Lisa; Contopoulos-Ioannidis, Despina; Bhutta, Zulfiqar A; Soll, Roger; Moher, David; Offringa, Martin

2016-01-01

Introduction Paediatric systematic reviews differ from adult systematic reviews in several key aspects such as considerations of child tailored interventions, justifiable comparators, valid outcomes and child sensitive search strategies. Available guidelines, including PRISMA-P (2015) and PRISMA (2009), do not cover all the complexities associated with reporting systematic reviews in the paediatric population. Using a collaborative, multidisciplinary structure, we aim to develop evidence-based and consensus-based PRISMA-P-C (Protocol for Children) and PRISMA-C (Children) Extensions to guide paediatric systematic review protocol and completed review reporting. Methods and analysis This project's methodology follows published recommendations for developing reporting guidelines and involves the following six phases; (1) establishment of a steering committee representing key stakeholder groups; (2) a scoping review to identify potential Extension items; (3) three types of consensus activities including meetings of the steering committee to achieve high-level decisions on the content and methodology of the Extensions, a survey of key stakeholders to generate a list of possible items to include in the Extensions and a formal consensus meeting to select the reporting items to add to, or modify for, the Extension; (4) the preliminary checklist items generated in phase III will be evaluated against the existing evidence and reporting practices in paediatric systematic reviews; (5) extension statements and explanation and elaboration documents will provide detailed advice for each item and examples of good reporting; (6) development and implementation of effective knowledge translation of the extension checklist, and an evaluation of the Extensions by key stakeholders. Ethics and Dissemination This protocol was considered a quality improvement project by the Hospital for Sick Children's Ethics Committee and did not require ethical review. The resultant checklists, jointly developed with all relevant stakeholders, will be disseminated through peer-reviewed journals as well as national and international conference presentations. Endorsement of the checklist will be sought simultaneously in multiple journals. PMID:27091820

Association of oxidative status and insulin sensitivity in periparturient dairy cattle: an observational study.

PubMed

Abuelo, A; Hernández, J; Benedito, J L; Castillo, C

2016-04-01

Post-parturient insulin resistance (IR) is a common feature in all mammalian animals. However, in dairy cows, it can be exacerbated because of high milk yield, leading to excessive negative energy balance, which is related with increased disease incidence, reduced milk production and worsened reproductive performance. IR has been extensively investigated in humans suffering from diabetes mellitus. In these subjects, it is known that oxidative stress (OS) plays a causative role in the onset of IR. Although OS occurs in transitional dairy cattle, there are yet no studies that investigated the association between IR and OS in dairy cattle. Therefore, the aim of this study was to investigate whether there is a relationship between OS and IR in dairy cattle. Serum samples were taken repeatedly from 22 dairy cows from 2 months prior to the expected calving date to 2 months after calving and were analysed for markers of metabolic and redox balance. Surrogate indices of insulin sensitivity were also calculated. Generalised linear mixed models revealed an effect of the oxidative status on peripheral insulin concentration and on indices of insulin sensitivity. Hence, field trials should investigate the effectiveness of antioxidant therapy on insulin sensitivity in peripheral tissues during the transition period of dairy cattle. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

The evaluation and validation of Phadebas® paper as a presumptive screening tool for saliva on forensic exhibits.

PubMed

Wornes, Danielle J; Speers, Samuel J; Murakami, Julie A

2018-07-01

The Phadebas ® Forensic Press Test is routinely used for the detection of saliva. However, assessment of the use of Phadebas ® paper for this purpose has not been studied extensively. The suitability of Phadebas ® paper as a presumptive screening tool for saliva on forensic exhibits, was investigated by analysing the following: (1) sensitivity, (2) specificity, (3) effects of temperature on sensitivity and specificity, (4) detection of saliva in mixed body fluid samples, and (5) influence of substrate porosity. The results of this study demonstrated that Phadebas ® paper is more sensitive to α-amylase activity and less specific for saliva than previously reported. The use of an examination temperature of 37°C had no effect on sensitivity, but increased the incidence of cross-reactivity with other forensically relevant body fluid stains. Blood, urine and vaginal secretions can inhibit the detection of α-amylase activity with Phadebas ® paper in mixed stains of saliva and body fluid. Substrate porosity is a weak predictor for the time taken for a saliva stain to achieve a strong positive result on Phadebas ® paper. Overall, this study demonstrated that the Phadebas ® Forensic Press Test has limitations as a presumptive test for the accurate identification of saliva. Copyright © 2018 Elsevier B.V. All rights reserved.

Modified RS2101 rocket engine study program

NASA Technical Reports Server (NTRS)

1971-01-01

The purpose of the program is to perform design studies and analyses to determine the effects of incorporating a 60:1 expansion area ratio nozzle extension, extended firing time, and modified operating conditions and environments on the MM'71 rocket engine assembly. An injector-to-thrust chamber seal study was conducted to define potential solutions for leakage past this joint. The results and recommendations evolving from the engine thermal analyses, the injector-to-thrust chamber seal studies, and the nozzle extension joint stress analyses are presented.

Different Imaging Strategies in Patients With Possible Basilar Artery Occlusion: Cost-Effectiveness Analysis.

PubMed

Beyer, Sebastian E; Hunink, Myriam G; Schöberl, Florian; von Baumgarten, Louisa; Petersen, Steffen E; Dichgans, Martin; Janssen, Hendrik; Ertl-Wagner, Birgit; Reiser, Maximilian F; Sommer, Wieland H

2015-07-01

This study evaluated the cost-effectiveness of different noninvasive imaging strategies in patients with possible basilar artery occlusion. A Markov decision analytic model was used to evaluate long-term outcomes resulting from strategies using computed tomographic angiography (CTA), magnetic resonance imaging, nonenhanced CT, or duplex ultrasound with intravenous (IV) thrombolysis being administered after positive findings. The analysis was performed from the societal perspective based on US recommendations. Input parameters were derived from the literature. Costs were obtained from United States costing sources and published literature. Outcomes were lifetime costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios, and net monetary benefits, with a willingness-to-pay threshold of $80,000 per QALY. The strategy with the highest net monetary benefit was considered the most cost-effective. Extensive deterministic and probabilistic sensitivity analyses were performed to explore the effect of varying parameter values. In the reference case analysis, CTA dominated all other imaging strategies. CTA yielded 0.02 QALYs more than magnetic resonance imaging and 0.04 QALYs more than duplex ultrasound followed by CTA. At a willingness-to-pay threshold of $80,000 per QALY, CTA yielded the highest net monetary benefits. The probability that CTA is cost-effective was 96% at a willingness-to-pay threshold of $80,000/QALY. Sensitivity analyses showed that duplex ultrasound was cost-effective only for a prior probability of ≤0.02 and that these results were only minimally influenced by duplex ultrasound sensitivity and specificity. Nonenhanced CT and magnetic resonance imaging never became the most cost-effective strategy. Our results suggest that CTA in patients with possible basilar artery occlusion is cost-effective. © 2015 The Authors.

Different Imaging Strategies in Patients With Possible Basilar Artery Occlusion

PubMed Central

Beyer, Sebastian E.; Hunink, Myriam G.; Schöberl, Florian; von Baumgarten, Louisa; Petersen, Steffen E.; Dichgans, Martin; Janssen, Hendrik; Ertl-Wagner, Birgit; Reiser, Maximilian F.

2015-01-01

Background and Purpose— This study evaluated the cost-effectiveness of different noninvasive imaging strategies in patients with possible basilar artery occlusion. Methods— A Markov decision analytic model was used to evaluate long-term outcomes resulting from strategies using computed tomographic angiography (CTA), magnetic resonance imaging, nonenhanced CT, or duplex ultrasound with intravenous (IV) thrombolysis being administered after positive findings. The analysis was performed from the societal perspective based on US recommendations. Input parameters were derived from the literature. Costs were obtained from United States costing sources and published literature. Outcomes were lifetime costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios, and net monetary benefits, with a willingness-to-pay threshold of $80 000 per QALY. The strategy with the highest net monetary benefit was considered the most cost-effective. Extensive deterministic and probabilistic sensitivity analyses were performed to explore the effect of varying parameter values. Results— In the reference case analysis, CTA dominated all other imaging strategies. CTA yielded 0.02 QALYs more than magnetic resonance imaging and 0.04 QALYs more than duplex ultrasound followed by CTA. At a willingness-to-pay threshold of $80 000 per QALY, CTA yielded the highest net monetary benefits. The probability that CTA is cost-effective was 96% at a willingness-to-pay threshold of $80 000/QALY. Sensitivity analyses showed that duplex ultrasound was cost-effective only for a prior probability of ≤0.02 and that these results were only minimally influenced by duplex ultrasound sensitivity and specificity. Nonenhanced CT and magnetic resonance imaging never became the most cost-effective strategy. Conclusions— Our results suggest that CTA in patients with possible basilar artery occlusion is cost-effective. PMID:26022634

Economic evaluation of strategies for restarting anticoagulation therapy after a first event of unprovoked venous thromboembolism.

PubMed

Monahan, M; Ensor, J; Moore, D; Fitzmaurice, D; Jowett, S

2017-08-01

Essentials Correct duration of treatment after a first unprovoked venous thromboembolism (VTE) is unknown. We assessed when restarting anticoagulation was worthwhile based on patient risk of recurrent VTE. When the risk over a one-year period is 17.5%, restarting is cost-effective. However, sensitivity analyses indicate large uncertainty in the estimates. Background Following at least 3 months of anticoagulation therapy after a first unprovoked venous thromboembolism (VTE), there is uncertainty about the duration of therapy. Further anticoagulation therapy reduces the risk of having a potentially fatal recurrent VTE but at the expense of a higher risk of bleeding, which can also be fatal. Objective An economic evaluation sought to estimate the long-term cost-effectiveness of using a decision rule for restarting anticoagulation therapy vs. no extension of therapy in patients based on their risk of a further unprovoked VTE. Methods A Markov patient-level simulation model was developed, which adopted a lifetime time horizon with monthly time cycles and was from a UK National Health Service (NHS)/Personal Social Services (PSS) perspective. Results Base-case model results suggest that treating patients with a predicted 1 year VTE risk of 17.5% or higher may be cost-effective if decision makers are willing to pay up to £20 000 per quality adjusted life year (QALY) gained. However, probabilistic sensitivity analysis shows that the model was highly sensitive to overall parameter uncertainty and caution is warranted in selecting the optimal decision rule on cost-effectiveness grounds. Univariate sensitivity analyses indicate variables such as anticoagulation therapy disutility and mortality risks were very influential in driving model results. Conclusion This represents the first economic model to consider the use of a decision rule for restarting therapy for unprovoked VTE patients. Better data are required to predict long-term bleeding risks during therapy in this patient group. © 2017 International Society on Thrombosis and Haemostasis.

Performance of the Assessment of Spondyloarthritis International Society criteria for the classification of spondyloarthritis in early spondyloarthritis clinics participating in the ESPERANZA programme.

PubMed

Tomero, Eva; Mulero, Juan; de Miguel, Eugenio; Fernández-Espartero, Cruz; Gobbo, Milena; Descalzo, Miguel A; Collantes-Estévez, Eduardo; Zarco, Pedro; Muñoz-Fernández, Santiago; Carmona, Loreto

2014-02-01

The objective of this study was to analyse the performance of the Assessment of SpondyloArthritis International Society (ASAS) criteria for the classification of SpA in early SpA clinics. We used a cross-sectional study of patients referred to early SpA units within the ESPERANZA programme (a Spanish nationwide health management programme designed to provide excellence in diagnosis and care for early SpA). Patients were eligible if they were <45 years of age and had any of the following: (i) a 2-year history of inflammatory back pain; (ii) back or joint pain with psoriasis, anterior uveitis, radiographic sacroiliitis, family history of SpA or positive HLA-B27; or (iii) asymmetric arthritis. We excluded patients for whom imaging (X-rays/MRI) or HLA-B27 results were not available. We analysed the performance (sensitivity and specificity) of different classification criteria sets, taking the rheumatologist's opinion as the gold standard. The analysis included 775 patients [mean age 33 (s.d. 7) years; 55% men; mean duration of symptoms 11 (s.d. 6) months]; SpA was diagnosed in 538 patients (69.5%). A total of 274 (67.9%) patients with chronic back pain met the ASAS axial criteria, 76 (56.3%) patients with arthritis but not chronic back pain fulfilled the ASAS criteria for peripheral SpA and 350 (65.1%) fulfilled all the ASAS criteria. The sensitivity and specificity of the ASAS criteria set were 65% and 93%, respectively (axial criteria: sensitivity 68%, specificity 95%). The sensitivity and specificity for the ESSG and Amor criteria were 58% and 90% and 59% and 86%, respectively. Despite performing better than the Amor or ESSG criteria, the ASAS criteria may be limited to detection of early forms, particularly in populations in which MRI is not extensively available or in populations with a low prevalence of HLA-B27.

Gender-Sensitive Approaches to Extension Programme Design

ERIC Educational Resources Information Center

Jafry, Tahseen; Sulaiman, V. Rasheed

2013-01-01

Purpose: Though women are engaged in farming and play a major role in almost every agricultural operation, they continue to receive very limited extension support. While several interventions have been made to address this "gender" bias in extension delivery, there continues to be a shortfall between the kind of support that is provided…

Protocol for the use of light upon extension real-time PCR for the determination of viral load in HBV infection.

PubMed

Li, Guimin; Li, Wangfeng; Liu, Lixia

2012-01-01

Real-time PCR has engendered wide acceptance for quantitation of hepatitis B virus (HBV) DNA in the blood due to its improved rapidity, sensitivity, reproducibility, and reduced contamination. Here we describe a cost-effective and highly sensitive HBV real-time quantitative assay based on the light upon extension real-time PCR platform and a simple and reliable HBV DNA preparation method using silica-coated magnetic beads.

Polymerase chain displacement reaction.

PubMed

Harris, Claire L; Sanchez-Vargas, Irma J; Olson, Ken E; Alphey, Luke; Fu, Guoliang

2013-02-01

Quantitative PCR assays are now the standard method for viral diagnostics. These assays must be specific, as well as sensitive, to detect the potentially low starting copy number of viral genomic material. We describe a new technique, polymerase chain displacement reaction (PCDR), which uses multiple nested primers in a rapid, capped, one-tube reaction that increases the sensitivity of normal quantitative PCR (qPCR) assays. Sensitivity was increased by approximately 10-fold in a proof-of-principle test on dengue virus sequence. In PCDR, when extension occurs from the outer primer, it displaces the extension strand produced from the inner primer by utilizing a polymerase that has strand displacement activity. This allows a greater than 2-fold increase of amplification product for each amplification cycle and therefore increased sensitivity and speed over conventional PCR. Increased sensitivity in PCDR would be useful in nucleic acid detection for viral diagnostics.

Cost-utility of transcatheter aortic valve implantation for inoperable patients with severe aortic stenosis treated by medical management: a UK cost-utility analysis based on patient-level data from the ADVANCE study

PubMed Central

Brecker, Stephen; Mealing, Stuart; Padhiar, Amie; Eaton, James; Sculpher, Mark; Busca, Rachele; Bosmans, Johan; Gerckens, Ulrich J; Wenaweser, Peter; Tamburino, Corrado; Bleiziffer, Sabine; Piazza, Nicolo; Moat, Neil; Linke, Axel

2014-01-01

Objective To use patient-level data from the ADVANCE study to evaluate the cost-effectiveness of transcatheter aortic valve implantation (TAVI) compared to medical management (MM) in patients with severe aortic stenosis from the perspective of the UK NHS. Methods A published decision-analytic model was adapted to include information on TAVI from the ADVANCE study. Patient-level data informed the choice as well as the form of mathematical functions that were used to model all-cause mortality, health-related quality of life and hospitalisations. TAVI-related resource use protocols were based on the ADVANCE study. MM was modelled on publicly available information from the PARTNER-B study. The outcome measures were incremental cost-effectiveness ratios (ICERs) estimated at a range of time horizons with benefits expressed as quality-adjusted life-years (QALY). Extensive sensitivity/subgroup analyses were undertaken to explore the impact of uncertainty in key clinical areas. Results Using a 5-year time horizon, the ICER for the comparison of all ADVANCE to all PARTNER-B patients was £13 943 per QALY gained. For the subset of ADVANCE patients classified as high risk (Logistic EuroSCORE >20%) the ICER was £17 718 per QALY gained). The ICER was below £30 000 per QALY gained in all sensitivity analyses relating to choice of MM data source and alternative modelling approaches for key parameters. When the time horizon was extended to 10 years, all ICERs generated in all analyses were below £20 000 per QALY gained. Conclusion TAVI is highly likely to be a cost-effective treatment for patients with severe aortic stenosis. PMID:25349700

Cost-utility of transcatheter aortic valve implantation for inoperable patients with severe aortic stenosis treated by medical management: a UK cost-utility analysis based on patient-level data from the ADVANCE study.

PubMed

Brecker, Stephen; Mealing, Stuart; Padhiar, Amie; Eaton, James; Sculpher, Mark; Busca, Rachele; Bosmans, Johan; Gerckens, Ulrich J; Wenaweser, Peter; Tamburino, Corrado; Bleiziffer, Sabine; Piazza, Nicolo; Moat, Neil; Linke, Axel

2014-01-01

To use patient-level data from the ADVANCE study to evaluate the cost-effectiveness of transcatheter aortic valve implantation (TAVI) compared to medical management (MM) in patients with severe aortic stenosis from the perspective of the UK NHS. A published decision-analytic model was adapted to include information on TAVI from the ADVANCE study. Patient-level data informed the choice as well as the form of mathematical functions that were used to model all-cause mortality, health-related quality of life and hospitalisations. TAVI-related resource use protocols were based on the ADVANCE study. MM was modelled on publicly available information from the PARTNER-B study. The outcome measures were incremental cost-effectiveness ratios (ICERs) estimated at a range of time horizons with benefits expressed as quality-adjusted life-years (QALY). Extensive sensitivity/subgroup analyses were undertaken to explore the impact of uncertainty in key clinical areas. Using a 5-year time horizon, the ICER for the comparison of all ADVANCE to all PARTNER-B patients was £13 943 per QALY gained. For the subset of ADVANCE patients classified as high risk (Logistic EuroSCORE >20%) the ICER was £17 718 per QALY gained). The ICER was below £30 000 per QALY gained in all sensitivity analyses relating to choice of MM data source and alternative modelling approaches for key parameters. When the time horizon was extended to 10 years, all ICERs generated in all analyses were below £20 000 per QALY gained. TAVI is highly likely to be a cost-effective treatment for patients with severe aortic stenosis.

Larval connectivity of pearl oyster through biophysical modelling; evidence of food limitation and broodstock effect

NASA Astrophysics Data System (ADS)

Thomas, Yoann; Dumas, Franck; Andréfouët, Serge

2016-12-01

The black-lip pearl oyster (Pinctada margaritifera) is cultured extensively to produce black pearls, especially in French Polynesia atoll lagoons. This aquaculture relies on spat collection, a process that experiences spatial and temporal variability and needs to be optimized by understanding which factors influence recruitment. Here, we investigate the sensitivity of P. margaritifera larval dispersal to both physical and biological factors in the lagoon of Ahe atoll. Coupling a validated 3D larval dispersal model, a bioenergetics larval growth model following the Dynamic Energy Budget (DEB) theory, and a population dynamics model, the variability of lagoon-scale connectivity patterns and recruitment potential is investigated. The relative contribution of reared and wild broodstock to the lagoon-scale recruitment potential is also investigated. Sensitivity analyses pointed out the major effect of the broodstock population structure as well as the sensitivity to larval mortality rate and inter-individual growth variability to larval supply and to the subsequent settlement potential. The application of the growth model clarifies how trophic conditions determine the larval supply and connectivity patterns. These results provide new cues to understand the dynamics of bottom-dwelling populations in atoll lagoons, their recruitment, and discuss how to take advantage of these findings and numerical models for pearl oyster management.

The Efficacy of Guanxinning Injection in Treating Angina Pectoris: Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Jia, Yongliang; Leung, Siu-wai; Lee, Ming-Yuen; Cui, Guozhen; Huang, Xiaohui; Pan, Fongha

2013-01-01

Objective. The randomized controlled trials (RCTs) on Guanxinning injection (GXN) in treating angina pectoris were published only in Chinese and have not been systematically reviewed. This study aims to provide a PRISMA-compliant and internationally accessible systematic review to evaluate the efficacy of GXN in treating angina pectoris. Methods. The RCTs were included according to prespecified eligibility criteria. Meta-analysis was performed to evaluate the symptomatic (SYMPTOMS) and electrocardiographic (ECG) improvements after treatment. Odds ratios (ORs) were used to measure effect sizes. Subgroup analysis, sensitivity analysis, and metaregression were conducted to evaluate the robustness of the results. Results. Sixty-five RCTs published between 2002 and 2012 with 6064 participants were included. Overall ORs comparing GXN with other drugs were 3.32 (95% CI: [2.72, 4.04]) in SYMPTOMS and 2.59 (95% CI: [2.14, 3.15]) in ECG. Subgroup analysis, sensitivity analysis, and metaregression found no statistically significant dependence of overall ORs upon specific study characteristics. Conclusion. This meta-analysis of eligible RCTs provides evidence that GXN is effective in treating angina pectoris. This evidence warrants further RCTs of higher quality, longer follow-up periods, larger sample sizes, and multicentres/multicountries for more extensive subgroup, sensitivity, and metaregression analyses. PMID:23634167

Nano-textured high sensitivity ion sensitive field effect transistors

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

Hajmirzaheydarali, M.; Sadeghipari, M.; Akbari, M.

2016-02-07

Nano-textured gate engineered ion sensitive field effect transistors (ISFETs), suitable for high sensitivity pH sensors, have been realized. Utilizing a mask-less deep reactive ion etching results in ultra-fine poly-Si features on the gate of ISFET devices where spacing of the order of 10 nm and less is achieved. Incorporation of these nano-sized features on the gate is responsible for high sensitivities up to 400 mV/pH in contrast to conventional planar structures. The fabrication process for this transistor is inexpensive, and it is fully compatible with standard complementary metal oxide semiconductor fabrication procedure. A theoretical modeling has also been presented to predict themore » extension of the diffuse layer into the electrolyte solution for highly featured structures and to correlate this extension with the high sensitivity of the device. The observed ultra-fine features by means of scanning electron microscopy and transmission electron microscopy tools corroborate the theoretical prediction.« less

Capillary electrophoresis hyphenated with UV-native-laser induced fluorescence detection (CE/UV-native-LIF).

PubMed

Couderc, François; Ong-Meang, Varravaddheay; Poinsot, Véréna

2017-01-01

Native laser-induced fluorescence using UV lasers associated to CE offers now a large related literature, for now 30 years. The main works have been performed using very expensive Ar-ion lasers emitting at 257 and 275 nm. They are not affordable for routine analyses, but have numerous applications such as protein, catecholamine, and indolamine analysis. Some other lasers such as HeCd 325 nm have been used but only for few applications. Diode lasers, emitting at 266 nm, cheaper, are extensively used for the same topics, even if the obtained sensitivity is lower than the one observed using the costly UV-Ar-ion lasers. This review presents various CE or microchips applications and different UV lasers used for the excitation of native fluorescence. We showed that CE/Native UV laser induced fluorescence detection is very sensitive for detection as well as small aromatic biomolecules than proteins containing Trp and Tyr amino acids. Moreover, it is a simple way to analyze biomolecules without derivatization. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reception and learning of electric fields in bees

PubMed Central

Greggers, Uwe; Koch, Gesche; Schmidt, Viola; Dürr, Aron; Floriou-Servou, Amalia; Piepenbrock, David; Göpfert, Martin C.; Menzel, Randolf

2013-01-01

Honeybees, like other insects, accumulate electric charge in flight, and when their body parts are moved or rubbed together. We report that bees emit constant and modulated electric fields when flying, landing, walking and during the waggle dance. The electric fields emitted by dancing bees consist of low- and high-frequency components. Both components induce passive antennal movements in stationary bees according to Coulomb's law. Bees learn both the constant and the modulated electric field components in the context of appetitive proboscis extension response conditioning. Using this paradigm, we identify mechanoreceptors in both joints of the antennae as sensors. Other mechanoreceptors on the bee body are potentially involved but are less sensitive. Using laser vibrometry, we show that the electrically charged flagellum is moved by constant and modulated electric fields and more strongly so if sound and electric fields interact. Recordings from axons of the Johnston organ document its sensitivity to electric field stimuli. Our analyses identify electric fields emanating from the surface charge of bees as stimuli for mechanoreceptors, and as biologically relevant stimuli, which may play a role in social communication. PMID:23536603

Reception and learning of electric fields in bees.

PubMed

Greggers, Uwe; Koch, Gesche; Schmidt, Viola; Dürr, Aron; Floriou-Servou, Amalia; Piepenbrock, David; Göpfert, Martin C; Menzel, Randolf

2013-05-22

Honeybees, like other insects, accumulate electric charge in flight, and when their body parts are moved or rubbed together. We report that bees emit constant and modulated electric fields when flying, landing, walking and during the waggle dance. The electric fields emitted by dancing bees consist of low- and high-frequency components. Both components induce passive antennal movements in stationary bees according to Coulomb's law. Bees learn both the constant and the modulated electric field components in the context of appetitive proboscis extension response conditioning. Using this paradigm, we identify mechanoreceptors in both joints of the antennae as sensors. Other mechanoreceptors on the bee body are potentially involved but are less sensitive. Using laser vibrometry, we show that the electrically charged flagellum is moved by constant and modulated electric fields and more strongly so if sound and electric fields interact. Recordings from axons of the Johnston organ document its sensitivity to electric field stimuli. Our analyses identify electric fields emanating from the surface charge of bees as stimuli for mechanoreceptors, and as biologically relevant stimuli, which may play a role in social communication.

How Efficacious is Danshen (Salvia miltiorrhiza) Dripping Pill in Treating Angina Pectoris? Evidence Assessment for Meta-Analysis of Randomized Controlled Trials.

PubMed

Jia, Yongliang; Leung, Siu-Wai

2017-09-01

More than 230 randomized controlled trials (RCTs) of danshen dripping pill (DSP) and isosorbide dinitrate (ISDN) in treating angina pectoris after the first preferred reporting items for systematic reviews and meta-analyses-compliant comprehensive meta-analysis were published in 2010. Other meta-analyses had flaws in study selection, statistical meta-analysis, and evidence assessment. This study completed the meta-analysis with an extensive assessment of the evidence. RCTs published from 1994 to 2016 on DSP and ISDN in treating angina pectoris for at least 4 weeks were included. The risk of bias (RoB) of included RCTs was assessed with the Cochrane's tool for assessing RoB. Meta-analyses based on a random-effects model were performed on two outcome measures: symptomatic (SYM) and electrocardiography (ECG) improvements. Subgroup analysis, sensitivity analysis, metaregression, and publication bias analysis were also conducted. The evidence strength was evaluated with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) method. Among the included 109 RCTs with 11,973 participants, 49 RCTs and 5042 participants were new (after 2010). The RoB of included RCTs was high in randomization and blinding. Overall effect sizes in odds ratios for DSP over ISDN were 2.94 (95% confidence interval [CI]: 2.53-3.41) on SYM (n = 108) and 2.37 (95% CI: 2.08-2.69) by ECG (n = 81) with significant heterogeneities (I 2  = 41%, p < 0.0001 on SYM and I 2  = 44%, p < 0.0001 on ECG). Subgroup, sensitivity, and metaregression analyses showed consistent results without publication bias. However, the evidence strength was low in GRADE. The efficacy of DSP was still better than ISDN in treating angina pectoris, but the confidence decreased due to high RoB and heterogeneities.

A novel on-line spatial-temporal k-anonymity method for location privacy protection from sequence rules-based inference attacks.

PubMed

Zhang, Haitao; Wu, Chenxue; Chen, Zewei; Liu, Zhao; Zhu, Yunhong

2017-01-01

Analyzing large-scale spatial-temporal k-anonymity datasets recorded in location-based service (LBS) application servers can benefit some LBS applications. However, such analyses can allow adversaries to make inference attacks that cannot be handled by spatial-temporal k-anonymity methods or other methods for protecting sensitive knowledge. In response to this challenge, first we defined a destination location prediction attack model based on privacy-sensitive sequence rules mined from large scale anonymity datasets. Then we proposed a novel on-line spatial-temporal k-anonymity method that can resist such inference attacks. Our anti-attack technique generates new anonymity datasets with awareness of privacy-sensitive sequence rules. The new datasets extend the original sequence database of anonymity datasets to hide the privacy-sensitive rules progressively. The process includes two phases: off-line analysis and on-line application. In the off-line phase, sequence rules are mined from an original sequence database of anonymity datasets, and privacy-sensitive sequence rules are developed by correlating privacy-sensitive spatial regions with spatial grid cells among the sequence rules. In the on-line phase, new anonymity datasets are generated upon LBS requests by adopting specific generalization and avoidance principles to hide the privacy-sensitive sequence rules progressively from the extended sequence anonymity datasets database. We conducted extensive experiments to test the performance of the proposed method, and to explore the influence of the parameter K value. The results demonstrated that our proposed approach is faster and more effective for hiding privacy-sensitive sequence rules in terms of hiding sensitive rules ratios to eliminate inference attacks. Our method also had fewer side effects in terms of generating new sensitive rules ratios than the traditional spatial-temporal k-anonymity method, and had basically the same side effects in terms of non-sensitive rules variation ratios with the traditional spatial-temporal k-anonymity method. Furthermore, we also found the performance variation tendency from the parameter K value, which can help achieve the goal of hiding the maximum number of original sensitive rules while generating a minimum of new sensitive rules and affecting a minimum number of non-sensitive rules.

A novel on-line spatial-temporal k-anonymity method for location privacy protection from sequence rules-based inference attacks

PubMed Central

Wu, Chenxue; Liu, Zhao; Zhu, Yunhong

2017-01-01

Analyzing large-scale spatial-temporal k-anonymity datasets recorded in location-based service (LBS) application servers can benefit some LBS applications. However, such analyses can allow adversaries to make inference attacks that cannot be handled by spatial-temporal k-anonymity methods or other methods for protecting sensitive knowledge. In response to this challenge, first we defined a destination location prediction attack model based on privacy-sensitive sequence rules mined from large scale anonymity datasets. Then we proposed a novel on-line spatial-temporal k-anonymity method that can resist such inference attacks. Our anti-attack technique generates new anonymity datasets with awareness of privacy-sensitive sequence rules. The new datasets extend the original sequence database of anonymity datasets to hide the privacy-sensitive rules progressively. The process includes two phases: off-line analysis and on-line application. In the off-line phase, sequence rules are mined from an original sequence database of anonymity datasets, and privacy-sensitive sequence rules are developed by correlating privacy-sensitive spatial regions with spatial grid cells among the sequence rules. In the on-line phase, new anonymity datasets are generated upon LBS requests by adopting specific generalization and avoidance principles to hide the privacy-sensitive sequence rules progressively from the extended sequence anonymity datasets database. We conducted extensive experiments to test the performance of the proposed method, and to explore the influence of the parameter K value. The results demonstrated that our proposed approach is faster and more effective for hiding privacy-sensitive sequence rules in terms of hiding sensitive rules ratios to eliminate inference attacks. Our method also had fewer side effects in terms of generating new sensitive rules ratios than the traditional spatial-temporal k-anonymity method, and had basically the same side effects in terms of non-sensitive rules variation ratios with the traditional spatial-temporal k-anonymity method. Furthermore, we also found the performance variation tendency from the parameter K value, which can help achieve the goal of hiding the maximum number of original sensitive rules while generating a minimum of new sensitive rules and affecting a minimum number of non-sensitive rules. PMID:28767687

Strategy for Realizing High-Precision VUV Spectro-Polarimeter

NASA Astrophysics Data System (ADS)

Ishikawa, R.; Narukage, N.; Kubo, M.; Ishikawa, S.; Kano, R.; Tsuneta, S.

2014-12-01

Spectro-polarimetric observations in the vacuum ultraviolet (VUV) range are currently the only means to measure magnetic fields in the upper chromosphere and transition region of the solar atmosphere. The Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP) aims to measure linear polarization at the hydrogen Lyman- α line (121.6 nm). This measurement requires a polarization sensitivity better than 0.1 %, which is unprecedented in the VUV range. We here present a strategy with which to realize such high-precision spectro-polarimetry. This involves the optimization of instrument design, testing of optical components, extensive analyses of polarization errors, polarization calibration of the instrument, and calibration with onboard data. We expect that this strategy will aid the development of other advanced high-precision polarimeters in the UV as well as in other wavelength ranges.

75 FR 63499 - Extension of Agency Information Collection Activity Under OMB Review: Sensitive Security...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-15

... Information Collection Activity Under OMB Review: Sensitive Security Information Threat Assessments AGENCY... Transportation Security Administration (TSA) has forwarded the Information Collection Request (ICR), Office of... of a party seeking access to sensitive security information (SSI) in a civil proceeding in Federal...

Quantitative analyses of cell behaviors underlying notochord formation and extension in mouse embryos.

PubMed

Sausedo, R A; Schoenwolf, G C

1994-05-01

Formation and extension of the notochord (i.e., notogenesis) is one of the earliest and most obvious events of axis development in vertebrate embryos. In birds and mammals, prospective notochord cells arise from Hensen's node and come to lie beneath the midline of the neural plate. Throughout the period of neurulation, the notochord retains its close spatial relationship with the developing neural tube and undergoes rapid extension in concert with the overlying neuroepithelium. In the present study, we examined notochord development quantitatively in mouse embryos. C57BL/6 mouse embryos were collected at 8, 8.5, 9, 9.5, and 10 days of gestation. They were then embedded in paraffin and sectioned transversely. Serial sections from 21 embryos were stained with Schiff's reagent according to the Feulgen-Rossenbeck procedure and used for quantitative analyses of notochord extension. Quantitative analyses revealed that extension of the notochord involves cell division within the notochord proper and cell rearrangement within the notochordal plate (the immediate precursor of the notochord). In addition, extension of the notochord involves cell accretion, that is, the addition of cells to the notochord's caudal end, a process that involves considerable cell rearrangement at the notochordal plate-node interface. Extension of the mouse notochord occurs similarly to that described previously for birds (Sausedo and Schoenwolf, 1993 Anat. Rec. 237:58-70). That is, in both birds (i.e., quail and chick) and mouse embryos, notochord extension involves cell division, cell rearrangement, and cell accretion. Thus higher vertebrates utilize similar morphogenetic movements to effect notogenesis.

Design and Construction of a Thermal Contact Resistance and Thermal Conductivity Measurement System

DTIC Science & Technology

2015-09-01

plate interface resistance control. Numerical heat transfer and uncertainty analyses with applied engineering judgement were extensively used to come... heat transfer issues facing the Department of Defense. 14. SUBJECT TERMS Thermal contact resistance, thermal conductivity, measurement system 15... heat transfer and uncertainty analyses with applied engineering judgement were extensively used to come up with an optimized design and construction

Impact of variation in the BDNF gene on social stress sensitivity and the buffering impact of positive emotions: replication and extension of a gene-environment interaction.

PubMed

van Winkel, Mark; Peeters, Frenk; van Winkel, Ruud; Kenis, Gunter; Collip, Dina; Geschwind, Nicole; Jacobs, Nele; Derom, Catherine; Thiery, Evert; van Os, Jim; Myin-Germeys, Inez; Wichers, Marieke

2014-06-01

A previous study reported that social stress sensitivity is moderated by the brain-derived-neurotrophic-factor(Val66Met) (BDNF rs6265) genotype. Additionally, positive emotions partially neutralize this moderating effect. The current study aimed to: (i) replicate in a new independent sample of subjects with residual depressive symptoms the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity, (ii) replicate the neutralizing impact of positive emotions, (iii) extend these analyses to other variations in the BDNF gene in the new independent sample and the original sample of non-depressed individuals. Previous findings were replicated in an experience sampling method (ESM) study. Negative Affect (NA) responses to social stress were stronger in "Val/Met" carriers of BDNF(Val66Met) compared to "Val/Val" carriers. Positive emotions neutralized the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity in a dose-response fashion. Finally, two of four additional BDNF SNPs (rs11030101, rs2049046) showed similar moderating effects on social stress-sensitivity across both samples. The neutralizing effect of positive emotions on the moderating effects of these two additional SNPs was found in one sample. In conclusion, ESM has important advantages in gene-environment (GxE) research and may attribute to more consistent findings in future GxE research. This study shows how the impact of BDNF genetic variation on depressive symptoms may be explained by its impact on subtle daily life responses to social stress. Further, it shows that the generation of positive affect (PA) can buffer social stress sensitivity and partially undo the genetic susceptibility. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

The RITA spectrometer at Risø - design considerations and recent results

NASA Astrophysics Data System (ADS)

Clausen, K. N.; McMorrow, D. F.; Lefmann, K.; Aeppli, G.; Mason, T. E.; Schröder, A.; Issikii, M.; Nohara, M.; Takagi, H.

In the new cold triple axis spectrometer RITA at Risø we have improved the front end by extensive use of state of the art optical elements and better shielding material. The analyser system is situated in one large open tank and consists of seven individually orientable PG(002) crystal analyser blades, and a 170 mm by 120 mm 2 areas sensitive micro-strip detector. In comparison to the old TAS6 spectrometer we have obtained a factor 2-5 gain in intensity on the sample, a substantially lower background, much more flexibility for optimising the instrument and the possibility to go beyond simple point-by-point inspection. The excellent performance of RITA in the standard TAS mode is exemplified by a study of the dynamics of ≈ 15 nm hematite (α-Fe 2O 3) nano-particles, and utilisation of horizontal and vertical focusing modes to study two dimensional systems is illustrated by a study of the spin fluctuations in the high Tc superconductor La 1.83Sr 0.17CuO 4.

The Validity of Conscientiousness Is Overestimated in the Prediction of Job Performance.

PubMed

Kepes, Sven; McDaniel, Michael A

2015-01-01

Sensitivity analyses refer to investigations of the degree to which the results of a meta-analysis remain stable when conditions of the data or the analysis change. To the extent that results remain stable, one can refer to them as robust. Sensitivity analyses are rarely conducted in the organizational science literature. Despite conscientiousness being a valued predictor in employment selection, sensitivity analyses have not been conducted with respect to meta-analytic estimates of the correlation (i.e., validity) between conscientiousness and job performance. To address this deficiency, we reanalyzed the largest collection of conscientiousness validity data in the personnel selection literature and conducted a variety of sensitivity analyses. Publication bias analyses demonstrated that the validity of conscientiousness is moderately overestimated (by around 30%; a correlation difference of about .06). The misestimation of the validity appears to be due primarily to suppression of small effects sizes in the journal literature. These inflated validity estimates result in an overestimate of the dollar utility of personnel selection by millions of dollars and should be of considerable concern for organizations. The fields of management and applied psychology seldom conduct sensitivity analyses. Through the use of sensitivity analyses, this paper documents that the existing literature overestimates the validity of conscientiousness in the prediction of job performance. Our data show that effect sizes from journal articles are largely responsible for this overestimation.

The Validity of Conscientiousness Is Overestimated in the Prediction of Job Performance

PubMed Central

2015-01-01

Introduction Sensitivity analyses refer to investigations of the degree to which the results of a meta-analysis remain stable when conditions of the data or the analysis change. To the extent that results remain stable, one can refer to them as robust. Sensitivity analyses are rarely conducted in the organizational science literature. Despite conscientiousness being a valued predictor in employment selection, sensitivity analyses have not been conducted with respect to meta-analytic estimates of the correlation (i.e., validity) between conscientiousness and job performance. Methods To address this deficiency, we reanalyzed the largest collection of conscientiousness validity data in the personnel selection literature and conducted a variety of sensitivity analyses. Results Publication bias analyses demonstrated that the validity of conscientiousness is moderately overestimated (by around 30%; a correlation difference of about .06). The misestimation of the validity appears to be due primarily to suppression of small effects sizes in the journal literature. These inflated validity estimates result in an overestimate of the dollar utility of personnel selection by millions of dollars and should be of considerable concern for organizations. Conclusion The fields of management and applied psychology seldom conduct sensitivity analyses. Through the use of sensitivity analyses, this paper documents that the existing literature overestimates the validity of conscientiousness in the prediction of job performance. Our data show that effect sizes from journal articles are largely responsible for this overestimation. PMID:26517553

Linear regression metamodeling as a tool to summarize and present simulation model results.

PubMed

Jalal, Hawre; Dowd, Bryan; Sainfort, François; Kuntz, Karen M

2013-10-01

Modelers lack a tool to systematically and clearly present complex model results, including those from sensitivity analyses. The objective was to propose linear regression metamodeling as a tool to increase transparency of decision analytic models and better communicate their results. We used a simplified cancer cure model to demonstrate our approach. The model computed the lifetime cost and benefit of 3 treatment options for cancer patients. We simulated 10,000 cohorts in a probabilistic sensitivity analysis (PSA) and regressed the model outcomes on the standardized input parameter values in a set of regression analyses. We used the regression coefficients to describe measures of sensitivity analyses, including threshold and parameter sensitivity analyses. We also compared the results of the PSA to deterministic full-factorial and one-factor-at-a-time designs. The regression intercept represented the estimated base-case outcome, and the other coefficients described the relative parameter uncertainty in the model. We defined simple relationships that compute the average and incremental net benefit of each intervention. Metamodeling produced outputs similar to traditional deterministic 1-way or 2-way sensitivity analyses but was more reliable since it used all parameter values. Linear regression metamodeling is a simple, yet powerful, tool that can assist modelers in communicating model characteristics and sensitivity analyses.

Pain after root canal treatment with different instruments: A systematic review and meta-analysis.

PubMed

Sun, Chengjun; Sun, Jicheng; Tan, Minmin; Hu, Bo; Gao, Xiang; Song, Jinlin

2018-03-07

The aims of this systematic review were to compare the incidence and intensity of postoperative pain after single-visit root canal treatment using manual, rotary and reciprocating instruments. An extensive literature search in PubMed, EMBASE, Cochrane Library, and Web of Science was performed to identify investigations that evaluated the effects of different instruments on post-endodontic pain. Meta-analyses and additional analyses, including subgroup and sensitivity analyses, were conducted. We included seventeen trials in this study. Pooled results showed that patients treated with rotary instruments experienced a significantly lower incidence of postoperative pain (RR, 0.32, P = 0.0005) and reduced pain intensity than did patients treated with manual instruments. In addition, patients treated with multiple rotary-file systems experienced a significantly lower incidence of postoperative pain than did those treated with reciprocating systems (RR, 0.73; P < 0.0001). The use of rotary instruments contributed to a lower incidence and intensity of postoperative pain than did the use of hand files in patients who received single-visit root canal treatment. In addition, the use of multiple rotary-file systems contributed to a lower incidence of postoperative pain than did the use of reciprocating systems. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Comparative statistical component analysis of transgenic, cyanophycin-producing potatoes in greenhouse and field trials.

PubMed

Schmidt, Kerstin; Schmidtke, Jörg; Mast, Yvonne; Waldvogel, Eva; Wohlleben, Wolfgang; Klemke, Friederike; Lockau, Wolfgang; Hausmann, Tina; Hühns, Maja; Broer, Inge

2017-08-01

Potatoes are a promising system for industrial production of the biopolymer cyanophycin as a second compound in addition to starch. To assess the efficiency in the field, we analysed the stability of the system, specifically its sensitivity to environmental factors. Field and greenhouse trials with transgenic potatoes (two independent events) were carried out for three years. The influence of environmental factors was measured and target compounds in the transgenic plants (cyanophycin, amino acids) were analysed for differences to control plants. Furthermore, non-target parameters (starch content, number, weight and size of tubers) were analysed for equivalence with control plants. The huge amount of data received was handled using modern statistical approaches to model the correlation between influencing environmental factors (year of cultivation, nitrogen fertilization, origin of plants, greenhouse or field cultivation) and key components (starch, amino acids, cyanophycin) and agronomic characteristics. General linear models were used for modelling, and standard effect sizes were applied to compare conventional and genetically modified plants. Altogether, the field trials prove that significant cyanophycin production is possible without reduction of starch content. Non-target compound composition seems to be equivalent under varying environmental conditions. Additionally, a quick test to measure cyanophycin content gives similar results compared to the extensive enzymatic test. This work facilitates the commercial cultivation of cyanophycin potatoes.

Tumor control by hypoxia-specific chemotargeting of iron-oxide nanoparticle - Berberine complexes in a mouse model.

PubMed

Sreeja, S; Krishnan Nair, C K

2018-02-15

To evaluate the therapeutic efficacy of hypoxic cell-sensitizer Sanazole (SAN) -directed targeting of cytotoxic drug Berberine (BBN) and Iron-oxide nanoparticle (NP) complexes, to solid tumor in Swiss albino mice. NP-BBN-SAN complexes were characterized by FTIR, XRD, TEM and Nano-size analyzer. This complex was orally administered to mice-bearing solid tumor in hind limb. Tumor regression was analysed by measuring tumor volume. Cellular DNA damages were assessed by comet assay. Transcriptional expression of genes related to tumor hypoxia and apoptosis was evaluated by quantitative real-time PCR and morphological changes in tissues were analysed by histopathology. Also levels of antioxidants and tumor markers in tissues and serum biochemical parameters were analysed. Administration of NP-BBN-SAN complexes reduced tumor volume and studies were focussed on the underlying mechanisms. Extensive damage to cellular-DNA; down-regulated transcription of hif-1α, vegf, akt and bcl2; and up-regulated expression of bax and caspases, were observed in tumor. Results on tumor markers, antioxidant-status and serum parameters corroborated the molecular findings. Histopathology of tumor, liver and kidney revealed the therapeutic specificity of NP-BBN-SAN. Thus SAN and NP can be used for specific targeting of drugs, to hypoxic solid tumor, to improve therapeutic efficacy. Copyright © 2017. Published by Elsevier Inc.

Development of automotive battery systems capable of surviving modern underhood environments

NASA Astrophysics Data System (ADS)

Pierson, John R.; Johnson, Richard T.

The starting, lighting, and ignition (SLI) battery in today's automobile typically finds itself in an engine compartment that is jammed with mechanical, electrical, and electronic devices. The spacing of these devices precludes air movement and, thus, heat transfer out of the compartment. Furthermore, many of the devices, in addition to the internal combustion engine, actually generate heat. The resulting underhood environment is extremely hostile to thermally-sensitive components, especially the battery. All indications point to a continuation of this trend towards higher engine-compartment temperatures as future vehicles evolve. The impact of ambient temperature on battery life is clearly demonstrated in the failure-mode analysis conducted by the Battery Council International in 1990. This study, when combined with additional failure-mode analyses, vehicle systems simulation, and elevated temperature life testing, provides insight into the potential for extension of life of batteries. Controlled fleet and field tests are used to document and quantify improvements in product design. Three approaches to battery life extension under adverse thermal conditions are assessed, namely: (i) battery design; (ii) thermal management, and (iii) alternative battery locations. The advantages and disadvantages of these approaches (both individually and in combination) for original equipment and aftermarket applications are explored.

Chemical quality of ground water in the eastern Sacramento Valley, California

USGS Publications Warehouse

Fogelman, Ronald P.

1979-01-01

The study area is about 1,300 square miles in the eastern Sacramento Valley, Calif., extending from the latitude of Roseville on the south to thelatitude of Chico on the north. Considering the increased agricultural development of the area, this report documents the chemical character of the ground water prior to water-level declines that could result from extensive pumping for irrigation or to changes caused by extensive use of imported surface water. Chemical analyses of samples from 222 wells show that most of the area is underlain by ground water of a quality suitable for most agricultural and domestic purposes. Ninety-five percent of the water sampled has dissolved-solids concentrations of less than 700 milligrams per liter. The general water type for the area is a calcium and magnesium bicarbonate water and there are negligible amounts of toxic trace elements. The potential for water-quality problems exists in the area south of Yuba City along the west bank of the Feather River. There, concentrations of chloride, sulfate, and dissolved solids are higher than in other parts of the area, and they could limit future agricultural activities if chloride- and sulfate-sensitive crops are grown. (Woodard-USGS)

The Universal Thermal Climate Index UTCI compared to ergonomics standards for assessing the thermal environment.

PubMed

Bröde, Peter; Błazejczyk, Krzysztof; Fiala, Dusan; Havenith, George; Holmér, Ingvar; Jendritzky, Gerd; Kuklane, Kalev; Kampmann, Bernhard

2013-01-01

The growing need for valid assessment procedures of the outdoor thermal environment in the fields of public weather services, public health systems, urban planning, tourism & recreation and climate impact research raised the idea to develop the Universal Thermal Climate Index UTCI based on the most recent scientific progress both in thermo-physiology and in heat exchange theory. Following extensive validation of accessible models of human thermoregulation, the advanced multi-node 'Fiala' model was selected to form the basis of UTCI. This model was coupled with an adaptive clothing model which considers clothing habits by the general urban population and behavioral changes in clothing insulation related to actual environmental temperature. UTCI was developed conceptually as an equivalent temperature. Thus, for any combination of air temperature, wind, radiation, and humidity, UTCI is defined as the air temperature in the reference condition which would elicit the same dynamic response of the physiological model. This review analyses the sensitivity of UTCI to humidity and radiation in the heat and to wind in the cold and compares the results with observational studies and internationally standardized assessment procedures. The capabilities, restrictions and potential future extensions of UTCI are discussed.

The impact of slice-reduced computed tomography on histogram-based densitometry assessment of lung fibrosis in patients with systemic sclerosis

PubMed Central

Maurer, Britta; Suliman, Yossra A.; Morsbach, Fabian; Distler, Oliver; Frauenfelder, Thomas

2018-01-01

Background To evaluate usability of slice-reduced sequential computed tomography (CT) compared to standard high-resolution CT (HRCT) in patients with systemic sclerosis (SSc) for qualitative and quantitative assessment of interstitial lung disease (ILD) with respect to (I) detection of lung parenchymal abnormalities, (II) qualitative and semiquantitative visual assessment, (III) quantification of ILD by histograms and (IV) accuracy for the 20%-cut off discrimination. Methods From standard chest HRCT of 60 SSc patients sequential 9-slice-computed tomography (reduced HRCT) was retrospectively reconstructed. ILD was assessed by visual scoring and quantitative histogram parameters. Results from standard and reduced HRCT were compared using non-parametric tests and analysed by univariate linear regression analyses. Results With respect to the detection of parenchymal abnormalities, only the detection of intrapulmonary bronchiectasis was significantly lower in reduced HRCT compared to standard HRCT (P=0.039). No differences were found comparing visual scores for fibrosis severity and extension from standard and reduced HRCT (P=0.051–0.073). All scores correlated significantly (P<0.001) to histogram parameters derived from both, standard and reduced HRCT. Significant higher values of kurtosis and skewness for reduced HRCT were found (both P<0.001). In contrast to standard HRCT histogram parameters from reduced HRCT showed significant discrimination at cut-off 20% fibrosis (sensitivity 88% kurtosis and skewness; specificity 81% kurtosis and 86% skewness; cut-off kurtosis ≤26, cut-off skewness ≤4; both P<0.001). Conclusions Reduced HRCT is a robust method to assess lung fibrosis in SSc with minimal radiation dose with no difference in scoring assessment of lung fibrosis severity and extension in comparison to standard HRCT. In contrast to standard HRCT histogram parameters derived from the approach of reduced HRCT could discriminate at a threshold of 20% lung fibrosis with high sensitivity and specificity. Hence it might be used to detect early disease progression of lung fibrosis in context of monitoring and treatment of SSc patients. PMID:29850118

The Acetylene-Ethylene Assay for N2 Fixation: Laboratory and Field Evaluation 1

PubMed Central

Hardy, R. W. F.; Holsten, R. D.; Jackson, E. K.; Burns, R. C.

1968-01-01

The methodology, characteristics and application of the sensitive C2H2-C2H4 assay for N2 fixation by nitrogenase preparations and bacterial cultures in the laboratory and by legumes and free-living bacteria in situ is presented in this comprehensive report. This assay is based on the N2ase-catalyzed reduction of C2H2 to C2H4, gas chromatographic isolation of C2H2 and C2H4, and quantitative measurement with a H2-flame analyzer. As little as 1 μμmole C2H4 can be detected, providing a sensitivity 103-fold greater than is possible with 15N analysis. A simple, rapid and effective procedure utilizing syringe-type assay chambers is described for the analysis of C2H2-reducing activity in the field. Applications to field samples included an evaluation of N2 fixation by commercially grown soybeans based on over 2000 analyses made during the course of the growing season. Assay values reflected the degree of nodulation of soybean plants and indicated a calculated seasonal N2 fixation rate of 30 to 33 kg N2 fixed per acre, in good agreement with literature estimates based on Kjeldahl analyses. The assay was successfully applied to measurements of N2 fixation by other symbionts and by free living soil microorganisms, and was also used to assess the effects of light and temperature on the N2 fixing activity of soybeans. The validity of measuring N2 fixation in terms of C2H2 reduction was established through extensive comparisons of these activities using defined systems, including purified N2ase preparations and pure cultures of N2-fixing bacteria. With this assay it now becomes possible and practicable to conduct comprehensive surveys of N2 fixation, to make detailed comparisons among different N2-fixing symbionts, and to rapidly evaluate the effects of cultural practices and environmental factors on N2 fixation. The knowledge obtained through extensive application of this assay should provide the basis for efforts leading to the maximum agricultural exploitation of the N2 fixation reaction. PMID:16656902

Seasonal Influenza Vaccination for Children in Thailand: A Cost-Effectiveness Analysis

PubMed Central

Meeyai, Aronrag; Praditsitthikorn, Naiyana; Kotirum, Surachai; Kulpeng, Wantanee; Putthasri, Weerasak; Cooper, Ben S.; Teerawattananon, Yot

2015-01-01

Background Seasonal influenza is a major cause of mortality worldwide. Routine immunization of children has the potential to reduce this mortality through both direct and indirect protection, but has not been adopted by any low- or middle-income countries. We developed a framework to evaluate the cost-effectiveness of influenza vaccination policies in developing countries and used it to consider annual vaccination of school- and preschool-aged children with either trivalent inactivated influenza vaccine (TIV) or trivalent live-attenuated influenza vaccine (LAIV) in Thailand. We also compared these approaches with a policy of expanding TIV coverage in the elderly. Methods and Findings We developed an age-structured model to evaluate the cost-effectiveness of eight vaccination policies parameterized using country-level data from Thailand. For policies using LAIV, we considered five different age groups of children to vaccinate. We adopted a Bayesian evidence-synthesis framework, expressing uncertainty in parameters through probability distributions derived by fitting the model to prospectively collected laboratory-confirmed influenza data from 2005-2009, by meta-analysis of clinical trial data, and by using prior probability distributions derived from literature review and elicitation of expert opinion. We performed sensitivity analyses using alternative assumptions about prior immunity, contact patterns between age groups, the proportion of infections that are symptomatic, cost per unit vaccine, and vaccine effectiveness. Vaccination of children with LAIV was found to be highly cost-effective, with incremental cost-effectiveness ratios between about 2,000 and 5,000 international dollars per disability-adjusted life year averted, and was consistently preferred to TIV-based policies. These findings were robust to extensive sensitivity analyses. The optimal age group to vaccinate with LAIV, however, was sensitive both to the willingness to pay for health benefits and to assumptions about contact patterns between age groups. Conclusions Vaccinating school-aged children with LAIV is likely to be cost-effective in Thailand in the short term, though the long-term consequences of such a policy cannot be reliably predicted given current knowledge of influenza epidemiology and immunology. Our work provides a coherent framework that can be used for similar analyses in other low- and middle-income countries. PMID:26011712

Seasonal influenza vaccination for children in Thailand: a cost-effectiveness analysis.

PubMed

Meeyai, Aronrag; Praditsitthikorn, Naiyana; Kotirum, Surachai; Kulpeng, Wantanee; Putthasri, Weerasak; Cooper, Ben S; Teerawattananon, Yot

2015-05-01

Seasonal influenza is a major cause of mortality worldwide. Routine immunization of children has the potential to reduce this mortality through both direct and indirect protection, but has not been adopted by any low- or middle-income countries. We developed a framework to evaluate the cost-effectiveness of influenza vaccination policies in developing countries and used it to consider annual vaccination of school- and preschool-aged children with either trivalent inactivated influenza vaccine (TIV) or trivalent live-attenuated influenza vaccine (LAIV) in Thailand. We also compared these approaches with a policy of expanding TIV coverage in the elderly. We developed an age-structured model to evaluate the cost-effectiveness of eight vaccination policies parameterized using country-level data from Thailand. For policies using LAIV, we considered five different age groups of children to vaccinate. We adopted a Bayesian evidence-synthesis framework, expressing uncertainty in parameters through probability distributions derived by fitting the model to prospectively collected laboratory-confirmed influenza data from 2005-2009, by meta-analysis of clinical trial data, and by using prior probability distributions derived from literature review and elicitation of expert opinion. We performed sensitivity analyses using alternative assumptions about prior immunity, contact patterns between age groups, the proportion of infections that are symptomatic, cost per unit vaccine, and vaccine effectiveness. Vaccination of children with LAIV was found to be highly cost-effective, with incremental cost-effectiveness ratios between about 2,000 and 5,000 international dollars per disability-adjusted life year averted, and was consistently preferred to TIV-based policies. These findings were robust to extensive sensitivity analyses. The optimal age group to vaccinate with LAIV, however, was sensitive both to the willingness to pay for health benefits and to assumptions about contact patterns between age groups. Vaccinating school-aged children with LAIV is likely to be cost-effective in Thailand in the short term, though the long-term consequences of such a policy cannot be reliably predicted given current knowledge of influenza epidemiology and immunology. Our work provides a coherent framework that can be used for similar analyses in other low- and middle-income countries.

Infant Auditory Sensitivity to Pure Tones and Frequency-Modulated Tones

ERIC Educational Resources Information Center

Leibold, Lori J.; Werner, Lynne A.

2007-01-01

It has been suggested that infants respond preferentially to infant-directed speech because their auditory sensitivity to sounds with extensive frequency modulation (FM) is better than their sensitivity to less modulated sounds. In this experiment, auditory thresholds for FM tones and for unmodulated, or pure, tones in a background of noise were…

Tapered GRIN fiber microsensor.

PubMed

Beltrán-Mejía, Felipe; Biazoli, Claudecir R; Cordeiro, Cristiano M B

2014-12-15

The sensitivity of an optical fiber microsensor based on inter-modal interference can be considerably improved by tapering a short extension of the multimode fiber. In the case of Graded Index fibers with a parabolic refractive index profile, a meridional ray exhibits a sinusoidal path. When these fibers are tapered, the period of the propagated beam decrease down-taper and increase up-taper. We take advantage of this modulation -along with the enhanced overlap between the evanescent field and the external medium- to substantially increase the sensitivity of these devices by tuning the sensor's maximum sensitivity wavelength. Moreover, the extension of this device is reduced by one order of magnitude, making it more propitious for reduced space applications. Numerical and experimental results demonstrate the success and feasibility of this approach.

Increased serum baseline tryptase levels and extensive skin involvement are predictors for the severity of mast cell activation episodes in children with mastocytosis

PubMed Central

Alvarez-Twose, I.; Vañó-Galván, S.; Sánchez-Muñoz, L.; Morgado, J. M.; Matito, A.; Torrelo, A.; Jaén, P.; Schwartz, L. B.; Orfao, A.; Escribano, L

2012-01-01

Background Despite the good prognosis of pediatric mastocytosis, some patients suffer from severe mast cell (MC) mediator-associated symptoms. The aim of this study was to identify predictors for severe MC mediator release symptoms in children with mastocytosis in the skin (MIS). Methods Serum baseline total tryptase (sbT) levels in 111 children with MIS – 80 maculopapular cutaneous mastocytosis/plaque mastocytosis, 22 nodular mastocytosis, and nine diffuse cutaneous mastocytosis – were investigated as a predictive biomarker for the occurrence of MC mediator-related signs and symptoms within the first 18 months after disease onset. Results Twelve children (11%) who showed extensive cutaneous disease involving >90% of body surface area (BSA) suffered from severe symptoms requiring hospitalization, with (n = 5) or without (n = 6) management in the intensive care unit (ICU) owing to life-threatening complications. The median sbT was significantly (P < 0.001) higher in patients with extensive cutaneous disease vs those with <90% of BSA involved (45.5 vs 5.2 µg/l, respectively), as well as in children with grade 4 (severe mastocytosis-related symptoms requiring emergency therapy and hospitalization) vs those with grade <4 (46.2 vs 5.2 µg/l, respectively). Receiver operating characteristics curve analyses showed that the optimal cutoff s for sbT to predict the need for daily antimediator therapy, hospitalization, and the management in an ICU were 6.6, 15.5, and 30.8 µg/l, respectively (sensitivity and specificity of 77% and 79%, 100% and 95%, and 100% and 96%, respectively). Conclusions Increased sbT in association with extensive cutaneous involvement identifies patients at risk for severe MC activation events in pediatric mastocytosis. PMID:22458675

Increased serum baseline tryptase levels and extensive skin involvement are predictors for the severity of mast cell activation episodes in children with mastocytosis.

PubMed

Alvarez-Twose, I; Vañó-Galván, S; Sánchez-Muñoz, L; Morgado, J M; Matito, A; Torrelo, A; Jaén, P; Schwartz, L B; Orfao, A; Escribano, L

2012-06-01

Despite the good prognosis of pediatric mastocytosis, some patients suffer from severe mast cell (MC) mediator-associated symptoms. The aim of this study was to identify predictors for severe MC mediator release symptoms in children with mastocytosis in the skin (MIS). Serum baseline total tryptase (sbT) levels in 111 children with MIS - 80 maculopapular cutaneous mastocytosis/plaque mastocytosis, 22 nodular mastocytosis, and nine diffuse cutaneous mastocytosis - were investigated as a predictive biomarker for the occurrence of MC mediator-related signs and symptoms within the first 18 months after disease onset. Twelve children (11%) who showed extensive cutaneous disease involving >90% of body surface area (BSA) suffered from severe symptoms requiring hospitalization, with (n = 5) or without (n = 6) management in the intensive care unit (ICU) owing to life-threatening complications. The median sbT was significantly (P < 0.001) higher in patients with extensive cutaneous disease vs those with <90% of BSA involved (45.5 vs 5.2 μg/l, respectively), as well as in children with grade 4 (severe mastocytosis-related symptoms requiring emergency therapy and hospitalization) vs those with grade <4 (46.2 vs 5.2 μg/l, respectively). Receiver operating characteristics curve analyses showed that the optimal cutoff s for sbT to predict the need for daily antimediator therapy, hospitalization, and the management in an ICU were 6.6, 15.5, and 30.8 μg/l, respectively (sensitivity and specificity of 77% and 79%, 100% and 95%, and 100% and 96%, respectively). Increased sbT in association with extensive cutaneous involvement identifies patients at risk for severe MC activation events in pediatric mastocytosis. © 2012 John Wiley & Sons A/S.

Performance of Stratified and Subgrouped Disproportionality Analyses in Spontaneous Databases.

PubMed

Seabroke, Suzie; Candore, Gianmario; Juhlin, Kristina; Quarcoo, Naashika; Wisniewski, Antoni; Arani, Ramin; Painter, Jeffery; Tregunno, Philip; Norén, G Niklas; Slattery, Jim

2016-04-01

Disproportionality analyses are used in many organisations to identify adverse drug reactions (ADRs) from spontaneous report data. Reporting patterns vary over time, with patient demographics, and between different geographical regions, and therefore subgroup analyses or adjustment by stratification may be beneficial. The objective of this study was to evaluate the performance of subgroup and stratified disproportionality analyses for a number of key covariates within spontaneous report databases of differing sizes and characteristics. Using a reference set of established ADRs, signal detection performance (sensitivity and precision) was compared for stratified, subgroup and crude (unadjusted) analyses within five spontaneous report databases (two company, one national and two international databases). Analyses were repeated for a range of covariates: age, sex, country/region of origin, calendar time period, event seriousness, vaccine/non-vaccine, reporter qualification and report source. Subgroup analyses consistently performed better than stratified analyses in all databases. Subgroup analyses also showed benefits in both sensitivity and precision over crude analyses for the larger international databases, whilst for the smaller databases a gain in precision tended to result in some loss of sensitivity. Additionally, stratified analyses did not increase sensitivity or precision beyond that associated with analytical artefacts of the analysis. The most promising subgroup covariates were age and region/country of origin, although this varied between databases. Subgroup analyses perform better than stratified analyses and should be considered over the latter in routine first-pass signal detection. Subgroup analyses are also clearly beneficial over crude analyses for larger databases, but further validation is required for smaller databases.

GIGAS: A set of microwave sensor arrays to detect molecular bremsstrahlung radiation from extensive air shower

NASA Astrophysics Data System (ADS)

Gaïor, R.; Al Samarai, I.; Berat, C.; Blanco Otano, M.; David, J.; Deligny, O.; Lebbolo, H.; Lecoz, S.; Letessier-Selvon, A.; Lhenry-Yvon, I.; Mariş, I. C.; Montanet, F.; Repain, P.; Salamida, F.; Settimo, M.; Stassi, P.; Stutz, A.

2018-04-01

We present the GIGAS (Gigahertz Identification of Giant Air Shower) microwave radio sensor arrays of the EASIER project (Extensive Air Shower Identification with Electron Radiometers), deployed at the site of the Pierre Auger cosmic ray observatory. The aim of these novel arrays is to probe the intensity of the molecular bremsstrahlung radiation expected from the development of the extensive air showers produced by the interaction of ultra high energy cosmic rays in the atmosphere. In the designed setup, the sensors are embedded within the surface detector array of the Pierre Auger observatory allowing us to use the particle signals at ground level to trigger the radio system. A series of seven, then 61 sensors have been deployed in the C-band, followed by a new series of 14 higher sensitivity ones in the C-band and the L-band. The design, the operation, the calibration and the sensitivity to extensive air showers of these arrays are described in this paper.

Sensitivity studies of pediatric material properties on juvenile lumbar spine responses using finite element analysis.

PubMed

Jebaseelan, D Davidson; Jebaraj, C; Yoganandan, Narayan; Rajasekaran, S; Kanna, Rishi M

2012-05-01

The objective of the study was to determine the sensitivity of material properties of the juvenile spine to its external and internal responses using a finite element model under compression, and flexion-extension bending moments. The methodology included exercising the 8-year-old juvenile lumbar spine using parametric procedures. The model included the vertebral centrum, growth plates, laminae, pedicles, transverse processes and spinous processes; disc annulus and nucleus; and various ligaments. The sensitivity analysis was conducted by varying the modulus of elasticity for various components. The first simulation was done using mean material properties. Additional simulations were done for each component corresponding to low and high material property variations. External displacement/rotation and internal stress-strain responses were determined under compression and flexion-extension bending. Results indicated that, under compression, disc properties were more sensitive than bone properties, implying an elevated role of the disc under this mode. Under flexion-extension moments, ligament properties were more dominant than the other components, suggesting that various ligaments of the juvenile spine play a key role in modulating bending behaviors. Changes in the growth plate stress associated with ligament properties explained the importance of the growth plate in the pediatric spine with potential implications in progressive deformities.

Extension of the Rejection Sensitivity Construct to the Interpersonal Functioning of Gay Men

ERIC Educational Resources Information Center

Pachankis, John E.; Goldfried, Marvin R.; Ramrattan, Melissa E.

2008-01-01

On the basis of recent evidence suggesting that gay men are particularly likely to fear interpersonal rejection, the authors set out to extend the "rejection sensitivity" construct to the mental health concerns of gay men. After establishing a reliable and valid measure of the gay-related rejection sensitivity construct, the authors use this to…

Acquisition of Raman Spectrometer and High Temperature and Pressure Reactor for Synthesis and Characterization of Carbon Based Hybrid Nanoparticles from Waste Wood

DTIC Science & Technology

2015-04-27

from waste biomass using these two high temperature reactors. We have extensively used a Raman spectrometer to analyse as synthesized carbon materials...corporation). These tools were fully installed and operational. We have also synthesized carbon materials from waste biomass using these two high...materials from waste biomass using these two high temperature reactors. We have extensively used a Raman spectrometer to analyse as synthesized carbon

Ancient rice cultivar extensively replaces phospholipids with non-phosphorus glycolipid under phosphorus deficiency.

PubMed

Tawaraya, Keitaro; Honda, Soichiro; Cheng, Weiguo; Chuba, Masaru; Okazaki, Yozo; Saito, Kazuki; Oikawa, Akira; Maruyama, Hayato; Wasaki, Jun; Wagatsuma, Tadao

2018-02-07

Recycling of phosphorus (P) from P-containing metabolites is an adaptive strategy of plants to overcome soil P deficiency. This study was aimed at demonstrating differences in lipid remodelling between low-P-tolerant and -sensitive rice cultivars using lipidome profiling. The rice cultivars Akamai (low-P-tolerant) and Koshihikari (low-P-sensitive) were grown in a culture solution with [2 mg l -1 (+P)] or without (-P) phosphate for 21 and 28 days after transplantation. Upper and lower leaves were collected. Lipids were extracted from the leaves and their composition was analysed by liquid chromatography/mass spectrometry (LC-MS). Phospholipids, namely phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG) and phosphatidylinositol (PI), lysophosphatidylcholine (lysoPC), diacylglycerol (DAG), triacylglycerol (TAG) and glycolipids, namely sulfoquinovosyl diacylglycerol (SQDG), digalactosyldiacylglycerol (DGDG), monogalactosyldiacylglycerol (MGDG) and 1,2-diacyl-3-O-alpha-glucuronosyl glycerol (GlcADG), were detected. GlcADG level was higher in both cultivars grown in -P than in +P and the increase was larger in Akamai than in Koshihikari. DGDG, MGDG and SQDG levels were higher in Akamai grown in -P than in +P and the increase was larger in the upper leaves than in the lower leaves. PC, PE, PG and PI levels were lower in both cultivars grown in -P than in +P and the decrease was larger in the lower leaves than in the upper leaves and in Akamai than in Koshihikari. Akamai catabolised more phospholipids in older leaves and synthesised glycolipids in younger leaves. These results suggested that extensive phospholipid replacement with non-phosphorus glycolipids is a mechanism underlying low-P-tolerance in rice cultivars. © 2018 Scandinavian Plant Physiology Society.

Characterization of long-term extension of isolated cell walls from growing cucumber hypocotyls

NASA Technical Reports Server (NTRS)

Cosgrove, D. J.

1989-01-01

Walls from frozen-thawed cucumber (Cucumis sativus L.) hypocotyls extend for many hours when placed in tension under acidic conditions. This study examined whether such "creep" is a purely physical process dependent on wall viscoelasticity alone or whether enzymatic activities are needed to maintain wall extension. Chemical denaturants inhibited wall creep, some acting reversibly and others irreversibly. Brief (15 s) boiling in water irreversibly inhibited creep, as did pre-incubation with proteases. Creep exhibited a high Q10 (3.8) between 20 degrees and 30 degrees C, with slow inactivation at higher temperatures, whereas the viscous flow of pectin solutions exhibited a much lower Q10 (1.35). On the basis of its temperature sensitivity, involvement of pectic gel-sol transitions was judged to be of little importance in creep. Pre-incubation of walls in neutral pH irreversibly inactivated their ability to creep, with a half-time of about 40 min. At 1 mM, Cu2+, Hg2+ and Al3+ were strongly inhibitory whereas most other cations, including Ca2+, had little effect. Sulfhydryl-reducing agents strongly stimulated creep, apparently by stabilizing wall enzyme(s). The physical effects of these treatments on polymer interactions were examined by Instron and stress-relaxation analyses. Some treatments, such as pH and Cu2+, had significant effects on wall viscoelasticity, but others had little or no apparent effect, thus implicating an enzymatic creep mechanism. The results indicate that creep depends on relatively rugged enzymes that are firmly attached to or entangled in the wall. The sensitivity of creep to SH-reducing agents indicates that thiol reduction of wall enzymes might provide a control mechanism for endogenous cell growth.

Extension of platelet shelf life from 4 to 5 days by implementation of a new screening strategy in Germany.

PubMed

Sireis, W; Rüster, B; Daiss, C; Hourfar, M K; Capalbo, G; Pfeiffer, H-U; Janetzko, K; Goebel, M; Kempf, V A J; Seifried, E; Schmidt, M

2011-10-01

The Paul-Ehrlich-Institute analysed all fatalities due to bacterial infections between 1997 and 2007. Thereafter, the platelet shelf life was reduced to a maximum of 4 days after blood donation because the majority of all cases of severe transfusion-transmitted bacterial infections occurred with day 5 platelets. The current study compares the analytical sensitivity and the diagnostic specificity of four rapid bacterial detection procedures. Nine transfusion-relevant bacterial strains were spiked in pooled platelets or apheresis platelets at a low concentration (10 CFU/bag). Samples were collected after day 3, day 4 and day 5 and investigated by four rapid bacterial detection methods (modified BacT/ALERT, Bactiflow, FACS method and 16s DNA PCR methods). Seven out of nine bacterial strains were adequately detected by BacT/ALERT, Bactiflow and PCR in apheresis platelets and pooled platelets after sample collection at day 3, day 4 and day 5. For three bacterial strains, analytical sensitivity was reduced for the FACS method. Two bacterial strains did not grow under the storage conditions in either pooled or apheresis platelets. A late sample collection on day 3, day 4 or day 5 after blood donation in combination with a rapid bacterial detection method offers a new opportunity to improve blood safety and reduce errors due to sampling., BacT/ALERT, Bactiflow or 16s ID-NAT are feasible for late bacterial screening in platelets may provide data which support the extension of platelet shelf life in Germany to 5 days. © 2011 The Author(s). Vox Sanguinis © 2011 International Society of Blood Transfusion.

Fuel consumption impacts of auto roof racks

DOE PAGES

Chen, Yuche; Meier, Alan

2016-03-23

The after-market roof rack is one of the most common components attached to a vehicle for carrying over-sized items, such as bicycles and skis. It is important to understand these racks' fuel consumption impacts on both individual vehicles and the national fleet because they are widely used. We estimate the national fuel consumption impacts of roof racks using a bottom-up approach. Our model incorporates real-world data and vehicle stock information to enable assessing fuel consumption impacts for several categories of vehicles, rack configurations, and usage conditions. In addition, the model draws on two new data-gathering techniques, on-line forums and crowd-sourcing.more » The results show that nationwide, roof racks are responsible for 0.8‰ of light duty vehicle fuel consumption in 2015, corresponding to 100 million gallons of gasoline per year. Sensitivity analyses show that results are most sensitive to the fraction of vehicles with installed roof racks but carrying no equipment. Here, the aerodynamic efficiency of typical roof racks can be greatly improved and reduce individual vehicle fuel consumption; however, government policies to minimize extensive driving with empty racks--if successful--could save more fuel nationally.« less

Optimizing Experimental Design for Comparing Models of Brain Function

PubMed Central

Daunizeau, Jean; Preuschoff, Kerstin; Friston, Karl; Stephan, Klaas

2011-01-01

This article presents the first attempt to formalize the optimization of experimental design with the aim of comparing models of brain function based on neuroimaging data. We demonstrate our approach in the context of Dynamic Causal Modelling (DCM), which relates experimental manipulations to observed network dynamics (via hidden neuronal states) and provides an inference framework for selecting among candidate models. Here, we show how to optimize the sensitivity of model selection by choosing among experimental designs according to their respective model selection accuracy. Using Bayesian decision theory, we (i) derive the Laplace-Chernoff risk for model selection, (ii) disclose its relationship with classical design optimality criteria and (iii) assess its sensitivity to basic modelling assumptions. We then evaluate the approach when identifying brain networks using DCM. Monte-Carlo simulations and empirical analyses of fMRI data from a simple bimanual motor task in humans serve to demonstrate the relationship between network identification and the optimal experimental design. For example, we show that deciding whether there is a feedback connection requires shorter epoch durations, relative to asking whether there is experimentally induced change in a connection that is known to be present. Finally, we discuss limitations and potential extensions of this work. PMID:22125485

Cell membrane water exchange effects in prostate DCE-MRI

NASA Astrophysics Data System (ADS)

Li, Xin; Priest, Ryan A.; Woodward, William J.; Siddiqui, Faisal; Beer, Tomasz M.; Garzotto, Mark G.; Rooney, William D.; Springer, Charles S.

2012-05-01

Prostate Dynamic-Contrast-Enhanced (DCE) MRI often exhibits fast and extensive global contrast reagent (CR) extravasation - measured by Ktrans, a pharmacokinetic parameter proportional to its rate. This implies that the CR concentration [CR] is high in the extracellular, extravascular space (EES) during a large portion of the DCE-MRI study. Since CR is detected indirectly, through water proton signal change, the effects of equilibrium transcytolemmal water exchange may be significant in the data and thus should be admitted in DCE-MRI pharmacokinetic modeling. The implications for parameter values were investigated through simulations, and analyses of actual prostate data, with different models. Model parameter correlation and precision were also explored. A near-optimal version of the exchange-sensitized model was found. Our results indicate that ΔKtrans (the Ktrans difference returned by this version and a model assuming exchange to be effectively infinitely fast) may be a very useful biomarker for discriminating malignant from benign prostate tissue. Using an exchange-sensitized model, we find that the mean intracellular water lifetime (τi) - an exchange measure - can be meaningfully mapped for the prostate. Our results show prostate glandular zone differences in τi values.

Estimating Mass Properties of Dinosaurs Using Laser Imaging and 3D Computer Modelling

PubMed Central

Bates, Karl T.; Manning, Phillip L.; Hodgetts, David; Sellers, William I.

2009-01-01

Body mass reconstructions of extinct vertebrates are most robust when complete to near-complete skeletons allow the reconstruction of either physical or digital models. Digital models are most efficient in terms of time and cost, and provide the facility to infinitely modify model properties non-destructively, such that sensitivity analyses can be conducted to quantify the effect of the many unknown parameters involved in reconstructions of extinct animals. In this study we use laser scanning (LiDAR) and computer modelling methods to create a range of 3D mass models of five specimens of non-avian dinosaur; two near-complete specimens of Tyrannosaurus rex, the most complete specimens of Acrocanthosaurus atokensis and Strutiomimum sedens, and a near-complete skeleton of a sub-adult Edmontosaurus annectens. LiDAR scanning allows a full mounted skeleton to be imaged resulting in a detailed 3D model in which each bone retains its spatial position and articulation. This provides a high resolution skeletal framework around which the body cavity and internal organs such as lungs and air sacs can be reconstructed. This has allowed calculation of body segment masses, centres of mass and moments or inertia for each animal. However, any soft tissue reconstruction of an extinct taxon inevitably represents a best estimate model with an unknown level of accuracy. We have therefore conducted an extensive sensitivity analysis in which the volumes of body segments and respiratory organs were varied in an attempt to constrain the likely maximum plausible range of mass parameters for each animal. Our results provide wide ranges in actual mass and inertial values, emphasizing the high level of uncertainty inevitable in such reconstructions. However, our sensitivity analysis consistently places the centre of mass well below and in front of hip joint in each animal, regardless of the chosen combination of body and respiratory structure volumes. These results emphasize that future biomechanical assessments of extinct taxa should be preceded by a detailed investigation of the plausible range of mass properties, in which sensitivity analyses are used to identify a suite of possible values to be tested as inputs in analytical models. PMID:19225569

Estimating mass properties of dinosaurs using laser imaging and 3D computer modelling.

PubMed

Bates, Karl T; Manning, Phillip L; Hodgetts, David; Sellers, William I

2009-01-01

Body mass reconstructions of extinct vertebrates are most robust when complete to near-complete skeletons allow the reconstruction of either physical or digital models. Digital models are most efficient in terms of time and cost, and provide the facility to infinitely modify model properties non-destructively, such that sensitivity analyses can be conducted to quantify the effect of the many unknown parameters involved in reconstructions of extinct animals. In this study we use laser scanning (LiDAR) and computer modelling methods to create a range of 3D mass models of five specimens of non-avian dinosaur; two near-complete specimens of Tyrannosaurus rex, the most complete specimens of Acrocanthosaurus atokensis and Strutiomimum sedens, and a near-complete skeleton of a sub-adult Edmontosaurus annectens. LiDAR scanning allows a full mounted skeleton to be imaged resulting in a detailed 3D model in which each bone retains its spatial position and articulation. This provides a high resolution skeletal framework around which the body cavity and internal organs such as lungs and air sacs can be reconstructed. This has allowed calculation of body segment masses, centres of mass and moments or inertia for each animal. However, any soft tissue reconstruction of an extinct taxon inevitably represents a best estimate model with an unknown level of accuracy. We have therefore conducted an extensive sensitivity analysis in which the volumes of body segments and respiratory organs were varied in an attempt to constrain the likely maximum plausible range of mass parameters for each animal. Our results provide wide ranges in actual mass and inertial values, emphasizing the high level of uncertainty inevitable in such reconstructions. However, our sensitivity analysis consistently places the centre of mass well below and in front of hip joint in each animal, regardless of the chosen combination of body and respiratory structure volumes. These results emphasize that future biomechanical assessments of extinct taxa should be preceded by a detailed investigation of the plausible range of mass properties, in which sensitivity analyses are used to identify a suite of possible values to be tested as inputs in analytical models.

Highly sensitive electrochemical detection of human telomerase activity based on bio-barcode method.

PubMed

Li, Ying; Liu, Bangwei; Li, Xia; Wei, Qingli

2010-07-15

In the present study, an electrochemical method for highly sensitive detection of human telomerase activity was developed based on bio-barcode amplification assay. Telomerase was extracted from HeLa cells, then the extract was mixed with telomerase substrate (TS) primer to perform extension reaction. The extension product was hybridized with the capture DNA immobilized on the Au electrode and then reacted with the signal DNA on Au nanoparticles to form a sandwich hybridization mode. Electrochemical signals were generated by chronocoulometric interrogation of [Ru(NH(3))(6)](3+) that quantitatively binds to the DNA on Au nanoparticles via electrostatic interaction. This method can detect the telomerase activity from as little as 10 cultured cancer cells without the polymerase chain reaction (PCR) amplification of telomerase extension product. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides

NASA Astrophysics Data System (ADS)

Chen, Yajing; Xiong, Zhichao; Zhang, Lingyi; Zhao, Jiaying; Zhang, Quanqing; Peng, Li; Zhang, Weibing; Ye, Mingliang; Zou, Hanfa

2015-02-01

Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g-1), high enrichment recovery (above 73.6%) and rapid magnetic separation. Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples.Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g-1), high enrichment recovery (above 73.6%) and rapid magnetic separation. Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05955g

Cost-effectiveness of memantine in moderate and severe Alzheimer's disease in Norway.

PubMed

Rive, B; Aarsland, D; Grishchenko, M; Cochran, J; Lamure, M; Toumi, M

2012-06-01

The cost-effectiveness of memantine for the treatment of moderate and severe Alzheimer's disease has been assessed in several European countries. Objective of the study was to assess it in Norwegian settings. This cost-utility analysis used a Markov modelling approach to simulate the evolution of patients until their need for full-time care (FTC) over a 5-year period. FTC was defined as a patient becoming either dependent or institutionalised. Transition probabilities were estimated using a newly developed predictive equation of time to FTC. Health resource use and utilities were obtained from the Scandinavian Study of Cost and Quality of Life in Alzheimer's Disease study, and mortality was obtained from the Oslo study. Memantine efficacy was based on a meta-analysis of six large trials. The model compared memantine with its alternative in this population, that is no pharmacological treatment or background therapy with acetylcholinesterase inhibitors. The model underwent extensive sensitivity analyses. In Norway, memantine was found to delay the need for FTC by 4.4 weeks compared with standard care and was associated with increased quality-adjusted life years. Memantine was the dominant strategy with cost savings of €3739 (30 041 NOK) per patient. The probability of being the dominant strategy was 98.8%. This result was confirmed across multiple sensitivity analyses. The model suggests that memantine prolongs time to FTC for no additional cost to the healthcare system and society. It can be regarded as a cost-effective choice in the management of moderate and severe Alzheimer's disease. Copyright © 2011 John Wiley & Sons, Ltd.

Predicting Dural Tear in Compound Depressed Skull Fractures: A Prospective Multicenter Correlational Study.

PubMed

Salia, Shemsedin Musefa; Mersha, Hagos Biluts; Aklilu, Abenezer Tirsit; Baleh, Abat Sahlu; Lund-Johansen, Morten

2018-06-01

Compound depressed skull fracture (DSF) is a neurosurgical emergency. Preoperative knowledge of dural status is indispensable for treatment decision making. This study aimed to determine predictors of dural tear from clinical and imaging characteristics in patients with compound DSF. This prospective, multicenter correlational study in neurosurgical hospitals in Addis Ababa, Ethiopia, included 128 patients operated on from January 1, 2016, to October 31, 2016. Clinical, imaging, and intraoperative findings were evaluated. Univariate and multivariate analyses were used to establish predictors of dural tear. A logistic regression model was developed to predict probability of dural tear. Model validation was done using the receiver operating characteristic curve. Dural tear was seen in 55.5% of 128 patients. Demographics, injury mechanism, clinical presentation, and site of DSF had no significant correlation with dural tear. In univariate and multivariate analyses, depth of fracture depression (odds ratio 1.3, P < 0.001), pneumocephalus (odds ratio 2.8, P = 0.005), and brain contusions/intracerebral hematoma (odds ratio 5.5, P < 0.001) were significantly correlated with dural tear. We developed a logistic regression model (diagnostic test) to calculate probability of dural tear. Using the receiver operating characteristic curve, we determined the cutoff value for a positive test giving the highest accuracy to be 30% with a corresponding sensitivity of 93.0% and specificity of 43.9%. Dural tear in compound DSF can be predicted with 93.0% sensitivity using preoperative findings and may guide treatment decision making in resource-limited settings where risk of extensive cranial surgery outweighs the benefit. Copyright © 2018 Elsevier Inc. All rights reserved.

Cost-effectiveness of rivaroxaban for stroke prevention in atrial fibrillation in the Portuguese setting.

PubMed

Morais, João; Aguiar, Carlos; McLeod, Euan; Chatzitheofilou, Ismini; Fonseca Santos, Isabel; Pereira, Sónia

2014-09-01

To project the long-term cost-effectiveness of treating non-valvular atrial fibrillation (AF) patients for stroke prevention with rivaroxaban compared to warfarin in Portugal. A Markov model was used that included health and treatment states describing the management and consequences of AF and its treatment. The model's time horizon was set at a patient's lifetime and each cycle at three months. The analysis was conducted from a societal perspective and a 5% discount rate was applied to both costs and outcomes. Treatment effect data were obtained from the pivotal phase III ROCKET AF trial. The model was also populated with utility values obtained from the literature and with cost data derived from official Portuguese sources. The outcomes of the model included life-years, quality-adjusted life-years (QALYs), incremental costs, and associated incremental cost-effectiveness ratios (ICERs). Extensive sensitivity analyses were undertaken to further assess the findings of the model. As there is evidence indicating underuse and underprescription of warfarin in Portugal, an additional analysis was performed using a mixed comparator composed of no treatment, aspirin, and warfarin, which better reflects real-world prescribing in Portugal. This cost-effectiveness analysis produced an ICER of €3895/QALY for the base-case analysis (vs. warfarin) and of €6697/QALY for the real-world prescribing analysis (vs. mixed comparator). The findings were robust when tested in sensitivity analyses. The results showed that rivaroxaban may be a cost-effective alternative compared with warfarin or real-world prescribing in Portugal. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Cost-effectiveness of ticagrelor versus clopidogrel for the prevention of atherothrombotic events in adult patients with acute coronary syndrome in Germany.

PubMed

Theidel, Ulrike; Asseburg, Christian; Giannitsis, Evangelos; Katus, Hugo

2013-06-01

The aim of this health economic analysis was to compare the cost-effectiveness of ticagrelor versus clopidogrel within the German health care system. A two-part decision model was adapted to compare treatment with ticagrelor or clopidogrel in a low-dose acetylsalicylic acid (ASA) cohort (≤150 mg) for all ACS patients and subtypes NSTEMI/IA and STEMI. A decision-tree approach was chosen for the first year after initial hospitalization based on trial observations from a subgroup of the PLATO study. Subsequent years were estimated by a Markov model. Following a macro-costing approach, costs were based on official tariffs and published literature. Extensive sensitivity analyses were performed to test the robustness of the model. One-year treatment with ticagrelor is associated with an estimated 0.1796 life-years gained (LYG) and gained 0.1570 quality-adjusted life-years (QALY), respectively, over the lifetime horizon. Overall average cost with ticagrelor is estimated to be EUR 11,815 vs. EUR 11,387 with generic clopidogrel over a lifetime horizon. The incremental cost-effectiveness ratio (ICER) was EUR 2,385 per LYG (EUR 2,728 per QALY). Comparing ticagrelor with Plavix(®) or the lowest priced generic clopidogrel, ICER ranges from dominant to EUR 3,118 per LYG (EUR 3,567 per QALY). These findings are robust under various additional sensitivity analyses. Hence, 12 months of ACS treatment using ticagrelor/ASA instead of clopidogrel/ASA may offer a cost-effective therapeutic option, even when the generic price for clopidogrel is employed.

Validation of a portable nitric oxide analyzer for screening in primary ciliary dyskinesias.

PubMed

Harris, Amanda; Bhullar, Esther; Gove, Kerry; Joslin, Rhiannon; Pelling, Jennifer; Evans, Hazel J; Walker, Woolf T; Lucas, Jane S

2014-02-10

Nasal nitric oxide (nNO) levels are very low in primary ciliary dyskinesia (PCD) and it is used as a screening test. We assessed the reliability and usability of a hand-held analyser in comparison to a stationary nitric oxide (NO) analyser in 50 participants (15 healthy, 13 PCD, 22 other respiratory diseases; age 6-79 years). Nasal NO was measured using a stationary NO analyser during a breath-holding maneuver, and using a hand-held analyser during tidal breathing, sampling at 2 ml/sec or 5 ml/sec. The three methods were compared for their specificity and sensitivity as a screen for PCD, their success rate in different age groups, within subject repeatability and acceptability. Correlation between methods was assessed. Valid nNO measurements were obtained in 94% of participants using the stationary analyser, 96% using the hand-held analyser at 5 ml/sec and 76% at 2 ml/sec. The hand-held device at 5 ml/sec had excellent sensitivity and specificity as a screening test for PCD during tidal breathing (cut-off of 30 nL/min,100% sensitivity, >95% specificity). The cut-off using the stationary analyser during breath-hold was 38 nL/min (100% sensitivity, 95% specificity). The stationary and hand-held analyser (5 ml/sec) showed reasonable within-subject repeatability(% coefficient of variation = 15). The hand-held NO analyser provides a promising screening tool for PCD.

SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool

PubMed Central

Zi, Zhike; Zheng, Yanan; Rundell, Ann E; Klipp, Edda

2008-01-01

Background It has long been recognized that sensitivity analysis plays a key role in modeling and analyzing cellular and biochemical processes. Systems biology markup language (SBML) has become a well-known platform for coding and sharing mathematical models of such processes. However, current SBML compatible software tools are limited in their ability to perform global sensitivity analyses of these models. Results This work introduces a freely downloadable, software package, SBML-SAT, which implements algorithms for simulation, steady state analysis, robustness analysis and local and global sensitivity analysis for SBML models. This software tool extends current capabilities through its execution of global sensitivity analyses using multi-parametric sensitivity analysis, partial rank correlation coefficient, SOBOL's method, and weighted average of local sensitivity analyses in addition to its ability to handle systems with discontinuous events and intuitive graphical user interface. Conclusion SBML-SAT provides the community of systems biologists a new tool for the analysis of their SBML models of biochemical and cellular processes. PMID:18706080

SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool.

PubMed

Zi, Zhike; Zheng, Yanan; Rundell, Ann E; Klipp, Edda

2008-08-15

It has long been recognized that sensitivity analysis plays a key role in modeling and analyzing cellular and biochemical processes. Systems biology markup language (SBML) has become a well-known platform for coding and sharing mathematical models of such processes. However, current SBML compatible software tools are limited in their ability to perform global sensitivity analyses of these models. This work introduces a freely downloadable, software package, SBML-SAT, which implements algorithms for simulation, steady state analysis, robustness analysis and local and global sensitivity analysis for SBML models. This software tool extends current capabilities through its execution of global sensitivity analyses using multi-parametric sensitivity analysis, partial rank correlation coefficient, SOBOL's method, and weighted average of local sensitivity analyses in addition to its ability to handle systems with discontinuous events and intuitive graphical user interface. SBML-SAT provides the community of systems biologists a new tool for the analysis of their SBML models of biochemical and cellular processes.

ELISA-type assays of trace biomarkers using microfluidic methods.

PubMed

Dong, Jinhua; Ueda, Hiroshi

2017-09-01

Recently, great progress has been achieved for analytical technologies for biological substances. Traditionally, detection methods for analytes mainly rely on large instrumental analyses. These methods require costly equipment, skilled operators and long measurement time despite their generally low sensitivity. In contrast, immunoassays are becoming more and more popular for it is powerful, inexpensive, and convenient nature. Immunoassay has a range of applications, because it employs antibody, a protein produced by plasma cells in the acquired immune system to identify and neutralize diverse pathogens and other exogenous substances. However, the sensitivity of conventional immunoassays so far is limited by their reaction principles and detection methods. The microfluidics technology is the one that manipulates small volumes of fluid and flow, which has the potential to miniaturize many laboratory procedures. Immunoassays on microfluidic devices have been studied extensively and have gained significant attention owing to intrinsic advantages offered by the assay platforms. The techniques have allowed the miniaturization of conventional immunoassay and bring the advantages such as small volumes of samples and reagents as well as the decrease of contamination, which results in the decline of false-positive results. Ultimately, the combination of immunoassays with microfluidics affords a promising platform for multiple, sensitive, and automatic point-of-care diagnostics. Recent achievements on microfluidic devices and immunoassay detection systems including digital assay employing single molecule will be introduced in detail and the strategies for faster and more sensitive configurations in microfluidic immunosensors will be highlighted. WIREs Nanomed Nanobiotechnol 2017, 9:e1457. doi: 10.1002/wnan.1457 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Cell Culture System for Analysis of Genetic Heterogeneity Within Hepatocellular Carcinomas and Response to Pharmacologic Agents.

PubMed

Gao, Qiang; Wang, Zhi-Chao; Duan, Meng; Lin, Yi-Hui; Zhou, Xue-Ya; Worthley, Daniel L; Wang, Xiao-Ying; Niu, Gang; Xia, Yuchao; Deng, Minghua; Liu, Long-Zi; Shi, Jie-Yi; Yang, Liu-Xiao; Zhang, Shu; Ding, Zhen-Bin; Zhou, Jian; Liang, Chun-Min; Cao, Ya; Xiong, Lei; Xi, Ruibin; Shi, Yong-Yong; Fan, Jia

2017-01-01

No targeted therapies have been found to be effective against hepatocellular carcinoma (HCC), possibly due to the large degree of intratumor heterogeneity. We performed genetic analyses of different regions of HCCs to evaluate levels of intratumor heterogeneity and associate alterations with responses to different pharmacologic agents. We obtained samples of HCCs (associated with hepatitis B virus infection) from 10 patients undergoing curative resection, before adjuvant therapy, at hospitals in China. We collected 4-9 spatially distinct samples from each tumor (55 regions total), performed histologic analyses, isolated cancer cells, and carried them low-passage culture. We performed whole-exome sequencing, copy-number analysis, and high-throughput screening of the cultured primary cancer cells. We tested responses of an additional 105 liver cancer cell lines to a fibroblast growth factor receptor (FGFR) 4 inhibitor. We identified a total of 3670 non-silent mutations (3192 missense, 94 splice-site variants, and 222 insertions or deletions) in the tumor samples. We observed considerable intratumor heterogeneity and branched evolution in all 10 tumors; the mean percentage of heterogeneous mutations in each tumor was 39.7% (range, 12.9%-68.5%). We found significant mutation shifts toward C>T and C>G substitutions in branches of phylogenetic trees among samples from each tumor (P < .0001). Of note, 14 of the 26 oncogenic alterations (53.8%) varied among subclones that mapped to different branches. Genetic alterations that can be targeted by existing pharmacologic agents (such as those in FGF19, DDR2, PDGFRA, and TOP1) were identified in intratumor subregions from 4 HCCs and were associated with sensitivity to these agents. However, cells from the remaining subregions, which did not have these alterations, were not sensitive to these drugs. High-throughput screening identified pharmacologic agents to which these cells were sensitive, however. Overexpression of FGF19 correlated with sensitivity of cells to an inhibitor of FGFR 4; this observation was validated in 105 liver cancer cell lines (P = .0024). By analyzing genetic alterations in different tumor regions of 10 HCCs, we observed extensive intratumor heterogeneity. Our patient-derived cell line-based model, integrating genetic and pharmacologic data from multiregional cancer samples, provides a platform to elucidate how intratumor heterogeneity affects sensitivity to different therapeutic agents. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Sex-specific thermal sensitivities of performance and activity in the asian house gecko, Hemidactylus frenatus.

PubMed

Cameron, Skye F; Wheatley, Rebecca; Wilson, Robbie S

2018-07-01

Studies of sexual selection primarily focus on morphological traits such as body size and secondary trait dimorphism, with less attention been given to the functional differences between the sexes and even more so their thermal performance capacities. Each sex may benefit from possessing different thermal performance capacities that would allow them to maximise their fitness relative to their different reproductive roles; especially when performances are closely related to reproductive success. Here, we examine sexual divergence in thermal sensitivities of performance across three populations of the Asian house gecko (Hemidactylus frenatus) over an extensive latitudinal cline. Using analyses of the thermal sensitivity of routine activity, bite force and sprint speed, we explored whether: (i) males and females differed in their optimal temperatures for performance, (ii) the sexes differed in their thermal sensitivities of performance, and (iii) the degree of sexual divergence in thermal sensitivity varied among the populations. Because male H. frenatus are highly aggressive and frequently engage in combat to gain territories and mating opportunities, we expected males would be active over a wider range of temperatures than females and this would favour broad thermal sensitivity curves for males. In addition, we expected a greater divergence between the sexes in thermal sensitivities for the temperate populations that experience greater daily and seasonal thermal variation. We found that males were more active, and had greater bite forces and faster sprint speeds than females, independent of body size. In addition, we found differences between the sexes in thermal sensitivities for the tropical population; female H. frenatus were less active and possessed lower sprint speeds at higher temperatures than males. Although H. frenatus from the most variable thermal environments also displayed the broadest thermal performance range, it was the more stable tropical population that exhibited the greatest divergence between the sexes in thermal sensitivity of performance. The divergence in thermal physiology that we detected between the sexes of H. frenatus is consistent with the idea that males will derive mating and territorial advantages for maintaining function over a broader range of temperatures.

Modular space station phase B extension preliminary system design. Volume 2: Operations and crew analyses

NASA Technical Reports Server (NTRS)

Meston, R. D.; Schall, M. R., Jr.; Brockman, C. L.; Bender, W. H.

1972-01-01

All analyses and tradeoffs conducted to establish the MSS operations and crew activities are discussed. The missions and subsystem integrated analyses that were completed to assure compatibility of program elements and consistency with program objectives are presented.

Environmental ground borne noise and vibration protection of sensitive cultural receptors along the Athens Metro Extension to Piraeus.

PubMed

Vogiatzis, Konstantinos

2012-11-15

Attiko Metro S.A., the state company ensuring the development of the Athens Metro network, has recently initiated a new extension of 7.6 km, has planned for line 3 of Athens Metro from Haidari to Piraeus "Dimotikon Theatre" towards "University of Piraeus" (forestation), connecting the major Piraeus Port with "Eleftherios Venizelos" International Airport. The Piraeus extension consists of a Tunnel Boring Machine, 2 tracks and, tunnel sections, as well as 6 stations and a forestation (New Austrian Tunnelling Method) at the end of the alignment. In order to avoid the degradation of the urban acoustic environment from ground borne noise and vibration during metro operation, the assessment of the required track types and possible noise mitigation measures was executed, and for each section and each sensitive building, the ground borne noise and vibration levels will be numerically predicted. The calculated levels were then compared with ground borne noise and vibration level criteria. The necessary mitigation measures were defined in order to guarantee, in each location along the extension, the allowable ground borne Noise and Vibration max. levels inside nearby sensitive buildings taking into account alternative Transfer Functions for ground borne noise diffusion inside the buildings. Ground borne noise levels were proven to be higher than the criterion where special track work is present and also in the case of the sensitive receptor: "Dimotikon Theatre". In order to reduce the ground borne noise levels to allowable values in these sections, the installation of tracks and special track work on a floating slab was assessed and recommended. Copyright © 2012 Elsevier B.V. All rights reserved.

Examining the Heterogeneity and Cost Effectiveness of a Complex Intervention by Segmentation of Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Sørensen, Sabrina Storgaard; Jensen, Morten Berg; Pedersen, Kjeld Møller; Ehlers, Lars

2018-02-01

To examine the heterogeneity in cost-effectiveness analyses of patient-tailored complex interventions. Latent class analysis (LCA) was performed on data from a randomized controlled trial evaluating a patient-tailored case management strategy for patients suffering from chronic obstructive pulmonary disease (COPD). LCA was conducted on detailed process variables representing service variation in the intervention group. Features of the identified latent classes were compared for consistency with baseline demographic, clinical, and economic characteristics for each class. Classes for the control group, corresponding to the identified latent classes for the intervention group, were identified using multinomial logistic regression. Cost-utility analyses were then conducted at the class level, and uncertainty surrounding the point estimates was assessed by probabilistic sensitivity analysis. The LCA identified three distinct classes: the psychologically care class, the extensive COPD care class, and the limited COPD care class. Patient baseline characteristics were in line with the features identified in the LCA. Evaluation of cost-effectiveness revealed highly disparate results, and case management for only the extensive COPD care class appeared cost-effective with an incremental cost-effectiveness ratio of £26,986 per quality-adjusted life-year gained using the threshold value set by the National Institute of Health and Care Excellence. Findings indicate that researchers evaluating patient-tailored complex interventions need to address both supply-side variation and demand-side heterogeneity to link findings with outcome. The article specifically proposes the use of LCA because it is believed to have the potential to enable more appropriate targeting of complex care strategies. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Investigating carbon dynamics in Siberian peat bogs using molecular-level analyses

NASA Astrophysics Data System (ADS)

Kaiser, K.; Benner, R. H.

2013-12-01

Total hydrolysable carbohydrates, and lignin and cutin acid compounds were analyzed in peat cores collected 56.8 N (SIB04), 58.4 N (SIB06), 63.8 N (G137) and 66.5 N (E113) in the Western Siberian Lowland to investigate vegetation, chemical compositions and the stage of decomposition. Sphagnum mosses dominated peatland vegetation in all four cores. High-resolution molecular analyses revealed rapid vegetation changes on timescales of 50-200 years in the southern cores Sib4 and Sib6. Syringyl and vanillyl (S/V) ratios and cutin acids indicated these vegetation changes were due to varying inputs of angiosperm and gymnosperm and root material. In the G137 and E113 cores lichens briefly replaced sphagnum mosses and vascular plants. Molecular decomposition indicators used in this study tracked the decomposition of different organic constituents of peat organic matter. The carbohydrate decomposition index was sensitive to the polysaccharide component of all peat-forming plants, whereas acid/aldehyde ratios of S and V phenols (Ac/AlS,V) followed the lignin component of vascular plants. Low carbohydrate decomposition indices in peat layers corresponded well with elevated (Ad/Al)S,V ratios. This suggested both classes of biochemicals were simultaneously decomposed, and decomposition processes were associated with extensive total mass loss in these ombrotrophic systems. Selective decomposition or transformation of lignin was observed in the permafrost-influenced northern cores G137 and E113. Both cores exhibited the highest (Ad/Al)S,V ratios, almost four-fold higher than measured in peat-forming plants. The extent of decomposition in the four peat cores did not uniformly increase with age, but showed episodic extensive decomposition events. Variable decomposition events independent of climatic conditions and vegetation shifts highlight the complexity of peatland dynamics.

Choice of regularization in adjoint tomography based on two-dimensional synthetic tests

NASA Astrophysics Data System (ADS)

Valentová, Lubica; Gallovič, František; Růžek, Bohuslav; de la Puente, Josep; Moczo, Peter

2015-08-01

We present synthetic tests of 2-D adjoint tomography of surface wave traveltimes obtained by the ambient noise cross-correlation analysis across the Czech Republic. The data coverage may be considered perfect for tomography due to the density of the station distribution. Nevertheless, artefacts in the inferred velocity models arising from the data noise may be still observed when weak regularization (Gaussian smoothing of the misfit gradient) or too many iterations are considered. To examine the effect of the regularization and iteration number on the performance of the tomography in more detail we performed extensive synthetic tests. Instead of the typically used (although criticized) checkerboard test, we propose to carry out the tests with two different target models-simple smooth and complex realistic models. The first test reveals the sensitivity of the result on the data noise, while the second helps to analyse the resolving power of the data set. For various noise and Gaussian smoothing levels, we analysed the convergence towards (or divergence from) the target model with increasing number of iterations. Based on the tests we identified the optimal regularization, which we then employed in the inversion of 16 and 20 s Love-wave group traveltimes.

Processing capacity under perceptual and cognitive load: a closer look at load theory.

PubMed

Fitousi, Daniel; Wenger, Michael J

2011-06-01

Variations in perceptual and cognitive demands (load) play a major role in determining the efficiency of selective attention. According to load theory (Lavie, Hirst, Fockert, & Viding, 2004) these factors (a) improve or hamper selectivity by altering the way resources (e.g., processing capacity) are allocated, and (b) tap resources rather than data limitations (Norman & Bobrow, 1975). Here we provide an extensive and rigorous set of tests of these assumptions. Predictions regarding changes in processing capacity are tested using the hazard function of the response time (RT) distribution (Townsend & Ashby, 1978; Wenger & Gibson, 2004). The assumption that load taps resource rather than data limitations is examined using measures of sensitivity and bias drawn from signal detection theory (Swets, 1964). All analyses were performed at two levels: the individual and the aggregate. Hypotheses regarding changes in processing capacity were confirmed at the level of the aggregate. Hypotheses regarding resource and data limitations were not completely supported at either level of analysis. And in all of the analyses, we observed substantial individual differences. In sum, the results suggest a need to expand the theoretical vocabulary of load theory, rather than a need to discard it.

The Model Optimization, Uncertainty, and SEnsitivity analysis (MOUSE) toolbox: overview and application

USDA-ARS?s Scientific Manuscript database

For several decades, optimization and sensitivity/uncertainty analysis of environmental models has been the subject of extensive research. Although much progress has been made and sophisticated methods developed, the growing complexity of environmental models to represent real-world systems makes it...

"Narrowing the transmission gap: A synthesis of three decades of research on intergenerational transmission of attachment": Correction.

PubMed

2018-04-01

Reports an error in "Narrowing the transmission gap: A synthesis of three decades of research on intergenerational transmission of attachment" by Marije L. Verhage, Carlo Schuengel, Sheri Madigan, R. M. Pasco Fearon, Mirjam Oosterman, Rosalinda Cassibba, Marian J. Bakermans-Kranenburg and Marinus H. van IJzendoorn ( Psychological Bulletin , 2016[Apr], Vol 142[4], 337-366). In the article, there are errors in Table 7. The percentages of the attachment classifications do not add up to 100%. The corrected version of Table 7 is provided in the erratum. (The following abstract of the original article appeared in record 2015-55801-001.) Twenty years ago, meta-analytic results (k = 19) confirmed the association between caregiver attachment representations and child-caregiver attachment (Van IJzendoorn, 1995). A test of caregiver sensitivity as the mechanism behind this intergenerational transmission showed an intriguing "transmission gap." Since then, the intergenerational transmission of attachment and the transmission gap have been studied extensively, and now extend to diverse populations from all over the globe. Two decades later, the current review revisited the effect sizes of intergenerational transmission, the heterogeneity of the transmission effects, and the size of the transmission gap. Analyses were carried out with a total of 95 samples (total N = 4,819). All analyses confirmed intergenerational transmission of attachment, with larger effect sizes for secure-autonomous transmission (r = .31) than for unresolved transmission (r = .21), albeit with significantly smaller effect sizes than 2 decades earlier (r = .47 and r = .31, respectively). Effect sizes were moderated by risk status of the sample, biological relatedness of child-caregiver dyads, and age of the children. Multivariate moderator analyses showed that unpublished and more recent studies had smaller effect sizes than published and older studies. Path analyses showed that the transmission could not be fully explained by caregiver sensitivity, with more recent studies narrowing but not bridging the "transmission gap." Implications for attachment theory as well as future directions for research are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Gravitational astrophysics

NASA Astrophysics Data System (ADS)

Hendry, Martin; Woan, Graham

2007-02-01

Like the surface of a busy swimming pool, spacetime is awash with waves generated by the local and distant motions of mass and, in principle, much of this activity can be reconstructed by analysing the waveforms. However, instrumentation with a reasonable chance of directly detecting these gravitational waves has only become available within the past year, with the LIGO detectors now running at design sensitivity. Here we review the burgeoning field of observational gravitational astrophysics: using gravitational wave detectors as telescopes to help answer a wide range of astrophysical questions from neutron-star physics to cosmology. The next generation of ground-based telescopes should be able to make extensive gravitational observations of some of the more energetic events in our local universe. Looking only slightly further ahead, the space-based LISA observatory will reveal the gravitational universe in phenomenal detail, supplying high-quality data on perhaps thousands of sources, and tackling some of the most fascinating questions in contemporary astronomy.

Trichloroethylene (TCE) in tree cores to complement a subsurface investigation on residential property near a former electroplating facility.

PubMed

Wilcox, Jeffrey D; Johnson, Kathy M

2016-10-01

Tree cores were collected and analyzed for trichloroethylene (TCE) on a private property between a former electroplating facility in Asheville, North Carolina (USA), and a contaminated wetland/spring complex. TCE was detected in 16 of 31 trees, the locations of which were largely consistent with a "plume core" delineated by a more detailed subsurface investigation nearly 2 years later. Concentrations in tree cores and nearby soil borings were not correlated, perhaps due to heterogeneities in both geologic and tree root structure, spatial and temporal variability in transpiration rates, or interferences caused by other contaminants at the site. Several tree cores without TCE provided evidence for significantly lower TCE concentrations in shallow groundwater along the margins of the contaminated spring complex in an area with limited accessibility. This study demonstrates that tree core analyses can complement a more extensive subsurface investigation, particularly in residential or ecologically sensitive areas.

An Efficient, Noniterative Method of Identifying the Cost-Effectiveness Frontier.

PubMed

Suen, Sze-chuan; Goldhaber-Fiebert, Jeremy D

2016-01-01

Cost-effectiveness analysis aims to identify treatments and policies that maximize benefits subject to resource constraints. However, the conventional process of identifying the efficient frontier (i.e., the set of potentially cost-effective options) can be algorithmically inefficient, especially when considering a policy problem with many alternative options or when performing an extensive suite of sensitivity analyses for which the efficient frontier must be found for each. Here, we describe an alternative one-pass algorithm that is conceptually simple, easier to implement, and potentially faster for situations that challenge the conventional approach. Our algorithm accomplishes this by exploiting the relationship between the net monetary benefit and the cost-effectiveness plane. To facilitate further evaluation and use of this approach, we also provide scripts in R and Matlab that implement our method and can be used to identify efficient frontiers for any decision problem. © The Author(s) 2015.

An Efficient, Non-iterative Method of Identifying the Cost-Effectiveness Frontier

PubMed Central

Suen, Sze-chuan; Goldhaber-Fiebert, Jeremy D.

2015-01-01

Cost-effectiveness analysis aims to identify treatments and policies that maximize benefits subject to resource constraints. However, the conventional process of identifying the efficient frontier (i.e., the set of potentially cost-effective options) can be algorithmically inefficient, especially when considering a policy problem with many alternative options or when performing an extensive suite of sensitivity analyses for which the efficient frontier must be found for each. Here, we describe an alternative one-pass algorithm that is conceptually simple, easier to implement, and potentially faster for situations that challenge the conventional approach. Our algorithm accomplishes this by exploiting the relationship between the net monetary benefit and the cost-effectiveness plane. To facilitate further evaluation and use of this approach, we additionally provide scripts in R and Matlab that implement our method and can be used to identify efficient frontiers for any decision problem. PMID:25926282

Mediation Analysis: A Practitioner's Guide.

PubMed

VanderWeele, Tyler J

2016-01-01

This article provides an overview of recent developments in mediation analysis, that is, analyses used to assess the relative magnitude of different pathways and mechanisms by which an exposure may affect an outcome. Traditional approaches to mediation in the biomedical and social sciences are described. Attention is given to the confounding assumptions required for a causal interpretation of direct and indirect effect estimates. Methods from the causal inference literature to conduct mediation in the presence of exposure-mediator interactions, binary outcomes, binary mediators, and case-control study designs are presented. Sensitivity analysis techniques for unmeasured confounding and measurement error are introduced. Discussion is given to extensions to time-to-event outcomes and multiple mediators. Further flexible modeling strategies arising from the precise counterfactual definitions of direct and indirect effects are also described. The focus throughout is on methodology that is easily implementable in practice across a broad range of potential applications.

[Comparison of simple pooling and bivariate model used in meta-analyses of diagnostic test accuracy published in Chinese journals].

PubMed

Huang, Yuan-sheng; Yang, Zhi-rong; Zhan, Si-yan

2015-06-18

To investigate the use of simple pooling and bivariate model in meta-analyses of diagnostic test accuracy (DTA) published in Chinese journals (January to November, 2014), compare the differences of results from these two models, and explore the impact of between-study variability of sensitivity and specificity on the differences. DTA meta-analyses were searched through Chinese Biomedical Literature Database (January to November, 2014). Details in models and data for fourfold table were extracted. Descriptive analysis was conducted to investigate the prevalence of the use of simple pooling method and bivariate model in the included literature. Data were re-analyzed with the two models respectively. Differences in the results were examined by Wilcoxon signed rank test. How the results differences were affected by between-study variability of sensitivity and specificity, expressed by I2, was explored. The 55 systematic reviews, containing 58 DTA meta-analyses, were included and 25 DTA meta-analyses were eligible for re-analysis. Simple pooling was used in 50 (90.9%) systematic reviews and bivariate model in 1 (1.8%). The remaining 4 (7.3%) articles used other models pooling sensitivity and specificity or pooled neither of them. Of the reviews simply pooling sensitivity and specificity, 41(82.0%) were at the risk of wrongly using Meta-disc software. The differences in medians of sensitivity and specificity between two models were both 0.011 (P<0.001, P=0.031 respectively). Greater differences could be found as I2 of sensitivity or specificity became larger, especially when I2>75%. Most DTA meta-analyses published in Chinese journals(January to November, 2014) combine the sensitivity and specificity by simple pooling. Meta-disc software can pool the sensitivity and specificity only through fixed-effect model, but a high proportion of authors think it can implement random-effect model. Simple pooling tends to underestimate the results compared with bivariate model. The greater the between-study variance is, the more likely the simple pooling has larger deviation. It is necessary to increase the knowledge level of statistical methods and software for meta-analyses of DTA data.

Cost-effectiveness of zoledronic acid in the prevention of skeletal-related events in patients with bone metastases secondary to advanced renal cell carcinoma: application to France, Germany, and the United Kingdom.

PubMed

Botteman, M F; Meijboom, M; Foley, I; Stephens, J M; Chen, Y M; Kaura, S

2011-12-01

The use of zoledronic acid (ZOL) has recently been shown to significantly reduce the risk of new skeletal-related events (SREs) in renal cell carcinoma (RCC) patients with bone metastases. The present exploratory study assessed the cost-effectiveness of ZOL in this population, adopting a French, German, and United Kingdom (UK) government payer perspective. This cost-effectiveness model was based on a post hoc retrospective analysis of a subset of patients with RCC who were included in a larger randomized clinical trial of patients with bone metastases secondary to a variety of cancers. In the trial, patients were randomized to receive ZOL (n = 27) or placebo (n = 19) with concomitant antineoplastic therapy every 3 weeks for 9 months (core study) plus 12 months during a study extension. Since the trial did not collect costs or data on the quality-adjusted life years (QALYs) of the patients, these outcomes had to be assumed via modeling exercises. The costs of SREs were estimated using hospital DRG tariffs. These estimates were supplemented with literature-based costs where possible. Drug, administration, and supply costs were obtained from published and internet sources. Consistent with similar economic analyses, patients were assumed to experience quality of life decrements lasting 1 month for each SRE. Uncertainty surrounding outcomes was addressed via multivariate sensitivity analyses. Patients receiving ZOL experienced 1.07 fewer SREs than patients on placebo. Patients on ZOL experienced a gain in discounted QALYs of approximately 0.1563 in France and Germany and 0.1575 in the UK. Discounted SRE-related costs were substantially lower among ZOL than placebo patients (-€ 4,196 in France, - € 3,880 in Germany, and -€ 3,355 in the UK). After taking into consideration the drug therapy costs, ZOL saved € 1,358, € 1,223, and € 719 in France, Germany, and the UK, respectively. In the multivariate sensitivity analyses, therapy with ZOL saved costs in 67-77% of simulations, depending on the country. The cost per QALY gained for ZOL versus placebo was below € 30,000 per QALY gained threshold in approximately 93-94% of multivariate sensitivity analyses simulations. The present analysis suggests that ZOL saves costs and increases QALYs compared to placebo in French, German, and UK RCC patients with bone metastases. Additional prospective research may be needed to confirm these results in a larger sample of patients.

Approaches for assessing risks to sensitive populations: Lessons learned from evaluating risks in the pediatric populations*

EPA Science Inventory

Assessing the risk profiles of potentially sensitive populations requires a 'tool chest' of methodological approaches to adequately characterize and evaluate these populations. At present, there is an extensive body of literature on methodologies that apply to the evaluation of...

Overview and application of the Model Optimization, Uncertainty, and SEnsitivity Analysis (MOUSE) toolbox

USDA-ARS?s Scientific Manuscript database

For several decades, optimization and sensitivity/uncertainty analysis of environmental models has been the subject of extensive research. Although much progress has been made and sophisticated methods developed, the growing complexity of environmental models to represent real-world systems makes it...

Inhibition of the spider heartbeat by gravity and vibration

NASA Technical Reports Server (NTRS)

Finck, A.

1984-01-01

The rate and vigor of the spider heartbeat is controlled by an external pacemaker. A mechanical feature of the spider cardio-vascular system is the production of high serum pressure in the prosoma and the legs. This appears to be the source for leg extension. The lyriform organ on the patella of the leg is sensitive to vibratory and kinesthetic stimuli. This sensitivity depends upon the degree of leg extension. Thus the activity of the heart and the response characteristics of the sense receptor are related. The effect of a supra-threshold vibratory or gravitational stimulus is to produce an inhibition and a tachycardia of the spider heartbeat.

"Signal-on" photoelectrochemical biosensor for sensitive detection of human T-Cell lymphotropic virus type II DNA: dual signal amplification strategy integrating enzymatic amplification with terminal deoxynucleotidyl transferase-mediated extension.

PubMed

Shen, Qingming; Han, Li; Fan, Gaochao; Zhang, Jian-Rong; Jiang, Liping; Zhu, Jun-Jie

2015-01-01

A novel "signal-on" photoelectrochemical (PEC) biosensor for sensitive detection of human T-cell lymphotropic virus type II (HTLV-II) DNA was developed on the basis of enzymatic amplification coupled with terminal deoxynucleotidyl transferase (TdT)-mediated extension strategy. The intensity of the photocurrent signal was proportional to the concentration of the HTLV-II DNA-target DNA (tDNA) by dual signal amplification. In this protocol, GR-CdS:Mn/ZnS nanocomposites were used as photoelectric conversion material, while pDNA was used as the tDNA recognizing unit. Moreover, the TdT-mediated extension and the enzymatic signal amplification technique were used to enhance the sensitivity of detection. Using this novel dual signal amplification strategy, the prototype of PEC DNA sensor can detect as low as ∼0.033 fM of HTLV-II DNA with a linear range of 0.1-5000 fM, with excellent differentiation ability even for single-base mismatches. This PEC DNA assay opens a promising platform to detect various DNA targets at ultralow levels for early diagnoses of different diseases.

A novel approach for modelling vegetation distributions and analysing vegetation sensitivity through trait-climate relationships in China

PubMed Central

Yang, Yanzheng; Zhu, Qiuan; Peng, Changhui; Wang, Han; Xue, Wei; Lin, Guanghui; Wen, Zhongming; Chang, Jie; Wang, Meng; Liu, Guobin; Li, Shiqing

2016-01-01

Increasing evidence indicates that current dynamic global vegetation models (DGVMs) have suffered from insufficient realism and are difficult to improve, particularly because they are built on plant functional type (PFT) schemes. Therefore, new approaches, such as plant trait-based methods, are urgently needed to replace PFT schemes when predicting the distribution of vegetation and investigating vegetation sensitivity. As an important direction towards constructing next-generation DGVMs based on plant functional traits, we propose a novel approach for modelling vegetation distributions and analysing vegetation sensitivity through trait-climate relationships in China. The results demonstrated that a Gaussian mixture model (GMM) trained with a LMA-Nmass-LAI data combination yielded an accuracy of 72.82% in simulating vegetation distribution, providing more detailed parameter information regarding community structures and ecosystem functions. The new approach also performed well in analyses of vegetation sensitivity to different climatic scenarios. Although the trait-climate relationship is not the only candidate useful for predicting vegetation distributions and analysing climatic sensitivity, it sheds new light on the development of next-generation trait-based DGVMs. PMID:27052108

Assessing the treatment effect in a randomized controlled trial with extensive non-adherence: the EVOLVE trial.

PubMed

Kubo, Yumi; Sterling, Lulu Ren; Parfrey, Patrick S; Gill, Karminder; Mahaffey, Kenneth W; Gioni, Ioanna; Trotman, Marie-Louise; Dehmel, Bastian; Chertow, Glenn M

2015-01-01

Intention-to-treat (ITT) analysis is widely used to establish efficacy in randomized clinical trials. However, in a long-term outcomes study where non-adherence to study drug is substantial, the on-treatment effect of the study drug may be underestimated using the ITT analysis. The analyses presented herein are from the EVOLVE trial, a double-blind, placebo-controlled, event-driven cardiovascular outcomes study conducted to assess whether a treatment regimen including cinacalcet compared with placebo in addition to other conventional therapies reduces the risk of mortality and major cardiovascular events in patients receiving hemodialysis with secondary hyperparathyroidism. Pre-specified sensitivity analyses were performed to assess the impact of non-adherence on the estimated effect of cinacalcet. These analyses included lag-censoring, inverse probability of censoring weights (IPCW), rank preserving structural failure time model (RPSFTM) and iterative parameter estimation (IPE). The relative hazard (cinacalcet versus placebo) of mortality and major cardiovascular events was 0.93 (95% confidence interval 0.85, 1.02) using the ITT analysis; 0.85 (0.76, 0.95) using lag-censoring analysis; 0.81 (0.70, 0.92) using IPCW; 0.85 (0.66, 1.04) using RPSFTM and 0.85 (0.75, 0.96) using IPE. These analyses, while not providing definitive evidence, suggest that the intervention may have an effect while subjects are receiving treatment. The ITT method remains the established method to evaluate efficacy of a new treatment; however, additional analyses should be considered to assess the on-treatment effect when substantial non-adherence to study drug is expected or observed. Copyright © 2015 John Wiley & Sons, Ltd.

The Anxiety Sensitivity Index--Revised: Confirmatory Factor Analyses, Structural Invariance in Caucasian and African American Samples, and Score Reliability and Validity

ERIC Educational Resources Information Center

Arnau, Randolph C.; Broman-Fulks, Joshua J.; Green, Bradley A.; Berman, Mitchell E.

2009-01-01

The most commonly used measure of anxiety sensitivity is the 36-item Anxiety Sensitivity Index--Revised (ASI-R). Exploratory factor analyses have produced several different factors structures for the ASI-R, but an acceptable fit using confirmatory factor analytic approaches has only been found for a 21-item version of the instrument. We evaluated…

Dandelions, tulips and orchids: evidence for the existence of low-sensitive, medium-sensitive and high-sensitive individuals.

PubMed

Lionetti, Francesca; Aron, Arthur; Aron, Elaine N; Burns, G Leonard; Jagiellowicz, Jadzia; Pluess, Michael

2018-01-22

According to empirical studies and recent theories, people differ substantially in their reactivity or sensitivity to environmental influences with some being generally more affected than others. More sensitive individuals have been described as orchids and less-sensitive ones as dandelions. Applying a data-driven approach, we explored the existence of sensitivity groups in a sample of 906 adults who completed the highly sensitive person (HSP) scale. According to factor analyses, the HSP scale reflects a bifactor model with a general sensitivity factor. In contrast to prevailing theories, latent class analyses consistently suggested the existence of three rather than two groups. While we were able to identify a highly sensitive (orchids, 31%) and a low-sensitive group (dandelions, 29%), we also detected a third group (40%) characterised by medium sensitivity, which we refer to as tulips in keeping with the flower metaphor. Preliminary cut-off scores for all three groups are provided. In order to characterise the different sensitivity groups, we investigated group differences regarding the Big Five personality traits, as well as experimentally assessed emotional reactivity in an additional independent sample. According to these follow-up analyses, the three groups differed in neuroticism, extraversion and emotional reactivity to positive mood induction with orchids scoring significantly higher in neuroticism and emotional reactivity and lower in extraversion than the other two groups (dandelions also differed significantly from tulips). Findings suggest that environmental sensitivity is a continuous and normally distributed trait but that people fall into three distinct sensitive groups along a sensitivity continuum.

Human Spaceflight Architecture Model (HSFAM) Data Dictionary

NASA Technical Reports Server (NTRS)

Shishko, Robert

2016-01-01

HSFAM is a data model based on the DoDAF 2.02 data model with some for purpose extensions. These extensions are designed to permit quantitative analyses regarding stakeholder concerns about technical feasibility, configuration and interface issues, and budgetary and/or economic viability.

Approaches for Assessing Risks to Sensitive Populations: Lessons Learned from Evaluating Risks in the Pediatric Population

EPA Science Inventory

Assessing the risk profiles of potentially sensitive populations requires a "tool chest" of methodological approaches to adequately characterize and evaluate these populations. At present, there is an extensive body of literature on methodologies that apply to the evaluation of t...

Molecular mimicry between cockroach and helminth glutathione S-transferases promotes cross-reactivity and cross-sensitization

USDA-ARS?s Scientific Manuscript database

The extensive similarities between helminth proteins and allergens are thought to contribute to helminth-driven allergic sensitization. We investigated the molecular and structural similarities between Bla g 5, a major glutathione-S transferase (GST) allergen of cockroaches, and the GST of Wucherer...

Age-related cutoffs for cervical movement behaviour to distinguish chronic idiopathic neck pain patients from unimpaired subjects.

PubMed

Niederer, Daniel; Vogt, Lutz; Wilke, Jan; Rickert, Marcus; Banzer, Winfried

2015-03-01

The present study aims to develop age-dependent cutoff values in a quasi-experimental, cross-sectional diagnostic test study. One hundred and twenty (120) asymptomatic subjects (n = 100, 36♀, 18 75 years, for normative values; n = 20, 23-75 years, 15♀, for selectivity analyses) and 20 patients suffering from idiopathic neck pain (selectivity analyses, 22-71 years, 15♀) were included. Subjects performed five repetitive maximal cervical flexion/extension movements in an upright sitting position. Cervical kinematic characteristics (maximal range of motion (ROM), coefficient of variation (CV) and mean conjunct movements in rotation and flexion (CM)) were calculated from raw 3D ultrasonic data. Regression analyses were conducted to reveal associations between kinematic characteristics and age and gender and thus to determine normative values for healthy subjects. Age explains 53 % of the variance in ROM (decrease 10.2° per decade), 13 % in CV (increase 0.003 per decade) and 9 % in CM (increase 0.57° per decade). Receivers operating characteristic (ROC) analyses were conducted for differences between individual values of the kinematic characteristics and normative values to optimise cutoff values for distinguishing patients from unimpaired subjects (20 patients and 20 healthy). Cutoff values distinguished asymptomatic subjects' and chronic nonspecific neck patient's movement characteristics with sufficient quality (sensitivity 70-80 %, specificity 65-70 %). By including such classifications, the present findings expand actual research stating an age-related decrease in kinematic behaviour only using categorising span widths across decades. Future study is warranted to reveal our results' potential applicability for intervention onset decision making for idiopathic neck pain patients.

Interaction of growth hormone receptor/binding protein gene disruption and caloric restriction for insulin sensitivity and attenuated aging

PubMed Central

Arum, Oge; Saleh, Jamal; Boparai, Ravneet; Turner, Jeremy; Kopchick, John; Khardori, Romesh; Bartke, Andrzej

2014-01-01

The correlation of physiological sensitivity to insulin ( vis-à-vis glycemic regulation) and longevity is extensively established, creating a justifiable gerontological interest on whether insulin sensitivity is causative, or even predictive, of some or all phenotypes of slowed senescence (including longevity). The growth hormone receptor/ binding protein gene-disrupted (GHR-KO) mouse is the most extensively investigated insulin-sensitive, attenuated aging model. It was reported that, in a manner divergent from similar mutants, GHR-KO mice fail to respond to caloric restriction (CR) by altering their insulin sensitivity. We hypothesized that maximized insulin responsiveness is what causes GHR-KO mice to exhibit a suppressed survivorship response to dietary (including caloric) restriction; and attempted to refute this hypothesis by assessing the effects of CR on GHR-KO mice for varied slow-aging-associated phenotypes. In contrast to previous reports, we found GHR-KO mice on CR to be less responsive than their ad libitum (A.L.) counterparts to the hypoglycemia-inducing effects of insulin. Further, CR had negligible effects on the metabolism or cognition of GHR-KO mice. Therefore, our data suggest that the effects of CR on the insulin sensitivity of GHR-KO mice do not concur with the effects of CR on the aging of GHR-KO mice. PMID:25789159

IceVeto: Extended PeV neutrino astronomy in the Southern Hemisphere with IceCube

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

Auffenberg, Jan; Collaboration: IceCube Collaboration

IceCube, the world's largest high-energy neutrino observatory, built at the South Pole, recently reported evidence of an astrophysical neutrino flux extending to PeV energies in the Southern Hemisphere. This observation raises the question of how the sensitivity in this energy range could be further increased. In the down-going sector, in IceCube's case the Southern Hemisphere, backgrounds from atmospheric muons and neutrinos pose a challenge to the identification of an astrophysical neutrino flux. The IceCube analysis, that led to the evidence for astrophysical neutrinos, is based on an in-ice veto strategy for background rejection. One possibility available to IceCube is themore » concept of an extended surface detector, IceVeto, which could allow the rejection of a large fraction of atmospheric backgrounds, primarily for muons from cosmic ray (CR) air showers as well as from neutrinos in the same air showers. Building on the experience of IceTop/IceCube, possibly the most cost-effective and sensitive way to build IceVeto is as an extension of the IceTop detector, with simple photomultiplier based detector modules for CR air shower detection. Initial simulations and estimates indicate that such a veto detector will significantly increase the sensitivity to an astrophysical flux of ν{sub μ} induced muon tracks in the Southern Hemisphere compared to current analyses. Here we present the motivation and capabilities based on initial simulations. Conceptual ideas for a simplified surface array will be discussed briefly.« less

Multiplex genotyping system for efficient inference of matrilineal genetic ancestry with continental resolution

PubMed Central

2011-01-01

Background In recent years, phylogeographic studies have produced detailed knowledge on the worldwide distribution of mitochondrial DNA (mtDNA) variants, linking specific clades of the mtDNA phylogeny with certain geographic areas. However, a multiplex genotyping system for the detection of the mtDNA haplogroups of major continental distribution that would be desirable for efficient DNA-based bio-geographic ancestry testing in various applications is still missing. Results Three multiplex genotyping assays, based on single-base primer extension technology, were developed targeting a total of 36 coding-region mtDNA variants that together differentiate 43 matrilineal haplo-/paragroups. These include the major diagnostic haplogroups for Africa, Western Eurasia, Eastern Eurasia and Native America. The assays show high sensitivity with respect to the amount of template DNA: successful amplification could still be obtained when using as little as 4 pg of genomic DNA and the technology is suitable for medium-throughput analyses. Conclusions We introduce an efficient and sensitive multiplex genotyping system for bio-geographic ancestry inference from mtDNA that provides resolution on the continental level. The method can be applied in forensics, to aid tracing unknown suspects, as well as in population studies, genealogy and personal ancestry testing. For more complete inferences of overall bio-geographic ancestry from DNA, the mtDNA system provided here can be combined with multiplex systems for suitable autosomal and, in the case of males, Y-chromosomal ancestry-sensitive DNA markers. PMID:21429198

The Effect of Polymeric Nanoparticles on Biocompatibility of Carrier Red Blood Cells

PubMed Central

Pan, Daniel; Vargas-Morales, Omayra; Zern, Blaine; Anselmo, Aaron C.; Gupta, Vivek; Zakrewsky, Michael; Mitragotri, Samir; Muzykantov, Vladimir

2016-01-01

Red blood cells (RBCs) can be used for vascular delivery of encapsulated or surface-bound drugs and carriers. Coupling to RBC prolongs circulation of nanoparticles (NP, 200 nm spheres, a conventional model of polymeric drug delivery carrier) enabling their transfer to the pulmonary vasculature without provoking overt RBC elimination. However, little is known about more subtle and potentially harmful effects of drugs and drug carriers on RBCs. Here we devised high-throughput in vitro assays to determine the sensitivity of loaded RBCs to osmotic stress and other damaging insults that they may encounter in vivo (e.g. mechanical, oxidative and complement insults). Sensitivity of these tests is inversely proportional to RBC concentration in suspension and our results suggest that mouse RBCs are more sensitive to damaging factors than human RBCs. Loading RBCs by NP at 1:50 ratio did not affect RBCs, while 10–50 fold higher NP load accentuated RBC damage by mechanical, osmotic and oxidative stress. This extensive loading of RBC by NP also leads to RBCs agglutination in buffer; however, addition of albumin diminished this effect. These results provide a template for analyses of the effects of diverse cargoes loaded on carrier RBCs and indicate that: i) RBCs can tolerate carriage of NP at doses providing loading of millions of nanoparticles per microliter of blood; ii) tests using protein-free buffers and mouse RBCs may overestimate adversity that may be encountered in humans. PMID:27003833

Sensitivity of directed networks to the addition and pruning of edges and vertices

NASA Astrophysics Data System (ADS)

Goltsev, A. V.; Timár, G.; Mendes, J. F. F.

2017-08-01

Directed networks have various topologically different extensive components, in contrast to a single giant component in undirected networks. We study the sensitivity (response) of the sizes of these extensive components in directed complex networks to the addition and pruning of edges and vertices. We introduce the susceptibility, which quantifies this sensitivity. We show that topologically different parts of a directed network have different sensitivity to the addition and pruning of edges and vertices and, therefore, they are characterized by different susceptibilities. These susceptibilities diverge at the critical point of the directed percolation transition, signaling the appearance (or disappearance) of the giant strongly connected component in the infinite size limit. We demonstrate this behavior in randomly damaged real and synthetic directed complex networks, such as the World Wide Web, Twitter, the Caenorhabditis elegans neural network, directed Erdős-Rényi graphs, and others. We reveal a nonmonotonic dependence of the sensitivity to random pruning of edges or vertices in the case of C. elegans and Twitter that manifests specific structural peculiarities of these networks. We propose the measurements of the susceptibilities during the addition or pruning of edges and vertices as a new method for studying structural peculiarities of directed networks.

Nonindependence and sensitivity analyses in ecological and evolutionary meta-analyses.

PubMed

Noble, Daniel W A; Lagisz, Malgorzata; O'dea, Rose E; Nakagawa, Shinichi

2017-05-01

Meta-analysis is an important tool for synthesizing research on a variety of topics in ecology and evolution, including molecular ecology, but can be susceptible to nonindependence. Nonindependence can affect two major interrelated components of a meta-analysis: (i) the calculation of effect size statistics and (ii) the estimation of overall meta-analytic estimates and their uncertainty. While some solutions to nonindependence exist at the statistical analysis stages, there is little advice on what to do when complex analyses are not possible, or when studies with nonindependent experimental designs exist in the data. Here we argue that exploring the effects of procedural decisions in a meta-analysis (e.g. inclusion of different quality data, choice of effect size) and statistical assumptions (e.g. assuming no phylogenetic covariance) using sensitivity analyses are extremely important in assessing the impact of nonindependence. Sensitivity analyses can provide greater confidence in results and highlight important limitations of empirical work (e.g. impact of study design on overall effects). Despite their importance, sensitivity analyses are seldom applied to problems of nonindependence. To encourage better practice for dealing with nonindependence in meta-analytic studies, we present accessible examples demonstrating the impact that ignoring nonindependence can have on meta-analytic estimates. We also provide pragmatic solutions for dealing with nonindependent study designs, and for analysing dependent effect sizes. Additionally, we offer reporting guidelines that will facilitate disclosure of the sources of nonindependence in meta-analyses, leading to greater transparency and more robust conclusions. © 2017 John Wiley & Sons Ltd.

Transportation elements assessment : Town of Milton, September 15, 2009.

DOT National Transportation Integrated Search

2009-09-15

During the summer of 2009, the Delaware T2 Center collected extensive data and completed analyses related to transportation infrastructure in the Town of Milton, Delaware. This report presents those data, the analyses, and resulting recommendations.

Transportation elements assessment : Town of Milton, November 2, 2009.

DOT National Transportation Integrated Search

2010-11-02

During the summer of 2009, the Delaware T2 Center collected extensive data and completed analyses related to transportation infrastructure in the Town of Milton, Delaware. This report presents those data, the analyses, and resulting recommendations.

Using a genetic, observational study as a strategy to estimate the potential cost-effectiveness of pharmacological CCR5 blockade in dialysis patients.

PubMed

Muntinghe, Friso L H; Vegter, Stefan; Verduijn, Marion; Boeschoten, Elisabeth W; Dekker, Friedo W; Navis, Gerjan; Postma, Maarten

2011-07-01

Randomized clinical trials are expensive and time consuming. Therefore, strategies are needed to prioritise tracks for drug development. Genetic association studies may provide such a strategy by considering the differences between genotypes as a proxy for a natural, lifelong, randomized at conception, clinical trial. Previously an association with better survival was found in dialysis patients with systemic inflammation carrying a deletion variant of the CC-chemokine receptor 5 (CCR5). We hypothesized that in an analogous manner, pharmacological CCR5 blockade could protect against inflammation-driven mortality and estimated if such a treatment would be cost-effective. A genetic screen and treat strategy was modelled using a decision-analytic Markov model, in which patients were screened for the CCR5 deletion 32 polymorphism and those with the wild type and systemic inflammation were treated with pharmacological CCR5 blockers. Kidney transplantation and mortality rates were calculated using patient level data. Extensive sensitivity analyses were performed. The cost-effectiveness of the genetic screen and treat strategy was &OV0556;18 557 per life year gained and &OV0556;21 896 per quality-adjusted life years gained. Concordance between the genetic association and pharmacological effectiveness was a main driver of cost-effectiveness. Sensitivity analyses showed that even a modest effectiveness of pharmacological CCR5 blockade would result in a treatment strategy that is good value for money. Pharmacological blockade of the CCR5 receptor in inflamed dialysis patients can be incorporated in a potentially cost-effective screen and treat programme. These findings provide formal rationale for clinical studies. This study illustrates the potential of genetic association studies for drug development, as a source of Mendelian randomized evidence from an observational setting.

Budget Impact Analysis of Biosimilar Trastuzumab for the Treatment of Breast Cancer in Croatia.

PubMed

Cesarec, August; Likić, Robert

2017-04-01

Breast cancer is the most common cancer in women and has considerable impact on healthcare budgets and patients' quality of life. Trastuzumab (Herceptin ® ) is a monoclonal antibody directed against the human epidermal growth factor receptor (HER2) for the treatment of breast cancer. Several trastuzumab biosimilars are currently in development. In 2015, trastuzumab was the drug with the highest financial consumption among all drugs in Croatia. This model estimates the 1-year budget impact of the introduction of biosimilar trastuzumab in Croatia. A budget impact model, based on approvals for trastuzumab treatment in 2015, was developed for the introduction of biosimilars. Two biosimilar scenarios were developed: biosimilar scenario 1, based on all approvals in 2015, and biosimilar scenario 2, based on approvals after February 2015 and the reimbursement of the subcutaneous formulation of trastuzumab in Croatia. Only trastuzumab-naïve patients and drug-acquisition costs were used in the model. Uptake of biosimilar was assumed at 50 %. Scenarios were calculated with price discounts of 15, 25 and 35 %. The robustness of the model was tested by extensive sensitivity analyses. The projected drug cost savings from the introduction of biosimilar trastuzumab range from €0.26 million (scenario 2, 15 % price discount) to €0.69 million (scenario 1, 35 % price discount). If budget savings were reinvested to treat additional patients with trastuzumab, 14 (scenario 2, 15 % price discount) to 47 (scenario 1, 35 % price discount) additional patients could be treated. Sensitivity analyses showed that the incidence of breast cancer had the highest impact on the model, with a 10 % decrease in incidence leading to an 11.3 % decrease in projected savings. The introduction of biosimilar trastuzumab could lead to significant drug cost savings in Croatia.

PRIORITIZING FUTURE RESEACH ON OFF-LABEL PRESCRIBING: RESULTS OF A QUANTITATIVE EVALUATION

PubMed Central

Walton, Surrey M.; Schumock, Glen T.; Lee, Ky-Van; Alexander, G. Caleb; Meltzer, David; Stafford, Randall S.

2015-01-01

Background Drug use for indications not approved by the Food and Drug Administration exceeds 20% of prescribing. Available compendia indicate that a minority of off-label uses are well supported by evidence. Policy makers, however, lack information to identify where systematic reviews of the evidence or other research would be most valuable. Methods We developed a quantitative model for prioritizing individual drugs for future research on off-label uses. The base model incorporated three key factors, 1) the volume of off-label use with inadequate evidence, 2) safety, and 3) cost and market considerations. Nationally representative prescribing data were used to estimate the number of off-label drug uses by indication from 1/2005 through 6/2007 in the United States, and these indications were then categorized according to the adequacy of scientific support. Black box warnings and safety alerts were used to quantify drug safety. Drug cost, date of market entry, and marketing expenditures were used to quantify cost and market considerations. Each drug was assigned a relative value for each factor, and the factors were then weighted in the final model to produce a priority score. Sensitivity analyses were conducted by varying the weightings and model parameters. Results Drugs that were consistently ranked highly in both our base model and sensitivity analyses included quetiapine, warfarin, escitalopram, risperidone, montelukast, bupropion, sertraline, venlafaxine, celecoxib, lisinopril, duloxetine, trazodone, olanzapine, and epoetin alfa. Conclusion Future research into off-label drug use should focus on drugs used frequently with inadequate supporting evidence, particularly if further concerns are raised by known safety issues, high drug cost, recent market entry, and extensive marketing. Based on quantitative measures of these factors, we have prioritized drugs where targeted research and policy activities have high potential value. PMID:19025425

Cost-Effectiveness of an Intervention to Reduce HIV/STI Incidence and Promote Condom Use among Female Sex Workers in the Mexico–US Border Region

PubMed Central

Burgos, José L.; Gaebler, Julia A.; Strathdee, Steffanie A.; Lozada, Remedios; Staines, Hugo; Patterson, Thomas L.

2010-01-01

Background Previous research demonstrated efficacy of a brief behavioral intervention to reduce incidence of HIV and sexually transmitted infections (STIs) among female sex workers (FSWs) in Tijuana and Ciudad Juarez, Mexico, cities on Mexico's border with the US. We assessed this intervention's cost-effectiveness. Methodology and Principal Findings A life-time Markov model was developed to estimate HIV cases prevented, changes in quality-adjusted life expectancy (QALE), and costs per additional quality-adjusted life year gained (QALY), comparing (in US$2,009) no intervention to a once-only and annual intervention. Future costs and health benefits were discounted annually at 3%. Sensitivity analyses evaluated model robustness. We found that for a hypothetical 1,000 FSWs receiving the once-only intervention, there were 33 HIV cases prevented and 5.7 months of QALE gained compared to no intervention. The additional cost per QALY gained was US$183. For FSWs receiving the intervention annually, there were 29 additional HIV cases prevented and 4.5 additional months of QALE compared to the once-only intervention. The additional cost per QALY was US$1,075. When highly active antiretroviral therapy (HAART) was included in the model, the annual intervention strategy resulted in net savings and dominated both once-only and no intervention strategies, and remained robust across extensive sensitivity analyses. Even when considering clinical benefits from HAART, ignoring added costs, the cost per QALY gained remained below three times the Mexican GDP per capita, and below established cost-effectiveness thresholds. Conclusions/Significance This brief intervention was shown to be cost-effective among FSWs in two Mexico-US border cities and may have application for FSWs in other resource-limited settings. Trial Registration ClinicalTrials.gov NCT00338845 PMID:20617193

Antidiabetogenic Effects of Chromium Mitigate Hyperinsulinemia-Induced Cellular Insulin Resistance via Correction of Plasma Membrane Cholesterol Imbalance

PubMed Central

Horvath, Emily M.; Tackett, Lixuan; McCarthy, Alicia M.; Raman, Priya; Brozinick, Joseph T.; Elmendorf, Jeffrey S.

2008-01-01

Previously, we found that a loss of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate (PIP2)-regulated filamentous actin (F-actin) structure contributes to insulin-induced insulin resistance. Interestingly, we also demonstrated that chromium picolinate (CrPic), a dietary supplement thought to improve glycemic status in insulin-resistant individuals, augments insulin-regulated glucose transport in insulin-sensitive 3T3-L1 adipocytes by lowering PM cholesterol. Here, to gain mechanistic understanding of these separate observations, we tested the prediction that CrPic would protect against insulin-induced insulin resistance by improving PM features important in cytoskeletal structure and insulin sensitivity. We found that insulin-induced insulin-resistant adipocytes display elevated PM cholesterol with a reciprocal decrease in PM PIP2. This lipid imbalance and insulin resistance was corrected by the cholesterol-lowering action of CrPic. The PM lipid imbalance did not impair insulin signaling, nor did CrPic amplify insulin signal transduction. In contrast, PM analyses corroborated cholesterol and PIP2 interactions influencing cytoskeletal structure. Because extensive in vitro study documents an essential role for cytoskeletal capacity in insulin-regulated glucose transport, we next evaluated intact skeletal muscle from obese, insulin-resistant Zucker (fa/fa) rats. Because insulin resistance in these animals likely involves multiple mechanisms, findings that cholesterol-lowering restored F-actin cytoskeletal structure and insulin sensitivity to that witnessed in lean control muscle were striking. Also, experiments using methyl-β-cyclodextrin to shuttle cholesterol into or out of membranes respectively recapitulated the insulin-induced insulin-resistance and protective effects of CrPic on membrane/cytoskeletal interactions and insulin sensitivity. These data predict a PM cholesterol basis for hyperinsulinemia-associated insulin resistance and importantly highlight the reversible nature of this abnormality. PMID:18165437

Pre-study feasibility and identifying sensitivity analyses for protocol pre-specification in comparative effectiveness research.

PubMed

Girman, Cynthia J; Faries, Douglas; Ryan, Patrick; Rotelli, Matt; Belger, Mark; Binkowitz, Bruce; O'Neill, Robert

2014-05-01

The use of healthcare databases for comparative effectiveness research (CER) is increasing exponentially despite its challenges. Researchers must understand their data source and whether outcomes, exposures and confounding factors are captured sufficiently to address the research question. They must also assess whether bias and confounding can be adequately minimized. Many study design characteristics may impact on the results; however, minimal if any sensitivity analyses are typically conducted, and those performed are post hoc. We propose pre-study steps for CER feasibility assessment and to identify sensitivity analyses that might be most important to pre-specify to help ensure that CER produces valid interpretable results.

Extended principle component analysis - a useful tool to understand processes governing water quality at catchment scales

NASA Astrophysics Data System (ADS)

Selle, B.; Schwientek, M.

2012-04-01

Water quality of ground and surface waters in catchments is typically driven by many complex and interacting processes. While small scale processes are often studied in great detail, their relevance and interplay at catchment scales remain often poorly understood. For many catchments, extensive monitoring data on water quality have been collected for different purposes. These heterogeneous data sets contain valuable information on catchment scale processes but are rarely analysed using integrated methods. Principle component analysis (PCA) has previously been applied to this kind of data sets. However, a detailed analysis of scores, which are an important result of a PCA, is often missing. Mathematically, PCA expresses measured variables on water quality, e.g. nitrate concentrations, as linear combination of independent, not directly observable key processes. These computed key processes are represented by principle components. Their scores are interpretable as process intensities which vary in space and time. Subsequently, scores can be correlated with other key variables and catchment characteristics, such as water travel times and land use that were not considered in PCA. This detailed analysis of scores represents an extension of the commonly applied PCA which could considerably improve the understanding of processes governing water quality at catchment scales. In this study, we investigated the 170 km2 Ammer catchment in SW Germany which is characterised by an above average proportion of agricultural (71%) and urban (17%) areas. The Ammer River is mainly fed by karstic springs. For PCA, we separately analysed concentrations from (a) surface waters of the Ammer River and its tributaries, (b) spring waters from the main aquifers and (c) deep groundwater from production wells. This analysis was extended by a detailed analysis of scores. We analysed measured concentrations on major ions and selected organic micropollutants. Additionally, redox-sensitive variables and environmental tracers indicating groundwater age were analysed for deep groundwater from production wells. For deep groundwater, we found that microbial turnover was stronger influenced by local availability of energy sources than by travel times of groundwater to the wells. Groundwater quality primarily reflected the input of pollutants determined by landuse, e.g. agrochemicals. We concluded that for water quality in the Ammer catchment, conservative mixing of waters with different origin is more important than reactive transport processes along the flow path.

Modular space station phase B extension preliminary systems design report. Volume 6: Trades and analyses

NASA Technical Reports Server (NTRS)

Jones, A. L.

1972-01-01

Requirements and concepts and the tradeoff analysis leading to the preferred concept are presented. Integrated analyses are given for subsystems and thermal control. Specific tradeoffs and analyses are also given for water management, atmosphere control, energy storage, radiators, navigation, control moment gyros, and system maintenance. The analyses of manipulator concepts and requirements, and supplemental analyses of information management issues are summarized. Subsystem reliability analyses include a detailed discussion of the critical failure analysis.

GLSENS: A Generalized Extension of LSENS Including Global Reactions and Added Sensitivity Analysis for the Perfectly Stirred Reactor

NASA Technical Reports Server (NTRS)

Bittker, David A.

1996-01-01

A generalized version of the NASA Lewis general kinetics code, LSENS, is described. The new code allows the use of global reactions as well as molecular processes in a chemical mechanism. The code also incorporates the capability of performing sensitivity analysis calculations for a perfectly stirred reactor rapidly and conveniently at the same time that the main kinetics calculations are being done. The GLSENS code has been extensively tested and has been found to be accurate and efficient. Nine example problems are presented and complete user instructions are given for the new capabilities. This report is to be used in conjunction with the documentation for the original LSENS code.

Using archived ITS data for sensitivity analyses in the estimation of mobile source emissions

DOT National Transportation Integrated Search

2000-12-01

The study described in this paper demonstrates the use of archived ITS data from San Antonio's TransGuide traffic management center (TMC) for sensitivity analyses in the estimation of on-road mobile source emissions. Because of the stark comparison b...

Sensitivity analysis in economic evaluation: an audit of NICE current practice and a review of its use and value in decision-making.

PubMed

Andronis, L; Barton, P; Bryan, S

2009-06-01

To determine how we define good practice in sensitivity analysis in general and probabilistic sensitivity analysis (PSA) in particular, and to what extent it has been adhered to in the independent economic evaluations undertaken for the National Institute for Health and Clinical Excellence (NICE) over recent years; to establish what policy impact sensitivity analysis has in the context of NICE, and policy-makers' views on sensitivity analysis and uncertainty, and what use is made of sensitivity analysis in policy decision-making. Three major electronic databases, MEDLINE, EMBASE and the NHS Economic Evaluation Database, were searched from inception to February 2008. The meaning of 'good practice' in the broad area of sensitivity analysis was explored through a review of the literature. An audit was undertaken of the 15 most recent NICE multiple technology appraisal judgements and their related reports to assess how sensitivity analysis has been undertaken by independent academic teams for NICE. A review of the policy and guidance documents issued by NICE aimed to assess the policy impact of the sensitivity analysis and the PSA in particular. Qualitative interview data from NICE Technology Appraisal Committee members, collected as part of an earlier study, were also analysed to assess the value attached to the sensitivity analysis components of the economic analyses conducted for NICE. All forms of sensitivity analysis, notably both deterministic and probabilistic approaches, have their supporters and their detractors. Practice in relation to univariate sensitivity analysis is highly variable, with considerable lack of clarity in relation to the methods used and the basis of the ranges employed. In relation to PSA, there is a high level of variability in the form of distribution used for similar parameters, and the justification for such choices is rarely given. Virtually all analyses failed to consider correlations within the PSA, and this is an area of concern. Uncertainty is considered explicitly in the process of arriving at a decision by the NICE Technology Appraisal Committee, and a correlation between high levels of uncertainty and negative decisions was indicated. The findings suggest considerable value in deterministic sensitivity analysis. Such analyses serve to highlight which model parameters are critical to driving a decision. Strong support was expressed for PSA, principally because it provides an indication of the parameter uncertainty around the incremental cost-effectiveness ratio. The review and the policy impact assessment focused exclusively on documentary evidence, excluding other sources that might have revealed further insights on this issue. In seeking to address parameter uncertainty, both deterministic and probabilistic sensitivity analyses should be used. It is evident that some cost-effectiveness work, especially around the sensitivity analysis components, represents a challenge in making it accessible to those making decisions. This speaks to the training agenda for those sitting on such decision-making bodies, and to the importance of clear presentation of analyses by the academic community.

Skin sensitizer identification by IL-8 secretion and CD86 expression on THP-1 cells.

PubMed

Parise, Carolina Bellini; Sá-Rocha, Vanessa Moura; Moraes, Jane Zveiter

2015-12-25

Substantial progress has been made in the development of alternative methods for skin sensitization in the last decade in several countries around the world. Brazil is experiencing an increasing concern about using animals for product development, since the publication of the Law 9605/1998, which prohibits the use of animals when an alternative method is available. In this way, an in vitro test to evaluate allergenic potential is a pressing need.This preliminary study started setting the use of myelomonocytic THP-1 cell line, according to the human cell line activation test (h-CLAT), already under validation process. We found that 48-h chemical exposure was necessary to identify 22 out of 23 sensitizers by the analyses of CD86 expression. In addition, the CD54 expression analyses presented a poor efficiency to discriminate sensitizers from non-sensitizers in our conditions. In view of these results, we looked for changes of pro-inflammatory interleukin profile. The IL-8 secretion analyses after 24-h chemical incubation seemed to be an alternative for CD54 expression assessing.Altogether, our findings showed that the combination of the analyses of CD86 expression and IL-8 secretion allowed predicting allergenicity.

Extense historical droughts in Spain derived from documentary sources

NASA Astrophysics Data System (ADS)

Dominguez-Castro, F.; García-Herrera, R.; Barriendos, M.

2009-09-01

Documentary records, specially those from rogation ceremonies have been extensively used to build proxy series of droughts and floods in Spain. Most of the work done previously has focused in the abstraction of the documents and building of the individual series, but less attention has been paid to the joint analysis of this type of records. This is problematic because, due to the diversity of Spanish climates, the climatological meaning of the rogation ceremonies changes depending on the considered region. This paper aims to analyse the spatial extension of drought events from the rogation records from Barcelona, Bilbao, Gerona, Murcia, Seville, Tarragona, Toledo, Tortosa and Zamora, which cover the 16th to 19th centuries. The representativeness of each of them is analysed taking into account the local climate and the series variability. Then the spatial scale of the recorded droughts is examined at seasonal scale. The results show high multidecadal variability, with the driest periods at national scale recorded during the 1680s, 1730s and 1780s. Finally, the dry years of 1680, 1683 and 1817 are analysed in detail.

Application of global sensitivity analysis methods to Takagi-Sugeno-Kang rainfall-runoff fuzzy models

NASA Astrophysics Data System (ADS)

Jacquin, A. P.; Shamseldin, A. Y.

2009-04-01

This study analyses the sensitivity of the parameters of Takagi-Sugeno-Kang rainfall-runoff fuzzy models previously developed by the authors. These models can be classified in two types, where the first type is intended to account for the effect of changes in catchment wetness and the second type incorporates seasonality as a source of non-linearity in the rainfall-runoff relationship. The sensitivity analysis is performed using two global sensitivity analysis methods, namely Regional Sensitivity Analysis (RSA) and Sobol's Variance Decomposition (SVD). In general, the RSA method has the disadvantage of not being able to detect sensitivities arising from parameter interactions. By contrast, the SVD method is suitable for analysing models where the model response surface is expected to be affected by interactions at a local scale and/or local optima, such as the case of the rainfall-runoff fuzzy models analysed in this study. The data of six catchments from different geographical locations and sizes are used in the sensitivity analysis. The sensitivity of the model parameters is analysed in terms of two measures of goodness of fit, assessing the model performance from different points of view. These measures are the Nash-Sutcliffe criterion and the index of volumetric fit. The results of the study show that the sensitivity of the model parameters depends on both the type of non-linear effects (i.e. changes in catchment wetness or seasonality) that dominates the catchment's rainfall-runoff relationship and the measure used to assess the model performance. Acknowledgements: This research was supported by FONDECYT, Research Grant 11070130. We would also like to express our gratitude to Prof. Kieran M. O'Connor from the National University of Ireland, Galway, for providing the data used in this study.

Effectiveness of Light Sources on In-Office Dental Bleaching: A Systematic Review and Meta-Analyses.

PubMed

SoutoMaior, J R; de Moraes, Sld; Lemos, Caa; Vasconcelos, Bc do E; Montes, Majr; Pellizzer, E P

2018-06-12

A systematic review and meta-analyses were performed to evaluate the efficacy of tooth color change and sensitivity of teeth following in-office bleaching with and without light gel activation in adult patients. This review was registered at PROSPERO (CRD 42017060574) and is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Electronic systematic searches of PubMed/MEDLINE, Web of Science, and the Cochrane Library were conducted for published articles. Only randomized clinical trials among adults that compared in-office bleaching with and without light activation with the same bleaching gel concentrations were selected. The outcomes were tooth color change and tooth sensitivity prevalence and intensity. Twenty-three articles from 1054 data sources met the eligibility criteria. After title and abstract screening, 39 studies remained. Sixteen studies were further excluded. Twenty-three studies remained for qualitative analyses and 20 for meta-analyses of primary and secondary outcomes. No significant differences in tooth color change or tooth sensitivity incidence were found between the compared groups; however, tooth sensitivity intensity decreased when light sources were applied. The use of light sources for in-office bleaching is not imperative to achieve esthetic clinical results.

Design and evaluation of a failure detection and isolation algorithm for restructurable control systems

NASA Technical Reports Server (NTRS)

Weiss, Jerold L.; Hsu, John Y.

1986-01-01

The use of a decentralized approach to failure detection and isolation for use in restructurable control systems is examined. This work has produced: (1) A method for evaluating fundamental limits to FDI performance; (2) Application using flight recorded data; (3) A working control element FDI system with maximal sensitivity to critical control element failures; (4) Extensive testing on realistic simulations; and (5) A detailed design methodology involving parameter optimization (with respect to model uncertainties) and sensitivity analyses. This project has concentrated on detection and isolation of generic control element failures since these failures frequently lead to emergency conditions and since knowledge of remaining control authority is essential for control system redesign. The failures are generic in the sense that no temporal failure signature information was assumed. Thus, various forms of functional failures are treated in a unified fashion. Such a treatment results in a robust FDI system (i.e., one that covers all failure modes) but sacrifices some performance when detailed failure signature information is known, useful, and employed properly. It was assumed throughout that all sensors are validated (i.e., contain only in-spec errors) and that only the first failure of a single control element needs to be detected and isolated. The FDI system which has been developed will handle a class of multiple failures.

The role of the geophysical template and environmental regimes in controlling stream-living trout populations

USGS Publications Warehouse

Penaluna, Brooke E.; Railsback, Steve F.; Dunham, Jason B.; Johnson, S.; Bilby, Richard E.; Skaugset, Arne E.

2015-01-01

The importance of multiple processes and instream factors to aquatic biota has been explored extensively, but questions remain about how local spatiotemporal variability of aquatic biota is tied to environmental regimes and the geophysical template of streams. We used an individual-based trout model to explore the relative role of the geophysical template versus environmental regimes on biomass of trout (Oncorhynchus clarkii clarkii). We parameterized the model with observed data from each of the four headwater streams (their local geophysical template and environmental regime) and then ran 12 simulations where we replaced environmental regimes (stream temperature, flow, turbidity) of a given stream with values from each neighboring stream while keeping the geophysical template fixed. We also performed single-parameter sensitivity analyses on the model results from each of the four streams. Although our modeled findings show that trout biomass is most responsive to changes in the geophysical template of streams, they also reveal that biomass is restricted by available habitat during seasonal low flow, which is a product of both the stream’s geophysical template and flow regime. Our modeled results suggest that differences in the geophysical template among streams render trout more or less sensitive to environmental change, emphasizing the importance of local fish–habitat relationships in streams.

A Serum Protein Profile Predictive of the Resistance to Neoadjuvant Chemotherapy in Advanced Breast Cancers*

PubMed Central

Hyung, Seok-Won; Lee, Min Young; Yu, Jong-Han; Shin, Byunghee; Jung, Hee-Jung; Park, Jong-Moon; Han, Wonshik; Lee, Kyung-Min; Moon, Hyeong-Gon; Zhang, Hui; Aebersold, Ruedi; Hwang, Daehee; Lee, Sang-Won; Yu, Myeong-Hee; Noh, Dong-Young

2011-01-01

Prediction of the responses to neoadjuvant chemotherapy (NACT) can improve the treatment of patients with advanced breast cancer. Genes and proteins predictive of chemoresistance have been extensively studied in breast cancer tissues. However, noninvasive serum biomarkers capable of such prediction have been rarely exploited. Here, we performed profiling of N-glycosylated proteins in serum from fifteen advanced breast cancer patients (ten patients sensitive to and five patients resistant to NACT) to discover serum biomarkers of chemoresistance using a label-free liquid chromatography-tandem MS method. By performing a series of statistical analyses of the proteomic data, we selected thirteen biomarker candidates and tested their differential serum levels by Western blotting in 13 independent samples (eight patients sensitive to and five patients resistant to NACT). Among the candidates, we then selected the final set of six potential serum biomarkers (AHSG, APOB, C3, C9, CP, and ORM1) whose differential expression was confirmed in the independent samples. Finally, we demonstrated that a multivariate classification model using the six proteins could predict responses to NACT and further predict relapse-free survival of patients. In summary, global N-glycoproteome profile in serum revealed a protein pattern predictive of the responses to NACT, which can be further validated in large clinical studies. PMID:21799047

Displaying chest X-ray by beamer or monitor: comparison of diagnostic accuracy for subtle abnormalities.

PubMed

Kuiper, L M; Thijs, A; Smulders, Y M

2012-01-01

The advent of beamer projection of radiological images raises the issue of whether such projection compromises diagnostic accuracy. The purpose of this study was to evaluate whether beamer projection of chest X-rays is inferior to monitor display. We selected 53 chest X-rays with subtle abnormalities and 15 normal X-rays. The images were independently judged by a senior radiologist and a senior pulmonologist with a state-of-art computer monitor. We used their unanimous or consensus judgment as the reference test. Subsequently, four observers (one senior pulmonologist, one senior radiologist and one resident from each speciality) judged these X-rays on a standard clinical computer monitor and with beamer projection. We compared the number of correct results for each method. Overall, the sensitivity and specificity did not differ between monitor and beamer projection. Separate analyses in senior and junior examiners suggested that senior examiners had a moderate loss of diagnostic accuracy (8% lower sensitivity, pp<0.05, and 6% lower specificity, p=ns) associated with the use of beamer projection, whereas juniors showed similar performance on both imaging modalities. These initial data suggest that beamer projection may be associated with a small loss of diagnostic accuracy in specific subgroups of physicians. This finding illustrates the need for more extensive studies.

Transportation elements assessment : Town of Milton, Delaware, September 29, 2009.

DOT National Transportation Integrated Search

2009-09-29

During the summer of 2009, the Delaware T2 Center collected extensive data : and completed analyses related to transportation infrastructure in the Town : of Milton, Delaware. This report presents those data, the analyses, and : resulting recommendat...

Community Concerns and Extension Youth Programs. Proceedings Regional Conference (February 18-20, 1981). Publication 28.

ERIC Educational Resources Information Center

White, Leigh Cree, Ed.

The 4-H/Community Resource Development workshop was designed to help people conducting Extension 4-H programs on sensitive and complex community issues improve their ability to create a better climate for discussion of alternatives and development of community projects. Topics of the presentations included the role of the 4-H administrator,…

Identification of Novel Glycosyltransferases Required for Assembly of the Pasteurella multocida A:1 Lipopolysaccharide and Their Involvement in Virulence▿ †

PubMed Central

Boyce, John D.; Harper, Marina; St. Michael, Frank; John, Marietta; Aubry, Annie; Parnas, Henrietta; Logan, Susan M.; Wilkie, Ian W.; Ford, Mark; Cox, Andrew D.; Adler, Ben

2009-01-01

We previously determined the structure of the Pasteurella multocida Heddleston type 1 lipopolysaccharide (LPS) molecule and characterized some of the transferases essential for LPS biosynthesis. We also showed that P. multocida strains expressing truncated LPS display reduced virulence. Here, we have identified all of the remaining glycosyltransferases required for synthesis of the oligosaccharide extension of the P. multocida Heddleston type 1 LPS, including a novel α-1,6 glucosyltransferase, a β-1,4 glucosyltransferase, a putative bifunctional galactosyltransferase, and two heptosyltransferases. In addition, we identified a novel oligosaccharide extension expressed only in a heptosyltransferase (hptE) mutant background. All of the analyzed mutants expressing LPS with a truncated main oligosaccharide extension displayed reduced virulence, but those expressing LPS with an intact heptose side chain were able to persist for long periods in muscle tissue. The hptC mutant, which expressed LPS with the shortest oligosaccharide extension and no heptose side chain, was unable to persist on the muscle or cause any disease. Furthermore, all of the mutants displayed increased sensitivity to the chicken antimicrobial peptide fowlicidin 1, with mutants expressing highly truncated LPS being the most sensitive. PMID:19168738

Testing Extension Services through AKAP Models

ERIC Educational Resources Information Center

De Rosa, Marcello; Bartoli, Luca; La Rocca, Giuseppe

2014-01-01

Purpose: The aim of the paper is to analyse the attitude of Italian farms in gaining access to agricultural extension services (AES). Design/methodology/approach: The ways Italian farms use AES are described through the AKAP (Awareness, Knowledge, Adoption, Product) sequence. This article investigated the AKAP sequence by submitting a…

Sensitivity analysis of static resistance of slender beam under bending

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

Valeš, Jan

2016-06-08

The paper deals with statical and sensitivity analyses of resistance of simply supported I-beams under bending. The resistance was solved by geometrically nonlinear finite element method in the programme Ansys. The beams are modelled with initial geometrical imperfections following the first eigenmode of buckling. Imperfections were, together with geometrical characteristics of cross section, and material characteristics of steel, considered as random quantities. The method Latin Hypercube Sampling was applied to evaluate statistical and sensitivity resistance analyses.

Prediction of coefficients of thermal expansion for unidirectional composites

NASA Technical Reports Server (NTRS)

Bowles, David E.; Tompkins, Stephen S.

1989-01-01

Several analyses for predicting the longitudinal, alpha(1), and transverse, alpha(2), coefficients of thermal expansion of unidirectional composites were compared with each other, and with experimental data on different graphite fiber reinforced resin, metal, and ceramic matrix composites. Analytical and numerical analyses that accurately accounted for Poisson restraining effects in the transverse direction were in consistently better agreement with experimental data for alpha(2), than the less rigorous analyses. All of the analyses predicted similar values of alpha(1), and were in good agreement with the experimental data. A sensitivity analysis was conducted to determine the relative influence of constituent properties on the predicted values of alpha(1), and alpha(2). As would be expected, the prediction of alpha(1) was most sensitive to longitudinal fiber properties and the prediction of alpha(2) was most sensitive to matrix properties.

Extension of the Thoracic Spine Sign: A New Sonographic Marker of Pleural Effusion.

PubMed

Dickman, Eitan; Terentiev, Victoria; Likourezos, Antonios; Derman, Anna; Haines, Lawrence

2015-09-01

Dyspnea is a common emergency department (ED) condition, which may be caused by pleural effusion and other thoracic diseases. We present data on a new sonographic marker, the extension of the thoracic spine sign, for diagnosis of pleural effusion. In this prospective study, we enrolled a convenience sample of undifferentiated patients who underwent computed tomography (CT) of the abdomen or chest, which was performed as part of their emergency department evaluations. Patients underwent chest sonography to assess the utility of the extension of the thoracic spine sign for diagnosing pleural effusion. The point-of-care sonographic examinations were performed and interpreted by emergency physicians who were blinded to information in the medical records. Sonographic results were compared to radiologists' interpretations of the CT results, which were considered the criterion standard. Forty-one patients were enrolled, accounting for 82 hemithoraces. Seven hemithoraces were excluded from the analysis due to various limitations, leaving 75 hemithoraces for the final analysis. The median time for completion of the sonographic examination was 3 minutes. The sensitivity and specificity for extension of the thoracic spine were 73.7% (95% confidence interval [CI], 48.6%-89.9%) and 92.9% (95%CI, 81.9%-97.7%), respectively. Overall, there were 5 hemithoraces with false-negative results when using the extension sign. Of those 5 cases, 4 were found to have trace pleural effusions on CT. When trace pleural effusions were excluded in a subgroup analysis, the sensitivity and specificity of extension of the thoracic spine were 92.9% (95% CI, 64.2%-99.6%) and 92.9% (95% CI, 81.9%-97.7%). We found the extension of the thoracic spine sign to be an excellent diagnostic tool for clinically relevant pleural effusion. © 2015 by the American Institute of Ultrasound in Medicine.

Changes in monosaccharides, organic acids and amino acids during Cabernet Sauvignon wine ageing based on a simultaneous analysis using gas chromatography-mass spectrometry.

PubMed

Zhang, Xin-Ke; Lan, Yi-Bin; Zhu, Bao-Qing; Xiang, Xiao-Feng; Duan, Chang-Qing; Shi, Ying

2018-01-01

Monosaccharides, organic acids and amino acids are the important flavour-related components in wines. The aim of this article is to develop and validate a method that could simultaneously analyse these compounds in wine based on silylation derivatisation and gas chromatography-mass spectrometry (GC-MS), and apply this method to the investigation of the changes of these compounds and speculate upon their related influences on Cabernet Sauvignon wine flavour during wine ageing. This work presented a new approach for wine analysis and provided more information concerning red wine ageing. This method could simultaneously quantitatively analyse 2 monosaccharides, 8 organic acids and 13 amino acids in wine. A validation experiment showed good linearity, sensitivity, reproducibility and recovery. Multiple derivatives of five amino acids have been found but their effects on quantitative analysis were negligible, except for methionine. The evolution pattern of each category was different, and we speculated that the corresponding mechanisms involving microorganism activities, physical interactions and chemical reactions had a great correlation with red wine flavours during ageing. Simultaneously quantitative analysis of monosaccharides, organic acids and amino acids in wine was feasible and reliable and this method has extensive application prospects. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Recent inner ear specialization for high-speed hunting in cheetahs.

PubMed

Grohé, Camille; Lee, Beatrice; Flynn, John J

2018-02-02

The cheetah, Acinonyx jubatus, is the fastest living land mammal. Because of its specialized hunting strategy, this species evolved a series of specialized morphological and functional body features to increase its exceptional predatory performance during high-speed hunting. Using high-resolution X-ray computed micro-tomography (μCT), we provide the first analyses of the size and shape of the vestibular system of the inner ear in cats, an organ essential for maintaining body balance and adapting head posture and gaze direction during movement in most vertebrates. We demonstrate that the vestibular system of modern cheetahs is extremely different in shape and proportions relative to other cats analysed (12 modern and two fossil felid species), including a closely-related fossil cheetah species. These distinctive attributes (i.e., one of the greatest volumes of the vestibular system, dorsal extension of the anterior and posterior semicircular canals) correlate with a greater afferent sensitivity of the inner ear to head motions, facilitating postural and visual stability during high-speed prey pursuit and capture. These features are not present in the fossil cheetah A. pardinensis, that went extinct about 126,000 years ago, demonstrating that the unique and highly specialized inner ear of the sole living species of cheetah likely evolved extremely recently, possibly later than the middle Pleistocene.

Calculations to support JET neutron yield calibration: Modelling of neutron emission from a compact DT neutron generator

NASA Astrophysics Data System (ADS)

Čufar, Aljaž; Batistoni, Paola; Conroy, Sean; Ghani, Zamir; Lengar, Igor; Milocco, Alberto; Packer, Lee; Pillon, Mario; Popovichev, Sergey; Snoj, Luka; JET Contributors

2017-03-01

At the Joint European Torus (JET) the ex-vessel fission chambers and in-vessel activation detectors are used as the neutron production rate and neutron yield monitors respectively. In order to ensure that these detectors produce accurate measurements they need to be experimentally calibrated. A new calibration of neutron detectors to 14 MeV neutrons, resulting from deuterium-tritium (DT) plasmas, is planned at JET using a compact accelerator based neutron generator (NG) in which a D/T beam impinges on a solid target containing T/D, producing neutrons by DT fusion reactions. This paper presents the analysis that was performed to model the neutron source characteristics in terms of energy spectrum, angle-energy distribution and the effect of the neutron generator geometry. Different codes capable of simulating the accelerator based DT neutron sources are compared and sensitivities to uncertainties in the generator's internal structure analysed. The analysis was performed to support preparation to the experimental measurements performed to characterize the NG as a calibration source. Further extensive neutronics analyses, performed with this model of the NG, will be needed to support the neutron calibration experiments and take into account various differences between the calibration experiment and experiments using the plasma as a source of neutrons.

Autocatalytic Patterning with Silver Using Tin(II) Chloride Sensitizer

ERIC Educational Resources Information Center

Mbindyo, Jeremiah K. N.; Anna, Laura J.; Fell, B. Andrew; Patton, David A.

2011-01-01

A silver mirror can be deposited on many types of surfaces from the reduction of the silver-diammine complex by a reducing sugar as proposed by Kemp in this "Journal". Three extensions of Kemp's demonstration that highlight the role of SnCl[subscript 2] sensitizer in the deposition of a silver mirror on surfaces are presented. The demonstration…

Preparation of the implementation plan of AASHTO Mechanistic-Empirical Pavement Design Guide (M-EPDG) in Connecticut : Phase II : expanded sensitivity analysis and validation with pavement management data.

DOT National Transportation Integrated Search

2017-02-08

The study re-evaluates distress prediction models using the Mechanistic-Empirical Pavement Design Guide (MEPDG) and expands the sensitivity analysis to a wide range of pavement structures and soils. In addition, an extensive validation analysis of th...

The Roles of MAPK Cascades in Synaptic Plasticity and Memory in "Aplysia": Facilitatory Effects and Inhibitory Constraints

ERIC Educational Resources Information Center

Sharma, Shiv K.; Carew, Thomas J.

2004-01-01

Synaptic plasticity is thought to contribute to memory formation. Serotonin-induced facilitation of sensory-motor (SN-MN) synapses in "Aplysia" is an extensively studied cellular analog of memory for sensitization. Serotonin, a modulatory neurotransmitter, is released in the CNS during sensitization training, and induces three temporally and…

Ultra-sensitive PSA Following Prostatectomy Reliably Identifies Patients Requiring Post-Op Radiotherapy

PubMed Central

Kang, Jung Julie; Reiter, Robert; Steinberg, Michael; King, Christopher R.

2015-01-01

PURPOSE Integrating ultra-sensitive PSA (uPSA) into surveillance of high-risk patients following radical prostatectomy (RP) potentially optimizes management by correctly identifying actual recurrences, promoting an early salvage strategy and minimizing overtreatment. The power of uPSA following surgery to identify eventual biochemical failures is tested. PATIENTS AND METHODS From 1991–2013, 247 high-risk patients with a median follow-up was 44 months after RP were identified (extraprostatic extension and/or positive margin). Surgical technique, initial PSA (iPSA), pathology and post-op PSA were analyzed. The uPSA assay threshold was 0.01 ng/mL. Conventional biochemical relapse (cBCR) was defined as PSA ≥0.2 ng/mL. Kaplan Meier and Cox multivariate analyses (MVA) compared uPSA recurrence vs. cBCR rates. RESULTS Sensitivity analysis identified uPSA ≥0.03 as the optimal threshold identifying recurrence. First post-op uPSA ≥0.03, Gleason grade, T-stage, iPSA, and margin status predicted cBCR. On MVA, only first post-op uPSA ≥0.03, Gleason grade, and T-stage independently predicted cBCR. First post-op uPSA ≥0.03 conferred the highest risk (HR 8.5, p<0.0001) and discerned cBCR with greater sensitivity than undetectable first conventional PSA (70% vs. 46%). Any post-op PSA ≥0.03 captured all failures missed by first post-op value (100% sensitivity) with accuracy (96% specificity). Defining failure at uPSA ≥0.03 yielded a median lead-time advantage of 18 months (mean 24 months) over the conventional PSA ≥0.2 definition. CONCLUSION uPSA ≥0.03 is an independent factor, identifies BCR more accurately than any traditional risk factors, and confers a significant lead-time advantage. uPSA enables critical decisions regarding timing and indication for post-op RT among high-risk patients following RP. PMID:25463990

Extensive human suffering: a point prevalence survey of patients' most distressing concerns during inpatient care.

PubMed

Fridh, Isabell; Kenne Sarenmalm, Elisabeth; Falk, Kristin; Henoch, Ingela; Öhlén, Joakim; Ozanne, Anneli; Jakobsson Ung, Eva

2015-09-01

To explore patients' most distressing concerns during a hospital stay. The characteristics of hospitalised patients have changed. Care is provided at a higher age, lengths of stay have fallen and the nursing workload is increasing. It is presumed that hospitalised patients are more seriously ill and have more palliative needs than previously. Studies show that inpatients suffer from more distress than similar outpatients although there is a lack of overall knowledge about inpatients' distress and major concerns, regardless of age, diagnosis or care setting. This study was part of a point prevalence survey (PPS) concerning symptom prevalence. Of the 710 patients who participated in the PPS, 678 (95%) answered an open-ended question in a questionnaire: What is your main concern or what is most distressing or troublesome for you at present? Using a life-world approach, the text was analysed qualitatively and patients' concerns were interpreted in two main dimensions, an intersubjective dimension and a temporal dimension. The patients reported extensive suffering due to illness, symptoms and failing health. Patients were concerned about family members, existential issues and the future. Three aspects of the patients' most distressing concerns were interpreted: The suffering self, The suffering person in close relations and The suffering person in a threatening world. Hospitalised patients are affected by severe illness, distressing symptoms and existential quandaries, revealing extensive human suffering in the midst of the demanding activities that take place during an ordinary day in a hospital. To support patients and alleviate suffering, hospital staff need to be more sensitive to patients' most distressing concerns. This presupposes a hospital environment in which the value system supports caring and comforting behaviour. © 2014 Nordic College of Caring Science.

Multiple primer extension by DNA polymerase on a novel plastic DNA array coated with a biocompatible polymer

PubMed Central

Kinoshita, Kenji; Fujimoto, Kentaro; Yakabe, Toru; Saito, Shin; Hamaguchi, Yuzo; Kikuchi, Takayuki; Nonaka, Ken; Murata, Shigenori; Masuda, Daisuke; Takada, Wataru; Funaoka, Sohei; Arai, Susumu; Nakanishi, Hisao; Yokoyama, Kanehisa; Fujiwara, Kazuhiko; Matsubara, Kenichi

2007-01-01

DNA microarrays are routinely used to monitor gene expression profiling and single nucleotide polymorphisms (SNPs). However, for practically useful high performance, the detection sensitivity is still not adequate, leaving low expression genes undetected. To resolve this issue, we have developed a new plastic S-BIO® PrimeSurface® with a biocompatible polymer; its surface chemistry offers an extraordinarily stable thermal property for a lack of pre-activated glass slide surface. The oligonucleotides immobilized on this substrate are robust in boiling water and show no significant loss of hybridization activity during dissociation treatment. This allowed us to hybridize the templates, extend the 3′ end of the immobilized DNA primers on the S-Bio® by DNA polymerase using deoxynucleotidyl triphosphates (dNTP) as extender units, release the templates by denaturalization and use the same templates for a second round of reactions similar to that of the PCR method. By repeating this cycle, the picomolar concentration range of the template oligonucleotide can be detected as stable signals via the incorporation of labeled dUTP into primers. This method of Multiple Primer EXtension (MPEX) could be further extended as an alternative route for producing DNA microarrays for SNP analyses via simple template preparation such as reverse transcript cDNA or restriction enzyme treatment of genome DNA. PMID:17135189

Self-perceived weather sensitivity and joint pain in older people with osteoarthritis in six European countries: results from the European Project on OSteoArthritis (EPOSA)

PubMed Central

2014-01-01

Background People with osteoarthritis (OA) frequently report that their joint pain is influenced by weather conditions. This study aimed to examine whether there are differences in perceived joint pain between older people with OA who reported to be weather-sensitive versus those who did not in six European countries with different climates and to identify characteristics of older persons with OA that are most predictive of perceived weather sensitivity. Methods Baseline data from the European Project on OSteoArthritis (EPOSA) were used. ACR classification criteria were used to determine OA. Participants with OA were asked about their perception of weather as influencing their pain. Using a two-week follow-up pain calendar, average self-reported joint pain was assessed (range: 0 (no pain)-10 (greatest pain intensity)). Linear regression analyses, logistic regression analyses and an independent t-test were used. Analyses were adjusted for several confounders. Results The majority of participants with OA (67.2%) perceived the weather as affecting their pain. Weather-sensitive participants reported more pain than non-weather-sensitive participants (M = 4.1, SD = 2.4 versus M = 3.1, SD = 2.4; p < 0.001). After adjusting for several confounding factors, the association between self-perceived weather sensitivity and joint pain remained present (B = 0.37, p = 0.03). Logistic regression analyses revealed that women and more anxious people were more likely to report weather sensitivity. Older people with OA from Southern Europe were more likely to indicate themselves as weather-sensitive persons than those from Northern Europe. Conclusions Weather (in)stability may have a greater impact on joint structures and pain perception in people from Southern Europe. The results emphasize the importance of considering weather sensitivity in daily life of older people with OA and may help to identify weather-sensitive older people with OA. PMID:24597710

Self-perceived weather sensitivity and joint pain in older people with osteoarthritis in six European countries: results from the European Project on OSteoArthritis (EPOSA).

PubMed

Timmermans, Erik J; van der Pas, Suzan; Schaap, Laura A; Sánchez-Martínez, Mercedes; Zambon, Sabina; Peter, Richard; Pedersen, Nancy L; Dennison, Elaine M; Denkinger, Michael; Castell, Maria Victoria; Siviero, Paola; Herbolsheimer, Florian; Edwards, Mark H; Otero, Angel; Deeg, Dorly J H

2014-03-05

People with osteoarthritis (OA) frequently report that their joint pain is influenced by weather conditions. This study aimed to examine whether there are differences in perceived joint pain between older people with OA who reported to be weather-sensitive versus those who did not in six European countries with different climates and to identify characteristics of older persons with OA that are most predictive of perceived weather sensitivity. Baseline data from the European Project on OSteoArthritis (EPOSA) were used. ACR classification criteria were used to determine OA. Participants with OA were asked about their perception of weather as influencing their pain. Using a two-week follow-up pain calendar, average self-reported joint pain was assessed (range: 0 (no pain)-10 (greatest pain intensity)). Linear regression analyses, logistic regression analyses and an independent t-test were used. Analyses were adjusted for several confounders. The majority of participants with OA (67.2%) perceived the weather as affecting their pain. Weather-sensitive participants reported more pain than non-weather-sensitive participants (M = 4.1, SD = 2.4 versus M = 3.1, SD = 2.4; p < 0.001). After adjusting for several confounding factors, the association between self-perceived weather sensitivity and joint pain remained present (B = 0.37, p = 0.03). Logistic regression analyses revealed that women and more anxious people were more likely to report weather sensitivity. Older people with OA from Southern Europe were more likely to indicate themselves as weather-sensitive persons than those from Northern Europe. Weather (in)stability may have a greater impact on joint structures and pain perception in people from Southern Europe. The results emphasize the importance of considering weather sensitivity in daily life of older people with OA and may help to identify weather-sensitive older people with OA.

Constitutive BAK activation as a determinant of drug sensitivity in malignant lymphohematopoietic cells

PubMed Central

Dai, Haiming; Ding, Husheng; Meng, X. Wei; Peterson, Kevin L.; Schneider, Paula A.; Karp, Judith E.; Kaufmann, Scott H.

2015-01-01

Mitochondrial outer membrane permeabilization (MOMP), a key step in the intrinsic apoptotic pathway, is incompletely understood. Current models emphasize the role of BH3-only BCL2 family members in BAX and BAK activation. Here we demonstrate concentration-dependent BAK autoactivation under cell-free conditions and provide evidence that this autoactivation plays a key role in regulating the intrinsic apoptotic pathway in intact cells. In particular, we show that up to 80% of BAK (but not BAX) in lymphohematopoietic cell lines is oligomerized and bound to anti-apoptotic BCL2 family members in the absence of exogenous death stimuli. The extent of this constitutive BAK oligomerization is diminished by BAK knockdown and unaffected by BIM or PUMA down-regulation. Further analysis indicates that sensitivity of cells to BH3 mimetics reflects the identity of the anti-apoptotic proteins to which BAK is constitutively bound, with extensive BCLXL•BAK complexes predicting navitoclax sensitivity, and extensive MCL1•BAK complexes predicting A1210477 sensitivity. Moreover, high BAK expression correlates with sensitivity of clinical acute myelogenous leukemia to chemotherapy, whereas low BAK levels correlate with resistance and relapse. Collectively, these results inform current understanding of MOMP and provide new insight into the ability of BH3 mimetics to induce apoptosis without directly activating BAX or BAK. PMID:26494789

Modular space station phase B extension preliminary system design. Volume 5: configuration analyses

NASA Technical Reports Server (NTRS)

Stefan, A. J.; Goble, G. J.

1972-01-01

The initial and growth modular space station configurations are described, and the evolutionary steps arriving at the final configuration are outlined. Supporting tradeoff studies and analyses such as stress, radiation dosage, and micrometeoroid and thermal protection are included.

Sources of sensitization, cross-reactions, and occupational sensitization to topical anaesthetics among general dermatology patients.

PubMed

Jussi, Liippo; Lammintausta, Kaija

2009-03-01

Contact sensitization to local anaesthetics is often from topical medicaments. Occupational sensitization to topical anaesthetics may occur in certain occupations. The aim of the study was to analyse the occurrence of contact sensitization to topical anaesthetics in general dermatology patients. Patch testing with topical anaesthetics was carried out in 620 patients. Possible sources of sensitization and the clinical histories of the patients are analysed. Positive patch test reactions to one or more topical anaesthetics were seen in 25/620 patients. Dibucaine reactions were most common (20/25), and lidocaine sensitization was seen in two patients. Six patients had reactions to ester-type and/or amide-type anaesthetics concurrently. Local preparations for perianal conditions were the most common sensitizers. One patient had developed occupational sensitization to procaine with multiple cross-reactions and with concurrent penicillin sensitization from procaine penicillin. Dibucaine-containing perianal medicaments are the major source of contact sensitization to topical anaesthetics. Although sensitization to multiple anaesthetics can be seen, cross-reactions are possible. Contact sensitization to lidocaine is not common, and possible cross-reactions should be determined when reactions to lidocaine are seen. Occupational procaine sensitization from veterinary medicaments is a risk among animal workers.

78 FR 65242 - Occupational Exposure to Crystalline Silica; Extension of Comment Period; Extension of Period To...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... scientific and technical analyses, OSHA requests that you disclose: (1) The nature of any financial... such as social security numbers and birthdates. If you submit scientific or technical studies or other... data and technical information submitted to the record. This request is consistent with Executive Order...

Factors of Role Conflict among Livestock Extension Professionals in Andhra Pradesh, India

ERIC Educational Resources Information Center

Sasidhar, P. V. K.; Rao, B. Sudhakar; Sreeramulu, Piedy

2008-01-01

To know the factors of role conflict among livestock extension professionals in Andhra Pradesh, India. Study was conducted following ex-post facto research design. Data were collected from 180 respondents through survey questionnaires. The data were subjected to multiple regression and path analyses to know the factors of role conflict.…

What Makes Small-Scale Farmers Participate in Financing Agricultural Research and Extension? Analysis of Three Case Studies from Benin

ERIC Educational Resources Information Center

Moumouni, Ismail M.; Vodouhe, Simplice D.; Streiffeler, Friedhelm

2009-01-01

This paper analyses the organizational, financial and technological incentives that service organizations used to motivate farmers to finance agricultural research and extension in Benin. Understanding the foundations and implications of these motivation systems is important for improving farmer financial participation in agricultural research and…

Overview of Sensitivity Analysis and Shape Optimization for Complex Aerodynamic Configurations

NASA Technical Reports Server (NTRS)

Newman, Perry A.; Newman, James C., III; Barnwell, Richard W.; Taylor, Arthur C., III; Hou, Gene J.-W.

1998-01-01

This paper presents a brief overview of some of the more recent advances in steady aerodynamic shape-design sensitivity analysis and optimization, based on advanced computational fluid dynamics. The focus here is on those methods particularly well- suited to the study of geometrically complex configurations and their potentially complex associated flow physics. When nonlinear state equations are considered in the optimization process, difficulties are found in the application of sensitivity analysis. Some techniques for circumventing such difficulties are currently being explored and are included here. Attention is directed to methods that utilize automatic differentiation to obtain aerodynamic sensitivity derivatives for both complex configurations and complex flow physics. Various examples of shape-design sensitivity analysis for unstructured-grid computational fluid dynamics algorithms are demonstrated for different formulations of the sensitivity equations. Finally, the use of advanced, unstructured-grid computational fluid dynamics in multidisciplinary analyses and multidisciplinary sensitivity analyses within future optimization processes is recommended and encouraged.

Differential effects of context on psychomotor sensitization to ethanol and cocaine.

PubMed

Didone, Vincent; Quoilin, Caroline; Dieupart, Julie; Tirelli, Ezio; Quertemont, Etienne

2016-04-01

Repeated drug injections lead to sensitization of their stimulant effects in mice, a phenomenon sometimes referred to as drug psychomotor sensitization. Previous studies showed that sensitization to cocaine is context dependent as its expression is reduced in an environment that was not paired with cocaine administration. In contrast, the effects of the test context on ethanol sensitization remain unclear. In the present study, female OF1 mice were repeatedly injected with 1.5 g/kg ethanol to test for both the effects of context novelty/familiarity and association on ethanol sensitization. A first group of mice was extensively pre-exposed to the test context before ethanol sensitization and ethanol injections were paired with the test context (familiar and paired group). A second group was not pre-exposed to the test context, but ethanol injections were paired with the test context (nonfamiliar and paired group). Finally, a third group of mice was not pre-exposed to the test context and ethanol was repeatedly injected in the home cage (unpaired group). Control groups were similarly exposed to the test context, but were injected with saline. In a second experiment, cocaine was used as a positive control. The same behavioral procedure was used, except that mice were injected with 10 mg/kg cocaine instead of ethanol. The results show a differential involvement of the test context in the sensitization to ethanol and cocaine. Cocaine sensitization is strongly context dependent and is not expressed in the unpaired group. In contrast, the expression of ethanol sensitization is independent of the context in which it was administered, but is strongly affected by the relative novelty/familiarity of the environment. Extensive pre-exposure to the test context prevented the expression of ethanol sensitization. One possible explanation is that expression of ethanol sensitization requires an arousing environment.

Sensitivity analyses of stopping distance for connected vehicles at active highway-rail grade crossings.

PubMed

Hsu, Chung-Jen; Jones, Elizabeth G

2017-02-01

This paper performs sensitivity analyses of stopping distance for connected vehicles (CVs) at active highway-rail grade crossings (HRGCs). Stopping distance is the major safety factor at active HRGCs. A sensitivity analysis is performed for each variable in the function of stopping distance. The formulation of stopping distance treats each variable as a probability density function for implementing Monte Carlo simulations. The result of the sensitivity analysis shows that the initial speed is the most sensitive factor to stopping distances of CVs and non-CVs. The safety of CVs can be further improved by the early provision of onboard train information and warnings to reduce the initial speeds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Balancing data sharing requirements for analyses with data sensitivity

USGS Publications Warehouse

Jarnevich, C.S.; Graham, J.J.; Newman, G.J.; Crall, A.W.; Stohlgren, T.J.

2007-01-01

Data sensitivity can pose a formidable barrier to data sharing. Knowledge of species current distributions from data sharing is critical for the creation of watch lists and an early warning/rapid response system and for model generation for the spread of invasive species. We have created an on-line system to synthesize disparate datasets of non-native species locations that includes a mechanism to account for data sensitivity. Data contributors are able to mark their data as sensitive. This data is then 'fuzzed' in mapping applications and downloaded files to quarter-quadrangle grid cells, but the actual locations are available for analyses. We propose that this system overcomes the hurdles to data sharing posed by sensitive data. ?? 2006 Springer Science+Business Media B.V.

The Sensitivity of Genetic Connectivity Measures to Unsampled and Under-Sampled Sites

PubMed Central

Koen, Erin L.; Bowman, Jeff; Garroway, Colin J.; Wilson, Paul J.

2013-01-01

Landscape genetic analyses assess the influence of landscape structure on genetic differentiation. It is rarely possible to collect genetic samples from all individuals on the landscape and thus it is important to assess the sensitivity of landscape genetic analyses to the effects of unsampled and under-sampled sites. Network-based measures of genetic distance, such as conditional genetic distance (cGD), might be particularly sensitive to sampling intensity because pairwise estimates are relative to the entire network. We addressed this question by subsampling microsatellite data from two empirical datasets. We found that pairwise estimates of cGD were sensitive to both unsampled and under-sampled sites, and FST, Dest, and deucl were more sensitive to under-sampled than unsampled sites. We found that the rank order of cGD was also sensitive to unsampled and under-sampled sites, but not enough to affect the outcome of Mantel tests for isolation by distance. We simulated isolation by resistance and found that although cGD estimates were sensitive to unsampled sites, by increasing the number of sites sampled the accuracy of conclusions drawn from landscape genetic analyses increased, a feature that is not possible with pairwise estimates of genetic differentiation such as FST, Dest, and deucl. We suggest that users of cGD assess the sensitivity of this measure by subsampling within their own network and use caution when making extrapolations beyond their sampled network. PMID:23409155

Temporal and taxonomic contrasts in coral growth at Davies Reef, central Great Barrier Reef, Australia

NASA Astrophysics Data System (ADS)

Anderson, Kristen D.; Cantin, Neal E.; Heron, Scott F.; Lough, Janice M.; Pratchett, Morgan S.

2018-06-01

Demographic processes, such as growth, can have an important influence on the population and community structure of reef-building corals. Importantly, ongoing changes in environmental conditions (e.g. ocean warming) are expected to affect coral growth, contributing to changes in the structure of coral populations and communities. This study quantified contemporary growth rates (linear extension and calcification) for the staghorn coral, Acropora muricata, at Davies Reef, central Great Barrier Reef, Australia. Growth rates were measured at three different depths (5, 10, and 15 m) over 2 yr (2012-2014) assessing both seasonal and inter-annual variability. Results of this study were compared to equivalent measurements made in 1980-1982 at the same location. To assist in understanding inter-annual variability in coral growth, we also examined annual growth bands from massive Porites providing continuous growth and records of flooding history for Davies Reef over the period 1979-2012. Linear extension rates of A. muricata were substantially (11-62%) lower in 2012-2014 compared to 1980-1982, especially at 10 and 15 m depths. These declines in growth coincide with a + 0.14 °C change in annual mean temperature. For massive Porites, however, calcification rates were highly variable among years and there was no discernible long-term change in growth despite sustained increases in temperature of 0.064 °C per decade. Apparent differences in the growth rates of Acropora between 1980-1982 and 2012-2014 may reflect inter-annual variation in coral growth (as seen for massive Porites), though it is known branching Acropora is much more sensitive to changing environmental conditions than massive corals. There are persistent issues in assessing the sensitivities of branching corals to environmental change due to limited capacity for retrospective analyses of growth, but given their disproportionate contribution to habitat complexity and reef structure, it is critical to ascertain whether there are increasing impacts on their demography.

Univariate and bivariate likelihood-based meta-analysis methods performed comparably when marginal sensitivity and specificity were the targets of inference.

PubMed

Dahabreh, Issa J; Trikalinos, Thomas A; Lau, Joseph; Schmid, Christopher H

2017-03-01

To compare statistical methods for meta-analysis of sensitivity and specificity of medical tests (e.g., diagnostic or screening tests). We constructed a database of PubMed-indexed meta-analyses of test performance from which 2 × 2 tables for each included study could be extracted. We reanalyzed the data using univariate and bivariate random effects models fit with inverse variance and maximum likelihood methods. Analyses were performed using both normal and binomial likelihoods to describe within-study variability. The bivariate model using the binomial likelihood was also fit using a fully Bayesian approach. We use two worked examples-thoracic computerized tomography to detect aortic injury and rapid prescreening of Papanicolaou smears to detect cytological abnormalities-to highlight that different meta-analysis approaches can produce different results. We also present results from reanalysis of 308 meta-analyses of sensitivity and specificity. Models using the normal approximation produced sensitivity and specificity estimates closer to 50% and smaller standard errors compared to models using the binomial likelihood; absolute differences of 5% or greater were observed in 12% and 5% of meta-analyses for sensitivity and specificity, respectively. Results from univariate and bivariate random effects models were similar, regardless of estimation method. Maximum likelihood and Bayesian methods produced almost identical summary estimates under the bivariate model; however, Bayesian analyses indicated greater uncertainty around those estimates. Bivariate models produced imprecise estimates of the between-study correlation of sensitivity and specificity. Differences between methods were larger with increasing proportion of studies that were small or required a continuity correction. The binomial likelihood should be used to model within-study variability. Univariate and bivariate models give similar estimates of the marginal distributions for sensitivity and specificity. Bayesian methods fully quantify uncertainty and their ability to incorporate external evidence may be useful for imprecisely estimated parameters. Copyright © 2017 Elsevier Inc. All rights reserved.

Local cost structures and the economics of robot assisted radical prostatectomy.

PubMed

Scales, Charles D; Jones, Peter J; Eisenstein, Eric L; Preminger, Glenn M; Albala, David M

2005-12-01

Robot assisted prostatectomy (RAP) is more costly than traditional radical retropubic prostatectomy (RRP) under the cost structures at certain hospitals. However, this finding may not be the case in all care settings. We investigated the sensitivity of RAP and RRP inpatient costs to variations in length of stay (LOS), local hospitalization costs and robotic case volume in the specialist and generalist settings. We developed a model of RAP vs RRP costs in the specialist and generalist settings using published data on operative time and LOS, and cost data from our academic medical center. All inpatient cost centers were included, namely surgery costs, professional fees, postoperative care, robotic equipment and service. Extensive 1 and 2-way sensitivity analyses were performed. Our base case model demonstrated a cost premium for RAP vs RRP of USD $783 and $195 in the specialist and generalist settings, respectively. Sensitivity analysis of our model assumptions demonstrated that RAP could achieve cost equivalence with RRP at a surgical volume of 10 cases weekly. If case volume increased to 14 cases weekly, RAP would be less expensive than RRP in some practice settings in which RAP LOS was less than 1.5 days. The inpatient costs of robotic assisted prostatectomy are volume dependent and cost equivalence with generalist radical retropubic prostatectomy is possible at higher volume RAP specialty centers. While RAP may be cost competitive with RRP at high cost hospitals or high volume RAP specialist centers, this procedure would exist at a cost premium to RRP in other practice settings.

Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles for highly specific capture of N-linked glycopeptides.

PubMed

Chen, Yajing; Xiong, Zhichao; Zhang, Lingyi; Zhao, Jiaying; Zhang, Quanqing; Peng, Li; Zhang, Weibing; Ye, Mingliang; Zou, Hanfa

2015-02-21

Highly selective and efficient capture of glycosylated proteins and peptides from complex biological samples is of profound significance for the discovery of disease biomarkers in biological systems. Recently, hydrophilic interaction liquid chromatography (HILIC)-based functional materials have been extensively utilized for glycopeptide enrichment. However, the low amount of immobilized hydrophilic groups on the affinity material has limited its specificity, detection sensitivity and binding capacity in the capture of glycopeptides. Herein, a novel affinity material was synthesized to improve the binding capacity and detection sensitivity for glycopeptides by coating a poly(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). The thick polymer shell endows the nanoparticles with excellent hydrophilic property and several functional groups on the polymer chains. The resulting Fe3O4@SiO2@PMSA demonstrated an outstanding ability for glycopeptide enrichment with high selectivity, extremely high detection sensitivity (0.1 fmol), large binding capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid magnetic separation. Furthermore, in the analysis of real complicated biological samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were reliably identified in three replicate analyses of a 65 μg protein sample extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the detection and identification of low-abundance N-linked glycopeptides in biological samples.

Multiplex Amplification Coupled with COLD-PCR and High Resolution Melting Enables Identification of Low-Abundance Mutations in Cancer Samples with Low DNA Content

PubMed Central

Milbury, Coren A.; Chen, Clark C.; Mamon, Harvey; Liu, Pingfang; Santagata, Sandro; Makrigiorgos, G. Mike

2011-01-01

Thorough screening of cancer-specific biomarkers, such as DNA mutations, can require large amounts of genomic material; however, the amount of genomic material obtained from some specimens (such as biopsies, fine-needle aspirations, circulating-DNA or tumor cells, and histological slides) may limit the analyses that can be performed. Furthermore, mutant alleles may be at low-abundance relative to wild-type DNA, reducing detection ability. We present a multiplex-PCR approach tailored to amplify targets of interest from small amounts of precious specimens, for extensive downstream detection of low-abundance alleles. Using 3 ng of DNA (1000 genome-equivalents), we amplified the 1 coding exons (2-11) of TP53 via multiplex-PCR. Following multiplex-PCR, we performed COLD-PCR (co-amplification of major and minor alleles at lower denaturation temperature) to enrich low-abundance variants and high resolution melting (HRM) to screen for aberrant melting profiles. Mutation-positive samples were sequenced. Evaluation of mutation-containing dilutions revealed improved sensitivities after COLD-PCR over conventional-PCR. COLD-PCR improved HRM sensitivity by approximately threefold to sixfold. Similarly, COLD-PCR improved mutation identification in sequence-chromatograms over conventional PCR. In clinical specimens, eight mutations were detected via conventional-PCR-HRM, whereas 12 were detected by COLD-PCR-HRM, yielding a 33% improvement in mutation detection. In summary, we demonstrate an efficient approach to increase screening capabilities from limited DNA material via multiplex-PCR and improve mutation detection sensitivity via COLD-PCR amplification. PMID:21354058

Hamstring and Quadriceps Isokinetic Strength Deficits Are Weak Risk Factors for Hamstring Strain Injuries: A 4-Year Cohort Study.

PubMed

van Dyk, Nicol; Bahr, Roald; Whiteley, Rodney; Tol, Johannes L; Kumar, Bhavesh D; Hamilton, Bruce; Farooq, Abdulaziz; Witvrouw, Erik

2016-07-01

A hamstring strain injury (HSI) has become the most common noncontact injury in soccer. Isokinetic muscle strength deficits are considered a risk factor for HSIs. However, underpowered studies with small sample sizes unable to determine small associations have led to inconclusive results regarding the role of isokinetic strength and strength testing in HSIs. To examine whether differences in isokinetic strength measures of knee flexion and extension represent risk factors for hamstring injuries in a large cohort of professional soccer players in an adequately powered study design. Cohort study; Level of evidence, 2. A total of 614 professional soccer players from 14 teams underwent isokinetic strength testing during preseason screening. Testing consisted of concentric knee flexion and extension at 60 deg/s and 300 deg/s and eccentric knee extension at 60 deg/s. A clustered multiple logistic regression analysis was used to identify variables associated with the risk of HSIs. Receiver operating characteristic (ROC) curves were calculated to determine sensitivity and specificity. Of the 614 players, 190 suffered an HSI during the 4 seasons. Quadriceps concentric strength at 60 deg/s (odds ratio [OR], 1.41; 95% CI, 1.03-1.92; P = .03) and hamstring eccentric strength at 60 deg/s (OR, 1.37; 95% CI, 1.01-1.85; P = .04) adjusted for bodyweight were independently associated with the risk of injuries. The absolute differences between the injured and uninjured players were 6.9 N·m and 9.1 N·m, with small effect sizes (d < 0.2). The ROC analyses showed an area under the curve of 0.54 and 0.56 for quadriceps concentric strength and hamstring eccentric strength, respectively, indicating a failed combined sensitivity and specificity of the 2 strength variables identified in the logistic regression models. This study identified small absolute strength differences and a wide overlap of the absolute strength measurements at the group level. The small associations between lower hamstring eccentric strength and lower quadriceps concentric strength with HSIs can only be considered as weak risk factors. The identification of these risk factors still does not allow the identification of individual players at risk. The use of isokinetic testing to determine the association between strength differences and HSIs is not supported. © 2016 The Author(s).

Health economic comparison of SLIT allergen and SCIT allergoid immunotherapy in patients with seasonal grass-allergic rhinoconjunctivitis in Germany.

PubMed

Verheggen, Bram G; Westerhout, Kirsten Y; Schreder, Carl H; Augustin, Matthias

2015-01-01

Allergoids are chemically modified allergen extracts administered to reduce allergenicity and to maintain immunogenicity. Oralair® (the 5-grass tablet) is a sublingual native grass allergen tablet for pre- and co-seasonal treatment. Based on a literature review, meta-analysis, and cost-effectiveness analysis the relative effects and costs of the 5-grass tablet versus a mix of subcutaneous allergoid compounds for grass pollen allergic rhinoconjunctivitis were assessed. A Markov model with a time horizon of nine years was used to assess the costs and effects of three-year immunotherapy treatment. Relative efficacy expressed as standardized mean differences was estimated using an indirect comparison on symptom scores extracted from available clinical trials. The Rhinitis Symptom Utility Index (RSUI) was applied as a proxy to estimate utility values for symptom scores. Drug acquisition and other medical costs were derived from published sources as well as estimates for resource use, immunotherapy persistence, and occurrence of asthma. The analysis was executed from the German payer's perspective, which includes payments of the Statutory Health Insurance (SHI) and additional payments by insurants. Comprehensive deterministic and probabilistic sensitivity analyses and different scenarios were performed to test the uncertainty concerning the incremental model outcomes. The applied model predicted a cost-utility ratio of the 5-grass tablet versus a market mix of injectable allergoid products of € 12,593 per QALY in the base case analysis. Predicted incremental costs and QALYs were € 458 (95% confidence interval, CI: € 220; € 739) and 0.036 (95% CI: 0.002; 0.078), respectively. Compared to the allergoid mix the probability of the 5-grass tablet being the most cost-effective treatment option was predicted to be 76% at a willingness-to-pay threshold of € 20,000. The results were most sensitive to changes in efficacy estimates, duration of the pollen season, and immunotherapy persistence rates. This analysis suggests the sublingual native 5-grass tablet to be cost-effective relative to a mix of subcutaneous allergoid compounds. The robustness of these statements has been confirmed in extensive sensitivity and scenario analyses.

Space shuttle orbiter digital data processing system timing sensitivity analysis OFT ascent phase

NASA Technical Reports Server (NTRS)

Lagas, J. J.; Peterka, J. J.; Becker, D. A.

1977-01-01

Dynamic loads were investigated to provide simulation and analysis of the space shuttle orbiter digital data processing system (DDPS). Segments of the ascent test (OFT) configuration were modeled utilizing the information management system interpretive model (IMSIM) in a computerized simulation modeling of the OFT hardware and software workload. System requirements for simulation of the OFT configuration were defined, and sensitivity analyses determined areas of potential data flow problems in DDPS operation. Based on the defined system requirements and these sensitivity analyses, a test design was developed for adapting, parameterizing, and executing IMSIM, using varying load and stress conditions for model execution. Analyses of the computer simulation runs are documented, including results, conclusions, and recommendations for DDPS improvements.

Interdependency of the maximum range of flexion-extension of hand metacarpophalangeal joints.

PubMed

Gracia-Ibáñez, V; Vergara, M; Sancho-Bru, J-L

2016-12-01

Mobility of the fingers metacarpophalangeal (MCP) joints depends on the posture of the adjacent ones. Current Biomechanical hand models consider fixed ranges of movement at joints, regardless of the posture, thus allowing for non-realistic postures, generating wrong results in reach studies and forward dynamic analyses. This study provides data for more realistic hand models. The maximum voluntary extension (MVE) and flexion (MVF) of different combinations of MCP joints were measured covering their range of motion. Dependency of the MVF and MVE on the posture of the adjacent MCP joints was confirmed and mathematical models obtained through regression analyses (RMSE 7.7°).

The Negative Affect Hypothesis of Noise Sensitivity

PubMed Central

Shepherd, Daniel; Heinonen-Guzejev, Marja; Heikkilä, Kauko; Dirks, Kim N.; Hautus, Michael J.; Welch, David; McBride, David

2015-01-01

Some studies indicate that noise sensitivity is explained by negative affect, a dispositional tendency to negatively evaluate situations and the self. Individuals high in such traits may report a greater sensitivity to other sensory stimuli, such as smell, bright light and pain. However, research investigating the relationship between noise sensitivity and sensitivity to stimuli associated with other sensory modalities has not always supported the notion of a common underlying trait, such as negative affect, driving them. Additionally, other explanations of noise sensitivity based on cognitive processes have existed in the clinical literature for over 50 years. Here, we report on secondary analyses of pre-existing laboratory (n = 74) and epidemiological (n = 1005) data focusing on the relationship between noise sensitivity to and annoyance with a variety of olfactory-related stimuli. In the first study a correlational design examined the relationships between noise sensitivity, noise annoyance, and perceptual ratings of 16 odors. The second study sought differences between mean noise and air pollution annoyance scores across noise sensitivity categories. Results from both analyses failed to support the notion that, by itself, negative affectivity explains sensitivity to noise. PMID:25993104

One Facility's Experience Using the Community Readiness Model to Guide Services for Gay, Lesbian, Bisexual, and Transgender Older Adults

ERIC Educational Resources Information Center

Carlson, Laurie A.; Harper, Kelly S.

2011-01-01

Service provision to gay, lesbian, bisexual, and transgender (GLBT) older adults is a dynamic and sensitive area, requiring rigorous and extensive inquiry and action. Examining the readiness and assets of organizations serving GLBT older adults requires not only heart and sensitivity but also resources and a clear vision. The Community Readiness…

10 CFR 2.307 - Extension and reduction of time limits; delegated authority to order use of procedures for access...

Code of Federal Regulations, 2010 CFR

2010-01-01

... authority to order use of procedures for access by potential parties to certain sensitive unclassified... authority to order use of procedures for access by potential parties to certain sensitive unclassified... Commission or the presiding officer. (b) If this part does not prescribe a time limit for an action to be...

Enviromentally sensitive patch index of desertification risk applied to the main habitats of Sicily

NASA Astrophysics Data System (ADS)

Duro, A.; Piccione, V.; Ragusa, M. A.; Rapicavoli, V.; Veneziano, V.

2017-07-01

The authors applied the MEDALUS - Mediterranean Desertification and Land Use - procedure to the most representative sicilian habitat by extension, socio-economic and environmental importance, in order to assess the risk of desertification. Thanks to the ESPI, Environmentally Sensitive Patch Index, in this paper the authors estimate the current and future regional levels of desertification risk.

Comparison of pelvic phased-array versus endorectal coil magnetic resonance imaging at 3 Tesla for local staging of prostate cancer.

PubMed

Kim, Bum Soo; Kim, Tae-Hwan; Kwon, Tae Gyun; Yoo, Eun Sang

2012-05-01

Several studies have demonstrated the superiority of endorectal coil magnetic resonance imaging (MRI) over pelvic phased-array coil MRI at 1.5 Tesla for local staging of prostate cancer. However, few have studied which evaluation is more accurate at 3 Tesla MRI. In this study, we compared the accuracy of local staging of prostate cancer using pelvic phased-array coil or endorectal coil MRI at 3 Tesla. Between January 2005 and May 2010, 151 patients underwent radical prostatectomy. All patients were evaluated with either pelvic phased-array coil or endorectal coil prostate MRI prior to surgery (63 endorectal coils and 88 pelvic phased-array coils). Tumor stage based on MRI was compared with pathologic stage. We calculated the specificity, sensitivity and accuracy of each group in the evaluation of extracapsular extension and seminal vesicle invasion. Both endorectal coil and pelvic phased-array coil MRI achieved high specificity, low sensitivity and moderate accuracy for the detection of extracapsular extension and seminal vesicle invasion. There were statistically no differences in specificity, sensitivity and accuracy between the two groups. Overall staging accuracy, sensitivity and specificity were not significantly different between endorectal coil and pelvic phased-array coil MRI.

Piezoresistive Cantilever Performance—Part I: Analytical Model for Sensitivity

PubMed Central

Park, Sung-Jin; Doll, Joseph C.; Pruitt, Beth L.

2010-01-01

An accurate analytical model for the change in resistance of a piezoresistor is necessary for the design of silicon piezoresistive transducers. Ion implantation requires a high-temperature oxidation or annealing process to activate the dopant atoms, and this treatment results in a distorted dopant profile due to diffusion. Existing analytical models do not account for the concentration dependence of piezoresistance and are not accurate for nonuniform dopant profiles. We extend previous analytical work by introducing two nondimensional factors, namely, the efficiency and geometry factors. A practical benefit of this efficiency factor is that it separates the process parameters from the design parameters; thus, designers may address requirements for cantilever geometry and fabrication process independently. To facilitate the design process, we provide a lookup table for the efficiency factor over an extensive range of process conditions. The model was validated by comparing simulation results with the experimentally determined sensitivities of piezoresistive cantilevers. We performed 9200 TSUPREM4 simulations and fabricated 50 devices from six unique process flows; we systematically explored the design space relating process parameters and cantilever sensitivity. Our treatment focuses on piezoresistive cantilevers, but the analytical sensitivity model is extensible to other piezoresistive transducers such as membrane pressure sensors. PMID:20336183

Piezoresistive Cantilever Performance-Part I: Analytical Model for Sensitivity.

PubMed

Park, Sung-Jin; Doll, Joseph C; Pruitt, Beth L

2010-02-01

An accurate analytical model for the change in resistance of a piezoresistor is necessary for the design of silicon piezoresistive transducers. Ion implantation requires a high-temperature oxidation or annealing process to activate the dopant atoms, and this treatment results in a distorted dopant profile due to diffusion. Existing analytical models do not account for the concentration dependence of piezoresistance and are not accurate for nonuniform dopant profiles. We extend previous analytical work by introducing two nondimensional factors, namely, the efficiency and geometry factors. A practical benefit of this efficiency factor is that it separates the process parameters from the design parameters; thus, designers may address requirements for cantilever geometry and fabrication process independently. To facilitate the design process, we provide a lookup table for the efficiency factor over an extensive range of process conditions. The model was validated by comparing simulation results with the experimentally determined sensitivities of piezoresistive cantilevers. We performed 9200 TSUPREM4 simulations and fabricated 50 devices from six unique process flows; we systematically explored the design space relating process parameters and cantilever sensitivity. Our treatment focuses on piezoresistive cantilevers, but the analytical sensitivity model is extensible to other piezoresistive transducers such as membrane pressure sensors.

Determining the strengths of HCP slip systems using harmonic analyses of lattice strain distributions

DOE PAGES

Dawson, Paul R.; Boyce, Donald E.; Park, Jun-Sang; ...

2017-10-15

A robust methodology is presented to extract slip system strengths from lattice strain distributions for polycrystalline samples obtained from high-energy x-ray diffraction (HEXD) experiments with in situ loading. The methodology consists of matching the evolution of coefficients of a harmonic expansion of the distributions from simulation to the coefficients derived from measurements. Simulation results are generated via finite element simulations of virtual polycrystals that are subjected to the loading history applied in the HEXD experiments. Advantages of the methodology include: (1) its ability to utilize extensive data sets generated by HEXD experiments; (2) its ability to capture trends in distributionsmore » that may be noisy (both measured and simulated); and (3) its sensitivity to the ratios of the family strengths. The approach is used to evaluate the slip system strengths of Ti-6Al-4V using samples having relatively equiaxed grains. These strength estimates are compared to values in the literature.« less

Search for the electroweak production of supersymmetric particles in $$\\sqrt{s}$$ = 8 TeV $pp$ collisions with the ATLAS detector

DOE PAGES

Aad, G.; Abbott, B.; Abdallah, J.; ...

2016-03-04

In this study, the ATLAS experiment has performed extensive searches for the electroweak production of charginos, neutralinos, and staus. This article summarizes and extends the search for electroweak supersymmetry with new analyses targeting scenarios not covered by previously published searches. New searches use vector-boson fusion production, initial-state radiation jets, and low-momentum lepton final states, as well as multivariate analysis techniques to improve the sensitivity to scenarios with small mass splittings and low-production cross sections. Results are based on 20 fb -1 of proton-proton collision data at √s = 8 TeV recorded with the ATLAS experiment at the Large Hadron Collider.more » No significant excess beyond Standard Model expectations is observed. The new and existing searches are combined and interpreted in terms of 95% confidence-level exclusion limits in simplified models, where a single production process and decay mode is assumed, as well as within phenomenological supersymmetric models.« less

Synthesis and characterization of an energetic compound Cu(Mtta)2(NO3)2 and effect on thermal decomposition of ammonium perchlorate.

PubMed

Yang, Qi; Chen, Sanping; Xie, Gang; Gao, Shengli

2011-12-15

An energetic coordination compound Cu(Mtta)(2)(NO(3))(2) has been synthesized by using 1-methyltetrazole (Mtta) as ligand and its structure has been characterized by X-ray single crystal diffraction. The central copper (II) cation was coordinated by four O atoms from two Mtta ligands and two N atoms from two NO(3)(-) anions to form a six-coordinated and distorted octahedral structure. 2D superamolecular layer structure was formed by the extensive intermolecular hydrogen bonds between Mtta ligands and NO(3)(-) anions. Thermal decomposition process of the compound was predicted based on DSC and TG-DTG analyses results. The kinetic parameters of the first exothermic process of the compound were studied by the Kissinger's and Ozawa-Doyle's methods. Sensitivity tests revealed that the compound was insensitive to mechanical stimuli. In addition, compound was explored as additive to promote the thermal decomposition of ammonium perchlorate (AP) by differential scanning calorimetry. Copyright © 2011 Elsevier B.V. All rights reserved.

Neuroimaging in psychiatric pharmacogenetics research: the promise and pitfalls.

PubMed

Falcone, Mary; Smith, Ryan M; Chenoweth, Meghan J; Bhattacharjee, Abesh Kumar; Kelsoe, John R; Tyndale, Rachel F; Lerman, Caryn

2013-11-01

The integration of research on neuroimaging and pharmacogenetics holds promise for improving treatment for neuropsychiatric conditions. Neuroimaging may provide a more sensitive early measure of treatment response in genetically defined patient groups, and could facilitate development of novel therapies based on an improved understanding of pathogenic mechanisms underlying pharmacogenetic associations. This review summarizes progress in efforts to incorporate neuroimaging into genetics and treatment research on major psychiatric disorders, such as schizophrenia, major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, and addiction. Methodological challenges include: performing genetic analyses in small study populations used in imaging studies; inclusion of patients with psychiatric comorbidities; and the extensive variability across studies in neuroimaging protocols, neurobehavioral task probes, and analytic strategies. Moreover, few studies use pharmacogenetic designs that permit testing of genotype × drug effects. As a result of these limitations, few findings have been fully replicated. Future studies that pre-screen participants for genetic variants selected a priori based on drug metabolism and targets have the greatest potential to advance the science and practice of psychiatric treatment.

Feasibility of Using Microsoft Kinect to Assess Upper Limb Movement in Type III Spinal Muscular Atrophy Patients

PubMed Central

Siebourg-Polster, Juliane; Wolf, Detlef; Czech, Christian; Bonati, Ulrike; Fischer, Dirk; Khwaja, Omar; Strahm, Martin

2017-01-01

Although functional rating scales are being used increasingly as primary outcome measures in spinal muscular atrophy (SMA), sensitive and objective assessment of early-stage disease progression and drug efficacy remains challenging. We have developed a game based on the Microsoft Kinect sensor, specifically designed to measure active upper limb movement. An explorative study was conducted to determine the feasibility of this new tool in 18 ambulant SMA type III patients and 19 age- and gender-matched healthy controls. Upper limb movement was analysed elaborately through derived features such as elbow flexion and extension angles, arm lifting angle, velocity and acceleration. No significant differences were found in the active range of motion between ambulant SMA type III patients and controls. Hand velocity was found to be different but further validation is necessary. This study presents an important step in the process of designing and handling digital biomarkers as complementary outcome measures for clinical trials. PMID:28122039

Analysis of telomerase activity based on a spired DNA tetrahedron TS primer.

PubMed

Li, Yan; Wen, Yanli; Wang, Lele; Liang, Wen; Xu, Li; Ren, Shuzhen; Zou, Ziying; Zuo, Xiaolei; Fan, Chunhai; Huang, Qing; Liu, Gang; Jia, Nengqin

2015-05-15

The development of sensitive telomerase biosensors is hindered by the restricted accessibility of telomere strand (TS) primer and the limited enzyme reaction space, which is mainly confined by the vertical distance. In this work, we designed an electrochemical telomerase biosensor based on a spired DNA tetrahedron TS primer (STTS). By adding a rigid dsDNA spire onto the top of the DNA tetrahedron, we successfully regulated the distance between the TS primer and the surface, and thus greatly facilitated the telomerase elongation on surface. The signal-to-noise ratio was 2 times higher than TSP without the spire structure. The limit of detection was calculated to be lower than 10 HeLa cells, which is at least 2 magnitudes lower than other surface extension-based electrochemical telomerase sensors without amplification. The practicability of STTS sensor was also demonstrated by analysing various other cell lines including cancer cells, stem cells of high telomerase activity and somatic cells of low telomerase activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Structural changes in white matter are uniquely related to children’s reading development

PubMed Central

Myers, Chelsea A.; Vandermosten, Maaike; Farris, Emily A.; Hancock, Roeland; Gimenez, Paul; Black, Jessica M.; Casto, Brandi; Drahos, Miroslav; Tumber, Mandeep; Hendren, Robert L.; Hulme, Charles; Hoeft, Fumiko

2014-01-01

This study examined whether variations in brain development between kindergarten and Grade 3 predicted individual differences in reading ability at the latter time point. Structural MRI measurements indicated that increases in volume of two left temporo-parietal white matter clusters are unique predictors of reading outcome at Grade 3. Using diffusion MRI, the larger of these two clusters was identified as a location where fibers of the long segment of arcuate fasciculus and superior corona radiata intersect, and the smaller cluster as the posterior arcuate fasciculus. Bias-free regression analyses using regions-of-interest from prior literature revealed white matter volume changes in temporo-parietal white matter, together with preliteracy measures, predicted 56% of the variance in reading outcomes. Our findings demonstrate the important contribution of developmental differences in areas of left dorsal white matter, often implicated in phonological processing, as a sensitive early biomarker for later reading abilities, and by extension, reading difficulties. PMID:25212581

Bayesian analysis of longitudinal dyadic data with informative missing data using a dyadic shared-parameter model.

PubMed

Ahn, Jaeil; Morita, Satoshi; Wang, Wenyi; Yuan, Ying

2017-01-01

Analyzing longitudinal dyadic data is a challenging task due to the complicated correlations from repeated measurements and within-dyad interdependence, as well as potentially informative (or non-ignorable) missing data. We propose a dyadic shared-parameter model to analyze longitudinal dyadic data with ordinal outcomes and informative intermittent missing data and dropouts. We model the longitudinal measurement process using a proportional odds model, which accommodates the within-dyad interdependence using the concept of the actor-partner interdependence effects, as well as dyad-specific random effects. We model informative dropouts and intermittent missing data using a transition model, which shares the same set of random effects as the longitudinal measurement model. We evaluate the performance of the proposed method through extensive simulation studies. As our approach relies on some untestable assumptions on the missing data mechanism, we perform sensitivity analyses to evaluate how the analysis results change when the missing data mechanism is misspecified. We demonstrate our method using a longitudinal dyadic study of metastatic breast cancer.

Feasibility of Using Microsoft Kinect to Assess Upper Limb Movement in Type III Spinal Muscular Atrophy Patients.

PubMed

Chen, Xing; Siebourg-Polster, Juliane; Wolf, Detlef; Czech, Christian; Bonati, Ulrike; Fischer, Dirk; Khwaja, Omar; Strahm, Martin

2017-01-01

Although functional rating scales are being used increasingly as primary outcome measures in spinal muscular atrophy (SMA), sensitive and objective assessment of early-stage disease progression and drug efficacy remains challenging. We have developed a game based on the Microsoft Kinect sensor, specifically designed to measure active upper limb movement. An explorative study was conducted to determine the feasibility of this new tool in 18 ambulant SMA type III patients and 19 age- and gender-matched healthy controls. Upper limb movement was analysed elaborately through derived features such as elbow flexion and extension angles, arm lifting angle, velocity and acceleration. No significant differences were found in the active range of motion between ambulant SMA type III patients and controls. Hand velocity was found to be different but further validation is necessary. This study presents an important step in the process of designing and handling digital biomarkers as complementary outcome measures for clinical trials.

The Matching Relation and Situation-Specific Bias Modulation in Professional Football Play Selection

PubMed Central

Stilling, Stephanie T; Critchfield, Thomas S

2010-01-01

The utility of a quantitative model depends on the extent to which its fitted parameters vary systematically with environmental events of interest. Professional football statistics were analyzed to determine whether play selection (passing versus rushing plays) could be accounted for with the generalized matching equation, and in particular whether variations in play selection across game situations would manifest as changes in the equation's fitted parameters. Statistically significant changes in bias were found for each of five types of game situations; no systematic changes in sensitivity were observed. Further analyses suggested relationships between play selection bias and both turnover probability (which can be described in terms of punishment) and yards-gained variance (which can be described in terms of variable-magnitude reinforcement schedules). The present investigation provides a useful demonstration of association between face-valid, situation-specific effects in a domain of everyday interest, and a theoretically important term of a quantitative model of behavior. Such associations, we argue, are an essential focus in translational extensions of quantitative models. PMID:21119855

Bayesian generalized least squares regression with application to log Pearson type 3 regional skew estimation

NASA Astrophysics Data System (ADS)

Reis, D. S.; Stedinger, J. R.; Martins, E. S.

2005-10-01

This paper develops a Bayesian approach to analysis of a generalized least squares (GLS) regression model for regional analyses of hydrologic data. The new approach allows computation of the posterior distributions of the parameters and the model error variance using a quasi-analytic approach. Two regional skew estimation studies illustrate the value of the Bayesian GLS approach for regional statistical analysis of a shape parameter and demonstrate that regional skew models can be relatively precise with effective record lengths in excess of 60 years. With Bayesian GLS the marginal posterior distribution of the model error variance and the corresponding mean and variance of the parameters can be computed directly, thereby providing a simple but important extension of the regional GLS regression procedures popularized by Tasker and Stedinger (1989), which is sensitive to the likely values of the model error variance when it is small relative to the sampling error in the at-site estimator.

Chemical, microbial and antibiotic susceptibility analyses of groundwater after a major flood event in Chennai

PubMed Central

Gowrisankar, Ganesan; Chelliah, Ramachandran; Ramakrishnan, Sudha Rani; Elumalai, Vetrimurugan; Dhanamadhavan, Saravanan; Brindha, Karthikeyan; Antony, Usha; Elango, Lakshmanan

2017-01-01

During floods, human exposure to pathogens through contaminated water leads to the outbreak of epidemic diseases. This research presents the first extensive assessment of surface and groundwater samples collected immediately after a flood (December 2015) and post-flood (April 2016) from the Adyar River of Chennai, a major city in India, for major ions, trace metals, bacterial population, and pathogens. Severe rains in a short period of time resulted in flooding which inundated the wells, allowing the entry of sewage contaminated river water into the groundwater zone. This has led to bacterial counts and chemical ions exceeding Bureau of Indian Standard’s recommended limits in most flood affected areas. Pathogens isolated from the groundwater showed resistance to antibiotics, namely ceftriaxone, doxycycline and nalidixic acid. However, they were sensitive to chloramphenicol, ciprofloxacin, norfloxacin, and tetracycline. Determining the antibiotic susceptibility of pathogens will help in the treatment of humans affected by contaminated water through an appropriate selection of prescribed medication. PMID:28994821

Mixing stops at the LHC

DOE PAGES

Agrawal, Prateek; Frugiuele, Claudia

2014-01-01

We study the phenomenology of a light stop NLSP in the presence of large mixing with either the first or the second generation. R-symmetric models provide a prime setting for this scenario, but our discussion also applies to the MSSM when a significant amount of mixing can be accommodated. In our framework the dominant stop decay is through the flavor violating mode into a light jet and the LSP in an extended region of parameter space. There are currently no limits from ATLAS and CMS in this region. We emulate shape-based hadronic SUSY searches for this topology, and find thatmore » they have potential sensitivity. If the extension of these analyses to this region is robust, we find that these searches can set strong exclusion limits on light stops. If not, then the flavor violating decay mode is challenging and may represent a blind spot in stop searches even at 13 TeV. Thus, an experimental investigation of this scenario is well motivated.« less

Ageing and brain white matter structure in 3,513 UK Biobank participants

PubMed Central

Cox, Simon R.; Ritchie, Stuart J.; Tucker-Drob, Elliot M.; Liewald, David C.; Hagenaars, Saskia P.; Davies, Gail; Wardlaw, Joanna M.; Gale, Catharine R.; Bastin, Mark E.; Deary, Ian J.

2016-01-01

Quantifying the microstructural properties of the human brain's connections is necessary for understanding normal ageing and disease. Here we examine brain white matter magnetic resonance imaging (MRI) data in 3,513 generally healthy people aged 44.64–77.12 years from the UK Biobank. Using conventional water diffusion measures and newer, rarely studied indices from neurite orientation dispersion and density imaging, we document large age associations with white matter microstructure. Mean diffusivity is the most age-sensitive measure, with negative age associations strongest in the thalamic radiation and association fibres. White matter microstructure across brain tracts becomes increasingly correlated in older age. This may reflect an age-related aggregation of systemic detrimental effects. We report several other novel results, including age associations with hemisphere and sex, and comparative volumetric MRI analyses. Results from this unusually large, single-scanner sample provide one of the most extensive characterizations of age associations with major white matter tracts in the human brain. PMID:27976682

Emergency School Aid Act (ESAA) Evaluation: Results of Supplemental Analyses Conducted in the Contract Extension Period.

ERIC Educational Resources Information Center

Carriere, Ronald A.; And Others

This report focuses on a set of supplemental analyses that were performed on portions of the Emergency School Aid Act (ESAA) evaluation data. The goal of these analyses was to explore additional relationships in the data that might help to inform program policy, to confirm and/or further explicate some of the findings reported earlier, and to put…

Meta-epidemiologic study showed frequent time trends in summary estimates from meta-analyses of diagnostic accuracy studies.

PubMed

Cohen, Jérémie F; Korevaar, Daniël A; Wang, Junfeng; Leeflang, Mariska M; Bossuyt, Patrick M

2016-09-01

To evaluate changes over time in summary estimates from meta-analyses of diagnostic accuracy studies. We included 48 meta-analyses from 35 MEDLINE-indexed systematic reviews published between September 2011 and January 2012 (743 diagnostic accuracy studies; 344,015 participants). Within each meta-analysis, we ranked studies by publication date. We applied random-effects cumulative meta-analysis to follow how summary estimates of sensitivity and specificity evolved over time. Time trends were assessed by fitting a weighted linear regression model of the summary accuracy estimate against rank of publication. The median of the 48 slopes was -0.02 (-0.08 to 0.03) for sensitivity and -0.01 (-0.03 to 0.03) for specificity. Twelve of 96 (12.5%) time trends in sensitivity or specificity were statistically significant. We found a significant time trend in at least one accuracy measure for 11 of the 48 (23%) meta-analyses. Time trends in summary estimates are relatively frequent in meta-analyses of diagnostic accuracy studies. Results from early meta-analyses of diagnostic accuracy studies should be considered with caution. Copyright © 2016 Elsevier Inc. All rights reserved.

Air pollution and subclinical airway inflammation in the SALIA cohort study

PubMed Central

2014-01-01

Background The association between long-term exposure to air pollution and local inflammation in the lung has rarely been investigated in the general population of elderly subjects before. We investigated this association in a population-based cohort of elderly women from Germany. Methods In a follow-up examination of the SALIA cohort study in 2008/2009, 402 women aged 68 to 79 years from the Ruhr Area and Borken (Germany) were clinically examined. Inflammatory markers were determined in exhaled breath condensate (EBC) and in induced sputum (IS). We used traffic indicators and measured air pollutants at single monitoring stations in the study area to assess individual traffic exposure and long-term air pollution background exposure. Additionally long-term residential exposure to air pollution was estimated using land-use regression (LUR) models. We applied multiple logistic and linear regression analyses adjusted for age, indoor mould, smoking, passive smoking and socio-economic status and additionally conducted sensitivity analyses. Results Inflammatory markers showed a high variability between the individuals and were higher with higher exposure to air pollution. NO derivatives, leukotriene (LT) B4 and tumour necrosis factor-α (TNF-α) showed the strongest associations. An increase of 9.42 μg/m3 (interquartile range) in LUR modelled NO2 was associated with measureable LTB4 level (level with values above the detection limit) in EBC (odds ratio: 1.38, 95% CI: 1.02 -1.86) as well as with LTB4 in IS (%-change: 19%, 95% CI: 7% - 32%). The results remained consistent after exclusion of subpopulations with risk factors for inflammation (smoking, respiratory diseases, mould infestation) and after extension of models with additional adjustment for season of examination, mass of IS and urban/rural living as sensitivity analyses. Conclusions In this analysis of the SALIA study we found that long-term exposure to air pollutants from traffic and industrial sources was associated with an increase of several inflammatory markers in EBC and in IS. We conclude that long-term exposure to air pollution might lead to changes in the inflammatory marker profile in the lower airways in an elderly female population. PMID:24645673

DGSA: A Matlab toolbox for distance-based generalized sensitivity analysis of geoscientific computer experiments

NASA Astrophysics Data System (ADS)

Park, Jihoon; Yang, Guang; Satija, Addy; Scheidt, Céline; Caers, Jef

2016-12-01

Sensitivity analysis plays an important role in geoscientific computer experiments, whether for forecasting, data assimilation or model calibration. In this paper we focus on an extension of a method of regionalized sensitivity analysis (RSA) to applications typical in the Earth Sciences. Such applications involve the building of large complex spatial models, the application of computationally extensive forward modeling codes and the integration of heterogeneous sources of model uncertainty. The aim of this paper is to be practical: 1) provide a Matlab code, 2) provide novel visualization methods to aid users in getting a better understanding in the sensitivity 3) provide a method based on kernel principal component analysis (KPCA) and self-organizing maps (SOM) to account for spatial uncertainty typical in Earth Science applications and 4) provide an illustration on a real field case where the above mentioned complexities present themselves. We present methods that extend the original RSA method in several ways. First we present the calculation of conditional effects, defined as the sensitivity of a parameter given a level of another parameters. Second, we show how this conditional effect can be used to choose nominal values or ranges to fix insensitive parameters aiming to minimally affect uncertainty in the response. Third, we develop a method based on KPCA and SOM to assign a rank to spatial models in order to calculate the sensitivity on spatial variability in the models. A large oil/gas reservoir case is used as illustration of these ideas.

Pain sensitivity and tactile spatial acuity are altered in healthy musicians as in chronic pain patients

PubMed Central

Zamorano, Anna M.; Riquelme, Inmaculada; Kleber, Boris; Altenmüller, Eckart; Hatem, Samar M.; Montoya, Pedro

2015-01-01

Extensive training of repetitive and highly skilled movements, as it occurs in professional classical musicians, may lead to changes in tactile sensitivity and corresponding cortical reorganization of somatosensory cortices. It is also known that professional musicians frequently experience musculoskeletal pain and pain-related symptoms during their careers. The present study aimed at understanding the complex interaction between chronic pain and music training with respect to somatosensory processing. For this purpose, tactile thresholds (mechanical detection, grating orientation, two-point discrimination) and subjective ratings to thermal and pressure pain stimuli were assessed in 17 professional musicians with chronic pain, 30 pain-free musicians, 20 non-musicians with chronic pain, and 18 pain-free non-musicians. We found that pain-free musicians displayed greater touch sensitivity (i.e., lower mechanical detection thresholds), lower tactile spatial acuity (i.e., higher grating orientation thresholds) and increased pain sensitivity to pressure and heat compared to pain-free non-musicians. Moreover, we also found that musicians and non-musicians with chronic pain presented lower tactile spatial acuity and increased pain sensitivity to pressure and heat compared to pain-free non-musicians. The significant increment of pain sensitivity together with decreased spatial discrimination in pain-free musicians and the similarity of results found in chronic pain patients, suggests that the extensive training of repetitive and highly skilled movements in classical musicians could be considered as a risk factor for developing chronic pain, probably due to use-dependent plastic changes elicited in somatosensory pathways. PMID:25610384

The march from early life food sensitization to allergic disease: a systematic review and meta-analyses of birth cohort studies.

PubMed

Alduraywish, S A; Lodge, C J; Campbell, B; Allen, K J; Erbas, B; Lowe, A J; Dharmage, S C

2016-01-01

There is growing evidence for an increase in food allergies. The question of whether early life food sensitization, a primary step in food allergies, leads to other allergic disease is a controversial but important issue. Birth cohorts are an ideal design to answer this question. We aimed to systematically investigate and meta-analyse the evidence for associations between early food sensitization and allergic disease in birth cohorts. MEDLINE and SCOPUS databases were searched for birth cohorts that have investigated the association between food sensitization in the first 2 years and subsequent wheeze/asthma, eczema and/or allergic rhinitis. We performed meta-analyses using random-effects models to obtain pooled estimates, stratified by age group. The search yielded fifteen original articles representing thirteen cohorts. Early life food sensitization was associated with an increased risk of infantile eczema, childhood wheeze/asthma, eczema and allergic rhinitis and young adult asthma. Meta-analyses demonstrated that early life food sensitization is related to an increased risk of wheeze/asthma (pooled OR 2.9; 95% CI 2.0-4.0), eczema (pooled OR 2.7; 95% CI 1.7-4.4) and allergic rhinitis (pooled OR 3.1; 95% CI 1.9-4.9) from 4 to 8 years. Food sensitization in the first 2 years of life can identify children at high risk of subsequent allergic disease who may benefit from early life preventive strategies. However, due to potential residual confounding in the majority of studies combined with lack of follow-up into adolescence and adulthood, further research is needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A pilot cost-effectiveness analysis of treatments in newly diagnosed high-grade gliomas: the example of 5-aminolevulinic Acid compared with white-light surgery.

PubMed

Esteves, Susana; Alves, Marta; Castel-Branco, Marta; Stummer, Walter

2015-05-01

High-grade gliomas are aggressive, incurable tumors characterized by extensive diffuse invasion of the normal brain parenchyma. Novel therapies at best prolong survival; their costs are formidable and benefit is marginal. Economic restrictions thus require knowledge of the cost-effectiveness of treatments. Here, we show the cost-effectiveness of enhanced resections in malignant glioma surgery using a well-characterized tool for intraoperative tumor visualization, 5-aminolevulinic acid (5-ALA). To evaluate the cost-effectiveness of 5-ALA fluorescence-guided neurosurgery compared with white-light surgery in adult patients with newly diagnosed high-grade glioma, adopting the perspective of the Portuguese National Health Service. We used a Markov model (cohort simulation). Transition probabilities were estimated with the use of data from 1 randomized clinical trial and 1 noninterventional prospective study. Utility values and resource use were obtained from published literature and expert opinion. Unit costs were taken from official Portuguese reimbursement lists (2012 values). The health outcomes considered were quality-adjusted life-years, life-years, and progression-free life-years. Extensive 1-way and probabilistic sensitivity analyses were performed. The incremental cost-effectiveness ratios are below &OV0556;10 000 in all evaluated outcomes, being around &OV0556;9100 per quality-adjusted life-year gained, &OV0556;6700 per life-year gained, and &OV0556;8800 per progression-free life-year gained. The probability of 5-ALA fluorescence-guided surgery cost-effectiveness at a threshold of &OV0556;20000 is 96.0% for quality-adjusted life-year, 99.6% for life-year, and 98.8% for progression-free life-year. 5-ALA fluorescence-guided surgery appears to be cost-effective in newly diagnosed high-grade gliomas compared with white-light surgery. This example demonstrates cost-effectiveness analyses for malignant glioma surgery to be feasible on the basis of existing data.

Immediate changes in widespread pressure pain sensitivity, neck pain, and cervical range of motion after cervical or thoracic thrust manipulation in patients with bilateral chronic mechanical neck pain: a randomized clinical trial.

PubMed

Martínez-Segura, Raquel; De-la-Llave-Rincón, Ana I; Ortega-Santiago, Ricardo; Cleland, Joshua A; Fernández-de-Las-Peñas, César

2012-09-01

Randomized clinical trial. To compare the effects of cervical versus thoracic thrust manipulation in patients with bilateral chronic mechanical neck pain on pressure pain sensitivity, neck pain, and cervical range of motion (CROM). Evidence suggests that spinal interventions can stimulate descending inhibitory pain pathways. To our knowledge, no study has investigated the neurophysiological effects of thoracic thrust manipulation in individuals with bilateral chronic mechanical neck pain, including widespread changes on pressure sensitivity. Ninety patients (51% female) were randomly assigned to 1 of 3 groups: cervical thrust manipulation on the right, cervical thrust manipulation on the left, or thoracic thrust manipulation. Pressure pain thresholds (PPTs) over the C5-6 zygapophyseal joint, lateral epicondyle, and tibialis anterior muscle, neck pain (11-point numeric pain rating scale), and cervical spine range of motion (CROM) were collected at baseline and 10 minutes after the intervention by an assessor blinded to the treatment allocation of the patients. Mixed-model analyses of covariance were used to examine the effects of the treatment on each outcome variable, with group as the between-subjects variable, time and side as the within-subject variables, and gender as the covariate. The primary analysis was the group-by-time interaction. No significant interactions were found with the mixed-model analyses of covariance for PPT level (C5-6, P>.210; lateral epicondyle, P>.186; tibialis anterior muscle, P>.268), neck pain intensity (P = .923), or CROM (flexion, P = .700; extension, P = .387; lateral flexion, P>.672; rotation, P>.192) as dependent variables. All groups exhibited similar changes in PPT, neck pain, and CROM (all, P<.001). Gender did not influence the main effects or the interaction effects in the analyses of the outcomes (P>.10). The results of the current randomized clinical trial suggest that cervical and thoracic thrust manipulation induce similar changes in PPT, neck pain intensity, and CROM in individuals with bilateral chronic mechanical neck pain. However, changes in PPT and CROM were small and did not surpass their respective minimal detectable change values. Further, because we did not include a control group, we cannot rule out a placebo effect of the thrust interventions on the outcomes. Therapy, level 1b.J Orthop Sports Phys Ther 2012;42(9):806-814, Epub 18 June 2012. doi:10.2519/jospt.2012.4151.

Apollo 14 microbial analyses

NASA Technical Reports Server (NTRS)

Taylor, G. R.

1972-01-01

Extensive microbiological analyses that were performed on the Apollo 14 prime and backup crewmembers and ancillary personnel are discussed. The crewmembers were subjected to four separate and quite different environments during the 137-day monitoring period. The relation between each of these environments and observed changes in the microflora of each astronaut are presented.

The Efficacy of a Nurse-Led Disease Management Program in Improving the Quality of Life for Patients with Chronic Kidney Disease: A Meta-Analysis.

PubMed

Chen, Chong-Cheng; Chen, Yi; Liu, Xia; Wen, Yue; Ma, Deng-Yan; Huang, Yue-Yang; Pu, Li; Diao, Yong-Shu; Yang, Kun

2016-01-01

The impacts of nurse-led disease management programs on the quality of life for patients with chronic kidney disease have not been extensively studied. Furthermore, results of the existing related studies are inconsistent. The focus of the proposed meta-analysis is to evaluate the efficacy of nurse-led disease management programs in improving the quality of life for patients with chronic kidney disease. Literature survey was performed to identify the eligible studies from PubMed, Current Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials with predefined terms. The outcome measured was quality of life. This meta-analysis was conducted in line with recommendations from the preferred reporting items for systematic reviews and meta-analyses. Eight studies comprising a total of 1520 patients were included in this meta-analysis, with 766 patients assigned to the nurse-led disease management program. Nurse-led disease management improved the quality of life in terms of symptoms, sleep, staff encouragement, pain, general health perception, energy/fatigue, overall health and mental component summary when evaluated 6 weeks after the beginning of intervention. When evaluated 12 weeks later, the quality of life in terms of symptoms, sleep, staff encouragement, energy/fatigue, and physical component summary was improved. Stratified by the modalities of dialysis, similar results of pooled analyses were observed for patients with peritoneal dialysis or hemodialysis, compared with the overall analyses. The results of sensitivity analyses were the same as the primary analyses. The symmetric funnel plot suggested that the possibility of potential publication bias was relatively low. Nurse-led disease management program seems effective to improve some parameters of quality of life for patients with chronic kidney disease. However, the seemingly promising results should be cautiously interpreted and generalized and still need to be confirmed through well-designed large-scale prospective randomized controlled trials.

Modular space station phase B extension, preliminary system design. Volume 4: Subsystems analyses

NASA Technical Reports Server (NTRS)

Antell, R. W.

1972-01-01

The subsystems tradeoffs, analyses, and preliminary design results are summarized. Analyses were made of the structural and mechanical, environmental control and life support, electrical power, guidance and control, reaction control, information, and crew habitability subsystems. For each subsystem a summary description is presented including subsystem requirements, subsystem description, and subsystem characteristics definition (physical, performance, and interface). The major preliminary design data and tradeoffs or analyses are described in detail at each of the assembly levels.

Transport calculations and sensitivity analyses for air-over-ground and air-over-seawater weapons environments

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

Pace, J.V. III; Bartine, D.E.; Mynatt, F.R.

1976-01-01

Two-dimensional neutron and secondary gamma-ray transport calculations and cross-section sensitivity analyses have been performed to determine the effects of varying source heights and cross sections on calculated doses. The air-over-ground calculations demonstrate the existence of an optimal height of burst for a specific ground range and indicate under what conditions they are conservative with respect to infinite air calculations. The air-over-seawater calculations showed the importance of hydrogen and chlorine in gamma production. Additional sensitivity analyses indicated the importance of water in the ground, the amount of reduction in ground thickness for calculational purposes, and the effect of the degree ofmore » Legendre angular expansion of the scattering cross-sections (P/sub l/) on the calculated dose.« less

Constitutive BAK activation as a determinant of drug sensitivity in malignant lymphohematopoietic cells.

PubMed

Dai, Haiming; Ding, Husheng; Meng, X Wei; Peterson, Kevin L; Schneider, Paula A; Karp, Judith E; Kaufmann, Scott H

2015-10-15

Mitochondrial outer membrane permeabilization (MOMP), a key step in the intrinsic apoptotic pathway, is incompletely understood. Current models emphasize the role of BH3-only BCL2 family members in BAX and BAK activation. Here we demonstrate concentration-dependent BAK autoactivation under cell-free conditions and provide evidence that this autoactivation plays a key role in regulating the intrinsic apoptotic pathway in intact cells. In particular, we show that up to 80% of BAK (but not BAX) in lymphohematopoietic cell lines is oligomerized and bound to anti-apoptotic BCL2 family members in the absence of exogenous death stimuli. The extent of this constitutive BAK oligomerization is diminished by BAK knockdown and unaffected by BIM or PUMA down-regulation. Further analysis indicates that sensitivity of cells to BH3 mimetics reflects the identity of the anti-apoptotic proteins to which BAK is constitutively bound, with extensive BCLXL•BAK complexes predicting navitoclax sensitivity, and extensive MCL1•BAK complexes predicting A1210477 sensitivity. Moreover, high BAK expression correlates with sensitivity of clinical acute myelogenous leukemia to chemotherapy, whereas low BAK levels correlate with resistance and relapse. Collectively, these results inform current understanding of MOMP and provide new insight into the ability of BH3 mimetics to induce apoptosis without directly activating BAX or BAK. © 2015 Dai et al.; Published by Cold Spring Harbor Laboratory Press.

Hospitalisation Rates for Ambulatory Care Sensitive Conditions for Persons with and without an Intellectual Disability--A Population Perspective

ERIC Educational Resources Information Center

Balogh, R.; Brownell, M.; Ouellette-Kuntz, H.; Colantonio, A.

2010-01-01

Background: There is evidence that persons with an intellectual disability (ID) face barriers to primary care; however, this has not been extensively studied at the population level. Rates of hospitalisation for ambulatory care sensitive conditions are used as an indicator of access to, and quality of, primary care. The objective of the study was…

Diagnostic performance of semi-quantitative and quantitative stress CMR perfusion analysis: a meta-analysis.

PubMed

van Dijk, R; van Assen, M; Vliegenthart, R; de Bock, G H; van der Harst, P; Oudkerk, M

2017-11-27

Stress cardiovascular magnetic resonance (CMR) perfusion imaging is a promising modality for the evaluation of coronary artery disease (CAD) due to high spatial resolution and absence of radiation. Semi-quantitative and quantitative analysis of CMR perfusion are based on signal-intensity curves produced during the first-pass of gadolinium contrast. Multiple semi-quantitative and quantitative parameters have been introduced. Diagnostic performance of these parameters varies extensively among studies and standardized protocols are lacking. This study aims to determine the diagnostic accuracy of semi- quantitative and quantitative CMR perfusion parameters, compared to multiple reference standards. Pubmed, WebOfScience, and Embase were systematically searched using predefined criteria (3272 articles). A check for duplicates was performed (1967 articles). Eligibility and relevance of the articles was determined by two reviewers using pre-defined criteria. The primary data extraction was performed independently by two researchers with the use of a predefined template. Differences in extracted data were resolved by discussion between the two researchers. The quality of the included studies was assessed using the 'Quality Assessment of Diagnostic Accuracy Studies Tool' (QUADAS-2). True positives, false positives, true negatives, and false negatives were subtracted/calculated from the articles. The principal summary measures used to assess diagnostic accuracy were sensitivity, specificity, andarea under the receiver operating curve (AUC). Data was pooled according to analysis territory, reference standard and perfusion parameter. Twenty-two articles were eligible based on the predefined study eligibility criteria. The pooled diagnostic accuracy for segment-, territory- and patient-based analyses showed good diagnostic performance with sensitivity of 0.88, 0.82, and 0.83, specificity of 0.72, 0.83, and 0.76 and AUC of 0.90, 0.84, and 0.87, respectively. In per territory analysis our results show similar diagnostic accuracy comparing anatomical (AUC 0.86(0.83-0.89)) and functional reference standards (AUC 0.88(0.84-0.90)). Only the per territory analysis sensitivity did not show significant heterogeneity. None of the groups showed signs of publication bias. The clinical value of semi-quantitative and quantitative CMR perfusion analysis remains uncertain due to extensive inter-study heterogeneity and large differences in CMR perfusion acquisition protocols, reference standards, and methods of assessment of myocardial perfusion parameters. For wide spread implementation, standardization of CMR perfusion techniques is essential. CRD42016040176 .

Effects of seawater acidification on gene expression: resolving broader-scale trends in sea urchins.

PubMed

Evans, Tyler G; Watson-Wynn, Priscilla

2014-06-01

Sea urchins are ecologically and economically important calcifying organisms threatened by acidification of the global ocean caused by anthropogenic CO2 emissions. Propelled by the sequencing of the purple sea urchin (Strongylocentrotus purpuratus) genome, profiling changes in gene expression during exposure to high pCO2 seawater has emerged as a powerful and increasingly common method to infer the response of urchins to ocean change. However, analyses of gene expression are sensitive to experimental methodology, and comparisons between studies of genes regulated by ocean acidification are most often made in the context of major caveats. Here we perform meta-analyses as a means of minimizing experimental discrepancies and resolving broader-scale trends regarding the effects of ocean acidification on gene expression in urchins. Analyses across eight studies and four urchin species largely support prevailing hypotheses about the impact of ocean acidification on marine calcifiers. The predominant expression pattern involved the down-regulation of genes within energy-producing pathways, a clear indication of metabolic depression. Genes with functions in ion transport were significantly over-represented and are most plausibly contributing to intracellular pH regulation. Expression profiles provided extensive evidence for an impact on biomineralization, epitomized by the down-regulation of seven spicule matrix proteins. In contrast, expression profiles provided limited evidence for CO2-mediated developmental delay or induction of a cellular stress response. Congruence between studies of gene expression and the ocean acidification literature in general validates the accuracy of gene expression in predicting the consequences of ocean change and justifies its continued use in future studies. © 2014 Marine Biological Laboratory.

A Two-Step Approach for Analysis of Nonignorable Missing Outcomes in Longitudinal Regression: an Application to Upstate KIDS Study.

PubMed

Liu, Danping; Yeung, Edwina H; McLain, Alexander C; Xie, Yunlong; Buck Louis, Germaine M; Sundaram, Rajeshwari

2017-09-01

Imperfect follow-up in longitudinal studies commonly leads to missing outcome data that can potentially bias the inference when the missingness is nonignorable; that is, the propensity of missingness depends on missing values in the data. In the Upstate KIDS Study, we seek to determine if the missingness of child development outcomes is nonignorable, and how a simple model assuming ignorable missingness would compare with more complicated models for a nonignorable mechanism. To correct for nonignorable missingness, the shared random effects model (SREM) jointly models the outcome and the missing mechanism. However, the computational complexity and lack of software packages has limited its practical applications. This paper proposes a novel two-step approach to handle nonignorable missing outcomes in generalized linear mixed models. We first analyse the missing mechanism with a generalized linear mixed model and predict values of the random effects; then, the outcome model is fitted adjusting for the predicted random effects to account for heterogeneity in the missingness propensity. Extensive simulation studies suggest that the proposed method is a reliable approximation to SREM, with a much faster computation. The nonignorability of missing data in the Upstate KIDS Study is estimated to be mild to moderate, and the analyses using the two-step approach or SREM are similar to the model assuming ignorable missingness. The two-step approach is a computationally straightforward method that can be conducted as sensitivity analyses in longitudinal studies to examine violations to the ignorable missingness assumption and the implications relative to health outcomes. © 2017 John Wiley & Sons Ltd.

Inhomogeneous Forcing and Transient Climate Sensitivity

NASA Technical Reports Server (NTRS)

Shindell, Drew T.

2014-01-01

Understanding climate sensitivity is critical to projecting climate change in response to a given forcing scenario. Recent analyses have suggested that transient climate sensitivity is at the low end of the present model range taking into account the reduced warming rates during the past 10-15 years during which forcing has increased markedly. In contrast, comparisons of modelled feedback processes with observations indicate that the most realistic models have higher sensitivities. Here I analyse results from recent climate modelling intercomparison projects to demonstrate that transient climate sensitivity to historical aerosols and ozone is substantially greater than the transient climate sensitivity to CO2. This enhanced sensitivity is primarily caused by more of the forcing being located at Northern Hemisphere middle to high latitudes where it triggers more rapid land responses and stronger feedbacks. I find that accounting for this enhancement largely reconciles the two sets of results, and I conclude that the lowest end of the range of transient climate response to CO2 in present models and assessments (less than 1.3 C) is very unlikely.

Role of root UV-B sensing in Arabidopsis early seedling development.

PubMed

Tong, Hongyun; Leasure, Colin D; Hou, Xuewen; Yuen, Gigi; Briggs, Winslow; He, Zheng-Hui

2008-12-30

All sun-exposed organisms are affected by UV-B [(UVB) 280-320 nm], an integral part of sunlight. UVB can cause stresses or act as a developmental signal depending on its fluence levels. In plants, the mechanism by which high-fluence-rate UVB causes damages and activates DNA-repair systems has been extensively studied. However, little is known about how nondamaging low-fluence-rate UVB is perceived to regulate plant morphogenesis and development. Here, we report the identification of an Arabidopsis mutant, root UVB sensitive 1 (rus1), whose primary root is hypersensitive to very low-fluence-rate (VLF) UVB. Under standard growth-chamber fluorescent white light, rus1 displays stunted root growth and fails to form postembryonic leaves. Experiments with different monochromatic light sources showed that rus1 phenotypes can be rescued if the seedlings are allowed to grow in light conditions with minimum UVB. We determined that roots, not other organs, perceive the UVB signal. Genetic and molecular analyses confirmed that the root light-sensitive phenotypes are independent of all other known plant photoreceptors. Three rus1 alleles have been identified and characterized. A map-based approach was used to identify the RUS1 locus. RUS1 encodes a protein that contains DUF647 (domain of unknown function 647), a domain highly conserved in eukaryotes. Our results demonstrate a root VLF UVB-sensing mechanism that is involved in Arabidopsis early seedling morphogenesis and development.

Subcutaneous vs intravenous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy: an Italian cost-minimization analysis.

PubMed

Lazzaro, Carlo; Lopiano, Leonardo; Cocito, Dario

2014-07-01

Prior researches have suggested that home-based subcutaneous immunoglobulin (SCIG) is equally effective and can be less expensive than hospital-based intravenous immunoglobulin (IVIG) in treating chronic inflammatory demyelinating polyneuropathy (CIDP) patients. This economic evaluation aims at comparing costs of SCIG vs IVIG for CIDP patients in Italy. A 1-year model-based cost-minimization analysis basically populated via neurologists' opinion was undertaken from a societal perspective. Health care resources included immunoglobulin; drugs for premedication and complications (rash, headache, and hypertension) management; time of various health care professionals; pump for SCIG self-administration; infusion disposables. Non-health care resources encompassed transport and parking; losses of working and leisure time for patients and caregivers. Unit or yearly costs for resources valuation were mainly obtained from published sources. Costs were expressed in Euro () 2013. An extensive one-way sensitivity analysis (OWSA) and a scenario SA tested the robustness of the base case findings. Overall costs per patient amount to 49,534.75 (SCIG) and 50,895.73 (IVIG); saving in favour of SCIG reaches 1360.98. For both SCIG and IVIG, the cost driver was immunoglobulin (94.06 vs 86.06 % of the overall costs, respectively). Sensitivity analyses confirmed the consistency of the baseline results. SCIG may be a cost-saving therapy for Italian CIDP patients.

Thin layer chromatography coupled to paper spray ionization mass spectrometry for cocaine and its adulterants analysis.

PubMed

De Carvalho, Thays C; Tosato, Flavia; Souza, Lindamara M; Santos, Heloa; Merlo, Bianca B; Ortiz, Rafael S; Rodrigues, Rayza R T; Filgueiras, Paulo R; França, Hildegardo S; Augusti, Rodinei; Romão, Wanderson; Vaz, Boniek G

2016-05-01

Thin layer chromatography (TLC) is a simple and inexpensive type of chromatography that is extensively used in forensic laboratories for drugs of abuse analysis. In this work, TLC is optimized to analyze cocaine and its adulterants (caffeine, benzocaine, lidocaine and phenacetin) in which the sensitivity (visual determination of LOD from 0.5 to 14mgmL(-1)) and the selectivity (from the study of three different eluents: CHCl3:CH3OH:HCOOHglacial (75:20:5v%), (C2H5)2O:CHCl3 (50:50v%) and CH3OH:NH4OH (100:1.5v%)) were evaluated. Aiming to improve these figures of merit, the TLC spots were identified and quantified (linearity with R(2)>0.98) by the paper spray ionization mass spectrometry (PS-MS), reaching now lower LOD values (>1.0μgmL(-1)). The method developed in this work open up perspective of enhancing the reliability of traditional and routine TLC analysis employed in the criminal expertise units. Higher sensitivity, selectivity and rapidity can be provided in forensic reports, besides the possibility of quantitative analysis. Due to the great simplicity, the PS(+)-MS technique can also be coupled directly to other separation techniques such as the paper chromatography and can still be used in analyses of LSD blotter, documents and synthetic drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

RNAi screen for rapid therapeutic target identification in leukemia patients

PubMed Central

Tyner, Jeffrey W.; Deininger, Michael W.; Loriaux, Marc M.; Chang, Bill H.; Gotlib, Jason R.; Willis, Stephanie G.; Erickson, Heidi; Kovacsovics, Tibor; O'Hare, Thomas; Heinrich, Michael C.; Druker, Brian J.

2009-01-01

Targeted therapy has vastly improved outcomes in certain types of cancer. Extension of this paradigm across a broad spectrum of malignancies will require an efficient method to determine the molecular vulnerabilities of cancerous cells. Improvements in sequencing technology will soon enable high-throughput sequencing of entire genomes of cancer patients; however, determining the relevance of identified sequence variants will require complementary functional analyses. Here, we report an RNAi-assisted protein target identification (RAPID) technology that individually assesses targeting of each member of the tyrosine kinase gene family. We demonstrate that RAPID screening of primary leukemia cells from 30 patients identifies targets that are critical to survival of the malignant cells from 10 of these individuals. We identify known, activating mutations in JAK2 and K-RAS, as well as patient-specific sensitivity to down-regulation of FLT1, CSF1R, PDGFR, ROR1, EPHA4/5, JAK1/3, LMTK3, LYN, FYN, PTK2B, and N-RAS. We also describe a previously undescribed, somatic, activating mutation in the thrombopoietin receptor that is sensitive to down-stream pharmacologic inhibition. Hence, the RAPID technique can quickly identify molecular vulnerabilities in malignant cells. Combination of this technique with whole-genome sequencing will represent an ideal tool for oncogenic target identification such that specific therapies can be matched with individual patients. PMID:19433805

[STandardized Reporting Of Secondary data Analyses (STROSA)—a recommendation].

PubMed

Swart, Enno; Schmitt, Jochen

2014-01-01

Secondary data analyses will play an increasingly important role in health services research. But to date, there is no guideline for the systematic, transparent and complete reporting of secondary data. We investigated whether the STROBE statement, i.e., the recommendations for reporting observational studies, satisfies the specific characteristics of secondary data analyses and whether any specifications/modifications and extensions are necessary. For the majority of the 22 STROBE criteria, specifications and extensions are needed to meet the requirements of systematic, transparent and complete reporting of secondary data analysis. Seven aspects of secondary data analysis not covered by STROBE (legal aspects, data flow, protocol, unit of analysis, internal validations/definitions, advantages of secondary data utilisation, role of data owners) should be considered as a specific complement to STROBE. The so called STROSA (STandardized Reporting Of Secondary data Analyses) checklist therefore includes 29 items that relate to the title/abstract, introduction, methods, results and discussion sections of articles. The STROSA checklist is intended to support authors and readers in the critical appraisal of secondary data analyses. This proposal will now be subject to continued scientific discussions. Copyright © 2014. Published by Elsevier GmbH.

Public-Private Policy Change and Its Influence on the Linkage of Agricultural Research, Extension and Farmers in Iran

ERIC Educational Resources Information Center

Karamidehkordi, Esmail

2013-01-01

Purpose: This article aims to show the linkage of Iranian agricultural research centres with extension and farmers, using three case studies in 1999, 2005 and 2010. Design/methodology/approach: The data were collected through document analyses, structured and semi-structured interviews and observations. Findings: The 1999 and 2005 cases were…

The Influence of Translation on Reading Amount, Proficiency, and Speed in Extensive Reading

ERIC Educational Resources Information Center

Sakurai, Nobuko

2015-01-01

This study attempted to examine the influence of a decrease in translation on the number of words read, reading comprehension, and reading rate in an extensive reading (ER) program. The participants were 70 first-year university students who experienced ER both in and outside the classroom for 15 weeks. The results of regression analyses confirmed…

Structure of Preschool Phonological Sensitivity: Overlapping Sensitivity to Rhyme, Words, Syllables, and Phonemes.

ERIC Educational Resources Information Center

Anthony, Jason L.; Lonigan, Christopher J.; Burgess, Stephen R.; Driscoll, Kimberly; Phillips, Beth M.; Cantor, Brenlee G.

2002-01-01

This study examined relations among sensitivity to words, syllables, rhymes, and phonemes in older and younger preschoolers. Confirmatory factor analyses found that a one-factor model best explained the date from both groups of children. Only variance common to all phonological sensitivity skills was related to print knowledge and rudimentary…

Modic Type 1 Changes: Detection Performance of Fat-Suppressed Fluid-Sensitive MRI Sequences.

PubMed

Finkenstaedt, Tim; Del Grande, Filippo; Bolog, Nicolae; Ulrich, Nils; Tok, Sina; Kolokythas, Orpheus; Steurer, Johann; Andreisek, Gustav; Winklhofer, Sebastian

2018-02-01

 To assess the performance of fat-suppressed fluid-sensitive MRI sequences compared to T1-weighted (T1w) / T2w sequences for the detection of Modic 1 end-plate changes on lumbar spine MRI.  Sagittal T1w, T2w, and fat-suppressed fluid-sensitive MRI images of 100 consecutive patients (consequently 500 vertebral segments; 52 female, mean age 74 ± 7.4 years; 48 male, mean age 71 ± 6.3 years) were retrospectively evaluated. We recorded the presence (yes/no) and extension (i. e., Likert-scale of height, volume, and end-plate extension) of Modic I changes in T1w/T2w sequences and compared the results to fat-suppressed fluid-sensitive sequences (McNemar/Wilcoxon-signed-rank test).  Fat-suppressed fluid-sensitive sequences revealed significantly more Modic I changes compared to T1w/T2w sequences (156 vs. 93 segments, respectively; p < 0.001). The extension of Modic I changes in fat-suppressed fluid-sensitive sequences was significantly larger compared to T1w/T2w sequences (height: 2.53 ± 0.82 vs. 2.27 ± 0.79, volume: 2.35 ± 0.76 vs. 2.1 ± 0.65, end-plate: 2.46 ± 0.76 vs. 2.19 ± 0.81), (p < 0.05). Modic I changes that were only visible in fat-suppressed fluid-sensitive sequences but not in T1w/T2w sequences were significantly smaller compared to Modic I changes that were also visible in T1w/T2w sequences (p < 0.05).  In conclusion, fat-suppressed fluid-sensitive MRI sequences revealed significantly more Modic I end-plate changes and demonstrated a greater extent compared to standard T1w/T2w imaging.   · When the Modic classification was defined in 1988, T2w sequences were heavily T2-weighted and thus virtually fat-suppressed.. · Nowadays, the bright fat signal in T2w images masks edema-like changes.. · The conventional definition of Modic I changes is not fully applicable anymore.. · Fat-suppressed fluid-sensitive MRI sequences revealed more/greater extent of Modic I changes.. · Finkenstaedt T, Del Grande F, Bolog N et al. Modic Type 1 Changes: Detection Performance of Fat-Suppressed Fluid-Sensitive MRI Sequences. Fortschr Röntgenstr 2018; 190: 152 - 160. © Georg Thieme Verlag KG Stuttgart · New York.

Sensitivity of water resources in the Delaware River basin to climate variability and change

USGS Publications Warehouse

Ayers, Mark A.; Wolock, David M.; McCabe, Gregory J.; Hay, Lauren E.; Tasker, Gary D.

1994-01-01

Because of the greenhouse effect, projected increases in atmospheric carbon dioxide levels might cause global warming, which in turn could result in changes in precipitation patterns and evapotranspiration and in increases in sea level. This report describes the greenhouse effect; discusses the problems and uncertainties associated with the detection, prediction, and effects of climate change; and presents the results of sensitivity analyses of how climate change might affect water resources in the Delaware River basin. Sensitivity analyses suggest that potentially serious shortfalls of certain water resources in the basin could result if some scenarios for climate change come true . The results of model simulations of the basin streamflow demonstrate the difficulty in distinguishing the effects that climate change versus natural climate variability have on streamflow and water supply . The future direction of basin changes in most water resources, furthermore, cannot be precisely determined because of uncertainty in current projections of regional temperature and precipitation . This large uncertainty indicates that, for resource planning, information defining the sensitivities of water resources to a range of climate change is most relevant . The sensitivity analyses could be useful in developing contingency plans for evaluating and responding to changes, should they occur.

The Intelligent System of Cardiovascular Disease Diagnosis Based on Extension Data Mining

NASA Astrophysics Data System (ADS)

Sun, Baiqing; Li, Yange; Zhang, Lin

This thesis gives the general definition of the concepts of extension knowledge, extension data mining and extension data mining theorem in high dimension space, and also builds the IDSS integrated system by the rough set, expert system and neural network, develops the relevant computer software. From the diagnosis tests, according to the common diseases of myocardial infarctions, angina pectoris and hypertension, and made the test result with physicians, the results shows that the sensitivity, specific and accuracy diagnosis by the IDSS are all higher than the physicians. It can improve the rate of the accuracy diagnosis of physician with the auxiliary help of this system, which have the obvious meaning in low the mortality, disability rate and high the survival rate, and has strong practical values and further social benefits.

Insecure Identities: Unaccompanied Minors as Refugees in Hamburg

ERIC Educational Resources Information Center

Schroeder, Joachim

2012-01-01

This paper analyses the financial circumstances and social income of nearly one hundred unaccompanied minors who have come to Hamburg as refugees from various regions of Africa. It is based on extensive qualitative surveys, analysing their objective conditions of life and in particular their legal situation. A wide range of interview material and…

76 FR 21700 - Notice of Request for Extension and Revision of a Currently Approved Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-18

... analyses has its own methodology and time necessary to perform the analyses. (3) Aflatoxin in Pistachios Program (A High Performance Liquid Chromatography (HPLC) method for exporting pistachios to European Union requested by the California Pistachio Committee) and the domestic program using HPLC or a test kit analysis...

Wavelet Analyses and Applications

ERIC Educational Resources Information Center

Bordeianu, Cristian C.; Landau, Rubin H.; Paez, Manuel J.

2009-01-01

It is shown how a modern extension of Fourier analysis known as wavelet analysis is applied to signals containing multiscale information. First, a continuous wavelet transform is used to analyse the spectrum of a nonstationary signal (one whose form changes in time). The spectral analysis of such a signal gives the strength of the signal in each…

2010 Review on the Extension of the AMedP-8(C) Methodology to New Agents, Materials, and Conditions

DTIC Science & Technology

2010-12-01

tularemia ). Applied Research Associates (ARA), under contract to the Defense Threat Reduction Agency (DTRA), has begun the development of similar...x P Included in IDA 2010 Analyses 1 Biological Staphylococcal Enterotoxin B x P Included in IDA 2010 Analyses 1 Biological Tularemia x P

Results of an independent evaluation of Project ALERT delivered in schools by Cooperative Extension.

PubMed

St Pierre, Tena L; Osgood, D Wayne; Mincemoyer, Claudia C; Kaltreider, D Lynne; Kauh, Tina J

2005-12-01

Reported are results of an independent effectiveness study of the Project ALERT drug prevention program implemented in eight Pennsylvania middle schools by outside program leaders employed by Cooperative Extension. In this randomized, 2-cohort longitudinal evaluation, 1,649 seventh-grade students completed a pretest and four waves of posttests over the 2-year program and 1-year follow-up. Project ALERT's effectiveness was tested through a 3-level hierarchical linear model. Analyses failed to yield any positive effects for substance use or mediators for use in the adult or teen-assisted delivery of the curriculum. An extensive set of additional analyses detected no differential program effects by student risk level, gender, school, or level of implementation quality. Potential explanations for outcomes relative to Project ALERT's original effectiveness trial are discussed, as well as implications for future research, including the need to conduct independent effectiveness studies of previously validated programs in a variety of contexts.

HYPNOTIC TACTILE ANESTHESIA: Psychophysical and Signal-Detection Analyses

PubMed Central

Tataryn, Douglas J.; Kihlstrom, John F.

2017-01-01

Two experiments that studied the effects of hypnotic suggestions on tactile sensitivity are reported. Experiment 1 found that suggestions for anesthesia, as measured by both traditional psychophysical methods and signal detection procedures, were linearly related to hypnotizability. Experiment 2 employed the same methodologies in an application of the real-simulator paradigm to examine the effects of suggestions for both anesthesia and hyperesthesia. Significant effects of hypnotic suggestion on both sensitivity and bias were found in the anesthesia condition but not for the hyperesthesia condition. A new bias parameter, C′, indicated that much of the bias found in the initial analyses was artifactual, a function of changes in sensitivity across conditions. There were no behavioral differences between reals and simulators in any of the conditions, though analyses of postexperimental interviews suggested the 2 groups had very different phenomenal experiences. PMID:28230465

Greenhouse gas accounting of the proposed landfill extension and advanced incineration facility for municipal solid waste management in Hong Kong.

PubMed

Woon, K S; Lo, Irene M C

2013-08-01

The burgeoning of municipal solid waste (MSW) disposal issue and climate change have drawn massive attention from people. On the one hand, Hong Kong is facing a controversial debate over the implementation of proposed landfill extension (LFE) and advanced incineration facility (AIF) to curb the MSW disposal issue. On the other hand, the Hong Kong Special Administrative Region Government is taking concerted efforts to reduce the carbon intensity in this region. This paper discusses the greenhouse gas (GHG) emissions from four proposed waste disposal scenarios, covering the proposed LFE and AIF within a defined system boundary. On the basis of the data collected, assumptions made, and system boundary defined in this study, the results indicate that AIF releases less GHG emissions than LFE. The GHG emissions from LFE are highly contributed by the landfill methane (CH4) emissions but offset by biogenic carbon storage, while the GHG emissions from AIF are mostly due to the stack discharge system but offset by the energy recovery system. Furthermore, parametric sensitivity analyses show that GHG emissions are strongly dependent on the landfill CH4 recovery rate, types of electricity displaced by energy recovery systems, and the heating value of MSW, altering the order of preferred waste disposal scenarios. This evaluation provides valuable insights into the applicability of a policy framework for MSW management practices in reducing GHG emissions. Copyright © 2013 Elsevier B.V. All rights reserved.

Phylogenetic Characterizations of Highly Mutated EV-B106 Recombinants Showing Extensive Genetic Exchanges with Other EV-B in Xinjiang, China.

PubMed

Song, Yang; Zhang, Yong; Fan, Qin; Cui, Hui; Yan, Dongmei; Zhu, Shuangli; Tang, Haishu; Sun, Qiang; Wang, Dongyan; Xu, Wenbo

2017-02-23

Human enterovirus B106 (EV-B106) is a new member of the enterovirus B species. To date, only three nucleotide sequences of EV-B106 have been published, and only one full-length genome sequence (the Yunnan strain 148/YN/CHN/12) is available in the GenBank database. In this study, we conducted phylogenetic characterisation of four EV-B106 strains isolated in Xinjiang, China. Pairwise comparisons of the nucleotide sequences and the deduced amino acid sequences revealed that the four Xinjiang EV-B106 strains had only 80.5-80.8% nucleotide identity and 95.4-97.3% amino acid identity with the Yunnan EV-B106 strain, indicating high mutagenicity. Similarity plots and bootscanning analyses revealed that frequent intertypic recombination occurred in all four Xinjiang EV-B106 strains in the non-structural region. These four strains may share a donor sequence with the EV-B85 strain, which circulated in Xinjiang in 2011, indicating extensive genetic exchanges between these strains. All Xinjiang EV-B106 strains were temperature-sensitive. An antibody seroprevalence study against EV-B106 in two Xinjiang prefectures also showed low titres of neutralizing antibodies, suggesting limited exposure and transmission in the population. This study contributes the whole genome sequences of EV-B106 to the GenBank database and provides valuable information regarding the molecular epidemiology of EV-B106 in China.

Phylogenetic Characterizations of Highly Mutated EV-B106 Recombinants Showing Extensive Genetic Exchanges with Other EV-B in Xinjiang, China

PubMed Central

Song, Yang; Zhang, Yong; Fan, Qin; Cui, Hui; Yan, Dongmei; Zhu, Shuangli; Tang, Haishu; Sun, Qiang; Wang, Dongyan; Xu, Wenbo

2017-01-01

Human enterovirus B106 (EV-B106) is a new member of the enterovirus B species. To date, only three nucleotide sequences of EV-B106 have been published, and only one full-length genome sequence (the Yunnan strain 148/YN/CHN/12) is available in the GenBank database. In this study, we conducted phylogenetic characterisation of four EV-B106 strains isolated in Xinjiang, China. Pairwise comparisons of the nucleotide sequences and the deduced amino acid sequences revealed that the four Xinjiang EV-B106 strains had only 80.5–80.8% nucleotide identity and 95.4–97.3% amino acid identity with the Yunnan EV-B106 strain, indicating high mutagenicity. Similarity plots and bootscanning analyses revealed that frequent intertypic recombination occurred in all four Xinjiang EV-B106 strains in the non-structural region. These four strains may share a donor sequence with the EV-B85 strain, which circulated in Xinjiang in 2011, indicating extensive genetic exchanges between these strains. All Xinjiang EV-B106 strains were temperature-sensitive. An antibody seroprevalence study against EV-B106 in two Xinjiang prefectures also showed low titres of neutralizing antibodies, suggesting limited exposure and transmission in the population. This study contributes the whole genome sequences of EV-B106 to the GenBank database and provides valuable information regarding the molecular epidemiology of EV-B106 in China. PMID:28230168

Extensive intragenic recombination and patterns of linkage disequilibrium at the CSN3 locus in European rabbit

PubMed Central

Carneiro, Miguel; Ferrand, Nuno

2007-01-01

Kappa-casein (CSN3) plays an important role in stabilising the Ca-sensitive caseins in the micelle. The European rabbit (Oryctolagus cuniculus) CSN3 has previously been shown to possess two alleles (A and B), which differ deeply in their intronic regions (indels of 100 and 1550 nucleotides in introns 1 and 4, respectively). Furthermore, a correlation between several reproductive performance traits and the different alleles was described. However, all these data were exclusively collected in rabbit domestic breeds, preventing a deeper understanding of the extensive polymorphism observed in the CSN3 gene. Additionally, the techniques available for the typing of both indel polymorphisms were until now not suitable for large-scale studies. In this report, we describe a simple, PCR-based typing method to distinguish rabbit CSN3 alleles. We analyse both ancient wild rabbit populations from the Iberian Peninsula and France, and the more recently derived English wild rabbits and domestic stocks. A new allele (C) showing another major indel (250 bp) in intron 1 was found, but exclusively detected in Iberian wild rabbits. In addition, our survey revealed the occurrence of new haplotypes in wild populations, suggesting that intragenic recombination is important in creating genetic diversity at this locus. This easy and low cost single-step PCR-based method results in an improvement over previous described techniques, can be easily set up in a routine molecular laboratory and would probably be a valuable tool in the management of rabbit domestic breeds. PMID:17433245

Automated haematology analysis to diagnose malaria

PubMed Central

2010-01-01

For more than a decade, flow cytometry-based automated haematology analysers have been studied for malaria diagnosis. Although current haematology analysers are not specifically designed to detect malaria-related abnormalities, most studies have found sensitivities that comply with WHO malaria-diagnostic guidelines, i.e. ≥ 95% in samples with > 100 parasites/μl. Establishing a correct and early malaria diagnosis is a prerequisite for an adequate treatment and to minimizing adverse outcomes. Expert light microscopy remains the 'gold standard' for malaria diagnosis in most clinical settings. However, it requires an explicit request from clinicians and has variable accuracy. Malaria diagnosis with flow cytometry-based haematology analysers could become an important adjuvant diagnostic tool in the routine laboratory work-up of febrile patients in or returning from malaria-endemic regions. Haematology analysers so far studied for malaria diagnosis are the Cell-Dyn®, Coulter® GEN·S and LH 750, and the Sysmex XE-2100® analysers. For Cell-Dyn analysers, abnormal depolarization events mainly in the lobularity/granularity and other scatter-plots, and various reticulocyte abnormalities have shown overall sensitivities and specificities of 49% to 97% and 61% to 100%, respectively. For the Coulter analysers, a 'malaria factor' using the monocyte and lymphocyte size standard deviations obtained by impedance detection has shown overall sensitivities and specificities of 82% to 98% and 72% to 94%, respectively. For the XE-2100, abnormal patterns in the DIFF, WBC/BASO, and RET-EXT scatter-plots, and pseudoeosinophilia and other abnormal haematological variables have been described, and multivariate diagnostic models have been designed with overall sensitivities and specificities of 86% to 97% and 81% to 98%, respectively. The accuracy for malaria diagnosis may vary according to species, parasite load, immunity and clinical context where the method is applied. Future developments in new haematology analysers such as considerably simplified, robust and inexpensive devices for malaria detection fitted with an automatically generated alert could improve the detection capacity of these instruments and potentially expand their clinical utility in malaria diagnosis. PMID:21118557

Single mode variable-sensitivity fiber optic sensors

NASA Technical Reports Server (NTRS)

Murphy, K. A.; Fogg, B. R.; Gunther, M. F.; Claus, R. O.

1992-01-01

We review spatially-weighted optical fiber sensors that filter specific vibration modes from one dimensional beams placed in clamped-free and clamped-clamped configurations. The sensitivity of the sensor is varied along the length of the fiber by tapering circular-core, dual-mode optical fibers. Selective vibration mode suppression on the order of 10 dB was obtained. We describe experimental results and propose future extensions to single mode sensor applications.

Comparison of Pelvic Phased-Array versus Endorectal Coil Magnetic Resonance Imaging at 3 Tesla for Local Staging of Prostate Cancer

PubMed Central

Kim, Bum Soo; Kim, Tae-Hwan; Kwon, Tae Gyun

2012-01-01

Purpose Several studies have demonstrated the superiority of endorectal coil magnetic resonance imaging (MRI) over pelvic phased-array coil MRI at 1.5 Tesla for local staging of prostate cancer. However, few have studied which evaluation is more accurate at 3 Tesla MRI. In this study, we compared the accuracy of local staging of prostate cancer using pelvic phased-array coil or endorectal coil MRI at 3 Tesla. Materials and Methods Between January 2005 and May 2010, 151 patients underwent radical prostatectomy. All patients were evaluated with either pelvic phased-array coil or endorectal coil prostate MRI prior to surgery (63 endorectal coils and 88 pelvic phased-array coils). Tumor stage based on MRI was compared with pathologic stage. We calculated the specificity, sensitivity and accuracy of each group in the evaluation of extracapsular extension and seminal vesicle invasion. Results Both endorectal coil and pelvic phased-array coil MRI achieved high specificity, low sensitivity and moderate accuracy for the detection of extracapsular extension and seminal vesicle invasion. There were statistically no differences in specificity, sensitivity and accuracy between the two groups. Conclusion Overall staging accuracy, sensitivity and specificity were not significantly different between endorectal coil and pelvic phased-array coil MRI. PMID:22476999

Improving anterior deltoid activity in a musculoskeletal shoulder model - an analysis of the torque-feasible space at the sternoclavicular joint.

PubMed

Ingram, David; Engelhardt, Christoph; Farron, Alain; Terrier, Alexandre; Müllhaupt, Philippe

2016-01-01

Modelling the shoulder's musculature is challenging given its mechanical and geometric complexity. The use of the ideal fibre model to represent a muscle's line of action cannot always faithfully represent the mechanical effect of each muscle, leading to considerable differences between model-estimated and in vivo measured muscle activity. While the musculo-tendon force coordination problem has been extensively analysed in terms of the cost function, only few works have investigated the existence and sensitivity of solutions to fibre topology. The goal of this paper is to present an analysis of the solution set using the concepts of torque-feasible space (TFS) and wrench-feasible space (WFS) from cable-driven robotics. A shoulder model is presented and a simple musculo-tendon force coordination problem is defined. The ideal fibre model for representing muscles is reviewed and the TFS and WFS are defined, leading to the necessary and sufficient conditions for the existence of a solution. The shoulder model's TFS is analysed to explain the lack of anterior deltoid (DLTa) activity. Based on the analysis, a modification of the model's muscle fibre geometry is proposed. The performance with and without the modification is assessed by solving the musculo-tendon force coordination problem for quasi-static abduction in the scapular plane. After the proposed modification, the DLTa reaches 20% of activation.

Atlantic Bluefin Tuna (Thunnus thynnus) Biometrics and Condition.

PubMed

Rodriguez-Marin, Enrique; Ortiz, Mauricio; Ortiz de Urbina, José María; Quelle, Pablo; Walter, John; Abid, Noureddine; Addis, Piero; Alot, Enrique; Andrushchenko, Irene; Deguara, Simeon; Di Natale, Antonio; Gatt, Mark; Golet, Walter; Karakulak, Saadet; Kimoto, Ai; Macias, David; Saber, Samar; Santos, Miguel Neves; Zarrad, Rafik

2015-01-01

The compiled data for this study represents the first Atlantic and Mediterranean-wide effort to pool all available biometric data for Atlantic bluefin tuna (Thunnus thynnus) with the collaboration of many countries and scientific groups. Biometric relationships were based on an extensive sampling (over 140,000 fish sampled), covering most of the fishing areas for this species in the North Atlantic Ocean and Mediterranean Sea. Sensitivity analyses were carried out to evaluate the representativeness of sampling and explore the most adequate procedure to fit the weight-length relationship (WLR). The selected model for the WLRs by stock included standardized data series (common measurement types) weighted by the inverse variability. There was little difference between annual stock-specific round weight-straight fork length relationships, with an overall difference of 6% in weight. The predicted weight by month was estimated as an additional component in the exponent of the weight-length function. The analyses of monthly variations of fish condition by stock, maturity state and geographic area reflect annual cycles of spawning and feeding behavior. We update and improve upon the biometric relationships for bluefin currently used by the International Commission for the Conservation of Atlantic Tunas, by incorporating substantially larger datasets than ever previously compiled, providing complete documentation of sources and employing robust statistical fitting. WLRs and other conversion factors estimated in this study differ from the ones used in previous bluefin stock assessments.

Extensions and applications of a second-order landsurface parameterization

NASA Technical Reports Server (NTRS)

Andreou, S. A.; Eagleson, P. S.

1983-01-01

Extensions and applications of a second order land surface parameterization, proposed by Andreou and Eagleson are developed. Procedures for evaluating the near surface storage depth used in one cell land surface parameterizations are suggested and tested by using the model. Sensitivity analysis to the key soil parameters is performed. A case study involving comparison with an "exact" numerical model and another simplified parameterization, under very dry climatic conditions and for two different soil types, is also incorporated.

JPL Contamination Control Engineering

NASA Technical Reports Server (NTRS)

Blakkolb, Brian

2013-01-01

JPL has extensive expertise fielding contamination sensitive missions-in house and with our NASA/industry/academic partners.t Development and implementation of performance-driven cleanliness requirements for a wide range missions and payloads - UV-Vis-IR: GALEX, Dawn, Juno, WFPC-II, AIRS, TES, et al - Propulsion, thermal control, robotic sample acquisition systems. Contamination control engineering across the mission life cycle: - System and payload requirements derivation, analysis, and contamination control implementation plans - Hardware Design, Risk trades, Requirements V-V - Assembly, Integration & Test planning and implementation - Launch site operations and launch vehicle/payload integration - Flight ops center dot Personnel on staff have expertise with space materials development and flight experiments. JPL has capabilities and expertise to successfully address contamination issues presented by space and habitable environments. JPL has extensive experience fielding and managing contamination sensitive missions. Excellent working relationship with the aerospace contamination control engineering community/.

Hyper-Acetylation of Histone H3K56 Limits Break-Induced Replication by Inhibiting Extensive Repair Synthesis

PubMed Central

Che, Jun; Smith, Stephanie; Kim, Yoo Jung; Shim, Eun Yong; Myung, Kyungjae; Lee, Sang Eun

2015-01-01

Break-induced replication (BIR) has been implicated in restoring eroded telomeres and collapsed replication forks via single-ended invasion and extensive DNA synthesis on the recipient chromosome. Unlike other recombination subtypes, DNA synthesis in BIR likely relies heavily on mechanisms enabling efficient fork progression such as chromatin modification. Herein we report that deletion of HST3 and HST4, two redundant de-acetylases of histone H3 Lysine 56 (H3K56), inhibits BIR, sensitizes checkpoint deficient cells to deoxyribonucleotide triphosphate pool depletion, and elevates translocation-type gross chromosomal rearrangements (GCR). The basis for deficiency in BIR and gene conversion with long gap synthesis in hst3Δ hst4Δ cells can be traced to a defect in extensive DNA synthesis. Distinct from other cellular defects associated with deletion of HST3 and HST4 including thermo-sensitivity and elevated spontaneous mutagenesis, the BIR defect in hst3Δ hst4Δ cannot be offset by the deletion of RAD17 or MMS22, but rather by the loss of RTT109 or ASF1, or in combination with the H3K56R mutation, which also restores tolerance to replication stress in mrc1 mutants. Our studies suggest that acetylation of H3K56 limits extensive repair synthesis and interferes with efficient fork progression in BIR. PMID:25705897

Get even and feel good? Moderating effects of justice sensitivity and counterproductive work behavior on the relationship between illegitimate tasks and self-esteem.

PubMed

Schulte-Braucks, Julia; Baethge, Anja; Dormann, Christian; Vahle-Hinz, Tim

2018-04-23

We proposed that effects of illegitimate tasks, which comprise unreasonable and unnecessary tasks, on self-esteem and counterproductive work behavior (CWB) are enhanced among employees who are highly sensitive to injustice. CWB was further proposed to be a moderating coping strategy, which restores justice and buffers the detrimental effects of illegitimate tasks on self-esteem. In this study, 241 employees participated in a diary study over five workdays and a follow-up questionnaire one week later. Daily effects were determined in multilevel analyses: Unreasonable tasks decreased self-esteem and increased CWB the same day, especially among employees high in trait justice sensitivity. Unnecessary tasks only related to more CWB the same day, regardless of one's justice sensitivity. Weekly effects were determined in cross-lagged panel analyses: Unreasonable and unnecessary tasks increased CWB, and justice sensitivity moderated the effect of unreasonable tasks on CWB and of unnecessary tasks on self-esteem. Moderating effects of CWB were split: In daily analyses, CWB buffered the negative effects of illegitimate tasks. In weekly analyses, CWB enhanced the negative effects of illegitimate tasks. Overall, illegitimate tasks rather affected CWB than self-esteem, with more consistent effects for unreasonable than for unnecessary tasks. Thus, we confirm illegitimate tasks as a relevant work stressor with issues of injustice being central to this concept and personality having an influence on what is perceived as (il)legitimate. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Validation and subsequent development of the DEREK skin sensitization rulebase by analysis of the BgVV list of contact allergens.

PubMed

Barratt, M D; Langowski, J J

1999-01-01

The DEREK knowledge-based computer system contains a subset of approximately 50 rules describing chemical substructures (toxophores) responsible for skin sensitization. This rulebase, based originally on Unilever historical in-house guinea pig maximization test data, has been subject to extensive validation and is undergoing refinement as the next stage of its development. As part of an ongoing program of validation and testing, the predictive ability of the sensitization rule set has been assessed by processing the structures of the 84 chemical substances in the list of contact allergens issued by the BgVV (German Federal Institute for Health Protection of Consumers). This list of chemicals is important because the biological data for each of the chemicals have been carefully scrutinized and peer reviewed, a key consideration in an area of toxicology in which much unreliable and potentially misleading data have been published. The existing DEREK rulebase for skin sensitization identified toxophores for skin sensitization in the structures of 71 out of the 84 chemicals (85%). The exercise highlighted areas of chemistry where further development of the rulebase was required, either by extension of the scope of existing rules or by generation of new rules where a sound mechanistic rationale for the biological activity could be established. Chemicals likely to be acting as photoallergens were identified, and new rules for photoallergenicity have subsequently been written. At the end of the exercise, the refined rulebase was able to identify toxophores for skin sensitization for 82 of the 84 chemicals in the BgVV list.

Optimum sensitivity derivatives of objective functions in nonlinear programming

NASA Technical Reports Server (NTRS)

Barthelemy, J.-F. M.; Sobieszczanski-Sobieski, J.

1983-01-01

The feasibility of eliminating second derivatives from the input of optimum sensitivity analyses of optimization problems is demonstrated. This elimination restricts the sensitivity analysis to the first-order sensitivity derivatives of the objective function. It is also shown that when a complete first-order sensitivity analysis is performed, second-order sensitivity derivatives of the objective function are available at little additional cost. An expression is derived whose application to linear programming is presented.

Decadal and seasonal changes in temperature, salinity, nitrate, and chlorophyll in inshore and offshore waters along southeast Australia

NASA Astrophysics Data System (ADS)

Kelly, Paige; Clementson, Lesley; Lyne, Vincent

2015-06-01

Sixty years of oceanographic in situ data at Port Hacking (34°S) and Maria Island (42°S) and 15 years of satellite-derived chlorophyll a (chl a) in inshore and offshore waters of southeast Australia show changes in the seasonality and trend of water properties consistent with long-term intensification and southerly extensions of East Australian Current (EAC) water. Decadal analyses reveal that the EAC extension water at Maria Island increased gradually from the 1940s to 1980s, followed by a rapid increase since the 1990s. This acceleration coincided with enhanced winter nitrate, implying increased injections of subantarctic water at Maria Island. Satellite-derived chl a at six coastal sites and offshore companion sites in the western Tasman Sea showed significant inshore-offshore variations in seasonal cycle and long-term trend. After 2004-2005, the Maria Island seasonal cycle became increasingly similar to those of Bass Strait and St. Helens, suggesting that the EAC extension water was extending further southward. Comparative analyses of inshore-offshore sites showed that the presence of EAC extension water declined offshore. Seasonal cycles at Maria Island show a recent shift away from the traditional spring bloom, toward increased winter biomass, and enhanced primary productivity consistent with extensions of warm, energetic EAC extension water and more frequent injections of cooler, fresher nitrate-replete waters. Overall, we find complex temporal, latitudinal, and inshore-offshore changes in multiple water masses, particularly at Maria Island, and changes in primary productivity that will profoundly impact fisheries and ecosystems.

Sensitivity and specificity of subacute computerized neurocognitive testing and symptom evaluation in predicting outcomes after sports-related concussion.

PubMed

Lau, Brian C; Collins, Michael W; Lovell, Mark R

2011-06-01

Concussions affect an estimated 136 000 high school athletes yearly. Computerized neurocognitive testing has been shown to be appropriately sensitive and specific in diagnosing concussions, but no studies have assessed its utility to predict length of recovery. Determining prognosis during subacute recovery after sports concussion will help clinicians more confidently address return-to-play and academic decisions. To quantify the prognostic ability of computerized neurocognitive testing in combination with symptoms during the subacute recovery phase from sports-related concussion. Cohort study (prognosis); Level of evidence, 2. In sum, 108 male high school football athletes completed a computer-based neurocognitive test battery within 2.23 days of injury and were followed until returned to play as set by international guidelines. Athletes were grouped into protracted recovery (>14 days; n = 50) or short-recovery (≤14 days; n = 58). Separate discriminant function analyses were performed using total symptom score on Post-Concussion Symptom Scale, symptom clusters (migraine, cognitive, sleep, neuropsychiatric), and Immediate Postconcussion Assessment and Cognitive Testing neurocognitive scores (verbal memory, visual memory, reaction time, processing speed). Multiple discriminant function analyses revealed that the combination of 4 symptom clusters and 4 neurocognitive composite scores had the highest sensitivity (65.22%), specificity (80.36%), positive predictive value (73.17%), and negative predictive value (73.80%) in predicting protracted recovery. Discriminant function analyses of total symptoms on the Post-Concussion Symptom Scale alone had a sensitivity of 40.81%; specificity, 79.31%; positive predictive value, 62.50%; and negative predictive value, 61.33%. The 4 symptom clusters alone discriminant function analyses had a sensitivity of 46.94%; specificity, 77.20%; positive predictive value, 63.90%; and negative predictive value, 62.86%. Discriminant function analyses of the 4 computerized neurocognitive scores alone had a sensitivity of 53.20%; specificity, 75.44%; positive predictive value, 64.10%; and negative predictive value, 66.15%. The use of computerized neurocognitive testing in conjunction with symptom clusters results improves sensitivity, specificity, positive predictive value, and negative predictive value of predicting protracted recovery compared with each used alone. There is also a net increase in sensitivity of 24.41% when using neurocognitive testing and symptom clusters together compared with using total symptoms on Post-Concussion Symptom Scale alone.

Near N-S paleo-extension in the western Deccan region, India: Does it link strike-slip tectonics with India-Seychelles rifting?

NASA Astrophysics Data System (ADS)

Misra, Achyuta Ayan; Bhattacharya, Gourab; Mukherjee, Soumyajit; Bose, Narayan

2014-09-01

This is the first detailed report and analyses of deformation from the W part of the Deccan large igneous province (DLIP), Maharashtra, India. This deformation, related to the India-Seychelles rifting during Late Cretaceous-Early Paleocene, was studied, and the paleostress tensors were deduced. Near N-S trending shear zones, lineaments, and faults were already reported without significant detail. An E-W extension was envisaged by the previous workers to explain the India-Seychelles rift at ~64 Ma. The direction of extension, however, does not match with their N-S brittle shear zones and also those faults (sub-vertical, ~NE-SW/~NW-SE, and few ~N-S) we report and emphasize in this work. Slickenside-bearing fault planes, brittle shear zones, and extension fractures in meso-scale enabled us to estimate the paleostress tensors (directions and relative magnitudes). The field study was complemented by remote sensing lineament analyses to map dykes and shear zones. Dykes emplaced along pre-existing ~N-S to ~NE-SW/~NW-SE shears/fractures. This information was used to derive regional paleostress trends. A ~NW-SE/NE-SW minimum compressive stress in the oldest Kalsubai Subgroup and a ~N-S direction for the younger Lonavala, Wai, and Salsette Subgroups were deciphered. Thus, a ~NW/NE to ~N-S extension is put forward that refutes the popular view of E-W India-Seychelles extension. Paleostress analyses indicate that this is an oblique rifted margin. Field criteria suggest only ~NE-SW and ~NW-SE, with some ~N-S strike-slip faults/brittle shear zones. We refer this deformation zone as the "Western Deccan Strike-slip Zone" (WDSZ). The observed deformation was matched with offshore tectonics deciphered mainly from faults interpreted on seismic profiles and from magnetic seafloor spreading anomalies. These geophysical findings too indicate oblique rifting in this part of the W Indian passive margin. We argue that the Seychelles microcontinent separated from India only after much of the DLIP erupted. Further studies of magma-rich passive margins with respect to timing and architecture of deformation and emplacement of volcanics are required.

New Uses for Sensitivity Analysis: How Different Movement Tasks Effect Limb Model Parameter Sensitivity

NASA Technical Reports Server (NTRS)

Winters, J. M.; Stark, L.

1984-01-01

Original results for a newly developed eight-order nonlinear limb antagonistic muscle model of elbow flexion and extension are presented. A wider variety of sensitivity analysis techniques are used and a systematic protocol is established that shows how the different methods can be used efficiently to complement one another for maximum insight into model sensitivity. It is explicitly shown how the sensitivity of output behaviors to model parameters is a function of the controller input sequence, i.e., of the movement task. When the task is changed (for instance, from an input sequence that results in the usual fast movement task to a slower movement that may also involve external loading, etc.) the set of parameters with high sensitivity will in general also change. Such task-specific use of sensitivity analysis techniques identifies the set of parameters most important for a given task, and even suggests task-specific model reduction possibilities.

Is there a role for pre-operative contrast-enhanced magnetic resonance imaging for radical surgery in malignant pleural mesothelioma?

PubMed

Stewart, Duncan; Waller, David; Edwards, John; Jeyapalan, Kanagaratnam; Entwisle, James

2003-12-01

To assess the use of contrast-enhanced magnetic resonance imaging (CEMRI) in addition to computed tomography in the pre-operative assessment of patients for radical surgery in malignant pleural mesothelioma. Over a 45-month period, 51 of 76 patients assessed (69 men and seven women), underwent extra-pleural pneumonectomy or radical pleurectomy/decortication. Post-operative pathological stage was correlated with radiological staging, with particular emphasis on tumour resectability. Seventeen (22%) patients were found on CEMRI to have unresectable, but histologically unconfirmed disease, not previously seen on CT. Fifty-one (67%) patients proceeded to radical surgery, but pathological nodal data were incomplete in three, so excluding these patients from further analyses. The median pre-operative interval after CEMRI was 17 days. Two patients were found to have unexpectedly extensive disease at thoracotomy, thus the sensitivity of CEMRI for prediction of resectability was 97%. Using the International Mesothelioma Interest Group system, tumour stage was correctly predicted by CEMRI in 48% of patients, but understaged in 50% of cases, largely due to the underestimation of pericardial involvement, but this did not affect resectability and had no significant effect on prognosis. Nodal stage was correctly identified in 60% of patients. CEMRI was successful in predicting pathological tumour stage T3 or less (sensitivity of 85%; specificity of 100%), but less so in identifying tumour stage T2 or less (sensitivity of 23%; specificity of 96%) or N2 nodal disease (sensitivity 66%; specificity 73%). CEMRI is most useful in the differentiation of T3 and T4 disease and may be unnecessary at earlier stages. Its multiplanar tumour localisation abilities are of value in the assessment of resectability. It is unlikely to contribute significantly to nodal staging, but it remains a valuable adjunct in the selection of patients for radical surgery.

Agreement between patients' self-report and medical records for vaccination: the PGRx database.

PubMed

Grimaldi-Bensouda, Lamiae; Aubrun, Elodie; Leighton, Pamela; Benichou, Jacques; Rossignol, Michel; Abenhaim, Lucien

2013-03-01

Patients' self-reported vaccine exposure (PS) may be subject to memory errors and other biases. Physicians' prescription records and other medical records (MR) do not capture noncompliance with vaccination. This study compared PS with MR for influenza, 23-valent pneumococcal, and human papillomavirus (HPV) vaccines. The Pharmacoepidemiologic General Research Extension (PGRx) database uses a network of over 300 general practitioners across France, who systematically recruit an age- and sex-stratified sample of patients (≥ 14 years old), without reference to their diagnoses or prescriptions. Patients received a structured telephone interview, combined with an interview guide listing vaccines commonly given. Patients' self-reported vaccination in the 3 years before their recruitment was compared with medical records kept by the physician or the patient. Concordance between PS and MR was assessed for 7613 patients for whom both sources of information were available. Agreement within 3 years before the recruitment date was substantial for influenza vaccines (prevalence and bias-adjusted kappa [PABAK] = 0.74, sensitivity PS relative to MR 81.5%) and high for 23-valent pneumococcal vaccines (PABAK = 0.98, sensitivity PS 49.6) and HPV vaccines (PABAK = 0.92, sensitivity PS 91.6). In adjusted analyses, agreement varied with sociodemographic and health-related factors, particularly for influenza and 23-valent pneumococcal vaccines. The PGRx method for drug exposure assessment is a new tool in pharmacoepidemiology that shows substantial to high agreement between PS and MR for exposure to various vaccines. Our finding of high agreement between PS and MR for HPV vaccination status in young women is a significant addition to the literature. Copyright © 2013 John Wiley & Sons, Ltd.

From the ultrasonic to the infrared: molecular evolution and the sensory biology of bats

PubMed Central

Jones, Gareth; Teeling, Emma C.; Rossiter, Stephen J.

2013-01-01

Great advances have been made recently in understanding the genetic basis of the sensory biology of bats. Research has focused on the molecular evolution of candidate sensory genes, genes with known functions [e.g., olfactory receptor (OR) genes] and genes identified from mutations associated with sensory deficits (e.g., blindness and deafness). For example, the FoxP2 gene, underpinning vocal behavior and sensorimotor coordination, has undergone diversification in bats, while several genes associated with audition show parallel amino acid substitutions in unrelated lineages of echolocating bats and, in some cases, in echolocating dolphins, representing a classic case of convergent molecular evolution. Vision genes encoding the photopigments rhodopsin and the long-wave sensitive opsin are functional in bats, while that encoding the short-wave sensitive opsin has lost functionality in rhinolophoid bats using high-duty cycle laryngeal echolocation, suggesting a sensory trade-off between investment in vision and echolocation. In terms of olfaction, bats appear to have a distinctive OR repertoire compared with other mammals, and a gene involved in signal transduction in the vomeronasal system has become non-functional in most bat species. Bitter taste receptors appear to have undergone a “birth-and death” evolution involving extensive gene duplication and loss, unlike genes coding for sweet and umami tastes that show conservation across most lineages but loss in vampire bats. Common vampire bats have also undergone adaptations for thermoperception, via alternative splicing resulting in the evolution of a novel heat-sensitive channel. The future for understanding the molecular basis of sensory biology is promising, with great potential for comparative genomic analyses, studies on gene regulation and expression, exploration of the role of alternative splicing in the generation of proteomic diversity, and linking genetic mechanisms to behavioral consequences. PMID:23755015

UNE-EN ISO/IEC 17025:2005-accredited method for the determination of pesticide residues in fruit and vegetable samples by LC-MS/MS.

PubMed

Camino-Sánchez, F J; Zafra-Gómez, A; Oliver-Rodríguez, B; Ballesteros, O; Navalón, A; Crovetto, G; Vílchez, J L

2010-11-01

A rapid, simple and sensitive multi-residue method was developed and validated for the simultaneous quantification and confirmation of 69 pesticides in fruit and vegetables using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The samples were extracted following the quick, easy, cheap, effective, rugged and safe method known as QuEChERS. Mass spectrometric conditions were individually optimised for each analyte in order to achieve maximum sensitivity in multiple reaction monitoring (MRM) mode. Using the developed chromatographic conditions, 69 pesticides can be separated in less than 17 min. Two selected reaction monitoring (SRM) assays were used for each pesticide to obtain simultaneous quantification and identification in one run. With this method in SRM mode, more than 150 pesticides can be analysed and quantified, but their confirmation is not possible in all cases according to the European regulations on pesticide residues. Nine common representative matrices (zucchini, melon, cucumber, watermelon, tomato, garlic, eggplant, lettuce and pepper) were selected to investigate the effect of different matrices on recovery and precision. Mean recoveries ranged from 70% to 120%, with relative standard deviations (RSDs) lower than 20% for all the pesticides. The proposed method was applied to the analysis of more than 2000 vegetable samples from the extensive greenhouse cultivation in the province of Almeria, Spain, during one year. The methodology combines the advantages of both QuEChERS and LC-MS/MS producing a very rapid, sensitive, accurate and reliable procedure that can be applied in routine analytical laboratories. The method was validated and accredited according to UNE-EN-ISO/IEC 17025:2005 international standard (accreditation number 278/LE1027).

Exploratory Hydrocarbon Drilling Impacts to Arctic Lake Ecosystems

PubMed Central

Thienpont, Joshua R.; Kokelj, Steven V.; Korosi, Jennifer B.; Cheng, Elisa S.; Desjardins, Cyndy; Kimpe, Linda E.; Blais, Jules M.; Pisaric, Michael FJ.; Smol, John P.

2013-01-01

Recent attention regarding the impacts of oil and gas development and exploitation has focused on the unintentional release of hydrocarbons into the environment, whilst the potential negative effects of other possible avenues of environmental contamination are less well documented. In the hydrocarbon-rich and ecologically sensitive Mackenzie Delta region (NT, Canada), saline wastes associated with hydrocarbon exploration have typically been disposed of in drilling sumps (i.e., large pits excavated into the permafrost) that were believed to be a permanent containment solution. However, failure of permafrost as a waste containment medium may cause impacts to lakes in this sensitive environment. Here, we examine the effects of degrading drilling sumps on water quality by combining paleolimnological approaches with the analysis of an extensive present-day water chemistry dataset. This dataset includes lakes believed to have been impacted by saline drilling fluids leaching from drilling sumps, lakes with no visible disturbances, and lakes impacted by significant, naturally occurring permafrost thaw in the form of retrogressive thaw slumps. We show that lakes impacted by compromised drilling sumps have significantly elevated lakewater conductivity levels compared to control sites. Chloride levels are particularly elevated in sump-impacted lakes relative to all other lakes included in the survey. Paleolimnological analyses showed that invertebrate assemblages appear to have responded to the leaching of drilling wastes by a discernible increase in a taxon known to be tolerant of elevated conductivity coincident with the timing of sump construction. This suggests construction and abandonment techniques at, or soon after, sump establishment may result in impacts to downstream aquatic ecosystems. With hydrocarbon development in the north predicted to expand in the coming decades, the use of sumps must be examined in light of the threat of accelerated permafrost thaw, and the potential for these industrial wastes to impact sensitive Arctic ecosystems. PMID:24223170

Exploratory hydrocarbon drilling impacts to Arctic lake ecosystems.

PubMed

Thienpont, Joshua R; Kokelj, Steven V; Korosi, Jennifer B; Cheng, Elisa S; Desjardins, Cyndy; Kimpe, Linda E; Blais, Jules M; Pisaric, Michael F J; Smol, John P

2013-01-01

Recent attention regarding the impacts of oil and gas development and exploitation has focused on the unintentional release of hydrocarbons into the environment, whilst the potential negative effects of other possible avenues of environmental contamination are less well documented. In the hydrocarbon-rich and ecologically sensitive Mackenzie Delta region (NT, Canada), saline wastes associated with hydrocarbon exploration have typically been disposed of in drilling sumps (i.e., large pits excavated into the permafrost) that were believed to be a permanent containment solution. However, failure of permafrost as a waste containment medium may cause impacts to lakes in this sensitive environment. Here, we examine the effects of degrading drilling sumps on water quality by combining paleolimnological approaches with the analysis of an extensive present-day water chemistry dataset. This dataset includes lakes believed to have been impacted by saline drilling fluids leaching from drilling sumps, lakes with no visible disturbances, and lakes impacted by significant, naturally occurring permafrost thaw in the form of retrogressive thaw slumps. We show that lakes impacted by compromised drilling sumps have significantly elevated lakewater conductivity levels compared to control sites. Chloride levels are particularly elevated in sump-impacted lakes relative to all other lakes included in the survey. Paleolimnological analyses showed that invertebrate assemblages appear to have responded to the leaching of drilling wastes by a discernible increase in a taxon known to be tolerant of elevated conductivity coincident with the timing of sump construction. This suggests construction and abandonment techniques at, or soon after, sump establishment may result in impacts to downstream aquatic ecosystems. With hydrocarbon development in the north predicted to expand in the coming decades, the use of sumps must be examined in light of the threat of accelerated permafrost thaw, and the potential for these industrial wastes to impact sensitive Arctic ecosystems.

Quantification of Kryptofix 2.2.2 in [18F]fluorine-labelled radiopharmaceuticals by rapid-resolution liquid chromatography.

PubMed

Lao, Yexing; Yang, Cuiping; Zou, Wei; Gan, Manquan; Chen, Ping; Su, Weiwei

2012-05-01

The cryptand Kryptofix 2.2.2 is used extensively as a phase-transfer reagent in the preparation of [18F]fluoride-labelled radiopharmaceuticals. However, it has considerable acute toxicity. The aim of this study was to develop and validate a method for rapid (within 1 min), specific and sensitive quantification of Kryptofix 2.2.2 at trace levels. Chromatographic separations were carried out by rapid-resolution liquid chromatography (Agilent ZORBAX SB-C18 rapid-resolution column, 2.1 × 30 mm, 3.5 μm). Tandem mass spectra were acquired using a triple quadrupole mass spectrometer equipped with an electrospray ionization interface. Quantitative mass spectrometric analysis was conducted in positive ion mode and multiple reaction monitoring mode for the m/z 377.3 → 114.1 transition for Kryptofix 2.2.2. The external standard method was used for quantification. The method met the precision and efficiency requirements for PET radiopharmaceuticals, providing satisfactory results for specificity, matrix effect, stability, linearity (0.5-100 ng/ml, r(2)=0.9975), precision (coefficient of variation < 5%), accuracy (relative error < ± 3%), sensitivity (lower limit of quantification=0.5 ng) and detection time (<1 min). Fluorodeoxyglucose (n=6) was analysed, and the Kryptofix 2.2.2 content was found to be well below the maximum permissible levels approved by the US Food and Drug Administration. The developed method has a short analysis time (<1 min) and high sensitivity (lower limit of quantification=0.5 ng/ml) and can be successfully applied to rapid quantification of Kryptofix 2.2.2 at trace levels in fluorodeoxyglucose. This method could also be applied to other [18F]fluorine-labelled radiopharmaceuticals that use Kryptofix 2.2.2 as a phase-transfer reagent.

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial.

PubMed

Kyriakopoulos, Christos E; Chen, Yu-Hui; Carducci, Michael A; Liu, Glenn; Jarrard, David F; Hahn, Noah M; Shevrin, Daniel H; Dreicer, Robert; Hussain, Maha; Eisenberger, Mario; Kohli, Manish; Plimack, Elizabeth R; Vogelzang, Nicholas J; Picus, Joel; Cooney, Matthew M; Garcia, Jorge A; DiPaola, Robert S; Sweeney, Christopher J

2018-04-10

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m 2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P < .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells.

PubMed

Woollhead, A M; Sivagnanasundaram, J; Kalsi, K K; Pucovsky, V; Pellatt, L J; Scott, J W; Mustard, K J; Hardie, D G; Baines, D L

2007-08-01

AMP-activated protein kinase (AMPK) is activated by metformin, phenformin, and the AMP mimetic, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). We have completed an extensive study of the pharmacological effects of these drugs on AMPK activation, adenine nucleotide concentration, transepithelial amiloride-sensitive (I(amiloride)) and ouabain-sensitive basolateral (I(ouabain)) short circuit current in H441 lung epithelial cells. H441 cells were grown on permeable filters at air interface. I(amiloride), I(ouabain) and transepithelial resistance were measured in Ussing chambers. AMPK activity was measured as the amount of radiolabelled phosphate transferred to the SAMS peptide. Adenine nucleotide concentration was analysed by reverse phase HPLC and NAD(P)H autofluorescence was measured using confocal microscopy. Phenformin, AICAR and metformin increased AMPK (alpha1) activity and decreased I(amiloride). The AMPK inhibitor Compound C prevented the action of metformin and AICAR but not phenformin. Phenformin and AICAR decreased I(ouabain) across H441 monolayers and decreased monolayer resistance. The decrease in I(amiloride) was closely related to I(ouabain) with phenformin, but not in AICAR treated monolayers. Metformin and phenformin increased the cellular AMP:ATP ratio but only phenformin and AICAR decreased cellular ATP. Activation of alpha1-AMPK is associated with inhibition of apical amiloride-sensitive Na(+) channels (ENaC), which has important implications for the clinical use of metformin. Additional pharmacological effects evoked by AICAR and phenformin on I(ouabain), with potential secondary effects on apical Na+ conductance, ENaC activity and monolayer resistance, have important consequences for their use as pharmacological activators of AMPK in cell systems where Na+K+ATPase is an important component.

Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells

PubMed Central

Woollhead, A M; Sivagnanasundaram, J; Kalsi, K K; Pucovsky, V; Pellatt, L J; Scott, J W; Mustard, K J; Hardie, D G; Baines, D L

2007-01-01

Background and purpose: AMP-activated protein kinase (AMPK) is activated by metformin, phenformin, and the AMP mimetic, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). We have completed an extensive study of the pharmacological effects of these drugs on AMPK activation, adenine nucleotide concentration, transepithelial amiloride-sensitive (Iamiloride) and ouabain-sensitive basolateral (Iouabain) short circuit current in H441 lung epithelial cells. Experimental approach: H441 cells were grown on permeable filters at air interface. Iamiloride, Iouabain and transepithelial resistance were measured in Ussing chambers. AMPK activity was measured as the amount of radiolabelled phosphate transferred to the SAMS peptide. Adenine nucleotide concentration was analysed by reverse phase HPLC and NAD(P)H autofluorescence was measured using confocal microscopy. Key results: Phenformin, AICAR and metformin increased AMPK (α1) activity and decreased Iamiloride. The AMPK inhibitor Compound C prevented the action of metformin and AICAR but not phenformin. Phenformin and AICAR decreased Iouabain across H441 monolayers and decreased monolayer resistance. The decrease in Iamiloride was closely related to Iouabain with phenformin, but not in AICAR treated monolayers. Metformin and phenformin increased the cellular AMP:ATP ratio but only phenformin and AICAR decreased cellular ATP. Conclusions and implications: Activation of α1-AMPK is associated with inhibition of apical amiloride-sensitive Na+ channels (ENaC), which has important implications for the clinical use of metformin. Additional pharmacological effects evoked by AICAR and phenformin on Iouabain, with potential secondary effects on apical Na+ conductance, ENaC activity and monolayer resistance, have important consequences for their use as pharmacological activators of AMPK in cell systems where Na+K+ATPase is an important component. PMID:17603555

Cost-utility of First-line Disease-modifying Treatments for Relapsing-Remitting Multiple Sclerosis.

PubMed

Soini, Erkki; Joutseno, Jaana; Sumelahti, Marja-Liisa

2017-03-01

This study evaluated the cost-effectiveness of first-line treatments of relapsing-remitting multiple sclerosis (RRMS) (dimethyl fumarate [DMF] 240 mg PO BID, teriflunomide 14 mg once daily, glatiramer acetate 20 mg SC once daily, interferon [IFN]-β1a 44 µg TIW, IFN-β1b 250 µg EOD, and IFN-β1a 30 µg IM QW) and best supportive care (BSC) in the health care payer setting in Finland. The primary outcome was the modeled incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained, 3%/y discounting). Markov cohort modeling with a 15-year time horizon was employed. During each 1-year modeling cycle, patients either maintained the Expanded Disability Status Scale (EDSS) score or experienced progression, developed secondary progressive MS (SPMS) or showed EDSS progression in SPMS, experienced relapse with/without hospitalization, experienced an adverse event (AE), or died. Patients׳ characteristics, RRMS progression probabilities, and standardized mortality ratios were derived from a registry of patients with MS in Finland. A mixed-treatment comparison (MTC) informed the treatment effects. Finnish EuroQol Five-Dimensional Questionnaire, Three-Level Version quality-of-life and direct-cost estimates associated with EDSS scores, relapses, and AEs were applied. Four approaches were used to assess the outcomes: cost-effectiveness plane and efficiency frontiers (relative value of efficient treatments); cost-effectiveness acceptability frontier, which demonstrated optimal treatment to maximize net benefit; Bayesian treatment ranking (BTR); and an impact investment assessment (IIA; a cost-benefit assessment), which increased the clinical interpretation and appeal of modeled outcomes in terms of absolute benefit gained with fixed drug-related budget. Robustness of results was tested extensively with sensitivity analyses. Based on the modeled results, teriflunomide was less costly, with greater QALYs, versus glatiramer acetate and the IFNs. Teriflunomide had the lowest ICER (24,081) versus BSC. DMF brought marginally more QALYs (0.089) than did teriflunomide, with greater costs over the 15 years. The ICER for DMF versus teriflunomide was 75,431. Teriflunomide had >50% cost-effectiveness probabilities with a willingness-to-pay threshold of <€77,416/QALY gained. According to BTR, teriflunomide was first-best among the disease-modifying therapies, with potential willingness-to-pay thresholds of up to €68,000/QALY gained. In the IIA, teriflunomide was associated with the longest incremental quality-adjusted survival and time without cane use. Generally, primary outcomes results were robust, based on the sensitivity analyses. The results were sensitive only to large changes in analysis perspective or mixed-treatment comparison. The results were sensitive only to large changes in analysis perspective or MTC. Based on the analyses, teriflunomide was cost-effective versus BSC or DMF with the common threshold values, was dominant versus other first-line RRMS treatments, and provided the greatest impact on investment. Teriflunomide is potentially the most cost-effective option among first-line treatments of RRMS in Finland. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Sunflower seeds as eliciting agents of Compositae dermatitis.

PubMed

Paulsen, Evy; El-Houri, Rime B; Andersen, Klaus E; Christensen, Lars P

2015-03-01

Sunflowers may cause dermatitis because of allergenic sesquiterpene lactones (SLs). Contact sensitization to sunflower seeds has also been reported, but the allergens are unknown. To analyse sunflower seeds for the presence of SLs and to assess the prevalence of sunflower sensitization in Compositae-allergic individuals. Sunflower-sensitive patients were identified by aimed patch testing. A dichloromethane extract of whole sunflower seeds was analysed by liquid chromatography-mass spectrometry and high-performance liquid chromatography. The prevalence of sensitivity to sunflower in Compositae-allergic individuals was 56%. A solvent wash of whole sunflower seeds yielded an extract containing SLs, the principal component tentatively being identified as argophyllin A or B, other SLs being present in minute amounts. The concentration of SLs on the sunflower seeds is considered high enough to elicit dermatitis in sensitive persons, and it seems appropriate to warn Compositae-allergic subjects against handling sunflower seeds. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Efficient Gradient-Based Shape Optimization Methodology Using Inviscid/Viscous CFD

NASA Technical Reports Server (NTRS)

Baysal, Oktay

1997-01-01

The formerly developed preconditioned-biconjugate-gradient (PBCG) solvers for the analysis and the sensitivity equations had resulted in very large error reductions per iteration; quadratic convergence was achieved whenever the solution entered the domain of attraction to the root. Its memory requirement was also lower as compared to a direct inversion solver. However, this memory requirement was high enough to preclude the realistic, high grid-density design of a practical 3D geometry. This limitation served as the impetus to the first-year activity (March 9, 1995 to March 8, 1996). Therefore, the major activity for this period was the development of the low-memory methodology for the discrete-sensitivity-based shape optimization. This was accomplished by solving all the resulting sets of equations using an alternating-direction-implicit (ADI) approach. The results indicated that shape optimization problems which required large numbers of grid points could be resolved with a gradient-based approach. Therefore, to better utilize the computational resources, it was recommended that a number of coarse grid cases, using the PBCG method, should initially be conducted to better define the optimization problem and the design space, and obtain an improved initial shape. Subsequently, a fine grid shape optimization, which necessitates using the ADI method, should be conducted to accurately obtain the final optimized shape. The other activity during this period was the interaction with the members of the Aerodynamic and Aeroacoustic Methods Branch of Langley Research Center during one stage of their investigation to develop an adjoint-variable sensitivity method using the viscous flow equations. This method had algorithmic similarities to the variational sensitivity methods and the control-theory approach. However, unlike the prior studies, it was considered for the three-dimensional, viscous flow equations. The major accomplishment in the second period of this project (March 9, 1996 to March 8, 1997) was the extension of the shape optimization methodology for the Thin-Layer Navier-Stokes equations. Both the Euler-based and the TLNS-based analyses compared with the analyses obtained using the CFL3D code. The sensitivities, again from both levels of the flow equations, also compared very well with the finite-differenced sensitivities. A fairly large set of shape optimization cases were conducted to study a number of issues previously not well understood. The testbed for these cases was the shaping of an arrow wing in Mach 2.4 flow. All the final shapes, obtained either from a coarse-grid-based or a fine-grid-based optimization, using either a Euler-based or a TLNS-based analysis, were all re-analyzed using a fine-grid, TLNS solution for their function evaluations. This allowed for a more fair comparison of their relative merits. From the aerodynamic performance standpoint, the fine-grid TLNS-based optimization produced the best shape, and the fine-grid Euler-based optimization produced the lowest cruise efficiency.

One-stop shop whole-body 68Ga-PSMA-11 PET/MRI compared to clinical Nomograms for preoperative T- and N-Staging of High-Risk Prostate Cancer.

PubMed

Thalgott, Mark; Düwel, Charlotte; Rauscher, Isabel; Heck, Matthias M; Haller, Bernhard; Gafita, Andrei; Gschwend, Jürgen E; Schwaiger, Markus; Maurer, Tobias; Eiber, Matthias

2018-05-24

Our aim was to assess the diagnostic potential of one-stop shop Prostate-specific membrane antigen-ligand Positron Emission Tomography/Magnetic Resonance Imaging ( 68 Ga-PSMA-11 PET/MRI) compared to preoperative staging nomograms in patients with high-risk prostate cancer (PC). Methods: A total of 102 patients underwent 68 Ga-PSMA-11 PET/MRI before intended radical prostatectomy (RP) with lymph node dissection. Preoperative variables determined the probabilities for lymph node metastases (LNM), extracapsular extension (ECE) and seminal vesical involvement (SVI) using the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and Partin tables. Receiver operating characteristic (ROC) analyses were performed to determine best discriminatory cutoffs. On cohort base, positivity rates of imaging and nomograms were compared to pathological prevalence. On patient base, sensitivity, specificity and its area under the curves (AUCs) were calculated. Finally, the full concordance of each method to postoperative T- and N-stage was determined. Results: 73 patients were finally analysed. On cohort base, the MSKCC nomogram (39.7%) positivity rate was most concordant with pathological prevalence for LNM (34.3%) compared to Partin tables (14.1%) and imaging (20.6). Prevalence of ECE (72.6%) was best predicted by MSKCC nomograms and imaging (83.6% each), compared to Partin tables (38.4%). For prevalence of SVI (45.2%), imaging (47.9%) performed superior to MSKCC (37.6%) and Partin tables (19.3%). On patient base, AUCs for LNM, ECE and SVI did not differ significantly between tests (p>0.05). Imaging revealed a high specificity (100%) for LNM and a sensitivity (60%) comparable to the MSKCC nomogram (68%) and Partin tables (60%). For ECE, imaging revealed the highest sensitivity (94.3%) compared to the MSKCC nomogram (66%) and Partin tables (71.1%). For SVI, sensitivity and specificity of imaging and MSKCC nomogram were comparable (81.5% and 80% vs. 87.9% and 75%). The rate of concordance to the final pTN-stage was 60.3% for imaging, 52.1% for the MSKCC nomogram and 39.7% for Partin tables. Conclusion: In our analysis, preoperative one-stop shop 68 Ga-PSMA-11 PET/MRI performs at least equally for T- and N-stage prediction compared to nomograms in high-risk PC patients. Despite, an improved prediction of the full final stage and the yield of additional anatomical information, the use of 68 Ga-PSMA-11 PET/MRI warrants further prospective evaluation. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Management of type 2 diabetes with Fixed-Ratio combination insulin degludec/liraglutide (IDEGLIRA) versus Basal-Bolus therapy (INSULIN GLARGINE U100 PLUS INSULIN ASPART): A Short-Term Cost-Effectiveness analysis in the UK setting.

PubMed

Drummond, R S; Malkin, Sjp; Du Preez, M; Lee, X Y; Hunt, B

2018-05-24

Insulin degludec/liraglutide (IDegLira) is a once-daily, single-injection, fixed-ratio combination of insulin degludec, a basal insulin with a half-life of more than 24 hours, and GLP-1 receptor agonist liraglutide. The present analysis evaluated the cost-effectiveness of IDegLira versus basal-bolus therapy (BBT) with insulin glargine U100 plus up to four times daily insulin aspart for management of type 2 diabetes in the UK. A Microsoft Excel model was used to evaluate the cost-utility of IDegLira versus BBT over a 1-year time horizon. Clinical input data were taken from the treat-to-target DUAL VII trial, conducted in patients unable to achieve adequate glycaemic control (Hb A1c <7.0%) with basal insulin, with IDegLira associated with lower rates of hypoglycaemia and reduced body mass index (BMI) in comparison with BBT, with similar Hb A1c reductions. Costs (GBP) and event-related disutilities were taken from published sources. Extensive sensitivity analyses were performed. IDegLira was associated with an improvement of 0.05 quality-adjusted life years (QALYs) versus BBT, due to reductions in non-severe hypoglycaemic episodes and BMI with IDegLira. Costs were higher with IDegLira by GBP 303 per patient, leading to an incremental cost-effectiveness ratio (ICER) of GBP 5,924 per QALY gained for IDegLira versus BBT. ICERs remained below GBP 20,000 per QALY gained across a range of sensitivity analyses. IDegLira is a cost-effective alternative to BBT with insulin glargine U100 plus insulin aspart, providing equivalent glycaemic control with a simpler treatment regimen for patients with type 2 diabetes inadequately controlled on basal insulin in the UK. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Single-Use Devices in Argentina: Cost Comparison Analysis of a "Re-Use" versus a "Single-Use" Policy for Trocars, Endocutters, Linear Cutters, and Harmonic Scalpels.

PubMed

Garay, Osvaldo Ulises; Elorrio, Ezequiel Garcia; Rodríguez, Viviana; Spira, Cintia; Augustovski, Federico; Pichon-Riviere, Andrés

2017-12-01

Re-use of medical devices labeled and marketed for single use only is a current practice around the world. To estimate the average difference per surgery in device-related costs (DRCs) when performed with single-use devices under a single-use policy (SUP) instead of a re-use policy (RP) from the perspective of the private health sector of Argentina. An analytical model was developed in Microsoft Excel and populated with data from a literature review, a Delphi-like panel, and local cost estimations. Four single-use devices were selected for analysis: plastic trocars, endocutters, linear cutters, and harmonic scalpels. DRCs were expressed in 2012 US dollars and divided into four cost categories: devices, adverse events, device failure, and surgical time extension. Outputs were expressed as DRCs per surgery under a SUP, under a RP, the difference between them expressed in US dollars (Diff_$), and the difference between them expressed as a percentage of surgery costs (Diff_%S). Deterministic and probabilistic sensitivity analyses were performed to analyze the impact of uncertainty on results. Expected DRCs per surgery were as follows: for trocars: SUP, US $424.6; RP, US $244.2; Diff_$, US $-180.4; and Diff_%S, -3.8%; for endocutters: SUP, US $1667.4; RP, US $1102.3; Diff_$, US $-565.1; and Diff_%S, -11.1%; for linear cutters: SUP, US $1228.1; RP, US $1045.9; Diff_$, US $-182.2; and Diff_%S, -3.4%; and for harmonic scalpels: SUP, US $1040.9; RP, US $292.4; Diff_$, US $-748.5; and Diff_%S, -14.8%. Sensitivity analyses showed results to be robust. RP was shown to be less costly in all devices and scenarios considered. Nevertheless, the real frequency of adverse events and their cost implications are still uncertain. More research is needed to assess the effectiveness and safety of these off-label policies. Copyright © 2017. Published by Elsevier Inc.

Sensitivity Analysis of a Lagrangian Sea Ice Model

NASA Astrophysics Data System (ADS)

Rabatel, Matthias; Rampal, Pierre; Bertino, Laurent; Carrassi, Alberto; Jones, Christopher K. R. T.

2017-04-01

Large changes in the Arctic sea ice have been observed in the last decades in terms of the ice thickness, extension and drift. Understanding the mechanisms behind these changes is of paramount importance to enhance our modeling and forecasting capabilities. For 40 years, models have been developed to describe the non-linear dynamical response of the sea ice to a number of external and internal factors. Nevertheless, there still exists large deviations between predictions and observations. There are related to incorrect descriptions of the sea ice response and/or to the uncertainties about the different sources of information: parameters, initial and boundary conditions and external forcing. Data assimilation (DA) methods are used to combine observations with models, and there is nowadays an increasing interest of DA for sea-ice models and observations. We consider here the state-of-the art sea-ice model, neXtSIM te{Rampal2016a}, which is based on a time-varying Lagrangian mesh and makes use of the Elasto-Brittle rheology. Our ultimate goal is designing appropriate DA scheme for such a modelling facility. This contribution reports about the first milestone along this line: a sensitivity analysis in order to quantify forecast error to guide model development and to set basis for further Lagrangian DA methods. Specific features of the sea-ice dynamics in relation to the wind are thus analysed. Virtual buoys are deployed across the Arctic domain and their trajectories of motion are analysed. The simulated trajectories are also compared to real buoys trajectories observed. The model response is also compared with that one from a model version not including internal forcing to highlight the role of the rheology. Conclusions and perspectives for the general DA implementation are also discussed. \\bibitem{Rampal2016a} P. Rampal, S. Bouillon, E. Ólason, and M. Morlighem. ne{X}t{SIM}: a new {L}agrangian sea ice model. The Cryosphere, 10 (3): 1055-1073, 2016.

Is testosterone replacement therapy in males with hypogonadism cost-effective? An analysis in Sweden.

PubMed

Arver, Stefan; Luong, Ba; Fraschke, Anina; Ghatnekar, Ola; Stanisic, Sanja; Gultyev, Dmitry; Müller, Elvira

2014-01-01

Testosterone replacement therapy (TRT) has been recommended for the treatment of primary and secondary hypogonadism. However, long-term implications of TRT have not been investigated extensively. The aim of this analysis was to evaluate health outcomes and costs associated with life-long TRT in patients suffering from Klinefelter syndrome and late-onset hypogonadism (LOH). A Markov model was developed to assess cost-effectiveness of testosterone undecanoate (TU) depot injection treatment compared with no treatment. Health outcomes and associated costs were modeled in monthly cycles per patient individually along a lifetime horizon. Modeled health outcomes included development of type 2 diabetes, depression, cardiovascular and cerebrovascular complications, and fractures. Analysis was performed for the Swedish health-care setting from health-care payer's and societal perspective. One-way sensitivity analyses evaluated the robustness of results. The main outcome measures were quality-adjusted life-years (QALYs) and total cost in TU depot injection treatment and no treatment cohorts. In addition, outcomes were also expressed as incremental cost per QALY gained for TU depot injection therapy compared with no treatment (incremental cost-effectiveness ratio [ICER]). TU depot injection compared to no-treatment yielded a gain of 1.67 QALYs at an incremental cost of 28,176 EUR (37,192 USD) in the Klinefelter population. The ICER was 16,884 EUR (22,287 USD) per QALY gained. Outcomes in LOH population estimated benefits of TRT at 19,719 EUR (26,029 USD) per QALY gained. Results showed to be considerably robust when tested in sensitivity analyses. Variation of relative risk to develop type 2 diabetes had the highest impact on long-term outcomes in both patient groups. This analysis suggests that lifelong TU depot injection therapy of patients with hypogonadism is a cost-effective treatment in Sweden. Hence, it can support clinicians in decision making when considering appropriate treatment strategies for patients with testosterone deficiency. © 2013 International Society for Sexual Medicine.

Admixture in Latin America.

PubMed

Adhikari, Kaustubh; Mendoza-Revilla, Javier; Chacón-Duque, Juan Camilo; Fuentes-Guajardo, Macarena; Ruiz-Linares, Andrés

2016-12-01

Latin Americans arguably represent the largest recently admixed populations in the world. This reflects a history of massive settlement by immigrants (mostly Europeans and Africans) and their variable admixture with Natives, starting in 1492. This process resulted in the population of Latin America showing an extensive genetic and phenotypic diversity. Here we review how genetic analyses are being applied to examine the demographic history of this population, including patterns of mating, population structure and ancestry. The admixture history of Latin America, and the resulting extensive diversity of the region, represents a natural experiment offering an advantageous setting for genetic association studies. We review how recent analyses in Latin Americans are contributing to elucidating the genetic architecture of human complex traits. Copyright © 2016 Elsevier Ltd. All rights reserved.

Social Regulation of Leukocyte Homeostasis: The Role of Glucocorticoid Sensitivity

PubMed Central

Cole, Steve W.

2010-01-01

Recent small-scale genomics analyses suggest that physiologic regulation of pro-inflammatory gene expression by endogenous glucocorticoids may be compromised in individuals who experience chronic social isolation. This could potentially contribute to the elevated prevalence of inflammation-related disease previously observed in social isolates. The present study assessed the relationship between leukocyte distributional sensitivity to glucocorticoid regulation and subjective social isolation in a large population-based sample of older adults. Initial analyses confirmed that circulating neutrophil percentages were elevated, and circulating lymphocyte and monocyte percentages were suppressed, in direct proportion to circulating cortisol levels. However, leukocyte distributional sensitivity to endogenous glucocorticoids was abrogated in individuals reporting either occasional or frequent experiences of subjective social isolation. This finding held in both nonparametric univariate analyses and in multivariate linear models controlling for a variety of biological, social, behavioral, and psychological confounders. The present results suggest that social factors may alter immune cell sensitivity to physiologic regulation by the hypothalamic-pituitary-adrenal axis in ways that could ultimately contribute to the increased physical health risks associated with social isolation. PMID:18394861

Conceptual analyses of extensible booms to support a solar sail

NASA Technical Reports Server (NTRS)

Crawford, R. F.; Benton, M. D.

1977-01-01

Extensible booms which could function as the diagonal spars and central mast of an 800 meter square, non-rotating Solar Sailing Vehicle were conceptually designed and analyzed. The boom design concept that was investigated is an extensible lattice boom which is stowed and deployed by elastically coiling and uncoiling its continuous longerons. The seven different free-span lengths in each spar which would minimize the total weights of the spars and mast were determined. Boom weights were calculated by using a semi-empirical formulation which related the overall weight of a boom to the weight of its longerons.

Parameter sensitivity and identifiability for a biogeochemical model of hypoxia in the northern Gulf of Mexico

EPA Science Inventory

Local sensitivity analyses and identifiable parameter subsets were used to describe numerical constraints of a hypoxia model for bottom waters of the northern Gulf of Mexico. The sensitivity of state variables differed considerably with parameter changes, although most variables ...

MOESHA: A genetic algorithm for automatic calibration and estimation of parameter uncertainty and sensitivity of hydrologic models

EPA Science Inventory

Characterization of uncertainty and sensitivity of model parameters is an essential and often overlooked facet of hydrological modeling. This paper introduces an algorithm called MOESHA that combines input parameter sensitivity analyses with a genetic algorithm calibration routin...

Development of a Pattern Recognition Methodology for Determining Operationally Optimal Heat Balance Instrumentation Calibration Schedules

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

Kurt Beran; John Christenson; Dragos Nica

2002-12-15

The goal of the project is to enable plant operators to detect with high sensitivity and reliability the onset of decalibration drifts in all of the instrumentation used as input to the reactor heat balance calculations. To achieve this objective, the collaborators developed and implemented at DBNPS an extension of the Multivariate State Estimation Technique (MSET) pattern recognition methodology pioneered by ANAL. The extension was implemented during the second phase of the project and fully achieved the project goal.

Sensitive and selective determination of methylenedioxylated amphetamines by high-performance liquid chromatography with fluorimetric detection.

PubMed

Sadeghipour, F; Veuthey, J L

1997-11-07

A rapid, sensitive and selective liquid chromatographic method with fluorimetric detection was developed for the separation and quantification of four methylenedioxylated amphetamines without interference of other drugs of abuse and common substances found in illicit tablets. The method was validated by examining linearity, precision and accuracy as well as detection and quantification limits. Methylenedioxylated amphetamines were quantified in eight tablets from illicit drug seizures and results were quantitatively compared to HPLC-UV analyses. To demonstrate the better sensitivity of the fluorimetric detection, methylenedioxylated amphetamines were analyzed in serum after a liquid-liquid extraction procedure and results were also compared to HPLC-UV analyses.

The mode of sensitization and its influence on allograft outcomes in highly sensitized kidney transplant recipients.

PubMed

Redfield, Robert R; Scalea, Joseph R; Zens, Tiffany J; Mandelbrot, Didier A; Leverson, Glen; Kaufman, Dixon B; Djamali, Arjang

2016-10-01

We sought to determine whether the mode of sensitization in highly sensitized patients contributed to kidney allograft survival. An analysis of the United Network for Organ Sharing dataset involving all kidney transplants between 1997 and 2014 was undertaken. Highly sensitized adult kidney transplant recipients [panel reactive antibody (PRA) ≥98%] were compared with adult, primary non-sensitized and re-transplant recipients. Kaplan-Meier survival analyses were used to determine allograft survival rates. Cox proportional hazards regression analyses were conducted to determine the association of graft loss with key predictors. Fifty-three percent of highly sensitized patients transplanted were re-transplants. Pregnancy and transfusion were the only sensitizing event in 20 and 5%, respectively. The 10-year actuarial graft survival for highly sensitized recipients was 43.9% compared with 52.4% for non-sensitized patients, P < 0.001. The combination of being highly sensitized by either pregnancy or blood transfusion increased the risk of graft loss by 23% [hazard ratio (HR) 1.230, confidence interval (CI) 1.150-1.315, P < 0.001], and the combination of being highly sensitized from a prior transplant increased the risk of graft loss by 58.1% (HR 1.581, CI 1.473-1.698, P < 0.001). The mode of sensitization predicts graft survival in highly sensitized kidney transplant recipients (PRA ≥98%). Patients who are highly sensitized from re-transplants have inferior graft survival compared with patients who are highly sensitized from other modes of sensitization. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Improving the Plasticity of LIMS Implementation: LIMS Extension through Microsoft Excel

NASA Technical Reports Server (NTRS)

Culver, Mark

2017-01-01

A Laboratory Information Management System (LIMS) is a databasing software with many built-in tools ideal for handling and documenting most laboratory processes in an accurate and consistent manner, making it an indispensable tool for the modern laboratory. However, a lot of LIMS end users will find that in the performance of analyses that have unique considerations such as standard curves, multiple stages incubations, or logical considerations, a base LIMS distribution may not ideally suit their needs. These considerations bring about the need for extension languages, which can extend the functionality of a LIMS. While these languages do provide the implementation team the functionality required to accommodate these special laboratory analyses, they are usually too complex for the end user to modify to compensate for natural changes in laboratory operations. The LIMS utilized by our laboratory offers a unique and easy-to-use choice for an extension language, one that is already heavily relied upon not only in science but also in most academic and business pursuits: Microsoft Excel. The validity of Microsoft Excel as a pseudo programming language and its usability and versatility as a LIMS extension language will be discussed. The NELAC implications and overall drawbacks of this LIMS configuration will also be discussed.

Twenty years of meta-analyses in orthopaedic surgery: has quality kept up with quantity?

PubMed

Dijkman, Bernadette G; Abouali, Jihad A K; Kooistra, Bauke W; Conter, Henry J; Poolman, Rudolf W; Kulkarni, Abhaya V; Tornetta, Paul; Bhandari, Mohit

2010-01-01

As the number of studies in the literature is increasing, orthopaedic surgeons highly depend on meta-analyses as their primary source of scientific evidence. The objectives of this review were to assess the scientific quality and number of published meta-analyses on orthopaedics-related topics over time. We conducted, in duplicate and independently, a systematic review of published meta-analyses in orthopaedics in the years 2005 and 2008 and compared them with a previous systematic review of meta-analyses from 1969 to 1999. A search of electronic databases (MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews) was performed to identify meta-analyses published in 2005 and 2008. We searched bibliographies and contacted content experts to identify additional relevant studies. Two investigators independently assessed the quality of the studies, using the Oxman and Guyatt index, and abstracted relevant data. We included forty-five and forty-four meta-analyses from 2005 and 2008, respectively. While the number of meta-analyses increased fivefold from 1999 to 2008, the mean quality score did not change significantly over time (p = 0.067). In the later years, a significantly lower proportion of meta-analyses had methodological flaws (56% in 2005 and 68% in 2008) compared with meta-analyses published prior to 2000 (88%) (p = 0.006). In 2005 and 2008, respectively, 18% and 30% of the meta-analyses had major to extensive flaws in their methodology. Studies from 2008 with positive conclusions used and described appropriate criteria for the validity assessment less often than did those with negative results. The use of random-effects and fixed-effects models as pooling methods became more popular toward 2008. Although the methodological quality of orthopaedic meta-analyses has increased in the past twenty years, a substantial proportion continues to show major to extensive flaws. As the number of published meta-analyses is increasing, a routine checklist for scientific quality should be used in the peer-review process to ensure methodological standards for publication.

msgbsR: An R package for analysing methylation-sensitive restriction enzyme sequencing data.

PubMed

Mayne, Benjamin T; Leemaqz, Shalem Y; Buckberry, Sam; Rodriguez Lopez, Carlos M; Roberts, Claire T; Bianco-Miotto, Tina; Breen, James

2018-02-01

Genotyping-by-sequencing (GBS) or restriction-site associated DNA marker sequencing (RAD-seq) is a practical and cost-effective method for analysing large genomes from high diversity species. This method of sequencing, coupled with methylation-sensitive enzymes (often referred to as methylation-sensitive restriction enzyme sequencing or MRE-seq), is an effective tool to study DNA methylation in parts of the genome that are inaccessible in other sequencing techniques or are not annotated in microarray technologies. Current software tools do not fulfil all methylation-sensitive restriction sequencing assays for determining differences in DNA methylation between samples. To fill this computational need, we present msgbsR, an R package that contains tools for the analysis of methylation-sensitive restriction enzyme sequencing experiments. msgbsR can be used to identify and quantify read counts at methylated sites directly from alignment files (BAM files) and enables verification of restriction enzyme cut sites with the correct recognition sequence of the individual enzyme. In addition, msgbsR assesses DNA methylation based on read coverage, similar to RNA sequencing experiments, rather than methylation proportion and is a useful tool in analysing differential methylation on large populations. The package is fully documented and available freely online as a Bioconductor package ( https://bioconductor.org/packages/release/bioc/html/msgbsR.html ).

Two endogenous proteins that induce cell wall extension in plants

NASA Technical Reports Server (NTRS)

McQueen-Mason, S.; Durachko, D. M.; Cosgrove, D. J.

1992-01-01

Plant cell enlargement is regulated by wall relaxation and yielding, which is thought to be catalyzed by elusive "wall-loosening" enzymes. By employing a reconstitution approach, we found that a crude protein extract from the cell walls of growing cucumber seedlings possessed the ability to induce the extension of isolated cell walls. This activity was restricted to the growing region of the stem and could induce the extension of isolated cell walls from various dicot stems and the leaves of amaryllidaceous monocots, but was less effective on grass coleoptile walls. Endogenous and reconstituted wall extension activities showed similar sensitivities to pH, metal ions, thiol reducing agents, proteases, and boiling in methanol or water. Sequential HPLC fractionation of the active wall extract revealed two proteins with molecular masses of 29 and 30 kD associated with the activity. Each protein, by itself, could induce wall extension without detectable hydrolytic breakdown of the wall. These proteins appear to mediate "acid growth" responses of isolated walls and may catalyze plant cell wall extension by a novel biochemical mechanism.

Control of growth of juvenile leaves of Eucalyptus globulus: effects of leaf age.

PubMed

Metcalfe, J C; Davies, W J; Pereira, J S

1991-12-01

Biophysical variables influencing the expansion of plant cells (yield threshold, cell wall extensibility and turgor) were measured in individual Eucalyptus globulus leaves from the time of emergence until cessation of growth. Leaf water relations variables and growth rates were determined as relative humidity was changed on an hourly basis. Yield threshold and cell wall extensibility were estimated from plots of leaf growth rate versus turgor. Cell wall extensibility was also measured by the Instron technique, and yield threshold was determined experimentally both by stress relaxation in a psychrometer chamber and by incubation in a range of polyethylene glycol solutions. Once emerging leaves reached approximately 5 cm(2) in size, increases in leaf area were rapid throughout the expansive phase and varied little between light and dark periods. Both leaf growth rate and turgor were sensitive to changes in humidity, and in the longer term, both yield threshold and cell wall extensibility changed as the leaf aged. Rapidly expanding leaves had a very low yield threshold and high cell wall extensibility, whereas mature leaves had low cell wall extensibility. Yield threshold increased with leaf age.

Extensive Radiation Shielding Analysis for Different Spacecraft Orbits

NASA Astrophysics Data System (ADS)

Çay, Yiǧit; Kaymaz, Zerefsan

2016-07-01

Radiation environment around Earth poses a great danger for spacecraft and causes immature de-orbiting or loss of the spacecraft in near Earth space environment. In this study, a student project has been designed to build a CubeSat, PolarBeeSail (PBS), with an orbit having inclination of 80°, 4 Re in perigee and 20 Re in apogee to study the polar magnetospheric environment. An extensive radiation dose analyses were carried out for PBS orbit, and integral and differential fluxes were calculated using SPENVIS tools. A shielding analysis was performed and an optimum Aluminum thickness, 3 mm, was obtained. These results for PBS were then compared for other orbits at different altitudes both for polar and equatorial orbits. For this purpose, orbital characteristics of POES-19 and GOES-15 were used. The resulting proton flux analyses, TID analyses, and further shielding studies were conducted; comparisons and recommendations were made for future design of spacecraft that will use these environments.

Nozzle extension design status report

NASA Technical Reports Server (NTRS)

Classen, L. B.

1972-01-01

Twenty possible concepts of a possible nozzle/nozzle extension interface were originated. Not all of the concepts were considered worthy of analysis time. Six of them were thermally analyzed and three were stress analyzed. These analyses were done to determine which of the concepts would have the best chance of succeeding, that is, they were a screening process which was to allow rating of one concept against another. This was done because adequate material properties to determine absolute stress levels were not available at the time of the analyses. Through all of the concepts still exhibit some areas of negative margin of safety, concept no. 1 shows good promise that, with slight modifications, it could have all positive margins of safety. Another significant question, regarding these designs, has to do with the Grafoil seals and insulators. Some additional data was just recently received on Grafoil properties, but it was too late to incorporate in the analyses. The new data were not significantly different from the properties which were used.

Groundwater sensitivity mapping in Kentucky using GIS and digitally vectorized geologic quadrangles

NASA Astrophysics Data System (ADS)

Croskrey, Andrea; Groves, Chris

2008-05-01

Groundwater sensitivity (Ray and O’dell in Environ Geol 22:345 352, 1993a) refers to the inherent ease with which groundwater can be contaminated based on hydrogeologic characteristics. We have developed digital methods for identifying areas of varying groundwater sensitivity for a ten county area of south central Kentucky at a scale of 1:100,000. The study area includes extensive limestone karst sinkhole plains, with groundwater extremely sensitive to contamination. Digitally vectorized geologic quadrangles (DVGQs) were combined with elevation data to identify both hydrogeologic groundwater sensitivity regions and zones of “high risk runoff” where contaminants could be transported in runoff from less sensitive to higher sensitivity (particularly karst) areas. While future work will fine-tune these maps with additional layers of data (soils for example) as digital data have become available, using DVGQs allows a relatively rapid assessment of groundwater sensitivity for Kentucky at a more useful scale than previously available assessment methods, such as DRASTIC and DIVERSITY.

Grid sensitivity for aerodynamic optimization and flow analysis

NASA Technical Reports Server (NTRS)

Sadrehaghighi, I.; Tiwari, S. N.

1993-01-01

After reviewing relevant literature, it is apparent that one aspect of aerodynamic sensitivity analysis, namely grid sensitivity, has not been investigated extensively. The grid sensitivity algorithms in most of these studies are based on structural design models. Such models, although sufficient for preliminary or conceptional design, are not acceptable for detailed design analysis. Careless grid sensitivity evaluations, would introduce gradient errors within the sensitivity module, therefore, infecting the overall optimization process. Development of an efficient and reliable grid sensitivity module with special emphasis on aerodynamic applications appear essential. The organization of this study is as follows. The physical and geometric representations of a typical model are derived in chapter 2. The grid generation algorithm and boundary grid distribution are developed in chapter 3. Chapter 4 discusses the theoretical formulation and aerodynamic sensitivity equation. The method of solution is provided in chapter 5. The results are presented and discussed in chapter 6. Finally, some concluding remarks are provided in chapter 7.

The Intercultural Sensitivity of Chilean Teachers Serving an Immigrant Population in Schools

ERIC Educational Resources Information Center

Morales Mendoza, Karla; Sanhueza Henríquez, Susan; Friz Carrillo, Miguel; Riquelme Bravo, Paula

2017-01-01

The objective of this article is to evaluate the intercultural sensitivity of teachers working in culturally diverse classrooms, and to analyse differences in intercultural sensitivity based on the gender, age, training (advanced training courses), and intercultural experience of the teachers. A quantitative approach with a comparative descriptive…

Analysis of Sensitivity and Uncertainty in an Individual-Based Model of a Threatened Wildlife Species

EPA Science Inventory

We present a multi-faceted sensitivity analysis of a spatially explicit, individual-based model (IBM) (HexSim) of a threatened species, the Northern Spotted Owl (Strix occidentalis caurina) on a national forest in Washington, USA. Few sensitivity analyses have been conducted on ...

Preparation for implementation of the mechanistic-empirical pavement design guide in Michigan : part 2 - evaluation of rehabilitation fixes (part 2).

DOT National Transportation Integrated Search

2013-08-01

The overall goal of Global Sensitivity Analysis (GSA) is to determine sensitivity of pavement performance prediction models to the variation in the design input values. The main difference between GSA and detailed sensitivity analyses is the way the ...

A spectral power analysis of driving behavior changes during the transition from nondistraction to distraction.

PubMed

Wang, Yuan; Bao, Shan; Du, Wenjun; Ye, Zhirui; Sayer, James R

2017-11-17

This article investigated and compared frequency domain and time domain characteristics of drivers' behaviors before and after the start of distracted driving. Data from an existing naturalistic driving study were used. Fast Fourier transform (FFT) was applied for the frequency domain analysis to explore drivers' behavior pattern changes between nondistracted (prestarting of visual-manual task) and distracted (poststarting of visual-manual task) driving periods. Average relative spectral power in a low frequency range (0-0.5 Hz) and the standard deviation in a 10-s time window of vehicle control variables (i.e., lane offset, yaw rate, and acceleration) were calculated and further compared. Sensitivity analyses were also applied to examine the reliability of the time and frequency domain analyses. Results of the mixed model analyses from the time and frequency domain analyses all showed significant degradation in lateral control performance after engaging in visual-manual tasks while driving. Results of the sensitivity analyses suggested that the frequency domain analysis was less sensitive to the frequency bandwidth, whereas the time domain analysis was more sensitive to the time intervals selected for variation calculations. Different time interval selections can result in significantly different standard deviation values, whereas average spectral power analysis on yaw rate in both low and high frequency bandwidths showed consistent results, that higher variation values were observed during distracted driving when compared to nondistracted driving. This study suggests that driver state detection needs to consider the behavior changes during the prestarting periods, instead of only focusing on periods with physical presence of distraction, such as cell phone use. Lateral control measures can be a better indicator of distraction detection than longitudinal controls. In addition, frequency domain analyses proved to be a more robust and consistent method in assessing driving performance compared to time domain analyses.

Diagnosing the impact of alternative calibration strategies on coupled hydrologic models

NASA Astrophysics Data System (ADS)

Smith, T. J.; Perera, C.; Corrigan, C.

2017-12-01

Hydrologic models represent a significant tool for understanding, predicting, and responding to the impacts of water on society and society on water resources and, as such, are used extensively in water resources planning and management. Given this important role, the validity and fidelity of hydrologic models is imperative. While extensive focus has been paid to improving hydrologic models through better process representation, better parameter estimation, and better uncertainty quantification, significant challenges remain. In this study, we explore a number of competing model calibration scenarios for simple, coupled snowmelt-runoff models to better understand the sensitivity / variability of parameterizations and its impact on model performance, robustness, fidelity, and transferability. Our analysis highlights the sensitivity of coupled snowmelt-runoff model parameterizations to alterations in calibration approach, underscores the concept of information content in hydrologic modeling, and provides insight into potential strategies for improving model robustness / fidelity.

Ground water flow modeling with sensitivity analyses to guide field data collection in a mountain watershed

USGS Publications Warehouse

Johnson, Raymond H.

2007-01-01

In mountain watersheds, the increased demand for clean water resources has led to an increased need for an understanding of ground water flow in alpine settings. In Prospect Gulch, located in southwestern Colorado, understanding the ground water flow system is an important first step in addressing metal loads from acid-mine drainage and acid-rock drainage in an area with historical mining. Ground water flow modeling with sensitivity analyses are presented as a general tool to guide future field data collection, which is applicable to any ground water study, including mountain watersheds. For a series of conceptual models, the observation and sensitivity capabilities of MODFLOW-2000 are used to determine composite scaled sensitivities, dimensionless scaled sensitivities, and 1% scaled sensitivity maps of hydraulic head. These sensitivities determine the most important input parameter(s) along with the location of observation data that are most useful for future model calibration. The results are generally independent of the conceptual model and indicate recharge in a high-elevation recharge zone as the most important parameter, followed by the hydraulic conductivities in all layers and recharge in the next lower-elevation zone. The most important observation data in determining these parameters are hydraulic heads at high elevations, with a depth of less than 100 m being adequate. Evaluation of a possible geologic structure with a different hydraulic conductivity than the surrounding bedrock indicates that ground water discharge to individual stream reaches has the potential to identify some of these structures. Results of these sensitivity analyses can be used to prioritize data collection in an effort to reduce time and money spend by collecting the most relevant model calibration data.

Validity of self-reported stroke in elderly African Americans, Caribbean Hispanics, and Whites.

PubMed

Reitz, Christiane; Schupf, Nicole; Luchsinger, José A; Brickman, Adam M; Manly, Jennifer J; Andrews, Howard; Tang, Ming X; DeCarli, Charles; Brown, Truman R; Mayeux, Richard

2009-07-01

The validity of a self-reported stroke remains inconclusive. To validate the diagnosis of self-reported stroke using stroke identified by magnetic resonance imaging (MRI) as the standard. Community-based cohort study of nondemented, ethnically diverse elderly persons in northern Manhattan. High-resolution quantitative MRIs were acquired for 717 participants without dementia. Sensitivity and specificity of stroke by self-report were examined using cross-sectional analyses and the chi(2) test. Putative relationships between factors potentially influencing the reporting of stroke, including memory performance, cognitive function, and vascular risk factors, were assessed using logistic regression models. Subsequently, all analyses were repeated, stratified by age, sex, ethnic group, and level of education. In analyses of the whole sample, sensitivity of stroke self-report for a diagnosis of stroke on MRI was 32.4%, and specificity was 78.9%. In analyses stratified by median age (80.1 years), the validity between reported stroke and detection of stroke on MRI was significantly better in the younger than the older age group (for all vascular territories: sensitivity and specificity, 36.7% and 81.3% vs 27.6% and 26.2%; P = .02). Impaired memory, cognitive skills, or language ability and the presence of hypertension or myocardial infarction were associated with higher rates of false-negative results. Using brain MRI as the standard, specificity and sensitivity of stroke self-report are low. Accuracy of self-report is influenced by age, presence of vascular disease, and cognitive function. In stroke research, sensitive neuroimaging techniques rather than stroke self-report should be used to determine stroke history.

Sensitivity analysis of FeCrAl cladding and U3Si2 fuel under accident conditions

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

Gamble, Kyle Allan Lawrence; Hales, Jason Dean

2016-08-01

The purpose of this milestone report is to highlight the results of sensitivity analyses performed on two accident tol- erant fuel concepts: U3Si2 fuel and FeCrAl cladding. The BISON fuel performance code under development at Idaho National Laboratory was coupled to Sandia National Laboratories’ DAKOTA software to perform the sensitivity analyses. Both Loss of Coolant (LOCA) and Station blackout (SBO) scenarios were analyzed using main effects studies. The results indicate that for FeCrAl cladding the input parameters with greatest influence on the output metrics of interest (fuel centerline temperature and cladding hoop strain) during the LOCA were the isotropic swellingmore » and fuel enrichment. For U3Si2 the important inputs were found to be the intergranular diffusion coefficient, specific heat, and fuel thermal conductivity. For the SBO scenario, Young’s modulus was found to be influential in FeCrAl in addition to the isotropic swelling and fuel enrichment. Contrarily to the LOCA case, the specific heat of U3Si2 was found to have no effect during the SBO. The intergranular diffusion coefficient and fuel thermal conductivity were still found to be of importance. The results of the sensitivity analyses have identified areas where further research is required including fission gas behavior in U3Si2 and irradiation swelling in FeCrAl. Moreover, the results highlight the need to perform the sensitivity analyses on full length fuel rods for SBO scenarios.« less

Clinicopathological characteristics including BRAF V600E mutation status and PET/CT findings in papillary thyroid carcinoma.

PubMed

Choi, Eun Kyoung; Chong, Ari; Ha, Jung-Min; Jung, Chan Kwon; O, Joo Hyun; Kim, Sung Hoon

2017-07-01

We assessed the associations between FDG uptake in primary papillary thyroid carcinomas (PTCs) and clinicopathological features, including the BRAF V600E mutation, using quantitative and qualitative analyses of preoperative PET/CT data. This was a retrospective review of 106 patients with PTC who underwent PET/CT scans between February 2009 and January 2011 before undergoing total thyroidectomy. Data collected from surgical specimens were compared with FDG uptake in the primary tumour using quantitative and qualitative analyses of preoperative PET/CT data. Clinicopathological data included the primary tumour size, subtype, capsular invasion, extrathyroid extension, multifocality, BRAF V600E mutation status, lymph node metastasis and distant metastasis. The SUVmax of the primary tumour was significantly higher in patients with a primary tumour >1 cm, extrathyroid extension or the BRAF V600E mutation than in patients without these features (P<.001, .049 and <.001). Univariate analyses showed that primary tumour size, extrathyroid extension and BRAF V600E mutation status were associated with the SUVmax of the PTC. Multivariate analysis indicated that primary tumour size and the BRAF V600E mutation were associated with the SUVmax of the PTC. In a visual assessment, the primary tumour size was larger in FDG-avid than in non-FDG-avid PTCs (P<.001). There was no significant difference in the presence of multifocality, thyroid capsular invasion, extrathyroid extension, BRAF V600E mutation, lymph node metastasis or distant metastasis between FDG-avid and non-FDG-avid PTCs. Primary tumour size and the BRAF V600E mutation are significant factors associated with the SUVmax on preoperative PET/CT in patients with PTC. © 2017 John Wiley & Sons Ltd.

Should cell-free DNA testing be used to target antenatal rhesus immune globulin administration?

PubMed

Ma, Kimberly K; Rodriguez, Maria I; Cheng, Yvonne W; Norton, Mary E; Caughey, Aaron B

2016-01-01

To compare the rates of alloimmunization with the use of cell-free DNA (cfDNA) screening to target antenatal rhesus immune globulin (RhIG) prenatally, versus routine administration of RhIG in rhesus D (RhD)-negative pregnant women in a theoretic cohort using a decision-analytic model. A decision-analytic model compared cfDNA testing to routine antenatal RhIG administration. The primary outcome was maternal sensitization to RhD antigen. Sensitivity and specificity of cfDNA testing were assumed to be 99.8% and 95.3%, respectively. Univariate and bivariate sensitivity analyses, Monte Carlo simulation, and threshold analyses were performed. In a cohort of 10,000 RhD-negative women, 22.6 sensitizations would occur with utilization of cfDNA, while 20 sensitizations would occur with routine RhIG. Only when the sensitivity of the cfDNA test reached 100%, the rate of sensitization was equal for both cfDNA and RhIG. Otherwise, routine RhIG minimized the rate of sensitization, especially given RhIG is readily available in the United States. Adoption of cfDNA testing would result in a 13.0% increase in sensitization among RhD-negative women in a theoretical cohort taking into account the ethnic diversity of the United States' population.

Cognition in Huntington's disease in manifest, premanifest and converting gene carriers over ten years.

PubMed

Hart, Ellen P; Dumas, Eve M; Giltay, Erik J; Middelkoop, Huub A M; Roos, Raymund A C

2013-01-01

Cognitive decline in Huntington's disease (HD) remains an area of inconsistencies, especially far from disease onset. To clarify the course of cognition in premanifest HD. Twenty-six premanifest HD, 19 manifest HD, and 87 control subjects were followed for ten years, using an extensive cognitive battery. Differences in baseline levels and change over time, on four factors (motor speed, global cognition, executive functioning (EF), and memory) were examined, using multilevel regression analyses. Converters were additionally analysed as a separate group. Also, the influence of motor speed and predicted years to disease onset on the cognitive factors was studied. Manifest HD subjects showed lower baseline scores compared to controls on the motor speed (p=0.002), memory (p<0.001) and EF (p<0.001). They additionally deteriorated over the ten-year follow-up on memory (p=0.01). Converters deteriorated on EF (p=0.04). Further analyses of premanifest subjects 'far from and close to predicted onset' revealed lower baseline scores for the 'close' group on EF, as compared to controls (p=0.001). They also deteriorated on memory (p=0.01). Motor speed substantially mediated the results of the three cognitive factors; when added as covariate to the model several baseline and slope differences for the cognitive factors ceased to be significant. Memory and EF are highly sensitive for ascertaining deterioration in premanifest HD gene carriers, especially in subjects close to onset. Lack of deterioration for the subjects further away from onset suggests that both domains are largely unaffected in those far from onset. Also, motor influence on cognition is substantial and should be taken into account in cognitive HD research.

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis

PubMed Central

Chen, Xiao-Han; Kim, Sehee; Zeng, Xiao-Xi; Chen, Zhi-Bing; Cui, Tian-Lei; Hu, Zhang-Xue; Li, Yi; Fu, Ping

2017-01-01

Background: Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. Methods: This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). Results: In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P = 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). Conclusions: In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP. PMID:28639575

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis.

PubMed

Chen, Xiao-Han; Kim, Sehee; Zeng, Xiao-Xi; Chen, Zhi-Bing; Cui, Tian-Lei; Hu, Zhang-Xue; Li, Yi; Fu, Ping

2017-07-05

Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P= 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP.

Analyses of Longitudinal Mode Combustion Instability in J-2X Gas Generator Development

NASA Technical Reports Server (NTRS)

Hulka, J. R.; Protz, C. S.; Casiano, M. J.; Kenny, R. J.

2011-01-01

The National Aeronautics and Space Administration (NASA) and Pratt & Whitney Rocketdyne are developing a liquid oxygen/liquid hydrogen rocket engine for future upper stage and trans-lunar applications. This engine, designated the J-2X, is a higher pressure, higher thrust variant of the Apollo-era J-2 engine. The contract for development was let to Pratt & Whitney Rocketdyne in 2006. Over the past several years, development of the gas generator for the J-2X engine has progressed through a variety of workhorse injector, chamber, and feed system configurations on the component test stand at the NASA Marshall Space Flight Center (MSFC). Several of the initial configurations resulted in combustion instability of the workhorse gas generator assembly at a frequency near the first longitudinal mode of the combustion chamber. In this paper, several aspects of these combustion instabilities are discussed, including injector, combustion chamber, feed system, and nozzle influences. To ensure elimination of the instabilities at the engine level, and to understand the stability margin, the gas generator system has been modeled at the NASA MSFC with two techniques, the Rocket Combustor Interaction Design and Analysis (ROCCID) code and a lumped-parameter MATLAB(TradeMark) model created as an alternative calculation to the ROCCID methodology. To correctly predict the instability characteristics of all the chamber and injector geometries and test conditions as a whole, several inputs to the submodels in ROCCID and the MATLAB(TradeMark) model were modified. Extensive sensitivity calculations were conducted to determine how to model and anchor a lumped-parameter injector response, and finite-element and acoustic analyses were conducted on several complicated combustion chamber geometries to determine how to model and anchor the chamber response. These modifications and their ramification for future stability analyses of this type are discussed.

Medical costs and quality-adjusted life years associated with smoking: a systematic review.

PubMed

Feirman, Shari P; Glasser, Allison M; Teplitskaya, Lyubov; Holtgrave, David R; Abrams, David B; Niaura, Raymond S; Villanti, Andrea C

2016-07-27

Estimated medical costs ("T") and QALYs ("Q") associated with smoking are frequently used in cost-utility analyses of tobacco control interventions. The goal of this study was to understand how researchers have addressed the methodological challenges involved in estimating these parameters. Data were collected as part of a systematic review of tobacco modeling studies. We searched five electronic databases on July 1, 2013 with no date restrictions and synthesized studies qualitatively. Studies were eligible for the current analysis if they were U.S.-based, provided an estimate for Q, and used a societal perspective and lifetime analytic horizon to estimate T. We identified common methods and frequently cited sources used to obtain these estimates. Across all 18 studies included in this review, 50 % cited a 1992 source to estimate the medical costs associated with smoking and 56 % cited a 1996 study to derive the estimate for QALYs saved by quitting or preventing smoking. Approaches for estimating T varied dramatically among the studies included in this review. T was valued as a positive number, negative number and $0; five studies did not include estimates for T in their analyses. The most commonly cited source for Q based its estimate on the Health Utilities Index (HUI). Several papers also cited sources that based their estimates for Q on the Quality of Well-Being Scale and the EuroQol five dimensions questionnaire (EQ-5D). Current estimates of the lifetime medical care costs and the QALYs associated with smoking are dated and do not reflect the latest evidence on the health effects of smoking, nor the current costs and benefits of smoking cessation and prevention. Given these limitations, we recommend that researchers conducting economic evaluations of tobacco control interventions perform extensive sensitivity analyses around these parameter estimates.

A model for growth of a single fungal hypha based on well-mixed tanks in series: simulation of nutrient and vesicle transport in aerial reproductive hyphae.

PubMed

Balmant, Wellington; Sugai-Guérios, Maura Harumi; Coradin, Juliana Hey; Krieger, Nadia; Furigo Junior, Agenor; Mitchell, David Alexander

2015-01-01

Current models that describe the extension of fungal hyphae and development of a mycelium either do not describe the role of vesicles in hyphal extension or do not correctly describe the experimentally observed profile for distribution of vesicles along the hypha. The present work uses the n-tanks-in-series approach to develop a model for hyphal extension that describes the intracellular transport of nutrient to a sub-apical zone where vesicles are formed and then transported to the tip, where tip extension occurs. The model was calibrated using experimental data from the literature for the extension of reproductive aerial hyphae of three different fungi, and was able to describe different profiles involving acceleration and deceleration of the extension rate. A sensitivity analysis showed that the supply of nutrient to the sub-apical vesicle-producing zone is a key factor influencing the rate of extension of the hypha. Although this model was used to describe the extension of a single reproductive aerial hypha, the use of the n-tanks-in-series approach to representing the hypha means that the model has the flexibility to be extended to describe the growth of other types of hyphae and the branching of hyphae to form a complete mycelium.

American grandparents providing extensive child care to their grandchildren: prevalence and profile.

PubMed

Fuller-Thomson, E; Minkler, M

2001-04-01

This study sought to determine the prevalence and profile of grandparents providing extensive care for a grandchild (grandparents who provide 30+ hours per week or 90+ nights per year of child care, yet are not the primary caregiver of the grandchild). Secondary analysis of the 3,260 grandparent respondents in the 1992-94 National Survey of Families and Households (NSFH). Extensively caregiving grandparents were compared with custodial grandparents (those with primary responsibility for raising a grandchild for 6+ months), noncaregivers, occasional caregivers (<10 hours per week), and intermediate caregivers using chi-square tests, one-way analysis of variance tests, and logistic regression analyses. Close to 7% of all grandparents provided extensive caregiving, as did 14.9% of those who had provided any grandchild care in the last month. Extensive caregivers most closely resembled custodial caregivers and had least in common with those grandparents who never provided child care. Areas for future research, policy, and practice are highlighted, including the potential impact of welfare reform legislation on extensively caregiving grandparents.

Molecular properties of the N-terminal extension of the fission yeast kinesin-5, Cut7.

PubMed

Edamatsu, M

2016-02-11

Kinesin-5 plays an essential role in spindle formation and function, and serves as a potential target for anti-cancer drugs. The aim of this study was to elucidate the molecular properties of the N-terminal extension of the Schizosaccharomyces pombe kinesin-5, Cut7. This extension is rich in charged amino acids and predicted to be intrinsically disordered. In S. pombe cells, a Cut7 construct lacking half the N-terminal extension failed to localize along the spindle microtubules and formed a monopolar spindle. However, a construct lacking the entire N-terminal extension exhibited normal localization and formed a typical bipolar spindle. In addition, in vitro analyses revealed that the truncated Cut7 constructs demonstrated similar motile velocities and directionalities as the wild-type motor protein, but the microtubule landing rates were significantly reduced. These findings suggest that the N-terminal extension is not required for normal Cut7 intracellular localization or function, but alters the microtubule-binding properties of this protein in vitro.

msap: a tool for the statistical analysis of methylation-sensitive amplified polymorphism data.

PubMed

Pérez-Figueroa, A

2013-05-01

In this study msap, an R package which analyses methylation-sensitive amplified polymorphism (MSAP or MS-AFLP) data is presented. The program provides a deep analysis of epigenetic variation starting from a binary data matrix indicating the banding pattern between the isoesquizomeric endonucleases HpaII and MspI, with differential sensitivity to cytosine methylation. After comparing the restriction fragments, the program determines if each fragment is susceptible to methylation (representative of epigenetic variation) or if there is no evidence of methylation (representative of genetic variation). The package provides, in a user-friendly command line interface, a pipeline of different analyses of the variation (genetic and epigenetic) among user-defined groups of samples, as well as the classification of the methylation occurrences in those groups. Statistical testing provides support to the analyses. A comprehensive report of the analyses and several useful plots could help researchers to assess the epigenetic and genetic variation in their MSAP experiments. msap is downloadable from CRAN (http://cran.r-project.org/) and its own webpage (http://msap.r-forge.R-project.org/). The package is intended to be easy to use even for those people unfamiliar with the R command line environment. Advanced users may take advantage of the available source code to adapt msap to more complex analyses. © 2013 Blackwell Publishing Ltd.

Consensus Contouring Guidelines for Postoperative Stereotactic Body Radiation Therapy for Metastatic Solid Tumor Malignancies to the Spine

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

Redmond, Kristin J., E-mail: kjanson3@jhmi.edu; Robertson, Scott; Lo, Simon S.

Purpose: To develop consensus contouring guidelines for postoperative stereotactic body radiation therapy (SBRT) for spinal metastases. Methods and Materials: Ten spine SBRT specialists representing 10 international centers independently contoured the clinical target volume (CTV), planning target volume (PTV), spinal cord, and spinal cord planning organ at risk volume (PRV) for 10 representative clinical scenarios in postoperative spine SBRT for metastatic solid tumor malignancies. Contours were imported into the Computational Environment for Radiotherapy Research. Agreement between physicians was calculated with an expectation minimization algorithm using simultaneous truth and performance level estimation with κ statistics. Target volume definition guidelines were established by finding optimizedmore » confidence level consensus contours using histogram agreement analyses. Results: Nine expert radiation oncologists and 1 neurosurgeon completed contours for all 10 cases. The mean sensitivity and specificity were 0.79 (range, 0.71-0.89) and 0.94 (range, 0.90-0.99) for the CTV and 0.79 (range, 0.70-0.95) and 0.92 (range, 0.87-0.99) for the PTV), respectively. Mean κ agreement, which demonstrates the probability that contours agree by chance alone, was 0.58 (range, 0.43-0.70) for CTV and 0.58 (range, 0.37-0.76) for PTV (P<.001 for all cases). Optimized consensus contours were established for all patients with 80% confidence interval. Recommendations for CTV include treatment of the entire preoperative extent of bony and epidural disease, plus immediately adjacent bony anatomic compartments at risk of microscopic disease extension. In particular, a “donut-shaped” CTV was consistently applied in cases of preoperative circumferential epidural extension, regardless of extent of residual epidural extension. Otherwise more conformal anatomic-based CTVs were determined and described. Spinal instrumentation was consistently excluded from the CTV. Conclusions: We provide consensus contouring guidelines for common scenarios in postoperative SBRT for spinal metastases. These consensus guidelines are subject to clinical validation.« less

Water quality and quantity investigation of green roofs in a dry climate.

PubMed

Beecham, S; Razzaghmanesh, M

2015-03-01

Low-energy pollutant removal strategies are now being sought for water sensitive urban design. This paper describes investigations into the water quality and quantity of sixteen, low-maintenance and unfertilized intensive and extensive green roof beds. The factors of Slope (1° and 25°), Depth (100 mm and 300 mm), Growing media (type A, type B and type C) and Species (P1, P2 and P3) were randomized according to a split-split plot design. This consisted of twelve vegetated green roof beds and four non-vegetated beds as controls. Stormwater runoff was collected from drainage points that were installed in each area. Samples of run-off were collected for five rainfall events and analysed for water retention capacity and the water quality parameters of NO₂, NO₃, NH₄, PO₄, pH, EC, TDS, Turbidity, Na, Ca, Mg and K. The results indicated significant differences in terms of stormwater water quality and quantity between the outflows of vegetated and non-vegetated systems. The water retention was between 51% and 96% and this range was attributed to the green roof configurations in the experiment. Comparing the quality of rainfall as inflow, and the quality of runoff from the systems showed that green roofs generally acted as a source of pollutants in this study. In the vegetated beds, the intensive green roofs performed better than the extensive beds with regard to outflow quality while in the non-vegetated beds, the extensive beds performed better than intensive systems. This highlights the importance of vegetation in improving water retention capacity as well as the role of vegetation in enhancing pollutant removal in green roof systems. In addition growing media with less organic matter had better water quality performance. Comparison of these results with national and international standards for water reuse confirmed that the green roof outflow was suitable for non-potable uses such as landscape irrigation and toilet flushing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Spaceborne SAR Data for Aboveground-Biomass Retrieval of Indian Tropical Forests

NASA Astrophysics Data System (ADS)

Khati, U.; Singh, G.; Musthafa, M.

2017-12-01

Forests are important and indispensable part of the terrestrial ecosystems, and have a direct impact on the global carbon cycle. Forest biophysical parameters such as forest stand height and forest above-ground biomass (AGB) are forest health indicators. Measuring the forest biomass using traditional ground survey techniques are man-power consuming and have very low spatial coverage. Satellite based remote sensing techniques provide synoptic view of the earth with continuous measurements over large, inaccessible forest regions. Satellite Synthetic Aperture Radar (SAR) data has been shown to be sensitive to these forest bio-physical parameters and have been extensively utilized over boreal and tropical forests. However, there are limited studies over Indian tropical forests due to lack of auxiliary airborne data and difficulties in manual in situ data collection. In this research work we utilize spaceborne data from TerraSAR-X/TanDEM-X and ALOS-2/PALSAR-2 and implement both Polarimetric SAR and PolInSAR techniques for retrieval of AGB of a managed tropical forest in India. The TerraSAR-X/TanDEM-X provide a single-baseline PolInSAR data robust to temporal decorrelation. This would be used to accurately estimate the forest stand height. The retrieved height would be an input parameter for modelling AGB using the L-band ALOS-2/PALSAR-2 data. The IWCM model is extensively utilized to estimate AGB from SAR observations. In this research we utilize the six component scattering power decomposition (6SD) parameters and modify the IWCM based technique for a better retrieval of forest AGB. PolInSAR data shows a high estimation accuracy with r2 of 0.8 and a RMSE of 2 m. With this accurate height provided as input to the modified model along with 6SD parameters shows promising results. The results are validated with extensive field based measurements, and are further analysed in detail.

CADDIS Volume 4. Data Analysis: Advanced Analyses - Controlling for Natural Variability

EPA Pesticide Factsheets

Methods for controlling natural variability, predicting environmental conditions from biological observations method, biological trait data, species sensitivity distributions, propensity scores, Advanced Analyses of Data Analysis references.

How Reducing was the Late Devonian Ocean? The Role of Extensive Expansion of Anoxia in Marine Biogeochemical Cycles of Redox Sensitive Metals.

NASA Astrophysics Data System (ADS)

Sahoo, S. K.; Jin, H.

2017-12-01

The evolution of Earth's biogeochemical cycles is intimately linked to the oxygenation of the oceans and atmosphere. The Late Devonian is no exception as its characterized with mass extinction and severe euxinia. Here we use concentrations of Molybdenum (Mo), Vanadium (V), Uranium (U) and Chromium (Cr) in organic rich black shales from the Lower Bakken Formation of the Williston Basin, to explore the relationship between extensive anoxia vs. euxinia and it's relation with massive release of oxygen in the ocean atmosphere system. XRF data from 4 core across the basin shows that modern ocean style Mo, U and Cr enrichments are observed throughout the Lower Bakken Formation, yet V is not enriched until later part of the formation. Given the coupling between redox-sensitive-trace element cycles and ocean redox, various models for Late Devonian ocean chemistry imply different effects on the biogeochemical cycling of major and trace nutrients. Here, we examine the differing redox behavior of molybdenum and vanadium under an extreme anoxia and relatively low extent of euxinia. The model suggests that Late Devonian was perhaps extensively anoxic- 40-50% compared to modern seafloor area, and a very little euxinia. Mo enrichments extend up to 500 p.p.m. throughout the section, representative of a modern reducing ocean. However, coeval low V enrichments only support towards anoxia, where anoxia is a source of V, and a sink for Mo. Our model suggests that the oceanic V reservoir is extremely sensitive to perturbations in the extent of anoxic condition, particularly during post glacial times.

Beyond Getting in and Fitting in: An Examination of Social Networks and Professionally Relevant Social Capital among Latina/o University Students

ERIC Educational Resources Information Center

Rios-Aguilar, Cecilia; Deil-Amen, Regina

2012-01-01

Social network analyses, combined with qualitative analyses, are examined to understand key components of the college trajectories of 261 Latina/o students. Their social network ties reveal variation in extensity and the relevance. Most ties facilitate social capital relevant to getting into college, fewer engage social capital relevant to…

LSAT Dimensionality Analysis for the December 1991, June 1992, and October 1992 Administrations. Statistical Report. LSAC Research Report Series.

ERIC Educational Resources Information Center

Douglas, Jeff; Kim, Hae-Rim; Roussos, Louis; Stout, William; Zhang, Jinming

An extensive nonparametric dimensionality analysis of latent structure was conducted on three forms of the Law School Admission Test (LSAT) (December 1991, June 1992, and October 1992) using the DIMTEST model in confirmatory analyses and using DIMTEST, FAC, DETECT, HCA, PROX, and a genetic algorithm in exploratory analyses. Results indicate that…

Bayesian spatiotemporal model of fMRI data using transfer functions.

PubMed

Quirós, Alicia; Diez, Raquel Montes; Wilson, Simon P

2010-09-01

This research describes a new Bayesian spatiotemporal model to analyse BOLD fMRI studies. In the temporal dimension, we describe the shape of the hemodynamic response function (HRF) with a transfer function model. The spatial continuity and local homogeneity of the evoked responses are modelled by a Gaussian Markov random field prior on the parameter indicating activations. The proposal constitutes an extension of the spatiotemporal model presented in a previous approach [Quirós, A., Montes Diez, R. and Gamerman, D., 2010. Bayesian spatiotemporal model of fMRI data, Neuroimage, 49: 442-456], offering more flexibility in the estimation of the HRF and computational advantages in the resulting MCMC algorithm. Simulations from the model are performed in order to ascertain the performance of the sampling scheme and the ability of the posterior to estimate model parameters, as well as to check the model sensitivity to signal to noise ratio. Results are shown on synthetic data and on a real data set from a block-design fMRI experiment. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Novel T-cell epitopes of ovalbumin in BALB/c mouse: Potential for peptide-immunotherapy

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

Yang, Marie; Mine, Yoshinori

The identification of food allergen T-cell epitopes provides a platform for the development of novel immunotherapies. Despite extensive knowledge of the physicochemical properties of hen ovalbumin (OVA), a major egg allergen, the complete T-cell epitope map of OVA has surprisingly not been defined in the commonly used BALB/c mouse model. In this study, spleen cells obtained from OVA-sensitized mice were incubated in the presence of 12-mer overlapping synthetic peptides, constructed using the SPOTS synthesis method. Proliferative activity was assessed by 72-h in vitro assays with use of the tetrazolium salt WST-1 and led to identification of four mitogenic sequences, i.e.,more » A39R50, S147R158, K263E274, and A329E340. ELISA analyses of interferon (IFN)-{gamma} and interleukin (IL)-4 productions in cell culture supernatants upon stimulation with increasing concentrations of peptides confirmed their immunogenicity. Knowledge of the complete T-cell epitope map of OVA opens the way to a number of experimental investigations, including the exploration of peptide-based immunotherapy.« less

Language barriers and professional identity: A qualitative interview study of newly employed international medical doctors and Norwegian colleagues.

PubMed

Skjeggestad, Erik; Gerwing, Jennifer; Gulbrandsen, Pål

2017-08-01

To explore how language barriers influence communication and collaboration between newly-employed international medical doctors and Norwegian health personnel. Interviews were conducted with 16 doctors who had recently started working in Norway and 12 Norwegian born health personnel who had extensive experience working with international medical doctors. Analyses were consistent with principles of systematic text condensation. All participants experienced that language barriers caused difficulties in their everyday collaboration. Furthermore, the participants' descriptions of "language barriers" encompassed a wide range of topics, including semantics (e.g., specialized professional vocabulary, system knowledge), pragmatics (e.g., using language in doctor-patient and interprofessional interactions), and specific culturally sensitive topics. All participants described that language barriers provoked uncertainty about a doctor's competence. Newly employed international medical doctors and their colleagues are concerned by ineffective communication due to language barriers. Experiences of language barriers threaten professional identity as a competent and effective doctor. Newly employed doctors who are non-native speakers could benefit from support in understanding and handling the array of barriers related to language. Copyright © 2017 Elsevier B.V. All rights reserved.

How much information is in a jet?

NASA Astrophysics Data System (ADS)

Datta, Kaustuv; Larkoski, Andrew

2017-06-01

Machine learning techniques are increasingly being applied toward data analyses at the Large Hadron Collider, especially with applications for discrimination of jets with different originating particles. Previous studies of the power of machine learning to jet physics have typically employed image recognition, natural language processing, or other algorithms that have been extensively developed in computer science. While these studies have demonstrated impressive discrimination power, often exceeding that of widely-used observables, they have been formulated in a non-constructive manner and it is not clear what additional information the machines are learning. In this paper, we study machine learning for jet physics constructively, expressing all of the information in a jet onto sets of observables that completely and minimally span N-body phase space. For concreteness, we study the application of machine learning for discrimination of boosted, hadronic decays of Z bosons from jets initiated by QCD processes. Our results demonstrate that the information in a jet that is useful for discrimination power of QCD jets from Z bosons is saturated by only considering observables that are sensitive to 4-body (8 dimensional) phase space.

A putative octopamine/tyramine receptor mediating appetite in a hungry fly

NASA Astrophysics Data System (ADS)

Ishida, Yuko; Ozaki, Mamiko

2011-07-01

In the blowfly Phormia regina, experience of simultaneous feeding with d-limonene exposure inhibits proboscis extension reflex (PER) due to decreased tyramine (TA) titer in the brain. To elucidate the molecular mechanism of TA signaling pathway related to the associated feeding behavior, we cloned cDNA encoding the octopamine/TA receptor (PregOAR/TAR). The deduced protein is composed of 607 amino acid residues and has 7 predicted transmembrane domains. Based on homology and phylogenetic analyses, this protein belongs to the OAR/TAR family. The PregOAR/TAR was mainly expressed in head, with low levels of expression in other tissues at adult stages. Gene expression profile is in agreement with a plethora of functions ascribed to TA in various insect tissues. The immunolabeled cell bodies and processes were localized in the medial protocerebrum, outer layer of lobula, antennal lobe, and subesophageal ganglion. These results suggest that decrease of TA level in the brain likely affects neurons expressing PregOAR/TAR, causing mediation of the sensitivity in the sensillum and/or output of motor neurons for PER.

Pesticide residues determination in Polish organic crops in 2007-2010 applying gas chromatography-tandem quadrupole mass spectrometry.

PubMed

Walorczyk, Stanisław; Drożdżyński, Dariusz; Kowalska, Jolanta; Remlein-Starosta, Dorota; Ziółkowski, Andrzej; Przewoźniak, Monika; Gnusowski, Bogusław

2013-08-15

A sensitive, accurate and reliable multiresidue method based on the application of gas chromatography-tandem quadrupole mass spectrometry (GC-QqQ-MS/MS) has been established for screening, identification and quantification of a large number of pesticide residues in produce. The method was accredited in compliance with PN-EN ISO/IEC 17025:2005 standard and it was operated under flexible scope as PB-11 method. The flexible scope of accreditation allowed for minor modifications and extension of the analytical scope while using the same analytical technique. During the years 2007-2010, the method was used for the purpose of verification of organic crop production by multiresidue analysis for the presence of pesticides. A total of 528 samples of differing matrices such as fruits, vegetables, cereals, plant leaves and other green parts were analysed, of which 4.4% samples contained pesticide residues above the threshold value of 0.01 mg/kg. A total of 20 different pesticide residues were determined in the samples. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multidisciplinary design optimization of aircraft wing structures with aeroelastic and aeroservoelastic constraints

NASA Astrophysics Data System (ADS)

Jung, Sang-Young

Design procedures for aircraft wing structures with control surfaces are presented using multidisciplinary design optimization. Several disciplines such as stress analysis, structural vibration, aerodynamics, and controls are considered simultaneously and combined for design optimization. Vibration data and aerodynamic data including those in the transonic regime are calculated by existing codes. Flutter analyses are performed using those data. A flutter suppression method is studied using control laws in the closed-loop flutter equation. For the design optimization, optimization techniques such as approximation, design variable linking, temporary constraint deletion, and optimality criteria are used. Sensitivity derivatives of stresses and displacements for static loads, natural frequency, flutter characteristics, and control characteristics with respect to design variables are calculated for an approximate optimization. The objective function is the structural weight. The design variables are the section properties of the structural elements and the control gain factors. Existing multidisciplinary optimization codes (ASTROS* and MSC/NASTRAN) are used to perform single and multiple constraint optimizations of fully built up finite element wing structures. Three benchmark wing models are developed and/or modified for this purpose. The models are tested extensively.

Recent mouse models and vaccine candidates for preventing chronic/latent tuberculosis infection and its reactivation.

PubMed

Pedroza-Roldán, César; Flores-Valdez, Mario Alberto

2017-08-31

Tuberculosis (TB) remains a major challenge in public health worldwide. Until today, the only widely used and approved vaccine is the Mycobacterium bovis bacille Calmette-Guerin (BCG). This vaccine provides a highly variable level of protection against the active, pulmonary form of tuberculosis, and practically none against the latent form of TB infection. This disparity in protection has been extensively studied, and for this reason, several groups have focused their research on the quest for attenuated vaccines based on M. tuberculosis or on the identification of latency-associated antigens that can be incorporated into modified BCG, or that can be used as adjuvanted subunit vaccines. In order to seek new potential antigens relevant for infection, some researchers have performed experiments with highly sensitive techniques such as transcriptomic and proteomic analyses using sputum samples from humans or by using mouse models resembling several aspects of TB. In this review, we focus on reports of new mouse models or mycobacterial antigens recently tested for developing vaccine candidates against chronic/latent tuberculosis and its reactivation.

The financial attractiveness assessment of large waste management projects registered as clean development mechanism.

PubMed

Bufoni, André Luiz; Oliveira, Luciano Basto; Rosa, Luiz Pinguelli

2015-09-01

This study illustrates the financial analyses for demonstration and assessment of additionality presented in the project design (PDD) and enclosed documents of the 431 large Clean Development Mechanisms (CDM) classified as the 'waste handling and disposal sector' (13) over the past ten years (2004-2014). The expected certified emissions reductions (CER) of these projects total 63.54 million metric tons of CO2eq, where eight countries account for 311 projects and 43.36 million metric tons. All of the projects declare themselves 'not financially attractive' without CER with an estimated sum of negative results of approximately a half billion US$. The results indicate that WM benchmarks and indicators are converging and reducing in variance, and the sensitivity analysis reveals that revenues have a greater effect on the financial results. This work concludes that an extensive financial database with simple standards for disclosure would greatly diminish statement problems and make information more comparable, reducing the risk and capital costs of WM projects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Millimeter wave satellite concepts, volume 1

NASA Technical Reports Server (NTRS)

Hilsen, N. B.; Holland, L. D.; Thomas, R. E.; Wallace, R. W.; Gallagher, J. G.

1977-01-01

The identification of technologies necessary for development of millimeter spectrum communication satellites was examined from a system point of view. Development of methodology based on the technical requirements of potential services that might be assigned to millimeter wave bands for identifying the viable and appropriate technologies for future NASA millimeter research and development programs, and testing of this methodology with selected user applications and services were the goals of the program. The entire communications network, both ground and space subsystems was studied. Cost, weight, and performance models for the subsystems, conceptual design for point-to-point and broadcast communications satellites, and analytic relationships between subsystem parameters and an overall link performance are discussed along with baseline conceptual systems, sensitivity studies, model adjustment analyses, identification of critical technologies and their risks, and brief research and development program scenarios for the technologies judged to be moderate or extensive risks. Identification of technologies for millimeter satellite communication systems, and assessment of the relative risks of these technologies, was accomplished through subsystem modeling and link optimization for both point-to-point and broadcast applications.

MICROANALYSIS OF MATERIALS USING SYNCHROTRON RADIATION.

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

JONES,K.W.; FENG,H.

2000-12-01

High intensity synchrotron radiation produces photons with wavelengths that extend from the infrared to hard x rays with energies of hundreds of keV with uniquely high photon intensities that can be used to determine the composition and properties of materials using a variety of techniques. Most of these techniques represent extensions of earlier work performed with ordinary tube-type x-ray sources. The properties of the synchrotron source such as the continuous range of energy, high degree of photon polarization, pulsed beams, and photon flux many orders of magnitude higher than from x-ray tubes have made possible major advances in the possiblemore » chemical applications. We describe here ways that materials analyses can be made using the high intensity beams for measurements with small beam sizes and/or high detection sensitivity. The relevant characteristics of synchrotron x-ray sources are briefly summarized to give an idea of the x-ray parameters to be exploited. The experimental techniques considered include x-ray fluorescence, absorption, and diffraction. Examples of typical experimental apparatus used in these experiments are considered together with descriptions of actual applications.« less

Potential of mean force between like-charged nanoparticles: Many-body effect

NASA Astrophysics Data System (ADS)

Zhang, Xi; Zhang, Jin-Si; Shi, Ya-Zhou; Zhu, Xiao-Long; Tan, Zhi-Jie

2016-03-01

Ion-mediated interaction is important for the properties of polyelectrolytes such as colloids and nucleic acids. The effective pair interactions between two polyelectrolytes have been investigated extensively, but the many-body effect for multiple polyelectrolytes still remains elusive. In this work, the many-body effect in potential of mean force (PMF) between like-charged nanoparticles in various salt solutions has been comprehensively examined by Monte Carlo simulation and the nonlinear Poisson-Boltzmann theory. Our calculations show that, at high 1:1 salt, the PMF is weakly repulsive and appears additive, while at low 1:1 salt, the additive assumption overestimates the repulsive many-body PMF. At low 2:2 salt, the pair PMF appears weakly repulsive while the many-body PMF can become attractive. In contrast, at high 2:2 salt, the pair PMF is apparently attractive while the many-body effect can cause a weaker attractive PMF than that from the additive assumption. Our microscopic analyses suggest that the elusive many-body effect is attributed to ion-binding which is sensitive to ion concentration, ion valence, number of nanoparticles and charges on nanoparticles.

Two-dimensional fuzzy fault tree analysis for chlorine release from a chlor-alkali industry using expert elicitation.

PubMed

Renjith, V R; Madhu, G; Nayagam, V Lakshmana Gomathi; Bhasi, A B

2010-11-15

The hazards associated with major accident hazard (MAH) industries are fire, explosion and toxic gas releases. Of these, toxic gas release is the worst as it has the potential to cause extensive fatalities. Qualitative and quantitative hazard analyses are essential for the identification and quantification of these hazards related to chemical industries. Fault tree analysis (FTA) is an established technique in hazard identification. This technique has the advantage of being both qualitative and quantitative, if the probabilities and frequencies of the basic events are known. This paper outlines the estimation of the probability of release of chlorine from storage and filling facility of chlor-alkali industry using FTA. An attempt has also been made to arrive at the probability of chlorine release using expert elicitation and proven fuzzy logic technique for Indian conditions. Sensitivity analysis has been done to evaluate the percentage contribution of each basic event that could lead to chlorine release. Two-dimensional fuzzy fault tree analysis (TDFFTA) has been proposed for balancing the hesitation factor involved in expert elicitation. Copyright © 2010 Elsevier B.V. All rights reserved.

Global and Local Stress Analyses of McDonnell Douglas Stitched/RFI Composite Wing Stub Box

NASA Technical Reports Server (NTRS)

Wang, John T.

1996-01-01

This report contains results of structural analyses performed in support of the NASA structural testing of an all-composite stitched/RFI (resin film infusion) wing stub box. McDonnell Douglas Aerospace Company designed and fabricated the wing stub box. The analyses used a global/local approach. The global model contains the entire test article. It includes the all-composite stub box, a metallic load-transition box and a metallic wing-tip extension box. The two metallic boxes are connected to the inboard and outboard ends of the composite wing stub box, respectively. The load-transition box was attached to a steel and concrete vertical reaction structure and a load was applied at the tip of the extension box to bend the wing stub box upward. The local model contains an upper cover region surrounding three stringer runouts. In that region, a large nonlinear deformation was identified by the global analyses. A more detailed mesh was used for the local model to obtain more accurate analysis results near stringer runouts. Numerous analysis results such as deformed shapes, displacements at selected locations, and strains at critical locations are included in this report.

Sensitivity Observing System Experiment (SOSE)-a new effective NWP-based tool in designing the global observing system

NASA Astrophysics Data System (ADS)

Marseille, Gert-Jan; Stoffelen, Ad; Barkmeijer, Jan

2008-03-01

Lacking an established methodology to test the potential impact of prospective extensions to the global observing system (GOS) in real atmospheric cases we developed such a method, called Sensitivity Observing System Experiment (SOSE). For example, since the GOS is non uniform it is of interest to investigate the benefit of complementary observing systems filling its gaps. In a SOSE adjoint sensitivity structures are used to define a pseudo true atmospheric state for the simulation of the prospective observing system. Next, the synthetic observations are used together with real observations from the existing GOS in a state-of-the-art Numerical Weather Prediction (NWP) model to assess the potential added value of the new observing system. Unlike full observing system simulation experiments (OSSE), SOSE can be applied to real extreme events that were badly forecast operationally and only requires the simulation of the new instrument. As such SOSE is an effective tool, for example, to define observation requirements for extensions to the GOS. These observation requirements may serve as input for the design of an operational network of prospective observing systems. In a companion paper we use SOSE to simulate potential future space borne Doppler Wind Lidar (DWL) scenarios and assess their capability to sample meteorologically sensitive areas not well captured by the current GOS, in particular over the Northern Hemisphere oceans.

LaRC design analysis report for National Transonic Facility for 304 stainless steel tunnel shell. Volume 1S: Finite difference analysis of cone/cylinder junction

NASA Technical Reports Server (NTRS)

Ramsey, J. W., Jr.; Taylor, J. T.; Wilson, J. F.; Gray, C. E., Jr.; Leatherman, A. D.; Rooker, J. R.; Allred, J. W.

1976-01-01

The results of extensive computer (finite element, finite difference and numerical integration), thermal, fatigue, and special analyses of critical portions of a large pressurized, cryogenic wind tunnel (National Transonic Facility) are presented. The computer models, loading and boundary conditions are described. Graphic capability was used to display model geometry, section properties, and stress results. A stress criteria is presented for evaluation of the results of the analyses. Thermal analyses were performed for major critical and typical areas. Fatigue analyses of the entire tunnel circuit are presented.

Gas chromatography/chemical ionization triple quadrupole mass spectrometry analysis of anabolic steroids: ionization and collision-induced dissociation behavior.

PubMed

Polet, Michael; Van Gansbeke, Wim; Van Eenoo, Peter; Deventer, Koen

2016-02-28

The detection of new anabolic steroid metabolites and new designer steroids is a challenging task in doping analysis. Switching from electron ionization gas chromatography triple quadrupole mass spectrometry (GC/EI-MS/MS) to chemical ionization (CI) has proven to be an efficient way to increase the sensitivity of GC/MS/MS analyses and facilitate the detection of anabolic steroids. CI also extends the possibilities of GC/MS/MS analyses as the molecular ion is retained in its protonated form due to the softer ionization. In EI it can be difficult to find previously unknown but expected metabolites due to the low abundance or absence of the molecular ion and the extensive (and to a large extent unpredictable) fragmentation. The main aim of this work was to study the CI and collision-induced dissociation (CID) behavior of a large number of anabolic androgenic steroids (AAS) as their trimethylsilyl derivatives in order to determine correlations between structures and CID fragmentation. Clarification of these correlations is needed for the elucidation of structures of unknown steroids and new metabolites. The ionization and CID behavior of 65 AAS have been studied using GC/CI-MS/MS with ammonia as the reagent gas. Glucuronidated AAS reference standards were first hydrolyzed to obtain their free forms. Afterwards, all the standards were derivatized to their trimethylsilyl forms. Full scan and product ion scan analyses were used to examine the ionization and CID behavior. Full scan and product ion scan analyses revealed clear correlations between AAS structure and the obtained mass spectra. These correlations were confirmed by analysis of multiple hydroxylated, methylated, chlorinated and deuterated analogs. AAS have been divided into three groups according to their ionization behavior and into seven groups according to their CID behavior. Correlations between fragmentation and structure were revealed and fragmentation pathways were postulated. Copyright © 2016 John Wiley & Sons, Ltd.

Sensitive periods in affective development: nonlinear maturation of fear learning.

PubMed

Hartley, Catherine A; Lee, Francis S

2015-01-01

At specific maturational stages, neural circuits enter sensitive periods of heightened plasticity, during which the development of both brain and behavior are highly receptive to particular experiential information. A relatively advanced understanding of the regulatory mechanisms governing the initiation, closure, and reinstatement of sensitive period plasticity has emerged from extensive research examining the development of the visual system. In this article, we discuss a large body of work characterizing the pronounced nonlinear changes in fear learning and extinction that occur from childhood through adulthood, and their underlying neural substrates. We draw upon the model of sensitive period regulation within the visual system, and present burgeoning evidence suggesting that parallel mechanisms may regulate the qualitative changes in fear learning across development.

Sensitive Periods in Affective Development: Nonlinear Maturation of Fear Learning

PubMed Central

Hartley, Catherine A; Lee, Francis S

2015-01-01

At specific maturational stages, neural circuits enter sensitive periods of heightened plasticity, during which the development of both brain and behavior are highly receptive to particular experiential information. A relatively advanced understanding of the regulatory mechanisms governing the initiation, closure, and reinstatement of sensitive period plasticity has emerged from extensive research examining the development of the visual system. In this article, we discuss a large body of work characterizing the pronounced nonlinear changes in fear learning and extinction that occur from childhood through adulthood, and their underlying neural substrates. We draw upon the model of sensitive period regulation within the visual system, and present burgeoning evidence suggesting that parallel mechanisms may regulate the qualitative changes in fear learning across development. PMID:25035083

US 93 preconstruction wildlife monitoring field methods handbook : final report.

DOT National Transportation Integrated Search

2006-11-01

The US 93 reconstruction project on the Flathead Indian Reservation in northwest Montana represents one of the most extensive wildlife-sensitive highway design efforts to occur in the continental United States. The reconstruction will include install...

77 FR 39459 - Fisheries of the United States; National Standard 1 Guidelines; Extension of Public Comment Period

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-03

... business information or otherwise sensitive or protected information. NMFS will accept anonymous comments (enter ``N/A'' in the required fields if you wish to remain anonymous). Attachments to electronic...

Permutation testing of orthogonal factorial effects in a language-processing experiment using fMRI.

PubMed

Suckling, John; Davis, Matthew H; Ooi, Cinly; Wink, Alle Meije; Fadili, Jalal; Salvador, Raymond; Welchew, David; Sendur, Levent; Maxim, Vochita; Bullmore, Edward T

2006-05-01

The block-paradigm of the Functional Image Analysis Contest (FIAC) dataset was analysed with the Brain Activation and Morphological Mapping software. Permutation methods in the wavelet domain were used for inference on cluster-based test statistics of orthogonal contrasts relevant to the factorial design of the study, namely: the average response across all active blocks, the main effect of speaker, the main effect of sentence, and the interaction between sentence and speaker. Extensive activation was seen with all these contrasts. In particular, different vs. same-speaker blocks produced elevated activation in bilateral regions of the superior temporal lobe and repetition suppression for linguistic materials (same vs. different-sentence blocks) in left inferior frontal regions. These are regions previously reported in the literature. Additional regions were detected in this study, perhaps due to the enhanced sensitivity of the methodology. Within-block sentence suppression was tested post-hoc by regression of an exponential decay model onto the extracted time series from the left inferior frontal gyrus, but no strong evidence of such an effect was found. The significance levels set for the activation maps are P-values at which we expect <1 false-positive cluster per image. Nominal type I error control was verified by empirical testing of a test statistic corresponding to a randomly ordered design matrix. The small size of the BOLD effect necessitates sensitive methods of detection of brain activation. Permutation methods permit the necessary flexibility to develop novel test statistics to meet this challenge.

Selective Expression of a Sodium Pump Isozyme by Cough Receptors and Evidence for Its Essential Role in Regulating Cough

PubMed Central

Mazzone, Stuart B.; Reynolds, Sandra M.; Mori, Nanako; Kollarik, Marian; Farmer, David G.; Myers, Allen C.

2009-01-01

We have identified a distinct subtype of airway vagal afferent nerve that plays an essential role in regulating the cough reflex. These afferents are exquisitely sensitive to punctate mechanical stimuli, acid, and decreases in extracellular chloride concentrations, but are insensitive to capsaicin, bradykinin, histamine, adenosine, serotonin, or changes in airway intraluminal pressures. In this study we used intravital imaging, retrograde neuronal tracing, and electrophysiological analyses to characterize the structural basis for their peculiar mechanical sensitivity and to further characterize the regulation of their excitability. In completing these experiments, we uncovered evidence for an essential role of an isozyme of Na+-K+ ATPase in regulating cough. These vagal sensory neurons arise bilaterally from the nodose ganglia and are selectively and brilliantly stained intravitally with the styryl dye FM2-10. Cough receptor terminations are confined and adherent to the extracellular matrix separating the airway epithelium and smooth muscle layers, a site of extensive remodeling in asthma and chronic obstructive pulmonary disease. The cough receptor terminals uniquely express the α3 subunit of Na+-K+ ATPase. Intravital staining of cough receptors by FM2-10, cough receptor excitability in vitro, and coughing in vivo are potently and selectively inhibited by the sodium pump inhibitor ouabain. These data provide the first detailed morphological description of the peripheral terminals of the sensory nerves regulating cough and identify a selective molecular target for their modulation. PMID:19864578

Simulation of a multistage fractured horizontal well in a water-bearing tight fractured gas reservoir under non-Darcy flow

NASA Astrophysics Data System (ADS)

Zhang, Rui-Han; Zhang, Lie-Hui; Wang, Rui-He; Zhao, Yu-Long; Huang, Rui

2018-06-01

Reservoir development for unconventional resources such as tight gas reservoirs is in increasing demand due to the rapid decline of production in conventional reserves. Compared with conventional reservoirs, fluid flow in water-bearing tight gas reservoirs is subject to more nonlinear multiphase flow and gas slippage in nano/micro matrix pores because of the strong collisions between rock and gas molecules. Economic gas production from tight gas reservoirs depends on extensive application of water-based hydraulic fracturing of horizontal wells, associated with non-Darcy flow at a high flow rate, geomechanical stress sensitivity of un-propped natural fractures, complex flow geometry and multiscale heterogeneity. How to efficiently and accurately predict the production performance of a multistage fractured horizontal well (MFHW) is challenging. In this paper, a novel multicontinuum, multimechanism, two-phase simulator is established based on unstructured meshes and the control volume finite element method to analyze the production performance of MFHWs. The multiple interacting continua model and discrete fracture model are coupled to integrate the unstimulated fractured reservoir, induced fracture networks (stimulated reservoir volumes, SRVs) and irregular discrete hydraulic fractures. Several simulations and sensitivity analyses are performed with the developed simulator for determining the key factors affecting the production performance of MFHWs. Two widely applied fracturing models, classic hydraulic fracturing which generates long double-wing fractures and the volumetric fracturing aimed at creating large SRVs, are compared to identify which of them can make better use of tight gas reserves.

Cost-Effectiveness Analysis of a National Newborn Screening Program for Biotinidase Deficiency.

PubMed

Vallejo-Torres, Laura; Castilla, Iván; Couce, María L; Pérez-Cerdá, Celia; Martín-Hernández, Elena; Pineda, Mercé; Campistol, Jaume; Arrospide, Arantzazu; Morris, Stephen; Serrano-Aguilar, Pedro

2015-08-01

There are conflicting views as to whether testing for biotinidase deficiency (BD) ought to be incorporated into universal newborn screening (NBS) programs. The aim of this study was to evaluate the cost-effectiveness of adding BD to the panel of conditions currently screened under the national NBS program in Spain. We used information from the regional NBS program for BD that has been in place in the Spanish region of Galicia since 1987. These data, along with other sources, were used to develop a cost-effectiveness decision model that compared lifetime costs and health outcomes of a national birth cohort of newborns with and without an early detection program. The analysis took the perspective of the Spanish National Health Service. Effectiveness was measured in terms of quality-adjusted life years (QALYs). We undertook extensive sensitivity analyses around the main model assumptions, including a probabilistic sensitivity analysis. In the base case analysis, NBS for BD led to higher QALYs and higher health care costs, with an estimated incremental cost per QALY gained of $24,677. Lower costs per QALY gained were found when conservative assumptions were relaxed, yielding cost savings in some scenarios. The probability that BD screening was cost-effective was estimated to be >70% in the base case at a standard threshold value. This study indicates that NBS for BD is likely to be a cost-effective use of resources. Copyright © 2015 by the American Academy of Pediatrics.

A biophysical model of kiwifruit (Actinidia deliciosa) berry development

PubMed Central

Hall, Alistair J.

2013-01-01

A model of kiwifruit berry development is presented, building on the model of Fishman and Génard used for peach fruit. That model has been extended to incorporate a number of important features of kiwifruit growth. First, the kiwifruit berry is attached to the stem through a pedicel/receptacle complex which contributes significantly to the hydraulic resistance between the stem and the fruit, and this resistance changes considerably during the season. Second, much of the carbohydrate in kiwifruit berries is stored as starch until the fruit matures late in the season, when the starch hydrolyses to soluble sugars. This starch storage has a major effect on the osmotic potential of the fruit, so an existing model of kiwifruit starch dynamics was included in the model. Using previously published approaches, we also included elasticity and extended the modelling period to cover both the cell division and cell expansion phases of growth. The resulting model showed close simulation of field observations of fresh weight, dry matter, starch, and soluble solids in kiwifruit. Comparison with continuous measurements of fruit diameter confirmed that elasticity was needed to adequately simulate observed diurnal variation in fruit size. Sensitivity analyses suggested that the model is particularly sensitive to variation in inputs relating to water (stem water potential and the humidity of the air), and to parameters controlling cell expansion (cell wall extensibility). Some limitations in the model structure were identified, suggesting that a revised model including current apoplastic/symplastic concepts needs to be developed. PMID:24123250

A biophysical model of kiwifruit (Actinidia deliciosa) berry development.

PubMed

Hall, Alistair J; Minchin, Peter E H; Clearwater, Michael J; Génard, Michel

2013-12-01

A model of kiwifruit berry development is presented, building on the model of Fishman and Génard used for peach fruit. That model has been extended to incorporate a number of important features of kiwifruit growth. First, the kiwifruit berry is attached to the stem through a pedicel/receptacle complex which contributes significantly to the hydraulic resistance between the stem and the fruit, and this resistance changes considerably during the season. Second, much of the carbohydrate in kiwifruit berries is stored as starch until the fruit matures late in the season, when the starch hydrolyses to soluble sugars. This starch storage has a major effect on the osmotic potential of the fruit, so an existing model of kiwifruit starch dynamics was included in the model. Using previously published approaches, we also included elasticity and extended the modelling period to cover both the cell division and cell expansion phases of growth. The resulting model showed close simulation of field observations of fresh weight, dry matter, starch, and soluble solids in kiwifruit. Comparison with continuous measurements of fruit diameter confirmed that elasticity was needed to adequately simulate observed diurnal variation in fruit size. Sensitivity analyses suggested that the model is particularly sensitive to variation in inputs relating to water (stem water potential and the humidity of the air), and to parameters controlling cell expansion (cell wall extensibility). Some limitations in the model structure were identified, suggesting that a revised model including current apoplastic/symplastic concepts needs to be developed.

Production of monoclonal antibody for okadaic acid and its utilization in an ultrasensitive enzyme-linked immunosorbent assay and one-step immunochromatographic strip.

PubMed

Liu, Biing-Hui; Hung, Chun-Tse; Lu, Chuan-Chen; Chou, Hong-Non; Yu, Feng-Yih

2014-02-12

Okadaic acid (OA) is a common marine biotoxin that accumulates in bivalves and causes diarrhetic shellfish poisoning (DSP). This study generated a monoclonal antibody (mAb) specific to OA from a hybridoma cell line, 6B1A3, which was obtained by fusion of myeloma cells (P3/NS1/1-AG4-1) with spleen cells isolated from a BALB/c mouse immunized with OA-γ-globulin. The 6B1A3 mAb belongs to the immunoglobulin G1 (κ chain) isotype. Both competitive direct and indirect enzyme-linked immunosorbent assays (ELISAs) were established for characterization of the antibody. The concentrations causing 50% inhibition of binding of OA-horseradish peroxidase to the antibody by OA were calculated to be 0.077 ng/mL in the cdELISA. A rapid and sensitive mAb-based gold nanoparticle immunochromatographic strip was also established. This proposed strip has a detection limit of 5 ng/mL for OA and can be finished in 10 min. Extensive analyses of 20 seafood samples with ELISA revealed that 10 were slightly contaminated with OA, with a mean concentration of 0.892 ng/g. Analysis of OA in shellfish samples showed that data acquired by the immunochromatographic strip agreed well with those acquired by the ELISA. The mAb-based ELISA and immunochromatographic strip assay developed in this study have adequate sensitivity and accuracy for rapid screening of OA in shellfish samples.

Aerodynamic shape optimization directed toward a supersonic transport using sensitivity analysis

NASA Technical Reports Server (NTRS)

Baysal, Oktay

1995-01-01

This investigation was conducted from March 1994 to August 1995, primarily, to extend and implement the previously developed aerodynamic design optimization methodologies for the problems related to a supersonic transport design. These methods had demonstrated promise to improve the designs (more specifically, the shape) of aerodynamic surfaces, by coupling optimization algorithms (OA) with Computational Fluid Dynamics (CFD) algorithms via sensitivity analyses (SA) with surface definition methods from Computer Aided Design (CAD). The present extensions of this method and their supersonic implementations have produced wing section designs, delta wing designs, cranked-delta wing designs, and nacelle designs, all of which have been reported in the open literature. Despite the fact that these configurations were highly simplified to be of any practical or commercial use, they served the algorithmic and proof-of-concept objectives of the study very well. The primary cause for the configurational simplifications, other than the usual simplify-to-study the fundamentals reason, were the premature closing of the project. Only after the first of the originally intended three-year term, both the funds and the computer resources supporting the project were abruptly cut due to their severe shortages at the funding agency. Nonetheless, it was shown that the extended methodologies could be viable options in optimizing the design of not only an isolated single-component configuration, but also a multiple-component configuration in supersonic and viscous flow. This allowed designing with the mutual interference of the components being one of the constraints all along the evolution of the shapes.

Does the Superior Colliculus Control Perceptual Sensitivity or Choice Bias during Attention? Evidence from a Multialternative Decision Framework

PubMed Central

Steinmetz, Nicholas A.; Moore, Tirin; Knudsen, Eric I.

2017-01-01

Distinct networks in the forebrain and the midbrain coordinate to control spatial attention. The critical involvement of the superior colliculus (SC)—the central structure in the midbrain network—in visuospatial attention has been shown by four seminal, published studies in monkeys (Macaca mulatta) performing multialternative tasks. However, due to the lack of a mechanistic framework for interpreting behavioral data in such tasks, the nature of the SC's contribution to attention remains unclear. Here we present and validate a novel decision framework for analyzing behavioral data in multialternative attention tasks. We apply this framework to re-examine the behavioral evidence from these published studies. Our model is a multidimensional extension to signal detection theory that distinguishes between two major classes of attentional mechanisms: those that alter the quality of sensory information or “sensitivity,” and those that alter the selective gating of sensory information or “choice bias.” Model-based simulations and model-based analyses of data from these published studies revealed a converging pattern of results that indicated that choice-bias changes, rather than sensitivity changes, were the primary outcome of SC manipulation. Our results suggest that the SC contributes to attentional performance predominantly by generating a spatial choice bias for stimuli at a selected location, and that this bias operates downstream of forebrain mechanisms that enhance sensitivity. The findings lead to a testable mechanistic framework of how the midbrain and forebrain networks interact to control spatial attention. SIGNIFICANCE STATEMENT Attention involves the selection of the most relevant information for differential sensory processing and decision making. While the mechanisms by which attention alters sensory encoding (sensitivity control) are well studied, the mechanisms by which attention alters decisional weighting of sensory evidence (choice-bias control) are poorly understood. Here, we introduce a model of multialternative decision making that distinguishes bias from sensitivity effects in attention tasks. With our model, we simulate experimental data from four seminal studies that microstimulated or inactivated a key attention-related midbrain structure, the superior colliculus (SC). We demonstrate that the experimental effects of SC manipulation are entirely consistent with the SC controlling attention by changing choice bias, thereby shedding new light on how the brain mediates attention. PMID:28100734

Does the Superior Colliculus Control Perceptual Sensitivity or Choice Bias during Attention? Evidence from a Multialternative Decision Framework.

PubMed

Sridharan, Devarajan; Steinmetz, Nicholas A; Moore, Tirin; Knudsen, Eric I

2017-01-18

Distinct networks in the forebrain and the midbrain coordinate to control spatial attention. The critical involvement of the superior colliculus (SC)-the central structure in the midbrain network-in visuospatial attention has been shown by four seminal, published studies in monkeys (Macaca mulatta) performing multialternative tasks. However, due to the lack of a mechanistic framework for interpreting behavioral data in such tasks, the nature of the SC's contribution to attention remains unclear. Here we present and validate a novel decision framework for analyzing behavioral data in multialternative attention tasks. We apply this framework to re-examine the behavioral evidence from these published studies. Our model is a multidimensional extension to signal detection theory that distinguishes between two major classes of attentional mechanisms: those that alter the quality of sensory information or "sensitivity," and those that alter the selective gating of sensory information or "choice bias." Model-based simulations and model-based analyses of data from these published studies revealed a converging pattern of results that indicated that choice-bias changes, rather than sensitivity changes, were the primary outcome of SC manipulation. Our results suggest that the SC contributes to attentional performance predominantly by generating a spatial choice bias for stimuli at a selected location, and that this bias operates downstream of forebrain mechanisms that enhance sensitivity. The findings lead to a testable mechanistic framework of how the midbrain and forebrain networks interact to control spatial attention. Attention involves the selection of the most relevant information for differential sensory processing and decision making. While the mechanisms by which attention alters sensory encoding (sensitivity control) are well studied, the mechanisms by which attention alters decisional weighting of sensory evidence (choice-bias control) are poorly understood. Here, we introduce a model of multialternative decision making that distinguishes bias from sensitivity effects in attention tasks. With our model, we simulate experimental data from four seminal studies that microstimulated or inactivated a key attention-related midbrain structure, the superior colliculus (SC). We demonstrate that the experimental effects of SC manipulation are entirely consistent with the SC controlling attention by changing choice bias, thereby shedding new light on how the brain mediates attention. Copyright © 2017 the authors 0270-6474/17/370480-32$15.00/0.

Evaluation of microarray data normalization procedures using spike-in experiments

PubMed Central

Rydén, Patrik; Andersson, Henrik; Landfors, Mattias; Näslund, Linda; Hartmanová, Blanka; Noppa, Laila; Sjöstedt, Anders

2006-01-01

Background Recently, a large number of methods for the analysis of microarray data have been proposed but there are few comparisons of their relative performances. By using so-called spike-in experiments, it is possible to characterize the analyzed data and thereby enable comparisons of different analysis methods. Results A spike-in experiment using eight in-house produced arrays was used to evaluate established and novel methods for filtration, background adjustment, scanning, channel adjustment, and censoring. The S-plus package EDMA, a stand-alone tool providing characterization of analyzed cDNA-microarray data obtained from spike-in experiments, was developed and used to evaluate 252 normalization methods. For all analyses, the sensitivities at low false positive rates were observed together with estimates of the overall bias and the standard deviation. In general, there was a trade-off between the ability of the analyses to identify differentially expressed genes (i.e. the analyses' sensitivities) and their ability to provide unbiased estimators of the desired ratios. Virtually all analysis underestimated the magnitude of the regulations; often less than 50% of the true regulations were observed. Moreover, the bias depended on the underlying mRNA-concentration; low concentration resulted in high bias. Many of the analyses had relatively low sensitivities, but analyses that used either the constrained model (i.e. a procedure that combines data from several scans) or partial filtration (a novel method for treating data from so-called not-found spots) had with few exceptions high sensitivities. These methods gave considerable higher sensitivities than some commonly used analysis methods. Conclusion The use of spike-in experiments is a powerful approach for evaluating microarray preprocessing procedures. Analyzed data are characterized by properties of the observed log-ratios and the analysis' ability to detect differentially expressed genes. If bias is not a major problem; we recommend the use of either the CM-procedure or partial filtration. PMID:16774679

Coupled Aerodynamic and Structural Sensitivity Analysis of a High-Speed Civil Transport

NASA Technical Reports Server (NTRS)

Mason, B. H.; Walsh, J. L.

2001-01-01

An objective of the High Performance Computing and Communication Program at the NASA Langley Research Center is to demonstrate multidisciplinary shape and sizing optimization of a complete aerospace vehicle configuration by using high-fidelity, finite-element structural analysis and computational fluid dynamics aerodynamic analysis. In a previous study, a multi-disciplinary analysis system for a high-speed civil transport was formulated to integrate a set of existing discipline analysis codes, some of them computationally intensive, This paper is an extension of the previous study, in which the sensitivity analysis for the coupled aerodynamic and structural analysis problem is formulated and implemented. Uncoupled stress sensitivities computed with a constant load vector in a commercial finite element analysis code are compared to coupled aeroelastic sensitivities computed by finite differences. The computational expense of these sensitivity calculation methods is discussed.

Obesity and gynaecological and obstetric conditions: umbrella review of the literature.

PubMed

Kalliala, Ilkka; Markozannes, Georgios; Gunter, Marc J; Paraskevaidis, Evangelos; Gabra, Hani; Mitra, Anita; Terzidou, Vasso; Bennett, Phillip; Martin-Hirsch, Pierre; Tsilidis, Konstantinos K; Kyrgiou, Maria

2017-10-26

Objective  To study the strength and validity of associations between adiposity and risk of any type of obstetric or gynaecological conditions. Design  An umbrella review of meta-analyses. Data sources  PubMed, Cochrane database of systematic reviews, manual screening of references for systematic reviews or meta-analyses of observational and interventional studies evaluating the association between adiposity and risk of any obstetrical or gynaecological outcome. Main outcomes  Meta-analyses of cohort studies on associations between indices of adiposity and obstetric and gynaecological outcomes. Data synthesis  Evidence from observational studies was graded into strong, highly suggestive, suggestive, or weak based on the significance of the random effects summary estimate and the largest study in the included meta-analysis, the number of cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings. Interventional meta-analyses were assessed separately. Results  156 meta-analyses of observational studies were included, investigating associations between adiposity and risk of 84 obstetric or gynaecological outcomes. Of the 144 meta-analyses that included cohort studies, only 11 (8%) had strong evidence for eight outcomes: adiposity was associated with a higher risk of endometrial cancer, ovarian cancer, antenatal depression, total and emergency caesarean section, pre-eclampsia, fetal macrosomia, and low Apgar score. The summary effect estimates ranged from 1.21 (95% confidence interval 1.13 to 1.29) for an association between a 0.1 unit increase in waist to hip ratio and risk endometrial cancer up to 4.14 (3.61 to 4.75) for risk of pre-eclampsia for BMI >35 compared with <25. Only three out of these eight outcomes were also assessed in meta-analyses of trials evaluating weight loss interventions. These interventions significantly reduced the risk of caesarean section and pre-eclampsia, whereas there was no evidence of association with fetal macrosomia. Conclusions  Although the associations between adiposity and obstetric and gynaecological outcomes have been extensively studied, only a minority were considered strong and without hints of bias. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Is the Prediction of Adolescent Outcomes From Early Child Care Moderated by Later Maternal Sensitivity? Results From the NICHD Study of Early Child Care and Youth Development

PubMed Central

Burchinal, Margaret R.; Vandell, Deborah Lowe; Belsky, Jay

2016-01-01

Longitudinal data are used to examine whether effects of early child care are amplified and/or attenuated by later parenting. Analyses tested these interactions using parenting as both a categorical and continuous variable to balance power and flexibility in testing moderation. The most consistent finding was that maternal sensitivity during adolescence accentuated the association between child care quality and adolescent academic-cognitive skills at age 15 years when maternal sensitivity during adolescence was high. This interaction was obtained in analyses with maternal sensitivity as both a categorical and continuous variable. Relations between early child care hours and adolescent behavioral outcomes also were moderated by maternal sensitivity, with longer child care hours predicting more impulsivity and externalizing at age 15 when maternal sensitivity during middle childhood, scored as a categorical variable, was low to moderate and when maternal sensitivity during adolescence, scored as a continuous variable, was lower. These findings suggest that some child care effects are moderated by subsequent parenting and that this moderation may take both linear and nonlinear forms. PMID:23937381

Computational Aspects of Sensitivity Calculations in Linear Transient Structural Analysis. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Greene, William H.

1989-01-01

A study has been performed focusing on the calculation of sensitivities of displacements, velocities, accelerations, and stresses in linear, structural, transient response problems. One significant goal was to develop and evaluate sensitivity calculation techniques suitable for large-order finite element analyses. Accordingly, approximation vectors such as vibration mode shapes are used to reduce the dimensionality of the finite element model. Much of the research focused on the accuracy of both response quantities and sensitivities as a function of number of vectors used. Two types of sensitivity calculation techniques were developed and evaluated. The first type of technique is an overall finite difference method where the analysis is repeated for perturbed designs. The second type of technique is termed semianalytical because it involves direct, analytical differentiation of the equations of motion with finite difference approximation of the coefficient matrices. To be computationally practical in large-order problems, the overall finite difference methods must use the approximation vectors from the original design in the analyses of the perturbed models.

Impaired temporal contrast sensitivity in dyslexics is specific to retain-and-compare paradigms.

PubMed

Ben-Yehudah, G; Sackett, E; Malchi-Ginzberg, L; Ahissar, M

2001-07-01

Developmental dyslexia is a specific reading disability that affects 5-10% of the population. Recent studies have suggested that dyslexics may experience a deficit in the visual magnocellular pathway. The most extensively studied prediction deriving from this hypothesis is impaired contrast sensitivity to transient, low-luminance stimuli at low spatial frequencies. However, the findings are inconsistent across studies and even seemingly contradictory. In the present study, we administered several different paradigms for assessing temporal contrast sensitivity, and found both impaired and normal contrast sensitivity within the same group of dyslexic participants. Under sequential presentation, in a temporal forced choice paradigm, dyslexics showed impaired sensitivity to both drifting and flickering gratings. However, under simultaneous presentation, with a spatial forced choice paradigm, dyslexics' sensitivity did not differ from that of the controls. Within each paradigm, dyslexics' sensitivity was poorer at higher temporal frequencies, consistent with the magnocellular hypothesis. These results suggest that a basic perceptual impairment in dyslexics may be their limited ability to retain-and-compare perceptual traces across brief intervals.

Sampling and sensitivity analyses tools (SaSAT) for computational modelling

PubMed Central

Hoare, Alexander; Regan, David G; Wilson, David P

2008-01-01

SaSAT (Sampling and Sensitivity Analysis Tools) is a user-friendly software package for applying uncertainty and sensitivity analyses to mathematical and computational models of arbitrary complexity and context. The toolbox is built in Matlab®, a numerical mathematical software package, and utilises algorithms contained in the Matlab® Statistics Toolbox. However, Matlab® is not required to use SaSAT as the software package is provided as an executable file with all the necessary supplementary files. The SaSAT package is also designed to work seamlessly with Microsoft Excel but no functionality is forfeited if that software is not available. A comprehensive suite of tools is provided to enable the following tasks to be easily performed: efficient and equitable sampling of parameter space by various methodologies; calculation of correlation coefficients; regression analysis; factor prioritisation; and graphical output of results, including response surfaces, tornado plots, and scatterplots. Use of SaSAT is exemplified by application to a simple epidemic model. To our knowledge, a number of the methods available in SaSAT for performing sensitivity analyses have not previously been used in epidemiological modelling and their usefulness in this context is demonstrated. PMID:18304361

CADDIS Volume 4. Data Analysis: Advanced Analyses - Controlling for Natural Variability: SSD Plot Diagrams

EPA Pesticide Factsheets

Methods for controlling natural variability, predicting environmental conditions from biological observations method, biological trait data, species sensitivity distributions, propensity scores, Advanced Analyses of Data Analysis references.

Experimental droughts with rainout shelters: A methodological review

USDA-ARS?s Scientific Manuscript database

Forecast increases in the frequency, intensity and duration of droughts with climate change may have extreme and extensive ecological consequences. There are currently hundreds of published, ongoing and new drought experiments worldwide aimed to assess ecosystem sensitivities to drought and identify...

COPPER PITTING AND PINHOLE LEAK RESEARCH STUDY

EPA Science Inventory

Localized copper corrosion or pitting is a significant problem at many water utilities across the United States. Copper pinhole leak problems resulting from extensive pitting are widely under reported. Given the sensitive nature of the problem, extent of damage possible, costs o...

Workshop Report: Juvenile toxicity testing protocols for chemicals

EPA Science Inventory

There is increased awareness of the specific position of children when it comes to hazards of xenobiotic exposures. Children are not small adults, since their exposure patterns, compound kinetics and metabolism, and sensitivity of their developing organs may differ extensively fr...

Control of Wheel/Rail Noise and Vibration

DOT National Transportation Integrated Search

1982-04-01

An analytical model of the generation of wheel/rail noise has been developed and validated through an extensive series of field tests carried out at the Transportation Test Center using the State of the Art Car. A sensitivity analysis has been perfor...

Treatment Outcomes of Patients With Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis According to Drug Susceptibility Testing to First- and Second-line Drugs: An Individual Patient Data Meta-analysis

PubMed Central

Bastos, Mayara L.; Hussain, Hamidah; Weyer, Karin; Garcia-Garcia, Lourdes; Leimane, Vaira; Leung, Chi Chiu; Narita, Masahiro; Penã, Jose M.; Ponce-de-Leon, Alfredo; Seung, Kwonjune J.; Shean, Karen; Sifuentes-Osornio, José; Van der Walt, Martie; Van der Werf, Tjip S.; Yew, Wing Wai; Menzies, Dick; Ahuja, S.; Ashkin, D.; Avendaño, M.; Banerjee, R.; Bauer, M.; Becerra, M.; Benedetti, A.; Burgos, M.; Centis, R.; Chan, E.D.; Chiang, C.Y.; Cobelens, F.; Cox, H.; D'Ambrosio, L.; de Lange, W.C.M.; DeRiemer, K.; Enarson, D.; Falzon, D.; Flanagan, K.; Flood, J.; Gandhi, N.; Garcia-Garcia, L.; Granich, R.M.; Hollm-Delgado, M.G.; Holtz, T.H.; Hopewell, P.; Iseman, M.; Jarlsberg, L.G.; Keshavjee, S.; Kim, H.R.; Koh, W.J.; Lancaster, J.; Lange, C.; Leimane, V.; Leung, C.C.; Li, J.; Menzies, D.; Migliori, G.B.; Mitnick, C.M.; Narita, M.; Nathanson, E.; Odendaal, R.; O'Riordan, P.; Pai, M.; Palmero, D.; Park, S.K.; Pasvol, G.; Pena, J.; Pérez-Guzmán, C.; Ponce-de-Leon, A.; Quelapio, M.I.D.; Quy, H.T.; Riekstina, V.; Robert, J.; Royce, S.; Salim, M.; Schaaf, H.S.; Seung, K.J.; Shah, L.; Shean, K.; Shim, T.S.; Shin, S.S.; Shiraishi, Y.; Sifuentes-Osornio, J.; Sotgiu, G.; Strand, M.J.; Sung, S.W.; Tabarsi, P.; Tupasi, T.E.; Vargas, M.H.; van Altena, R.; van der Walt, M.; van der Werf, T.S.; Viiklepp, P.; Westenhouse, J.; Yew, W.W.; Yim, J.J.

2014-01-01

Background. Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis. Methods. We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis. We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center. Results. DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for second-line injectables and fluoroquinolones, odds ranged from 2.4 to 4.6. Conclusions. DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis. PMID:25097082

No Evidence for Extensions to the Standard Cosmological Model.

PubMed

Heavens, Alan; Fantaye, Yabebal; Sellentin, Elena; Eggers, Hans; Hosenie, Zafiirah; Kroon, Steve; Mootoovaloo, Arrykrishna

2017-09-08

We compute the Bayesian evidence for models considered in the main analysis of Planck cosmic microwave background data. By utilizing carefully defined nearest-neighbor distances in parameter space, we reuse the Monte Carlo Markov chains already produced for parameter inference to compute Bayes factors B for many different model-data set combinations. The standard 6-parameter flat cold dark matter model with a cosmological constant (ΛCDM) is favored over all other models considered, with curvature being mildly favored only when cosmic microwave background lensing is not included. Many alternative models are strongly disfavored by the data, including primordial correlated isocurvature models (lnB=-7.8), nonzero scalar-to-tensor ratio (lnB=-4.3), running of the spectral index (lnB=-4.7), curvature (lnB=-3.6), nonstandard numbers of neutrinos (lnB=-3.1), nonstandard neutrino masses (lnB=-3.2), nonstandard lensing potential (lnB=-4.6), evolving dark energy (lnB=-3.2), sterile neutrinos (lnB=-6.9), and extra sterile neutrinos with a nonzero scalar-to-tensor ratio (lnB=-10.8). Other models are less strongly disfavored with respect to flat ΛCDM. As with all analyses based on Bayesian evidence, the final numbers depend on the widths of the parameter priors. We adopt the priors used in the Planck analysis, while performing a prior sensitivity analysis. Our quantitative conclusion is that extensions beyond the standard cosmological model are disfavored by Planck data. Only when newer Hubble constant measurements are included does ΛCDM become disfavored, and only mildly, compared with a dynamical dark energy model (lnB∼+2).

No Evidence for Extensions to the Standard Cosmological Model

NASA Astrophysics Data System (ADS)

Heavens, Alan; Fantaye, Yabebal; Sellentin, Elena; Eggers, Hans; Hosenie, Zafiirah; Kroon, Steve; Mootoovaloo, Arrykrishna

2017-09-01

We compute the Bayesian evidence for models considered in the main analysis of Planck cosmic microwave background data. By utilizing carefully defined nearest-neighbor distances in parameter space, we reuse the Monte Carlo Markov chains already produced for parameter inference to compute Bayes factors B for many different model-data set combinations. The standard 6-parameter flat cold dark matter model with a cosmological constant (Λ CDM ) is favored over all other models considered, with curvature being mildly favored only when cosmic microwave background lensing is not included. Many alternative models are strongly disfavored by the data, including primordial correlated isocurvature models (ln B =-7.8 ), nonzero scalar-to-tensor ratio (ln B =-4.3 ), running of the spectral index (ln B =-4.7 ), curvature (ln B =-3.6 ), nonstandard numbers of neutrinos (ln B =-3.1 ), nonstandard neutrino masses (ln B =-3.2 ), nonstandard lensing potential (ln B =-4.6 ), evolving dark energy (ln B =-3.2 ), sterile neutrinos (ln B =-6.9 ), and extra sterile neutrinos with a nonzero scalar-to-tensor ratio (ln B =-10.8 ). Other models are less strongly disfavored with respect to flat Λ CDM . As with all analyses based on Bayesian evidence, the final numbers depend on the widths of the parameter priors. We adopt the priors used in the Planck analysis, while performing a prior sensitivity analysis. Our quantitative conclusion is that extensions beyond the standard cosmological model are disfavored by Planck data. Only when newer Hubble constant measurements are included does Λ CDM become disfavored, and only mildly, compared with a dynamical dark energy model (ln B ˜+2 ).

Differential cellular responses in healthy mice and in mice with established airway inflammation when exposed to hematite nanoparticles

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

Gustafsson, Åsa, E-mail: asa.gustafsson@foi.se; Dept of Public Health and Clinical Medicine, Umeå University; Bergström, Ulrika

The aim of this study was to investigate the inflammatory and immunological responses in airways and lung-draining lymph nodes (LDLNs), following lung exposure to iron oxide (hematite) nanoparticles (NPs). The responses to the hematite NPs were evaluated in both healthy non-sensitized mice, and in sensitized mice with an established allergic airway disease. The mice were exposed intratracheally to either hematite NPs or to vehicle (PBS) and the cellular responses were evaluated on days 1, 2, and 7, post-exposure. Exposure to hematite NPs increased the numbers of neutrophils, eosinophils, and lymphocytes in the airways of non-sensitized mice on days 1 andmore » 2 post-exposure; at these time points the number of lymphocytes was also elevated in the LDLNs. In contrast, exposing sensitized mice to hematite NPs induced a rapid and unspecific cellular reduction in the alveolar space on day 1 post-exposure; a similar decrease of lymphocytes was also observed in the LDLN. The results indicate that cells in the airways and in the LDLN of individuals with established airway inflammation undergo cell death when exposed to hematite NPs. A possible explanation for this toxic response is the extensive generation of reactive oxygen species (ROS) in the pro-oxidative environment of inflamed airways. This study demonstrates how sensitized and non-sensitized mice respond differently to hematite NP exposure, and it highlights the importance of including individuals with respiratory disorders when evaluating health effects of inhaled nanomaterials. - Highlights: • Hematite NPs induce differential responses in airways of healthy and allergic mice. • Hematite induced an airway inflammation in healthy mice. • Hematite induced cellular reduction in the alveolus and lymph nodes of allergic mice. • Cell death is possible due to extensive pro-oxidative environment in allergic mice. • It is important to include sensitive individuals when valuing health effects of NPs.« less

Access to pedestrian roads, daily activities, and physical performance of adolescents.

PubMed

Sjolie, A N

2000-08-01

A cross-sectional study using a questionnaire and physical tests was performed. To study how access to pedestrian roads and daily activities are related to low back strength, low back mobility, and hip mobility in adolescents. Although many authorities express concern about the passive lifestyle of adolescents, little is known about associations between daily activities and physical performance. This study compared 38 youths in a community lacking access to pedestrian roads with 50 youths in nearby area providing excellent access to pedestrian roads. A standardized questionnaire was used to obtain data about pedestrian roads, school journeys, and activities from the local authorities and the pupils. Low back strength was tested as static endurance strength, low back mobility by modified Schober techniques, and hip mobility by goniometer. For statistical analyses, a P value of 0.05 or less determined significance. In the area using school buses, the pupils had less low back extension, less hamstring flexibility, and less hip abduction, flexion, and extension than pupils in the area with pedestrian roads. Multivariate analyses showed no associations between walking or bicycling to school and anatomic function, but regular walking or bicycling to leisure-time activities associated positively with low back strength, low back extension, hip flexion, and extension. Distance by school bus associated negatively with hip abduction, hip flexion, hip extension, and hamstring flexibility (P<0.001). Time spent on television or computer associated negatively but insignificantly with low back strength, hamstring flexibility, hip abduction, and flexion (P<0.1). The results indicate that access to pedestrian roads and other lifestyle factors are associated with physical performance.

Optimization of the High-Frequency Radar Sites in the Bering Strait Region

DTIC Science & Technology

2015-02-01

and Daley 2000; Köhl and Stammer 2004) and was used extensively in dynam- ical sensitivity studies (e.g., Marotzke et al. 1999; Losch and Heimbach 2007 ...modeling (Winsor and Chapman 2004; Spall 2007 ; Watanabe and Hasumi 2009) studies suggest that Pacific waters enter the open AO through two pathways (Fig...S5 Ŵ21/2DBQT (11) is the sensitivity matrix (e.g., Köhl and Stammer 2004). By electing the trace of the covariance matrix as its norm, we employ the

Characterization and limits of a cold-atom Sagnac interferometer

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

Gauguet, A.; Canuel, B.; Leveque, T.

2009-12-15

We present the full evaluation of a cold-atom gyroscope based on atom interferometry. We have performed extensive studies to determine the systematic errors, scale factor and sensitivity. We demonstrate that the acceleration noise can be efficiently removed from the rotation signal, allowing us to reach the fundamental limit of the quantum projection noise for short term measurements. The technical limits to the long term sensitivity and accuracy have been identified, clearing the way for the next generation of ultrasensitive atom gyroscopes.

Semi-quantitative proteomics of mammalian cells upon short-term exposure to non-ionizing electromagnetic fields.

PubMed

Kuzniar, Arnold; Laffeber, Charlie; Eppink, Berina; Bezstarosti, Karel; Dekkers, Dick; Woelders, Henri; Zwamborn, A Peter M; Demmers, Jeroen; Lebbink, Joyce H G; Kanaar, Roland

2017-01-01

The potential effects of non-ionizing electromagnetic fields (EMFs), such as those emitted by power-lines (in extremely low frequency range), mobile cellular systems and wireless networking devices (in radio frequency range) on human health have been intensively researched and debated. However, how exposure to these EMFs may lead to biological changes underlying possible health effects is still unclear. To reveal EMF-induced molecular changes, unbiased experiments (without a priori focusing on specific biological processes) with sensitive readouts are required. We present the first proteome-wide semi-quantitative mass spectrometry analysis of human fibroblasts, osteosarcomas and mouse embryonic stem cells exposed to three types of non-ionizing EMFs (ELF 50 Hz, UMTS 2.1 GHz and WiFi 5.8 GHz). We performed controlled in vitro EMF exposures of metabolically labeled mammalian cells followed by reliable statistical analyses of differential protein- and pathway-level regulations using an array of established bioinformatics methods. Our results indicate that less than 1% of the quantitated human or mouse proteome responds to the EMFs by small changes in protein abundance. Further network-based analysis of the differentially regulated proteins did not detect significantly perturbed cellular processes or pathways in human and mouse cells in response to ELF, UMTS or WiFi exposure. In conclusion, our extensive bioinformatics analyses of semi-quantitative mass spectrometry data do not support the notion that the short-time exposures to non-ionizing EMFs have a consistent biologically significant bearing on mammalian cells in culture.

Circulating 25-hydroxyvitamin D and insulin resistance in older adults: The Cardiovascular Health Study

PubMed Central

Danziger, John; Biggs, Mary L.; Niemi, Matt; Ix, Joachim H.; Kizer, Jorge R.; Djoussé, Luc; de Boer, Ian H.; Siscovick, David S.; Kestenbaum, Bryan; Mukamal, Kenneth J.

2014-01-01

Background Despite extensive study, the role of vitamin D in insulin resistance and secretion remains unclear. Objective To examine the cross-sectional and longitudinal relationships between 25-hydroxyvitamin D (25(OH)D) concentrations and indices of insulin resistance and secretion in older adults. Methods and Results Among 2134 participants of the Cardiovascular Health Study who were free from cardiovascular disease, we measured serum 25(OH)D concentrations in samples collected in 1992–1993. We examined insulin resistance and secretion using Homeostasis Model Assessment (HOMA) estimates cross-sectionally and among 1469 participants who had repeated HOMA measures four years later (1996–1997). In cross-sectional analysis, each 10 ng/mL increment in 25(OH)D concentration was associated with a 0.09 lower adjusted HOMA-IR [95%CI (−0.17, −0.02), p=0.01]. However, baseline 25(OH)D concentrations were not associated with change in HOMA-IR over 4 years of follow up (p=0.48). 25(OH)D concentrations were not associated with insulin secretion, as determined by HOMA-β, in either cross-sectional or longitudinal analysis. Conclusions Circulating 25(OH)D concentrations are associated with lower insulin resistance in cross-sectional but not longitudinal analyses. Whether this reflects residual confounding in cross-sectional analyses or the short-term nature of the relationship between vitamin D and insulin sensitivity will require trials with repeated measures of these factors. PMID:23987236

Quantifying the Diversity and Similarity of Surgical Procedures Among Hospitals and Anesthesia Providers.

PubMed

Dexter, Franklin; Ledolter, Johannes; Hindman, Bradley J

2016-01-01

In this Statistical Grand Rounds, we review methods for the analysis of the diversity of procedures among hospitals, the activities among anesthesia providers, etc. We apply multiple methods and consider their relative reliability and usefulness for perioperative applications, including calculations of SEs. We also review methods for comparing the similarity of procedures among hospitals, activities among anesthesia providers, etc. We again apply multiple methods and consider their relative reliability and usefulness for perioperative applications. The applications include strategic analyses (e.g., hospital marketing) and human resource analytics (e.g., comparisons among providers). Measures of diversity of procedures and activities (e.g., Herfindahl and Gini-Simpson index) are used for quantification of each facility (hospital) or anesthesia provider, one at a time. Diversity can be thought of as a summary measure. Thus, if the diversity of procedures for 48 hospitals is studied, the diversity (and its SE) is being calculated for each hospital. Likewise, the effective numbers of common procedures at each hospital can be calculated (e.g., by using the exponential of the Shannon index). Measures of similarity are pairwise assessments. Thus, if quantifying the similarity of procedures among cases with a break or handoff versus cases without a break or handoff, a similarity index represents a correlation coefficient. There are several different measures of similarity, and we compare their features and applicability for perioperative data. We rely extensively on sensitivity analyses to interpret observed values of the similarity index.

Impact of implementation choices on quantitative predictions of cell-based computational models

NASA Astrophysics Data System (ADS)

Kursawe, Jochen; Baker, Ruth E.; Fletcher, Alexander G.

2017-09-01

'Cell-based' models provide a powerful computational tool for studying the mechanisms underlying the growth and dynamics of biological tissues in health and disease. An increasing amount of quantitative data with cellular resolution has paved the way for the quantitative parameterisation and validation of such models. However, the numerical implementation of cell-based models remains challenging, and little work has been done to understand to what extent implementation choices may influence model predictions. Here, we consider the numerical implementation of a popular class of cell-based models called vertex models, which are often used to study epithelial tissues. In two-dimensional vertex models, a tissue is approximated as a tessellation of polygons and the vertices of these polygons move due to mechanical forces originating from the cells. Such models have been used extensively to study the mechanical regulation of tissue topology in the literature. Here, we analyse how the model predictions may be affected by numerical parameters, such as the size of the time step, and non-physical model parameters, such as length thresholds for cell rearrangement. We find that vertex positions and summary statistics are sensitive to several of these implementation parameters. For example, the predicted tissue size decreases with decreasing cell cycle durations, and cell rearrangement may be suppressed by large time steps. These findings are counter-intuitive and illustrate that model predictions need to be thoroughly analysed and implementation details carefully considered when applying cell-based computational models in a quantitative setting.

Discovery of the photosynthetic relatives of the "Maltese mushroom" Cynomorium

PubMed Central

Nickrent, Daniel L; Der, Joshua P; Anderson, Frank E

2005-01-01

Background Although recent molecular phylogenetic studies have identified the photosynthetic relatives of several enigmatic holoparasitic angiosperms, uncertainty remains for the last parasitic plant order, Balanophorales, often considered to include two families, Balanophoraceae and Cynomoriaceae. The nonphotosynthetic (holoparasitic) flowering plant Cynomorium coccineum has long been known to the Muslim world as "tarthuth" and to Europeans as the "Maltese mushroom"; C. songaricum is known in Chinese medicine as "suo yang." Interest in these plants is increasing and they are being extensively collected from wild populations for use in herbal medicines. Results Here we report molecular phylogenetic analyses of nuclear ribosomal DNA and mitochondrial matR sequence data that strongly support the independent origin of Balanophoraceae and Cynomoriaceae. Analyses of single gene and combined gene data sets place Cynomorium in Saxifragales, possibly near Crassulaceae (stonecrop family). Balanophoraceae appear related to Santalales (sandalwood order), a position previously suggested from morphological characters that are often assumed to be convergent. Conclusion Our work shows that Cynomorium and Balanophoraceae are not closely related as indicated in all past and present classifications. Thus, morphological features, such as inflorescences bearing numerous highly reduced flowers, are convergent and were attained independently by these two holoparasite lineages. Given the widespread harvest of wild Cynomorium species for herbal medicines, we here raise conservation concerns and suggest that further molecular phylogenetic work is needed to identify its photosynthetic relatives. These relatives, which will be easier to cultivate, should then be examined for phytochemical activity purported to be present in the more sensitive Cynomorium. PMID:15969755

Trace detection of perchlorate in industrial-grade emulsion explosive with portable surface-enhanced Raman spectroscopy.

PubMed

Nuntawong, N; Eiamchai, P; Limwichean, S; Wong-ek, B; Horprathum, M; Patthanasettakul, V; Leelapojanaporn, A; Nakngoenthong, S; Chindaudom, P

2013-12-10

Recent analyses by ion-exchange chromatography (IC) showed that, beside nitrate, the majority of the industrial-grade emulsion explosives, extensively used by most separatists in the southern Thailand insurgency, contained small traces of perchlorate anions. In demand for the faster, reliable, and simple detection methods, the portable detection of nitrate and perchlorate became the great interest for the forensic and field-investigators. This work proposed a unique method to detect the trace amount of perchlorate in seven industrial-grade emulsion explosives under the field tests. We utilized the combination of the portable Raman spectroscope, the developed surfaced-enhanced Raman substrates, and the sample preparation procedures. The portable Raman spectroscope with a laser diode of 785 nm for excitation and a thermoelectric-cooled CCD spectrometer for detection was commercially available. The SERS substrates, with uniformly distributed nanostructured silver nanorods, were fabricated by the DC magnetron sputtering system, based on the oblique-angle deposition technique. The sample preparation procedures were proposed based on (1) pentane extraction technique and (2) combustion technique, prior to being dissolved in the purified water. In comparison to the ion chromatography and the conventional Raman measurements, our proposed methods successfully demonstrated the highly sensitive detectability of the minimal trace amount of perchlorate from five of the explosives with minimal operating time. This work was therefore highly practical to the development for the forensic analyses of the post-blast explosive residues under the field-investigations. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Semi-quantitative proteomics of mammalian cells upon short-term exposure to non-ionizing electromagnetic fields

PubMed Central

Laffeber, Charlie; Eppink, Berina; Bezstarosti, Karel; Dekkers, Dick; Woelders, Henri; Zwamborn, A. Peter M.; Demmers, Jeroen; Lebbink, Joyce H. G.; Kanaar, Roland

2017-01-01

The potential effects of non-ionizing electromagnetic fields (EMFs), such as those emitted by power-lines (in extremely low frequency range), mobile cellular systems and wireless networking devices (in radio frequency range) on human health have been intensively researched and debated. However, how exposure to these EMFs may lead to biological changes underlying possible health effects is still unclear. To reveal EMF-induced molecular changes, unbiased experiments (without a priori focusing on specific biological processes) with sensitive readouts are required. We present the first proteome-wide semi-quantitative mass spectrometry analysis of human fibroblasts, osteosarcomas and mouse embryonic stem cells exposed to three types of non-ionizing EMFs (ELF 50 Hz, UMTS 2.1 GHz and WiFi 5.8 GHz). We performed controlled in vitro EMF exposures of metabolically labeled mammalian cells followed by reliable statistical analyses of differential protein- and pathway-level regulations using an array of established bioinformatics methods. Our results indicate that less than 1% of the quantitated human or mouse proteome responds to the EMFs by small changes in protein abundance. Further network-based analysis of the differentially regulated proteins did not detect significantly perturbed cellular processes or pathways in human and mouse cells in response to ELF, UMTS or WiFi exposure. In conclusion, our extensive bioinformatics analyses of semi-quantitative mass spectrometry data do not support the notion that the short-time exposures to non-ionizing EMFs have a consistent biologically significant bearing on mammalian cells in culture. PMID:28234898

Preliminary performance assessment for the Waste Isolation Pilot Plant, December 1992. Volume 5, Uncertainty and sensitivity analyses of gas and brine migration for undisturbed performance

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

Not Available

1993-08-01

Before disposing of transuranic radioactive waste in the Waste Isolation Pilot Plant (WIPP), the United States Department of Energy (DOE) must evaluate compliance with applicable long-term regulations of the United States Environmental Protection Agency (EPA). Sandia National Laboratories is conducting iterative performance assessments (PAs) of the WIPP for the DOE to provide interim guidance while preparing for a final compliance evaluation. This volume of the 1992 PA contains results of uncertainty and sensitivity analyses with respect to migration of gas and brine from the undisturbed repository. Additional information about the 1992 PA is provided in other volumes. Volume 1 containsmore » an overview of WIPP PA and results of a preliminary comparison with 40 CFR 191, Subpart B. Volume 2 describes the technical basis for the performance assessment, including descriptions of the linked computational models used in the Monte Carlo analyses. Volume 3 contains the reference data base and values for input parameters used in consequence and probability modeling. Volume 4 contains uncertainty and sensitivity analyses with respect to the EPA`s Environmental Standards for the Management and Disposal of Spent Nuclear Fuel, High-Level and Transuranic Radioactive Wastes (40 CFR 191, Subpart B). Finally, guidance derived from the entire 1992 PA is presented in Volume 6. Results of the 1992 uncertainty and sensitivity analyses indicate that, conditional on the modeling assumptions and the assigned parameter-value distributions, the most important parameters for which uncertainty has the potential to affect gas and brine migration from the undisturbed repository are: initial liquid saturation in the waste, anhydrite permeability, biodegradation-reaction stoichiometry, gas-generation rates for both corrosion and biodegradation under inundated conditions, and the permeability of the long-term shaft seal.« less

TSUNAMI Primer: A Primer for Sensitivity/Uncertainty Calculations with SCALE

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

Rearden, Bradley T; Mueller, Don; Bowman, Stephen M

2009-01-01

This primer presents examples in the application of the SCALE/TSUNAMI tools to generate k{sub eff} sensitivity data for one- and three-dimensional models using TSUNAMI-1D and -3D and to examine uncertainties in the computed k{sub eff} values due to uncertainties in the cross-section data used in their calculation. The proper use of unit cell data and need for confirming the appropriate selection of input parameters through direct perturbations are described. The uses of sensitivity and uncertainty data to identify and rank potential sources of computational bias in an application system and TSUNAMI tools for assessment of system similarity using sensitivity andmore » uncertainty criteria are demonstrated. Uses of these criteria in trending analyses to assess computational biases, bias uncertainties, and gap analyses are also described. Additionally, an application of the data adjustment tool TSURFER is provided, including identification of specific details of sources of computational bias.« less

Genome-wide bisulfite sensitivity profiling of yeast suggests bisulfite inhibits transcription.

PubMed

Segovia, Romulo; Mathew, Veena; Tam, Annie S; Stirling, Peter C

2017-09-01

Bisulfite, in the form of sodium bisulfite or metabisulfite, is used commercially as a food preservative. Bisulfite is used in the laboratory as a single-stranded DNA mutagen in epigenomic analyses of DNA methylation. Recently it has also been used on whole yeast cells to induce mutations in exposed single-stranded regions in vivo. To understand the effects of bisulfite on live cells we conducted a genome-wide screen for bisulfite sensitive mutants in yeast. Screening the deletion mutant array, and collections of essential gene mutants we define a genetic network of bisulfite sensitive mutants. Validation of screen hits revealed hyper-sensitivity of transcription and RNA processing mutants, rather than DNA repair pathways and follow-up analyses support a role in perturbation of RNA transactions. We propose a model in which bisulfite-modified nucleotides may interfere with transcription or RNA metabolism when used in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

Variation of a test's sensitivity and specificity with disease prevalence.

PubMed

Leeflang, Mariska M G; Rutjes, Anne W S; Reitsma, Johannes B; Hooft, Lotty; Bossuyt, Patrick M M

2013-08-06

Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. We used data from 23 meta-analyses, each of which included 10-39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p < 0.05) for either sensitivity or specificity in 8 meta-analyses (35%). Overall, specificity tended to be lower with higher disease prevalence; there was no such systematic effect for sensitivity. The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation.

Variation of a test’s sensitivity and specificity with disease prevalence

PubMed Central

Leeflang, Mariska M.G.; Rutjes, Anne W.S.; Reitsma, Johannes B.; Hooft, Lotty; Bossuyt, Patrick M.M.

2013-01-01

Background: Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. Methods: We used data from 23 meta-analyses, each of which included 10–39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. Results: Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p < 0.05) for either sensitivity or specificity in 8 meta-analyses (35%). Overall, specificity tended to be lower with higher disease prevalence; there was no such systematic effect for sensitivity. Interpretation: The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation. PMID:23798453

[Microscopic extensions of head and neck squamous cell carcinomas: impact for clinical target volume definition].

PubMed

Fleury, B; Thariat, J; Barnoud, R; Buiret, G; Lebreton, F; Bancel, B; Poupart, M; Devouassoux-Shisheboran, M

2014-11-01

To assess microscopic extensions of head and neck squamous cell carcinomas aiming at a proposal for target volumes of radiation therapy. Surgical specimens were prospectively analysed macroscopically and microscopically. Tumour borders were identified per macroscopic visual examination and inked on stained slides. Then microscopic implants (perineural or lymphatic involvement, or in situ carcinomas) were looked for with an optic microscope in the macroscopic healthy tissue surrounding the tumour. The maximal length from tumour border was correlated with the maximal length of macroscopically healthy tissues assessable. Twenty-one specimens were analysed and 12 were locally advanced tumours. Mean and median maximal microscopic extensions were 2.9 and 1.0mm (0-15mm), respectively. The 90th and 95th percentiles were 5 and 11mm, respectively. The ratio between healthy tissue length and maximal microscopic tumour extension was 10%. No correlation was found with tumour grade or volume. The presence of microscopic tumour was unlikely after 5mm from macroscopic tumour (≤5% of patients in this series) but should be assessed along with other histoclinical factors and particularities of tumour behaviour by anatomic site. A rigorous terminology should authorize a relevant appreciation of local risk of recurrence, particularly in adjuvant setting or for clinical target volume definition. Larger and more homogenous confirmatory series are needed. Copyright © 2014. Published by Elsevier SAS.

Taxometric and Factor Analytic Models of Anxiety Sensitivity among Youth: Exploring the Latent Structure of Anxiety Psychopathology Vulnerability

ERIC Educational Resources Information Center

Bernstein, Amit; Zvolensky, Michael J.; Stewart, Sherry; Comeau, Nancy

2007-01-01

This study represents an effort to better understand the latent structure of anxiety sensitivity (AS), a well-established affect-sensitivity individual difference factor, among youth by employing taxometric and factor analytic approaches in an integrative manner. Taxometric analyses indicated that AS, as indexed by the Child Anxiety Sensitivity…

The Role of Reinforcement Sensitivity in the Development of Childhood Personality

ERIC Educational Resources Information Center

Slobodskaya, Helena R.; Kuznetsova, Valeriya B.

2013-01-01

The study examined the contribution of reinforcement sensitivity to childhood personality at three levels of the hierarchical structure, mid-level traits, the Big Five and two higher-order factors, and the moderating role of sex and age in a sample of 3-18-year-olds. The canonical correlation analyses indicated that reinforcement sensitivity and…

SeaWiFS Postlaunch Calibration and Validation Analyses

NASA Technical Reports Server (NTRS)

Hooker, Stanford B. (Editor); Firestone, Elaine R. (Editor); McClain, Charles R.; Ainsworth, Ewa J.; Barnes, Robert A.; Eplee, Robert E., Jr.; Patt, Frederick S.; Robinson, Wayne D.; Wang, Menghua; Bailey, Sean W.

2000-01-01

The effort to resolve data quality issues and improve on the initial data evaluation methodologies of the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) Project was an extensive one. These evaluations have resulted, to date, in three major reprocessings of the entire data set where each reprocessing addressed the data quality issues that could be identified up to the time of each reprocessing. The number of chapters (21) needed to document this extensive work in the SeaWiFS Postlaunch Technical Report Series requires three volumes. The chapters in Volumes 9, 10, and 11 are in a logical order sequencing through sensor calibration, atmospheric correction, masks and flags, product evaluations, and bio-optical algorithms. The first chapter of Volume 9 is an overview of the calibration and validation program, including a table of activities from the inception of the SeaWiFS Project. Chapter 2 describes the fine adjustments of sensor detector knee radiances, i.e., radiance levels where three of the four detectors in each SeaWiFS band saturate. Chapters 3 and 4 describe the analyses of the lunar and solar calibration time series, respectively, which are used to track the temporal changes in radiometric sensitivity in each band. Chapter 5 outlines the procedure used to adjust band 7 relative to band 8 to derive reasonable aerosol radiances in band 7 as compared to those in band 8 in the vicinity of Lanai, Hawaii, the vicarious calibration site. Chapter 6 presents the procedure used to estimate the vicarious calibration gain adjustment factors for bands 1-6 using the waterleaving radiances from the Marine Optical Buoy (MOBY) offshore of Lanai. Chapter 7 provides the adjustments to the coccolithophore flag algorithm which were required for improved performance over the prelaunch version. Chapter 8 is an overview of the numerous modifications to the atmospheric correction algorithm that have been implemented. Chapter 9 describes the methodology used to remove artifacts of sun glint contamination for portions of the imagery outside the sun glint mask. Finally, Chapter 10 explains a modification to the ozone interpolation method to account for actual time differences between the SeaWiFS and Total Ozone Mapping Spectrometer (TOMS) orbits.

A Pilot Cost-Effectiveness Analysis of Treatments in Newly Diagnosed High-Grade Gliomas: The Example of 5-Aminolevulinic Acid Compared With White-Light Surgery

PubMed Central

Alves, Marta; Castel-Branco, Marta; Stummer, Walter

2015-01-01

BACKGROUND: High-grade gliomas are aggressive, incurable tumors characterized by extensive diffuse invasion of the normal brain parenchyma. Novel therapies at best prolong survival; their costs are formidable and benefit is marginal. Economic restrictions thus require knowledge of the cost-effectiveness of treatments. Here, we show the cost-effectiveness of enhanced resections in malignant glioma surgery using a well-characterized tool for intraoperative tumor visualization, 5-aminolevulinic acid (5-ALA). OBJECTIVE: To evaluate the cost-effectiveness of 5-ALA fluorescence-guided neurosurgery compared with white-light surgery in adult patients with newly diagnosed high-grade glioma, adopting the perspective of the Portuguese National Health Service. METHODS: We used a Markov model (cohort simulation). Transition probabilities were estimated with the use of data from 1 randomized clinical trial and 1 noninterventional prospective study. Utility values and resource use were obtained from published literature and expert opinion. Unit costs were taken from official Portuguese reimbursement lists (2012 values). The health outcomes considered were quality-adjusted life-years, life-years, and progression-free life-years. Extensive 1-way and probabilistic sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratios are below €10 000 in all evaluated outcomes, being around €9100 per quality-adjusted life-year gained, €6700 per life-year gained, and €8800 per progression-free life-year gained. The probability of 5-ALA fluorescence-guided surgery cost-effectiveness at a threshold of €20000 is 96.0% for quality-adjusted life-year, 99.6% for life-year, and 98.8% for progression-free life-year. CONCLUSION: 5-ALA fluorescence-guided surgery appears to be cost-effective in newly diagnosed high-grade gliomas compared with white-light surgery. This example demonstrates cost-effectiveness analyses for malignant glioma surgery to be feasible on the basis of existing data. ABBREVIATIONS: 5-ALA, 5-aminolevulinic acid ICER, incremental cost-effectiveness ratio LY, life-year PFLY, progression-free life-year QALY, quality-adjusted life-year PMID:25714513

Sobol method application in dimensional sensitivity analyses of different AFM cantilevers for biological particles

NASA Astrophysics Data System (ADS)

Korayem, M. H.; Taheri, M.; Ghahnaviyeh, S. D.

2015-08-01

Due to the more delicate nature of biological micro/nanoparticles, it is necessary to compute the critical force of manipulation. The modeling and simulation of reactions and nanomanipulator dynamics in a precise manipulation process require an exact modeling of cantilevers stiffness, especially the stiffness of dagger cantilevers because the previous model is not useful for this investigation. The stiffness values for V-shaped cantilevers can be obtained through several methods. One of them is the PBA method. In another approach, the cantilever is divided into two sections: a triangular head section and two slanted rectangular beams. Then, deformations along different directions are computed and used to obtain the stiffness values in different directions. The stiffness formulations of dagger cantilever are needed for this sensitivity analyses so the formulations have been driven first and then sensitivity analyses has been started. In examining the stiffness of the dagger-shaped cantilever, the micro-beam has been divided into two triangular and rectangular sections and by computing the displacements along different directions and using the existing relations, the stiffness values for dagger cantilever have been obtained. In this paper, after investigating the stiffness of common types of cantilevers, Sobol sensitivity analyses of the effects of various geometric parameters on the stiffness of these types of cantilevers have been carried out. Also, the effects of different cantilevers on the dynamic behavior of nanoparticles have been studied and the dagger-shaped cantilever has been deemed more suitable for the manipulation of biological particles.

Evaluation of a Method for Remote Detection of Fuel Relocation Outside the Original Core Volumes of Fukushima Reactor Units 1-3

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

Douglas W. Akers; Edwin A. Harvego

2012-08-01

This paper presents the results of a study to evaluate the feasibility of remotely detecting and quantifying fuel relocation from the core to the lower head, and to regions outside the reactor vessel primary containment of the Fukushima 1-3 reactors. The goals of this study were to determine measurement conditions and requirements, and to perform initial radiation transport sensitivity analyses for several potential measurement locations inside the reactor building. The radiation transport sensitivity analyses were performed based on reactor design information for boiling water reactors (BWRs) similar to the Fukushima reactors, ORIGEN2 analyses of 3-cycle BWR fuel inventories, and datamore » on previously molten fuel characteristics from TMI- 2. A 100 kg mass of previously molten fuel material located on the lower head of the reactor vessel was chosen as a fuel interrogation sensitivity target. Two measurement locations were chosen for the transport analyses, one inside the drywell and one outside the concrete biological shield surrounding the drywell. Results of these initial radiation transport analyses indicate that the 100 kg of previously molten fuel material may be detectable at the measurement location inside the drywell, but that it is highly unlikely that any amount of fuel material inside the RPV will be detectable from a location outside the concrete biological shield surrounding the drywell. Three additional fuel relocation scenarios were also analyzed to assess detection sensitivity for varying amount of relocated material in the lower head of the reactor vessel, in the control rods perpendicular to the detector system, and on the lower head of the drywell. Results of these analyses along with an assessment of background radiation effects and a discussion of measurement issues, such as the detector/collimator design, are included in the paper.« less

iTOUGH2 v7.1

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

FINSTERLE, STEFAN; JUNG, YOOJIN; KOWALSKY, MICHAEL

2016-09-15

iTOUGH2 (inverse TOUGH2) provides inverse modeling capabilities for TOUGH2, a simulator for multi-dimensional, multi-phase, multi-component, non-isothermal flow and transport in fractured porous media. iTOUGH2 performs sensitivity analyses, data-worth analyses, parameter estimation, and uncertainty propagation analyses in geosciences and reservoir engineering and other application areas. iTOUGH2 supports a number of different combinations of fluids and components (equation-of-state (EOS) modules). In addition, the optimization routines implemented in iTOUGH2 can also be used for sensitivity analysis, automatic model calibration, and uncertainty quantification of any external code that uses text-based input and output files using the PEST protocol. iTOUGH2 solves the inverse problem bymore » minimizing a non-linear objective function of the weighted differences between model output and the corresponding observations. Multiple minimization algorithms (derivative-free, gradient-based, and second-order; local and global) are available. iTOUGH2 also performs Latin Hypercube Monte Carlo simulations for uncertainty propagation analyses. A detailed residual and error analysis is provided. This upgrade includes (a) global sensitivity analysis methods, (b) dynamic memory allocation (c) additional input features and output analyses, (d) increased forward simulation capabilities, (e) parallel execution on multicore PCs and Linux clusters, and (f) bug fixes. More details can be found at http://esd.lbl.gov/iTOUGH2.« less

A Model for Growth of a Single Fungal Hypha Based on Well-Mixed Tanks in Series: Simulation of Nutrient and Vesicle Transport in Aerial Reproductive Hyphae

PubMed Central

Balmant, Wellington; Sugai-Guérios, Maura Harumi; Coradin, Juliana Hey; Krieger, Nadia; Furigo Junior, Agenor; Mitchell, David Alexander

2015-01-01

Current models that describe the extension of fungal hyphae and development of a mycelium either do not describe the role of vesicles in hyphal extension or do not correctly describe the experimentally observed profile for distribution of vesicles along the hypha. The present work uses the n-tanks-in-series approach to develop a model for hyphal extension that describes the intracellular transport of nutrient to a sub-apical zone where vesicles are formed and then transported to the tip, where tip extension occurs. The model was calibrated using experimental data from the literature for the extension of reproductive aerial hyphae of three different fungi, and was able to describe different profiles involving acceleration and deceleration of the extension rate. A sensitivity analysis showed that the supply of nutrient to the sub-apical vesicle-producing zone is a key factor influencing the rate of extension of the hypha. Although this model was used to describe the extension of a single reproductive aerial hypha, the use of the n-tanks-in-series approach to representing the hypha means that the model has the flexibility to be extended to describe the growth of other types of hyphae and the branching of hyphae to form a complete mycelium. PMID:25785863

Plasmonic light-sensitive skins of nanocrystal monolayers

NASA Astrophysics Data System (ADS)

Akhavan, Shahab; Gungor, Kivanc; Mutlugun, Evren; Demir, Hilmi Volkan

2013-04-01

We report plasmonically coupled light-sensitive skins of nanocrystal monolayers that exhibit sensitivity enhancement and spectral range extension with plasmonic nanostructures embedded in their photosensitive nanocrystal platforms. The deposited plasmonic silver nanoparticles of the device increase the optical absorption of a CdTe nanocrystal monolayer incorporated in the device. Controlled separation of these metallic nanoparticles in the vicinity of semiconductor nanocrystals enables optimization of the photovoltage buildup in the proposed nanostructure platform. The enhancement factor was found to depend on the excitation wavelength. We observed broadband sensitivity improvement (across 400-650 nm), with a 2.6-fold enhancement factor around the localized plasmon resonance peak. The simulation results were found to agree well with the experimental data. Such plasmonically enhanced nanocrystal skins hold great promise for large-area UV/visible sensing applications.

Reinforcement Sensitivity, Coping, and Delinquent Behaviour in Adolescents

ERIC Educational Resources Information Center

Hasking, Penelope A.

2007-01-01

Since 1964, the relationship between personality and criminal behaviour has been extensively studied. However, studies, which have examined the Eysenckian dimensions of extraversion, neuroticism and psychoticism have produced mixed results. Gray's [Gray, J. A. (1970). The psychophysiological basis of introversion-extroversion. "Behavior Research…

77 FR 14367 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

.... SUPPLEMENTARY INFORMATION: Proposal to request approval from OMB of the extension for three years, with revision...: 12 U.S.C. 3105(c)(2), 1817(a)(1) and (3), and 3102(b). Except for select sensitive items, the FFIEC...

Surface energy fluxes in complex terrain

NASA Technical Reports Server (NTRS)

Reiter, E. R.; Sheaffer, J. D.; Bossert, J. E.

1986-01-01

The emphasis of the 1985 NASA project activity was on field measurements of wind data and heat balance data. Initiatives included a 19 station mountaintop monitoring program, testing and refining the surface flux monitoring systems and packing and shipping equipment to the People's Republic of China in preparation for the 1986 Tibet Experiment. Other work included more extensive analyses of the 1984 Gobi Desert and Rocky Mountain observations plus some preliminary analyses of the 1985 mountaintop network data. Details of our field efforts are summarized and results of our data analyses are presented.

Sensitivity-Enhanced Wearable Active Voiceprint Sensor Based on Cellular Polypropylene Piezoelectret.

PubMed

Li, Wenbo; Zhao, Sheng; Wu, Nan; Zhong, Junwen; Wang, Bo; Lin, Shizhe; Chen, Shuwen; Yuan, Fang; Jiang, Hulin; Xiao, Yongjun; Hu, Bin; Zhou, Jun

2017-07-19

Wearable active sensors have extensive applications in mobile biosensing and human-machine interaction but require good flexibility, high sensitivity, excellent stability, and self-powered feature. In this work, cellular polypropylene (PP) piezoelectret was chosen as the core material of a sensitivity-enhanced wearable active voiceprint sensor (SWAVS) to realize voiceprint recognition. By virtue of the dipole orientation control method, the air layers in the piezoelectret were efficiently utilized, and the current sensitivity was enhanced (from 1.98 pA/Hz to 5.81 pA/Hz at 115 dB). The SWAVS exhibited the superiorities of high sensitivity, accurate frequency response, and excellent stability. The voiceprint recognition system could make correct reactions to human voices by judging both the password and speaker. This study presented a voiceprint sensor with potential applications in noncontact biometric recognition and safety guarantee systems, promoting the progress of wearable sensor networks.

Impact of animal health programmes on poverty reduction and sustainable livestock development.

PubMed

Pradere, J P

2017-04-01

Based on data from publications and field observations, this study analyses the interactions between animal health, rural poverty and the performance and environmental impact of livestock farming in low-income countries and middle-income countries. There are strong statistical correlations between the quality of Veterinary Services, livestock productivity and poverty rates. In countries with effective Veterinary Services, livestock growth stems mainly from productivity gains and poverty rates are the lowest. Conversely, these analyses identify no statistical link between the quality of Veterinary Services and increased livestock production volumes. However, where animal diseases are poorly controlled, productivity is low and livestock growth is extensive, based mainly on a steady increase in animal numbers. Extensive growth is less effective than intensive growth in reducing poverty and aggravates the pressure of livestock production on natural resources and the climate.

Spatiotemporal sensitivity analysis of vertical transport of pesticides in soil

EPA Science Inventory

Environmental fate and transport processes are influenced by many factors. Simulation models that mimic these processes often have complex implementations, which can lead to over-parameterization. Sensitivity analyses are subsequently used to identify critical parameters whose un...

permGPU: Using graphics processing units in RNA microarray association studies.

PubMed

Shterev, Ivo D; Jung, Sin-Ho; George, Stephen L; Owzar, Kouros

2010-06-16

Many analyses of microarray association studies involve permutation, bootstrap resampling and cross-validation, that are ideally formulated as embarrassingly parallel computing problems. Given that these analyses are computationally intensive, scalable approaches that can take advantage of multi-core processor systems need to be developed. We have developed a CUDA based implementation, permGPU, that employs graphics processing units in microarray association studies. We illustrate the performance and applicability of permGPU within the context of permutation resampling for a number of test statistics. An extensive simulation study demonstrates a dramatic increase in performance when using permGPU on an NVIDIA GTX 280 card compared to an optimized C/C++ solution running on a conventional Linux server. permGPU is available as an open-source stand-alone application and as an extension package for the R statistical environment. It provides a dramatic increase in performance for permutation resampling analysis in the context of microarray association studies. The current version offers six test statistics for carrying out permutation resampling analyses for binary, quantitative and censored time-to-event traits.

Human mtDNA hypervariable regions, HVR I and II, hint at deep common maternal founder and subsequent maternal gene flow in Indian population groups.

PubMed

Sharma, Swarkar; Saha, Anjana; Rai, Ekta; Bhat, Audesh; Bamezai, Ramesh

2005-01-01

We have analysed the hypervariable regions (HVR I and II) of human mitochondrial DNA (mtDNA) in individuals from Uttar Pradesh (UP), Bihar (BI) and Punjab (PUNJ), belonging to the Indo-European linguistic group, and from South India (SI), that have their linguistic roots in Dravidian language. Our analysis revealed the presence of known and novel mutations in both hypervariable regions in the studied population groups. Median joining network analyses based on mtDNA showed extensive overlap in mtDNA lineages despite the extensive cultural and linguistic diversity. MDS plot analysis based on Fst distances suggested increased maternal genetic proximity for the studied population groups compared with other world populations. Mismatch distribution curves, respective neighbour joining trees and other statistical analyses showed that there were significant expansions. The study revealed an ancient common ancestry for the studied population groups, most probably through common founder female lineage(s), and also indicated that human migrations occurred (maybe across and within the Indian subcontinent) even after the initial phase of female migration to India.

Predicting extracapsular involvement in prostate cancer through the tumor contact length and the apparent diffusion coefficient.

PubMed

Granja, M F; Pedraza, C M; Flórez, D C; Romero, J A; Palau, M A; Aguirre, D A

To evaluate the diagnostic performance of the length of the tumor contact with the capsule (LTC) and the apparent diffusion coefficient (ADC) map in the prediction of microscopic extracapsular extension in patients with prostate cancer who are candidates for radical prostatectomy. We used receiver operating curves to retrospectively study the diagnostic performance of the ADC map and the LTC as predictors of microscopic extracapsular extension in 92 patients with prostate cancer and moderate to high risk who were examined between May 2011 and December 2013. The optimal cutoff for the ADC map was 0.87× 10 -3 mm 2 /s, which yielded an area under the ROC curve of 72% (95% CI: 57%-86%), corresponding to a sensitivity of 83% and a specificity of 61%. The optimal cutoff for the LTC was 17.5mm, which yielded an area under the ROC curve of 74% (95% CI: 61%-87%), corresponding to a sensitivity of 91% and a specificity of 57%. Combining the two criteria improved the diagnostic performance, yielding an area under the ROC curve of 77% (95% CI: 62%-92%), corresponding to a sensitivity of 77% and a specificity of 61%. We elaborated a logistic regression model, obtaining an area under the ROC curve of 82% (95% CI: 73%-93%). Using quantitative measures improves the diagnostic accuracy of multiparametric magnetic resonance imaging in the staging of prostate cancer. The values of the ADC and LTC were predictors of microscopic extracapsular extension, and the best results were obtained when both values were used in combination. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

In Vivo Patellofemoral Contact Mechanics During Active Extension Using a Novel Dynamic MRI-based Methodology

PubMed Central

Borotikar, Bhushan S.; Sheehan, Frances T.

2017-01-01

Objectives To establish an in vivo, normative patellofemoral cartilage contact mechanics database acquired during voluntary muscle control using a novel dynamic magnetic resonance (MR) imaging-based computational methodology and validate the contact mechanics sensitivity to the known sub-millimeter methodological inaccuracies. Design Dynamic cine phase-contrast and multi-plane cine images were acquired while female subjects (n=20, sample of convenience) performed an open kinetic chain (knee flexion-extension) exercise inside a 3-Tesla MR scanner. Static cartilage models were created from high resolution three-dimensional static MR data and accurately placed in their dynamic pose at each time frame based on the cine-PC data. Cartilage contact parameters were calculated based on the surface overlap. Statistical analysis was performed using paired t-test and a one-sample repeated measures ANOVA. The sensitivity of the contact parameters to the known errors in the patellofemoral kinematics was determined. Results Peak mean patellofemoral contact area was 228.7±173.6mm2 at 40° knee angle. During extension, contact centroid and peak strain locations tracked medially on the femoral and patellar cartilage and were not significantly different from each other. At 30°, 35°, and 40° of knee extension, contact area was significantly different. Contact area and centroid locations were insensitive to rotational and translational perturbations. Conclusion This study is a first step towards unfolding the biomechanical pathways to anterior patellofemoral pain and OA using dynamic, in vivo, and accurate methodologies. The database provides crucial data for future studies and for validation of, or as an input to, computational models. PMID:24012620

Knee extension range of motion and self-report physical function in total knee arthroplasty: mediating effects of knee extensor strength

PubMed Central

2013-01-01

Background Knee extensor strength and knee extension range of motion (ROM) are important predictors of physical function in patients with a total knee arthroplasty (TKA). However, the relationship between the two knee measures remains unclear. The purpose of this study was to examine whether changes in knee extensor strength mediate the association between changes in knee extension ROM and self-report physical function. Methods Data from 441 patients with a TKA were collected preoperatively and 6 months postoperatively. Self-report measure of physical function was assessed by the Short Form 36 (SF-36) questionnaire. Knee extensor strength was measured by handheld dynamometry and knee extension ROM by goniometry. A bootstrapped cross product of coefficients approach was used to evaluate mediation effects. Results Mediation analyses, adjusted for clinicodemographic measures, revealed that the association between changes in knee extension ROM and SF-36 physical function was mediated by changes in knee extensor strength. Conclusions In patients with TKA, knee extensor strength mediated the influence of knee extension ROM on physical function. These results suggest that interventions to improve the range of knee extension may be useful in improving knee extensor performance. PMID:23332039

Digital data processing system dynamic loading analysis

NASA Technical Reports Server (NTRS)

Lagas, J. J.; Peterka, J. J.; Tucker, A. E.

1976-01-01

Simulation and analysis of the Space Shuttle Orbiter Digital Data Processing System (DDPS) are reported. The mated flight and postseparation flight phases of the space shuttle's approach and landing test configuration were modeled utilizing the Information Management System Interpretative Model (IMSIM) in a computerized simulation modeling of the ALT hardware, software, and workload. System requirements simulated for the ALT configuration were defined. Sensitivity analyses determined areas of potential data flow problems in DDPS operation. Based on the defined system requirements and the sensitivity analyses, a test design is described for adapting, parameterizing, and executing the IMSIM. Varying load and stress conditions for the model execution are given. The analyses of the computer simulation runs were documented as results, conclusions, and recommendations for DDPS improvements.

A study of multiplex data bus techniques for the space shuttle

NASA Technical Reports Server (NTRS)

Kearney, R. J.; Kalange, M. A.

1972-01-01

A comprehensive technology base for the design of a multiplexed data bus subsystem is provided. Extensive analyses, both analytical and empirical, were performed. Subjects covered are classified under the following headings: requirements identification and analysis; transmission media studies; signal design and detection studies; synchronization, timing, and control studies; user-subsystem interface studies; operational reliability analyses; design of candidate data bus configurations; and evaluation of candidate data bus designs.

Research of Extension of the Life Cycle of Helicopter Rotor Blade in Hungary

DTIC Science & Technology

2003-02-01

Radiography (DXR), and (iii) Vibration Diagnostics (VD) with Statistical Energy Analysis (SEA) were semi- simultaneously applied [1]. The used three...2.2. Vibration Diagnostics (VD)) Parallel to the NDT measurements the Statistical Energy Analysis (SEA) as a vibration diagnostical tool were...noises were analysed with a dual-channel real time frequency analyser (BK2035). In addition to the Statistical Energy Analysis measurement a small

A review of mechanistic insight and application of pH-sensitive liposomes in drug delivery.

PubMed

Paliwal, Shivani Rai; Paliwal, Rishi; Vyas, Suresh P

2015-05-01

The pH-sensitive liposomes have been extensively used as an alternative to conventional liposomes in effective intracellular delivery of therapeutics/antigen/DNA/diagnostics to various compartments of the target cell. Such liposomes are destabilized under acidic conditions of the endocytotic pathway as they usually contain pH-sensitive lipid components. Therefore, the encapsulated content is delivered into the intracellular bio-environment through destabilization or its fusion with the endosomal membrane. The therapeutic efficacy of pH-sensitive liposomes enables them as biomaterial with commercial utility especially in cancer treatment. In addition, targeting ligands including antibodies can be anchored on the surface of pH-sensitive liposomes to target specific cell surface receptors/antigen present on tumor cells. These vesicles have also been widely explored for antigen delivery and serve as immunological adjuvant to enhance the immune response to antigens. The present review deals with recent research updates on application of pH-sensitive liposomes in chemotherapy/diagnostics/antigen/gene delivery etc.

Improvements to the YbF electron electric dipole moment experiment

NASA Astrophysics Data System (ADS)

Sauer, B. E.; Rabey, I. M.; Devlin, J. A.; Tarbutt, M. R.; Ho, C. J.; Hinds, E. A.

2017-04-01

The standard model of particle physics predicts that the permanent electric dipole moment (EDM) of the electron is very nearly zero. Many extensions to the standard model predict an electron EDM just below current experimental limits. We are currently working to improve the sensitivity of the Imperial College YbF experiment. We have implemented combined laser-radiofrequency pumping techniques which both increase the number of molecules which participate in the EDM experiment and also increase the probability of detection. Combined, these techniques give nearly two orders of magnitude increase in the experimental sensitivity. At this enhanced sensitivity magnetic effects which were negligible become important. We have developed a new way to construct the electrodes for electric field plates which minimizes the effect of magnetic Johnson noise. The new YbF experiment is expected to comparable in sensitivity to the most sensitive measurements of the electron EDM to date. We will also discuss laser cooling techniques which promise an even larger increase in sensitivity.

Variations in the crustal structure beneath western Turkey

NASA Astrophysics Data System (ADS)

Saunders, Paul; Priestley, Keith; Taymaz, Tuncay

1998-08-01

We use teleseismic receiver functions to investigate the crustal structure at two locations in western Turkey using seismic data recorded on small arrays of temporary broad-band seismographs. The results from these analyses are compared with receiver function results from the GDSN station ANTO on the Anatolian Plateau in central Turkey. The crust is ~ 30 km thick in the region of western Turkey where active normal faulting reveals present-day extension in the upper crust and alkali-basaltic volcanism reveals recent extension within the subcrustal lithosphere The crust is ~ 34 km thick further east where crustal extension is still evident but less pronounced. In the Anatolian Plateau, which is not currently extending, the crust is ~ 38 km thick. The level of extension estimated from these measurements of crustal thickness implies a β -factor of ~ 1.2. This value agrees with the amount of extension estimated in the upper crust from the integrated seismic strain rate (β -factor of ~ 1.3), from surface faulting(β -factor of ~ 1.25) and from the amount of extension in the subcrustal lithosphere estimated from the volcanism (β -factor < 2), all indicating that the extension is approximately uniformly distributed vertically throughout the lithosphere. The Moho transition in this region appears to thin slightly as the degree of extension increases westwards.

Taxometric and Factor Analytic Models of Anxiety Sensitivity: Integrating Approaches to Latent Structural Research

ERIC Educational Resources Information Center

Bernstein, Amit; Zvolensky, Michael J.; Norton, Peter J.; Schmidt, Norman B.; Taylor, Steven; Forsyth, John P.; Lewis, Sarah F.; Feldner, Matthew T.; Leen-Feldner, Ellen W.; Stewart, Sherry H.; Cox, Brian

2007-01-01

This study represents an effort to better understand the latent structure of anxiety sensitivity (AS), as indexed by the 16-item Anxiety Sensitivity Index (ASI; S. Reiss, R. A. Peterson, M. Gursky, & R. J. McNally, 1986), by using taxometric and factor-analytic approaches in an integrative manner. Taxometric analyses indicated that AS has a…

Ecological consequences of antibiotic exposure to periphyton in naturally colonizing stream mesocosms

EPA Science Inventory

Tetracycline and its derivatives are extensively used human and animal antibiotics, and enter stream ecosystems via point and non-point sources. Laboratory studies indicate that microbial organisms are more sensitive to antibiotics than invertebrates or fish, and may indicate t...

PRNP variants in goats reduce sensitivity of detection of PrPSc by immunoassay

USDA-ARS?s Scientific Manuscript database

Immunoassays are extensively utilized in disease diagnostics with monoclonal antibodies serving as critical tools within the assay. Detection of scrapie in sheep and goats relies heavily on immunoassays including immunohistochemistry, western blotting, and ELISA. In the United States, regulatory tes...

Testing sterile neutrino extensions of the Standard Model at future lepton colliders

NASA Astrophysics Data System (ADS)

Antusch, Stefan; Fischer, Oliver

2015-05-01

Extending the Standard Model (SM) with sterile ("right-handed") neutrinos is one of the best motivated ways to account for the observed neutrino masses. We discuss the expected sensitivity of future lepton collider experiments for probing such extensions. An interesting testable scenario is given by "symmetry protected seesaw models", which theoretically allow for sterile neutrino masses around the electroweak scale with up to order one mixings with the light (SM) neutrinos. In addition to indirect tests, e.g. via electroweak precision observables, sterile neutrinos with masses around the electroweak scale can also be probed by direct searches, e.g. via sterile neutrino decays at the Z pole, deviations from the SM cross section for four lepton final states at and beyond the WW threshold and via Higgs boson decays. We study the present bounds on sterile neutrino properties from LEP and LHC as well as the expected sensitivities of possible future lepton colliders such as ILC, CEPC and FCC-ee (TLEP).

Identification of mission sensitivities for high-power electric propulsion systems

NASA Technical Reports Server (NTRS)

Frisbee, Robert H.; Moeller, Robert C.

2005-01-01

This paper presents the results of mission analyses that expose various mission performance sensitivities and system advantages of the ALFA technology for a small but representative subset of nuclear electric propulsion (NEP) missions considered under NASA's Project Prometheus.

18 CFR 12.38 - Time for inspections and reports.

Code of Federal Regulations, 2011 CFR

2011-04-01

... reaches its normal maximum surface elevation, whichever occurs first. (3) For any development not set... information and analyses required by § 12.37(b). (c) Extension of time. For good cause shown, the Regional...

AHRQ series on complex intervention systematic reviews-paper 6: PRISMA-CI extension statement and checklist.

PubMed

Guise, Jeanne-Marie; Butler, Mary E; Chang, Christine; Viswanathan, Meera; Pigott, Terri; Tugwell, Peter

2017-10-01

Complex interventions are widely used in health systems, public health, education, and communities and are increasingly the subject of systematic reviews. Oversimplification and inconsistencies in reporting about complex interventions can limit the usability of review findings. Although guidance exists to ensure that reports of individual studies and systematic reviews adhere to accepted scientific standards, their design-specific focus leaves important reporting gaps relative to complex interventions in health care. This paper provides a stand-alone extension to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting tool for complex interventions-PRISMA-CI-to help authors, publishers, and readers understand and apply to systematic reviews of complex interventions. PRISMA-CI development followed the Enhancing the QUAlity and Transparency Of health Research Network guidance for extensions and focused on adding or modifying only essential items that are truly unique to complex interventions and are not covered by broader interpretation of current PRISMA guidance. PRISMA-CI provides an important structure and guidance for systematic reviews and meta-analyses for the highly prevalent and dynamic field of complex interventions. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Helmholtz and Gibbs ensembles, thermodynamic limit and bistability in polymer lattice models

NASA Astrophysics Data System (ADS)

Giordano, Stefano

2017-12-01

Representing polymers by random walks on a lattice is a fruitful approach largely exploited to study configurational statistics of polymer chains and to develop efficient Monte Carlo algorithms. Nevertheless, the stretching and the folding/unfolding of polymer chains within the Gibbs (isotensional) and the Helmholtz (isometric) ensembles of the statistical mechanics have not been yet thoroughly analysed by means of the lattice methodology. This topic, motivated by the recent introduction of several single-molecule force spectroscopy techniques, is investigated in the present paper. In particular, we analyse the force-extension curves under the Gibbs and Helmholtz conditions and we give a proof of the ensembles equivalence in the thermodynamic limit for polymers represented by a standard random walk on a lattice. Then, we generalize these concepts for lattice polymers that can undergo conformational transitions or, equivalently, for chains composed of bistable or two-state elements (that can be either folded or unfolded). In this case, the isotensional condition leads to a plateau-like force-extension response, whereas the isometric condition causes a sawtooth-like force-extension curve, as predicted by numerous experiments. The equivalence of the ensembles is finally proved also for lattice polymer systems exhibiting conformational transitions.

Using GIS to analyze animal movements in the marine environment

USGS Publications Warehouse

Hooge, Philip N.; Eichenlaub, William M.; Solomon, Elizabeth K.; Kruse, Gordon H.; Bez, Nicolas; Booth, Anthony; Dorn, Martin W.; Hills, Susan; Lipcius, Romuald N.; Pelletier, Dominique; Roy, Claude; Smith, Stephen J.; Witherell, David B.

2001-01-01

Advanced methods for analyzing animal movements have been little used in the aquatic research environment compared to the terrestrial. In addition, despite obvious advantages of integrating geographic information systems (GIS) with spatial studies of animal movement behavior, movement analysis tools have not been integrated into GIS for either aquatic or terrestrial environments. We therefore developed software that integrates one of the most commonly used GIS programs (ArcView®) with a large collection of animal movement analysis tools. This application, the Animal Movement Analyst Extension (AMAE), can be loaded as an extension to ArcView® under multiple operating system platforms (PC, Unix, and Mac OS). It contains more than 50 functions, including parametric and nonparametric home range analyses, random walk models, habitat analyses, point and circular statistics, tests of complete spatial randomness, tests for autocorrelation and sample size, point and line manipulation tools, and animation tools. This paper describes the use of these functions in analyzing animal location data; some limited examples are drawn from a sonic-tracking study of Pacific halibut (Hippoglossus stenolepis) in Glacier Bay, Alaska. The extension is available on the Internet at www.absc.usgs.gov/glba/gistools/index.htm.

[Dynamic analysis in the knees with chronic anterior cruciate ligament insufficiency--an evaluation of antero-posterior instability, leg rotation and ground reaction force].

PubMed

Kanai, H

1993-07-01

A dynamic analysis was made on the knees with chronic anterior cruciate ligament (ACL) insufficiency for antero-posterior instability and abnormal rotation, also evaluating them for ground reaction force and muscle strength of knee extension. Studies were carried out on 51 patients with chronic unilateral ACL insufficiency and 80 knees of 40 healthy male and female young adults as controls. Using a knee motion analyser, an apparatus designed to analyse three dimensional knee motion, the gait was studied on a force plate. At the same time, the muscle strength of knee extension was measured with a Kinetic-Communicator (KIN-COM). In the dynamic analysis of the knee motion anterior instability was notable at a small angle of flexion. Qualitative evaluation of the knee motion revealed three patterns of rotation. The evaluation of ground reaction force showed that the rise from the heel strike was slow, its slope was gentle and the effect of weight removal was unclear. The evaluation of the muscle strength of knee extension revealed a decrease in torque of muscular contraction at 20 degrees of knee flexion.

Decreased pain sensitivity due to trimethylbenzene exposure ...

EPA Pesticide Factsheets

Traditionally, human health risk assessments have relied on qualitative approaches for hazard identification, often using the Hill criteria and weight of evidence determinations to integrate data from multiple studies. Recently, the National Research Council has recommended the development of quantitative approaches for evidence integration, including the application of meta-analyses. The following hazard identification case study applies qualitative as well as meta-analytic approaches to trimethylbenzene (TMB) isomers exposure and the potential neurotoxic effects on pain sensitivity. In the meta-analytic approach, a pooled effect size is calculated, after consideration of multiple confounding factors, in order to determine whether the entire database under consideration indicates that TMBs are likely to be a neurotoxic hazard. The pain sensitivity studies included in the present analyses initially seem discordant in their results: effects on pain sensitivity are seen immediately after termination of exposure, appear to resolve 24 hours after exposure, and then reappear 50 days later following foot-shock. Qualitative consideration of toxicological and toxicokinetic characteristics of the TMB isomers suggests that the observed differences between studies are due to testing time and can be explained through a complete consideration of the underlying biology of the effect and the nervous system as a whole. Meta-analyses and –regressions support this conclus

Genetic moderation of effects of maternal sensitivity on girl's age of menarche: Replication of the Manuck et al. study.

PubMed

Hartman, Sarah; Widaman, Keith F; Belsky, Jay

2015-08-01

Manuck, Craig, Flory, Halder, and Ferrell (2011) reported that a theoretically anticipated effect of family rearing on girls' menarcheal age was genetically moderated by two single nucleotide polymorphisms (SNPs) of the estrogen receptor-α gene. We sought to replicate and extend these findings, studying 210 White females followed from birth. The replication was general because a different measure of the rearing environment was used in this inquiry (i.e., maternal sensitivity) than in the prior one (i.e., family cohesion). Extensions of the work included prospective rather than retrospective measurements of the rearing environment, reports of first menstruation within a year of its occurrence rather than decades later, accounting for some heritability of menarcheal age by controlling for maternal age of menarche, and using a new model-fitting approach to competitively compare diathesis-stress versus differential-susceptibility models of Gene × Environment interaction. The replication/extension effort proved successful in the case of both estrogen receptor-α SNPs, with the Gene × Environment interactions principally reflecting diathesis-stress: lower levels of maternal sensitivity predicted earlier age of menarche for girls homozygous for the minor alleles of either SNP but not for girls carrying other genotypes. Results are discussed in light of the new analytic methods adopted.

SCALE Continuous-Energy Eigenvalue Sensitivity Coefficient Calculations

DOE PAGES

Perfetti, Christopher M.; Rearden, Bradley T.; Martin, William R.

2016-02-25

Sensitivity coefficients describe the fractional change in a system response that is induced by changes to system parameters and nuclear data. The Tools for Sensitivity and UNcertainty Analysis Methodology Implementation (TSUNAMI) code within the SCALE code system makes use of eigenvalue sensitivity coefficients for an extensive number of criticality safety applications, including quantifying the data-induced uncertainty in the eigenvalue of critical systems, assessing the neutronic similarity between different critical systems, and guiding nuclear data adjustment studies. The need to model geometrically complex systems with improved fidelity and the desire to extend TSUNAMI analysis to advanced applications has motivated the developmentmore » of a methodology for calculating sensitivity coefficients in continuous-energy (CE) Monte Carlo applications. The Contributon-Linked eigenvalue sensitivity/Uncertainty estimation via Tracklength importance CHaracterization (CLUTCH) and Iterated Fission Probability (IFP) eigenvalue sensitivity methods were recently implemented in the CE-KENO framework of the SCALE code system to enable TSUNAMI-3D to perform eigenvalue sensitivity calculations using continuous-energy Monte Carlo methods. This work provides a detailed description of the theory behind the CLUTCH method and describes in detail its implementation. This work explores the improvements in eigenvalue sensitivity coefficient accuracy that can be gained through the use of continuous-energy sensitivity methods and also compares several sensitivity methods in terms of computational efficiency and memory requirements.« less

An approach to measure parameter sensitivity in watershed hydrological modelling

EPA Science Inventory

Hydrologic responses vary spatially and temporally according to watershed characteristics. In this study, the hydrologic models that we developed earlier for the Little Miami River (LMR) and Las Vegas Wash (LVW) watersheds were used for detail sensitivity analyses. To compare the...